Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

In this paper, we study the symmetry between the supersingular prime number according to smallest sphenic number. With this symmetry, we show that the elements of sporadic group generates all prime numbers with the order by a simple application.

Linear state estimation (SE) formulation under a rectangular coordinate system has been proved to be applicable for real-time distribution network management. Micro phasor measurements’ model can be accommodated into this kind of SE easily. However, voltage magnitude, active power and reactive power measurements are transformed to linear measurements with large node voltage error. To cope with this issue, a linear state estimation under a polar coordinate system is adopted at the first stage to obtain accurate enough complex node voltage, and then nonlinear measurements are transformed to be linear with complex node voltage. At the second stage, linear SE under a rectangular coordinate system can be adopted to satisfy more strict network constraints. The proposed two-stage linear SE is validated on balanced 14, 33, 70,84, 119, 135 nodes network and IEEE 13, 34, 37,123 unbalanced test feeders.

Mapping forest extent and forest cover classification are important for the assessment of forest resources in socio-economic as well as ecological terms. Novel developments in the availability of remotely sensed data, computational resources, and advances in areas of statistical learning have enabled fusion of multi-sensor data, often yielding superior classification results. Most former studies of nemoral forests fusing multi-sensor and multi-temporal data have been limited in spatial extent and typically to a simple classification of landscapes into major land cover classes. We hypothesize that multi-temporal, multi-censor data will have a specific strength in further classification of nemoral forest landscapes owing to the distinct seasonal patterns of the phenology of broadleaves. This study aimed to classify the Danish landscape into forest/non-forest and further into forest types (broadleaved/coniferous) and species groups, using a cloud-based approach based on multi-temporal Sentinel 1 and 2 data and machine learning (random forest) trained with National Forest Inventory (NFI) data. Mapping of non-forest and forest resulted in producer accuracies of 99% and 90 %, respectively. The mapping of forest types (broadleaf and conifer) within the forested area resulted in producer accuracies of 95% for conifer and 96% for broadleaf forest. Tree species groups were classified with producer accuracies ranging 34-74%. Species groups with coniferous species were the least confused whereas the broadleaf groups, especially Oak, had higher error rates. The results are applied in Danish National accounting of greenhouse gas emissions from forests, resource assessment and assessment of forest biodiversity potentials.

The objective of this study was to determine the effects of supplementing L-isoleucine (L-Ile) on milk protein synthesis, using an immortalized bovine mammary epithelial (MAC-T) cell line. In this case, the cells were treated with 0, 0.3, 0.6, 0.9, 1.2 and 1.5 mM of supplemental Isoleucine (Ile), and the most efficient time for protein synthesis for each amino acid was determined by measuring the cell, medium and total protein at 0, 24, 48, 72 and 96 h. Confirmatory tests showed that 48h incubation time and 0.6 mM dosage of L-Ile are considered as the optimal time and dosage. The mechanism of milk protein synthesis was elucidated through proteomics analysis to clarify the metabolic pathway. When the L-Ile was supplemented, extracellular protein (medium protein) reached a peak at 48h, whereas in the case of the intracellular cell protein, it was shown to have reached to its peak at 24h in all L-Ile dosage treatments. In total, it is noted that there were 63 upregulated and 52 downregulated proteins. The results of the protein pathway analysis showed that the L-Ile group stimulated insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade, insulin/IGF pathway-protein kinase B signaling cascade, p53 pathway, de novo purine biosynthesis, Wnt signaling pathway, glycolysis, pentose phosphate pathway, and ATP synthesis which are pathways involved and related to protein and energy metabolism. Together, these results demonstrate that L-Ile supplementation was effective in stimulating β-casein synthesis by stimulating genes and pathways which are significantly related to protein and energy metabolism.

Copulas are useful tools for modeling the dependence structure between two or more variables. Copulas are becoming a quite flexible tool in modeling dependence among the components of a multivariate vector, in particular to predict losses in insurance and finance. In this article, we study the dependence structure of some well-known real life insurance data (with two components mainly) and subsequently identify the best bivariate copula to model such a scenario via VineCopula package in R. Associated structural properties of these bivariate copulas are also discussed.

Surface area and pore size distribution of Eucalyptus samples pretreated by different methods were determined by the Brunauer-Emmett-Teller (BET) technique. Three methods were applied to prepare cellulosic biomass samples for BET measurements: air, freeze, and critical point drying (CPD). Air and freeze drying caused severe collapse of biomass pore structures, but CPD effectively preserved biomass morphology. Surface area of CPD prepared Eucalyptus samples was determined to be 58–161 m2/g, whereas air and freeze dried samples were 0.5–1.3 and 1.0–2.4 m2/g, respectively. Average pore diameter of CPD prepared Eucalyptus samples were 61–70Å. CPD preserved Eucalyptus sample morphology by replacing water with a non-polar solvent, CO2 fluid, which prevented hydrogen bond reformation in the cellulose.

In this research first, a sequence of properties called delta is assigned to each prime number and then examined. Deltas are only dependent on the distribution of prime numbers, so the results obtained for the delta distribution can be considered as a proxy for the distribution of prime numbers. The first observation was that these properties are not unique and different prime numbers may have the same value of delta of a given order. It was found that a small number of deltas cover a large portion of prime numbers, so by recognizing repetitive deltas, the next prime numbers can be predicted with a certain probability, but the most important observation of this study is the normal distribution of deltas. This research has not tried to justify the obtained observations and instead of answering the questions, it seeks to ask the right question.

A numerical approach for generating a limited number of water demand scenarios and estimating their occurrence probabilities in a Water Distribution Network (WDN) is proposed. This approach makes use of the demand scaling laws in order to consider the natural variability and spatial correlation of nodal consumptions. The scaling laws are employed to determine the statistics of nodal consumption as a function of the number of users and the main statistical features of the unitary user's demand. Besides, consumption at each node is considered to follow a Gamma probability distribution. A high number of groups of cross-correlated demands, i.e., scenarios, for the entire network were generated using Latin Hypercube Sampling (LHS) and the numerical procedure proposed by Iman and Conover. The Kantorovich distance is used to reduce the number of scenarios and estimate their corresponding probabilities, while keeping the statistical information on nodal consumptions. By hydraulic simulation, the whole number of generated demand scenarios was used to obtain a corresponding number of pressure scenarios on which the same reduction procedure was applied. The probabilities of the reduced scenarios of pressure were compared with the corresponding probabilities of demand.

The emergence of proteins in the prebiotic world was a watershed event at the origin of life. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Five major biochemical innovations followed in succession after availability of various kinds of protein molecules during decoding and translation of mRNAs. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) primitive gene regulation; (4) the beginnings of the virus world; and (5) the advent of DNA. The creative role of viruses during prebiotic synthesis led to the origin of the DNA world, when DNA replaced mRNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification by mutation. The habitat of the earliest fossil record (≥ 3.5 Ga) from the Archean sedimentary rocks of Canada, Greenland, Australia, South Africa, and India offers a new window on the early radiation of microbial life. The development of anoxygenic and then oxygenic photosynthesis from early hyperthermophiles would have allowed life to escape the hydrothermal setting to the mesophilic global ocean.

The asymmetric bimodal exponential power (ABEP) distribution is an extension of the generalized gamma distribution to the real line via adding two parameters which fit the shape of peakedness in bimodality on real line. The special values of peakedness parameters of the distribution are combination of half Laplace and half normal distributions on real line. The distribution has two parameters fitting the height of bimodality, so capacity of bimodality is enhanced by using these parameters. Adding a skewness parameter is considered to model asymmetry in data. The location-scale form of this distribution is proposed. The Fisher information matrix of these parameters in ABEP is obtained explicitly. Properties of ABEP are examined. Real data examples are given to illustrate the modelling capacity of ABEP. The replicated artificial data from maximum likelihood estimates of parameters of ABEP and distributions having an algorithm for artificial data generation procedure are provided to test the similarity with real data.

In recent years, distributed generation technology has developed rapidly. Renewable energy, represented by wind energy and solar energy, has been widely studied and utilized. In order to give full play to the advantages of Distributed Generation (DG) and meet the challenges after power grid access, Active Distribution Network (ADN) is considered as the future development direction of traditional distribution network because of its ability of active management. Nowadays, multi-scenario analysis is widely used in the research of optimal allocation of distributed power supply in active distribution network. Aiming at the problems that may arise when using multi-scenario analysis to plan DG with uncertainties in large-scale scenarios, a scenario reduction method based on improved clustering algorithm is proposed. The validity of the scene reduction method is tested, and the feasibility of the method is verified. At present, there are few studies on the optimal allocation of DG in ADN under fault state. In this paper, comprehensive safety indicators are introduced. Considering the timing characteristics of DG and the influence of active management mode, a bi-level programming model is established, which aims at minimizing the investment of annual life cycle and the removal of active power. The bi-level model is a complex mixed integer non-linear programming model. A hybrid algorithm combining cuckoo search algorithm and primal dual interior point method is used to solve the model. Finally, through the simulation of the IEEE-33 node system, the superiority of the scenario reduction method and the comprehensive security index used in this paper to optimize the configuration of DG in ADN is verified.

In this paper we describe a nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions. Given $N$ independent observations, convexity theory shows that the NPML estimator is discrete with at most $N$ support points. The original infinite NPML problem then becomes the finite dimensional problem of finding the location and probability of the support points. The probability of the support points is found by a Primal-Dual Interior-Point method; the location of the support points is found by an Adaptive Grid method. Our method is able to handle high-dimensional and complex multivariate mixture models.An important application is discussed for the problem of population pharmacokinetics and a non-trivial example is treated.Our algorithm has been successfully applied in hundreds of published pharmacometric studies. In addition to population pharmacokinetics, this research also applies to empirical Bayes estimation and many other areas of applied mathematics.

Species have shown their habital variations in responding to climate change, especially during the spring and summer spawning seasons. The species distribution model (SDM) is considered the most favorable tool to study the potential effects of climate change on species distribution. Therefore, we developed the ensemble SDM to predict the changes in species distribution of Portunus trituberculatus among different seasons in 2050 and 2100 under the climate scenarios RCP4.5 and RCP8.5. The results of SDM indicate that the distribution of this species will move northward and have obviouse seasonal variations. Meanwhile, the suitable habitat for the species will be significantly reduced in summer, with loses rates ranging from 45.23% (RCP4.5) to 88.26% (RCP.8.5) by 2100s. Habitat reduction will mainly occur in the East China Sea and southern part of the Yellow Sea, while there will be a small increase in the northern Bohai Sea. These findings will be important to manage the ecosystem and fishery, provide an information forecast of this species in the future, and maintain species diversity if the seawater temperature rises.

The heavy demand of water resources from the Zarqa River Basin (ZRB) has resulted in a base-flow reduction of the River from 5m³/s to less than 1m³/s. This paper aims at predicting Curve Numbers (CN) as a baseline scenario and proposing restoration scenarios for ZRB. The method includes classifying the soil type and land use, predicting CNs, and proposing CN restoration scenarios. Prediction of existing CNs will be in parallel with the runoff prediction using the US Army Corps of Engineers HEC-1 Model, and Rainfall-Runoff Model (RRM). The models have been set up at the land use distribution of 0.3% water body, 9.3% forest and orchard, 71% mixture of grass, weeds, and desert shrubs, 7.0% crops, 4.0% urban areas, and 8.4% bare soil. The results show that CN under dry condition are 59, 78 under a normal condition and 89 under a wet condition. During vegetation period, CN are 52, 72 and 86 for the dry, normal and wet condition respectively. The restoration scenarios; CN decreases runoff, and increases soil moisture when using the contours, terraces and crop residues. Analyzing results of CN scenarios will be a fundamental tool to support end-users related to their targets to achieve watershed restoration.

Climate change and the overall increase of seawater temperature is causing a poleward shift in species distribution, which includes a phenomenon described as tropicalization of temperate regions. This work aims at reporting the first records of four species off the southwestern Iberian Peninsula, namely oceanic puffer Lagocephalus lagocephalus Linnaeus, 1758, Madeira rockfish Scorpaena maderensis Valenciennes, 1833, ornate wrasse Thalassoma pavo Linnaeus, 1758, and bearded fireworm Hermodice carunculata Pallas, 1766. These last three species, along with other occurrences of aquatic fauna and flora along the Portuguese coast, reveal an ongoing process of poleward expansion of several species for which a comprehensive survey along the entire Iberian Peninsula is urgent. The putative origins of these subtropical and tropical species off continental Portugal are discussed, as well as the urgent need of public awareness due to potential health risks resulting from the toxicity of two of the four species reported in this paper.

Transient receptor potential vanilloid (TRPV) channels act as sensors of pain, temperature, and other external stimuli. We have recently shown that DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can modulate the activity of TRPV on human primary keratinocytes, suggesting their potential as a possible pain modulator [1]. CD4+ T lymphocytes also express TRPV channels, and we sought with special interest to examine the effect of DPV576 in modulating the functions of TRPV channel expression and secretion of cytokines on human CD4+ T lymphocytes. Human primary CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:25 and 1:100 dilutions for 24 hours in vitro. TRPV Receptor expression (TRPV1 and TRPV4) on CD4+ T cells was examined by flow cytometry. The capacity of DPV576 to modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also determined. Activation of CD4+ T cells was determined by production of cytokines TNF-α, IFN-γ, and IL-10 using specific ELISA kits. DPV576 treatment of CD4+ T cells that were activated with anti CD3/CD28, resulted in increased expression of TRPV1 channel but had no effect on TRPV4. This was accompanied by increased secretion of IFN-g and reduced expression of TRPV1 in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin, induced the production of both IFN-g and TNF-α, and enhanced the secretion of IL-10. We conclude that short term exposure to DPV576 inhibits the activity of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible beneficial use for pain management.

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

Visceral Leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we have designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from 3 previously identified antigen genes of Leishmania donovani from our lab, by immune-informatic approach using IFNepiotpe, NET-MHC-1 and NET MHC-2 webservers. We have tested the protective potential of these three multiepitope proteins as vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th-1 biased protective immune response in-vivo in a hamster model of experimental visceral Leishmaniasis, with one of the candidates inducing a sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of designed candidates.

The location and number data of individual fruit trees are critical for planting area investigation, fruit yield prediction, and smart orchard management and planning. These data are conventionally obtained through manual investigation and statistics with time-consuming and laborious effort. Object detection models in deep learning used widely in computer vision could provide an opportunity for accurate detection of individual fruit trees, which is essential for rapidly obtaining the data and reducing human operations errors. This study proposes an approach to detecting individual fruit trees and mapping their spatial distribution by integrating deep learning with unmanned aerial vehicle (UAV) remote sensing. UAV remote sensing collected high-resolution true-color images of fruit trees in the experimental pomelo tree orchards in Meizhou city, South China. An image dataset of deep learning samples of individual pomelo trees (IPTs) was constructed through visual interpretation and field investigation based on the fruit tree images captured by UAV remote sensing. Four different scales of YOLOv5 (YOLOv5s, YOLOv5m, YOLOv5l, and YOLOv5x) for object detection were selected to train, validate, and test on the image dataset of pomelo trees. The results show that the average precision (AP@0.5) of the four YOLOv5 models for validation reach 87.8%, 88.5%, 89.1%, and 90.7%, respectively. The larger the model scale, the higher the average accuracy of the detection result of validation. It suggests that YOLOv5x is a preferred high-accuracy model among the YOLOv5 family and is suitable to realize the detection of IPTs. The number of the IPTs in the study area was counted using YOLOv5x, and their spatial distribution map was made using the non-maximum suppression method and ArcGIS software. This study will provide primary data and technical support for smart orchard management in Meizhou city and other fruit-producing areas.

The development and optimization of an effective non-viral gene delivery method for genetic manipulation of primary human T cells is a major challenge in clinical immunotherapy researches. According to the low transfection efficiency of conventional methods in human primary T cells, there is an effort in order to increase the transfection rate in these cells. Protamine is an FDA-approved compound with a documented safety profile that enhances DNA condensation for gene delivery. In this study, the effect of protamine on the transfection efficiency of standard transfection reagents, TurboFect, and Lipofectamine 2000 was evaluated in order to transfect primary human T cells. Results demonstrated that protamine condenses DNA and increases the positive charge of DNA/Cargo complex efficiently without any cytotoxic effect on the primary human T cells. The results also revealed that the DNA/Protamine/Cargo complexes effectively transfect human primary T cells.

The mechanisms involved in immune responses to cancer have been extensively studied for several decades and, considerable attention has been paid to harnessing the immune system's therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell-cancer therapy and immune test therapy have gained prominence through immunotherapy. However, it remains to be accomplished the full potential of cancer immunotherapy. In spite of having startling aspects, the cancer immunotherapies have some difficulties including the inability to effectively targeting the cancer antigens and the abnormalities in patient response. With the advancement of technology, this system has changed the genome-based immunotherapy process in the human body including generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome-editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR-T cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR-T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against the cancer. In this review, we have broadly focused on the use of CRISPR-Cas9 technology for the modification of the T-cell, which can specifically recognize cancer cells and be used as immune therapeutics against cancer. We have also demonstrated the other potential strategies for the treatment of cancer.

Historical maps constitute unique sources of retrospective geographic information. Recently, several map archives containing map series covering large spatial and temporal extents have been systematically scanned and made available to the public. The geographic information contained in such data archives allows extending geospatial analysis retrospectively beyond the era of digital cartography. However, given the large data volumes of such archives and the low graphical quality of older map sheets, the processes to extract geographic information need to be automated to the highest degree possible. In order to understand the salient characteristics, data quality variation, and potential challenges in large-scale information extraction tasks, preparatory analytical steps are required to efficiently assess spatio-temporal coverage, approximate map content, and spatial accuracy of such georeferenced map archives across different cartographic scales. Such preparatory steps are often neglected or ignored in the map processing literature but represent highly critical phases that lay the foundation for any subsequent computational analysis and recognition. In this contribution we demonstrate how such preparatory analyses can be conducted using classical analytical and cartographic techniques as well as visual-analytical data mining tools originating from machine learning and data science, exemplified for the United States Geological Survey topographic map and Sanborn fire insurance map archives.

This paper predict and effectively control the temperature distribution of the steady-state and transient states of anisotropic four-layer composite materials online, knowing the density, specific heat, heat conductivity and thickness of the composite materials. Based on the transfer function, a mathematical model was established to study the dynamic characteristics of heat transfer of the composite materials. First of all, the Fourier heat transfer law was used to establish a one-dimensional Fourier heat conduction differential equation for each composite layer, and the Laplace transformation was carried out to obtain the system function. Then the approximate second-order transfer function of the system was obtained by Taylor expansion, and the Laplace inverse transformation was carried out to obtain the transfer function of the whole system in the time domain. Finally, the accuracy of the simplified analytical solutions of the first, second and third order approximate transfer functions was compared with computer simulation. The results showed that the second order approximate transfer functions can describe the dynamic process of heat transfer better than others. The research on the dynamic characteristics of heat transfer in the composite layer and the dynamic model of heat transfer in composite layer proposed in this paper have a reference value for practical engineering application. It can effectively predict the temperature distribution of composite layer material and reduce the cost of experimental measurement of heat transfer performance of materials.

The distribution of noble metal nanoparticles in hydrogels are influencing their nanoplasmonic response and signal used for biosensor purposes. By controlling the particle distribution, it is possible to obtain new nanoplasmonic features with new sensing modalities. Particle distributions can be characterized by using volume-imaging methods such as the focused ion beam-scanning electron microscope (FIB-SEM) and the serial block-face scanning electron microscopy (SBFSEM) techniques . Since the pore structure of hydrogels is contained by the water absorbed in the polymer network it may pose challenges for volume-imaging based on electron microscope techniques since the sample must be in a vacuum chamber. The structure of hydrogels can be conserved by choosing appropriate preparation methods, which also depends on the composition of the hydrogel used. In this paper, we have prepared low-weight percentage hydrogels, with and without gold nanorods (GNR) for conventional SEM imaging by using two different drying techniques; (1) the critical point drying (CPD) technique and (2) hexamethyldisilazane (HMDS) drying of hydrogels. A qualitative characterization of the GNR-hydrogels was carried out to study the GNRs positioned in the polymer network. The effect of the two different drying methods on the hydrogel morphology were also compared. The use of HMDS as an alternative to the CPD has several advantages involving less parametrical variables for drying, involving less effort, being cost-effective, and requires no equipment use. In addition, choosing an optimized sample preparation method for SEM with optimized imaging parameters is highly important for obtaining accurate information about materials that is not correlated to artifacts. Hence, the results obtained from the preparation methods and SEM imaging parameters in this paper are useful for developing methods for mapping the metal particle distributions in micro-hydrogels by using FIB-SEM and SBFSEM techniques.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

This paper presents the development, comparison and analysis of several implementations of the B92 Quantum Key Distribution (QKD) protocol. In order to achieve this objective a prototype which consists of traditional (non-quantum) simulators was created, one for B92 protocol, one for B92 protocol with eavesdropper and one for B92 protocol with Quantum Bit Travel Time (QBTT) eavesdropper detection method. The principles of quantum mechanics were studied, as a foundation of quantum cryptography, for the realization of simulation programs that were written in C ++, focusing mainly on the B92 protocol and QBTT eavesdropper detection method. We compared the Quantum Bit Error Rate (QBER) for implementation of B92 protocol without eavesdropper, B92 protocol with eavesdropper and B92 protocol with QBTT eavesdropper detection method and found that QBTT eavesdropper detection method significantly reduces the QBER from the final key.

Abstract The last mile has to deliver the goods at the right time and at the right cost for business logistics services to enhance the customer service experience. The objective of this paper is to examine the challenges of retail omni-channel distribution influencing the effective last mile fulfilment operations processes in the apparel group (organisation phase). It further establishes the extent of how the last mile for demand-driven store replenishment influences the level of retailers’ order fulfilment (in full and on time) (environment phase). This paper, persistently assesses the contribution of integrated information systems on brick and mortar and virtual omni-channel distribution networks to improve timeousness, order accuracy and fill rate (technology phase). The mixed method has triangulated the methods from both quantitative methodology using frequencies and binomial testing and subjective thematic analysis of qualitative data from interviewees. The sample of 175 questionnaires were received with a response rate is 85 per cent (148 responses). The main findings of the paper revealed that the current order fulfilment process aligned with the last mile is effective on the basis of the fill rate, lead time and order condition of orders delivered via store economy and store express.

Solar energy is a renewable resources of energy which is broadly utilized and have the least pollution impact between the available alternatives of fossil fuels. In this investigation, machine leaening approaches of neural networks (NN), neuro-fuzzy and least squares support vector machine (LSSVM) are used to build the models for prediction of the thermal performance of a photovoltaic-thermal solar collector (PV/T) by estimating its efficiency as an output of the model while inlet temperature, flow rate, heat, solar radiation, and heat of sun are input of the designed model. Experimental measurements was prepared by designing a solar collector system and 100 data extracted. Different analyses are also performed to examine the credibility of the introduced approaches revealing great performance. The suggested LSSVM model represented the best performance regarding the mean squared error (MSE) of 0.003 and correlation coefficient (R²) value of 0.99, respectively.

This paper introduces an approach that chooses the fault detection by calculating probabilities using probability mass function (pmf) and cumulative distribution function (CDF). This work used a method for multiple stuck-at faults by producing a new test pattern in combinational circuits. We assumed that existence of all multiple faults is only because of one single component that is faulty. A complete test set can be created by all possible single stuck-at faults in a combinational circuit using some combination of gates. The test set generation fault detection method is applied on two different 3-bit input variable and 4-bit input variable circuits. The probability of error occurrence is calculated at both 3-bit and 4-bit input variable circuits. The resulting feature is used to obtain maximum error occurrence probability to detect faults by the logic used that the complexity of the circuit is inversely proportional to the fault occurrence probability. Then again, undetectability is directly proportional to the complexity of the circuit. Therefore, finest feasible circuit should have large input variable components with less complexity to reduce the fault occurrence probability.

This study investigated whether biogas reactor performance, including microbial community development, in response to a change in substrate composition is influenced by initial inoculum source. Test reactors were first started with two different inocula and operated with the same grass-manure mixture for more than 120 days. These reactors initially showed great differences depending on inoculum source, but eventually showed similar performance and overall microbial community structure. At the start of the present experiment, the substrate was complemented with milled feed wheat, added all at once or divided into two portions. The starting hypothesis was that process performance depends on initial inoculum source and microbial diversity, and thus that reactor performance is influenced by the feeding regime. In response to the substrate change, all reactors showed increases and decreases in volumetric and specific methane production, respectively. However, specific methane yield and development of the microbial community showed differences related to initial inoculum source, confirming the hypothesis. The different feeding strategies had however only minor effects on process performance and overall community structure, but still induced differences in the cellulose-degrading community and in cellulose degradation.

One of the biggest challenges for European industry is to introduce sustainability principles into business models. This is particularly important in raw material and energy intensive manufacturing sectors such as the ceramic industry. The present state of knowledge lacks a comprehensive operational tool for industry to support decision-making processes geared towards sustainability. In the ceramic sector, the economic and social dimensions of the product and processes have not yet been given sufficient importance. Moreover, the traditional research on industrial districts lacks an analysis of the relations between firms and the territory with a view to sustainability. Finally, the attention of scholars in the field of economic and social sustainability, has not yet turned to the analysis of the Sassuolo district. Therefore, in this paper we define the Territorial Life Cycle Sustainability Assessment (T-LCSA), a method that can be a suitable tool to fill this gap, because through a mathematical model it is possible to obtain the information useful for decision makers to integrate the principles of sustainability both at the microeconomic level in enterprises, and at the meso-economic level for the definition of economic policies and territorial governance. Environmental and socio-economic analysis was performed from the extraction of raw materials to the packaging of the product on different product categories manufactured by the Italian ceramic industries of the Sassuolo district (northern Italy). For the first time the T-LCSA model, usually applied to unitary processes, is extended to the economic and industrial activities of the entire district, extending the prospect of investigation from the enterprise and its value chain to the integrated network of district enterprises.

This paper presents the results of hot smoke tests, conducted in a real road tunnel. The tunnel is located within the expressway S69 in southern Poland between cities Żywiec and Zwardoń. Its common name is Laliki tunnel. It is a bi-directional non-urban tunnel. The length of the tunnel is 678 m and it is inclined by 4%. It is equipped with the longitudinal ventilation system. Two hot smoke tests have been carried out according to Australian Standard AS 4391-1999. Hot smoke tests corresponded to a HRR (Heat Release Rate) equal to respectively 750 kW and 1500 kW. The fire source was located in the middle of the road lane imitating an initial phase of a car fire (respectively 150 m and 265 m from S portal). The temperature distribution was recorded during both tests using a set of fourteen thermocouples mounted at two stand poles located at the main axis of the tunnel on windward. The stand poles were placed at distances of 5 m and 10 m. The recorded data were applied to validate of a numerical model built and solved using Ansys Fluent. The calculated temperature distribution matched the measured values.

Factorization reduces computational complexity and is therefore an important tool in statistical machine learning of high dimensional systems. Conventional molecular modeling, including molecular dynamics and Monte Carlo simulations of molecular systems, is a large research field based on approximate factorization of molecular interactions. Recently, the local distribution theory was proposed to factorize global joint distribution of a given molecular system into trainable local distributions. Belief propagation algorithms are a family of exact factorization algorithms for trees and are extended to approximate loopy belief propagation algorithms for graphs with loops. Despite the fact that factorization of probability distribution is their common foundation, computational research in molecular systems and machine learning studies utilizing belief propagation algorithms have been carried out independently with respective track of algorithm development. The connection and differences among these factorization algorithms are briefly presented in this perspective, with the hope to intrigue further development in factorization algorithms for physical modeling of complex molecular systems.

This study presents an analysis of the spatial and temporal distribution of the two large destructive earthquakes that occurred in Lake Van area on October 23, and November 9, 2011, together with the azimuth-dependent distribution of the seismic activity and microseismicity clusters after the mainshocks, associated with the complex rupture processes of their aftershock sequence. The sequence began with the magnitude Mw 7.1 earthquake of 23 October and a second destructive earthquake of Mw 5.6. The aftershock sequences of the two mainshocks were linked to the local crustal faults beneath Lake Van area, followed successively and produced unusually intense activity and significant damage in the area. The main purposes of this study are to document the spatial and temporal distribution and evolution of the October 23, 2011 aftershock hypocenters and the azimuth-dependent distribution of seismic activity, and to understand the spatial and temporal character of the aftershock sequence using the distributional and evolutional patterns of the aftershock hypocenters. A total of 10,000 aftershocks were obtained from seismic data with a high signal-to-noise ratio over collected over three years from October 23, 2011 to March 2014. These aftershocks were plotted for the time periods from November 2011 through March 2012 to March 2014 and ≈ 5000 aftershocks were retained in the depth versus distance cross-sections to detect the clusters in the first step of study (November 2011–March 2012). The focal depth distribution of the aftershock clusters, the migration of hypocenter activity and microseismicity clusters were analyzed and the distributional patterns of the detected clusters were assessed using the geometric distribution of the aftershock hypocenters. The spatial and temporal distribution of aftershocks reveal interesting key features of the deep rupture complexity of the Van earthquake: (1) most prominent aftershocks have been located in the upper crust at depths shallower than 10 km beneath ruptured area, indicating that the upper crust is brittle and seismogenic; (2) two spatial clusters have been detected at 8-10 km depths and the upward extrapolation of these clusters intersects with faults; the main cluster (60 km wide) bounded by inferred reverse faults (f3 and f4) and the central cluster (25–30 km wide) bounded by faults (f1 and f2); (3) these spatial clusters form the largest volumetric pattern of the conical-shaped cluster at depths of about 25–30 km of the azimuth-dependent rotational projections, suggesting azimuthal distributions of deep rupture characteristics; and (4) the strongest temporal cluster of microseismicity derived from temporal distribution of aftershocks has been detected within an area of about 2.5–3.0 km² and it is spatially observed at 20 km depth within the central cluster, suggesting progressive failure of the adjacent patches of possible fault.

Long non-coding RNA (lncRNA) aberrant expression have been found in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped in transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated in pediatric ALL and uc.112 expression was higher in T-ALL compared to patients with B-ALL and in patients with hyperdiploid karyotype. These findings suggest a potential role of this uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

This paper examines the regional changes of corn production and the relationship between ethanol production and corn production. The underlying hypothesis is that the rapid growth in ethanol production causes regional expansion of corn production outside the traditional regions. This paper introduces the information approach developed by entropy theory to describe these regional changes. The results support the hypothesis that ethanol production leads to expansion of corn production outside traditional corn producing regions.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

Integer is either a composite number or a prime number. Therefore, detecting composite numbers is important for solving prime numbers. The study of prime numbers, apart from satisfying human curiosity, can be very important. In this article, the order of composite numbers has been detected. And explained with a simple method and a simple function. And, a method has been developed in which all composite numbers and therefore prime numbers can be determined by using the specified methods, functions and formulas.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

Due to the increase in the emission of greenhouse gases, the hydrologic cycle is being altered on the daily basis. This has affected the variations in relations of intensity, duration, and frequency of rainfall events. Intensity Duration Frequency (IDF) curves describe the relationship between rainfall intensity, rainfall duration and return period. IDF curves are one of the most often applied implements in water resource engineering, in areas such as for operating, planning and designing of water resource projects, or for numerous engineering projects aimed at controlling floods. In particular, IDF curves for precipitation answer problems of improper drainage systems or conditions and extreme characters of precipitation which are the main cause of floods in Nyabugogo catchment. This study aims to establish Rainfall IDF empirical equations, curves and hydrological discharge (predicted peak rate of runoff (Qlogy)) equations for eight Districts that will be used for designing an appropriate and sustainable hydraulic structures for controlling flood to reduce potential loss of human and aquatic life, degradation of water, air and soil quality and property damage and economic lessen caused by flood in Nyabugogo catchment. However Goodness of Fit tests revealed that Gumbel’s Extreme-Value Distribution method appears to have the most appropriate fit compared with Pearson type III distribution for validating the Intensity-Duration-Frequency curves and equations through the use of daily annual for each meteorological station. The findings of the study show that the intensity of rainfall increases with a decrease in rainfall duration. Additionally, a rainfall of every known duration will have a higher intensity if its return period is high, while the predicted peak rate of runoff (Qlogy) increases also with an increase in the intensity of rainfall.

Research Highlights: Hagenia abyssinica is geographically localized, poor regenerated and endangered species in Ethiopia. Ethiopia has been experiencing variability of rainfall and rise in temperature due to the climate change. This study has hypothesized that the suitable areas for the species will be narrowed by the year 2070. Background and Objective The prediction of species distribution models help to implement appropriate conservation actions. The aim of this research was to identify the current and likely future distribution range and suitable areas for the species, and to determine the presence of H. absyssinica in risk in a short-term future. Material and method: To this end, occurrence data, bioclim variables, soil, elevation, and land cover map of Ethiopia were used. MaxEnt was used to predict distribution. Climate change impacts on the distribution of the species was performed using bioclimatic variables of the future climate data, 2070 (average for 2061-2080) was obtained from IPPC5 (CMIP5) at 30 seconds (1km) spatial resolution. The climate data was projected from GCMs, downscaled and calibrated using rcp4.5. Results: Both current and likely future distribution models were excellent and significantly better than random performance. This study has computed 59987 km2 to be the low impact area for the species under current conditions and will remain habitat under future climates and 39025 km2 area has been identified as the possible high impact areas or declining habitat. The model has also determined that 1238724 km2 of the areas are unsuitable at present and for future climates. The current study found that 15751 km2 of the area will be modified as a new suitable area for H. abyssinica due to climate change. Conclusion: Species distribution modeling is essential for the implementation of conservation actions that are compatible with the inevitable changing climatic conditions of the country.

The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all 4 included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.

Precipitation processes are technologies commonly used in hydrometallurgical plants to recover metals or to treat wastewaters. Moreover, solid-liquid separation technologies, such as thickening or filtering, are relevant unit operations, included in the precipitation technologies. These methods are strongly dependent on the characteristics of the solid precipitates formed during the specific precipitation reaction. One of these characteristics is the particle size distribution (PSD) of the solid precipitates which are fed into a solid-liquid separation process. Therefore, PSD determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes have a colloidal or aggregation behavior, depending on the operational conditions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or ciclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativity in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used have been obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction. Our results show significant differences between the methods analyzed, demonstrating that image processing and analysis by microscopy is an excellent and non-invasive alternative to obtaining size distribution of aggregates in precipitation processes.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis, and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.

A Wireless Body Area Sensor Network (WBASN) is combination of numerous sense nodes, positioned onto/close or inside a person body. Wireless Body Area Sensor Networks (WBASN) is a developing automation trend that exploits wireless sensor nodes to put instantaneous wearable well-being of ill person to improve individual’s existence. The sensor nodes might be used outwardly to observe abundant health parameters (like heart activity, blood pressure and cholesterol) of an ill person at a vital site within hospital. Hence the goal of WBASN is much crucial, enhancing the lifetime of nodes is compulsory to sustain many issues such as utility and efficiency. It is essential to evaluate time that when the first node will die it we want to refresh or change the battery reason is that loss of crucial information is not tolerable. The lifetime is termed as the time interval when a first node dies out due to battery exhaustion. In our proposed protocol life time of a network is the main concern as well other protocol related issues such as throughput, path loss, and residual energy. Bio-sensors are used for deployment on human body. Poisson distribution and equilibrium model techniques have been used for attaining the required results. Multi-hop network topology and random network node deployment used to achieve minimum energy consumption and longer network lifetime.

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4⁺ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

In the paper, a coordinated control methodology of single-phase (1-P) end-users switching oper-ations on the phases of an active electric distribution network (AEDN) has been proposed to ob-tain a minimum unbalance degree at the coupling common point (CCP) level with the main dis-tribution system. The phase load balancing (PLB) process considers the smart devices that switch from one phase to another phase the 1-P end-users (consumers and prosumers) to compensate for the phase load unbalance. The proposed methodology has been tested successfully in an AEDN belonging to a Romanian Distribution Network Operator (DNO) containing 114 end-users (104 consumers/10 prosumers) integrated into the Smart Metering System (SMS). The op-timal solution leads to a value of the objective function by 1.00004, represented by the unbalance factor, very close to the ideal target, 1.00. A comparative analysis was conducted considering other possible PLB cases (the consumer-level PLB and prosumer-level PLB), obtaining similar values of the UF (1.027 vs. 1.028), slightly higher than in the hybrid-level PLB. Also, the signifi-cant technical benefits were quantified through an energy-saving of 58.73% and decreasing the phase voltage unbalance rate by 91 % compared to the initial case (without PLB). These results emphasized the positive impact of the proposed coordinated control methodology on the PLB process and evidenced its effectiveness and applicability in the AEDNs.

Objective: To investigate the effects and mechanisms of different concentrations of CCCP on mitophagy in human peripheral blood regulatory T cells. Methods: Tregs were isolated, identified and then grouped, treating with CCCP at a concentration of 2.5 μM, 5 μM, 10 μM, 20 μM and 40 μM for 24h in an incubator. Flow cytometry detected the reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial quality, and fluorescence microscopy observed the co-localization of mitochondria and lysosomes in each group. Results: The purity of CD4⁺CD25⁺Tregs was (93.36 ± 1.87) %. With the increase of CCCP concentration, the level of ROS gradually increased, while the MMP decreased gradually. About the mitochondria and lysosome fusion, the fluorescence intensity of orange (yellow) was the highest when the concentration of CCCP was in the range of 5-10 μM while decreased with the CCCP concentration continually increasing. The mitochondrial quality decreased with the increase of CCCP concentration. However, there was no significant difference between groups C, D and E. The mitochondrial quality of groups F and G were significantly lower than that of group E. Conclusions: With the concentration of CCCP gradually increased, the level of ROS in Treg cells increased, and MMP decreased, which promoted the mitophagy, mitochondrial quality maintains homeostasis; When ROS accumulated, and MMP decreased significantly, the mitophagy was inhibited, and the mitochondrial quality was significantly decreased.

While entropy was introduced in the second half of the 19th century in the international vocabulary as a scientific term, in the 20th century it became common in colloquial use. Popular imagination has loaded “entropy” with almost every negative quality in the universe, in life and in society, with a dominant meaning of disorder and disorganization. Exploring the history of the term and many different approaches on it, we show that entropy has a universal stochastic definition which is not disorder. The accompanying principle of maximum entropy, which lies behind the Second Law, gives explanatory and inferential power to the concept and promotes entropy as the mother of creativity and evolution. As social sciences are often contaminated by subjectivity and ideological influences, we try to explore whether the maximum entropy, applied to the distribution of wealth quantified by annual income, can give an objective description. Using publicly available income data, we show that the income distribution is consistent with the principle of the maximum entropy. The increase of entropy is associated to increase of society’s wealth yet a standardized form of entropy can be used to quantify inequality. Historically, technology has played a major role in development and increase of the entropy of income. Such findings are contrary to the theories of ecological economics and other theories which use the term entropy in a Malthusian perspective.

Hamacher operation which is generalization of the Algebraic and Einstein operation, can widely provide a large number of arithmetical operation with respect to uncertainty information, and Heronian mean can deal with correlations of the input arguments or different criteria and don’t make calculation redundancy, meanwhile, the normal intuitionistic fuzzy numbers (NIFNs) can depict distinctively normal distribution information in practical decision making. In this paper, a multi-criteria group decision-making (MCGDM) problem is researched under the NIFNs environment, and a new MCGDM approach is introduced on the basis of the Hamacher operation. Firstly, according to Hamacher t-conorm and t-norm, some operational laws of NIFNs are presented. Secondly, it is noticed that Heronian mean can’t only once take into account mutual relation between attribute values once, but also consider the correlation between input argument and itself. Therefore, we develop some operators and study their properties in order to aggregate normal intuitionistic fuzzy numbers information, these operators include Hamacher Heronian mean (NIFHHM), Hamacher weighted Heronian mean (NIFHWHM), Hamacher geometric Heronian mean (NIFHGHM) and Hamacher weighted geometric Heronian mean (NIFHWGHM). Furthermore, we apply the proposed operators to the MCGDM problem and present a new method. The main characteristics of this new method involve that: (1) it is suitable to make decision under the normal intuitionistic fuzzy numbers environment and more reliable and reasonable to aggregate the normal distribution information. (2) it utilizes Hamacher operation which can provide more reliable and flexible decision-making results and offer an effective and powerful mathematic tool for the MAGDM under uncertainty. (3) it uses the Heronian mean operator which can considers relationships between the input arguments or the attributes and don’t brings subsequently about redundancy. Lastly, an application is given for showing the feasibility and effectiveness of the presented method in this paper.

In the paper, an improved smart meter data-based three-stage algorithm to calculate the power/energy losses in the three-phase networks with the voltage level below 0.4 kV (low voltage - LV) is presented. In the first stage, a loading function of input data was built having as main feature the working at the same time with files from the database of smart metering system (SMS) containing the hourly electricity records, and files including the characteristic load profiles established by the Distribution Network Operator (DNO) for the consumers with standard energy meters depending the following factors: consumption class, day and season. In the second stage, a function which is based on the work with the structure vectors was implemented to identify easy the configuration of analysed networks. In the third stage, an improved version of forward/backward sweep-based algorithm was proposed to calculate fast the power/energy losses to three-phase LV distribution networks in balanced and unbalanced regime. A real LV rural distribution network from a pilot zone belonging to a Distribution Network Operator (DNO) from Romania was used to confirm the accuracy of the proposed approach. The comparison with the results obtained using the DigSilent PowerFactory Simulation Package certified the performance of the algorithm, the mean absolute percentage error (MAPE) being 0.94%.

Adaptive T cell immunotherapy holds great promise for the successful treatment of leukemia as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system allowing deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Extracellular vesicles (EV) are a very heterogeneous group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular communication, both locally and systemically, since they induce signals and transfer their contents (proteins, lipids, RNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. How-ever, cell surface receptor-induced EV release is limited to cells from the immune system, includ-ing T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptor for antigen and several bioactive molecules, including proapoptotic proteins. These EV are thus specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we discuss the generation of EV by T lymphocytes and some potential therapeutic approaches of these EV.

Biogeography research is flawed by the poor understanding of microbial distributions due to the lack of a systematic research framework, especially regarding appropriate study units. By combining pure culture and molecular methods, we studied the biogeographic patterns of nematode-trapping fungi by collecting and analysing 2,250 specimens from 228 sites in Yunnan Province, China. We found typical watershed patterns at the species and genetic levels of nematode-trapping fungi. The results showed that microbial biogeography could be better understood by 1) using watersheds as research units, 2) removing the coverup of widespread species, and 3) applying good sampling efforts and strategies. We suggest that watersheds could help unify the understanding of the biogeographic patterns of animals, plants, and microbes and may also help account for the historical and contemporary factors driving species distributions.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

Dispersion tests based on the second order component of smooth test statistics are related to Fisher’s Index of Dispersion test, used for testing for the Poisson distribution when there are no covariates present. Such tests have been recommended in [1] to test for the Poisson distribution when covariates are present. The modified Borel-Tanner (MBT) distribution seems suited to data with extra zeroes, a monotonic decline in counts and longer tails. Here we recommend a dispersion test for the MBT distribution for both when covariates are absent and when they are present.

In this paper we define a continuous wavelet transform of a Schwartz tempered distribution $f \in S^{'}(\mathbb R^n)$ with wavelet kernel $\psi \in S(\mathbb R^n)$ and derive the corresponding wavelet inversion formula interpreting convergence in the weak topology of $S^{'}(\mathbb R^n)$. It turns out that the wavelet transform of a constant distribution is zero and our wavelet inversion formula is not true for constant distribution, but it is true for a non-constant distribution which is not equal to the sum of a non-constant distribution with a non-zero constant distribution.

We show that an exponential income distribution will emerge spontaneously in a peer-to-peer economic network that shares the publicly available technology. Based on this finding, we identify the exponential income distribution as the benchmark structure of the well-functioning market economy. However, a real market economy may deviate from the well-functioning market economy. We show that the deviation is partly reflected as the invalidity of exponential distribution in describing the super-low income class that involves unemployment. In this regard, we find, theoretically, that the lower-bound u of exponential income distribution has a linear relationship with (per capita) unemployment compensation. In this paper, we test this relationship for the United Kingdom from 2001 to 2015. Our empirical investigation confirms that the income structure of low and middle classes (about 90% of populations) in the United Kingdom exactly obeys exponential distribution, in which the lower-bound u is exactly in line with the evolution of unemployment compensation.

This study presents the B92 Quantum Key Distribution scheme and its optimization and implementation considerations. Simulation software was developed to model and analyze the B92 protocol under varying conditions. Another contribution of this work is investigating how this protocol runs on real quantum computing hardware. New eavesdropping schemes were proposed and modeled.

Growing energy demand in the distributed energy system (DES) besides new charging loads of electric vehicles (EVs) make DES infrastructure unavailable earlier than normal projections. DES lines need to be upgraded to carry the modern demand of customers. DES line upgrade (LU) cost minimized and deferred to the next years by using energy storage system (ESS). ESS offers the opportunity to use energy flexibly in the distribution grid. It is possible to use ESS to shift the inevitable upgrade costs of the distribution grid elements and increase the power quality of the distribution grid. In this study, a method is proposed to extend the lifespan of DES with ESS and reduce line upgrade and investment costs in the distribution system. For this purpose, the IEEE 33 bus test grid is used, and the proposed method is tested and analyzed with different case studies. According to the results, the proposed method can reduce the investment cost by up to 80%. Besides, ESS usage considering load increase and line conditions of the distribution grid, upgrade costs of distribution grid are shifted, resulting in an optimal dimensioning and positioning while extending the lifespan of the distribution grid elements and, at the same time, offering significant improvements in energy quality. Additionally, it is seen that the power losses of the distribution grid are reduced up to 26%, and the voltage profile of buses is improved with the usage of ESS.

Widespread poverty is the most serious threat and social problem that Bangladesh faces. Regional vulnerability to climate change threatens to escalate the magnitude of this poverty. It is essential that projections of poverty be made while bearing in mind the effects of climate change. The main purpose of this paper is to investigate the agrarian sub-national regional analysis of climate change vulnerability in Bangladesh under various climate change scenarios and its potential impact on poverty. This study is relevant to socio-economic research on climate change vulnerability and agriculture risk management and has the potential to contribute new insights to the complex interactions in household income and climate change risks to agricultural communities in Bangladesh and South Asia. The current study uses analysis of variance, cluster analysis, decomposition of variance and log-normal distribution to estimate the parameters of income variability that ascertain vulnerability levels and help us to understand the poverty levels that climate change could potentially incur. It is found that the income share in income sources revealed that income category shares across the various regions of Bangladesh are far from uniform. The variance decomposition of income showed that agricultural income in Mymensingh and Rangpur is the main cause of income difference. Moreover, large variance of agricultural income in the regions is induced by gross income from rice production. Additionally, constant reduction of rice yield due to climate change in Bangladesh is not such a severe problem for farmers, however, the extreme events like flood, flash flood, drought, sea level rise, and greenhouse gas emission based on RCPs could increase the poverty rates in Mymensingh, Rajshahi, Barisal, and Khulna regions that would be highly affected by unexpected yield loss due to extreme climatic events. Therefore, research and development of adaptation measures to climate change for regions where farmers are largely dependent on agricultural income is important.

Recently, the demand for electric vehicle is increasing worldwide due to eco-friendly policies and stricter emission regulations. As a traction motor for electric vehicle, interior permanent magnet synchronous motors are mainly used. For the design of the interior permanent magnet synchronous motor, the magnetic equivalent circuit method, which is a method of lumped constant circuit, and the finite element method, which is a method of distributed constant circuit, mainly are used. Magnetic equivalent circuit method is useful for simple design through fast and intuitive parameters, but it cannot derive the distribution of magnetic field. The finite element method can derive an accurate magnetic field distribution, but it takes a long time to analyze and it is difficult to analyze intuitive design parameters. In this paper, magnetic equivalent circuit method and Carter coefficient are mixed for rotor structure design. This design method will be called the hybrid magnetic equivalent circuit method. Intuitive design parameters are derived through this hybrid magnetic equivalent circuit method. We will derive the Air gap flux density distribution according to rotor shape, no-load induced voltage, and cogging torque, and compare and verify it with the finite element method.

Novel Cellular Immunotherapy with engineered T cells has improved cancer treatment and established therapeutic promises to prevent tumor formation in clinical studies. Due to certain restrictions and difficulties, CAR and TCR T cells therapies were inadequate at points. CRISPR Cas9 genome-editing tool has a significant potential for these two cell-based therapies. As a specialized gene-editing technique, CRISPR Cas9 is used to repair genetic alternation with minimum damage. It is used as an adjunct to Immunotherapy to stimulate a more robust immune response. CRISPR has long outpaced other target-specific genome editing methods such as ZFNs and TALEN due to its high efficiency, competence in targeting, and stable operating condition. CRISPR can overcome the two major drawbacks of universal CAR T cells: allorejection and graft-vs-host disease. TCR-based T cell treatment can reduce inappropriate binding between endogenous and transgenic TCR, resulting in a reduction of severe toxicity. The CAR and TCR T based cell therapies uphold an excellent future for tumor malignancies This article has elucidated the administration of CRISPR Cas9 in Novel Cellular Immunotherapy, CAR, and TCR T cell therapy. However, this article did not fail to observe this technology's ethical concerns, limitations, and challenges. Furthermore, the article compares CRISPR-mediated allogeneic CAR T cell to TCR-T cell therapy.

In statistics and probability theory, one of the most important statistics is the sums of random variables. After introducing a probability distribution, determining the sum of n independent and identically distributed random variables is one of the interesting topics for authors. This paper presents the probability density functions for the sum of n independent and identically distributed random variables such as Shanker, Akash, Ishita, Pranav, Rani, and Ram Awadh. In order to determine all aforementioned distributions, the problem-solving methods are applied which is based on the change-of-variables technique.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

This research focuses on the customer orientation of insurance brokers, whose activity is regulated by the Law of 26/2006 of July 17 on the mediation of private insurances and reinsurances. The goal is to ascertain whether the intermediation inherent in the insurance broker’s activity, which implies a customer-oriented service, entails a positive behaviour that transcends the immediate environment, reaching society. This study presents a comparative analysis between the insurance brokerage society, characterised by providing a personalised customer service, and banks’ advisory services on insurance. To this end, we study the evolution of the total volume of business and new production, compared for a portfolio of insurance products. The results presented in this research suggest that the customer values the advisory service provided by the broker. However, for a particular business segment in standardised insurance products and products related to banking assets, customers are more likely to resort to the bank’s services. In addition, the results indicate that the commission percentages applied by the entities operating in the banking insurance channel exceed those perceived by the insurance broker. With all this, intermediation in the development of the insurer’s activity can entail an ethical and social behaviour that involves customer-orientation and, possibly, social service, which does not always benefit the insurer.

Inflammatory bowel disease (IBD) has evoked a significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising of Crohn’s disease and Ulcerative colitis manifest as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes, elicits both innate and adaptive immune responses in the gut culminating in aberrant intestinal inflammation. Interestingly, IBD leukocyte repertoire is significantly entwined with chemokine assisted chemotactic navigation into the sites of inflammation which is also thought to generate favourable immune suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims at critically examining the CCR6 driven immune pathways; T_H1/T_H2, T_H1/T_H17, T_H17/ T_reg, IL-23/IL-17, Akt/ERK-1 /2, ILC3 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD aetiopathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

To obtain drop-in fuel properties from non-feed biomass, we herein report the catalytic hydrotreatment of microalgae biocrude, produced from hydrothermal liquefaction (HTL) of Spirulina. Our contribution focuses on the effect of temperature, initial H2 pressure, and residence time on the removal of heteroatoms (O and N). In contrast to common hydrotreating experimental protocols at batch scale, we devised a set of two-level factorial experiments and studied the most influential parameters affecting the removal of heteroatoms. It was found that up to 350 °C, the degree of deoxygenation (de-O) is mainly driven by temperature, whereas the degree of denitrogenation (de-N) also relies on initial H2 pressure and temperature-pressure interaction.Based on this, complete deoxygenation was obtained at mild operating conditions (350 °C), reaching a concurrent 47 % denitrogenation. Moreover, three optimized experiments are reported with 100 % removal of oxygen. In addition, the analysis by GC-MS and Sim-Dis gives insight to the fuel quality. The distribution of heteroatom N in lower (<340 °C) and higher (>340 °C) fractional cuts is studied by a fractional distillation unit following ASTM D-1160. Final results show that 63-68 % of nitrogen is concentrated in higher fractional cuts.

Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e thiazolidinedione (TZD) class of drugs on Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and NOR mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independant mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies.

Species distribution models have become tools of great importance in ecology since the advanced knowledge of suitable habitat of species is needed in the process of the world's biodiversity conservation. Models that use presence-only data are of great interests and are widely used in ecology due to their easy access. However, these models do not estimate accurately the true spatial species distribution based solely on presence-only data since they do not account for biases induced by the sampling techniques used and imperfect detection. To address this gap, Hierarchical integrated models have been recently introduced. Through this study, we assessed the relative performance of these new SDMs models using simulated data. The performance of the models was tested by comparing the estimates of parameters of the distribution models they provide with parameters used to simulate the distribution of the virtual species. The best model was the one whose estimates were close to the true distribution parameters of the virtual species. Results showed that analyzing Presence-only data in conjunction with Point-counts data through the Dorazio's Hierarchical model produced estimates of the coecients of the species intensity models with high precision and less bias while the Koshkina integrated model showed poor performance. Site-occupancy data, being not informative of species abundance, did not allow reducing biases in Presence-only data. The Dorazio's Hierarchical model produced estimates with high precision even with low detection probability. We have also found that the species rarity tends to in ate the variability of the models' estimates making modelling abundant species to be more accurate than modelling less abundant species. Hence, to model the species distribution with high precision based on Presence-only data, additional Point-counts data are required to account for sampling bias and imperfect detection.

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.

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood-brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure-activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, q²_CV = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

With the accelerating urbanization process, the population increasingly concentrates in urban areas. In view of the special situation in China and a series of problems in the process of rapid urbanization, there were no reasonable measures for optimizing the population pattern. This study explored the distribution pattern of the Chinese population and proposed an optimization plan for the population distribution using GIS analysis. The main findings were as follows. (1) From 2010 to 2015, the distribution of population density in China presented a pattern of high in the southeast and low in the northwest based on the county-level administrative regions. The population still showed a tendency to migrate to the southeast of the country based on the “Hu Huanyong Line”. (2) There was a great difference in the land use efficiency in terms of population and economic production in China. The economic concentration in China was higher than the population concentration. In the areas where population and economic production were aggregated, GDP per capita and land use efficiency were higher. (3) Based on the land use efficiency in terms of population and economic production, the optimized urbanization plan of “1+4+11” for China’s urbanization was put forward, namely, one national-level aggregated area of population and economic production, 4 regional-level aggregated areas of population and economic production, and 11 local regionally aggregated areas of population and economic production. This optimization plan for urbanization represents an attempt to explore the direction of China’s urbanization, and it can be used to optimize the spatial development pattern and provide scientific guidance for the new urbanization plan.

The main purpose of this paper is to introduce and investigate degenerate Poisson distrib- ution which is a new extension of the Poisson distribution including the degenerate expo- nential function. We then provide several properties of the degenerate Poisson distribution such as the first and the second raw moments and di¤erence operator property. Moreover, we acquired the skewness and the kurtosis for the degenerate Poisson distribution. We also derive its moment generating function by which we define the degenerate Bell polynomials and give a connection for these polynomials related to the unsigned Stirling numbers of the …rst kind.

It was once thought that high QoS (Quality of Service) performance solves recurrent problems of low-quality multimedia services. Since then, solutions have been proposed to ensure a high level of QoE (Quality of Experience). In this document, the authors attempt to outline their understanding of an accurate meaning of quality of multimedia services. Starting from QoS and passing through generalised QoE, the authors focus on aspects of subjective and objective quality modelling and optimisation of visual performance for TRV (Target Recognition Video) applications (such as video surveillance), outlining the path of ITU-T standardisation in this area. The authors revised the ITU-T Recommendation P.912 to reflect improved subjective test techniques developed since this Recommendation was approved. The authors also attempt to predict at least some existing errors of reasoning, which are likely to become evident for the industry in the next decade.

Synthesis of zeolite T with a variety of desired characteristics necessitate extensive work in the formulation and practical experiments either by conventional hydrothermal methods or aided with different approaches and synthesis techniques such as secondary growth or microwave irradiation. The objectives of this review are to adduce the potential work in zeolite T (Offretite-Erionite) synthesis evaluating determining factors affecting the synthesis and quality of the zeolite T crystals. Attention is given to the extensive studies that interconnect with other significant findings.

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.

In the world industry plant, solid and solid metals are always in contact even their motions not independent. Modeling of rolling die contact with slab primarily needs to describe the Tribology of contact phenomena. Consideration of continuum theory of rolling contact how a contact region is formed between rolling die and slab, and how the tangential force is distributed over the contact area with coefficient of friction is important. The central concern of numerical model is used in this work to indicate a set of equations, derived from the contact principle, that transfer the physical event into the mathematical equations including the laws of nature, such as newton’s laws, boundary conditions, state of stresses and their derivatives at particular time and locations. In this paper the elasticity stress behavior of rolling die contact with slab for number of cyclic loads is modeled. The model is including new proposed constitutive equations for discontinuity of the velocity, pressure distribution in rolling contact from the enter side to exit side of the neutral point. To verify the model, finite element simulation and experimental data from the literature are considered. The results show good agreement with finite element simulation and experimental data.

Water distribution networks are vital infrastructure, needed for providing consumers with sufficient water of appropriate quality. The cost of construction, operation, and maintenance of such networks is extremely large. The problem of optimization of a water distribution network is governed by the type of water distribution network and the size of pipelines placed in the distribution network. This problem of the optimal diameter allocation of pipes in a distribution network has been heavily researched over the past few decades. This study describes the development of a computer program, ‘Smart Optimization Program for Water Distribution Networks’ (SOP–WDN), which applies Genetic Algorithm to the problem of the least-cost design of water distribution networks. SOP–WDN demonstrates the application of an evolutionary optimization technique, Genetic Algorithm, linked with a hydraulic simulation solver EPANET, for the optimal design of water distribution networks. The developed program was applied to three benchmark water distribution network optimization problems and produced consistently good results. SOP–WDN can be utilized as a tool for guiding engineers during the design and rehabilitation of water distribution pipelines.

The information entropy for Smoluchowski coagulation equation is proposed based on statistical mechanics. And the normalized particle size distribution is a lognormal function at equilibrium from the principle of maximum entropy and moment constraint. The geometric mean volume and standard deviation in the distribution function are determined as simple constant. The results reveal that the assumption that algebraic mean volume be unit in self-preserving hypothesis is reasonable in some sense. Based on the present definition of information entropy, the Cercignani’s conjecture holds naturally for Smoluchowski coagulation equation. Together with the proof that the conjecture is also true for Boltzmann equation, Cercignani’s conjecture will holds for any two-body collision systems, which will benefit the understanding of Brownian motion and molecule kinematic theory, such as the stability of the dissipative system, and the mathematical theory of convergence to thermodynamic equilibrium.

This study generalized the best copula to characterize the joint probability distribution between rainfall severity and duration in Peninsular Malaysia using two dimensional copulas. Specifically, to construct copulas, Inference Function for Margins (IFM) and Canonical Maximum Likelihood (CML) methods were specially exploited. For the purpose of achieving copula fitting, the derived rainfall variables by making use of the Standardized Precipitation Index (SPI) were fitted into several distributions. Five copulas, namely Gaussian, Clayton, Frank, Joe and Gumbel were put to the tests to establish the best data fitted copula. The tests produced acknowledged and satisfactory results of copula fitting for rainfall severity and duration. Surveying the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC), only three copulas produced a better fit for parametric and semi parametric approaches. Finally, two consistency tests were conducted and the results had shown that Frank Copula produced consistent results.

The past two decades have seen a revolution in multiple myeloma (MM) therapy with the introduction of several small molecules, mostly orally effective, whose mechanisms are based on proteasome inhibition, histone deacetylase (HDAC) blockade, and immunomodulation. Immunotherapeutic approaches to MM treatment using monoclonal antibodies (mAbs), while long in development, began to reap success with the identification of CD38 and SLAMF7 as suitable targets for development, culminating in the 2015 FDA approval of daratumumab and elotuzumab, respectively. This review highlights additional mAbs now in the developmental pipeline. Isatuximab, another anti-CD38 mAb, currently is under study in four phase III trials and may offer certain advantages over daratumumab. Several antibody-drug conjugates (ADCs) in the early stages of development are described, including JNJ-63723283, which has attained FDA breakthrough status for MM. Other mAbs described in this review include denosumab, recently approved for myeloma-associated bone loss, and checkpoint inhibitors, although the future status of the latter combined with immunomodulators has been clouded by unacceptably high death rates that caused the FDA to issue clinical holds on several of these trials. Also highlighted are therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development.

In this paper we present the measurement of charged pion two-particle femtoscopic correlation functions in $\sqrt{S_{NN}}$= 200 GeV Au+Au collisions, in 31 average transverse mass bins, separately for positive and negative pion pairs. Lévy-shaped source distributions yield a statistically acceptable description of the measured correlation functions, with three physical parameters: correlation strength parameter λ , Lévy index α and Lévy scale parameter R. The transverse mass dependence of these Lévy parameters is then investigated. Their physical interpretation is also discussed, and the appearance of a new scaling variable is observed.

This work addresses the problem of sampling from Gaussian probability distributions by means of uniform samples obtained deterministically and directly from space-filling curves (SFCs), a purely topological concept. To that end, the well-known inverse cumulative distribution function method is used, with the help of the probit function,which is the inverse of the cumulative distribution function of the standard normal distribution. Mainly due to the central limit theorem, the Gaussian distribution plays a fundamental role in probability theory and related areas, and that is why it has been chosen to be studied in the present paper. Numerical distributions (histograms) obtained with the proposed method, and in several levels of granularity, are compared to the theoretical normal PDF, along with other already established sampling methods, all using the cited probit function. Final results are validated with the Kullback-Leibler and two other divergence measures, and it will be possible to draw conclusions about the adequacy of the presented paradigm. As is amply known, the generation of uniform random numbers is a deterministic simulation of randomness using numerical operations. That said, sequences resulting from this kind of procedure are not truly random. Even so, and to be coherent with the literature, the expression ”random number” will be used along the text to mean ”pseudo-random number”.

Sea surface partial pressure of CO2 (pCO2) is a critical parameter in the quantification of air-sea CO2 flux, which plays an important role in calculating the global carbon budget and ocean acidification. In this study, we use chlorophyll-a concentration (Chla), sea surface temperature (SST), absorption due to dissolved and particulate detrital matter (Adg), diffuse attenuation coefficient of downwelling irradiance at 490nm (Kd) and mixed layer depth (MLD) as input data for retrieving the sea surface pCO2 in the North Atlantic based on a remote sensing empirical approach with the Categorical Boosting (CatBoost) algorithm. The results show that the root mean square error (RMSE) is 8.25μatm, the mean bias error (MAE) is 4.92μatm and the coefficient of determination (R2) can reach 0.946 in the validation set, which mean that the CatBoost model makes an improvement compared to other models in the published studies. In the further analysis of the spatial and temporal distribution of the sea surface pCO2 in the North Atlantic, it can be found that the North Atlantic sea surface pCO2 has a clear trend with latitude variations and have strong seasonal changes. Furthermore, the sea surface pCO2 in this area is mainly affected by sea temperature and salinity, and influenced by biological activities in some sub-regions.

The Ramanujan primes are the least positive integers Rn having the property that if m ≥ Rn, then π_m − π_(m/2) ≥ n. This document develops several bounds related to the Ramanujan primes, sharpening the currently known results. The theory presented is by no means exhaustive, however it provides insights for future research work. Alternatively, we may say that it is a road map which may be followed to make further discoveries.

In this paper we discuss a problem of generalization of binomial distributed triangle, that is sequence A287326 in OEIS. The main property of A287326 that it returns a perfect cube n as sum of n-th row terms over k; 0 ≤ k ≤ n−1 or 1 ≤ k ≤ n, by means of its symmetry. In this paper we have derived a similar triangles in order to receive powers m = 5; 7 as row items sum and generalized obtained results in order to receive every odd-powered monomial n^2m+1; m ≥ 0 as sum of row terms of corresponding triangle. In other words, in this manuscript are found and discussed the polynomials D_m(n,k) and U_m(n,k), such that, when being summed up over k in some range with respect to m and n returns the monomial n^2m+1.

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

(1) Aim of the study was to investigate the spatial and temporal characteristics of the airflow created by two commercially available non-contact tonometers, the CorvisST and the Ocular Re-sponse Analyser. (2) The airflow pressure was measured using a MEMS pressure sensor to inves-tigate the spatial and temporal distribution. The airflow from the CorvisST and Ocular Response Analyser were mapped to a 600µm and a 1mm resolution grid, respectively. (3) Central airflow pressure of the CorvisST (96.4 ± 1.4)mmHg was higher than the Ocular Response Analyser (91.7 ± 0.7)mmHg. The duration of the air-puffs also differed, with the CorvisST showing a shorter du-ration (21.483 ± 0.2881)ms than the ORA (23.061 ± 0.1872)ms. The rising edge of the CorvisST airflow pressure profile demonstrated a lower gradient (+8.94mmHg/ms) compared to the Oc-ular Response Analyser (+11.00mmHg/ms). Both had similar decay response edges; CorvisST -11.18mmHg/ms, Ocular Response Analyser -11.65mmHg/ms. (4) The study presents a valid method to investigate physical dimensions of the airflow pressure of non-contact tonometers. Novel findings relating to the magnitude, duration and spatial characteristics of the respective airflow pressures are reported. It is anticipated that this information will better inform clinical studies and theoretical models relating to ocular biomechanics.

The main aim of this paper is to investigate multifarious properties and relations for the gamma distribution. The approach to reach this purpose will be introducing a special polynomial including gamma distribution. Several formulas covering addition formula, derivative property, integral representation and explicit formula are derived by means of the series manipulation method. Furthermore, two correlations including Bernoulli and Euler polynomials for gamma distribution polynomials are provided by utilizing of their generating functions.

A new attack against the Kirchhoff-Law-Johnson-Noise (KLJN) key distribution system is introduced. The attack is based on 1) Utilizing the dc-voltage-source - which we put at Alice’s end in our mathematical modeling of the attack-that could exist due to errors, imbalances, Electromagnetic interference and etc.2) On studying the number of samples per bit in the security key that the measured Alice/Bob voltages exceeds or falls below a threshold voltage, respectively. The threshold voltage is the average between dc voltages across low and high resistors- generated by a dc-voltage source. We count the number of samples the voltage at Bob’s end (containing both the noise and dc components) exceeds the threshold voltage and how many times it falls below the threshold to judge whether the resistor can be guessed as low or high for every cycle. Also for a pre-specified key-length we count the number of high resistance estimations per bit –at Bob’s end-according to the previous criterion and the non-successful estimations per bit to judge the final guessed resistor value at Alice’s end and Bob’s end, where if we have more bits with most of its measured samples are above the threshold voltage then we will predict Bob’s resistance as high resistance, otherwise we predict Bob’s resistance to be low resistance. The Simulation was conducted and the attack proved that it is successful unless the temperature increased dramatically to ranges more than a threshold temperature ~ Kelvin that increases when the number of samples per bit increases.

In this paper, the definition of information entropy of Smoluchowski coagulation equation for Brownian motion is introduced based on coagulation probability. The expression of entropy is the function of geometric average particle volume and standard deviation with lognormal distribution assumption. The asymptotic solution with moment method shows that the entropy is a monotone increasing function of time, which is equivalence to the entropy based on particle size distribution. the result reveals that the present definition of entropy of Smoluchowski coagulation equation are inadequate because the particle average volume at equilibrium cannot be determined from the principle of maximum entropy. This provides a basis for further exploring the global properties of Smoluchowski coagulation equation.

Polyolefin fibre reinforced concrete (PFRC) has become an attractive alternative to steel for the reinforcement of concrete elements mainly due to its chemical stability and the residual strengths that can be reached with lower weights. The use of polyolefin fibres can meet the requirements in the standards, although the main constitutive relations are based on the experience with steel fibres. Therefore, the structural contributions of the fibres should be assessed by inverse analysis. In this study, the fibre dosage has been fixed at 6kg/m³ and both self-compacting concrete and conventional concrete have been used to compare the influence of the positioning of the fibres. An idealized homogeneous distribution of the fibres with such fibres crossing from side to side of the specimen has been added to self-compacting concrete. The experimental results of three-point bending tests on notched specimens have been reproduced by using the cohesive crack approach. Hence, the constitutive relations were found. The significance of this research relies on the verification of the formulations found to build the constitutive relations. Moreover, with these results it is possible to establish the higher threshold of the performance of PFRC and the difficulties of limiting the first unloading branch typical of fracture tests of PFRC.

Among the biggest challenges facing the contemporary human condition, and therefore also education, is responding to the climate crisis. The source of the crisis is assumed to be absent-mindedness, presented by Leslie Dewart as a distortion of the development of human consciousness. Dewart's poorly-known philosophical consciousness study is presented in this paper in broad outline. The problems in the study of consciousness, the most important of which are the qualitative representations – qualia – and the question of free will, are also briefly discussed. These problems are then examined transcendental analytically, with the question of what one must assume in order to allow the emergence of these phenomena. From the resulting conception of causal relationship, we proceed to the circular causality as a prerequisite for life, namely the homeostatic systems and negative feedback. An organization of action that is essential to animals and humans is presented, using William Powers’ perceptual control theory (PCT), and the role of consciousness in this organization is drafted according to the studies of Martin Taylor. Action is seen as continuous problem solving, in which negative feedback is used to bring perceptions into line with the goals. The fundamental function of consciousness is revealed as the direction and enhancement of learning. Based on PCT, it can be shown that the main practical problems in animal and, especially, human action, are related to adverse side effects of action and the resulting various conflicts. The climate crisis is a typical example of the problematic side effects of collective action. Dewart's concept of absent-mindedness can therefore be defined as an inability to responsibly account for the side effects of action. Thus, the main task of education is to forestall, through negative feedback and in cooperation with learner consciousness, absent-mindedness and the problems it causes.

Electric power systems are experiencing relevant changes involving the growing penetration of distributed generation and energy storage systems, the introduction of electric vehicles, the management of responsive loads, the proposals for new energy markets and so on. Such evolution is pushing for a paradigm shift: the management must move from traditional planning and manual intervention to full “smartization” of medium and low voltage networks. Peculiarities and criticalities of future power distribution networks originate from the complexity of the system that includes both the physical aspects of electric networks and the cyber aspects, like data elaboration, feature extraction, communication, supervision and control; only fully integrated advanced monitoring systems can foster this transition towards network automation. The design and development of such future networks require distinct kinds of expertise in the industrial and information engineering fields. In this context, this paper provides a comprehensive review of current challenges and multidisciplinary interactions in the development of smart distribution networks.