**4.1 TCs and signaling processes**

Recently, some of the TCs located on the extracellular matrix of blood vessels were described as having a primary cilium (Cantarero et al., 2011). The presumed functions of such a nonmotile cilium could be:- organizer of the mitotic spindle (Alieva et al., 2004), sensory organelle involved in signal transduction - hedgehog pathway (Singla et al., 2006), mechanical sensing and mechano-chemical conversion in endothelial cells (Egorova et al., 2011; Nauli et al., 2008). By analogy, we can presume that TCs could be involved in the signaling process if located near the stromal colony-forming cells/units in human endometrium or might act as stretch sensors if located near smooth muscle structures in both Fallopian tubes and uterus.

Telocytes in Human Fallopian Tube and Uterus Express Estrogen and Progesterone Receptors 111

endometrial stem cell colony), either by direct stimulation of target cells (immunoreactive cells). Recent evidence suggests that TCs may play a role as putative actors in neo-

In conclusion, the presence of steroid hormone receptors suggests that TCs could behave as sensors controlling the Fallopian tube peristalsis by signaling mechanisms (para- or juxtacrine), depending on ovarian hormone levels, by opposite effects (accelerated by estrogens and delayed by progesterone). Our findings might even explain infertility in patients without any proven Fallopian tube abnormalities. At uterine level, the discovery of TCs is fundamental for a totally new approach regarding the mechanisms controlling myometrial contractility during and outside pregnancy. The evidence for steroid hormone receptors at the level of myometrial TCs might open a path towards the understanding of contractility modulation using steroid hormones. This effect could be the result of intercellular connections between TCs and myocytes. The particular structure of the podoms with energetic (mitochondria) and functional (proteins from ER) resources favours the extension of Tp in the extracellular environment for signalling purposes of for intercellular communication. The steroid receptors occurrence in TCs could also suggest that these cells participate in the exchange of genetic information with other cells (myocytes, immune cells, nerve fibres) or for sensing changes in stromal microenvironment. If some of the supposed functions will be proven, TCs could be used in the future as molecular tools for delivering

This work was partially supported by the "Sectorial Operational Programme" Human Resources Development, financed from the European Social Fund and by the Romanian

Akao, Y.; Iio, A.; Itoh, T.; Noguchi, S.; Itoh, Y.; Ohtsuki, Y. & Naoe, T. (2011).Microvesicle-

Alieva, I.B. & Vorobjev, I.A. (2004).Vertebrate primary cilia: a sensory part of centrosomal

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Carmona, I.C.; Bartolomé, M.J. & Escribano, C.J. (2011).Identification of telocytes in the lamina

*molecular medicine*, Vol.15, No.1, (January 2011), pp. 26-30, ISSN 1582-4934

*therapy*, Vol.19, No.2, (February 2011), pp. 395-399, ISSN 1525-0024

*international*, Vol.28, No.2, (April 2004), pp. 139-150, ISSN 1095-8355 Bani, D.; Formigli, L.; Gherghiceanu, M. & Faussone-Pellegrini, M.S. (2010).Telocytes as

*medicine*, doi: 10.1111/j.1582-4934.2011.01312.x, ISSN 1582-4934

mediated RNA molecule delivery system using monocytes/macrophages.*Molecular*

complex in tissue cells, but a "sleeping beauty" in cultured cells? *Cell biology*

supporting cells for myocardial tissue organization in developing and adult heart.*Journal of cellular and molecular medicine*,Vol.14, No.10, (October 2010) pp. 2531-

the vasculature: electron microscope imaging. *Journal of cellular and molecular*

propria of rat duodenum: transmission electron microscopy. *Journal of cellular and*

Government under the contract number POSDRU/89/1.5/S/64109.

angiogenesis (Manole et al., 2011).

biological drugs at genital organs level.

2538, ISSN 1582-4934

**7. Acknowledgment**

**8. References**

**6. Conclusions**

TPs usually form and release vesicles (or exosomes) which might indicate the possible involvement of TCs in intercellular communication. For example, in the heart, heterocellular communication between TCs and cardiomyocytes seems to occur by shed vesicles and close apposition (Gherghiceanu et al., 2011). Intercellular signaling can occur by two mechanisms: a paracrine and/or juxtacrine secretion of small signaling molecules and shedding microvesicles which transport 'horizontal' "packets" of macromolecules to the target cells, modifying their physiology. These vesicles can even transport DNA or RNA among neighbouring cells, inducing epigenetic changes (Akao et al., 2010; Zomer et al., 2010). We suspect a complex interplay between TCs, immune cells, cells involved in epithelial or even myometrial regeneration and cancer spreading (Pap et al., 2011).

#### **4.2 TCs and stem cells**

It is known that the remodeling events which take place in the uterus (endo- and myometrium) during implantation and pregnancy are coordinated by sequential actions of estrogen and progesterone (Szotek et al., 2007). TCs, as a special type of stromal cells, could be involved in uterine remodeling since they express ER and PR, and are also located in the lamina propria, beneath the epithelium and in between myocytes. There are fundamental studies that provide evidence that both epithelial and stromal stem/progenitor cells are found in human and mouse uterus (Gargett et al., 2008). The discovery of relationships between TCs and these uterine stem cells could provide new insights into the pathophysiology of various gynecological and obstetrical disorders. In 2009, Shynlova et al. proposed a new model of phenotypic modulation of uterine myocytes during pregnancy. These changes evolve in an early proliferative phase, an intermediate phase of cellular hypertrophy and matrix elaboration, a third phase in which the cells assume a contractile phenotype and the final phase in which cells become highly active and committed to labour. The final phase of myometrial differentiation is postpartum uterine involution. These stages are in fact the result of integration of endocrine signals and mechanical stimulation of the uterus by the growing fetus (Shynlova et al., 2009). In our opinion, TCs could be themselves stem cells (Popescu et al., 2011b), playing a part in muscle regeneration (Popescu et al., 2011a), these processes possibly depending on steroid hormones receptors.

#### **4.3 TCs and immune cells**

TCs often establish contacts with targets, such as smooth muscle cells, nerve fibres, and capillaries (Popescu et al., 2011). Over time, we also described close contact between TCs and cells of the immune system, found in the interstitial space (e.g. eosinophils, plasma cell, etc.). We considered that this is a new type of synapse - the stromal synapse - in addition to the existing neuronal and immunological synapse (Popescu et al., 2005b). The intercellular contact can either be "plain" uniform or "kiss-and-run" multicontact, based on synaptic cleft tracing.

## **5. Perspectives**

TCs can be putative cellular mechanotransducers in smooth muscle tissue. They may sense and translate stretch information for the nucleus, and activate genes responsible for protein synthesis which can influence the surrounding cells by juxta- or paracrine mechanisms. TCs could also be 'hormonal sensors' in human myometrium and the Fallopian tube since they express estrogen and progesterone receptors *in vitro*. The presence of steroid hormone receptors suggests that TCs could also be responsible for myogenic contractility modulation under hormonal control, either by transferring bioactive molecules (towards cells from an endometrial stem cell colony), either by direct stimulation of target cells (immunoreactive cells). Recent evidence suggests that TCs may play a role as putative actors in neoangiogenesis (Manole et al., 2011).


**2.4 Breeding of larva and nymphs**

The collected larvae were immediately placed into breeding boxes; transparent, with holes on the sides and on the top of the boxes to ensure oxygenation and avoid asphyxiation. The holes on the boxes are closed with a fabric scrim (muslin type). Rectangular boxes were used for rearing larvae harvested from *P. canariensis* and

*Biotechnological Applications of Biomass*

which annually produce around 30 million m3

*P. opaca* larvae in date palm, especially in *P. dactylifera* L.

**2. Materials and methods**

**2.1 Study area and plant material**

down contaminated trees [8, 9]. In Spain, red palm weevil has appeared since 1999 and damaged almost 20,000 palms of *Phoenix dactylifera* [10]. In the North of Morocco and more precisely in Tangier, the number of *Phoenix canariensis* prospected during 2009–2016 is 244,393 [11]. The number of *P. canariens is* infested with *R. ferrugineus* was 904, which 896 were incinerated [11], whereas no *P. dactylifera* has been infested with *R. ferrugineus*. In Morocco, *Potosia opaca* var. cardui Gyllenhal has been observed for the first time by Meddich and Boumezzough [12]. Indeed, in Marrakesh and Errachidia regions, it attacks *P. dactylifera* L. and *P. canariensis* by consuming their wood, which causes faster degradation. Thus, to remedy the damage caused by *P. opaca*, most farmers were forced to use synthetic pesticides. However, the intensive use of these pesticides are generally effective in protecting crops [13], but they are toxic to wildlife and to organisms from different levels of the ecosystems [14–17]. Over time, the permanent use of insecticides may be accompanied by the development of resistant strains in some treated species. Biocontrol strategies for pests need to be investigated and developed to provide an ecological substitute or alternative approach to the conventional methods. Some sub-products such as olive oil mill waste waters (OMW) are currently used to control pests, which is essential for crop protection [18, 19]. Most of the OMW phenolic compounds derived from olive polyphenols have many other biological properties [20, 21], as well as biocide activities [22] and phytotoxic effects [23]. Due to their particular characteristics, these effluents are a serious problem for the Mediterranean region,

environment [23] and accounts for approximately 95% of olive oil production in the world [19]. In addition, different physicochemical methods have been proposed to treat OMW, including natural and forced evaporation [24], electro-coagulation [25], oxidation by ozone and Fenton reagent [26] as well as their agricultural spreading [21], which is an alternative among the suggested solutions. However, the agronomic application of OMW is limited by the doses to be applied and the risk of polyphenols accumulation in the soil after consecutive applications [21–27]. In parallel with researches made on the treatment of OMW, many studies have been carried out aiming the recovery of OMW phenolic compounds. Recent studies tried to take its advantage from the antimicrobial and phytotoxic properties by using it as biopesticide for crops protection [28–30] or as insecticides to control *P. opaca* larvae [31]. This contribution summarized the quality of palm health status, OMW characteristics and its application as insecticides to control

This study was conducted during the period of 2014–2016 in the oasis of Marrakesh located in the central region of Morocco and the oasis of Errachidia situated in the southeastern part of the country. The majority of their territory presents arid climate, hot summer and cold winter. Palms (*Phoenix*) constitute one of the important botanical families, and include some of the world's most important economic plants. In North Africa regions, dates production provides jobs for estimated around 50 million people [32]. It plays by now an undeniable role in maintaining human populations in arid regions where natural resources are limited and living conditions are difficult [32, 33]. Like in Zagora, Errachidia, Ouarzazate which are located in the Draa-Tafilalet region. It is built on terraces, crowned by an old Glaoui kasbah of a hill and surrounded by a major oasis of palm grove. This includes in particular the biosphere reserve of the oases of south-eastern Morocco [34], which forms an agglomeration of ksours (small castles). This area is located in an

of OMW with a damaging effect on the

**490**

**Figure 2.** *Exploration of the* P. canariensis *palm crown using a scaffold (A); base of leaves (B and C).*

*P. dactylifera*. The breeding substrate was composed of a mixture of untreated natural soil and debris of dead wood, rotted wood and sawdust. Care was taken not to import diseases on bringing boxes of dry dung in breeding substrate in order to increase its acidity, which disadvantages the development of diseases. The breeding substrate was constantly renewed as soon as the feces of larvae appear in large quantities on the surface and more debris and wood in the rearing environment was observed. This breeding operation continued in incubators refrigerated and illuminated with controlled temperature and humidity. However, larvae are lucifugous (escape behavior of light); the optimum temperature is between 25 and 30°C. The nymphal hulls were placed in boxes with slightly damp peat. The duration of pupation varies according to the temperature supported by the larvae and also the male or female sex. The infected nymphal hulls were removed as soon as possible from the breeding environment to avoid pathological contamination of the rest of the cocoons.


**4. Methodology**

This work utilizes the trajectories, including the spatial position coordinates and time obtained by the PDR technique to quantitatively estimate the time-dependent changes in the virus quanta concentration derived from the movement and lifespan of the virus in various places of the considered indoor environment. The overview of the proposed

scheme is systematically introduced in Section 4.1. In Section 4.2, we provided the data processing approaches utilized in PDR-based trajectory construction and the estimation of droplet exhalation. The PDR technique (with a calibration of the landmark recognized by a landmark identification model based on a residual Bi-LSTM and CNN structure) is discussed in Section 4.3. Further, the contact awareness model relying on the precisely constructed pedestrian trajectory is detailed in Section 4.4.

### *4.1. System Overview*

An overview of the proposed iSTCA system is presented in Figure 1. More precisely, the data flow of various sensors for the analysis was primarily collected from the existing sensors in handhold smartphones, which record the changes in the environment and body motion. The signals need to be processed, including data filtering and scaling, to reduce the noise for a better state of motion estimation before training the landmark identification model and performing the PDR. The trajectory can be achieved based on the PDR technique and properly corrected with the assistance of the identified landmark distinguished by the trained landmark recognition model. The trajectory is defined as a set of points consisting of the time and position, {(*t*0, *x*0, *y*0),(*t*1, *x*1, *y*1),...(*tn*, *xn*, *yn*)} where (*xi*, *yi*) represents the location coordinates and *ti* is the moment when the individual passes the location. The virus quanta concentrations in different spaces at various moments can be measured quantitatively to achieve sufficient awareness with the help of the estimated spatial distance, temporal distance, and infectivity model, as shown in Equation (1).

**Figure 1.** Overview of iSTCA.

### *4.2. Data Preprocessing*

**Data alignment.** The same sampling rate for data collection is set to 50 Hz due to the low frequency of human movements [32]. Although the constant rate is defined, the time interval between the recorded adjacent readings of each sensor is not always the same because of the observational error and random error, and it oscillates within a certain range in practice. To acquire the same number of samples for conveniently performing the subsequent procedures, we take the timestamp of the first data collected as the starting time to align the sensor readings at the same time interval with the help of data interpolation.

**Data interpolation.** During the practical data collection using smartphone sensors, some data points in the acquired dataset are lost due to malfunctioning; such data points are typically replaced by 0, NaN, or none [33]. To fill in the missing values, the data interpolation technique was developed, in which the new data point is estimated based

on the known information. Linear interpolation, as the prevalent type of interpolation approach, was adopted in this paper, using linear polynomials to construct new data points [34]. Generally, the strategy for linear interpolation is to use a straight line to connect the known data points on either side of the unknown point and, thus, it is defined as the concatenation of linear interpolation between each pair of data points on a set of samples.

**Data filtering.** Due to the environmental noise and interference caused by the unconscious jittering of the human body, there are many undesirable components in the obtained signals that need to be dealt with [34]. This usually means removing some frequencies to suppress interfering signals and reduce the background noise. A low-pass filter is a type of electronic filter that attempts to pass low-frequency signals through the filter unchanged while reducing the amplitude of signals with a frequency above what is known as the cutoff frequency. A Butterworth low-pass filter with a cutoff frequency of 3 Hz is applied to denoise and smooth the raw signals.

**Data scaling.** The difference in the scale of each input variable increases the difficulty of the problem being modeled. If one of the features has a broad range of values, the objective functions of THE established model will be highly probably governed by the particular feature without normalization, suffering from poor performance during learning and sensitivity to input values and further resulting in a higher generalization error [35]. Therefore, the range of all data should be normalized so that each feature contributes approximately proportionately to the final result. Standardization makes the values of each feature in the data have zero means by subtracting from the mean in the numerator and unit variance, as shown in Equation (3):

$$X'\_i = \frac{X\_i - \mu}{\sigma} \text{ ( $i = 1, 2, 3 \dots$ ,  $n$ )}\tag{3}$$

where the *Xi* is the standardized data, *n* represents the number of data channels, and *μ* and *σ* are the mean and standard deviations of the *i*-th channel of the samples [35]. This method is widely used for normalization in many machine learning algorithms and is also adopted in this work to normalize the range of data we obtained.

**Data segmentation.** A sensor-based landmark recognition model is typically fed with a short sequence of continuously recorded sensor readings since only a single data point cannot reflect the characteristics of landmarks. The sequence consists of all the channels of selected sensors. To preserve the temporal relationship between the acquired data points with the aligned times, we partition the multivariate time-series sensor signals into sequences or segments leveraging the sliding operation, which consists of 128 samples (corresponding to 2.56 s for the sampling frequency at 50 Hz) [34,36]. It is noteworthy that the length of the window is picked empirically to achieve the segments for all considered landmarks, in which the features of the landmarks can be precisely captured to promote the landmark identification model training [32,37].

### *4.3. PDR-Based Trajectory Construction Model*

For the quantitative evaluation of the virus quanta concentration, the precise spatial distance and temporal distance between two individuals should be efficiently estimated. To reach this objective, a variety of indoor positioning techniques have been proposed for various scenarios. The widely studied fingerprinting-based method relies on the latest fingerprint database that needs to be precisely updated in time. In addition to the time-consuming and labor-intensive collection and re-establishment, the instability of RSS due to environmental uncertainties poses another challenge to the accuracy [38]. Moreover, coverage and distribution are also not satisfied in countries with poor ICT infrastructure [39]. Therefore, the self-contained PDR algorithm without extra requirements and coverage limitations is employed in this work, and its accuracy is improved by the identified landmark.


**3.4 Nivolumab**

Clinicians have also applied the use immunomodulatory checkpoint inhibitors as treatment for advanced HCC. Nivolumab is an immunoglobulin (IgG) 4 antibody that targets program death 1 (PD-1) on the surface of T cells to promote the antitumor properties of T cells [39]. Clinical trials have shown nivolumab to be a safe treatment option for advanced HCC with non-comparison studies showing durable and effective clinical response to treatment [40]. Multicenter phase III clinical trials comparing nivolumab to sorafenib are currently underway [41, 42]. Interim results of the CheckMate 459 trial, a randomized, multicenter phase III study, have shown no significant difference in median OS between nivolumab and sorafenib; however, the objective response rate was as high as 15% in those taking nivolumab vs. 7% in those taking sorafenib [41, 42]. Additionally, nivolumab was associated with superior health-related quality of life with patients reporting fewer side effects [43].


**5. Surgical technique and pearls**

## **5.1 Patient positioning**

Patients commonly notice posterior neck pain following disc arthroplasty. The pain can be a result of surgical positioning, intraoperative distraction on the facet joints and capsules, or an indirect distraction on the endplates from the implant itself. Often these implants are inserted with a considerable amount of force so in order to limit the unsupported transfer of these forces to the paraspinal musculature and facet joints, a properly contoured support should be placed along the posterior aspect of the neck (**Figure 2a**).


3.1.3. Soil Moisture

Plant available water at planting was 3.35 cm for the 60 cm profile in 2016 and was 1.9 cm for the 75 cm profile in 2017. Mean PAW (soil depth 75 cm) at harvest across all treatments in 2016 (0.63 cm) was 20% of mean PAW in 2017 (3.09 cm). Harvest PAW in 2016 was influenced by irrigation, there was no influence of row spacing or tillage treatments, averaging 0.64 cm. High and M irrigation levels averaged 0.86 cm, which was different from L at 0.19 cm of PAW. Differences in PAW were found in 2017 among irrigation levels and in an irrigation × tillage interaction. Plant available water was highest in M (3.52 cm) and lowest in L (2.49 cm), a difference of 41%; H (3.1 cm) was not different from the M and L levels. The interaction resulted from L irrigation × no-till, 1.8 cm PAW, being 47% lower than the average of all other treatments (3.42 cm; SE = 0.42 cm), ranging from 2.7 to 3.8 cm. The primary reason harvest PAW in 2016 was 80% less than 2017 is the additional 31 d of growing season in 2016 and the rainfall prior to harvest in 2017 (Figure 1).