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S1462901119307853 | The production and use of Engineered Nanoparticles or materials containing ENPs has increased astonishingly leading to increased exposure to workers and consumers . The invention and applications of new materials either create new opportunities or pose new risks and uncertainties . The uncertainties concerning application of ENPs are posing disturbances to the ecosystem and human health . This review first addresses in vitro and | Impacts of ENPs on the ecology and the humans are evaluated. Ethical justifications are provided from the view point of IRG J and EC J. The burden and benefits of ENPs on the environment are identified and discussed. Mitigation strategies in sustaining ENPs for environmental applications are provided. Future research directions for sustainable use of ENPs are elucidated. |
S1462901119307890 | The textile industry presents one of the most threatening patterns of production concerning the global environmental impact . In this article we investigated the textile fiber composition of women s clothing in the retail trade of Santos through information read on the labels during July 2017 and January 2018 in three types of stores department popular and thrift stores . The inspected garments consisted mainly of polyester viscose and cotton fibers although fibers such as elastane polyamide and acrylic were eventually present as fabric complements . We calculate clothes ecological footprints by multiplying the fibers proportions by their sustainability notes and adapt the results to the current Brazilian labeling system . We did not detect ecological footprints differences in types of stores nor seasons of the year . There was predominance of clothes with a high ecological footprint . Exposure of the ecological footprint to clothing labels can influence consumer purchasing decisions and encourage the development of more sustainable products . Thus we propose the application of the labeling system as an environmental management tool for the Brazilian fashion sector . | We investigated the textile fiber composition of women s clothing in the retail trade of Santos Brazil and we verify that the inspected garments consisted mainly of polyester viscose and cotton fibers. We calculate clothes ecological footprints by multiplying the fibers proportions by their sustainability notes and adapt the results to the current Brazilian labeling system. Ecological footprint to clothing labels can influence consumer purchasing decisions and encourage the development of more sustainable products. Then we propose the application of the labeling system as an environmental management tool for the Brazilian fashion sector. |
S1462901119308044 | Global environmental change and other site specific pressures are threating coral reefs and the livelihoods of dependent coastal communities . Multiple strategies are used to build the resilience of both coral reefs and reef dependent communities but the effectiveness of these strategies is largely unknown . Using the Western Indian Ocean as a case study this paper combines published literature and expert opinion elicited through a multi stakeholder workshop to assess the intended and realised social and ecological implications of strategies commonly applied in the region . Findings suggest that all strategies can contribute to building social and ecological resilience but this varies with context and the overall strategy objectives . The ability of strategies to be successful in the future is questioned . To support effective resilience policy development more nuanced lesson learning requires effective monitoring and evaluation as well as a disaggregated understanding of resilience in terms of gender agency and the interaction between ecological and social resilience . Opportunities for further lesson sharing between experts in the region are needed . | Multiple strategies used to build resilience of coral reefs and reef dependent communities. Intended and realised social and ecological implications of strategies explored. Disaggregated understanding of ecological and social resilience is needed. Policy must encourage strategies contributing across the social ecological spectrum. Clear opportunity to strengthen knowledge networks and sharing. |
S1462901119308718 | Water systems are experiencing dynamic societal demands and extreme environmental changes . The integration of modular water systems into existing centralized infrastructures creating hybrid systems could mitigate these challenges by enabling more resilient water management . However the existence of technological alternatives has not changed the continuous reliance on centralized water infrastructure . Supportive policy instruments are key to foster the operation of modular technology within hybrid water systems . This article focuses on the role of substantive and procedural policy instruments for the successful operation of modular water systems within a hybrid water infrastructure . Based on Qualitative Comparative Analysis we can confirm the claim in the literature that relying on regulatory instruments is relevant for operating modular technology within hybrid systems . However we also find combinations of policy instruments where regulatory instruments do not matter . Furthermore we find that procedural instruments emphasizing stakeholder participation interplay with different substantive policy instruments to support the successful operation of modular systems . | Policy instrument mixes are key for the successful operation of modular water technology within hybrid water systems. Multiple policy instrument configurations exist showing that there is no silver bullet for operating modular technology. Regulatory instruments are relevant for operating modular technology within hybrid water systems but not omnipresent. Participation and user responsibility support the operation of modular technology within hybrid systems by engaging users. Information dissemination is important in the context of modular technology linking substantive and procedural instruments. |
S1462901119308822 | Despite numerous efforts to promote and implement more integrated approaches coordination problems persist and impede sustainable water governance and management . This paper introduces a framework for guiding a transdisciplinary diagnostic approach to address such coordination problems . The approach aims at addressing some of the challenges identified in scientific scholarship and water governance practice by combining context specific participatory assessments of individual cases with comparative case analysis guided by a generic conceptual framework . The focus is on implementation processes at regional and local scale and their embedding in a multi level water governance system and a specific environmental and societal context . | Framework for complex coordination challenges in water governance and management. Diagnostic approach supports context sensitive assessment. Structured case study comparison enhances strength of diagnosis. |
S1462901119308858 | Traditionally water energy and food resources are governed in many countries by separate sets of laws rules and institutions . However recent studies have increasingly underlined the WEF nexus approach as a framework for coherent holistic and integrated implementation of the Sustainable Development Goals to address fragmentations and ensure cleaner and efficient production methods in each sector . | Develops a profile of legal and institutional challenges that arise with a nexus approach to WEF governance from a comparative lens. Identifies the ways in which an integrative legal framework can help close these gaps. Proposes framework for enhancing rule linkage and integrated governance across WEF domains. |
S1462901119309116 | Small scale fishing communities are expected to adapt to fish catch fluctuations linked to global environmental change . Notwithstanding impacts from severe climate events and overexploitation of fisheries resources can compromise functions and resilience of ecosystems and associated species and thereby jeopardize long term population trend stability and fisheries productivity . To date most assessments and vulnerability studies of fisheries dependent populaces have focused on global regional and national levels while studies at village and community levels where adaptive planning in the context of climate and environmental changes is important are less common . Based on data from official fishery records over a three decadal period and recent interviews with artisanal fishermen along the Tanzanian coast we assessed small scale fisheries with regard to | Long term records and artisanal fishers congruently confirmed a substantial decline in fish landings in Tanzania. Overfishing environmental changes and destruction of habitats were perceived the drivers of fish catch declines. Fishers adapt to declining fish stocks by changing their resource use behaviours. Most fishers mentioned they will continue fishing in the future even if the fish landings would be further reduced. Strategic policies should include fishers perceptions to adapt and cope with ongoing climate and environmental changes. |
S1462901119309451 | Ship traffic has nearly tripled in the Canadian Arctic over the past decade and additional growth is expected as climate change continues to increase navigability in the region . In response the Canadian Government is developing Low Impact Shipping Corridors as an adaptation strategy that supports safety and sustainability under rapidly changing environmental conditions . The corridors are voluntary maritime routes where services and infrastructure investments are prioritized . While a large amount of data from different sources were used to establish the location of the corridors important local and Indigenous knowledge from Arctic communities has yet to be considered in much detail . The Arctic Corridors and Northern Voices project was established in response to this fundamental gap in knowledge . The purpose of this paper is to outline perspectives and recommendations for the corridors from 13 Canadian Arctic communities across Inuit Nunangat that were involved in the ACNV project through a series of participatory community mapping workshops . A summary of the recommendations for the corridors that emerged from communities is presented including spatial representations for 1 preferred corridors 2 areas to avoid 3 restrictions by season 4 modification of vessel operation and 5 areas where charting is needed . The findings of the study further reiterate the vital need for meaningful inclusion of northern voices in the development of Arctic shipping policy and governance . | Climate change and sea ice reduction have influenced an increase in Arctic ship traffic. Climate change and increased Arctic shipping are impacting Inuit livelihoods. Low impact shipping corridors need to consider culturally significant marine areas. Communities recommend changes to the low impact shipping corridors in Arctic Canada. Findings reiterate the need for inclusion of northern voices in Arctic shipping policy. |
S1462901119309463 | We elevate the undervalued role of wetland protective services for mitigating disastrous consequences of unprecedented weather related events for human communities . Scientific evidence increasingly reveals that wetlands play critical hydrologic roles in landscapes helping to mitigate flood drought and in some cases fire risks . However wetland protective services have not received sufficient policy action . We propose national wetland commissions modeled after the concept of lake and river commissions as one way to strategically link wetland protection to other societal objectives including human disaster risk planning infrastructure investments and climate adaptation strategies . We offer an example applicable to the United States describing an institutional design for a National Interagency Wetland Commission . We suggest it could be patterned after existing federal commissions statutorily created by Congress with delegated administrative and regulatory authority and designated independent agency status within the executive branch . It is time for bold and innovative policy action to incorporate wetland protective services into societies defenses against extreme weather events . | Wetlands can help protect human communities from consequences of extreme weather events. Society has not valued the protective services of wetlands. Coordinated and effective policy action is needed to protect wetlands to protect people. We propose countries take policy action to create national wetland commissions. Commissions can link wetland protection to disaster planning infrastructure investments and climate adaptation strategies. |
S1462901119309530 | Public perception of climate change can either facilitate or hinder the implementation of climate policies . This perception is dependent on a number of influencing factors called drivers in ways that are still not clearly understood . Our study quantifies the relative strength of drivers of climate change perception taking into account differences in the social political geographical economic and educational identities of any considered community . In addition to investigating the direct influence of the main drivers on climate change perception we particularly examine the interactions among drivers identifying in this way indirect pathways of influence . We find that perceptions are directly influenced by the share of principles and ideals within a community and by the physical experience of weather change . Indirect influences are found to be related to the level of development of a community to its level of social interaction and to the spread of climate change information . A deeper understanding of interactions among drivers should prove especially useful for the design of effective climate change mitigation and adaptation measures . | We present a new framework to study the drivers of climate change perception. We identify 33 community independent drivers. We quantify the relative importance of the identified drivers. The study of interactions among drivers reveals indirect paths of influence. Indirect paths of influence to climate change perception are key to unravel effective climate actions. |
S1462901119309591 | The partisan divide on climate policy in the United States is well documented . Decarbonizing the energy system is key to addressing climate change and social support for many energy policies is not as starkly partisan as the question of the existence of climate change . In this analysis we blend insights from social psychology and political science that suggest that partisanship is a social identity with varying salience across individuals . We integrate the concept of | Climate change and climate change policies are highly partisan in the U.S. The effect of expressive partisanship on climate change attitudes is unknown. Identity based vs. instrumental accounts of partisan identity. Results are consistent with an identity based perspective on partisanship. |
S1462901119309645 | The last decades have seen changes in the water innovation landscape in Africa with many countries introducing innovative approaches to managing water resources and the provision of water services . However little knowledge exists on how water innovators operate in this changing environment . The objective of this explorative study is to shed light on the dynamics of water innovation in African cities . We draw on the experience of 12 water innovators from Kenya Mozambique and Ghana complemented by insights from key actors in the national innovation systems of the three countries . The study finds that the dynamics of water innovation in African cities are manifested at different levels the innovation itself the innovating entity and the innovation system . The three countries have made efforts to create an enabling environment for innovation but many system gaps still exist that need to be addressed . Fragmentation of the water innovation systems and securing scale up capital and long term investment for water innovation appear to be the most important bottlenecks . The former could be addressed by actively promoting interactive learning based approaches to innovation the latter by developing new financing models that allow water innovators and financiers to share the risks and benefits associated with water innovations . | Dynamics of water innovation are manifested at three levels innovation itself innovating entity and innovation system. Fragmentation of innovation systems and lack of scale up capital are the most important bottlenecks for water innovation. Interactive learning based approaches and risk sharing financing models are key to addressing water innovation gaps in Africa. |
S1462901119309657 | In different parts of the world a variety of initiatives are being implemented to promote water innovation . This paper explores the role of virtual incubators in fostering water related innovations in Africa using the case of VIA Water a Dutch programme that promotes water innovation in African cities . Virtual incubators operate and provide their services primarily online . The results of this study confirm the additionality and disruptive nature of virtual incubators . In virtue of the gaps they are likely to fill in the innovation systems for water these incubators can be an effective policy instrument for fostering water related innovations in Africa . However given their limitation to perform some functions in local innovation systems virtual water incubators should be used along with other support mechanisms . The paper concludes that to realise their full potential water innovation support programmes must be locally embedded and target at least three levels the micro mezzo and macro levels . Only then can they attract full recognition and significantly influence the performance of water innovation systems . | Virtual incubators fill important gaps in the African innovation systems for water. Virtual incubators have inherent limitations to perform some functions in local innovation systems. Virtual incubators should be conceived as structural elements of innovation systems. |
S1462901119309669 | The past years have seen a rising number of initiatives to foster water related innovations around the world . Many of such initiatives take the incubation approach to support individuals or entities with potential for developing marketable water innovations . Despite the growing research on incubation the innovation processes of incubatees which are generally intertwined with the incubation process itself have arguably received the least attention of researchers . Using the process perspective to innovation this paper sheds light on the issue of how incubated innovators manage their innovation processes and the extent to which these processes are influenced by the incubator support . Empirical evidence was collected from 12 water innovators supported by VIA Water a Dutch programme on water innovation in Africa . The study finds that innovation activities of incubated water innovators during the period preceding the incubation process are in essence informal hardly planned and with little focus . The incubator support enables innovators to innovate systematically notably by maintaining linkages between the different phases of the innovation processes and to build convincing innovation cases . | Innovation activities of water incubatees prior to incubation are in essence informal hardly planned and with little focus. The incubation process increases the degree of formality and predictability of the innovation processes. The incubator support enables incubatees to innovate systematically by linking the different phases of the innovation processes. The incubator support allows water incubatees to become confident of their ideas and to build convincing innovation cases. |
S1462901119309712 | Scenario planning is a popular decision support method that is increasingly being applied to climate change adaptation . However evaluation of scenario planning for adaptation is lacking . In this paper we summarise a science policy session held at the European Climate Change Adaptation Conference in May 2019 where practitioners explored the strengths and weaknesses of scenario planning for climate adaptation and identified modifications to enhance the methods utility . Eight case studies spanning three scenario planning types from varied socio cultural contexts were presented by the authors followed by discussion amongst the 40 participants . Strengths focussed on opportunities provided by scenario planning for stakeholder participation and raising their awareness about future risks vulnerability and uncertainty . Participatory scenario planning was most useful for building stakeholder consensus at the local scale over shorter timeframes . Weaknesses centred on the inability of scenarios to generate quantitative predictions and concrete adaptation solutions . This was partly attributed to practitioners limited understanding of stakeholder politics and power dynamics and the resulting lack of integration of scenario exercises within decision making processes . Scenarios were also limited by being static and participatory processes were resource intensive . Suggested modifications were to develop iterative scenario planning embedded within decision making cycles . Such transient scenarios could absorb system feedbacks and updated information to prioritise adaptation responses thus actively contributing to ongoing adaptation pathways . Applying monitoring evaluating and learning would enable reflexive refinement of the method adapting it to become an agile approach applicable to varied socio cultural and political contexts . | Scenario planning for climate adaptation is increasingly popular but has not been evaluated. We present reflections from practitioners at the European Climate Change Adaptation conference. Participatory processes focussed locally over short 20year timeframes were most effective. Scenario planning did not sufficiently engage in decision making processes limiting outcomes. Reflexive transient scenarios embedded in iterative adaptation pathways were recommended. |
S1467089518300058 | Evaluation of IT value is challenging due to the complex nature of IT impacts and multifaceted interpretations of value . We introduce a conceptual framework for tackling the complexity of IT value evaluation within the scope of a single company . Our study applies design science research with analysis of experiences from five cases . The conceptual framework covers perspectives 1 analysis levels for varying stakeholder views on value 2 valuing logics for different interpretations of value and 3 evaluation views for understanding systemic value . Together these perspectives create a basis for evaluating and communicating multifaceted IT value and help to understand what kind of specific value information can serve the needs of IT related decision making . | Conceptual Framework offers a systemic basis for understanding and communicating multifaceted IT value. Conceptual Framework connects multi level system analysis multi logic value judgements and different value explications. The utility of Conceptual Framework is demonstrated in five industrial cases. |
S1467089518300411 | Despite the usefulness of computer assisted audit tools and techniques in increasing audit productivity and reducing costs their adoption by audit firms is low in developing countries . The aim of this study is to investigate whether organizational and environmental factors can help explain CAATTs adoption in less developed countries such as Malaysia . The research framework was developed based on the Technology Organization Environment framework . The results reveal that for environmental factors the complexity of clients accounting information systems and perceived level of support of professional accounting bodies affect CAATTs adoption . For organizational factors firm size top management commitment and employee IT competency were found to be significant factors . Moreover firm size partially moderates the influence of clients AIS complexity on CAATTs adoption . This paper contributes to existing adoption theory by extending our understanding of the impact of factors unique to CAATTs adoption . | Computer assisted audit tools and techniques CAATTs adoption in developing countries is low. Developed a research model based on the Technology Organization Environment framework. Found organizational and environmental factors explained CAATTs adoption. |
S146708951830071X | The near universal organizational participation in social media is predicated on the belief there are some tangible or intangible new resources to be had through tweeting pinning posting friending and sharing . We argue the linchpin of any payoff from engagement in social media is a special form of social capital we refer to as | Social media capital SMC is a special form of social capital with a distinct nature determinants and outcomes. Social media capital is THE proximate resource obtained via social media efforts P1 . Social media capital is observable P2 unequally distributed P3 and built only via messages and connecting actions P4 . SMC can be leveraged to achieve strategic objectives via capital conversion P5 or direct expenditure P6 . Understanding this causal chain is critical for measuring the return on investment from social media. |
S1467089518300897 | Strategic performance measurement systems are employed by senior management as a means of translating strategy into performance measures . Recent research suggests that this translation can lead managers to focus on personal performance measures as opposed to overall organizational strategya phenomenon referred to as strategy surrogation . Emerging technologies are increasingly used to operationalize SPMS via smart phone tablet laptop formats that inherently promote the use of small subsets of performance measures and have the potential to exacerbate strategy surrogation effects . This study explores executive managers motivations in deploying dashboards and the resulting effect on operational managers focus on associated performance measures . An exploratory cross sectional field study is conducted with 27 executive to mid level managers to establish a theoretical model explaining how and why organizations deploy dashboards and why managers use dashboards to facilitate their activities and decisions . Despite concerns over the propensity of managers to focus on performance measures and lose sight of strategic objectives the interview data indicate that executive management intentionally designs dashboards to achieve strategy surrogation . The impact of this intentional surrogation appears to arise through operational managers beliefs that dashboard measures align with organizational strategy and lead to improved managerial and organizational performance . However this relationship between perceived alignment of performance measures and managerial and organizational performance is mediated by dashboard quality and information quality . These findings have important implications as the effects of SPMS on strategy surrogation are further explored by researchers and as system designers consider the side effects of emerging technologies on effective strategic performance measurement . | Dashboards play an important role in an organization s SPMS at the operational level. Strategy alignment and interactive management control are the most important constructs. Executive management perceives strategy surrogation positively at the operational levels. |
S1467089518301350 | A third wave of technological advancements which is often referred to as digitalization is affecting organizations across the board . This paper aims to present a comprehensive synthesis of the extant scholarly work on digitalization in the accounting literature . It does so through a systematic literature review that focuses on articles on digitalization published by the highest ranked accounting journals in the period 20072017 . By conducting a thorough review we extend Rom and Rohde s literature review on integrated information systems in management accounting . Furthermore we utilize a modified version of the framework proposed by Rom and Rohde to classify and interpret the literature . This allows us to understand the differences between IIS and digitalization in accounting and to illuminate avenues for future research . The paper concludes with an overview of three main differences in how IIS and digitalization have influenced accounting and three concurrent avenues for future research on digitalization in accounting the elusive boundaries of accounting power relations and knowledge production for decision making . | Digitalization is the impetus for increasingly elusive boundaries of accounting. Digitalization is changing power relations. Digitalization raises new issues of knowledge production in decision making. |
S1467089520300191 | Based on a cross sectional field study Reinking et al . propose a complex theoretical model for understanding the characteristics of dashboards that promote use and lead to individual and organizational performance gains . This study tests the theoretical model using survey data collected from 323 middle and upper level managers with experience using corporate dashboards . The data were analyzed using components based structural equation modeling and the results provide strong support for the external validity of the Reinking et al . theoretical model . The results show that two primary constructs strategy alignment and interactive management control are important factors impacting the extent of dashboard use perceived managerial performance and perceived organizational performance . Prior research has expressed concerns over the tendency of managers to lose sight of strategic objectives and focus solely on performance measures . However our results indicate that operational managers perceive that dashboards focused on specifically tailored KPIs lead to both improved managerial and organizational performance . This study contributes to management control and strategy research in two important ways . While prior research has examined strategy in the executive level context through evaluations changes or initiative implementations this study investigates strategy alignment at the operational levels of the organization . Second the results suggest that intentional strategy surrogation may have beneficial effects at the lower operational levels in an organization . | Provides strong support and external validity for Reinking et al. 2019 theoretical model. Provides insights into the strategy surrogation concerns that have been raised in literature. Strong association between strategy alignment and interactive controls in dashboards. The extend of dashboard use is mediated by dashboard quality and dashboard information. Indicates the characteristics of dashboards that promote use and lead to performance gains |
S1467089520300208 | The gradual but marked decline in the correspondence between aggregated accounting numbers and market valuations such as stock returns is a well documented phenomenon in the research literature . Rapid advances in technology have paved the way for the collection of unprecedented volumes of data . Currently the slow speed of information dissemination laggard accounting systems and a focus on high levels of aggregation are perhaps the largest contributors to waning relevance of financial reporting . The fight for trading superiority is leading users to seek relevant data elsewhere and may contribute to these observed effects . This paper proposes an accounting system known as User XBRL designed to overcome these issues . This system collects analyzes and displays information in such a way that caters to the speed detail and customization demands of modern day stakeholders . U XBRL amalgamates all types of data pertinent to a business including both internal company data and exogenous source data . Each piece of data is assigned to a firm resource according to the resource based view . Then U XBRL standardizes the information according to data standards and feeds it to a central repository . This repository is primarily organized through XBRL tags and is governed secondarily by other standards and taxonomies . A number of applications can be used individually to select data from the repository for analysis . Using U XBRL the recognition monitoring and assurance of resources are streamlined . | There is an increasing focus on information items outside of financial reports. Propose a new accounting information system based on REA and resource based view. Operationalized through XBRL which supports hierarchy and is machine readable. Data are tagged with data standards such as resource Audit Data Standards and XBRL GL. Assurance of data and monitoring of firm changes are completed in real time. Finally displayed on a completely customizable user interface |
S146708952030021X | The PCAOB s audit firm inspections drive audit focus and costs . The PCAOB s 2010 initiated increased emphasis on internal control audit work intensified concern over internal control weaknesses . IT related material weaknesses have emerged as particularly significant with PCAOB reports highlighting on going deficiencies in IT controls auditing and the 2015 PCAOB brief noting an on going focus on recurring audit deficiencies . We explore how ICW affect audit fees and how alternative types of | Fee premiums associated with ITMW linger longer than fee premiums for non IT entity level material weaknesses ELMW. ITMW premiums linger longer than premiums for account specific material weaknesses. Fee premiums by type of internal control weakness remediated is strongest for ITMW linked to data processing integrity. Findings underscore the importance of also distinguishing between. of. as identified in data quality research |
S1467089520300221 | Digitization is said to strongly disrupt business and professional life . Especially tax consulting has aroused public interest in this respect . Frey and Osborne even go so far as to predict that tax consulting will become obsolete . Although these statements are misleading without further interpretation there is no denying the fact that some change in the accounting and tax profession is inevitable . In Germany however business digitization currently does not seem to be urgently necessary in the tax consulting field since this profession is protected by law from competition . Thus by examining the digitization efforts of German tax consultants we are able to exclude almost all effects of outside pressure and therefore take a look at intrinsic motivation . This study focuses on psychological factors and explores the relationship between tax consultants Big Five personality and their level of digitization . Personality is measured using the ten item Big Five inventory provided by Rammstedt and John . We develop a digital maturity model based on 20 questions relating to digitization in business and tax consulting . After carrying out a factor analysis five factors are extracted . To interpret our results we develop two business model transformation indices as well as an overall digitization index . Our analysis is based on a survey of 968 members of the chamber of tax consultants in Munich Germany . We are able to show that tax consultants scoring high on extraversion and openness to experience and low on neuroticism exhibit a higher level of digitization . This is to the best of our knowledge the first study to discuss intrinsic motivation and digitization in an accounting context . Moreover an index for digitization as a whole and two business model transformation indices are provided shedding light upon a hard to grasp phenomenon . | Digitization is said to disrupt whole occupational areas e.g. the accounting profession. This paper develops a digital maturity framework for the accounting tax consulting industry. This paper takes into account personality when investigating success in digitization. We find that extraversion openness and neuroticism affect digitization behavior of accountants tax consultants in Germany. |
S1467089520300385 | Given exponential growth in the size of big data its multi channel sources and variability in quality that create challenges concerning cost effective use firms have invested significantly in databases and analytical tools to inform decision making . In this regard one means to avoid the costs associated with producing less than insightful reports and negative effects on performance through wasted resources is prioritizing data in terms of relevance and quality . The aim of this study is to investigate this approach by developing and testing a scale to evaluate Big Data Availability and the role of Big Data Prioritization for more effective use of big data in decision making and performance . Focusing on the context of supply chain management we validate this scale through a survey involving 84 managers . Findings support a positive association between Big Data Availability and its use in SCM decision making and suggest that Big Data Prioritization as conceptualized in the study has a positive impact on the use of big data in SCM decision making and SCM performance . Through developing a scale to evaluate association between Big Data Availability and use in SCM decision making we make an empirical contribution to value generation from big data . | A survey of 84 managers in a supply chain management context. Positive association between Big Data Availability and use in SCM decision making. Big Data Availability positively influences Big Data Prioritization. Big Data Prioritization positively impacts use of big data in SCM decision making. The use of big data in SCM decision making positively impacts SCM performance. |
S1467089520300543 | This study experimentally examines potential non professional investors understanding of a random sample of SOX 404 reports containing both IT weaknesses and non IT weaknesses as reflected in their internal control weakness severity ratings and their accuracy in identifying the reported ICWs . We find that the number of perceived non ITWs and report length are positively associated with potential investors ICW severity ratings and that failing to perceive non ITWs reduces potential investors ratings of weakness severity . However the number of perceived ITWs is not associated with potential non professional investors ratings of the overall severity of ICWs . Potential investors errors in identifying both non ITWs and ITWs are associated with the number of non ITWs and ITWs reported . Also errors are positively associated with lower readability of SOX 404 reports . We identify specific types of ITWs and non ITWs that contribute the most to the total number of errors made by non professional investors in perceiving ICWs . | Potential investors do not fully understand SOX 404 reports. Perceived rather than reported ICWs are associated with ICW severity assessment. Failing to perceive non ITWs but not ITWs reduces ICW severity assessment. Perception errors are associated with lower readability of SOX 404 reports. Specific non ITWs and ITWs that contribute most to perception errors are identified. |
S1467089520300555 | This study is based on a longitudinal in depth case study conducted in a Portuguese public sector organization where the accountants adopted a strategic business partner role and promoted the implementation of two new accounting information systems under the context of increasing business competition . Given their role we examined how the implementation processes of such AIS were influenced by the accountants power strategies adopting an organizational power narrative inquiry grounded on the four power dimensions proposed in Hardys framework power over resources power over decision making processes power over meanings and power of the system . As a result this study contributes to the literature available on AIS by discussing the strategic business partner role of accountants in a specific case and by offering new insights into AIS research under the topic of accounting change through the exercise of power . Our research also contributes to the literature on organizational power by providing theoretical developments to Hardys power framework . | We analysed the implementation processes of two AIS in a public sector organization. We pointed out the accountants strategic business partner role in AIS implementation processes. We studied the ways accountants exercised power throughout AIS implementations. We offered new insights into AIS research under the topic of accounting change through the exercise of power. We extended the Hardys 1996 power framework. |
S1476927118300550 | Hepatitis C Virus infection is a major public health concern across the globe . At present direct acting antivirals are the treatment of choice . However the long term effect of this therapy has yet to be ascertained . Previously fluoroquinolones have been reported to inhibit HCV replication by targeting NS3 protein . Therefore it is logical to hypothesize that the natural analogs of fluoroquinolones will exhibit NS3 inhibitory activity with substantially lesser side effects . In this study we tested the application of a recently devised integrated In our analysis we were able to shortlist 18 active natural analogs out of 10 399 that shared physicochemical properties with the template drugs . These analogs showed comparable binding efficacy with fluoroquinolones in targeting 32 amino acids in the HCV NS3 active site that are crucial for NS3 activity . Our approach had around 80 sensitivity and 70 specificity in identifying physicochemically similar analogs of fluoroquinolones . Our current data suggest that our approach can be efficiently applied to identify putative HCV drug inhibitors that can be taken for | Hepatitis C Virus HCV infection is a major public health concern across the globe. At present direct acting antivirals are the treatment of choice. However the long term effect of this therapy has yet to be ascertained. We have applied a cheminformatics molecular docking approach to identify putative HCV drug inhibitors. This approach can be applied to discover physiochemically similar analogs of virtually any drug. This approach provides a speedy and inexpensive approach to complement drug discovery and design. |
S1476927118301671 | The genetic information encoded in structural genes is decoded by an intracellular process called gene expression . This mechanism is regulated by epigenetic processes such as histone acetylation . Histone acetylation which happens in nucleosomes exposes DNA to transcription factors . Therefore the correlation between histone acetylation and gene expression has been assessed as a fundamental issue in many previous studies . In the proposed research we investigate which marks of histone acetylation are informative and which ones are redundant in the vicinity of SP1 transcription factor binding sites in human CD4 T cell . To achieve this we use information theory methods . Subsequently we apply a multilayer perceptron neural network to show that the selected histone acetylation marks by information theory methods are sufficiently informative . Finally we use the neural network to predict binding sites of 17 other transcription factors on chromosomes 1 and 2 . The results suggest that information conveyed by the selected histone acetylation marks are equivalent to that of all 18 marks associated with SP1 transcription factor binding sites on chromosome 1 . Furthermore almost 91.75 of SP1 binding sites of chromosome 2 are predicted by the selected histone acetylation marks while all 18 marks predict 90.56 correctly . Moreover the selected histone acetylation marks are efficient at predicting 17 other types of transcription factor binding sites . | Finding the correlation between histone acetylation marks HAms and transcription factor binding sites TFBSs . Using information theory methods to evaluate the importance of HAms in distinguishing TFBSs and random positions. Using the selected HAms as input features for multilayer perceptron neural network to predict TFBSs. |
S1476927118302524 | In psoriasis skin disease psoriatic cells develop rapidly than the normal healthy cells . This speedy growth causes accumulation of dead skin cells on the skins surface resulting in thick patches of red dry and itchy skin . This patches or psoriatic skin legions may exhibit similar characteristics as healthy skin which makes lesion detection more challenging . However for accurate disease diagnosis and severity detection lesion segmentation has prime importance . In that context our group had previously performed psoriasis lesion segmentation using the conventional clustering algorithm . However it suffers from the constraint of falling into the local sub optimal centroids of the clusters . The main objective of this paper is to implement an optimal lesion segmentation technique with aims at global convergence by reducing the probability of trapping into the local optima . This has been achieved by integrating swarm intelligence based algorithms with conventional K means and Fuzzy C means clustering algorithms . There are a total of eight different suitable combinations of conventional clustering and four swarm intelligence techniques artificial bee colony ant colony optimization and particle swarm optimization have been implemented in this study . The experiments are performed on the dataset of 780 psoriasis images from 74 patients collected at Psoriasis Clinic and Research Centre Psoriatreat Pune Maharashtra India . In this study we are employing swarm intelligence optimization techniques in combination with the conventional clustering algorithms to increase the probability of convergence to the optimal global solution and hence improved clustering and detection . The performance has been quantified in terms of four indices namely accuracy sensitivity specificity and Jaccard index . Among the eight different combinations of clustering and optimization techniques considered in this study FCM SO outperformed with mean JI 0.83 mean A 90.89 mean SN 92.84 and mean SP 88.27 . FCM SO found statistical significant than other approaches with 96.67 of the reliability index . The results obtained reflect the superiority of the proposed techniques over conventional clustering techniques . Hence our research development will lead to an objective analysis for automatic accurate and quick diagnosis of psoriasis . | Objective analysis of psoriasis disease over a larger dataset of 780 images. Implementation of swarm intelligence algorithms to obtain optimum clusters. Effective psoriasis lesion detection using four swarm intelligence techniques. Quantitative analysis of the result using different metrics. Calculation of computational complexity for each swarm intelligence algorithms. |
S1476927118306078 | Plant molecular breeding largely depends on the relationship between molecular markers and major traits . Herein a total of 32 962 genomic simple sequence repeats were detected in the whole genome of chickpea with an average density of 94.93 SSRs Mb . Chickpea chromosomes uniformity test indicated that the genomic SSRs were steadily distributed across the genome . Moreover 48 667 transcriptome sequences were analyzed and 1949 SSR containing transcript assembly contigs were identified . The analysis showed that di and trinucleotide SSRs were the most frequent SSR motifs within the transcriptome sequences . Among them AT and TTA and AG and TTC motifs within the transcriptome showed the highest frequencies among di and trinucleotide repeat motifs respectively . The SSRs containing TACs were compared to the GenBank non redundant database using BLASTX and subsequently gene ontology analysis was performed using QuickGO browser to reduce complexity and highlight biological processes associated with the SSRs containing TACs . The identified SSRs containing TACs were categorized into 35 enriched functional related gene group . The mapping of characterized SSRs containing TACs onto chickpea chromosomes was performed using BLASTN . The mapping result showed that a total of 1798 SSRs containing TACs were mapped onto the chickpea genome . Based on the functional analysis result 249 and 242 of the mapped SSRs containing TACs were found in the genes encoding for putative stress related proteins and transcription factors respectively . The results presented here can be applied to improve and speed up the chickpea breeding programs . | Uniformity testing showed that the frequency distribution of the gSSRs was uniformly across the eight chickpea chromosomes. A total of 1798 simple sequence repeats SSRs containing transcript assembly contigs TACs were mapped onto chickpea chromosomes. The chromosomal location and distribution of TAC SSRs appeared to be unevenly dispersed across the chickpea genome. Transcription regulation proteins were identified for 13.44 of SSR containing TACs 253 TAC SSRs . The maximum number of TAC SSRs 56.6 or 141 TAC SSRs was observed in genes encoding proteins that play a common role in various stresses. |
S1476927118306637 | Multi drug resistance bacteria pose a significant threat to our ability to effectively treat infections due to the development of several antibiotic resistant mechanisms . A major component in the development of the MDR phenotype in MDR bacteria is over expression of different type of efflux pumps which actively pump out antibacterial agents and biocides from the periplasm to the outside of the cell . Consequently bacterial efflux pumps are an important target for developing novel antibacterial treatments . Potent efflux pump inhibitors could be used as adjunctive therapies that would increase the potency of existing antibiotics and decrease the emergence of MDR bacteria . Several potent inhibitors of efflux pumps have been reported which has been summarized here . All the natural and synthetic EPIs were optimized with Gaussian and Avogadro software . The optimized structures were docked with each class of efflux pumps and their bonding parameters were computed . The theoretical analyses were performed with density functional theory . Overall computational study revealed a good trend of electrophilicity and ionization potential of the EPIs the obtained average values are within in the range of 0.001414 AU 0.00032 and 0.208821 AU 0.015545 respectively . Interestingly cathinone interacts with most of the efflux pumps among the tested inhibitors . The electrophilicity and ionization potential of cathinone are 0.00198 and 0.2388 AU respectively . The study opens a new road for designing future generation target specific efflux pump inhibitors as well as one molecule with multiple inhibition abilities . | Twenty six potent bacterial efflux pumps inhibitors EPIs are summarized here. All the EPIs were docked with efflux pumps from five different classes. Molecules were optimized and theoretically analyzed following density functional theory. Electrophilicity and ionization potential of the molecules are important criteria to be a good EPI. Cathinone is the most effective one that may interact with four types of efflux pumps. |
S1476927118307114 | ATP dependent ParE enzyme is as an attractive target for the development of antibacterial agents . Atom based 3D QSAR model AADHR.187 was developed based on the thirty eight | A highly predictive five point 3D QSAR model AADHR.187 was developed. Model was validated by the external data set and enrichment study. We identified five potential hits against. ParE by. pharmacophore based HTVS. 30 ns MD simulation was performed to validate the docking pose. Three new molecules have been proposed having high binding affinity for. ParE enzyme. |
S1476927118307126 | Post translational modifications are considered important molecular interactions in protein science . One of these modifications is sumoylation whose computational detection has recently become a challenge . In this paper we propose a new computational predictor which makes use of the sine and cosine of backbone torsion angles and the accessible surface area for predicting sumoylation sites . The aforementioned features were computed for all the proteins in our benchmark dataset and a training matrix consisting of sumoylation and non sumoylation sites was ultimately created . This training matrix was balanced by undersampling the majority class using the NearMiss method . Finally an AdaBoost classifier was used for discriminating between sumoylation and non sumoylation sites . Our predictor was called C iSumo because of its effective use of circular functions . C iSumo was compared with another predictor which was outperformed in statistical metrics such as sensitivity accuracy and Matthews correlation coefficient . | New computational predictor for detecting sumoylation sites. Combination of the sine and cosine of torsion angles and the accessible surface area. Remarkable performance improvement by undersampling the majority class. Prediction of sumoylation non sumoylation sites using an AdaBoost algorithm. |
S1476927118307242 | This paper proposed an improved simulated annealing algorithm for protein structure optimization based on a three dimensional AB off lattice model . In the algorithm we provided a general formula used for producing initial solution and designed a multivariable disturbance term relating to the parameters of simulated annealing and a tuned constant to generate neighborhood solution . To avoid missing optimal solution storage operation was performed in searching process . We applied the algorithm to test artificial protein sequences from literature and constructed a benchmark dataset consisting of 10 real protein sequences from the Protein Data Bank . Otherwise we generated C | The improved algorithm outperforms those reported algorithms on the testing of artificial protein sequences. The improved algorithm can obtain folding conformations with C. RMSD less than 3.0 from PDB structures for real proteins. space filling model can provide dynamic change of protein folding conformation at atomic level. |
S1476927118307448 | The cyclotides are the largest known family of cyclic proteins which are found in several plant families including Violaceae . They are circular bioactive peptides consisting of 28 37 amino acids which possess a cyclic cystine knot motif and could be useful in biotechnology and drug design as scaffolds for peptide based drugs . This study describes our finding of a potentially novel gene transcript from the petals of the Iranian | A potentially novel gene product suggested here which may encode a cyclotide like precursor with a conserved ER signal sequence a cysteine rich sequence forming 2 zin. finger motifs and a cyclotide like region containing two highly conserved C residues. studies have provided interesting homologies between the suggested cyclotide like precursor and several other unidentified sequences. Three dimensional prediction of cyclotide like precursor demonstrates unusual structure without CCK motif. This report may challenge the current viewpoints about the evolution of cyclotides. |
S147692711830803X | Bottom up i.e . molecule to medicine strategy for the discovery of new drugs takes enormous time and cost . In most of the cases inherent toxicity and undesired side effects of the developed drug hinder its way beyond the early stages of development . In this regard the systems pharmacology can play an excellent role by reducing the cost and time of drug development through rationalization and or repurposing of traditional drugs with known side effects . In the present study our aim was to develop an integrated systems biology method for the prediction of active ingredients of a traditional medicine and their potential targets inside the body . Further we evaluated the predictive capacity of the developed method in a preclinical animal model . | A combined computational and experimental approach for rationalization and repurposing of traditional medicine. The method accurately predicts active ingredients of a polyherbal extract or extract from other biological sources . It also computes the molecular mechanism of action of the active ingredients. The results are verified with animal studies. This unique method can reduce the time and cost of the conventional drug discovery process. |
S1476927118308612 | is declared as antibiotic resistant by WHO with the critical urgency of developing novel antimicrobial therapeutics as drug resistance is the second most dangerous threat after terrorism . Besides many attempts still there is no effective vaccine available against | To predict novel antigenic peptides for vaccine development against. by utilizing reverse vaccinology approach. The whole proteome of. e was analyzed using bioinformatics tools. Eight antigenic proteins were predicted as novel targets for vaccine design against multidrug resistant |
S1476927118309368 | In plants NAC is a class of transcription factors involved in growth regulation and is associated with abiotic stress morphogenesis and metabolism . Celery | A total of 111 putative NAC TFs were found and identified based on celery transcriptome and genome database. The AgNAC TFs were classified into 18 subfamilies and their physicochemical properties were preliminary analyzed. Expression profiles of selected. genes in response to abiotic stress were detected. |
S1476927119300623 | In order to identify the signature genes of tumorigenesis the pattern recognition method was used to analyze the gene methylation data which included only normal and cancer samples and was collected from the TCGA database . Here we analyzed the DNA methylation profiles of the six types of cancer and the ME signature genes for each cancer were selected by means of a combination of correlation student s | Focus on the early occurrence of cancer. The efficient and versatile method of gene screening for the occurrence of early cancer. The recognition accuracy and sensitivity greater than 97 for all cancers. The occurrence of early cancer is closely related to immune and inflammatory responses. |
S1476927119300817 | We study the origin of TB epidemic and complex distributions of various populations of TB infection within the stochastic framework . The stochastic nature of this disease infection could be linked to the stochastic behaviour at genome level which is exhibited in SNP distributions of experimentally identified hotspot driver genes . Our results show the emergence of random clusters and well defined discrete domains of the respective species populations in the model driven by demographic stochasticity and intrinsic complex species interaction . The multifractal analysis of the time series of the species populations indicate that TB epidemic could be mainly caused by contact communication and is directional . We propose that any TB epidemic may have high chance of approximately periodic recurrence and can be controlled by optimizing some of the parameters involved in the system modelling . | We propose that any TB epidemic may have high chance of periodic recurrence and can be controlled by optimizing parameters. We studied SNP distributions of experimentally identified drug resistance genes. We try to study sequence evolution of these genes. We found emergence of random clusters driven by demographic stochasticity. We observe development of time reversal oscillation after threshold value of stress signal. Multifractal analysis indicate that TB epidemic is caused by contact communication. |
S1476927119301185 | Congenital insensitivity to pain classified as a type of hereditary sensory and autonomic neuropathies is a rare disease in which the affected individuals fail to perceive sensation of pain . One of the PR SET Domain Proteins | Whole Exome Sequencing identified reported mutation in. gene in a patient with insensitivity to pain. All 19 PRDM domain containing proteins were structurally analyzed. Some of them cause neurological disorders in human including PRDM12. PRDM12 was further studied through. approaches. |
S1476927119301252 | Motivated by the characteristics of highly clustered single nucleotide polymorphism across the human genome we propose a set of chromosome wise fractal dimensions as a measure for identifying an individual for human polymorphism . The fractal dimension quantifies the degree of clustered distribution of SNPs and represents parsimoniously the genetic variation in a chromosome . In this sense the proposed scheme projects the SNP genotype data into a new space which is simpler and lower in dimension . As an illustrative example we estimate the chromosome wise fractal dimensions of SNPs that are extracted from the HapMap of Phase III data set . To determine the validity of the proposed measure we apply principal component analysis to the set of estimated fractal dimensions and demonstrate that the set more or less described the population structure of 11 global populations . We also use multidimensional scaling to relate the genetic distances based on PCA to the geographical distances between global populations . This shows that similar to the SNP genotype data the fractal dimensions also has a role in genetic distance in the population structure . In addition we apply the proposed measure to a signature for the classification of global populations by developing a support vector machine model . The selected feature model predicts the global population with a balanced accuracy of about 77 . These results support that the fractal dimension is an efficient way to describe the genetic variation of global populations . | We analyzed genome wide SNPs in individuals from different populations. We proposed a set of chromosome wise fractal dimensions. The fractal dimension quantified the degree of clustered distribution of SNPs. A set of fractal dimension described the genetic variation of global populations. The selected feature model predicted the global population with an accuracy of 77 . |
S1476927119301550 | Elementary flux mode analysis is a well studied method in constraint based modeling of metabolic networks . In EFM analysis a network is decomposed into minimal functional pathways based on the assumption of balanced metabolic fluxes . In this paper a system architecture is proposed that approximately models the functionality of metabolic networks . The AND OR graph model is used to represent the metabolic network and each processing element in the system emulates the functionality of a metabolite . The system is implemented on a graphics processing unit as the hardware platform using CUDA environment . The proposed architecture takes advantage of the inherent parallelism in the network structure in terms of both pathway and metabolite traversal . The function of each element is defined such that it can find flux balanced pathways . Pathways in both small and large metabolic networks are applied to the proposed architecture and the results are discussed . | Proposing a modular system architecture to calculate minimal flux balanced metabolic pathways. The architecture is based on the AND OR graph model. The proposed architecture was implemented on a GPU platform to take advantage of the parallel architecture provided in the GPU based on multiple cores and hierarchical memory. The topology based parallelism obtained by the system was the main achievement of the model. The simplified metabolic network of the CHO cell was studied to prove the concept of the design on metabolic networks to find EFMs. Besides the potential of the model was studied on shortest pathways of the. model. |
S1476927119301951 | Ovarian Cancer is the most occurring gynecological cancer worldwide often diagnosed at a later stage and ultimate results in a high death rate . To overcome this serious health concern it is important to understand the molecular mechanisms and equally significant to identify the putative biomarkers as well as the therapeutic drug targets for the early diagnosis and treatment of OVCA . In doing so a strategy is designed to study the most frequently diagnosed cases of OVCA called as High Grade Serous Ovarian Carcinoma cell lines with the combination of computational biology biostatistics and cancer informatics approaches . This study is directed to investigate the global gene expression profiling and to perform the analyses of identified global Differently Expressed Genes of OVCA . The microarray dataset is comprised of tumor and cell line samples of OVCA and it was used for the identification of DEGs in the current study . The STRING database was used to construct Protein Protein Interaction network of DEGs and hub genes were identified by the CytoHubba . In addition a functional enrichment analysis of up and down regulated DEGs was performed by a bioinformatics database called as DAVID . The microRNAs and transcription factors analyses were conducted with the aid of biological tools MAGIA and GenCOdis3 respectively . As a result the genes comprised of CSF1R TYROBP PLEK FGR ACLY ACACA LAPTM5 C1 or f162 IL10RA and CD163 were identified as hub genes . Additionally miRNA analysis resulted in finding an association of zinc finger protein with OVCA comes out after implementing different algorithms . On the other hand in the TFs analysis resulted in various DEGs that were enriched by NFAT NF1 and GABP TFs . In this study it was observed that ACACA ACLY and CSF1R DEGs showed significant occurrence in different steps and therefore these genes were studied precisely . Nevertheless the results may help to discover the potential biomarkers with deep understanding of molecular mechanisms . However further validation is required to explain the OVCA pathogenesis . | We identified 154 DEGs in OVCA tumor and cell line samples. DEGs have been used to investigate hub genes for complex networks. Functional enrichment analysis of miRNAs and TFs of DEGs have been carried out. In various steps the DEGs ACACA ACLY and CSF1R showed significant enrichment and were effectively studied. |
S1476927119302440 | Graphs are powerful structures able to capture topological and semantic information from data hence suitable for modelling a plethora of real world systems . For this reason graph based pattern recognition gained a lot of attention in recent years . In this paper a general purpose classification system in the graphs domain is presented . When most of the information of the available patterns can be encoded in edge labels an information granulation based approach is highly discriminant and allows for the identification of semantically meaningful edges . The proposed classification system has been tested on the entire set of organisms for which metabolic networks are known allowing for both a perfect mirroring of the underlying taxonomy and the identification of most discriminant metabolic reactions and pathways . The widespread diffusion of graph structures in biology makes the proposed pattern recognition approach potentially very useful in many different fields of application . More specifically the possibility to have a reliable metric to compare different metabolic systems is instrumental in emerging fields like microbiome analysis and more in general for proposing metabolic networks as a universal phenotype spanning the entire tree of life and in direct contact with environmental cues . | Novel information granulation and knowledge discovery technique for structured data. Information granules as relevant substructures high sensitivity and specificity . Information granules are further filtered at classification stage suboptimal subset . Tests on real metabolic pathways data classification show remarkable performances. Knowledge discovery over filtered granules paves the way for further studies. |
S1476927119302622 | Metastasis is the main cause of breast cancer lethality especially in early stages led to improvements in therapeutic procedures . Lately by improvements in our perception of biological processes and immune system new classes of vaccines are emerged that grant us the opportunity of designing resolute constructs against desired antigens . In the current study we used a variety of immunoinformatics tools to design a novel cancer vaccine against Preferentially Expressed Antigen of Melanoma which counts as a cancer testis antigen for various human cancers including BC . The PRAME up regulation leads to strengthen BC stem cells maintenance drug resistance cell survival adaptation and apoptosis evading in cancerous cells . The PRAME co expressed genes were mined and validated through BC RNA sequencing of TCGA data . The immunodominant T cell predicted epitopes were fused and engineered to form the vaccine . The safety allergenicity and immunogenic capabilities of the vaccine were confirmed by promising immunoinformatics tools . The vaccines structure was verified to be hydrophilic in most areas through Kyte and Doolittle hydrophobicity plotting . The interactions between the designed vaccine and immune receptors of TLR4 and IL1R were confirmed by protein protein docking after modeling its tertiary structure . Finally codon optimization and In conclusion concerning | Investigating and validation of PRAME co expressed genes. Establishing protein protein interaction network of PRAME and enrichment analysis. Design novel multi epitope BC vaccine against PRAME. Prediction and modeling of secondary and tertiary structures of PRAME derived vaccine. In silico validation of the designed construct by studying modelled tertiary structure physiochemical characterization safety antigenicity post translational modification solubility and docking simulation. |
S1476927119302750 | Oncogenic human papilloma viruses are the cause of various types of cancer specifically cervical cancer . L1 protein is the main protein of HPV capsid which targeted in many vaccine producing attempts . However they have not enough coverage on the various high risk HPV types . Therefore having a low cost potent HPV vaccine to protect against all members of the papillomaviridea family will be promising . In this study L1 protein based peptide vaccine was designed using immunoinformatics methods which provides physicochemical properties such as stability in room temperature potential of antigenicity non allergic properties and no requirement with eukaryotic host system . The designed vaccine has two HPV conserved epitopes with lengths 18 and 27 amino acids in all members of papillomaviridea . These peptides promote humoral and cellular immunity and INF responses . In order to ensure strong induction of immune responses Flagellin a Toll like receptor 5 agonist and a short synthetic toll like receptor 4 agonist were also joined to the epitopes . Structure of the designed vaccine was validated using Rampage and ERRAT and a high quality 3D structure of the vaccine protein was provided . Docking studies demonstrated an appropriate and stable interaction between the vaccine and TLR 5 . The vaccine is expected to have a high quality structure and suitable properties including high stability solubility and a high potential to be expressed in | The vaccine consists of four major sections toll like receptor 4 adjuvant toll like receptor 5 adjuvant and two epitopes. Each section was joined together by appropriate linkers. Different strategies were applied to enhance immunogenicity of peptide vaccine. The vaccine is able to protection of population on all members of papillomaviridea family. The vaccine has a high quality structure and appropriate physicochemical properties in E. coli as host. |
S1476927119303871 | Aggression is a complex behavior underpinned by cross talk between several biomolecules . To date a composite molecular network of the behavioral disorder has not been constructed . The present study aims to develop the same from the system network analyses recruiting genes with empirical evidence demonstrating their role in the incidence and progression of aggression . In short 327 genes were recruited in the study after extensive literature survey and subsequent shortlisting by sieving out the comorbidities like cancer and other pathological and physiological ailments other languages and repeated citations . Subsequent String network analysis coalesces 275 genes in a network with 2223 edges . The developed network was then subjected to delineate modules using MCODE which via gene clustering on the basis of gene ontology segregate all genes into 14 modules . Of these as expected top 5 modules involved entailing of neuronal signaling pathways with redundant repetitions . Finally 10 genes were picked randomly accounting average module size and subjected to the network analysis with 100 000 bootstrap replicates . This results in the detection of certain novel genes that lacks empirical evidence for their association with the aggression . Amongst those most notable are genes involved in protein turnover regulation like | From 275 finally selected repertoire of genes 14 molecular modules were observed. Modules with high gene clustering entail both serotonin and dopamine related pathways. Several novel genes were predicted that potentially contributes in aggression physiology. |
S1476927119303913 | Protein Protein Interaction Network analysis unveils molecular level mechanisms involved in disease condition . To explore the complex regulatory mechanisms behind epilepsy and to address the clinical and biological issues of epilepsy | The result revealed eight pivotal genes like DNM1 CCND1 ITPR1 HRAS SRC BRAF CREBBP SPTAN1 present in epilepsy. This study identified pathways like PI3 kinase VEGF CCKR Ras PDGF Integrin Wnt TGF beta EGF receptor signaling etc. Functional enrichment analysis discloses critical tasks during neuron excitation as a dominating function in epileptic state. Validation of key epileptic genes linked up pathways are investigated using clinical level results and Gene Ontology GO . |
S1476927119303998 | Tamoxifen is a prodrug and cytochrome P450 2C9 has a significant role in the formation of a therapeutically more potent metabolite than tamoxifen . Since CYP2C9 exhibits genetic polymorphism it may contribute to different phenotypic drug response . Moreover it may be misleading if the possibility of heterogeneous clinical observations of pharmacogenetic investigations is ignored . Above all clinical investigation of all the polymorphic variants is beyond the scope of a pharmacogenetic study . Therefore in order to understand the genotype phenotype association it is aimed to study the interatomic interactions of amino acid substitutions in CYP2C9 variants in the presence of tamoxifen . Computational structural biology approach was adopted to study the effect of amino acid substitutions of polymorphic variants of CYP2C9 R144C I359L D360E R150H R335W and L90P on the flexibility of the enzyme in the presence of tamoxifen . The mutations were selected based on previously determined associations on genotype and clinical outcome of drugs . | CYP2C9 is involved in the metabolism of tamoxifen evident in the described study. Docking study concludes the formation of 4 hydroxytamoxifen by CYP2C9. MD simulations of CYP2C9 amino acid substitutions 2 3 5 8 11 and 13 bound with tamoxifen exhibit structural changes. Modulations were apparent in the substrate specificity determining region and the substrate access egress channels. Structural changes in CYP2C9 2 3 5 8 11 and 13 are involved in the variable enzyme activity of tamoxifen. |
S1476927119304050 | Stem cells are crucial in the field of tissue regeneration and developmental biology . Embryonic stem cells which are pluripotent in nature are derived from the inner cell mass of blastocyst . The gene expression profiles of ESCs and Induced pluripotent stem cells were compared to identify the differences . Spermatogonial stem cells are also known as Germ line stem cells present in testis is having the capability of producing the sperm in their whole lifetime . Therefore can be reprogrammed into pluripotent cells called male germline pluripotent cells . It is very difficult to interpret the larger genomic data sets which are available in public databases without high computational facilities . In order to identify the similar groups We studied the co expression clustering of the transcriptome and variation of the transcriptome of the GSCs gPSCs ESCs and other cell types using fuzzy clustering using AutoSOME . The series matrix file with GSE ID GSE11274 was retrieved and subjected to the various normalization methods corresponding rows and columns were clustered using p values ensemble runs and different running modes . Transcriptome analysis using the proposed approach intuitively and consistently characterized the variation in cell cell significantly . Collectively our results suggest that the GSCs and the ESCs displayed differential gene expression profiles and the GSCs possessed the potential to acquire pluripotency based on the high expression of epigenetic factors and transcription factors . These data may provide novel insights into the reprogramming mechanism of GSCs . | We studied the clustering of gene expression data and co expression modules of different cellular phenotypes. Heat maps generated reflects the distinct expression patterns of cells and also intrinsic status of the cells. The Transcriptome variation among GSCs ESCs and gPSCs was studied using fuzzy cluster network. |
S1476927119304128 | Human African trypanosomiasis also known as sleeping sickness causes millions of deaths worldwide . HAT is primarily transmitted by the vector tsetse fly | We have re annotated the genome of tsetse fly and identified novel miRNAs based on a series of reliable bioinformatics tools. 25 proteins and 35 miRNAs were found to be associated with trypanosome survival. Two miRNAs miR 619 5p and miR 2490 3p were observed to target several critical genes that participated in the infection of human African trypanosomiasis. Ten miRNAs were found to be unique in tsetse fly compared to other insects. |
S1476927119304190 | Glutaredoxins the oxidoreductase proteins are involved in several cellular processes including maintenance of cellular redox potential and iron sulfur homeostasis . The analysis of 503 amino acid sequences from 167 cyanobacterial species led to the identification of four classes of cyanobacterial Grxs i.e . class I II V and VI Grxs . Class III and IV Grxs were absent in cyanobacteria . Class I and II Grxs are single module oxidoreductase while class V and VI Grxs are multimodular proteins having additional modules at their C terminal and N terminal end respectively . Furthermore class VI Grxs were exclusively present in marine cyanobacteria . We also report the identification of class VI Grxs with two novel active site motif compositions . Detailed phylogenetic analysis of all four classes of Grxs revealed the presence of several subgroups within each class of Grx having variable dithiol and or monothiol catalytic active site motif and putative glutathione binding sites . However class II Grxs possess CGFS type highly conserved monothiol catalytic active site motif . Sequence analysis confirmed the highly diverse nature of Grx proteins in terms of their amino acid composition though sequence diversity does not affect the overall 3D structure of cyanobacterial Grxs . The active site residues and putative GSH binding residues are uncharged amino acids which are present on the surface of the protein . Additionally the presence of hydrophilic residues at the surface of Grxs confirms their solubility . Protein ligand interaction analysis identified novel glutathione binding sites on Grxs . Regulation of Grxs encoding genes expression by light quality and quantity as well as salinity suggests their role in determining the fitness of organisms under abiotic factors . | Four classes of Grxs were found in 167 cyanobacteria based on phylogenetic analyses. Two novel active site motifs CPFS and CPFC were identified in class VI Grxs for the first time. Active site and putative glutathione binding site are composed of uncharged amino acids. Protein ligand interaction analysis identified novel glutathione binding sites. Grx encoding genes of. PCC 7942 are regulated by high PAR UVR and salinity. |
S147692711930475X | The Protein Structure Prediction problem comprises among other issues forecasting the three dimensional native structure of proteins using only their primary structure information . Most computational studies in this area use synthetic data instead of real biological data . However the closer to the real world the more the impact of results and their applicability . This work presents 17 real protein sequences extracted from the Protein Data Bank for a benchmark to the PSP problem using the tri dimensional Hydrophobic Polar with Side Chains model . The native structure of these proteins was found by maximizing the number of hydrophobic contacts between the side chains of amino acids . The problem was treated as an optimization problem and solved by means of an Integer Programming approach . Although the method optimally solves the problem the processing time has an exponential trend . Therefore due to computational limitations the method is a proof of concept and it is not applicable to large sequences . For unknown sequences an upper bound of the number of hydrophobic contacts can be found due to a linear relationship with the number of hydrophobic residues . The comparison between the predicted and the biological structures showed that the highest similarity between them was found with distance thresholds around 5.28.2 . Both the dataset and the programs developed will be freely available to foster further research in the area . | The proposed method finds optimal folds with maximum number of hydrophobic side chain contacts. The computational effort of the method grows exponentially with the number of hydrophobic amino acids. The linear correlation between the number of hydrophobic side chain contacts and the number of hydrophobic amino acids may establish an upper bound for further studies. Results indicate that the best range of thresholds to define a hydrophobic contact is between 5.2 and 8.2. In this range the proposed method give conformations most similar to the real world proteins. Using only the maximization of hydrophobic contacts to drive the folding process is not enough to accurately predict real protein structures. It is provided a benchmark with 17 real protein sequences optimally folded according the 3D HP SC model. All the software developed are made freely available including the program for extracting and converting biological sequences to the HP 3D SC model and integer programming optimization. |
S1476927119304785 | Hepatocellular carcinoma is the major histological form of primary liver cancer . It has usually reached the disease state once the patient is diagnosed since there are no specific symptoms in the early stages of HCC . This fact increases the difficulty of curing HCC . Recently quantities of evidence have shown that many mathematical methods can be used to detect critical states or tipping points of complex diseases . However it is difficult to apply the DNB theory to the clinic since multiple samples are generally unavailable for individual patient . This paper constructs a novel method based on landscape dynamic network biomarkers which aims to detect early warning signals from cirrhosis state to very advanced HCC state in individual patient . The selected dataset contains multiple samples for each HCC state . A score that indicates the disease characteristics is calculated for each sample by RNA seq data and several scores constitute a distribution in the same state . Quantifying the statistical characteristics of these distributions and determining that low grade dysplastic and high grade dysplastic are the critical states of HCC . These results can provide scientific advice for early warning indicators and optimal treatment time for HCC . | Our algorithm improves the original landscpe DNB method with strong clinical applicability. We identify the critical states of HCC based on the characteristics of the distribution of the sample population. In our study low grade dysplastic and high grade dysplastic were identified as critical states of HCC. |
S1476927119304815 | At present tertiary structure discovery growth rate is lagging far behind discovery of primary structure . The prediction of protein structural class using Machine Learning techniques can help reduce this gap . The Structural Classification of Protein Extended is latest and largest dataset available at present . The protein sequences with less than 40 identity to each other are used for predicting and SCOPe classes . The sensitive features are extracted from primary and secondary structure representations of Proteins . Features are extracted experimentally from secondary structure with respect to its frequency pitch and spatial arrangements . Primary structure based features contain species information for a protein sequence . The species parameters are further validated with uniref100 dataset using TaxId . As it is known protein tertiary structure is manifestation of function . Functional differences are observed in species . Hence the species are expected to have strong correlations with structural class which is discovered in current work . It enhances prediction accuracy by 7 10 . The subset of SCOPe 2.07 is trained using 65 dimensional feature vector using Random Forest classifier . The test result for the rest of the set gives consistent accuracy of better than 95 . The accuracy achieved on benchmark datasets ASTRAL 1.73 25PDB and FC699 is better than 86 91 and 97 respectively which is best reported to our knowledge . | The latest and largest dataset SCOPe 2.07 used along with benchmark datasets ASTRAL 1.73 25PDB and FC699. The Random Forest algorithm uses Primary and Secondary Structure based feature vectors for prediction. The species based features are recognized as sensitive features for predictions. The performance of class and increased significantly. |
S1476927119305067 | By using the available expression datasets of mRNAs and small RNAs we constructed and compared the salt responsive gene regulatory networks involving both transcriptional and post transcriptional regulations between model plants rice and Arabidopsis . The salt responsive GRNs involve the transcription factors microRNAs and their target genes . Here we describe 552 miRNA target interactions 95 up regulated TF target interactions and 56 down regulated TTIs in rice while 332 MTIs 138 up regulated and 4 down regulated TTIs in Arabidopsis . Interestingly we observed the networks in rice are more complicated where target genes were enriched in rice development and growth while more stress related genes were detected in Arabidopsis networks . With the construction and comparison of GRNs between rice and Arabidopsis in response to salt stress we can basically describe the differences of salt responsive mechanisms in two species rice tends to respond slower and chooses to manipulate its development and growth to avoid salt stress while Arabidopsis prefers to trigger a serious salt defending genes to protect itself from stress . Our work provides the foundation for further exploring the molecular basis of plant salt response and the potential breeding practice by engineering the critical components in the networks in improving plant salt tolerance . | Based on public salt related microArray data small RNA seq and degradome sequence we constructed and compared salt response networks in rice and Arabidopsis consisting of miRNAs genes and transcription factors TFs . In rice more target genes of networks were enriched in development and growth while more stress directly related genes were detected in Arabidopsis networks. Salt response networks of Arabidopsis are typically organized. Salt response mechanisms of rice are emphasized on avoiding salt stress by regulating growth and development according to rice miRNA TF genes networks. MiRNA171 GRAS and miRNA169 NFYA are possible species conserved salt response patterns. Not only are they detected in our results but also reported in other signaling pathways. For instance miRNA169 NFYA is found work in ABA signaling pathways. |
S1476927119305365 | Recent advances in high throughput experimental technologies have generated a huge amount of data on interactions between proteins and nucleic acids . Motivated by the big experimental data several computational methods have been developed either to predict binding sites in a sequence or to determine if an interaction exists between protein and nucleic acid sequences . However most of the methods can not be used to discover new nucleic acid sequences that bind to a target protein because they are classifiers rather than generators . In this paper we propose a generative model for constructing protein binding RNA sequences and motifs using a long short term memory neural network . Testing the model for several target proteins showed that RNA sequences generated by the model have high binding affinity and specificity for their target proteins and that the protein binding motifs derived from the generated RNA sequences are comparable to the motifs from experimentally validated protein binding RNA sequences . The results are promising and we believe this approach will help design more efficient | LSTM based model for constructing protein binding RNA sequences. Computationally deriving protein binding motifs from generated RNA sequences. The derived motifs are comparable to experimentally validated motifs. |
S1476927119305511 | Major Histocompatibility Complex is a cell surface glycoprotein that binds to foreign antigens and presents them to T lymphocyte cells on the surface of Antigen Presenting Cells for appropriate immune recognition . Recently studies focusing on peptide based vaccine design have allowed a better understanding of peptide immunogenicity mechanisms which is defined as the ability of a peptide to stimulate CTL mediated immune response . Peptide immunogenicity is also known to be related to the stability of peptide loaded MHC complex . In this study ENCoM server was used for structure based estimation of the impact of single point mutations on pMHC complex stabilities . For this purpose two human MHC molecules from the HLA B 27 group in complex with four different peptides and three HLA B 44 molecules in complex with two different peptides were analyzed . We found that the stability of pMHC complexes is dependent on both peptide sequence and MHC allele . Furthermore we demonstrate that allele specific peptide binding preferences can be accurately revealed using structure based computational methods predicting the effect of mutations on protein stability . | Normal Mode Analysis can be used to estimate the relative importance of mutations of residues. Stability of pMHC complexes is found to depend on both sequence of the bound peptide and type of the MHC allele. It is shown that pMHC complex stability can be varied by substituting peptide residues. |
S1476927119305687 | Metastases are the main cause of death in advanced breast cancer patients . Although chemotherapy and hormone therapy are current treatment strategies drug resistance is frequent and still not completely understood . | Metastases are the main cause of death in advanced breast cancer BC patients. A bioinformatics analysis was performed on BC patients to explore the molecular mechanisms associated with BC metastasis. We identified pathway co expression network that could contribute to understanding the mechanism and development of BC metastases. |
S1476927119305705 | WRKY genes comprises one among a large clan of transcription factor genes in the plant kingdom playing a fundamental role in the vegetative and reproductive growth development and stress responses of a plant . In spite of several studies on cucumber | Total of 62 putative WRKY genes were identified in cucumber genome and classified in to three major groups Group I IIa IIe and III . Physicochemical properties variants of WD in identified WRKY proteins were analyzed and based on chemical nature WRKY genes are serine rich proteins. STRING analysis were performed for selected CsWRKY for their protein protein interactions. elements of. genes were analyzed for their expression patterns under different growth development and other environmental conditions. |
S1476927119305845 | High mobility group proteins are the major architectural proteins . Among HMG proteins High Mobility Group A is characterized by AT hook motifs which have an affinity for AT rich DNA . In this study we characterized the plant HMGAs from the Poaceae family using | Three major evolutionary clades of Poaceae HMGAs were identified. Poaceae HMGAs from all the clades except clade 2 HMGAs were identified to lack the high affinity type I DNA binding domain. No. of AT hook ATH motif in Poaceae ranges from 3 to 5. The C terminal tail following the last ATH in Poaceae HMGAs is significantly smaller compared to that of mammalian HMGAs. The length of the C terminal tail following the last ATH is smallest and highly conserved in clade 2 HMGAs. |
S1476927119306206 | The mitochondrial solute carrier genes are highly conserved during vertebrate evolution . In most SLC25 genes of zebrafish chicken mouse and human the introns are located at exactly superimposable positions . In these topographically corresponding introns we studied the composition of the initial and terminal hexanucleotides which are instrumental in splicing signaling focusing on the evolutionary conservation mutation dynamics of these genetically related sequences . At each position the per cent conservation of zebrafish individual nucleotides in chicken mouse and human is proportional to their percent frequency in zebrafish furthermore nucleotide mutations are biased in favor of the more represented nucleotides thus compensating for those highly represented zebrafish nucleotides which have not been conserved . As a result of these evolutionary dynamics the general nucleotide composition at each position has remained relatively conserved throughout vertebrates . At 5ss following the canonical GT A and G are largely prevailing at position 3 A at 4 and G at 5 AGx . At 3ss T and C are largely prevailing at positions 6 5 and 3 preceding the canonical intron terminal AG xAG . However the actual composition of the tetranucleotides at 5 and 3 often does not conform to the above scheme . At 5ss the more canonical sequence is completely expressed in 63 of cases and partially in 37 of cases . At 3ss the more canonical sequence is completely expressed in 71 of cases and partially in 29 of cases . The nucleotide conservation loss is higher in the evolution from fish to the last common ancestor of birds and mammals then diminishes in the successive evolution steps up to the mammalian common ancestor and becomes still lower at the divergence of rodents and primates . | In this analysis of the zebrafish chicken mouse and human homologous SLC25 gene introns we describe the conservation mutation dynamics of the zebrafish 5ss and 3ss in the evolution to birds and mammals. Mitochondrial solute carrier genes of zebrafish chicken mouse and human the introns are located at exactly superimposable positions. As a result of evolutionary dynamics the general nucleotide composition at each position has remained remarkably conserved throughout vertebrates. Conservation loss is higher in the evolution from fish to the last common ancestor of birds and mammals and diminishes in the successive evolution steps up to the mammalian common ancestor and becomes still lower at the divergence of rodents and primates. The family of the SLC25 homologous genes presents aspects of an overall long term evolutionary exon intron architecture stability which contrasts with the wide range variability of the intron ends signals. |
S1476927119306243 | Family based multi locus tests integrate information from individual loci by weighted averaging of the marginal statistics and have been proven to be more efficient and robust than the single locus tests in genetic association studies . The power depends on how much information the weights can extract from data . The currently published weighted sum methods are only applicable to either common or rare variants and may suffer from substantial power loss especially for rare variants . In this paper we propose a novel data driven weight to improve the power under both common and rare variant circumstances . We use the | Family based association test FBAT are robust against the population stratification. Multi SNP tests are more powerful than single SNP methods as taking the covariance structure into consideration. Rare variant analysis is crucial to finding genetic causes for some complex diseases. Weighted sum statisitc using LASSO regression outperforms other tests in various GWAs designs. |
S1476927119306334 | Members of the let 7 family of miRNAs are well known with their tumor suppressor properties as they are expressed at low levels in several types of human malignancies . Among them let 7b and let 7c have gained special attention due their broad significance . Although the role of let 7b and let 7c have been widely reported in various types of cancers their functional importance and role in oncogenic signaling of breast cancer is poorly investigated . Therefore in the present study prognostic and diagnostic significance of let 7b and let 7c in breast cancer and the effects these miRNAs on genes involved in cancer progression were determined by using several bioinformatics analysis and validated in vitro mimic assays respectively . Using data of TCGA OncomiR and dbDEMC 2.0 overall expression analysis of let 7b and let 7c was performed . The effect of let 7b and let 7c on genes involved in cancer progression was investigated by mimic transfection assays . We found that both let 7b and let 7c were significantly altered in breast cancer and associated with the clinicopathological findings of patients . Additionally both let 7b and let 7c significantly altered oncogenic signaling in breast cancer cells . Consequently both miRNAs might have fundamental roles in breast cancer progression and can be considered as potential targets for breast cancer therapy and diagnosis . | Let 7b and let 7c were significantly altered in breast cancer. Let 7b and let 7c significantly altered cancer related gene expression. Both miRNA might have crucial roles in breast cancer progression |
S1476927119306504 | Gastric cancer is a common malignant tumor in the clinic with a high mortality rate ranking the first among malignant tumors of the digestive system . Early gastric cancer exhibits no specific clinical symptoms and signs and most of the patients were diagnosed as advanced gastric cancer . The prognosis is poor and the 5 year overall survival rate is still lower than 30 seriously threatening peoples life and health . However the pathogenesis of gastric cancer is still unclear . This study aimed to identify methylated differentially expressed genes in gastric cancer and to study the cellular functions and pathways that may be involved in its regulation as well as the biological functions of key methylated differentially expressed genes . The gene expression data set and methylation data set of gastric cancer genes based on TCGA were analyzed to identify prognostic methylated genes . This study showed that the methylation of the DERL3 promoter was correlated with the clinical analysis of tumors . Further studies were conducted on genes co expressed with DERL3 whose functions and pathways to inhibit gastric cancer were adaptive immune response T cell activation immune response regulating pathway cell surface on molecules and natural killer cell mediated cytotoxicity . Finally cell proliferation assay cell scratch assay and cell invasion assay confirmed that DERL3 as a tumor suppressor gene inhibited the malignant evolution of gastric cancer . The analysis of key methylated differentially expressed genes helped elucidate the epigenetic regulation mechanism in the development of gastric cancer . DERL3 as a methylation biomarker has a predictive and prognostic value in the accurate diagnosis and treatment of gastric cancer and provides potential targets for the precision treatment of gastric cancer . Not applicable . | A comprehensive analysis of STAD pathogenesis was conducted. High expression of DERL3 suppresses the invasion migration and proliferation of gastric cancer cells. DERL3 was screened and validated as a candidate diagnostic marker gene of STAD. DERL3 is a potential molecular target for the treatment of STAD. |
S1476927119306607 | The present study was to illustrate the agonistic property of arjungenin and arjunic acid towards farnesoid X receptor protein .The pharmacokinetic properties like molecular interactions absorption distribution metabolism elimination and toxicity of the ligands were checked through | Structure based pharmacophores screening of arjungenin and arjunic acid were predicted potential FXR agonist. ADMET studies of arjungenin and arjunic acid identified as non toxic and has druggable property. Molecular docking studies confirmed arjungenin and arjunic acid as a strong and stable binding towards FXR protein. studies with 3T3 L1 adipocytes confirm decreased cyp7a1 levels and increased FXR PPAR and SREBP 1c levels. |
S1476927119307054 | Protein kinases are enzymes acting as a source of phosphate through ATP to regulate protein biological activities by phosphorylating groups of specific amino acids . For that reason inhibiting protein kinases with an active small molecule plays a significant role in cancer treatment . To achieve this aim computational drug design especially QSAR model is one of the best economical approaches to reduce time and save in costs . In this respect active inhibitors are attempted to be distinguished from inactive ones using hybrid QSAR model . Therefore genetic algorithm and K Nearest Neighbor method were suggested as a dimensional reduction and classification model respectively . Finally to evaluate the proposed models performance support vector machine and Nave Bayesian algorithm were examined . The outputs of the proposed model demonstrated significant superiority to other QSAR models . | Protein kinases are enzymes acting as a source of phosphate through ATP to regulate protein biological activities. Inhibiting protein kinases with an active small molecule plays a significant role in cancer treatment. To achieve this aim QSAR model is one of the best economical approaches to reduce time and save in costs. Genetic algorithm and K Nearest Neighbor method were suggested as QSAR model. The outputs of the proposed model demonstrated significant superiority to the SVM and Nave Bayesian algorithms. |
S147692711930711X | Insight into the key genes of pluripotency in human and their interrelationships is necessary for understanding the underlying mechanism of pluripotency and hence their successful application in regenerative medicine . The recent advances in transcriptomics technologies have created new opportunities to decipher the genes involved in pluripotency genetic network that governs the unique properties of embryonic stem cells and lineage differentiation mechanisms in a deeper scale . There are a large number of experimental studies on human embryonic stem cells being routinely conducted for unfolding the underlying biology of embryogenesis and their clinical prospects . However the outcome of these studies often lacks consensus due to differences in samples experimental techniques and or analysis protocols . A universal stemness gene list is still lacking . Thus we aim to identify the pluripotency associated genes and their interaction network . In this quest we compared transcriptomic profiles of pluripotent and non pluripotent samples from diverse cell lines types generated through RNA sequencing . We used a uniform pipeline for the analysis of raw RNA seq data in order to reduce the amount of variation . Our analysis revealed a consensus set of 498 pluripotency associated genes and 432 genes as potential pluripotent cell differentiation markers . Furthermore we predicted 32 genes as pluripotency critical genes . These pluripotency critical genes formed a tightly bound co expression network with small world architecture . Gene ontology and pathway enrichment analysis StemChecker and literature survey confirmed the involvement of the genes in the induction and maintenance of pluripotency though more experimental studies are required for understanding their molecular mechanisms in human . | Transcriptome profiles of human pluripotent and non pluripotent samples were compared. Identified 498 pluripotency associated genes and 432 differentiation markers. 32 genes identified to be critical for pluripotency. List includes some of the well known stemness genes like NANOG POU5F1 and LIN28. We report several genes whose exact molecular function need to be explored. |
S1476927119307297 | Colorectal cancer is one of the most frequent and diagnosed diseases . Accumulating evidences showed that mRNAs and noncoding RNAs play important regulatory roles in tumorigenesis . Identification and determining the relationship between them can help diagnosis and treatment of cancer . Here we analyzed three microarray datasets GSE110715 GSE32323 and GSE21510 to identify differentially expressed lncRNAs and mRNAs in CRC . The adjusted p value 0.05 was considered statistically significant . Gene set enrichment analysis was carried out using DAVID tool . The miRCancer database was searched to obtain differentially expressed miRNAs in colorectal cancer and the miRDB database was used to attain the targets of the obtained miRNAs . To predict the lncRNA miRNA interactions we used DIANA LncBase v2 and RegRNA 2.0 . Finally the lncRNA miRNA mRNA signaling pathway network was constructed using Cytoscape v3.1 . By analyzing the three datasets a total of 21 mRNAs and 24 lncRNAs were identified as common differentially expressed genes between CRC tumor and marginal tissues . Nevertheless the constructed lncRNA miRNA mRNA signaling pathway network revealed a convergence on 6 lncRNAs 7 mRNAs and 6 miRNAs . We found that dysregulation of lncRNAs such as PCBP1 AS1 UCA1 and SNHG16 could sequester several miRNAs such as hsa miR 582 5p and hsa miR 198 and promote the proliferation invasion and drug resistance of colorectal cancer cells . We introduced a set of lncRNAs mRNAs and miRNAs differentially expressed in CRC which might be considered for further experimental research as potential biomarkers of CRC development . | The microarray data analysis was conducted to identify differentially expressed lncRNAs and mRNAs in CRC. The lncRNA miRNA mRNA interactions network analyses let to identify potential contributors involved in CRC pathobiology. The lncRNA miRNA mRNA interactions network analyses might be considered for further experimental research and biomarker development. |
S1476927119307601 | The present study is focused on a series of newly synthesized 1 aryl 3 ethyl 3 methylsuccinimide derivatives as potential anticonvulsants . The retention behavior of eleven succinimide derivatives was determined by using reversed phase high performance liquid chromatography and reversed phase high performance thin layer chromatography . The estimated retention behavior was correlated with partition log | A set of newly synthesized succinimides was analyzed by RP HPLC and RP HPTLC. Chromatographic lipophilicity ChL of the studied derivatives was determined. Correlations between their ChL and pharmacokinetic parameters were defined. Their ability to pass the blood brain barrier and other ADMET features were estimated. Some of the analyzed succinimide derivatives have high potential to become anticonvulsant candidates. |
S1476927119307972 | The tumor suppressor p53 a transcription factor plays a critical role in many cellular processes including DNA repair and apoptosis and cell cycle arrest . Missense mutations in the p53 have closely related to human cancer . R249S mutation at the p53 core DNA binding domain is frequently observed in hepatocellular carcinoma . This mutation is away from the p53 DBD DNA binding interface . However how the R249S mutation causes the structural changes of p53 DBD that lead to weak the binding of p53 mutant to DNA has not been clearly understood . Here microsecond scale molecular dynamics simulations of p53 DBD in the wild type and R249S mutated states in the absence of DNA binding were performed to explore the effect of the R249S mutation on the conformational dynamics of p53 DBD . The R249S mutation does not cause the global conformational changes and it only affects the local domains at the mutation site and the DNA binding interface particularly at the S1 S2 turn . The allosteric effects of the S1 S2 turn induced by the R249S mutation lead to the extension of the S1 S2 turn into the strands which in turn interferes with the binding of DNA at the major groove . The results can help decipher the allosteric regulatory mechanism by which the R249S mutation of p53 DBD affects the p53 DBD DNA interactions . | MD simulations were performed to explore the allosteric effect of the R249S mutation on the p53 DBD. R249S mutation allosterically affects the S1 S2 turn at the DNA binding interface. 3. The results can decipher the allosteric regulatory mechanism induced the R249S mutation. |
S1476927119308096 | MicroRNAs have been proved to play an indispensable role in many fundamental biological processes and the dysregulation of miRNAs is closely correlated with human complex diseases . Many studies have focused on the prediction of potential miRNA disease associations . Considering the insufficient number of known miRNA disease associations and the poor performance of many existing prediction methods a novel model combining gradient boosting decision tree with logistic regression is proposed to prioritize miRNA candidates for diseases . To balance positive and negative samples GBDT LR firstly adopted k means clustering to screen negative samples from unknown miRNA disease associations . Then the gradient boosting decision tree model which has an intrinsic advantage in finding many distinguishing features and feature combinations is applied to extract features . Finally the new features extracted by the GBDT model are input into a logistic regression model for predicting the final miRNA disease association score . The experimental results show that the average AUC of GBDT LR in 5 fold cross validation can achieve 0.9274 . Besides in the case studies 90 94 and 88 of the top 50 miRNAs potentially associated with colon cancer gastric cancer and pancreatic cancer were confirmed by databases respectively . Compared with the other three state of the art methods GBDT LR can achieve the best prediction performance . The source code and dataset of GBDT LR are freely available at | A combinatorial model that combines gradient boosting decision tree with logistic regression GBDT LR was proposed. Gradient boosting decision tree model has the natural advantage to discover new distinguishing features and feature combinations throughout iterative process. GBDT LR obtained AUC of 0.9274 and AUPR of 0.9014 in 5 fold cross validation. |
S1476927119308151 | For a long time the structural basis of TXA2 receptor is limited due to the lack of crystal structure information till the release of the crystal structure of TXA2 receptor which deepens our understanding about ligand recognition and selectivity mechanisms of this physiologically important receptor . In this research we report the successful implementation in the discovery of an optimal pharmacophore model of human TXA2 receptor antagonists through virtual screening . Structure based pharmacophore models were generated based on two crystal structures of human TXA2 receptor . Docking simulation revealed interaction modes of the virtual screening hits against TXA2 receptor which was validated through molecular dynamics simulation and binding free energy calculation . ADMET properties were also analyzed to evaluate the toxicity and physio chemical characteristics of the hits . The research would provide valuable insight into the binding mechanisms of TXA2 receptor antagonists and thus be helpful for designing novel antagonists . | The pharmacophores were established using newly resolved crystal structures of human thromboxane A2 receptor. Structure based virtual screening was performed to identify lead molecules with stable dynamics trajectory. Safety of the top molecules was analyzed using publicly available wares like pkCSM and SwissADME. Binding free energies of VS this were predicted using MM GBSA. |
S1476927119308692 | Octopamine is a neurotransmitter in invertebrates and a phenol analog of norepinephrine . The crystallographic and spectral characteristics of octopamine were investigated experimentally and theoretically by applying appropriate level of theory B3LYP D3BJ 6 311 G which reproduced well the experimental bond lengths and angles . The intramolecular interactions governing the stability of conformers were described by NBO and QTAIM analyses . The antiradical potencies of octopamine and norepinephrine towards DPPH | A suitable level of theory for the description of octopamine is B3LYP D3BJ 6311G d p . Additional OH group influences the scavenging reaction rates and thermodynamics. The dominant mechanism of DPPH. and ABTS. scavenging is SPLET. Additional bonds are present in 1 2 adrenergic receptors norepinephrine complex. Protein complexes have similar flexibility interatomic distances and compactness. |
S1476927119308795 | Angiotensinogen is a key component of renin angiotensin aldosterone system which plays central role in blood pressure homeostasis . Association of AGT polymorphisms have been investigated in different ethnic populations in variety of cardiovascular and non cardiovascular conditions . In this study 354 non synonymous SNPs of AGT were evaluated to predict damaging and structurally important variants . Majority of the deleterious nsSNPs occurred in the evolutionary conserved regions . Several of these nsSNPs were found to affect post translational modifications like methylation glycosylation phosphorylation ubiquitination etc . Structural evaluations predicted 19 variants as destabilizing and some of them were also predicted to destabilize the renin AGT interaction . Therefore the present computational investigation predicted pathogenic and functionally important variants of human | Highly damaging and pathogenic nsSNPs in human angiotensinogen gene are predicted. Majority of deleterious nsSNPs in human angiotensinogen are evolutionary conserved. Several nsSNPs are found to affect thermodynamic stability and post translational modifications of angiotensinogen. Various nsSNPs are found to destabilize the renin angiotensinogen interaction. Angiotensinogen deregulation is observed to impact survival in patients with gastric and breast cancer. |
S1476927119308837 | The heterocyclic aromatic compounds are primarily used to make pharmaceutical and agrochemicals . In addition these compounds can be chosen as antioxidants corrosion inhibitors electro and opto electronic devices polymer material dye stuff developers etc . On the account of this the heterocyclic aromatic 6 nitro 2 3 dihydro 1 4 benzodioxine was chosen and the structure is optimized to predict the important properties of it . The structural parameters such as bond length and bond angle have been obtained by DFT B3LYP 6 311 G basis set to know the geometry and orientation of 6N3DB . The molecule has been characterized by FT IR and FT Raman spectroscopic techniques to predict the functional groups vibrational modes and aromatic nature of 6N3DB . The chemical shifts of | Molecular docking has been performed for the biological activity of 6N3DB. Vibrational studies were performed to know chemically active atoms of 6N3DB. HOMO LUMO has been explained for NLO corrosion inhibition and electronic properties. ELF LOL RDG have been visualized and steric vdW intramolecular interactions are explained. |
S147692711930893X | Stearyl coenzyme A desaturase enzyme 1 is a key enzyme that catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids and plays a vital role in lipid metabolism of tumor cells . SCD1 is overexpressed in a variety of malignant tumors and its related inhibitors showed significant anti tumor activity | Crucial protein ligand interactions of SCD1 receptor antagonists were elucidated. TCMNP ACDNP and IBSNP databases were screened for SCD1 receptor antagonists. MD simulation binding free energy calculation and ADMET prediction were applied to evaluate the virtual screening hits. |
S1476927119309107 | The electron conformational genetic algorithm method had been employed by distinguishing between enantiomers for the first time as a 4D QSAR approach to reveal the pharmacophore and to predict the bioactivity of the dipeptidyl boron compounds . | The biological activities of the stereoisomers of dipeptidyl boron derivatives were successfully distinguished for the first time. EC GA method is capable of distinguishing between the stereoisomers including both enantiomers and diastereomers. The compound 99 which is the diastereomer of 27 is a promising candidate for future studies of more potent proteasome inhibitors. |
S1476927119309181 | With the application of new high throughput sequencing technology a large number of protein sequences is becoming available . Determination of the functional characteristics of these proteins by experiments is an expensive endeavor that requires a lot of time . Furthermore at the organismal level such kind of experimental functional analyses can be conducted only for a very few selected model organisms . Computational function prediction methods can be used to fill this gap . The functions of proteins are classified by Gene Ontology which contains more than 40 000 classifications in three domains Molecular Function Biological Process and Cellular Component . Additionally since proteins have many functions function prediction represents a multi label and multi class problem . We developed a new method to predict protein function from sequence . To this end natural language model was used to generate word embedding of sequence and learn features from it by deep learning and additional features to locate every protein . Our method uses the dependencies between GO classes as background information to construct a deep learning model . We evaluate our method using the standards established by the Computational Assessment of Function Annotation and have noticeable improvement over several algorithms such as FFPred DeepGO GoFDR and other methods compared on the CAFA3 datasets . | DeepAdd is proposed to predict protein functions using a deep convolutional neural network CNN framework. DeepAdd utilizes a Word2Vec method on defining the set of features to represent a protein. DeepAdd consists of two CNN models with multiple convolution blocks that map the presented protein sequence to two feature vectors representation. One feature representation is for the sequence similarity profile by SSP model. The other feature representation is the PPI network by PPI model. |
S1476927119309211 | The resistances of matrix protein 2 protein inhibitors and neuraminidase inhibitors for influenza virus have attracted much attention and there is an urgent need for new drug . The antiviral drugs that selectively act on RNA polymerase are less prone to resistance and possess fewer side effects on the patient . Therefore there is increased interest in screening compounds that can inhibit influenza virus RNA polymerase . Three natural compounds were found by using molecular docking based virtual screening which could bind tightly within the polymerase acidic protein polymerase basic protein 1 subunit of influenza virus polymerase . Firstly their drug likeness properties were evaluated which showed that the hepatotoxicity values of all the three compounds indicating they had less or no hepatotoxicity and did not have the plasma protein biding ability the three compounds needed to be modified in some aspects like bulky molecular size . The stability of the complexes of PA hits was validated through molecular dynamics simulation revealing compound | Structure based virtual screening was performed to discover influenza virus polymerase inhibitors. Three natural compounds were identified to potentially block the interaction of PA PB1 subunit of influenza virus polymerase. The three compounds showed less or no hepatotoxicity nor plasma protein biding PPB ability. The stability of the complexes of PA hits was validated through molecular dynamics MD simulation. Four key residues of PA subunit participating in the interactions were revealed. |
S1476927119309223 | Obstructive sleep apnoea is a prevalent form of sleep disordered breathing which results in sleep fragmentation and deprivation . Obesity and cardiovascular disorders are the major risk factors associated with OSA . Molecular analysis of the factors associated with OSA could demarcate the clinical analysis pattern in a population . This study pertains to miRDB TargetScan and miRanda databases were used to identify targets of miR 27 and let 7 that have documented role in OSA and co related obesity and cardiovascular disorders . Quantitative PCR was used to analyze expression pattern of miR 27 and let 7 in obese and non obese OSA patient cohorts with respective controls . Downregulation of miR 27 and let 7 in OSA compared to controls was observed . Our study gives insights to the expression profiling of miR 27 and let 7 and explore a set of potential target genes of these two miRNAs for a promising clinical relevance in OSA . | Downregulation of miR 27 and let 7 in OSA. Prediction of miRNA secondary structures. Molecular docking of miRNA and their target genes. CNR1 and CRY2 are better targets for miR 27 and let 7 respectively. Differential expression of miRNA target genes in OSA compared to healthy. |
S1476927119309338 | The underlying molecular characteristics of osteoarthritis a common age related joint disease remains elusive . Here we aimed to identify potential early diagnostic biomarkers and elucidate underlying mechanisms of OA using weighted gene co expression network analysis . We obtained the gene expression profile dataset GSE55235 GSE55457 and GSE55584 from the Gene Expression Omnibus . WGCNA was used to investigate the changes in co expressed genes between normal and OA synovial membrane samples . Modules that were highly correlated to OA were subjected to functional enrichment analysis using the R clusterProfiler package . Differentially expressed genes between the two samples were screened using the limma package in R. A Venn diagram was constructed to intersect the genes in significant modules and DEGs . RT PCR was used to further verify the hub gene expression levels between normal and OA samples . The preserved significant module was found to be highly associated with OA development and progression We identified 13 hub genes correlated to the development and progression of OA which may provide new biomarkers and drug targets for OA . | WGCNA was employed to identify highly correlated gene modules associated with OA synovial membrane. The genes in significant module were enriched in the FoxO signaling pathway and the metabolism of fatty acids and 2 oxocarboxylic acid. 13 hub genes correlated to the development and progression of OA were identified. |
S1476927119309466 | Thyroid carcinoma is one of the most frequent endocrine cancers and has increasing morbidity . Annexin A2 has been found to be highly expressed in various cancers however its expression level and potential mechanism in THCA remain unknown . This study investigated the clinicopathological value and primary molecular machinery of ANXA2 in THCA . Public RNA sequencing and microarray data were obtained and analyzed with ANXA2 expression in THCA and corresponding non cancerous thyroid tissue . A Pearson correlation coefficient calculation was used for the acquisition of ANXA2 coexpressed genes while edgR limma and Robust Rank Aggregation were employed for differentially expressed gene in THCA . The probable mechanism of ANXA2 in THCA was predicted by gene ontology and pathway enrichment . A dual luciferase reporter assay was employed to confirm the targeting relationships between ANXA2 and its predicted microRNA . Expression of ANXA2 was significantly upregulated in THCA tissues with a summarized standardized mean difference of 1.09 based on 992 THCA cases and 589 cases of normal thyroid tissue . Expression of ANXA2 was related to pathologic stage . Subsequently 1442 genes were obtained when overlapping 4542 ANXA2 coexpressed genes with 2248 DEGs in THCA these genes were mostly enriched in pathways of extracellular matrix receptor interaction cell adhesion molecules and complement and coagulation cascades . MiR 23b 3p was confirmed to target ANXA2 by dual luciferase reporter assay . Upregulated expression of ANXA2 may promote the malignant biological behavior of THCA by affecting the involving pathways or being targeted by miR 23b 3p . | Significant upregulation of ANXA2 expression is evidenced in thyroid carcinoma by multiple detecting approaches. Upregulated ANXA2 is strongly related to the development of thyroid carcinoma. ANXA2 coexpressed genes are mostly enriched in the pathway of extracellular matrix receptor interaction. ANXA2 is a target of miR 23b 3p in thyroid carcinoma. |
S1476927119309624 | Calreticulin is localized to and has functions in multiple cellular compartments including the cell surface the endoplasmic reticulum and the extracellular matrix . Mutagenesis studies have identified several residues on a concave sheet surface of CRT critical for CRT binding to carbohydrate and other proteins peptides . How the mutations of these key residues in CRT affect the conformation and dynamics of CRT further influencing CRT binding to carbohydrates and other proteins to signal the important biological activities remain unknown . In this study we investigated the effect of three key point mutations on CRT conformation and dynamics via atomistic molecular dynamics simulations . Results show that these three key residues mutations induced the changes of CRT local backbone flexibility and secondary structure of CRT N domain which could further affect CRTs binding activity . C137A mutation led to dramatic decrease of the overall size of CRT due to the P domain fold back to the globular domain and formed new inter domain contacts which can cause blockage of CRTs binding with other large substrates . Furthermore for CRT concave strand surface patch containing lectin binding site CRT C105A C137A and W319A point mutation resulted in the changes in solvent accessible surface area key residues side chain atom positions and dynamical correlated motions between residues . All these changes could directly affect CRT binding behavior . Results of this study provide molecular and structural insights into understanding the role of key residues of CRT in its binding behavior . | Calreticulin CRT C105A C137A and W319A mutations changed local backbone flexibility and secondary structure. C137A mutation decreased overall size of CRT and formed new inter domain contacts. C105A C137A and W319A mutations changed dynamical correlated motions between residues of CRT. |
S1476927119309831 | the primary causative agent of bacterial panicle blight in rice has been reported as an opportunistic pathogen in patients with chronic infections . This study aimed to re sequence the clinical isolate | Genome of. strain AU6208 was re sequenced. The genome size of strain AU6208 was revealed higher than previous version. Specialty genes including virulent genes were identified. The toxoflavin genes resourced from strain AU6208 have variation compared to strain BGR1. Proteins structural variations were noted among both strains |
S1476927119309909 | Biomarkers are important in the study of tumor processes for early detection and precise treatment . The biomarkers that have been previously detected are not useful for clinical application for primary colorectal carcinoma . The aim of this study was to explore clinically valuable biomarkers of PCRC based on integrated bioinformatic analysis . Gene expression data were acquired from the GSE41258 dataset and the differentially expressed genes were determined between PCRC and normal colorectal samples . Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were implemented via Gene Set Enrichment Analysis . A protein protein interaction network was constructed . The significant modules and hub genes were screened and identified in the PPI network . A total of 202 DEGs were identified including 58 upregulated and 144 downregulated genes in PCRC samples compared to those in normal colorectal samples . Enrichment analysis demonstrated that the gene sets enriched in PCRC were significantly related to bicarbonate transport regulation of sodium ion transport potassium ion homeostasis regulation of telomere maintenance and other processes . A total of 10 hub genes was identified by cytoHubba PYY CXCL3 CXCL11 CXCL8 CXCL12 CCL20 MMP3 P2RY14 NPY1R and CXCL1 . The hub genes such as NPY1R P2RY14 and CXCL12 and the electrolyte disequilibrium resulting from the differential expression of genes especially bicarbonate imbalance may provide novel insights and evidence for the future diagnosis and targeted therapy of PCRC . | The DEGs between PCRC and normal colorectal samples were screened. The DEGs were mainly enriched in extracellular matrix organization bicarbonate transport and cellular response to lipid. Ten hub genes were identified via cytoHubba PYY CXCL3 CXCL11 CXCL8 CXCL12 CCL20 MMP3 P2RY14 NPY1R and CXCL1. The hub genes might provide a new perspective to better understand pathogenesis of PCRC. |
S147692711931000X | In this study the network pharmacology analysis method was used to explore the bioactive components and targets of Xianlinggubao and further elucidate its potential biological mechanisms of action in the treatment of osteoporosis . The bioactive compounds and predictive targets of XLGB were collected from the traditional Chinese medicine systems pharmacology databases and analysis platform the Encyclopeida of traditional Chinese medicine traditional Chinese medicine | Identify bioactive components and targets of Xianlinggubao XLGB. Seek common targets for XLGB against Osteoporosis. Understand the underlying action mechanisms of the common targets. |
S1476927119310011 | As part of the type I IFN signaling the 2 5 oligoadenylate synthetase proteins have been involved in the progression of several non viral diseases . Notably OAS has been correlated with immune modulatory functions that promote chronic inflammatory conditions autoimmune disorders cancer and infectious diseases . In spite of this OAS enzymes have been ignored as drug targets and to date there are no reports of compounds that can inhibit their activity . In this study we have used homology modeling and virtual high throughput screening to identify potential inhibitors of the human proteins OAS1 OAS2 and OAS3 . Altogether we have found 37 molecules that could exert a competitive inhibition in the ATP binding sites of OAS proteins independently of the activation state of the enzyme . This latter characteristic which might be crucial for a versatile inhibitor was observed in compounds interacting with the residues Asp75 Asp77 Gln229 and Tyr230 in OAS1 and their equivalents in OAS2 and OAS3 . Although there was little correlation between specific chemical fragments and their interactions intermolecular contacts with OAS catalytic triad and other critical amino acids were mainly promoted by heterocycles with electrons and hydrogen bond acceptors . In conclusion this study provides a potential set of OAS inhibitors as well as valuable information for their design development and optimization . | Although OAS proteins exert an antiviral role they are also involved in the progression of several non viral diseases. OAS acts as an immune modulator in chronic inflammatory conditions autoimmune disorders cancer and infectious diseases. OAS enzymes have been ignored as drug targets and to date there are no compounds that can inhibit their activity. We found 37 molecules that could compete for the ATP binding sites of OAS regardless of the activation state of the enzyme. Potential OAS inhibitors are provided as well as valuable information for their design development and optimization. |
S1476927119310035 | Identifying significant protein groups is of great importance for further understanding protein functions . This paper introduces a novel three phase heuristic method for identifying such groups in weighted PPI networks . In the first phase a variable neighborhood search algorithm is applied on a weighted PPI network in order to support protein complexes by adding a minimum number of new PPIs . In the second phase proteins from different complexes are merged into larger protein groups . In the third phase these groups are expanded by a number of 2 level neighbor proteins favoring proteins that have higher average gene co expression with the base group proteins . Experimental results show that the proposed VNS algorithm outperforms the existing approach described in literature and the above mentioned three phase method identifies protein groups with very high statistical significance . | A novel variable neighborhood search heuristic approach for supporting known complexes in weighted PPI networks by integrating data from different sources PPI networks protein complexes and gene co expression. The proposed approach efficiently searches the overall searching space and is a successful method for solving both artificial and large real PPI networks. The proposed three phase method revealed meaningful protein groups with high enrichment scores which previously were not interconnected in PPI networks. Grouping the proteins in PPI networks in the described way may help to understand their intrinsic structures and functions. |
S1476927119310072 | Seasonal and pandemic influenza infections are serious threats to public health and the global economy . Since antigenic drift reduces the effectiveness of conventional therapies against the virus herbal medicine has been proposed as an alternative . | Seasonal and pandemic influenza infections are serious threats to public health. Computational research serves as a time saving alternative to the experimental research that yields promising compounds and targets. A network pharmacology based strategy was used to predict potential compounds and target genes from Fritillaria thunbergii FT against influenza. Compound target C T Compound Disease Target C D protein protein interaction PPI and Compound Disease Target Pathway C D P networks were constructed to analyze FTs effect against influenza. Network analyses predicted two compounds beta sitosterol and pelargonidin derived from FT that may be potent candidates for influenza treatment. |
S1476927119310114 | Accumulating studies have indicated that long non coding RNAs play crucial roles in large amount of biological processes . Predicting lncRNA disease associations can help biologist to understand the molecular mechanism of human disease and benefit for disease diagnosis treatment and prevention . In this paper we introduce a computational framework based on graph autoencoder matrix completion to identify lncRNA disease associations . In our method the graph convolutional network is utilized to encode local graph structure and features of nodes for learning latent factor vectors of lncRNA and disease . Further the inner product of lncRNA factor vector and disease factor vector is used as decoder to reconstruct the lncRNA disease association matrix . In addition the cost sensitive neural network is utilized to deal with the imbalance between positive and negative samples . The experimental results show GAMLDA outperforms other state of the art methods in prediction performance which is evaluated by AUC value AUPR value PPV and F1 score . Moreover the case study shows our method is the effectively tool for potential lncRNA disease prediction . | We introduce a graph autoencoder matrix completion to predict associations between lncRNAs and diseases. The imbalance between positive and negative tackled by the cost sensitive neural networks. The experimental results show our method outperforms than other state of the art methods in prediction performance. |
S1476927119310254 | Tripeptidyl peptidase II is primarily considered a house keeping exopeptidase which contributes to the functions of the ubiquitin proteasome system by the maintenance of the cellular amino acid homeostasis . Although functionally well characterised | The identification of the molecular mechanisms driving TPP2 interaction network. Adaptive and innate immunity ID Kit Receptor BCR IL 2 G CSF and NFB signalling . Aerobic glycolysis ID and IL 2 signalling . Tumorigenesis TGF. and p53 signalling MAPKs the control of mTOR . Potential functional link to lung cancer pathology. |
S1476927119310357 | With the development of cancer research various gene expression datasets containing cancer information show an explosive growth trend . In addition due to the continuous maturity of single cell RNA sequencing technology the protein information and pedigree information of a single cell are also continuously mined . It is a technical problem of how to classify these high dimensional data correctly . In recent years Extreme Learning Machine has been widely used in the field of supervised learning and unsupervised learning . However the traditional ELM does not consider the robustness of the method . To improve the robustness of ELM in this paper a novel ELM method based on | Based on L. norm a robust Extreme Learning Machine method called L. ELM is proposed. Various benchmark datasets downloaded from the UCI database and some image datasets are used to train and test the model. The proposed L. ELM is applied to the classification of cancer samples and single cell data. The proposed method not only inherits the advantages of original ELM such as easy implementation and fast speed but also shows better generalization performance. |
S1476927119310680 | Partner and localizer of BRCA2 is regarded as a colorectal cancer risk gene but the prognostic implication of PALB2 in CRC remains unclear . In this study we evaluate the prognostic value of the gene copy number alteration and mRNA expression of PALB2 in The Cancer Genome Atlas database and then validated with our database . We downloaded the copy number and mRNA data of PALB2 from TCGA database and examined the relationship among the genetic alterations expression levels and survival outcomes . Gene ontology analysis was performed to study the function of PALB2 . cBioPortal database was used to explore the potential co expression genes of PALB2 . There were 6.3 CRC patients diagnosed as PALB2 gene deletion . The PALB2 deletion group expressed significantly lower of PALB2 mRNA than the non deletion group | We evaluated the prognostic value of PALB2 gene in colorectal cancer. PALB2 gene could be novel prognostic biomarkers for colorectal cancer. Function analyses showed that PALB2 is primarily involved in the DNA repair process. |
S1476927119310710 | Cell wall lytic enzymes as an important biotechnical tool in drug development agriculture and the food industry have attracted more research attention . In this research the accurate identification of cell wall lytic enzymes is one of the key and fundamental tasks . In this study in order to eliminate the inefficiency of in vitro experiments a support vector machine based cell wall lytic enzyme identification model was constructed using bioinformatics . This machine learning process includes feature extraction feature selection model training and optimization . According to the jackknife cross validation test this model obtained a sensitivity of 0.853 a specificity of 0.977 an MCC of 0.845 and an AUC of 0.915 . These benchmark results demonstrate that the proposed model outperforms the state of the art method and that it has powerful cell wall lytic enzyme identification ability . Furthermore we comprehensively analyzed the selected optimal features and used the proposed model to construct a user friendly web server called the CWLy SVM to identify cell wall lytic enzymes which is available at | We identified cell wall lytic enzymes in bioinformatic way to overcome inefficiency of in vitro experiments and provide a website tool by wrapping the proposed model. Our proposed model outperforms the state of the art method in jackknife cross validation test. We comprehensively analyzed the optimal feature set of proposed model from the prospective of data and biological meaning. |
S1476927119310886 | One of the hallmarks of Parkinsons disease a long term neurodegenerative syndrome is the accumulation of alpha synuclein fibrils . Despite numerous studies and efforts inhibition of syn protein aggregation is still a challenge . To overcome this issue we propose an | The first report to identify drugs for repositioning against alpha synuclein aggregation inhibition. 3D ligand based pharmacophore model for alpha synuclein inhibition developed. Key pharmacophore features consist of three HBD two HBA and two AR. New compounds identified as potential alpha synuclein inhibitors. |
S1476927119310904 | Preterm birth defined as a delivery before 37 weeks gestation continues to affect 815 of all pregnancies and is associated with significant neonatal morbidity and mortality . Effective prediction of timing of delivery among women identified to be at significant risk for preterm birth would allow proper implementation of prophylactic therapeutic interventions . This paper aims first to develop a model that acts as a decision support system for pregnant women at high risk of delivering prematurely before having cervical cerclage . The model will predict whether the pregnancy will continue beyond 26 weeks gestation and the potential value of adding the cerclage in prolonging the pregnancy . The second aim is to develop a model that predicts the timing of spontaneous delivery in this high risk cohort after cerclage . The model will help treating physicians to define the chronology of management in relation to the risk of preterm birth reducing the neonatal complications associated with it . Data from 274 pregnancies managed with cervical cerclage were included . 29 of the procedures involved multiple pregnancies . To build the first model a data balancing technique called SMOTE was applied to overcome the problem of highly imbalanced class distribution in the dataset . After that four classification models namely Decision Tree Random Forest K Nearest Neighbors | Machine learning models are developed to predict of preterm birth for women with cervical cerclage. Data from 274 pregnancies managed with cervical cerclage are used. Model predicts whether the pregnancy will continue beyond 26 weeks gestation. |
S1476927119310928 | The nickel nanoparticles are harmful atmospheric pollutants and the damage caused by them in humans has become a topic of great relevance . In this study we investigate the interaction of the Ni | Nickel nanoparticles Ni. and Ni. are harmful atmospheric pollutants which damage humans. Quantum molecular simulations for the molecular system under realistic thermodynamic conditions NVT are performed. The results show the formation of stable organometallic compounds of the Ni nanoparticles with the DNA nucleic acid bases. The organometallic compounds may be a factor in the development of diseases for the people exposed to the Ni nanoparticles. |
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