**2. Experimental**

Coatings are being developed with a nanolayer architecture, characterized by a

number of significant advantages compared to traditional monolithic coatings [3, 6–8]. In particular, the studies detect improved crack and impact resistance of the coatings with a nanolayer architecture [9–13]. The influence of a nanolayer structure of the coating on its tribological properties is of great importance. The studies have found that the coatings with a nanolayer structure are characterized by a reduced COF, high hardness, and a low level of residual stresses [6], while with a decrease in a thickness of the binary nanolayer λ, the COF decreases and the wear resistance increases [8]. The investigation has also demonstrated that a decrease in the nanolayer period λ leads to an increase in hardness, a decrease in the

*Tribology in Materials and Manufacturing - Wear, Friction and Lubrication*

COF, and an improvement in the resistance to the failure of cohesive bonds between nanolayers [14–17]. In particular, in [15], the studies of the TiAlCN/VCN nanostructured coating with λ = 2.2 nm have found that for this coating, the COF grows with an increase in temperature up to 200°C, but begins to decrease at temperatures above 650°C. The experiments found a decrease in the COF for the CrAlYN/CrN nanolayer coating with λ = 4.2 nm with an increase in temperature up to 650°C [16]. The study of the Ti/TiAlN/TiAlCN nanolayer coating detected its low COF and high wear resistance [17]. The tribological properties of the TiAlN/CNx nanostructured coating with λ = 7 nm were considered in [18]. The tests have found that the TiAlN/CNx nanostructured coating is characterized by small grain sizes and lower surface roughness in comparison with a monolithic coating of a similar

composition and also by a lower COF and higher wear resistance.

temperature and 0.6–0.7 – at a temperature of 550°C.

decrease with a further increase in temperature;

• for coated products, the COF varies significantly with an increasing

• in general, the above variation of the COF is initially characterized by its

• the parameters of the nanolayer structure (in particular, the value of the nanolayer period λ) have a noticeable influence on the COF variation.

gradual increase with a growth of temperature and then by its more significant

Thus, it can be asserted that:

temperature;

**152**

The influence of the elemental composition of the coatings on their tribological properties was also investigated. The experiments revealed the COF value at room temperature for the coatings of TiN (0.55), TiCN (0.40), TiAlN (0.50), AlTiN (0.7), as well as AlTiN/Si3N4 consisting of AlTiN nanoparticles embedded into amorphous Si3N4 matrix (0.45) [19]. During the studies focused on the TiAlCrN/ TiAlYN and TiAlN/VN coatings, Hovsepian et al. [20] found that the introduction of Y in the coating composition led to a decrease in the COF from 0.9 up to 0.65 during the tests conducted at temperatures ranging from 850 to 950°C. For the TiAlCrN coating, the COF was 1.1–1.6 (at temperatures of 600–900°C), while for the TiAlN/VN coating, the COF was 0.5 (at 700°C). Mo et al. [21] found that the COF of the AlCrN and TiAlN coatings was 0.75 and 0.85, respectively. With an increase in the Cr content in the CrAlN coating, a slight increase in the COF was detected [22]. Nohava et al. [23] studied the properties of the AlCrN, AlCrON, and α-(Al,Cr)2O3 coatings in comparison with the properties of the TiN-AlTiN reference coating at temperatures of 24, 600, and 800°C. The maximum value of the COF was detected at a temperature of 600°C for all the studied samples, while at a temperature of 800°C, there was a significant decrease in the COF (to 0.6–0.8) to the values lower than those detected at a room temperature (0.3–0.5). Bao et al. [24] found that for the TiCN/TiC/TiN coating, the COF was 0.4–0.5 at a room


**Author details**

**3. Meniett device**

170 Up to Date on Meniere's Disease

pressure in the middle ear.

**4. Vestibular rehabilitation**

stabilized vestibular function [44].

consequences that have been promoted.

**5. Conclusion**

H2

During the decade of 1970, the demand for a more effective and a nondestructive method for the treatment of MD, Inglestad et al. [41] observed that some patients reported improvement with changes of pressure in a pressure chamber. Densert et al. [42] showed that the manipulation of the middle ear pressure influences the pressure in the inner ear; later, improved hearing and dizziness in patients with MD were described after the application of positive

Additionally, there was improvement of the cochlear electrical potentials after administration of positive pressure in the middle ear, which finally led to the development of the device

The Meniett device emits a pulse of repeated pressure of 0.6 second in the range of 0–20 cm

The FDA approved the use of the device in 2002, demand is still low, despite recent work showing the effectiveness of the device. Meniett reduces the frequency of dizziness in patients with Meniere's disease activity, an improvement of AAO-HNS Meniere's disease functional level scale, but the device does not significantly improve hearing, showing a safe option for

Vestibular rehabilitation is a form of body and eye movement stimulation therapy designed to improve vestibular function and mechanisms of central adaptation and compensation. It is mainly useful to treat the MD squeal; vestibular adaptation exercises to prevent falls have proven to be particularly effective. This type of treatment is quite effective for patients with

Treatments in Meniere's disease are generally aimed at reducing the acute symptomology vertiginous episodes. The cure currently does not exist. To date, the treatment has convincingly been shown to be effective in altering the natural course of the disease, thereby preventing end organ damage, which results in hearing loss and vestibular impairment. The clinical spectrum of the disease of Meniere's symptoms is wide, with the possibility of remission and recurrence of symptoms, and even fairly unfavorable developments, with irreversible hearing loss and damage the vestibular function. A good treatment must be individualized for each patient, taking into consideration these possibilities, the stage of disease, and the possible

O at 6 Hz. Treatment consists of three to four cycles of a sequence of treatment of 5 min, this device requires only a short-term ventilation tube (Sheppard) to allow the transmission

known as the Meniett (Medtronic Xomed Surgical Products, Jacksonville, FL).

of impulses in an auditory external pressure to the middle ear.

patients with refractory diseases to the conventional treatments [43].

Eduardo Amaro Bogaz1,2\*, André Freitas Cavallini da Silva1 , Davi Knoll Ribeiro1 and Gabriel dos Santos Freitas1

2 Department of Otology and Neurotology, São Camilo Hospital, São Paulo, Brazil

## **References**

[25] Burneo JG, Montori VM, Faught E. Magnitude of the placebo effect in randomized trials of antiepileptic agents. Epilepsy & Behavior. 2002;**3**(6):532-534

[11] Burgess A, Kundu S. Diuretics for Ménière's disease or syndrome. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003599. DOI: 10.1002/14651858.CD003599.

[12] Lacour M, Sterkers O. Histamine and betahistine in the treatment of vertigo: Elucidation

[13] Van Cauwenberge PB, De Moor SE. Physiopathology of H3-receptors and pharmacol-

[14] Mira E, Guidetti G, Ghilardi L, Fattori B, Malannino N, Maiolino L, et al. Betahistine dihydrochloride in the treatment of peripheral vestibular vertigo. European Archives of

[15] Lezius F, Adrion C, Mansmann U, Jahn K, Strupp M. High-dosage betahistine dihydrochloride between 288 and 480 mg/day in patients with severe Meniere's disease: A case

[16] Adrion C, et al. Efficacy and safety of betahistine treatment in patients with Meniere's disease: Primary results of a long term, multicentre, double blind, randomised, placebo

[17] James A, Burton MJ. Betahistine for Ménière's disease or syndrome. Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No.: CD001873. DOI: 10.1002/14651858.CD00

[18] Ganança MM, Munhoz MSL, Caovilla HH, Silva MLG. Managing vertigo. Hannover: Solvay; 2006/Clostre F. Ginkgo biloba extract (egb761): State of knowledge in the dawn

of the year 2000. Annales Pharmaceutiques Francaises. 1999;**57**(Suppl 1):1S8-188.

[19] Ganança MM, Munhoz MSL, Caovilla HH, Silva, MLG. Managing vertigo. Hannover: Solvay; 2006/Cesarani A, Meloni F, Alpini D, Barozzi S, Verderio L, Boscani PF. Ginkgo biloba (egb 761) in the treatment of equilibrium disorders. Advances in Therapy. 1998;**15**(5):291-304 [20] Chi FL, Yang MQ, Zhou YD, Wang B. Therapeutic efficacy of topical application of dexamethasone to the round window niche after acoustic trauma caused by intensive impulse noise in guinea pigs. Journal of Laryngology and Otology. 2011;**125**(7):673-685

[21] She W, Lv L, Du X, Li H, Dai Y, Lu L, Ma X, Chen F. Long-term effects of intratympanic methylprednisolone perfusion treatment on intractable Ménière's disease. The Journal

[22] Boleas-Aguirre MS, Lin FR, Della Santina CC, Minor LB, Carey JP. Longitudinal results with intratympanic dexamethasone in the treatment of Ménière's disease. Otology &

[23] Phillips JS, Westerberg B. Intratympanic steroids for Ménière's disease or syndrome.

[24] Schuknecht HF. Ablation therapy for the relief of Meniere's disease. Laryngoscope.

controlled, dose defining trial (BEMED trial). British Medical Journal. 2016;**352**

ogy of betahistine. Acta Oto-laryngologica Supplementum. 1997;**526**:43-46

series. European Archives of Oto-rhino-laryngology. 2011;**268**:1237-1240

of mechanisms of action. CNS Drugs. 2001;**15**:853-870

Oto-Rhino-Laryngology. 2003;**260**(2):73-77

of Laryngology & Otology. 2015;**129**:232-237

Cochrane Database of Systematic Reviews. 2011;**6**(7)

Neurotology. 2008;**29**(1):33-38

1956;**66**:859-870

pub2. 1-14

172 Up to Date on Meniere's Disease

1873. 1-11


**1. Introduction**

Malaria is one of the major threats to human health, affecting an estimated number of 216 million peoples in 2016 all over the world, leading to 445,000 deaths, mainly in the African continent [1]. The human malaria is caused by six different species of the genus *Plasmodium*, which are *P. falciparum, P. vivax, P. ovale, P. malariae, Plasmodium knowlesi* and *P. simium,* where the last one is exclusive to the Brazilian Atlantic Forest [2].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Plasmodium* was first described in 1880 by Laveran, who observed it in human erythrocytes. In human *Plasmodium* genus, the life cycle is very similar between species, being characterized by a sexual phase in vector *Anopheles* and an asexual phase in the human host that can be divided into liver phase and intraerythrocytic phase [3] (**Figure 1**).

are triggered without cytokinesis, forming schizonts. Each schizont holds an average of 32 merozoites (10 merozoites in average for *P. knowlesi* [7]) that are unleashed upon the RBC lysis. The whole process can take about 36–48 h in *P. falciparum*, 48 h in *P. vivax* and can reach even 72 h in *P. malariae*, but in *P. knowlesi* the cycle is 24 h, which is one factor that leads to its high virulence in humans [8]. Cell lysis coincides with fever symptoms, a response of immune system to the

Terpenes as Potential Antimalarial Drugs http://dx.doi.org/10.5772/intechopen.75108 41

Within the red blood cells, the parasite can follow another path of development, differentiating into gametocytes. During a blood meal in an infected individual, the *Anopheles* female ingests those gametocytes. In the female of the *Anopheles* mosquito the parasite undergoes a meiotic division. Inside the mosquito gut, the gametocytes mature to form male and female gametes. The gametes undergo fertilization, forming the zygote, which transforms into an ookinete. The ookinete then penetrates the midgut and installs itself developing into oocyst. Under multiple cellular divisions, thousands of sporozoites are formed, which migrate to the salivary glands of the mosquito, to get expelled with anticoagulant factor contained in saliva

Although *P. vivax* is the most prevalent parasite in the world, *P. falciparum* is responsible for most cases of severe malaria, being the most prevalent malarial parasite in the African continent, which accounts for 80% of the global disease burden. The groups with higher risk of malaria disease includes pregnant women, patients with HIV/AIDS, infants and children under 5 years old, whereas *P. falciparum* is responsible for about 70% of the malaria-related deaths. Although a lot of efforts have been made aiming to eradicate malaria, the World Health Organization (WHO) strives to reduce the mortality rates and malaria cases in 90% up to the year of 2030 [11]. The acquired drug resistance of the parasite continues to be a struggle

The resistance to antimalarial drugs is due to the indiscriminate use of the drugs and its incorrect use in treatment of malaria cases, such as wrong dosage, drug quality problems, erroneous diagnosis, not sticking to treatment, and others. These are characterized as treatment failure but can lead to a strong selective pressure in parasites, resulting in drug resistance. In recent years, with the emergence of artemisinin derivatives, resistance has allowed the number of cases to grow fast, especially in East Asia. Artemisinin, a sesquiterpene lactone, and its derivatives were adopted in the early 2000s as a first-line treatment in combined therapy for *P. falciparum* [12]. Artemisinin and its derivate can clear early trophozoites (ring stage), but the drug has a short span in vertebrate organisms, making it necessary to combined it with other drugs. In countries where *P. vivax* is the main malaria transmitter, the first-line treatment remains using chloroquine and primaquine, although WHO suggests that changes must be made to artemisininbased combined therapy (ACT) when the rate of chloroquine resistance have reached more than 10%. Some strategies have been adapted to control malaria, such as vector control; insecticide-treated bed nets, indoor residual spraying, preventive treatment for pregnant women, and rapid diagnosis and treatment of infected individuals [1, 12, 13]. But considering the fast acquirement of resistance by parasites and vectors to drugs and insecticides, respectively, the development of an effective vaccine turns out to be an important issue. However *Plasmodium* species, especially *P. falciparum*, has a highly variant antigen pool, responsible for the adhesion

liberation of hemozoin and other parasite products into the bloodstream [9].

during the next blood meal, restarting the cycle [10] (**Figure 1**).

in the fight against the disease, which led to rising of malaria-related death.

The cycle begins with the injection of infective sporozoites of salivary glands of *Anopheles* into the human host bloodstream. Once there, the sporozoites make their way into the liver, where they infect hepatocytes to start the first massive replication, an asexual process, known as exoerythrocytic schizogony. After 9–16 days, those new-formed merozoites are then released into the bloodstream in hepatocyte-derived vesicles [4], called merosomes, to avoid its capture by Kupffer cell. This liver endures this phase differently across different species which can last an average of 6 days (*P. falciparum*), 10 days (*P. vivax*), or 15 days (*P. ovale* and *P. malariae*) [5].

In the bloodstream, the merosomes are then disrupted liberating the merozoites, each merozoite infecting a single red blood cell (RBC). The process of invasion is complex, relying on diverse cell machineries, which permit the parasite to attach, reorientate, and invade, forming the parasitophorous vacuole [6]. Once in the erythrocyte, the parasite starts its asexual division, passing through different stages. The early trophozoite, called "ring stage", starts to develop, enlarging to a mature trophozoite that has a high metabolic index. In the late stage, multiple nuclear divisions

**Figure 1.** Malaria parasite life cycle. Schematic life cycle of *P. falciparum* in the invertebrate (left) and vertebrate hosts (right). 1. Hepatocytes invasion and exoerythrocytic schizogony to merozoites formation. 2. Release of merosomes in the blood stream. 3. Intraerythrocytic phase. 4. Parasite differentiation to gametocytes which ones could be ingested by invertebrate host. 5. Sexual phase in the midgut of invertebrate host. 6. Migration of sporozoites into salivary glands. 7. Injection of sporozoites during the blood meal.

are triggered without cytokinesis, forming schizonts. Each schizont holds an average of 32 merozoites (10 merozoites in average for *P. knowlesi* [7]) that are unleashed upon the RBC lysis. The whole process can take about 36–48 h in *P. falciparum*, 48 h in *P. vivax* and can reach even 72 h in *P. malariae*, but in *P. knowlesi* the cycle is 24 h, which is one factor that leads to its high virulence in humans [8]. Cell lysis coincides with fever symptoms, a response of immune system to the liberation of hemozoin and other parasite products into the bloodstream [9].

*Plasmodium* was first described in 1880 by Laveran, who observed it in human erythrocytes. In human *Plasmodium* genus, the life cycle is very similar between species, being characterized by a sexual phase in vector *Anopheles* and an asexual phase in the human host that can be

The cycle begins with the injection of infective sporozoites of salivary glands of *Anopheles* into the human host bloodstream. Once there, the sporozoites make their way into the liver, where they infect hepatocytes to start the first massive replication, an asexual process, known as exoerythrocytic schizogony. After 9–16 days, those new-formed merozoites are then released into the bloodstream in hepatocyte-derived vesicles [4], called merosomes, to avoid its capture by Kupffer cell. This liver endures this phase differently across different species which can last an average of 6 days (*P. falciparum*), 10 days (*P. vivax*), or 15 days (*P. ovale* and *P. malariae*) [5]. In the bloodstream, the merosomes are then disrupted liberating the merozoites, each merozoite infecting a single red blood cell (RBC). The process of invasion is complex, relying on diverse cell machineries, which permit the parasite to attach, reorientate, and invade, forming the parasitophorous vacuole [6]. Once in the erythrocyte, the parasite starts its asexual division, passing through different stages. The early trophozoite, called "ring stage", starts to develop, enlarging to a mature trophozoite that has a high metabolic index. In the late stage, multiple nuclear divisions

**Figure 1.** Malaria parasite life cycle. Schematic life cycle of *P. falciparum* in the invertebrate (left) and vertebrate hosts (right). 1. Hepatocytes invasion and exoerythrocytic schizogony to merozoites formation. 2. Release of merosomes in the blood stream. 3. Intraerythrocytic phase. 4. Parasite differentiation to gametocytes which ones could be ingested by invertebrate host. 5. Sexual phase in the midgut of invertebrate host. 6. Migration of sporozoites into salivary glands. 7.

Injection of sporozoites during the blood meal.

divided into liver phase and intraerythrocytic phase [3] (**Figure 1**).

40 Terpenes and Terpenoids

Within the red blood cells, the parasite can follow another path of development, differentiating into gametocytes. During a blood meal in an infected individual, the *Anopheles* female ingests those gametocytes. In the female of the *Anopheles* mosquito the parasite undergoes a meiotic division. Inside the mosquito gut, the gametocytes mature to form male and female gametes. The gametes undergo fertilization, forming the zygote, which transforms into an ookinete. The ookinete then penetrates the midgut and installs itself developing into oocyst. Under multiple cellular divisions, thousands of sporozoites are formed, which migrate to the salivary glands of the mosquito, to get expelled with anticoagulant factor contained in saliva during the next blood meal, restarting the cycle [10] (**Figure 1**).

Although *P. vivax* is the most prevalent parasite in the world, *P. falciparum* is responsible for most cases of severe malaria, being the most prevalent malarial parasite in the African continent, which accounts for 80% of the global disease burden. The groups with higher risk of malaria disease includes pregnant women, patients with HIV/AIDS, infants and children under 5 years old, whereas *P. falciparum* is responsible for about 70% of the malaria-related deaths. Although a lot of efforts have been made aiming to eradicate malaria, the World Health Organization (WHO) strives to reduce the mortality rates and malaria cases in 90% up to the year of 2030 [11]. The acquired drug resistance of the parasite continues to be a struggle in the fight against the disease, which led to rising of malaria-related death.

The resistance to antimalarial drugs is due to the indiscriminate use of the drugs and its incorrect use in treatment of malaria cases, such as wrong dosage, drug quality problems, erroneous diagnosis, not sticking to treatment, and others. These are characterized as treatment failure but can lead to a strong selective pressure in parasites, resulting in drug resistance. In recent years, with the emergence of artemisinin derivatives, resistance has allowed the number of cases to grow fast, especially in East Asia. Artemisinin, a sesquiterpene lactone, and its derivatives were adopted in the early 2000s as a first-line treatment in combined therapy for *P. falciparum* [12]. Artemisinin and its derivate can clear early trophozoites (ring stage), but the drug has a short span in vertebrate organisms, making it necessary to combined it with other drugs. In countries where *P. vivax* is the main malaria transmitter, the first-line treatment remains using chloroquine and primaquine, although WHO suggests that changes must be made to artemisininbased combined therapy (ACT) when the rate of chloroquine resistance have reached more than 10%. Some strategies have been adapted to control malaria, such as vector control; insecticide-treated bed nets, indoor residual spraying, preventive treatment for pregnant women, and rapid diagnosis and treatment of infected individuals [1, 12, 13]. But considering the fast acquirement of resistance by parasites and vectors to drugs and insecticides, respectively, the development of an effective vaccine turns out to be an important issue. However *Plasmodium* species, especially *P. falciparum*, has a highly variant antigen pool, responsible for the adhesion of infected red blood cells (RBCs) to small vessels, which causes aggregation that leads to severe stage of the disease, making difficult advances in this area of interest [9]. The pathogenesis of *P. falciparum* relies on a complex interaction of RBC alterations, microcirculatory anomalies, and immune response. The infected RBCs start to agglomerate in small vessels by action of adhesins expressed by the parasite on the surface of infected RBCs. Those adhesins are capable of interacting with endothelial cells of small vessels, to avoid the clearance of infected RBCs by the spleen, leading to a sequestration in diverse organs, such as brain, lungs, and placenta. This, together with other factors, causes the severe forms of malaria [9].

The increasing resistance of the parasite to practically all current medications, such as artemisinin in five countries in Asia, Southeast Asia and probably South America [1], calls for the use of combination drug therapy, as well as for the identification of new targets [12, 13]. Targets targeting the parasite for the development of new therapies for the treatment of malaria encompass both cellular functions, such as detoxification of heme or ferriprotoporphyrin IX (Fe (III) PPIX), and folate metabolism, already explored for drugs established as antimalarial, as well as other metabolic pathways, such as fatty acid synthesis, and isoprenoid biosynthesis, both of which are found in the apicoplast [14].

The apicoplast, an organelle originating from a secondary endosymbiotic origin of red algae, has lost its photosynthetic function in the course of evolution [15], and speculations have demonstrated its importance in the formation of essential components incorporated into the membrane of the parasitophorous vacuole [16]. Recently, it has been shown that isoprenoid biosynthesis is not only essential for the parasite but, in fact, is the only function of the apicoplast during blood stage growth [17] and sexual forms [18]. Parasites that lacked apicoplast can be chemically rescued by addition of isopentenyl pyrophosphate (IPP) to the growth media [17].


**An Experiment on Autoregressive and Threshold Autoregressive Models with Non-Gaussian Error with Application to Realized Volatility**

#### **Ziyi Zhang †,‡ and Wai Keung Li \*,‡**

Department of Statistics and Actuarial Science, University of Hong Kong, Hong Kong, China<EMAIL_ADDRESS>or<EMAIL_ADDRESS>

Received: 27 February 2019; Accepted: 11 June 2019; Published: 17 June 2019

**Abstract:** This article explores the fitting of Autoregressive (AR) and Threshold AR (TAR) models with a non-Gaussian error structure. This is motivated by the problem of finding a possible probabilistic model for the realized volatility. A Gamma random error is proposed to cater for the non-negativity of the realized volatility. With many good properties, such as consistency even for non-Gaussian errors, the maximum likelihood estimate is applied. Furthermore, a non-gradient numerical Nelder–Mead method for optimization and a penalty method, introduced for the non-negative constraint imposed by the Gamma distribution, are used. In the simulation experiments, the proposed fitting method found the true model with a rather insignificant bias and mean square error (MSE), given the true AR or TAR model. The AR and TAR models with Gamma random error are then tested on empirical realized volatility data of 30 stocks, where one third of the cases are fitted quite well, suggesting that the model may have potential as a supplement for current Gaussian random error models with proper adaptation.

**Keywords:** Autoregressive Model; non-Gaussian error; realized volatility; Threshold Autoregressive Model


**Acknowledgements**

introduction of MWCNT and the *in‐situ* N‐doped carbon carbonized from ligands could significantly improve the electronic conductivity of the catalysts. Thus, better OERactivity was observed with an onset potential of only 1.5 V (vs. RHE). Ma et al. [64] synthesized MOF‐ derived Co3O4‐carbon porous nanowire arrays. The Co3O4‐carbon were directly prepared on Cu foil as a working electrode. Since this electrode is binder‐free and carbon is formed *in situ*, the charge conductivity performance is greatly improved, resulting in excellent OER catalyt‐ ic activity in 0.1 M KOH solution. It shows a sharp onset potential of 1.47 V (vs. RHE), very close to that of IrO2/C (1.45 V vs. RHE). The durability is also an important criterion for OER catalysts. The chronopotentiometric response at a current density of 10 mA·cm−2 was also recorded, and only 6.5% attenuation was observed within 30 h on Co3O4‐carbon, while that of

The above results demonstrate that MOFs‐derived catalysts show much enhanced OER catalytic performance than pristine MOFs. There are likely several reasons for that. On one hand, carbon materials formed *in situ* or *ex situ* in catalysts can promote electronic conductiv‐ ity and accelerate charge transfer. On the other hand, the OER active species can be well‐ dispersed on carbon materials, resulting in improved OER activity. In addition, the strong interactions between OER active species and carbon materials stabilize the OER active site

MOFs‐based electrocatalysts for HER and/or OER are rapidly developed in recent years due to unique structures of MOFs. These catalysts mainly include MOFs catalysts, MOFs sup‐ ports for catalysts, and MOFs‐derived catalysts. Due to the fact that the pore structures and functions are tunable and devisable, it is convenient to directly design and construct the active sites for HER and/or OER in MOFs during the synthesis process. However, the vast majority of the synthesized MOFs suffer from poor electronic conductivity, leading to low electron transfer efficiency, which restricts catalytic performance. MOFs are highly porous materials and have ultrahigh specific surface area, thus they are regarded as the most promising support materials for catalysts. The active species for HER or OER can be well dispersed at the surfaces of MOFs or embedded in MOFs matrix, resulting in improved catalytic performance for HER or OER. However, MOFs are microporous materials with small aperture size (<2 nm).On one hand, the active species are difficult to be introduced in their pore channels. Hence, one cannot obtain the catalysts with high activity and stability for HER or OER. On the other hand, the accommodation of electrolyte in the pore channels is very limited. Thus, the active centers in MOFs cannot access the electrolytes with high efficiency. In addition, the poor electronic conductivity of MOFs is another drawback of these catalysts. Some post‐treatment methods can greatly improve the electrical conductivity of MOFs‐derived catalysts. However, the collapse of the pore structures of MOFs usually occurs during the preparation of the MOFs‐ derived catalysts leading to a decreased specific surface area of the catalysts, which is adverse to the development of MOFs‐derived catalysts with high catalytic performance for HER or

IrO2/C is 4.7 times lager under the same condition.

**6. Conclusions**

126 128Metal-Organic Frameworks

OER.

structures, thus leading to enhanced OER activity durability.

This work is supported by the National Natural Science Foundation of China (Project No. 21276018), the Natural Science Foundation of Jiangsu Province of China (Project No. BK20140268), the Fundamental Research Funds for the Central Universities (Project No. buctrc201526), and the Changzhou Sci&Tech Program (Project No. CJ20159006).


*5.1. Comprehensibility*

The values obtained for each question of comprehensibility indicated a positive evaluation. The responses to QC1 and QC5 had a median of 6.0 and a mean over 5.5. All the others had a median of 5.0 and a mean between 4.91 and 5.27. Item QC6 received the lowest, and item QC1 obtained the highest score. This showed that the application was easy to use and it was intuitive, but there were still small stability tracking issues that determined a slight flickering of the 3D content.

At the same time, the overall values obtained from the three surveys were very similar: Constanta (mean = 91.58), Rome (mean = 89.76), and Sulmona (mean = 90.23).