Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH　(LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.

The R&D and propagation of sustainable appropriate technology requires the provision of stable funding. Crowdfunding is a form of funding whereby small sums of investments or contributions are collected from among the general public and used to finance the development of goods or services. This method has been in use widely in arts and culture fields, and presents a useful alternative means for funding appropriate technology projects. The aim of this study is to identify the factors influencing the backers who participate in appropriate technology projects through crowdfunding platforms, analyzing the relationships between these factors, and thereby establishing the usefulness of crowdfunding as a viable new alternative. The analysis results indicate that key factors influencing user intention to crowdfund appropriate technology projects include social influence, effort expectancy, and perceived trust. In contrast to the findings of previous studies, performance expectancy was not found to have a significant effect. This reflects the fact that, compared to the crowdfunding conducted for other purposes, crowdfunding for appropriate technology is closer in nature to donations. These findings indicate that for funding to be successful, aggressive online exposure using the SNS of backers should be pursued from the early stages of funding.

Various type of soils have been identified based on their electrical and magnetic properties, especially with regards to peat soils. Peat soils are commonly considered as partly decomposed vegetation. In this study, electrical and magnetic properties have been used in K-means clustering to identify layers of peat soils. K-means clustering is a partitioning method that treats observations in the data. Data cores were obtained at every centimeter and examined for their electrical conductivity (σ) and magnetic susceptibility (χ_m) properties. A 291 cm core was obtained at Tegal Arum Village in South Kalimantan, Indonesia. The K-means clustering results indicate two different layers at 148 cm, and this is supported by loss on ignition (LOI) measurements. In the first layers, a 87.65% LOI was found associated with peat soils (above 248 cm). Whereas, in the second layers, there was a 26.11% LOI associated with mineral soils (below 248 cm). The results of this study using K-means clustering can be used to delineate soil layers.

Clustering, or otherwise known as cluster analysis, is a learning problem that takes place without any human supervision. This technique has often been utilized, much efficiently, in data analysis, and serves for observing and identifying interesting, useful, or desired patterns in the said data. The clustering technique functions by performing a structured division of the data involved, in similar objects based on the characteristics that it identifies. This process results in the formation of groups, and each group that is formed, is called a cluster. A single said cluster consists of objects from the data, that have similarities among other objects found in the same cluster, and resemble differences when compared to objects identified from the data that now exist in other clusters. The process of clustering is very significant in various aspects of data analysis, as it determines and presents the intrinsic grouping of objects present in the data, based on their attributes, in a batch of unlabeled raw data. A textbook or otherwise said, good criteria, does not exist in this method of cluster analysis. That is because this process is so different and so customizable for every user, that needs it in his/her various and different needs. There is no outright best clustering algorithm, as it massively depends on the user’s scenario and needs. This paper is intended to compare and study two different clustering algorithms. The algorithms under investigation are k-mean and mean shift. These algorithms are compared according to the following factors: time complexity, training, prediction performance and accuracy of the clustering algorithms.

Growth-regulating factor (GRF) is a plant-specific transcription factor family, which is involved in nearly all of the central developmental processes in plants. However, little is known about GRF family genes in cultivated sunflower. In this study, 17 GRF genes were identified and characterized from sunflower genome. Their gene structures, conserved motifs, chromosomal distributions and phylogenetic relationships were analyzed. The expression patterns of these genes were detected in various tissues of sunflower inbred line SK02R, which revealed that the 10 seed-specific GRF genes may play important roles during seed development in sunflower. Additionally, transcripts changes of the GRFs under two major abiotic stresses and phytohormones showed that most of the detected GRFs were reduced significantly by GA3 treatment, and other treatments(ABA, NaCl and PEG6000) differently regulated various sunflower growth-regulating factors at different time points. MiR396 target analysis indicated that there may exist a complicated homeostasis between miR396 and its targets GRF and WRKY transcription factor genes in cultivated sunflower. The phylogenetic and expression analyses of the GRF gene family in sunflower would be useful for further cloning and function exploration of the HaGRF genes.

Wind power output is highly dependent on the wind speed at the selected site, therefore wind-speed distribution modeling is the most important step in the assessment of wind energy potential. This study aims at accurate evaluation of onshore wind energy potential in seven coastal cities in the south of Iran. Six Probability Distribution Functions (PDFs) were examined over representative stations. It has been deduced that the Weibull function, which was the most used PDF in similar studies, was only applicable to one station. Here, Gamma offered the best fit for three stations and for the other ones, Generalized Extreme Value (GEV) performed better. Considering the ranking of six examined PDFs and the simplicity of Gamma, it was identified as the effective function in the southern coasts of Iran bearing in mind the geographic distribution of stations. Besides, six turbine power curve functions were contributed to investigate the capacity factor. That was very important, as using only one function could cause under- or over-estimation. Then, stations were classified based on the National Renewable Energy Laboratory system. Last but not least, examining a range of wind turbines enabled scholars to extend this study into the practice and prioritize development of stations considering budget limits.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

Systems biology has been established for more than a decade in the post-genomic era. With the help of the computational and mathematical tools, systems biology reconstitutes the entire scenario of the cell, tissue and even organism from the pieces data generated in the past decades. However, the modern biology is mainly focusing on the structure and function of the biomolecule, cell, tissue or organ, which are far from the essence of the life because of missing thermodynamic information. It is doubtable that the current systems biology-based omics is no-how to fully understand the dynamic courses of the structure, function and information in life. For this reason, we promote a novel concept of aquamoleculomics, in which the biological structure and function as well as thermodynamic characteristics and bioinformation of the aquamolecule complexes are included in this theoretical model of systems biology. Water is mother of life, matter and matrix of organism. Indeed, the fundamental roles of H₂O molecules in biological processes might be dramatically underestimated. Extremely speaking, H₂O networks in the living system might be engaged in all the biological processes including building all the biological structures, the residential places of the motherhood molecules as the honeycombs of honeybees.

The objective of this research is to develop an experimental-theoretical analysis about the influence of the cooling medium and the geometry of the welding bead profile in fatigue life and associated parameters with structural integrity of welded joints. A welded joint with cruciform geometry is considered using SMAW, plates in structural steel ASTM A36 HR of 8 mm of thickness and E6013 electrode input. A three-dimensional computational model of the cruciform joint was created using the finite element method. For this model, the surface undulation of the cord and differentiation in the mechanical properties of the fusion zone were considered, the heat-affected zone (HAZ) and base material, respectively. In addition, an initial residual stress field which was established experimentally was considered. The results were a set of analytical expressions for the weld magnification factor Mk. It was found that values for the latter decrease markedly in function of the intensity of the cooling medium used in the post welding cooling phase, mainly due to the effect of the residual compressive stresses. The obtained models of behavior of the weld magnification factor are compared with the results from other researchers with some small differences, mainly due to the inclusion of the cooling effect of the post weld and the variation of the leg of the weld bead. The obtained analytical equations in the present research for Mk can be used in management models of life and structural integrity for this type of welded joint.

This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement to synthesizes the existing literature with a goal to review current conceptual frameworks of mental health of forced migrants for further practice research priorities in social work. The search was done between January 2015 to January 2021. As a result, 29 studies met inclusion criteria. Medicalizing mental health issues by relying solely on the effectiveness of medicine was a controversial risk factor that negatively affected the daily life activities of refugees and reduced their willingness for seeking professional mental health services. Empowering vulnerable minorities by giving them back their power and agency to be able to speak for themselves and raise voices of trauma and recovery was the missing protective factor for sustainable mental health practice. The benefits of group-based interventions are highlighted in which communities and individuals address mental health issues as well as isolation through building collective identities and support networks. Information and communication technologies (ICTs) can add more strength to any kind of mental health intervention. Finally, the benefits of applying ecological perspective for the mental health of refugees, and its implications for a sustainable intercultural practice are discussed. Social workers in this model are the representatives of at-risk groups, thus need more agency and creativity in reflecting client’s concrete needs.

This study presents a new form of velocity distribution in laminar liquid flow in rectangular microchannels using the eigenfunction expansion technique. Darcy friction factor and Poiseuille number are also obtained analytically. Due to the symmetry of the solutions, the effects of changing the aspect ratio from 0 to ∞ are also discussed. Using finite element method (FEM), the obtained analytical results are further compared with the 3D numerical simulations for the rectangular microchannels with different range of aspect ratio and pressure gradient, and excellent agreements were found. These findings provide additional insights in interpreting the results of the pressure-driven flows in finite aspect ratio microchannels, in which very precise comparison with the macroscale theory is crucial.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wavefunction just prior to the entrance of ‘gravitons’ to a small region of space-time prior to a nonsingular start to the universe. We compare this to a solution worked out using Klauder Enhanced quantization, for the same given problem. The solution of the first Cosmological Constant problem relies upon the geometry of the multiverse generalization of CCC cosmology which is explained in this paper. The second solution, used involves Klauder enhanced quantization. We look at energy given by our methods and compare and contrast it with the negative energy of the Rosen model for a mini sub universe and estimate GW frequencies

To evaluate whether autologous mesenchymal cells, adipose derived stem cells and platelet-rich plasma, grafted into the supracoroideal space by surgical treatment according to Limoli retinal restoration technique (LRRT), can produce growth factors in order to exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and divided based on retinal foveal thickness ≤ 190 or >190 µm into group A and group B, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed an improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of RP, it can be confirmed that further research is needed on tapeto-retinal degenerations both from a clinical and molecular point of view to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation times, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

Atmospheric correction is a necessary step in image processing data and spectra recorded by spaceborne sensors for pure cloudless atmosphere, primarily in the visible and near-IR spectral range. We have present a fast and sufficiently accurate method of atmospheric correction based on the proposed analytical solutions describing with high accuracy the spectrum of outgoing radiation at the top boundary of the cloudless atmosphere. This technique includes the model of the atmosphere and its optical parameters that are important in terms of radiation transfer. The solution of the inverse problem for finding unknown parameters of the model is carried out by the method of non-linear least squares (Levenberg-Marquardt algorithm) for an individual selected pixel of the image (its spectrum), taking into account the adjacency effects. Using the found parameters of the atmosphere and the average surface albedo, assuming homogeneity of the atmosphere within a certain area of the hyperspectral image (or the whole frame), the spectral albedo at the Earth's surface is calculated for all other pixels. It is essential that the procedure of the numerical simulation with non-linear least squares of the direct transfer problem is based on using analytical solutions, which provides a very short calculation time of the atmospheric parameters (seconds or less) and the ability to perform atmospheric correction "on-fly." Testing methods of atmospheric correction was performed using the synthetic outgoing radiation spectra at the top of the atmosphere (TOA), obtained by numerical simulation in the LibRadTran code, as well as spectra of real space images of the Hyperion hyperspectrometer. A comparison with the results of atmospheric correction in module FLAASH of ENVI package has been performed. Finally, to validate our data obtained by the SHARK method, a comparative analysis with ground-based measurements of Radiometric Calibration Network (RadCalNet) was carried out.

As a complementary and alternative medicine in the western countries for decades, traditional Chinese medicine (TCM) has been used for more than 2000 years in China. Because of the characteristics of the philosophical style and the unknown mechanism of action, TCM sometimes has been biasedly described as "fraught with pseudoscience". From the scientific basis of the systems biology, here we promoted a novel medical model called the entropic systems medicine which could be applied to scientize TCM in future. In entropic systems medicine, TCM and Western modern biomedicine target the different variables of the entropic system. For instance, while Western modern biomedicine directly targets the phenotypes and its SOCs of macrostates, TCM differently targets the microstates, entropy and entropic force to generate SOTFs gradually causing the differentiated syndromes to be slowly rearranged. The prerequisites to modernize TCM are the entropic systems biology having been well established so that the variables could be precisely monitored and mathematically calculated.

The RAINBOW Phase III study established the efficacy of the combination of paclitaxel and ramucirumab, a monoclonal antibody targeting VEGF receptor-2 (VEGF-R2), as second-line therapy. We retrospectively analyzed the data of patients treated with ramucirumab plus paclitaxel at our Institution to evaluate the impact of clinical heterogeneous figures on the efficacy and safety of this combination paclitaxel/ramucirumab in a real- life cohort of patients. After a median follow-up of 10.74 months, the median progression-free survival (PFS) was 5.8 months (95% CI: 3.04 - 5,63). Disease control rate (DCR) was 61% and the median duration of response (DOR) was 5.8 months. Median overall survival (OS) was 8.3 months. A trend toward better outcome was observed in HER2 positive patients. In multivariate analysis, nutritional status (p = 0.0001) and number of metastatic sites (p = 0.0266) resulted significantly related with longer PFS. Our analysis confirmed the efficacy and safety of the combination of ramucirumab with paclitaxel also in the real-life practice and the median PFS is significantly longer than that reported for Western population in previous studies. Subgroup analysis confirms the key-role of nutritional status as prognostic factor and suggests a possible interaction between EGF and angiogenesis pathways that deserves further investigations.

Nowadays, the research and development of on-chip LiDAR sensors for vehicle collision avoidance is growing very fast. Therefore, the assessment of the reliability in obstacle detection using the information provided by LiDAR sensors has become a key issue to be explored by the scientific community. This paper presents the design and implementation of a self-tuning method in order to maximize the reliability of an Internet-of-Things sensors network and to minimize the number of sensors to localize with the required accuracy obstacles by a detection threshold. In order to achieve this goal, models that predict accuracy (i.e., prediction error) for object localization using data collected by LIDAR sensors are designed and implemented in Webots Automobile 3D simulation tool. The approach is based on combining different techniques. Firstly, point-cloud clustering technique and an error prediction model library composed by a multilayer perceptron neural network with backpropagation, k-nearest neighbors and linear regression are explored. Secondly the above-mentioned techniques for modeling are also combined with a supervised and reinforcement machine learning technique, Q-learning in order to minimize the detection threshold. In addition, a IoT driving assistance simulated scenario with a LiDAR sensor network is designed in order to validate the prediction model and the optimal configuration of the sensor network to guarantee reliability in obstacle localization. The results demonstrate that the self-tuning method is appropriate to increase the reliability of the sensor network whereas minimizing the detection threshold

The aim of this study was to develop a basic model to predict enteric methane emission from dairy cows and to update operational calculations for the national inventory in Norway. Basic models were developed using a database with 63 treatment means from 19 studies. The database included records for enteric CH4 production (MJ/day), dry matter intake (DMI), and dietary nutrient composition. The basic models were evaluated against an external database (n=36, from ten studies) along with other extant models. When evaluated by low root mean square prediction errors and high concordance correlation coefficients, the developed basic models that included DMI, dietary concentrations of fatty acids and neutral detergent fiber performed slightly better in predicting CH4 emissions than extant models. In order to propose country-specific values for the CH4 conversion factor Ym (% of gross energy intake partitioned into CH4) and thus to carry out the national inventory for Norway, the existing operational model was updated for the prediction of Ym over a wide range of feeding situations using energy corrected milk and dietary concentrate share as predictor variables. Input values of Ym were updated based on the results from the basic models. The predicted Ym ranged from 6.22 to 6.72%. In conclusion, the prediction of CH4 production from dairy cows was improved with the help of newly published data, which enabled an update of the operational model for calculating the national inventory of CH4 in Norway.

In this study, the prevalent methodology for design of the industrial policy in developing countries was critically assessed, and it was shown that the mechanism and content of classical method is fundamentally contradictory to the goals and components of the endogenous growth theories. This study, by proposing a new approach, along settling Schumpeter's economic growth theory as a policy framework, designed the process of entering, analyzing and processing data as the mechanism of the industrial policy in order to provide "theoretical consistency" and "technical and Statistical requirements" for targeting the growth stimulant factor effectively.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

At present more than 9 million people die of cancer every year. Simple and broad-spectrum drugs are still an urgent need for cancer patients. Recently, we proposed a new hypothesis that intracellular osmotic pressure (IOP) is the driving force of cell division, and abnormal tumor proliferation is the result of uncontrolled IOP in cells. On the one hand, aneuploidy and abnormal function of Na⁺/K⁺ pump lead to a faster rise of IOP in tumor cell than normal cells, on the other hand, abnormality of cytoskeleton assembly leads to the decrease of tolerance limit of cell membrane (TLCM) of tumor cells for resisting IOP. This hypothesis predicts: 1)Tumor cells were more intolerant to hypotonic stress than normal cells. 2) Maligancies may be sellectively killed by a suddenn increase of IOP and combined with decrease of the TLCM of tumors. Na⁺/K⁺ pump inhibitors can promotely increase the IOP of tumor cells and cytoskeleton inhibitors can dramatically lower the TLCM of tumor cells. Therefore, Na⁺/K⁺ pump and cytoskeleton inhibitors may have a synergetic effect to kill tumor cells. 3) Molecules regulating cell osmolality may be new targets for cancer treatment.

Quadruplex-interactive small molecules have a wide potential application, not only as drugs but also as sensors of quadruplexes structures. The purpose of this work is the synthesis of analogues of the bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure-activity relationships to apply to the design of other G4-interactive small molecules bearing bis-quinoline or bis-isoquinoline moieties. Thermal denaturation experiments revealed that non-methylated derivatives with a relative 1,4 position between the amide linker and the nitrogen of the quinoline ring are moderate G4 stabilizers, with a preference for the hybrid h-Telo G4. Insertion of a positive charge upon methylation of quinoline/isoquinoline nitrogen increases compounds capacity to selectively stabilize G4s compared to duplex DNA, with a preference for parallel structures. Among these, compounds having a relative 1,3-position between the charged methylquinolinium/isoquinolinium nitrogen and the amide linker are the best G4 stabilizers. More interestingly, these ligands showed different capacities to selectively block DNA polymer-ization in a PCR-stop assay and to induce G4 conformation switches of hybrid h-Telo G4. Mo-lecular dynamic simulations with the parallel k-RAS G4 structure showed that the relative spatial orientation of the two methylated quinoline/isoquinoline rings determines the ligands mode and strength of binding to G4s.

Three-phase to single-phase matrix converter (TSMC) is used as the transmitter for transient electromagnetic method (TEM) instrument, instead of an AC-DC converter and an H-bridge inverter. The transmitter produces excitation current for primary field. The output current has a waveform with a bipolar square of half duty cycle, which is required by TEM. The space vector PWM based on input currents is discussed in detail. The control method of input power factor is proposed for TSMC. The simulation model of TSMC is established and the simulations of different conditions are completed. The simulation results show the controllability of the input power factor is illustrated.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

This paper considers the detection of fluctuating target in heavy-tailed clutter through the use of dynamic programming based on track-before-detect (DP-TBD) in radar systems. The clutter is modeled in terms of K-distribution, which can be widely used to describe non-Gaussian clutter received from high-resolution radars and radars working at small grazing angle. Swerling type 1 is considered to describe the target fluctuation between scans. Conventional TBD techniques suffer from significant performance loss in heavy-tailed environments due to the more frequent occurrences of target-like outliers. In this paper, we resort to DP-TBD algorithm based on prior information, which can enhance the detection performance by using the environment and target fluctuating information during the integration process of TBD. Under non-Gaussian background, the expressions of the likelihood ratio merit function for Swerling type 1 target are derived first. However, the closed analytical form of the merit function is difficult to be obtained. In order to reduce the complexity of evaluating the merit function and the computational load, an efficient approximation method as well as a two-stage detection approach is proposed and used in the integration process. Finally, several numerical simulations of the new strategy and the comparisons are presented to verify that the proposed algorithm can improve the detection performance, especially for fluctuating target in heavy-tailed clutter.

In South Korea, landslides are caused by localized heavy rainfall and typhoons, which often occur in the summer season at natural slopes in mountainous areas and artificial slopes in urban surroundings. Flow-type landslides frequently occur in mountainous areas. To evaluate flow-type landslides, it is essential to identify the physical characteristics of soil, giving focus to the soil on the top layers of various types of slope. This study conducts a survey and an analysis of the characteristics of landslides that occurred in the study area with different geological conditions of granite and gneiss. The characteristics of soil in the area and its surroundings that have or have not undergone landslides for every geological condition is also evaluated. Based on these characteristics and a statistics method, it extracts the triggering factors, permeability coefficients (k), and shearing strength with cohesion (c) and internal friction angel (φ) of soils that are highly related to landslides around weathered soil layers. As a result, the permeability coefficients show significant relevance with void ratio (e), the effective size of grains (D10), and uniformity coefficient (cu), while the shearing strength with the proportion of fine-grained soil (Fines), uniformity coefficient (cu), degree of saturation (S), dry weight density (rd), and void ratio (e). By obtaining this result, the study uses the regression analysis to suggest models to estimate the permeability coefficients and shearing strength. For the gneiss area, the statistics-based estimation model (SEM) is proposed as k_gn = (1.488 × 10^-02 × e) + (1.076 × D₁₀) + (-1.629 × 10^-04 × c_u) - (1.893 × 10^-02) for permeability coefficients; cgn = (-0.712 × Fines) + (-0.131 × c_u) + 15.335 for cohesion; and φgn = (27.01 × r_d) + (-12.594 × e) + 6.018 for internal frictional angle of soils. For the granite area, the statistics-based estimation model (SEM) is proposed as kgr = (8.281 × 10^-03 × e) + (0.639 × D₁₀) + (-2.766 × 10^-05 × c_u) - (9.907 × 10^-03) for permeability coefficients; c_gr = (-0.689 × Fines) + (-0.0744 × S) + 18.59 for cohesion; and φ_gr = (33.640 × r_d) + (-0.875 × e) - 9.685 for internal frictional angle of soils. The use of statistics-based estimation models (SEMs) for landslide-triggering factors that trigger landslides will support the simple calculation of permeability coefficient and shearing strength (cohesion and internal frictional angle), only requiring information about the physical properties of soil at the natural slopes that have different geological features such as gneiss and granite areas.

A Pogorelov polytope is a combinatorial simple 3-polytope realizable in the Lobachevsky (hyperbolic) space as a bounded right-angled polytope. It has no 3- and 4-gons and may have any prescribed numbers of k-gons, k ≥ 7. Any polytope with only 5-, 6- and at most one 7-gon is Pogorelov. For any other prescribed numbers of k-gons, k ≥ 7, we give an explicit construction of a Pogorelov and a non-Pogorelov polytopes. Any Pogorelov polytope different from Löbel polytopes can be constructed from the 5- or the 6-barrel by cuttings off pairs of adjacent edges and connected sums with the 5-barrel along a 5-gon with the intermediate polytopes being Pogorelov. For fullerenes there is a stronger result. Any fullerene different from the 5-barrel and the (5, 0)-nanotubes can be constructed by only cuttings off adjacent edges from the 6-barrel with all the intermediate polytopes having 5-, 6- and at most one additional 7-gon adjacent to a 5-gon. This result can not be literally extended to the latter class of polytopes. We prove that it becomes valid if we additionally allow connected sums with the 5-barrel and 3 new operations, which are compositions of cuttings off adjacent edges. We generalize this result to the case when the 7-gon may be isolated from 5-gons.

Abstract: Escherichia coli are remarkably versatile microorganisms and important members of the normal intestinal microbiota of humans and animals. This harmless commensal organism can acquire a mixture of comprehensive mobile genetic elements that contain genes encoding viru-lence factors, becoming an emerging human pathogen capable of causing a broad spectrum of intestinal and extraintestinal diseases. Nine definite enteric E. coli pathotypes have been well characterized, causing diseases ranging from various gastrointestinal disorders to urinary tract infections. These pathotypes employ many virulence factors and effectors subverting the func-tions of host cells to mediate its virulence and pathogenesis. This review summarizes new de-velopments in our understanding of diverse virulence factors associated encoding genes used by different pathotypes of enteric pathogenic E. coli to cause intestinal and extraintestinal diseases in humans.

For shear-critical structural elements where the use of stirrups is not desirable, such as slabs or beams with reinforcement congestion, steel fibers can be used as shear reinforcement. The contribution of the steel fibers to the shear capacity lies in the action of the steel fibers bridging the shear crack, which increases the shear capacity and prevents a brittle failure mode. This study evaluates the effect of the amount of fibers in a concrete mix on the shear capacity of steel fiber reinforced concrete beams with mild steel tension reinforcement and without stirrups. For this purpose, twelve beams were tested. Five different fiber volume fractions were studied: 0.0%, 0.3%, 0.6%, 0.9%, and 1.2%. For each different steel fiber concrete mix, the concrete compressive strength was determined on cylinders and the tensile strength was determined in a flexural test on beam specimens. Additionally, the influence of fibers on the shear capacity is analyzed based on results reported in the literature, as well as based on the expressions derived for estimating the shear capacity of steel fiber reinforced concrete beams. The outcome of these experiments is that a fiber percentage of 1.2% or fiber factor of 0.96 can be used to replace minimum stirrups according to ACI 318-14 and a 0.6% fiber volume fraction or fiber factor of 0.48 to replace minimum stirrups according to Eurocode 2. A fiber percentage of 1.2% or fiber factor of 0.96 was observed to change the failure mode from shear failure to flexural failure. The results of this presented study support the inclusion of provisions for steel fiber reinforced concrete in building codes and provides recommendations for inclusion in ACI 318-14 and Eurocode 2, so that a wider adoption of steel fiber reinforced concrete can be achieved in the construction industry.

A non-Newtonian fluid model is used to investigate the two-dimensional pulsatile blood flow through a tapered artery with a stenosis. The mixed convection effects of heat and mass transfer are also taken into account. By applying non-dimensionalization and radial coordinate transformation, we simplify the system in a tube. Under the finite difference scheme, numerical solutions are calculated for velocity, temperature concentration, resistance, impedance, wall shear stress and shearing stress at the stenosis throat. Finally, Quantitative analysis is carried out.

In this paper, we consider the relation of more than four harmonic points in a line. For this purpose, starting from the dependence of the harmonic points, Desargues’ theorems, and perspectivity, we note that it is necessary to conduct a generalization of the Desargues’ theorems for projective complete n-points, which are used to implement the definition of the generalization of harmonic points. We present new findings regarding the uniquely determined and constructed sets of H-points and their structure. The well-known fourth harmonic points represent the special case (n=4) of the sets of H-points of rank 2, which is indicated by P42.

Preprints are regularly cited in peer reviewed journal articles, books and conference paper. Are preprint citations somehow less important than citations to peer reviewed research papers? This study investigates citation patterns between 2017 and 2020 for preprints published in three preprint servers, one specializing in biology (bioRxiv), one in chemistry (ChemRxiv), and another hosting preprints in all disciplines (Research Square). As evaluation of scholarship continues to largely rely on citation-based metrics, this analysis and its outcomes will be useful to inform new research-based education in today’s scholarly communication.

Pancreatic cancer is a fatal disease with mortality rate of 5% and a with a limited survival rate of 5 years. Despite of the extensive efforts that has been made to cure the disease it still has been considered as ‘undruggable’. It is characterized by epithelial to dense stromal tumor formation however due to lack of diagnosis options and treatment test available to detect the disease to the point at which resection of the tumor is possible, it makes it the fourth leading cause of cancer related death. The unavailable information regarding the early detection of biological markers along with the increased invasive tumor, the inherit chemoresistance against medication radiation and chemotherapy stubbornly fail the therapeutic options available. These associated problems made the scientists to reevaluate the approaches that are currently in practice and take a step back to fully understand the basic biological pathways that are involved in the pancreatic cancer, the heterogeneity of the tumor itself along with expression and a number of mutations that are observed at different locations. Clinical trial along with new approaches are nowadays focus of research to treat this tumor. The review paper describes the basic cellular pathways involved in pancreatic cancer, the gene mutations and their expression having effect on the pathology of the diseases along with treatment options that are available to treat the tumor. These efforts will help with the expansion of our knowledge to undergo the clinical trial and the synthesis of novel medicines for the prognosis of the disease.

The violation of privacy, others people or personal, is a very current problem, which concerns not only on the web but also in private life. In the years 1990 it was expected that nowadays, that any routine operation was carried out "manually", and it would be performed through mobile phones or personal computers. The problem pertains the distribution network that allows to share and bring together information and as result the network becomes unsafe, if subjected to attacks. Nowaday we put personal information on web because otherwise we are seen as “weak”. This work aims to measure and analyze how much information are shared by users of a pre-established social network and it is carried out through a set of algorithms techniques of machine learning.

A via ferrata (from the German “klettersteig”, hereinafter VF) is a sports route located on forest and mountains vertical rock walls equipped with steps, chains, artificial dams, bridges and other fixed elements and which have a steel cable (safety cable) all the way along allowing users to secure their progress and avoid possible falls [1]. This article aims to analyse the state of the art of the VF sector in Spain, especially in terms of the regulations of obligatory compliance, in addition to defining the basic characteristics of the installations to ensure that these are safe for users, providing a previously non-existent summary of the most important recommendations regardless of the country where they are installed.

A COVID-19 disease threatens the population and the economies of the countries significantly. Till now, this pandemic has affected 215 counties or territories. Unavailability of vaccine is the primary concern for the society. To avoid the spread of this disease, social isolation must be preserved and the inter and intra-population movement must be minimized. To reduce the possibility of transmission, the categorization of regions based on susceptibility to COVID-19 infection is a must.Due to the unavailability of a large amount of paper collection for this novel COVID-19 diseases, we used current literature available on a COVID-19 susceptibility of the diabetic patient, human reproductivity, hemodialysis patient’s, pregnant women and meteorological factors and geographical location. Countries in the cold region are more susceptible to the risk of COVID-19 transmission. There was no evidence of the spread of this disease from non-respiratory bodies. Diabetic patients and pregnant women were found to be more susceptible to COVID-19 infection. Anosmia was observed in the majority of the COVID-19 infected cases in European countries. No evidence indicates COVID-19's impact on the human reproductive system explicitly. No cases of vertical transmission of this disease have been observed until now. All the studies available till now is the small scale study. Correlation with something always does not mean causation. There are certain factor like pollution level, temperature Diurnal temperature range, geographical factor, humidity, pollution level, wind speed, population density, medical healthcare facilities social and political factor plays a critical role in transmitting the SARS-COV-2 virus. Besides the adverse effects, it has taught us to shed our selfish goals and to promote the welfare of all.

Separation and detection of cells and particles in a suspension are essential for various applications, including biomedical investigations and clinical diagnostics. Microfluidics realizes the miniaturization of analytical devices by controlling the motion of a small volume of fluids in microchannels and microchambers. Accordingly, microfluidic devices have been widely used in particle/ cell manipulation processes. Different microfluidic methods for particle separation include dielectrophoretic, magnetic, optical, acoustic, hydrodynamic, and chemical techniques. Dielectrophoresis (DEP) is a method for manipulating polarizable particles’ trajectories in non-uniform electric fields using unique dielectric characteristics. It provides several advantages for dealing with neutral bioparticles owing to its sensitivity, selectivity, and noninvasive nature. This review provides a detailed study on the signal-based DEP methods that use the applied signal parameters, including frequency, amplitude, phase, and shape for cell/particle separation and manipulation. Rather than employing complex channels or time-consuming fabrication procedures, these methods realize sorting and detecting the cells/particles by modifying the signal parameters while using a simple device. In addition, these methods can significantly impact clinical diagnostics by making low-cost and rapid separation possible.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

Classical k-ratio models, e.g. ZAF and phi(rho z), used in electron probe microanalysis (EPMA) assume a homogeneous or multi-layered material structure, which essentially limits the spatial resolution of EPMA to the size of the interaction volume where characteristic x-rays are produced. We present a new model for characteristic x-ray emission that avoids assumptions on the material structure to not restrict the resolution of EPMA a-priori. Our model bases on the spherical harmonic (PN) approximation of the Boltzmann equation for electron transport in continuous slowing down approximation. PN models have a simple structure, are hierarchical in accuracy and well-suited for efficient adjoint-based gradient computation, which makes our model a promising alternative to classical models in terms of improving the resolution of EPMA in the future. We present results of various test cases including a comparison of the PN model to a minimum entropy moment model as well as Monte-Carlo (MC) trajectory sampling, a comparison of PN-based k-ratios to k-ratios obtained with MC, a comparison with experimental data of electron backscattering yields as well as a comparison of PN and Monte-Carlo based on characteristic X-ray generation in a three-dimensional material probe with fine structures.

The effect of CO2 pre-treatments on tomato quality prior to cold storage was investigated using physiochemical and transcriptome changes. Three hours CO2 treated fruits were firmer than untreated fruits and had a good appearance even after being transferred from 4°C storage to 20°C for 8 d. CO2 pretreatment with cold storage showed a synergistic effect on delayed ripening through reduced respiration; these tomatoes exhibited a lower lycopene content than untreated fruit under cold storage. Tomatoes treated with 30% CO2 had fewer pits than untreated fruits subjected to chilling temperatures, even after being transferred to 20°C for 8 d. Functional enrichment analyses from transcriptome and metabolome commonly showed that CO2-responsive genes or metabolites were involved in the sucrose and starch and biosynthesis of secondary metabolisms. The most frequently detected domain, ethylene-responsive factor domain and reduced glycolysis provide insights into the mechanism that CO2 regulates tomato quality.

Alfalfa (Medicago sativa L.) is the most cultivated forage legume around the world. Under a variety of growing conditions, forage yield in alfalfa is stymied by biotic and abiotic stresses including heat, salt, drought, and disease. Given the sessile nature of plants, they use strategies such as differential gene expression to respond to environmental cues. Transcription factors control the expression of genes that contribute to or enable tolerance and survival during periods of stress. Basic-leucine zipper (bZIP) transcription factors have been demonstrated to play a critical role in regulating plant growth and development as well as mediate the responses to abiotic stress in several species, including Arabidopsis thaliana, Oryza sativa, Lotus japonicus, and Medicago truncatula. However, there is little information about bZIP transcription factors in cultivated alfalfa. In the present study, 237 bZIP genes were identified in alfalfa from publicly available sequencing data. Multiple sequence alignments showed the presence of intact bZIP motifs in the identified sequences. Based on previous phylogenetic analyses in Arabidopsis thaliana, alfalfa bZIPs were similarly divided and fell into 10 groups. The physicochemical properties, motif analysis, and phylogenetic study of the alfalfa bZIPs revealed high specificity within groups. The differential expression of alfalfa bZIPs in a suite of tissues indicates that particular bZIP genes are specifically expressed at different developmental stages in alfalfa. Similarly, expression analysis in response to ABA, cold, drought, and salt stresses, indicates that a subset of bZIP genes are also differentially expressed and likely play a role in abiotic stress signaling and/or tolerance. These expression patterns were further verified by qRT-PCR. However, further functional characterization of bZIP transcription factors in alfalfa will help illuminate the role they play in stress tolerance mechanisms in legumes and facilitate the molecular breeding of stress tolerance in alfalfa.

A Natural gas is increasingly being sought after as a vital source of energy, given that its production is very cheap and does not cause the same environmental harms that other resources, such as coal combustion, do. Understanding and characterizing the behavior of natural gas is essential in hydrocarbon reservoir engineering, natural gas transport, and process. Natural gas compressibility factor, as a critical parameter, defines the compression and expansion characteristics of natural gas under different conditions. In this study, a simple second-order polynomial model based on the group method of data handling (GMDH) is presented to determine the compressibility factor of different natural gases at different conditions, using corresponding state principles. The accuracy of the model evaluated through graphical and statistical analyses. The results show that the model is capable of predicting natural gas compressibility with an average absolute error of only 2.88%, a root means square of 0.03, and a regression coefficient of 0.92. The performance of the developed model compared to widely known, previously published equations of state (EOSs) and correlations, and the precision of the results demonstrates its superiority over all other correlations and EOSs.

Improving air quality and reducing human exposure to unhealthy levels of airborne chemicals are important global missions, particularly in China. Satellite remote sensing offers a powerful tool to examine regional trends in NO2, thus providing a direct measure of key parameters that strongly affect surface air quality. To accurately resolve spatial gradients in NO2 concentration using satellite observations and thus understand local and regional aspects of air quality, a priori input data at sufficiently high spatial and temporal resolution to account for pixel-to-pixel variability in the characteristics of the land and atmosphere are required. In this paper, we adapt the Berkeley High Resolution product (BEHR v3.0A, v3.0B and v3.0C) and meteorological outputs from the Weather Research and Forecasting (WRF) model to describe column NO2 in southern China. The BEHR approach is particularly useful for places with large spatial variabilities and terrain height differences such as China. We retrieved tropospheric NO2 vertical column density (TVCD) within part of southern China, for four seasons of 2015, based upon satellite datasets from Ozone Monitoring Instrument (OMI). Retrieval results are validated by comparing with MAX-DOAS tropospheric column measurements conducted in Guangzhou. BEHR retrieval algorithms are more consistent with MAX-DOAS measurements than OMI-NASA retrieval, opening new windows into research questions that require high spatial resolution, for example retrieving NO2 vertical column and ground pollutant concentration in China and other countries.

This article focuses on the current state-of-the-art in the area of cellular and molecular biotechnology for over-production of clinically relevant therapeutic growth factors and how the technology can be used for the treatment of osteoarthritis (OA). Transfected and irradiated protein packaging cell lines may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage matrix regeneration. We discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging cell lines are superior to bacterial expression systems and are likely to have a significant impact on the development of new biological therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA.

Trichomes are a common morphological defense against pests, in particular, type IV glandular trichomes have been associated with resistance against different invertebrates. Cultivated tomatoes usually lack or have a very low density of type IV trichomes. Thus, specific breeding programs to incorporate these natural defences, that are common within the Solanum genus, might improve a more sustainable management. We have identified a S. pimpinellifolium accession with very high density of this type of trichomes. Two F2 mapping populations using two different parents have been developed, characterized and genotyped using a new genotype methodology, K-seq. We have been able to build an ultra-dense genetic map with 147,326 markers with an average distance between markers of 0.2 cM that has allowed us to perform a detailed mapping. We have used two different families and two different approaches, QTL mapping and QTL-seq, to identify several QTLs implicated in the control of trichome type IV developed in this accession on the chromosomes 5, 6, 9 and 11. The QTL located on chromosome 9 is a major QTL that has not been previously reported in S. pimpinellifolium that increases by a factor of 9 the density of trichomes.

The cellular stress response corresponds to the molecular changes that cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression, at transcriptional and post-transcriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support translation of specific mRNAs. One of the major mechanisms involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Importantly, cellular mRNA IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents an update of the reported ITAFs regulating cellular mRNA translation and of the different mechanisms allowing them to control translation initiation in specific conditions. The impact of ITAFs on coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.

The main regulatory factors during the adaptation of cancer cells to hypoxic stress are the hypoxia-inducible factors (HIFs), which are being increasingly recognized as an interesting and challenging target for the design of new chemotherapeutic molecules. HIF2A was found to have an large internal hydrophilic cavity within its PAS-B domain, unique to this sub-unit and is suggested to be a possible ligand-binding site. Regulation of HIF2A by cellular molecules is still greatly unknown. In This paper we have employed in-silico techniques, such as molecular docking and dynamic simulation, to design new direct inhibitors against HIF-2A subunit via targeting one of its critical domains and the final top screened molecules have been tested on hypoxic cancer cells for further validation of their inhibitory potential. we targeted the hydrophilic cavity inside the PAS-B domain of the HIF2A to identify novel molecules with a high binding capacity. Virtual Screening methodology was used for molecular docking of NSC library against the target domain inside the HIF2A PAS-B domain with the top 5% compounds with significant MolDock and Re-rank scores were selected for further analysis. The NSC 106416, NSC 217021, NSC 217026, and NSC 215639 compounds were selected based on their docking scores. NSC 215639 had the minimum polar solvation energy and also had a relative strong binding energy. NSC 217026 had the strongest binding energy among other compounds.

Penicillium digitatum is the major postharvest pathogen of citrus fruit under Mediterranean climate conditions. In the present work, we have addressed the study of the role of P. digitatum’s proteases in virulence following two complementary approaches. In a first approach, we have undertaken the functional characterization of the P. digitatum prtT gene, which codes for a transcription factor previously shown to regulate extracellular proteases in other filamentous fungi. Deletion of prtT caused a significant loss in secreted protease activity during in vitro growth assays. However, there was no effect on virulence. Gene expression of the two major secreted acid proteases was barely affected in the ΔprtT deletant during infection of citrus fruit. Hence, no conclusion could be drawn on the role of these secreted acidic proteases on the virulence of P. digitatum. In a second approach, we have studied the effect of different protease inhibitors and chelators in virulence. Co-inoculation of citrus fruit with P. digitatum conidia and a cocktail of protease inhibitors resulted in almost a complete absence of disease development. Analysis of individual inhibitors revealed that the metalloprotease inhibitor 1,10-phenanthroline was responsible for the observed effect. The application of metal ions reverted the protective effect caused by the metallopeptidase inhibitor. These results may set the basis for the development of new alternative treatments to combat this important postharvest pathogen.

The Equator Principle is the goal of promoting the harmonious development of my country's economy and society. It promotes the green transformation and upgrading of the industrial structure by strictly controlling the flow of commercial bank funds, so as to achieve the goal of environmental protection and the coordinated development of the national economy. This paper uses factor analysis to reduce the dimensions of 10 financial indicators and non-financial indicators that measure the operating performance and development potential of joint-stock commercial banks, and then compares the comprehensive operating performance, liquidity, and safety of Industrial Bank and comparable banks. And the level of profitability, analyze the difference in comprehensive operating performance of joint-stock commercial banks joining the Equator Principles compared with commercial banks that have not joined the Equator Principles. The results of the study found that joining the Equator Principles of joint-stock commercial banks can improve comprehensive operating performance in the short term. In the long run, the development trend of Industrial Bank will be similar to that of comparable banks in the same category. Joining the Equator Principles of Industrial Bank can improve its liquidity and profitability, but it will not in the long run. Conducive to the improvement of the asset quality of joint-stock commercial banks. In this regard, the government, enterprises and financial institutions should work together to help commercial banks achieve an effective balance between operating performance and social responsibility, so as to achieve the goals of "carbon peak" and "carbon neutral".

The Lamiaceae belong to the species-richest families of flowering plants and harbor many species used as herbs or for medicinal applications, such as Basils or Mints. Evolution of this group has been driven by chemical speciation, mainly of Volatile Organic Compounds (VOCs). The commercial use of these plants is characterized by a large extent of adulteration and surrogation. To authenticate and discern the species, is, thus, relevant for consumer safety, but usually requires cumbersome analytics, such as Gas Chromatography, often to be coupled with Mass Spectroscopy. We demon-strate here that quartz-crystal microbalance (QCM)-based electronic noses provide a very cost-efficient alternative, allowing for a fast, automated discrimination of scents emitted from leaves of different plants. To explore the range of this strategy, we used leaf material from four genera of Lamiaceae along with Lemongrass as similarly scented, but non-related outgroup. In order to unambiguously differentiate the scents from the different plants, the output of the 6 different SURMOF/QCM sensors was analyzed using machine learning (ML) methods, together with a thorough statistical analysis. The exposure and purging datasets (4 cycles) obtained from a QCM-based, low-cost homemade portable e-Nose were analyzed with Linear Discriminant Analysis (LDA) classification model. Prediction accuracies with repeating test measurements reached values of up to 90%. We show that it is not only possible to discern and identify plants on the genus level, but even to discriminate closely related sister clades within a genus (Basil), demonstrating that e-Noses are a powerful technology to safeguard consumer safety against the challenges of globalized trade.

Non-linear loads in circuits cause the appearance of harmonic disturbances both in voltage and current. In order to minimize the effects of these disturbances and, therefore, to control over the flow of electricity between the source and the load, they are often used passive or active filters. Nevertheless, determining the type of filter and the characteristics of their elements is not a trivial task. In fact, the development of algorithms for calculating the parameters of filters is still an open question. This paper analyzes the use of genetic algorithms to maximize the power factor compensation in non-sinusoidal circuits using passive filters, while concepts of geometric algebra theory are used to represent the flow of power in the circuits. According to the results obtained in different case studies, it can be concluded that the genetic algorithm obtain high quality solutions that could be generalized to similar problems of any dimension.

Background: The treatment plan of prosthetic restorations supported by dental implants require comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A systematic review of the literature was conducted with a PICO question: "For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?". A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS* OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%) or prospective evaluations of prosthesis with various kinds of events (18%). But also narrative reviews of literature (14%) and in vitro/animal studies (16%) were found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.

Advances of Relativity Theory are in the replacement of the space-time model with time-invariant universal space that has a variable energy density. Every physical object with mass m and energy E is diminishing the energy density of space exactly for the amount of its energy. Lorentz factor has its origin in the variable energy density of universal space, we call it "superfluid quantum space" - SQS that is the primordial energy of the universe. Universal SQS is the absolute frame of reference for all observers as confirmed experimentally by the GPS system, which demonstrates that the relative rate of clocks is valid for all observers. A planet's perihelion precession and the Sagnac effect are the results of the SQS dragging effect.

Matrix metalloproteinase 3 (MMP3) plays multiple roles in pro-tumorigenic proteolysis and in intracellular transcription. These include inducing connective tissue growth factor [CTGF, also known as cellular communication network factor 2 (CCN2)] and prompting a new definition of MMP3 as a moonlighting metalloproteinase. Members of the MMP family have been found within tumor-derived extracellular vesicles (EVs) such as oncosomes or exosomes. We here investigated the roles of MMP3-rich oncosomes in tumor progression, molecular transmission, and gene regulation. MMP3 and CCN2/CTGF were significantly co-expressed in tumor samples derived from patients suffering from colorectal adenocarcinoma. We found that oncosomes derived from a rapidly metastatic colon cancer cells (LuM1) were enriched in MMP3 and a C-terminal half fragment of CCN2/CTGF. MMP3-rich oncosomes were highly transmissive into recipient cells and were pro-tumorigenic in an allograft mouse model. Oncosome-derived MMP3 was transmissive into recipient cell nuclei, trans-activated CCN2/CTGF promoter, and induced CCN2/CTGF production at 1 to 6 hours after the addition of oncosomes to culture media. In addition, CRISPR/Cas9-mediated knockout of MMP3 showed significant anti-tumor effects, including inhibition of migration and invasion of LuM1 cells in vitro, inhibition of tumor growth in vivo, and reduction of CCN2/CTGF and its promoter activity in vitro. These data newly demonstrate that the oncosome-derived moonlighting metalloproteinase promotes metastasis and is pro-tumorigenic at distant sites as well as a transmissive trans-activator for the cellular communication network gene.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, spectral CT has emerged in the field of computed tomographies, utilizing detailed information from extracted spectral parameters of the specimen. Metal nanoparticle platforms enable effective payload delivery for this technique. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 functionalized gold nanoparticles (AuNPs) for tumor specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities, but not on corresponding normal tissue cells, predestining this target epitope for tumor-selective in vivo targeting. In vitro microscopical analysis revealed the presence of cmHsp70.1-AuNP in the cytosol of tumor cell lines, being internalized via the endosomal-lysosomal pathway. In tumor bearing mice the biodistribution as well as the intratumorally enrichment of AuNP were examined 24h after i.v. application, in vivo. In parallel to spectral CT analysis, histological analysis confirmed the presence of tumor cells. In contrast to control NP, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively in tumors of different preclinical mouse models. Furthermore, the biodistribution of AuNP, following i.v. injection, was analyzed by a machine-learning approach on digitalized slides. In summary, utilizing mHsp70 on tumor cells for guidance of cmHsp70.1 antibody functionalized nanoparticles enables sufficient enrichment and uniform distribution of AuNPs in mHsp70-expressing tumor cells, adequate for various microscopical imaging techniques and spectral-CT-based tumor delineation, in vivo.

Ubiquitous computing comprises scenarios where networks, devices within the network, and software components change frequently. Market demand and cost-effectiveness are forcing device manufacturers to introduce new-age devices. Also, the Internet of Things (IoT) is transitioning rapidly from the IoT to the Internet of Everything (IoE). Due to this enormous scale, effective management of these devices becomes vital to support trustworthy and high-quality applications. One of the key challenges of IoT device management is automatic device classification with the logically semantic type and using that as a parameter for device context management. This would enable smart security solutions. In this paper, a device classification approach is proposed for the context management of ubiquitous devices based on unsupervised machine learning. To classify unknown devices and to label them logically, a proactive device classification model is framed using a k-Means clustering algorithm. To group devices, it uses the information of network parameters such as Received Signal Strength Indicator (rssi), packet_size, number_of_nodes in the network, throughput, etc. Experimental analysis suggests that the well-formedness of clusters can be used to derive cluster labels as a logically semantic device type which would be a context for resource management and authorization of resources. This paper fulfills an identified need of proactive device classification for device management.

Immersion in salt-lake solution was adopted to periodically test the concrete chloride-ion diffusion coefficient. The regression analysis was also completed. Also investigated was the time-dependent law of concrete chloride-ion diffusion coefficient with time. The influence of chloride-ion concentration in solution, water-to-cement ratio, and corrosion time on the largeness and accumulation rate of the concrete chloride-ion diffusion coefficient was also analyzed. Test results show that the concrete chloride-ion diffusion coefficient gradually decreased with increasing time and increased with increasing chloride-ion concentration in a salt lake . Taking into account the influence of factors such as water–binder ratio, chloride-ion concentration, and time-varying characteristics, a multi-factor calculation model for the concrete chloride-ion diffusion coefficient was established. Combining the prediction results and the measured data reported in this paper, the effectiveness and applicability of the established concrete chloride-ion diffusion coefficient calculation model were compared and verified, and the durability design and service life of a concrete structure under cool chlorine were compared. The results of analysis provide important boundary conditions.

The node position information is critical in the wireless sensor network (WSN). However, the existing positioning algorithms commonly have low positioning accuracy because of noise interferences in communication. To solve this problem, this paper presents an iterative positioning model based on distance correction to improve the positioning accuracy of the target node in WSN. First, the log-distance distribution model of received signal strength indication (RSSI) ranging is built and the noise impact factor is derived based on the model. Second, the initial position coordinates of the target node are obtained based on the triangle centroid localization algorithm, thereby calculating the distance deviation coefficient under the influence of noise. Then, the ratio of the distance measured by the log-normal distribution model to the median distance deviation coefficient is taken as the new distance between the anchor node and the target node. Based on the new distance, the triangular centroid positioning algorithm is used again to calculate the target node coordinates. Finally, the iterative positioning model is constructed, and the distance deviation coefficient is updated repeatedly to update the positioning result until the set number of iterations is reached. Experiment results show that the proposed iterative positioning model can improve positioning accuracy effectively.

The Rybczynski theorem describes the trade effect within production analyses between factor endowments and outputs. The Stolper-Samuelson theorem focuses on cost analyses between factor reward and commodity price. This paper examines the trade effect of changes of factor endowments on prices, based on general equilibrium. The study shows that changes of factor endowments cause domestic output changes (the Rybczynski effect), which affect output prices and factor prices (the Stolper-Samuelson effect). It is like a chain of effects that the Rybczynski’s trade effect triggers the Stolper-Samuelson’s trade effect. The analysis of this paper shows that a small increase of a factor endowment of any country rewards another factor and the commodity using the latter factor intensively. It displays a tuneful circle. Trade brings a well-balanced development to the world.

Hypoxia is one of the most common pathological conditions which results from ischemic injury, trauma, inflammatory conditions, tumors, The adaptation of the body to hypoxia is a phenomenon that is of great importance both in normal conditions and in Most of the cellular response’ reactions to hypoxia is associated with a family of transcription factors called hypoxia-inducible factors (HIF). They induce the expression of a wide range of genes that help cells adapt to a hypoxic HIF functions are currently being extensively studied. In 2019, William G. Kaelin and Gregg Semenza from the USA and Sir Peter J. Ratcliffe from the UK received the Nobel Prize in Physiology or Medicine for the discovery of the basic mechanisms of adaptation to hypoxia and investigation of the role of HIF factor in the regulation of the hormone erythropoietin Based on its pivotal physiological importance, the HIF factor attracts more and more attention as a new potential target for treating a large number of diseases associated with Most of the experimental work dealing with the HIF factor is focused on its role in liver and However, increasing amount of experimental results clearly demonstrates that the HIF factor-based response represents an universal adaptation mechanism for all kinds of tissues, including the nervous system where HIF is critical for regulating neurogenesis, nerve cell differentiation, and neuronal This review provides actual overview about the complex role of HIF-1 in the adaptation of nerve cells to hypoxia with the focus on its potential role by various neuronal

Introduction: This study aimed to validate the psychometric properties of the German eHealth Impact Questionnaire (eHIQ-G), which is divided into two independently administered and scored parts. Methods: 162 people with MS browsed one of two possible websites containing information on MS and completed an online survey. Internal consistency was assessed by Cronbach’s alpha and structural validity by Confirmatory Factor Analysis. Construct validity was examined by assessing correlations with the eHealth Literacy Questionnaire and the General Self-Efficacy Scale. Moreover, the mean difference of the eHIQ-G score between the two websites was investigated. Results: Cronbach’s alpha for the eHIQ-G subscales ranged from .833 to .885. The eHIQ-G part 1 achieved acceptable levels of goodness-of-fit indices, whereas the fit for the eHIQ-G part 2 was poor and likewise for the alternative modified models. The correlations with the reference instruments were 0.08 – 0.62 and as expected. Older age was related with lower eHIQ-G part 1 score, whereas no significant effect was found for education. Although not significant, the website ‘AMSEL’ reached higher mean scores on eHIQ part 2. Conclusion: The eHIQ-G has good internal consistency, and sufficient structural and construct validity. It will facilitate the measurement of the impact of websites providing health information.

Abstract: Periodontal disease is the main reason for tooth loss in adults. Tissue engineering and regenerative medicine are the advanced technologies used to manage soft and hard tissue defects caused by periodontal disease. We developed a transforming growth factor-β3 chitosan sponge (TGF-β3/CS) to repair periodontal soft and hard tissue defects. We investigated the proliferation and osteogenic differentiation behaviors of primary human periodontal ligament stem cells (hPDLSCs) to discuss the bioactivity and application of TGF-β3 in periodontal disease. We separately used Calcein-AM/PI double-labeling or CM-Dil-labeling coupled with fluorescence microscopy to trace the survival and function of the cells after implantation in vitro or in vivo. The mineralization of osteogenic differentiated hPDLSCs was confirmed by measuring ALP activity and calcium content. The levels of COL I, ALPL, TGF-βRI, TGF-βRII, and Pp38/t-p38 were tested using Western blot to explore the mechanism of bone repair prompted by TGF-β3. When hPDLSCs were inoculated with different concentrations of TGF-β3/CS (62.5–500 ng/mL), ALP activity was the highest in TGF-β3 (250 ng/mL) group after seven days (P < 0.05 vs. control); the calcium content in each group increased significantly after 21 and 28 days (P < 0.001 vs. control). The best result was achieved in the TGF-β3 (500 ng/mL) group. All results showed that TGF-β3/CS can promote osteogenic differentiation of hPDLSC and may be involved in the p38 MAPK signaling pathway. TGF-β3/CS has the potential for application in the repair of incomplete alveolar bone defects.

The COVID-19 disease spreads swiftly, and nearly three months after the first positive case was confirmed in China, Coronavirus started to spread all over the United States. Some states and counties reported an extremely high number of positive cases and deaths, while some reported too few COVID-19 related cases and mortality. In this paper, the factors that could affect the transmission of COVID-19 and its risk level in different counties have been determined and analyzed. Using Pearson Correlation, K-means clustering, and several classification models, the most critical ones were determined. Results showed that mean temperature, percent of people below poverty, percent of adults with obesity, air pressure, percentage of rural areas, and percent of uninsured people in each county were the most significant and effective attributes.

Increasing the quality factor (Q) of an optical resonator device has been a research focus to be utilized in various applications. Higher Q-factor means light is confined in a longer time which will produce a shaper peak and higher transmission. In this paper, we introduce a novel technique to increase further the Q-factor of a one-dimensional photonic crystal (1D PhC) cavity device by using an end loop-mirror (ELM). The technique utilizes and recycles the light transmission from the conventional 1D PhC cavity design. The design has been proved to work by using the 2.5D FDTD simulation with Lumerical FDTD and MODE softwares. By using the ELM technique, the Q- factor of a 1D PhC design has been shown to have increased up to 79.53 % from the initial Q value without the ELM. This novel design technique can be combined with any high Q-factor and very high Q-factor designs to increase more the Q-factor value of a photonic crystal cavity devices or any other suitable optical resonator devices. The experimental result shows that the device is measurable by adding a Y-branch component to the one-port structure and able to get the high-Q result.

Concept Knowledge (C-K) theory has been used in engineering and science-based research for more than a decade. Design of an Information Technology (IT) artefact is mostly pragmatic in nature. Design Science Research (DSR) methodology applied and studied in many Information Systems (IS) research. Many sub design decisions involved through the design of an IT artefact from a concept (idea) to a working prototype. A DSR artefact is based on a combination of decisions made during several sub-design stages. Artefacts are built based on the selection of elements in each sub-design space. Recording the design decisions on each sub-design space would be beneficial for future researchers. By knowing the design decisions on each sub-design space, researchers would be able to try different combinations of the design. C-K theory provides the ability to capture the design processes’ several sub-design spaces. In this paper, we discuss the DSR research methodology by looking at the stages proposed in the literature, and the application of C-K theory in an IT-based DSR. This paper also proposed a C-K theory-based protocol called Concept Tree for tracking and reporting artefact design steps. The application of C-K theory in DSR is exhibited using the implementation of the Concept Tree for a prototype design IT artefact.

Environmental assessment is a concept that has been designed to facilitate the present generation to meet their needs without compromising the ability of future generations to meet their own needs as well. Thus, this concept has drawn significant attention from various scholars, researchers and industrial practitioners around the world over the past three decades. Life Cycle Environmental Assessment (LCEA) is a widely metric used to assess the potential ecological impacts, which can be caused by electricity generating supply systems or by other systems than power production plants. However, the current LCEA model is biased and ineffective. Because, its omits factors that are increasingly contributing to the ecological degradation. This study has identified the omitted factors through a critical analysis of a set of previous journal articles conducted in the energy sector. In light of this, this study has developed a novel LCEA framework addressing those blind spots. The framework developed in this study is holistic in nature including all the life cycle stages of a power supply system such as Extraction of the Raw Material (ERM), Transport of Raw Material (TRM), Conversion of Raw into Electricity (CRE), and Transmission and Distribution of Electricity (TDE) to the end users. The novel developed LCEA model has been tested and applied to nine power generation plants such as coal, gas, nuclear, biomass, geothermal, hydro, solar thermal, wind onshore and wind offshore. The results have demonstrated that of conventional technologies including coal, gas, and nuclear, coal energy generating source has got the highest life cycle greenhouse gas Grid Emission Factor (GEF) of 2866 kg CO2e/MWh, followed by gas with 728 kg CO2e/MWh, and nuclear has got the least GEF of 35 kg CO2e/MWh. Whereas of renewable energy sources biomass has got the highest GEF of 1508 kg CO2e/MWh, followed by solar thermal with 46.6 kg CO2e/MWh, hydro 39 kg CO2e/MWh, wind offshore 25.25 kg CO2e/MWh, wind onshore 10.1 kg CO2e/MWh, and geothermal closes the ranking with 6.23 kg CO2e/MWh.

Annually, millions of people (including children) across the world face minor to severe impact from natural or human-induced disasters. Diverse models have been conceptualized and adopted at global scale to increase resiliency of children from disasters focusing on preparedness, response and recover. As children spend most of their lives at school or at home, this paper discusses on factors contributing towards improving or degrading resiliency of children from disasters. Giving low priority to institutional resilience, this paper highlights the behavioral aspects of children which becomes their strength on demonstrating appropriate practices to mitigate disaster risks on self at school, home and community. While doing so, attributes from Ajzen’s Theory of Planned Behavior has been linked with the components of resilience to explain the causative factors. Adopting desk review, this paper describes behavioral attributes of children and emphasizes on need of having multi-dimensional framework to enhance resiliency of children.

Data mining plays a critical role in the sustainable decision making. The k-prototypes algorithm is one of the best-known algorithm for clustering both numeric and categorical data. Despite this, however, clustering a large number of spatial object with mixed numeric and categorical attributes is still inefficient due to its high time complexity. In this paper, we propose an efficient grid-based k-prototypes algorithms, GK-prototypes, which achieves high performance for clustering spatial objects. The first proposed algorithm utilizes both maximum and minimum distance between cluster centers and a cell, which can remove unnecessary distance calculation. The second proposed algorithm as extensions of the first proposed algorithm utilizes spatial dependence that spatial data tend to be more similar as objects are closer. Each cell has a bitmap index which stores categorical values of all objects in the same cell for each attribute. This bitmap index can improve the performance in case that a categorical data is skewed. Our evaluation experiments showed that proposed algorithms can achieve better performance than the existing pruning technique in the k-prototypes algorithm.

FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage

Continuous and emerging advances in Information and Communication Technology (ICT) have enabled IoT-to-Cloud applications to be induced by data pipelines coupled with Edge Intelligence-based architectures. Advanced vehicular networks greatly benefit from these architectures due to the implicit functionalities that are focused on realizing the Internet-of-Vehicle (IoV) vision. However, IoV is susceptible to attacks, where adversaries can easily exploit existing vulnerabilities. Several attacks may succeed due to inadequate or weaker authentication techniques. Hence, there is a timely need for hardening the authentication process through cutting-edge access control mechanisms. This paper proposes a Blockchain-based Multi-Factor authentication model that uses an embedded Digital Signature (MFBC_eDS) for vehicular clouds and Cloud-enabled IoV. Our proposed MFBC_eDS model consists of a scheme that integrates the Security Assertion Mark-up Language (SAML) to the Single Sign-On (SSO) capabilities for a connected Edge-to Cloud ecosystem. MFBC_eDS draws an essential comparison with the baseline authentication scheme suggested by Karla and Sood. Based on the foundations of Karla and Sood’s scheme, an embedded Probabilistic Polynomial-Time Algorithm (ePPTA) and an additional Hash function for the Pi generated during Karla and Sood’s authentication are proposed and discussed. The preliminary analysis of the proposition shows that the approach is more suitable to counter major adversarial attacks in an IoV-centered environment based on Dolev-Yao adversarial model while satisfying aspects of the CIA triad.

Abstract Due to the relatively low efficiency of thermoelectric (TE) generators, they have mostly been used in niche applications where the unique properties of TE generators outweigh their lack of efficiency, or conditions where it is more reasonable to base the optimal design on maximum generated power rather than maximum efficiency. The aim of this work is to investigate how the different fundamental transport properties (Seebeck coefficient, thermal conductivity and electrical resistivity) in materials with equal figure of merit (ZT) impact TE module design and maximum power output. Further, we discuss and review the strategies to enhance material properties and the latest studies on the TE module performance. It is shown, that by increasing the power factor by a factor of 15 and decreasing the thermal conductivity by 13.33 in order to maintain ZT=1, power output is increased by 45%. This effect is stronger in lower module fill factor and thermal resistance of the heat source and heat sink.

Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.

The growing market penetration of heat pumps indicates the need for a performance test method which better reflects the dynamic behavior of heat pumps. In this contribution, we developed and implemented a dynamic test method for the evaluation of the seasonal performance of heat pumps by means of laboratory testing. Current standards force the heat pump control inactive by fixing the compressor speed. In contrast, during dynamic testing, the compressor runs unfixed while the heat pump is subjected to a temperature profile. The profile consists of the different outdoor temperatures of a typical heating season based on the average European climate and also includes temperature changes to reflect the dynamic behavior of the heat pump. The seasonal performance can be directly obtained from the measured heating energy and electricity consumption making subsequent data interpolation and recalculation with correction factors obsolete. The method delivers results with high precision and high reproducibility and could be an appropriate method for a fair rating of heat pumps.

Focusing geophysics to improve recovery factor of hydrocarbon reservoirs adds value and contributes toward ZERO carbon footprint by increasing the recovery factor by of 30-40 % and thus reducing the cost/carbon emission per produced barrel. Thus, the Enhanced Oil Recovery (EOR) market is expected to grow more than 3.5% annually. This will be even more fueled by the Green-House-Gas (GHG) reduction and subsequent CO2 injection into the reservoirs as they are being produced. Presently, geophysics only ac-counts for a small percentage of this market, thus its growth is inevitable since more deterministic observation lead higher operating efficiency. Imaging the fluids (hydro-carbon, water, and CO2) is a key component to optimized production and injection. We designed a novel electromagnetic (EM) acquisition system that combines mul-ti-physics fluid imaging and acquires surface and borehole data with high fidelity. Borehole calibration is needed to upscale reservoir data and parameters to measurement scale. Multiple electromagnetic methods are used as well as microseismics in one layout for Exploration and Production (E & P) problems. Multi-components in electromagnetics allows resolving oil and water-bearing zones equally well while achieving the best ac-curacy suitable for repeat measurements. Because sedimentary basins are intrinsically anisotropic, considering 3-dimensional anisotropy is essential from measurement and 3D modeling viewpoint. Thus, the results have the better subsurface images. Here, we combine hardware design, methodology, 3D modeling, processing, and interpretations into an integrated technology and demonstrate the success with verifiable case histories.

Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.

With quick improvement in the field of network, everything becomes online. Remote user authentication is a mechanism in which remote server verify the correctness of user over common or public channel. Remote user authentication can be Single server authentication or Multi server authentication. The disadvantage of single server authentication is that the user needs to recall user id and password for each service, he/she need to utilize, however it can overcome by Multi-server authentication in which user needs to register himself with Registration Center (RC) for the first run through and after that onwards he can utilize each service (which are given by servers, associated with RC) by recollecting only one user id and password. In this paper, we analyze Chen's authentication scheme (based on multi server authentication) and show that this scheme is vulnerable to password guessing attack, replay attack, RC spoofing attack, session key verification attack and perfect forward secrecy attack. In this Paper, we propose a biometric based remote user authentication scheme in multi-server environment. Proposed scheme is more secure and efficient as compared to chen's scheme\cite{23}.

This retrospective study aimed to investigate the effect of known risk factors on nonsurgical periodontal treatment (NSPT) response using a pocket depth fine-tuning multilevel linear model (MLM). Thirty-seven patients (24 males and 13 females) with moderate to severe chronic periodontitis were treated with nonsurgical periodontal therapy. Follow-up visits at 3, 6, and 12 months included measurement of several clinical periodontal parameters. Data were extracted from a database system. Probing depth (PD) and Clinical Attachment Loss (CAL) reductions after NSPT in an overall of 1416 initially affected sites (baseline PD ≥ 4 mm), distributed on 536 teeth, were analyzed against known risk factors at three hierarchical levels (patient, tooth and site). The variance component models fitted to assess the three-level variance of PD and CAL decrease for each post-treatment follow-up showed that all levels contributed significantly to the overall variance (P < 0.001). Patients that underwent NSPT and were continually monitored had very curative results. All three hierarchical levels included risk factors who had impact on the to influence the magnitude of PD and CAL reduction. Specifically, the tooth’s type, surfaces involved and teeth mobility site-level risk factors showed the highest influence on these reductions, being highly relevant factors for the NSPT success.

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (3a-3i) exhibited significant clot lysis with respect to negative control and reference drug streptokinase (30,000 IU) while enhanced clotting time (CT) values were observed (130-342 sec) for these tested compounds than the standard drug heparin (110 sec.). High affinity towards 1NFY with greater docking score was observed for the compounds (3a, 3i, 3e, 3d and 3h) than the control ligand RPR200095. In addition, very good inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612-6270) with ACE values (–189.68 to –352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE –197.81 kcal/mol. In vitro, in vivo and in silico results proposed that these newly synthesized compounds can be used as anti-coagulant agents.

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

An important moment in the establishment of forestry seed orchards is the formation of their optimal composition, avoiding inbreeding depression in the outgoing seed material which occurs due to crossbreeding between closely related plus trees, the clones of which comprise the orchards. It is possible to minimize the negative effect of inbreeding by considering the hereditary aspect of the heterogeneous seed orchard material. The purpose of our work is to provide a comparative assessment of the formation and lignification of xylem in annual shoots of the plus trees of Scots pine. We investigated the formation and lignification of xylem in the annual shoots of the plus trees of Scots pine (Pinus sylvestris L.), found in natural forests in the Nizhny Novgorod region of the Russian Federation. Their vegetative progeny were cultivated in the clone archive stationed in the same region. Analyzing the one-type of the 1-year shoots, the time that the shoots were cut from the branches corresponded to the presence of plants in the characteristic phenological phases of seasonal development. A histochemical study of xylem was conducted, using the qualitative reactions of phloroglucinol to lignin. The power of xylem development was estimated by counting, in the radial direction, the cell rows from the core to the cambium in the microscope’s field of view. A significant differentiation of plus trees was revealed in a complex of signs characterizing the level of xylem development and the degree of xylem cell lignification in the tissues of annual shoots. Phenotypic differences in the physiological state of plus trees appeared given a leveled ecological background, indicating their genotypic determinism. This was confirmed by an analysis of variance. The share of the influence of differences between the proper plus trees was between 25.16% ± 8.91% and 53.98% ± 5.48% of the total phenotypic variance of the signs of the seasonal state of xylem. Factor analysis was used to reduce the number of considered indicators of xylem physiological state. The results allowed a cluster analysis to be carried out on the basis of the normalized values of the initial xylem features as well as the principal components derived from them. The association of plus trees was done on the basis of the similarity of the multidimensional estimates of xylem seasonal condition. The objects that were the most remote from the others were identified. This information provides a reasonable approach to the formation of an assortment of Scots pine seed orchards.

The notion of enhancement of the image is to ameliorate the perceptibility of information contained in an image. In the present research, a novel technique for the enhancement of image quality is propounded using fuzzy logic technique with a cuckoo optimization algorithm. Generally, the image is transformed from RGB domain to HSV domain keeping the color information intact within the image. The image has been categorized into three regions: underexposed, overexposed and mixed region on the basis of two threshold values. For the fuzzification of under and overexposed area the degree of membership is defined by the Gaussian membership, while the mixed area is fuzzified by parametric sigmoid function. The key parameters like visual factors and fuzzy contrast provide the quantitative analysis of an image. An objective function is framed which involves entropy and visual factor has been optimized by a new evolutionary cuckoo optimization algorithm. The results procured after simulation by the cuckoo optimization algorithm are compared with Bacterial foraging algorithm and ant colony optimization based image enhancement and this approach is found to be improved.

The basic equation for estimating the aerodynamic power captured by an Anderson Vertical Axis Wind Turbine (AVAWT) is a solution of the Navier-Stokes(N-S) equations for a baroclinic, inviscid flow. In a nutshell, the pressure difference across the AVAWT is derived from Bernoulli’s equation; an upshot of the integration of the N-S momentum equation for a baroclinic inviscid flow, Euler’s momentum equation. The resulting expression for the pressure difference across the AVAWT rotor is plotted as a function of freestream speed. Experimentally determined airstream speeds at the AVAWT inlet and outlet, coupled with corresponding freestream speeds are used in estimating the aerodynamic power captured. The aerodynamic power is subsequently used in calculating the aerodynamic power coefficient of the AVAWT. The actual power coefficient is calculated from the power generated by the AVAWT at various free stream speeds and plotted as a function of the latter. Experimental results show that, at all free stream speeds and tip speed ratios, the aerodynamic power coefficient is higher than the actual power coefficient of the AVAWT. Consequently, the power generated by the AVAWT prototype is lower than the aerodynamic power captured, given the same inflow wind condition.

Phosphorus (P) is an important element in a complete and balanced fertility program that can improve crop P use efficiency and ultimately productivity and profitability. Phosphatic fertilizers use without organic fertilizers leads to gradual decline in soil organic matter, native nutrient status and ultimately reduction in agricultural productivity and economic growth. The objectives of this was to evaluate P efficiencies with incorporation of peach sources, beneficial microbes and P application. From sustainability points of view, alternative use of different sources and forms of organic sources alone or in combination with inorganic P and beneficial microbes possess potential for improving productive capacity of the soil. Separate field experiments (one each on maize and soybean as a test crop) were conducted at Agriculture Research Institute Mingora Swat (ARI) for two consecutive years in summer season of 2016 (year one) and 2017 (year two). For the first time such a study were conducted to utilize peach leftovers and biomass (leaves, twigs, fruits, stones and barks partially decomposed, its compost and biochar) along with three phosphorus (P) levels (50, 75, 100 kg P ha-1) and two beneficial microbes (PSB and Trichoderma) on such a way to enhance soil sustainability and P use efficiency of soybean and maize. The results revealed that organic sources had significant effect on soybean and maize P use efficiency (PUE), P agronomic efficiency (PAE), partial factor productivity (PFPp) and soil P concentration. In experiment 1 among the organic sources, peach residues increased soil P (12.0 mg kg-1) as compared to peach compost and biochar (8.6 & 11.7 mg kg-1). Soil P concentration was maximum (12.1 mg kg-1) with PSB than Trichoderma (9.5 mg kg-1). Application of P at 100 kg ha-1increased soil P contents (16.9 mg kg-1) as compared to 50 and 75 kg P ha 1 (5.9 & 9.6 mg kg-1) respectively. P concentration was increased drastically in year 2 (12.4 mg kg-1) than year one (9.1 mg kg-1). PUE in both crops (soybean and maize) was maximum (25.6 & 28.4%) with peach biochar than compost and residues along with Trichoderma (21.7 & 27.8%). Highest PUE in soybean was recorded with 75 kg P ha-1(22.2%) however in maize maximum PUE was noted with 50 kg P ha-1(33.5%). PAE and PFPp in both crops was maximum with biochar and soil application of Trichoderma than other organic sources and PSB. Among the P levels highest PAE in soybean and maize was recorded with 75 kg ha-1whereas PFPp in soybean was maximum with 75 kg P ha-1 and interestingly in maize it was noted with 50 kg ha-1. Conclusively soybean and maize PAE, PFPp and PUE was higher with biochar, soil incorporation of Trichoderma and P at the rate of 75 kg ha-1 and can improve soybean and maize yield and soil productivity on sustainable basis.

Neuroinflammatory responses are implicated in the pathogenesis of neurodegenerative diseases. In neurodegenerative diseases, neuroinflammatory reactions to neuronal injury are modulated by microglial cells, which are vital innate immune cells in the central nervous system. Activated microglial cells release proinflammatory cytokines, mediators, and neurotoxic factors that induce fatal neuronal injury. The present study investigated the anti-neuroinflammatory effects of cudratricusxanthone L (1), which was isolated from Cudrania tricuspidata. This compound reduced the levels of lipopolysaccharide-stimulated inflammatory mediators and cytokines, including nitric oxide, prostaglandin E2, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and IL-12. These effects suggested that cudratricusxanthone L (1) suppressed the nuclear factor-kappa B (NF-κB) signaling pathway. Specifically, cudratricusxanthone L (1) also attenuated the phosphorylation of Jun kinase and inhibited p38 mitogen-activated protein kinase (MAPK) signaling in BV2 and rat primary microglial cells. These results indicated that cudratricusxanthone L (1) effectively repressed neuroinflammatory processes in BV2 and rat primary microglial cells by inhibiting NF-κB and the MAPK signaling pathway.

The comparison of group means in latent variable models plays a vital role in empirical research in the social sciences. The present article discusses extensions of invariance alignment and Haberman linking concerning the choice of linking functions for comparisons of many groups. Robust linking functions are proposed for invariance alignment and robust Haberman linking that are particularly suited to item response data under partial invariance. In a simulation study, it is shown that both linking approaches have comparable performance, and in some conditions, the newly proposed robust Haberman linking outperforms invariance alignment.

The Short-Term Assessment of Risk and Treatability (START) is deemed the most appropriate instrument for assessing violence risks and management because of its balanced approach between dynamic risk and protective factors. Although several facets of reliability and predictive validity of this tool were strong, its inter-rater reliability, construct validity, and implementation in Asian population were under-investigated. The objective of this research was to examine the inter-rater reliability and construct validity of the START: Thai version within forensic psychiatric inpatients. The participants consisted of 118 forensic psychiatric inpatients hospitalized at Galya Rajanagarindra Institute in Thailand. Trained mental health professionals (i.e., psychiatrists, forensic nurses, clinical psychologists, social workers, and occupational therapists) assessed each participant across twenty domains of the Thai START. The inter-rater reliability was examined using the intraclass correlation coefficient and a confirmatory factor analysis for ordinal data was used to test the construct validity of the scale. The main finding showed a good-to-excellent inter-rater reliability and supported two relational constructs (i.e., strength vs vulnerability subscales) of the Thai START. The Thai START is a promising tool for using in Thai forensic psychiatric setting but some items were not significant in contributing to the scale. This study also provides the guideline for implementing the tool in non-Western forensic psychiatric populations.

The feed-forward loop (FFL) is an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs like araBAD and araFGH operons and adapt to fluctuating environmental nutrients thus enhancing the survivability of E. coli. Although computational simulations have been used to explore the potential functionality of FFLs, a comprehensive study of the functions of all structural types based on in vivo data is lacking. Also, the regulatory role of CRP-mediated feed-forward loops (CRP-FFLs) remain unclear to date. Using EcoCyc and RegulonDB, we identified 393 CRP-FFLs in the E. coli. Dose-response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, that were further divided into five functional groups. Microarray and reported regulatory relationships identified 202 CRP-FFLs which were directly regulated by CRP in these eight types of FFLs. Interestingly, 30% (147/482) of genes were directly regulated by CRP and CRP-regulated TFs, indicating that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs.

As an emerging building solution, cross-laminated timber (CLT) floors have been increasingly used in mass timber construction. The current vibration design of CLT floors is conservative due to the assumption of simple support conditions in the floor-to-wall connections. It is noted that end fixity occurs as a result of clamping action at the ends, arising from the gravity load applied by the structure above the floor and by the mechanical fasteners. In this paper, the semi-rigid floor-to-wall connections are treated as elastically restrained edges against rotations to account for the effect of partial constraint. A rotational end-fixity factor was first defined to reflect the relative bending stiffness between CLT floors and elastic restraints at the edges. Then, for the design of vibration serviceability of CLT floors as per the Canadian Standard for Engineering Design in Wood (CSA O86), restraint coefficients were defined and their analytical expressions were derived for natural frequencies and the mid-span deflection under a concentrated load, respectively. In particular, a simplified formula of the restraint coefficient for the fundamental frequency was developed to assist engineers in practical design. At last, by comparing with reported experimental data, the proposed design formula showed excellent agreement with test results. In the end, the proposed end fixity factor with their corresponding restraint coefficients is recommended as an effective mechanics-based approach to account for the effect of end support conditions of CLT floors.

Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli, thus exerting crucial neuroprotection for cerebellar ataxias and corticospinal motor neuron degeneration. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. Earliest changes were detected at 3 months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, impacting communication and excitability of cerebellar neurons. Discovery of such risk versus progression markers improves the assessment of pre-symptomatic treatments in SCA2 and related disorders.

General characteristics of K changes together with their fine structure associated with ground flashes in Sri Lanka in the tropics are presented. It is found that on average there are about 2 K changes associated with each return stroke. Analysis of the fine structure of the K changes shows that the K change is a chaotic pulse burst. Some of these chaotic pulse bursts start and the others end as a regular pulse bursts. Sometimes the chaotic part occurs in between two regular pulse bursts. This is in agreement with the recent published results that claim that chaotic pulse bursts are a random superposition of regular pulse bursts. The results show that the small step fields identified in the literature as K changes are the static fields associated with these pulse bursts.

Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.

Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.

Cornea severe inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. The cornea can be used to study the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, Methanol (Met) and Hexane (Hex), from the seed of Cucurbita argyrosperma, in the inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. Clinical manifestation as opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological evaluation were performed. Inflammatory (COX-2, NF-κB, and IL-1β), and angiogenic (VEGF-A, VEGFR1, VEGFR2) markers were assessed by immunohistochemistry. Cox-2, Il-1β, and Vegf-a mRNA levels were also determined. After treatments, we observed slim corneal thickness with lower opacity scores and low cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased CNV area. The staining of inflammatory and angiogenic factors was significantly decreased. These effects are related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed can be used to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.

According to current guidelines, growth hormone (GH) therapy is strongly recommended in children and adolescents with GH deficiency (GHD) in order to accelerate growth rate and attain normal adult height. The diagnosis of GHD requires demonstration of decreased GH secretion in stimulation tests, below the established threshold value. Currently, GHD in children is classified as secondary insulin-like growth factor-1 (IGF-1) deficiency. Most of children diagnosed with isolated GHD presents with normal GH secretion at the attainment of near-final height or even in mid-puberty. The most important clinical problems, related to the diagnosis of isolated GHD in children and to optimal duration of rhGH therapy include: arbitrary definition of subnormal GH peak in stimulation tests, disregarding factors influencing GH secretion, insufficient diagnostic accuracy and poor reproducibility of GH stimulation tests, discrepancies between spontaneous and stimulated GH secretion, clinical entity of neurosecretory dysfunction, discrepancies between IGF-1 concentrations and results of GH stimulation tests, significance of IGF-1 deficiency for the diagnosis of GHD, a need for validation IGF-1 reference ranges. Many of these issues have remained unresolved for 25 years or even longer. It seems that finding solutions to them should optimize diagnostics and therapy of children with short stature.

Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In search for therapeutic alternatives to treat the cancer disease, a se-ries of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a-h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in EtOH, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evalu-ated for their binding interactions with two well-known anticancer targets, namely the epider-mal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. CD experi-ments suggested 5a as a stabilizer agent of the G-quadruplex from the KRAS oncogene promot-er. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hy-drazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds.

There are no studies that quantitatively compare life histories among scorpion species. Statistical procedures applied to 94 scorpion species indicate that those with larger bodies do not necessarily have larger litters or longer life cycles, opposite to some theoretical predictions.

CD44 glycoprotein is ubiqutously present and situated at the extracellular surface of cell. Its role as an adhesion recptor was modified depending upon the state of post addition of glycomoeties under varied microenvironment. Many alternative spliced variants of CD44 were expressed by human cells depending upon the attainment during mutifunctional signal disposition. The function of splice factors, and hnRNPA family (Heterogenous ribonucleoproteins A) were dicussed in context to CD44 alternative variants. Glioma cell cline U87 MG were used in this study to search more about the affect of hnRNPA1 and hnRNPA2/B1 knockdown in CD44 V6 and CD44V10 expression. We found in preliminary study that splice factor knock down reduces the alternative splice variants of CD44 such as V6 & V10. Therefore, potential of this study to elaborate further the mechanism in vivo model, to validate the alternative spliced variant in context to interaction with extracellular microenvironment.

A risk of ischemic stroke increases exponentially after menopause. Even a mild-ischemic stroke can result in increased frailty. Frailty is a state of increased vulnerability to adverse outcomes, which subsequently increases risk of cerebrovascular events and severe cognitive decline, particularly after menopause. Several interventions to reduce frailty and subsequent risk of stroke and cognitive decline have been proposed in laboratory animals and patients. One of them is whole body vibration (WBV). WBV recuperates cerebral function and cognitive ability that deteriorates with increased frailty. The goal of the current study is to test the efficacy of WBV in reducing post-ischemic stroke frailty and brain damage in reproductively senescent female rats. Reproductively senescent Sprague–Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to either WBV or control groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz) treatment performed twice daily for 15 min each session, 5 days each week. The motor functions of animals belonging to both groups were tested intermittently and at the end of treatment period. Brains were then harvested for inflammatory markers and histopathological analysis. The results demonstrate a significant reduction in inflammatory markers and infarct volume with significant increases in brain-derived neurotrophic factor and improvement in functional activity after tMCAO in middle-aged female rats that were treated with WBV as compared to the control group. Our results may facilitate a faster translation of the WBV intervention for improved outcome after stroke, particularly among frail women.

In this project, we use a statistical multiple regression to study the impact of eight various predictors (relative compactness, surface area, wall area, roof area, overall height, orientation, glazing area, glazing area distribution) to estimate the cooling load energy efficiency of residential buildings. We try to analyze and visualize the effect of each predictor with each of the response variable using different classical statistical analysis tools used in describing linear models, in such a way so that we can find out the most strongly related predictor variables. Before starting all of this, we use the idea of model selection by stepwise regression technique and compare the AIC of these models and identified a better model between all of them. Then, we compare a classical linear regression approach by simulations on 768 diverse residential buildings show that we can predict CL with low mean absolute error. By using ANOVA we determine variation in the different residuals. Also, we use non constant variance test to verify it. Furthermore, we check leverage and influence points as well as outliers as well as determined cook distance for influential points. By taking box cox transformation and weights, we also introduce WLS technique to fit the model for better results and did all type of important analysis to understand the energy efficiency. Finally, we show 5-fold cross validation to verify our model.

Age estimation in dental radiographs Orthopantomography (OPG) is a medical imaging technique that physicians and pathologists utilise for disease identification and legal matters. For example, for estimating post-mortem interval, detecting child abuse, drug trafficking, and identifying an unknown body. Recent development in automated image processing models improved the age estimation's limited precision to an approximate range of +/- one year. While this estimation is often accepted as accurate measurement, age estimation should be as precise as possible in most serious matters, such as homicide. Current age estimation techniques are highly dependent on manual and time-consuming image processing. Age estimation is often a time-sensitive matter in which the image processing time is vital. Recent development in Machine learning-based data processing methods has decreased the imaging time processing; however, the accuracy of these techniques remains to be further improved. We proposed an ensemble method of image classifiers and transfer learning techniques to enhance the accuracy of age estimation using OPGs from one year to a couple of months (1-3-6). This hybrid model is based on convolutional neural networks (CNN) and K nearest neighbours (KNN). The hybrid (HCNN-KNN) model was used to investigate 1,922 panoramic dental radiographs of patients aged 15 to 23. These OPGs were obtained from the various teaching institutes and private dental clinics in Malaysia. To minimise the chance of overfitting in our model, we used the principal component analysis (PCA) algorithm and eliminated the features with high correlation. To further enhance the performance of our hybrid model, we performed systematic image pre-processing. We applied a series of classifications to train our model. We have successfully demonstrated that combining these innovative approaches has improved the classification and segmentation and thus the age-estimation outcome of the model. Our findings suggest that our innovative model, for the first time, to the best of our knowledge, successfully estimated the age in classified studies of one year old, six months, three months and one-month-old cases with accuracies of 99.98, 99.96, 99.87, and 98.78 respectively.