Since the 21st century, China's urbanization process has been rapid development, the concept and function of urban public space in the city has been gradually paid attention to. In order to guarantee life and water, most urban construction relies on rivers, and Bridges are the most important way to communicate between urban areas. The main functional part of the bridge is the span structure, that is, the bearing structure of the bridge, and the lower part of the "gray" space formed by the bridge structure. Considering the social level, with the economic growth and urbanization development, people have brought a better living environment and quality of life, and also improved the requirements for urban public environment. In the increasingly tense urban space, how to use and transform the space under the bridge is a problem that needs to be considered and solved. In view of this problem, in this study, we try to solve the micro-transformation of space under Bridges in cities through public art from the perspective of "regional culture" and "art for all". This paper analyzes the micro-transformation of space art under Bridges in two large cities of Shanghai and Foshan, namely, the space under Bridges under Songhong Road in Shanghai, the space under Bridges under Central Of Suzhou River and the space under Bridges under Pingsheng Bridge in Foshan. This paper discusses the cultural intervention of "regional culture" in the micro-transformation of the space under the bridge, and the influence and effect of "art for all" on the public art space under the bridge after the transformation to the community and the public.

A theoretical description of quantum jumps at the level of elementary particles is proposed, based on a micro-cosmological interpretation of their de Broglie phase. The third quantization formalism proposed in current literature for the description of baby universes in quantum cosmology is used here to describe the breakdown of unitarity in the transition from the pre-jump to the post-jump wave function. The corpuscular aspect manifested by the particle in the micro-interaction that originates the jump is represented by a pair of evanescent "micro-universes", respectively pre- and post-jump, connected by a wormhole. The latter represents the actual implementation of the interaction that leads to the projection on the outgoing state; this interaction is always local, even when the selected outgoing state is entangled. Therefore, the decoherence which leads to the emergence of classicality is originated by the same fundamental interactions of the Standard Model involved in the unitary evolution of the wave function. The objective nature of the reduction process admits implications on the possibility of using the formalism in the cosmological context, which are briefly discussed.

Mutations that provide environment dependent selective advantages drive adaptive divergence among species. Many phenotypic differences among related species are more likely to result from gene expression divergence rather than from non-synonymous mutations. In this regard, cis-regulatory mutations play an important part in generating functionally significant variation. Some proposed mechanisms that explore the role of cis-regulatory mutations in gene expression divergence involve microsatellites. Microsatellites exhibit high mutation rates and are abundant in both coding and non-coding regions and could influence gene function and products. Here we tested the hypothesis that microsatellites contribute to gene expression divergence among species with 50 individuals from nine closely related Helianthus species using an RNA-seq approach. Differential expression analyses of the transcriptomes revealed that genes containing microsatellites in non-coding regions (UTRs and introns) are more likely to be differentially expressed among species when compared to genes with microsatellites in the coding regions and transcripts lacking microsatellites. We detected a greater proportion of shared microsatellites in 5’UTRs and coding regions compared to 3’UTRs and non-coding transcripts among Helianthus spp. Further, allele frequency differences measured by pairwise FST at single nucleotide polymorphisms (SNPs), indicate greater genetic divergence in transcripts containing microsatellites compared to those lacking microsatellites. A gene ontology (GO) analysis revealed that microsatellite-containing differentially expressed genes are significantly enriched for GO terms associated with regulation of transcription and transcription factor activity. Collectively, our study provides compelling evidence to support the role of microsatellites in gene expression divergence.

Artificial Intelligence is increasingly being used by social media platforms to tackle online hate speech. The sheer quantity of content, the speed at which is it developed and the enhanced pressure companies are facing by States to remove hate speech quickly from their platforms have led to a tricky situation. This commentary argues that automated mechanisms, which may have biased datasets and be unable to pick up on the nuances of language, should not be left unattended with hate speech as this can lead to issues of violating freedom of expression and the right to non-discrimination.

Many cellular functions important for tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell adhesion receptors. With recent studies emphasising on the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that a lot of attention is being given to integrins. Several integrins are under trial with many demonstrating appealing activity in patients with different cancers. A deeper knowledge of the functions of integrins within the tumor microenvironment is still required, and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. This review report new data on the differential expression of integrins within solid tumors using two publicly available resources: The Cancer Genomic Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA). In this analysis, I investigated the expression of integrin alpha 2 (ITGα2), ITGα3, ITGβ4 and ITGβ6 in tumor tissues versus adjacent normal tissues. This analysis showed that integrins were differentially expressed in cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), esophageal carcinoma (ESCA) and lung adenocarcinoma (LUAD). This analysis showed that ITGα2 and ITGβ6 expression are upregulated in CESC and ESCA, ITGα3 is upregulated in HNSC and ESCA whilst ITGβ4 is highly expressed in CESC, HNSC, ESCA and LUAD tumor tissues compared to adjacent normal tissues. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This review offers the latest synthesis in terms of current knowledge of integrins functions within the tumor microenvironment and potential targets for different cancers.

Abstract: Bacillus subtilis fmb60, which has broad-spectrum antimicrobial activities was isolated from plant straw compost. A hybrid NRPS/PKS cluster was screened from the genome. Sixteen secondary metabolites produced by the gene cluster were isolated and identified using LC-HRMS and NMR. Three lipoamides D–F (1-3) and two amicoumacin derivatives, amicoumacins D, E (4, 5), were identified, and are reported here for the first time. Lipoamides D–F exhibited strong antibacterial activities against harmful foodborne bacteria, with the MIC ranging from 6.25 to 25 µg/mL. Amicoumacin E scavenged 38.8% of ABTS+ radicals at 1 mg/mL. Direct cloning and heterologous expression of the NRPS/PKS and ace gene cluster identified its importance for the biosynthesis of amicoumacins. This study demonstrated that there is a high potential for biocontrol utilization of B. subtilis fmb60, and genome mining for clusters of secondary metabolites of B. subtilis fmb60 has revealed a greater biosynthetic potential for the production of novel natural products than previously anticipated.

We assessed the growth performance, physiological traits, and gene expressions in steers fed with dietary rumen-protected L-tryptophan (RPT) under cold environment. Eight Korean native steers were assigned to two dietary groups, no RPT (Control) and RPT (0.1% RPT supplementation on a dry matter basis), 6 wks. Maximum and minimum temperatures throughout the experiment were 6.7°C and -7.0°C, respectively. Supplementation of 0.1% RPT to a total mixed ration did not increase body weight but had positive effects of elevating average daily gain (ADG) and reducing the feed conversion ratio (FCR) at day 27 and 48. Metabolic parameter showed higher glucose level (at day 27) in the 0.1% RPT group compared to the control group. Real-time PCR analysis showed no significant differences in the expression of muscle (MYF6, MyoD, and Desmin) metabolism genes between the two groups, whereas the expression of fat (PPARγ, C/EBPα, and FABP4) metabolism genes was lower in the 0.1% RPT group than in the control group. Thus, we demonstrate that long-term (6 wks) dietary supplementation of 0.1% RPT was beneficial owing to enhanced growth performance by increasing ADG and glucose level, decreasing FCR, and maintaining homeostasis in immune responses in beef steers during cold environment.

This study investigated the roles of transactions cost in MSMEs access to finance. This was done by investigating the impact of transactions cost on access to credit from both MSMEs and financial institutions (commercial banks and microfinance banks). From the MSMEs’ side, borrowing experience, decision lag, firm size and borrowers’ distance to the loan office were investigated. On the financial institution’s side, the costs of information gathering, loan administration, monitoring and loan enforcement were investigated. We used the questionnaire survey method, in-depth interviews and case studies, as well as the annual financial statements of the banks. We identified interest rate and collateral value as constraints to access to finance for MSMEs. We also found financial institutions’ attitude to MSMEs access to credit was not friendly. Financial institutions need to do more to bring down transaction cost of lending. This hopefully can be achieved by investing more in agent banking which would lower operating costs, as well as spreading risk, and ultimately increase credit intermediation to small businesses.

As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high performance computing(HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enables the explainable-AI eQTL analysis of SNP sets with over a million SNPs. Using this implementation we also present a new method, iRF Leave One Out Prediction (iRF-LOOP), for the creation of Predictive Expression Networks on the order of 40,000 genes or more. We compare the new implementation of iRF with the previous R version and analyze its time to completion on two of the world's fastest supercomputers Summit and Titan. We also show iRF-LOOP's ability to capture biologically significant results when creating Predictive Expression Networks. This new implementation of iRF will enable the analysis of biological data sets at scales that were previously not possible.

Neural networks models are mostly represented by oriented graphs where only the components, constitutive elements of the graph, are transcribed into mathematical xpression. Indeed, accurate knowledge of the full expression of the model is required in certain situations such as selecting among several reference models, the one that best fits the available data or comparing the explanatory and predictive performance of an established model with respect to some reference models. In this paper, we establish a formalism of the mathematical expression for multilayer perceptron neural network in a general framework, MLP-p-n-q, with p, n and q natural integers and show its restriction to cases where one has a hidden layer and multivariate outputs (MLP-p-1-q), and then a single output (MLP-p-1-1). Then, we give some specific cases of the most commonly used models. An application case is presented in the context of solving a nonlinear regression problem.

Corynebacterium pseudotuberculosis is a Gram-positive bacterium that causes caseous lymphadenitis, a disease that predominantly affects sheep, goat, cattle, buffalo, and horses, but has also been recognized in other animals. This bacterium generates a severe economic impact on countries producing meat. Gene expression studies using RNA-seq is one of the most commonly used techniques to perform transcriptional experiments. Computational analysis on such data through reverse-engineering algorithms leads to a better understanding of the genome-wide complexity of gene interactomes, enabling the identification of genes having the most significant functions inferred by the activated stress response pathways. In this study, we identified the influential or causal genes from four RNA-seq data-sets from different stress conditions (high iron, low iron, acid, osmosis, and PH) in C. pseudotuberculosis, using a consensus-based network inference algorithm called miRsig and identified the causal genes in the network using the miRinfluence tool, which is based on the influence diffusion model. We found that over 50\% of the genes identified as influential have some essential cellular functions in the genomes. In the strains analyzed, most of the causal genes have crucial roles or participate in processes associated with response to extracellular stresses, pathogenicity, membrane components, and essential genes. This research brings new insight into the understanding of virulence and infection by C. pseudotuberculosis.

This work presents an approach for detecting mathematical formulas in scanned document images. The proposed approach is end-to-end trainable. Since many OCR engines cannot reliably work with the formulas, it is essential to isolate them to obtain the clean text for information extraction from the document. Our proposed pipeline comprises a hybrid task cascade network with deformable convolutions and a Resnext101 backbone. Both of these modifications help in better detection. We evaluate the proposed approaches on the ICDAR-2017 POD and Marmot datasets and achieve an overall accuracy of 96% for the ICDAR-2017 POD dataset. We achieve an overall reduction of error of 13%. Furthermore, the results on Marmot datasets are improved for the isolated and embedded formulas. We achieved an accuracy of 98.78% for the isolated formula and 90.21% overall accuracy for embedded formulas. Consequently, it results in an error reduction rate of 43% for isolated and 17.9% for embedded formulas.

The paper investigates the possible use of a low strength domestic sand (D) (up to today useless – not considered as proppant source) of small particle sizes, instead to that of high strength imported commercial sand (C), as a prospective micro-proppant for low permeability reservoirs in Poland. There is need to develop national unconventional gas resources like tight gas, shale gas and coalbed methane. An important energy source of value and readily available in Poland is coal. The basins of this resource are large and bears low permeability coalbed methane reservoirs which needs to be developed to contribute to the energy security, economy and environmental needs of the country. These reservoirs need technological assistance such as hydraulic fracturing which makes use of proppants for development. Most of the commonly used proppants over the years for fracturing have been large grain size commercial proppants of high strength material content bought abroad. Investigated finer proppants are known to have the ability to penetrate narrow fracture networks to ensure effective high reservoir volume and conductivity for production. Results from presented laboratory research shows the D - proppant, which is cheaper and readily available, has the 3K class with low settling rates as a potential micro-proppant for effective transportation, enhancement of conductivity and production rate in the narrow fractures of low permeability reservoirs. Future using of domestic proppant will decrease stimulation cost and will have positive impact on the environment due to omitting long distance transportation from abroad.

The Pashmina and Barbari are two famous goat breeds found in the wide areas of the Indo-Pak region. Pashmina is famous for its long hair-fiber (Cashmere) production while Barbari is not-selected for this trait. So, the mRNA expression profiling in the skin samples of both breeds would be an attractive and judicious approach for detecting putative genes involved in this valued trait. Here, we performed differential gene expression analysis on publicly available RNA-Seq data from both breeds. Out of 44,617,994 filtered reads of Pashmina and 55,995,999 of Barbari which are 76.48% and 73.69% mapped to the ARS1 reference transcriptome assembly respectively. A pairwise comparison of both breeds resulted in 47,159 normalized expressed transcripts while 8,414 transcripts are differentially expressed above the significant threshold. Among these, 4,788 are upregulated in Pashmina while 3,626 transcripts are upregulated in Barbari. Fifty-nine transcripts harbor 57 genes including 32 LOC genes and 24 are annotated genes which were selected on the basis of TMM counts > 500. Genes with ectopic expressions other than uncharacterized and LOC symbol genes are Keratins (KRT) and Keratin Associated Proteins (KRTAPs), CystatinA&6, TCHH, SPRR4, PPIA, SLC25A4, S100A11, DMKN, LOR, ANXA2, PRR9 and SFN. All of these genes are likely to be involved in keratinocyte differentiation, sulfur matrix proteins, dermal papilla cells, hair follicles proliferation, hair curvature, wool fiber diameter, hair transition, hair shaft differentiation and its keratinization. These differentially expressed reported genes are critically valuable for enhancing the quality and quantity of the pashmina fiber and overall breed improvement. This study will also provide important information on hair follicle differentiation for further enrichment analyses and introducing this valued trait to other goat breeds as well.

During March and April 2020, the European Union (EU) was the center of the COVID-19 pandemic. Many National Governments imposed severe lockdown policies to mitigate the health crisis. The European Parliament commissioned a survey to analyse the citizens’ attitudes over a number of issues related to the COVID-19 pandemic. 21804 European citizens in 21 EU countries responded the survey between 23 April and 1 May 2020. The paper analyses empirically the individual satisfaction that European citizens have experienced over the measures taken by the respective National Governments to control the COVID-19 pandemic. The analysis is based on a micro-econometric model (ordered probit) that explains the citizens’ satisfaction by a number of attitudes and sociodemographic factors. Our results reveal that Spaniards are the least satisfied citizens in comparison with Danes, Irelanders, Greeks and Croats who are the most satisfied nationals. The years of education and the social class also play a determinant role. We also find that the most important determinant is the political support to the Government, and that those who are more worried by the economy and the protection of individual rights are usually more critic with the measures than those who are more worried by the health consequences.

A phosphate/molybdate and cerium-modified phosphate/molybdate conversion coatings were deposited on a carbon steel surface and their protective and self-healing abilities were evaluated. Surface morphology and inner structure of the coatings were examined using FE-SEM-FIB and TEM techniques, chemical composition and element distribution depth profiles in conversion layers were determined using EDX measurements, whereas XPS was applied for the analysis of Mo and Ce oxidation states. Voltammetric measurements and EIS were performed to assess the corrosion behavior of the samples. The higher protective and stronger self-healing abilities were found for phosphate/molybdate/cerium conversion coating deposited in a sulphate-containing solution. This was attributed to higher values of both: total cerium and Ce(IV) content in the conversion layer as well as to lower number of structural defects in the coating. It was demonstrated that the micro-structural characteristics of protective coatings are also important in determining self-healing abilities.

The rapid expansion of transcriptomics from increased affordability of next-generation sequencing (NGS) technologies generates rocketing amounts of gene expression data across biology and medicine, and notably in cancer research. Concomitantly, many bioinformatics tools were developed to streamline gene expression analysis and quantification. We tested the concordance of NGS RNA sequencing (RNA-seq) analysis outcomes between the two predominant programs for reads alignment, HISAT2 and STAR, and the two most popular programs for quantifying gene expression in NGS experiments, edgeR and DESeq2, using RNA-seq data from a series of breast cancer progression specimens, which include histologically confirmed normal, early neoplasia, ductal carcinoma in situ and infiltrating ductal carcinoma samples microdissected from formalin fixed, paraffin embedded (FFPE) breast tissue blocks. We identified significant differences in aligners’ performance: HISAT2 was prone to misalign reads to retrogene genomic loci, STAR generated more precise alignments, especially for early neoplasia samples. edgeR and DESeq2 produced similar lists of differentially expressed genes in stage comparisons, with edgeR producing more conservative, though shorter, lists of genes. Albeit, Gene Ontology (GO) enrichment analysis revealed no skewness in significant GO categories identified among differentially expressed genes by edgeR vs DESeq2. As transcriptome analysis of archived FFPE samples becomes a vanguard of precision medicine, identification and fine-tuning of bioinformatics tools becomes critical for clinical research. Our results indicate that STAR and edgeR are well-suited tools for differential gene expression analysis from FFPE samples.

Transporter associated with antigen processing 1 (TAP1) gene codes for a transporter protein, which is responsible for tumor antigen presentation in the MHC I or HLA complex. A defect in the gene results in an inadequate tumor tracking. TAP1 may also influence multi drug resistance, which is an extreme threat in providing treatment by drugs which are chemotherapeutic. The gene of TAP1 was analyzed bioinformatically. It gave us prognostic data as a confirmation of whether it should be used as a biomarker. The expression level and pattern analysis were conducted using ONCOMINE, GENT2 and GEPIA2 online platforms. Samples with different clinical outcomes were investigated for expression and promoter methylation analysis was done in cancer vs normal tissues using UALCAN. The copy number alteration and mutation frequency and expression in different cancer studies were analyzed using cBioPortal. The PrognoScan and KM plotter survival analysis of significant data (p-value<0.05) was representing graphically. Pathway and Gene ontology analysis of gene correlated to TAP1 gene was presented using bar charts. After arranging the data in a single panel and correlating expression to prognosis, understanding mutational and alterations and comparing pathways, TAP1 may be a potential novel target to evade a threat against chemotherapy and the study gives new aspects to consider for immunotherapy in human breast, lung, liver and ovarian cancer.

Membrane transporters (MTs) are mainly localized at the plasma membrane (PM), tonoplast and vacuolar membrane (VM) of cells in all plant organs. Their work is to maintain the cellular homeostasis by controlling ionic movements across PM channels from roots to upper plant parts, xylem loading and remobilization of sugar molecules from photosynthesis tissues in the leaf (source) to roots, stem and seeds (sink) via phloem loading. The plant’s whole source-to-sink relationship is regulated by multiple transporting proteins in a highly sophisticated manner and driven based on different stages of plant growth and development (PG&D), and environmental changes. The MTs play a pivotal role in PG&D in terms of increased plant height, branches/tiller numbers, enhanced numbers, length and filled panicles per plant, seed yield and grain quality. Dynamic climatic changes disturbed the ionic balance (salt, drought and heavy metals) and sugar supply (cold and heat stress). Due to poor selectivity, some of the MTs also uptake toxic elements in the roots that negatively impact on PG&D, later on also exported to upper parts and then deteriorate the grain quality. As an adaptive strategy, in response to salt and HMs plants activated PM and VM localized MTs that export toxic elements into vacuole, and also translocate in the root’s tips and shoot. However, in case of drought, cold and heat stresses, MTs increased the water and sugar supply to all organs. In this review, we mainly reviewed recent literature from Arabidopsis, halophytes, and major field crops such as rice, wheat, maize and oilseed rape to argue on the global role of MTs in PG&D and abiotic stress tolerance. We also discussed the gene expression level changes and genomic variations within a species as well as within a family in response to developmental and environmental cues.

Successful engineering of a microbial host for efficient production of a target product from a given substrate can be viewed as an extensive optimization task. Such a task involves the selection of high activity enzymes as well as their gene expression regulatory control elements (i.e., promoters and ribosome binding sites). Finally, there is also the need to tune expression of multiple genes along a heterologous pathway to relieve constraints from rate-limiting step and help reduce metabolic burden on cells from unnecessary over-expression of high activity enzymes. While the aforementioned tasks could be performed through combinatorial experiments, such an approach incurs significant cost, time and effort, which is a handicap that can be relieved by application of modern machine learning tools. Such tools could attempt to predict high activity enzymes from sequence, but they are currently most usefully applied in classifying strong promoters from weaker ones as well as combinatorial tuning of expression of multiple genes. This perspective reviews the application of machine learning tools to aid metabolic pathway optimization through identifying challenges in metabolic engineering that could be overcome with the help of machine learning tools.

Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.

Emotion recognition defined as identifying human emotion and is directly related to different fields such as human-computer interfaces, human emotional processing, irrational analysis, medical diagnostics, data-driven animation, human-robot communi- cation and many more. The purpose of this study is to propose a new facial emotional recognition model using convolutional neural network. Our proposed model, “ConvNet”, detects seven specific emotions from image data including anger, disgust, fear, happiness, neutrality, sadness, and surprise. This research focuses on the model’s training accuracy in a short number of epoch which the authors can develop a real-time schema that can easily fit the model and sense emotions. Furthermore, this work focuses on the mental or emotional stuff of a man or woman using the behavioral aspects. To complete the training of the CNN network model, we use the FER2013 databases, and we test the system’s success by identifying facial expressions in the real-time. ConvNet consists of four layers of convolution together with two fully connected layers. The experimental results show that the ConvNet is able to achieve 96% training accuracy which is much better than current existing models. ConvNet also achieved validation accuracy of 65% to 70% (considering different datasets used for experiments), resulting in a higher classification accuracy compared to other existing models. We also made all the materials publicly accessible for the research community at: https://github.com/Tanoy004/Emotion-recognition-through-CNN.

Extracellular vesicles (EV) such as exosomes, are newly recognized fundamental, natural and physiologic particles of life that seemingly are involved all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and the potential therapeutic uses of these nano-vesicles requires innovative experimental approaches, in virtually every field. Of the EV group, exosome nano-vesicles and larger companion extracellular micro vesicles (MV) can mediate completely new phenomena dependent on intercellular transfer of proteins and selected RNAs; particularly miRNAs, between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern day exosomes to withstand unusually harsh conditions; perhaps due to unusual membrane lipid compositions. This is exemplified by maternal milk exosome survival of the neonatal acid/enzyme rich stomach. It is postulated that this also applies to their durable presence in phagolysosomes; suggesting unique intracellular release of contents. A major issue discussed is the generally poorly realized superiority of these naturally evolved nano vesicles to therapies compared human engineered artificial nanoparticles; say for treatment of cancers.

Animal welfare is not only an ethically important consideration in good animal husbandry, but can also have a significant effect on an animal’s productivity. The aim of this paper is to show that a reduction in animal welfare, in the form of increased stress, can be identified in pigs from frontal images of the animals. We train a Convolutional Neural Network (CNN) using a leave-one-out design and show that it is able to discriminate between stressed and unstressed pigs with an accuracy of >90% in unseen animals. Grad-CAM is used to identify the animal regions used, and these support those used in manual assessments such as the Pig Grimace Scale. This innovative work paves the way for further work examining both positive and negative welfare states with a view to the development of an automated system that can be used in precision livestock farming to improve animal welfare.

In Acropora, the complex canals in a coral colony connect all polyps into a holistic network to collaborate in performing biological processes, while axial canal is the largest canal amongst the network and distributes at the center of a coral branch. However, previous studies indicated that, in the non-radial symmetry transport system of Acropora, axial canal do not play a major role in the transport of hydroplasm, and the action of axial canal in coral growth is still obscure. In this study, we reconstructed six Acropora muricata samples by high resolution micro-computed tomography to investigate the growth patterns of axial canals during the processes of new branch forming and truncated branch rebuilding. We found that the axial canal of a new branch is transformed from a calice and the polyps in the new branch are budded from the polyp in the axial canal. Meanwhile, the axial canal can transport the calcareous skeletons to rebuild the tip of a truncated branch, which represents as the change in the diameter of axial canal and calcareous deposition/reduction in it. This work indicate the regulation of axial canal in the growth processes including budding, branching, and mineralising of an Acropora colony.

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 165 peers in over 30 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability - which is also indicated by an increasing adaptation of the pharmaceutical industry but a lack of complexity can challenge their use as a predictive platform. Self-made systems on the other hand are less robust and standardized but provide the opportunity to develop customized and more complex models which are often needed for human disease modeling. This review serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs.

Parts of shotgun cartridges are a significant source of plastic litter in the marine environment. Empty cartridge shells may not be picked up by the hunter who fired them, and plastic wads that serve to separate the propellant from the shot load, are lost down-range when a shot is fired. Such litter items constitute a cosmetic and aesthetic problem on coastlines and may cause harm to marine animals and in the later stages of decomposition break down into harmful micro plastic particles. There exists no reliable estimate of the global exposure of marine ecosystems to this plastic source. However, in some countries it has been subject to closer examination, including for example, Denmark where the annual contribution of plastic wads into marine systems was estimated to 600,000 pieces (c2 tonnes), and the accumulated density of washed-up items (both wads and shells) was 3.7 items per 100 m coastline. Increasing awareness of this problem has caused scientists, hunters’ communities and governments to suggest altered practice including transition to the use of biodegradable cartridge components, first and foremost wads as this item is invariable lost during hunting. Several manufacturers provide shotgun cartridges containing biodegradable wads based on different types of materials, including fibers and various types of plastics, for example PVAL (poly(vinyl alcohol)) and PHA (polyhydroxyalkanoate). In this paper, we review the most recent literature on the amounts and related environmental hazards of plastic dispersed from hunting ammunition into marine ecosystems. We summarize the market availability of shotgun cartridges with biodegradable wads and discuss chemical, technical, economical and legal aspects of a transition to the use of such products.

This paper proposes a novel micro-grid structure, which can operate fully-autonomously with inherent seamless switching. It can operate independently in both grid-connected and islanded mode as a self-governed entity without relying on the utility grid. An AC/DC/AC converter is employed as the interface between the micro-grid and the utility grid, which enables the two entities to have different voltages in grid-connected mode. Seamless switching between operation modes can be achieved naturally. The micro-grid is regulated to exchange predefined amount of power with the utility grid in grid-connected mode. This will benefit the power dispatching algorithm of the power system. The predefined power is estimated based on power forecasting of local renewable generations and loads with consideration of the Sate of Charge (SOC) of the battery, and is updated and broadcasted every certain period. A small scale AC micro-grid with a rotating generator, battery storage and solar arrays etc. is built for investigation. Matlab/Simulink results are provided to validate the robustness and flexibility of proposed micro-grid and its operation strategy.

Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in the toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (Expectation-Maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. We observed that Word’s HC method with each of Euclidean, Manhattan and Minkowski distance measures produces better clustering/co-clustering results. For an example, in case of glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the PPAR signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. These results are validated by the available literature and functional annotation.

Minerals play many important functions in plant and animal metabolism. Therefore, we investigated the concentration of Se and other minerals and their relationships in soils and fodder plants in Kosovo. Seventy-three samples of each soil and fodder plants (grass, maize, and wheat) from 30 farms were collected. Both soil and plant samples, after processing and digestion, were analyzed for mineral concentration by ICP-MS. Mineral concentrations in soil and fodder crops, and the best predicting/explanatory models for micro minerals concentration, achieved by stepwise linear regression, are presented. Results showed very low concentration of Se in most of the soil and all fodder samples. In addition, the concentration of Co, Zn and Fe was not sufficient to satisfy requirements for all categories of farm animals. Plant Se concentration showed a positive relationship with Se concentration in soils. Plant Zn, Mo, Mn, Fe and Pb, in general, showed no significant relationship with their concentration in soil, while plant Co and Cd showed positive relationship only in maize, and Cu in wheat grain. Among the soil properties, pH had the highest effect on the concentrations of Co, Mo, Mn, Cd and Pb in fodder crops.

Artificial intelligence, a key technological tool in the era of the 4th Industrial Revolution, is being actively applied to education beyond industry, economy, and culture. In the future society, understanding and using artificial intelligence technology will be considered an essential skill for everyone, and the professionalism of AI education for pre-service teachers nurturing future talents is also important. This study verifies the effectiveness of pre-service teachers after undergoing a 15-week extension program consisting of AI Literacy Education (10 weeks), AI-Linked Subjet Education (3 weeks), and Micro-teaching (2 weeks) which was designed to enhance the AI ​​education professionalism of pre-service teachers. The AI Literacy Education section consisted of understanding AI, AI ethics, and basic programming, and the education was conducted through both experience and practice. After that, the pre-service teachers analyzed the curriculum of the 5th and 6th grades of an elementary school, and developed a subject-related education program using AI tools in three stages. Using the developed program, micro-teaching classes were conducted twice. The study results are as follows. First, there was a change in the positive perception of AI (p<.05). Second, the understanding of AI educational technology tools was improved and the recognition of the usefulness of developing a curriculum-related program was expanded. Third, the importance of teacher competency development was learned through the micro-teaching, and the students' understanding of the learning process was expanded.

Layered two-dimensional (2D) graphene oxide (GO) films are integrated with micro-ring resonators (MRRs) to experimentally demonstrate enhanced nonlinear optics in the form of four-wave mixing (FWM). Both uniformly coated and patterned GO films are integrated on CMOS-compatible doped silica MRRs using a large-area, transfer-free, layer-by-layer GO coating method together with photolithography and lift-off processes, yielding precise control of the film thickness, placement, and coating length. The high Kerr nonlinearity and low loss of the GO films combined with the strong light-matter interaction within the MRRs results in a significant improvement in the FWM efficiency in the hybrid MRRs. Detailed FWM measurements are performed at different pump powers and resonant wavelengths for the uniformly coated MRRs with 1−5 layers of GO as well as the patterned devices with 10−50 layers of GO. The experimental results show good agreement with theory, achieving up to ~7.6-dB enhancement in the FWM conversion efficiency (CE) for an MRR uniformly coated with 1 layer of GO and ~10.3-dB for a patterned device with 50 layers of GO. By fitting the measured CE as a function of pump power for devices with different numbers of GO layers, we also extract the dependence of GO’s third-order nonlinearity on layer number and pump power, revealing interesting physical insights about the evolution of the layered GO films from 2D monolayers to quasi bulk-like behavior. These results confirm the high nonlinear optical performance of integrated photonic resonators incorporated with 2D layered GO films.

Molecular studies regarding regulatory elements such as small ncRNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humanity, and it is still a challenge to prevent and treat it. The control of the infection as well as its diagnosis are still complex, and treatments used are linked to several side effects. This study aimed to investigate miRNA’s expression profile to identify possible biomarkers for tuberculosis. We applied NGS techniques to investigate miRNA’s global expression profile from blood samples of infected patients with tuberculosis, their respective healthy physicians, and external healthy individuals as controls. Samples from 22 individuals run through a differential expression, target genes, gene set enrichment, and miRNA-gene network analysis. We observed 153 altered miRNAs, among which, only three DEmiRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p) were found between the investigated patients and their respective physicians. These DEmiRNAs are suggested to play an important role in granuloma regulation and their immune physiopathology. Our results propose that miRNAs may be involved in immune modulation, regulating the repertoire of genes expressed in the immune system’s cells. Our findings encourage the application of miRNAs as potential biomarkers for tuberculosis.

Direct laser writing based on non-linear 3D nanolithography (also known as 3D laser lithography, 3DLL) is a powerful technology to manufacture polymeric micro-optical components. However, practical applications of these elements are limited due to the lack of knowledge of their optical resilience and durability. In this work, we employ 3DLL for the fabrication of bulk (i.e. fully filled) and woodpile structures out of different photopolymers. We then characterize them using S-on-1 laser induced damage threshold (LIDT) measurements. In this way, quantitative data of LIDT values can be collected. Furthermore, this method permits to gather damage morphologies. The results presented in this work demonstrate that LIDT values depend on the material and the geometry of the structure. Bulk non-photosensitized hybrid organic-inorganic photopolymer SZ2080 structures are found to be the most resilient with a damage threshold being of 169±15 mJ/cm².

Substantial research is required to ensure that micro-mobility ride sharing provides a better fulfillment of user needs. This study proposes a novel crowdsourcing model for the ride-sharing system where light vehicles such as scooters and bikes are crowdsourced. The proposed model consists of three entities: suppliers, customers, and a management party responsible for receiving, renting, booking, and demand matching with offered resources. It can allow suppliers to define the location of their private e-scooters/e-bikes and the period of time they are available for rent. Using a dataset of over 9 million e-scooter trips in Austin, Texas, we ran an agent-based simulation six times using three maximum battery ranges (i.e., 35, 45, and 60 km) and different numbers of e-scooters (e.g., 50 and 100) at each origin. Computational results show that the proposed model is promising and might be advantageous to shift the charging and maintenance efforts to a crowd of suppliers.

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal-end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices remains a critical challenge, particularly in a way suitable for large scale adoption. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3 ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Cas endonuclease-mediated genome editing provides a long-awaited molecular biological approach to the modification of predefined genomic target sequences in living organisms. Although cas9/guide (g)RNA constructs are straightforward to assemble and can be customized to target virtually any site in the plant genome, the implementation of this technology can be cumbersome, especially in species like Triticale that are difficult to transform, for which only limited genome information is available and/or which carry comparatively large genomes. To cope with these challenges, we have pre-validated cas9/gRNA constructs (1) by frameshift restitution of a reporter gene co-introduced by ballistic DNA transfer to barley epidermis cells, and (2) via transfection in Triticale protoplasts followed by either a T7E1-based cleavage assay or by deep-sequencing of target-specific PCR amplicons. For exemplification, we addressed the Triticale ABA 8’-hydroxylase 1 gene, one of the putative determinants of pre-harvest sprouting of grains. We further show that in-del induction frequency in Triticale can be increased by TREX2 nuclease activity, which holds true for both well- and poorly performing gRNAs. The presented results constitute a sound basis for the targeted induction of heritable modifications in Triticale genes.

Microgrids can be used for securing power supply during network outages. Underground cabling of distribution networks is another effective, but conventional and expensive alternative to enhance reliability of power supply. This paper presents firstly an analysis method for the determination of microgrid power supply adequacy during islanded operation, and secondly, a comparison method for overall cost calculation of microgrids vs. underground cabling. The microgrid power adequacy during a rather long network outage is required in order to indicate high level of reliability of supply. The overall cost calculations consider the economic benefits and costs incurred combined for both the distribution network company and the consumer. Whereas the microgrid setup determines the islanded operation power adequacy and thus the reliability of supply, the economic feasibility results from the normal operations and services. The methods are illustrated by two typical, and even critical, case studies in rural distribution networks: an electric-heated detached house and a dairy farm. These case studies show that even in case of a single consumer, a microgrid option could be more economical than network renovation by underground cabling of a branch in order to increase reliability.

Poliovirus 2A protease (PV2Apro) plays a vital role in viral replication and down-regulation of host cell protein synthesis. In order to understand more concerning PV2Apro, the protein was over-expressed in bacteria following amplification using sense and antisense primers and cloning in pET15b. Several expression hosts were tested and BL21 (DE3) pLysS cells gave the best expression of PV2Apro with minimal unwanted protein expression following IPTG induction. The 2Apro protein was purified to homogeneity using column chromatography, its solubility determined and its molecular weight and composition determined by MALDI-TOF mass spectrometry. The protease was found in the insoluble fraction and the purified protein had a slightly lower molecular weight than predicted. Moreover, three dimensional structure was modelled using template 1z8r with 58% identity and validated using ramachandran plot. Results revealed that most of the residues lie in favoured and allowed regions. These findings could help in a better understanding of PV2Apro structure and inhibition thus, highlighting potential targets for antiviral drug development.

Inorganic polyphosphate (polyP) is an important factor of stress tolerance in microbial cells. In yeast, the major enzyme of polyP biosynthesis is Vtc4, a subunit of the vacuole transporter chaperone (VTC) complex. In this study, we demonstrated that Vtc4 knockout in Saccharomyces cerevisiae not only decreased polyP content but also caused shifts in the composition of the intracellular polyP pool and changed the stress tolerance profile. In the mutant S. cerevisiae, the level of short-chain acid-soluble polyPs was decreased nearly 10-fold, whereas that of longer acid-insoluble polyPs was decreased only 2-fold, suggesting the existence of other enzymes compensating the production of long-chain polyPs. The Δvtc4 mutant showed inhibition of Mg2+-dependent phosphate uptake and decreased resistance to alkaline stress but increased tolerance to oxidation and heavy metal ions, especially Mn2+. Quantitative PCR revealed the upregulation of the DDR2 gene implicated in multiple stress responses and downregulation of PHO84 encoding a phosphate and Mn2+ transporter, which could account for the effects on phosphate uptake and Mn2+-related stress response in the Δvtc4 mutant. Our study indicates that short-chain polyPs, plays an important role in the regulation of stress response in yeast.

In this paper, we critically examine the burgeoning role of advanced computational methodologies in deciphering the complex tapestry of farm animal behaviors and emotions. Leveraging digital imaging and artificial intelligence, we unearth nuanced behavioral patterns and micro-expressions, offering predictive insights into animal emotional states. Sound vocalization analysis, often overlooked, emerges as a pivotal tool, decoding intricate communicative nuances and emotional undertones. Cognitive tests, including mirror and bias assessments, challenge long-standing perceptions, revealing surprising depths of animal self-awareness and cognitive sophistication. However, the paper also underscores the imperative of integrating these tools with a profound understanding of animal psyche, ensuring technology serves as an enhancer, not a replacement, of traditional observational methods. This research not only highlights the transformative potential of cognitive computing in animal welfare but also calls for a judicious application, ensuring technology augments, not undermines, the intrinsic value of human-animal interactions and understanding.

Molecular mechanisms associated with the pathogenesis of Vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle and pigs. To gain more insight on the molecular mechanisms used by VSV to impair the immune response in macrophages, we used microarrays to determine the transcriptomic changes produced by VSV infection in primary cultures of porcine macrophages. The results indicated that VSV infection induced the massive expression of multiple anorexic, pyrogenic, proinflammatory and immunosuppressive genes. Overall, the interferon (IFN) response appeared suppressed, leading to the absence of stimulation of interferon-stimulated genes (ISG). Interestingly, VSV infection promoted the expression of several genes known to downregulate the expression of IFNb. This represents an alternate mechanism for VSV control of the IFN response, beyond the recognized mechanisms mediated by the matrix protein. Although there was no significant differential gene expression in macrophages infected with a highly virulent epidemic strain compared to a less virulent endemic strain, the endemic strain consistently induced higher expression of all upregulated cytokines and chemokines. Collectively, this study provides novel insights into VSV molecular pathogenesis and immune evasion that warrants further investigation

Formalism proofing general derivation, applying matrix properties operations, showing fundamental relationships with inner product to outer product has been advanced here. This general proof formalism has direct application with physics to quantify quantum density at micro scale level to time commutator at macro scale level. System of operator algebraic equations have been rigorously derived to obtain analytic solutions which are physically acceptable. Extended physics application will include metricizing towards unitarization to achieve gaging Hamiltonian mechanics to electromagnetic gravitational strong theory, towards grand unifying physics atomistic to astrophysics or vice versa via quantum relativistic general physics thereby patching to classical physics fields energy.

Abstract: Microstructural and mechanical properties of the eutectic Sn58Bi and micro-alloyed Sn57.6Bi0.4Ag solder alloys were compared. With the addition of Ag micro-alloy, the tensile strength was improved and this is attributed to a combination of microstructure refinement and an Ag3Sn precipitation hardening mechanism. However, ductility is slightly deteriorated due to the brittle nature of the Ag3Sn intermetallic compounds (IMCs). Additionally, a board level reliability study of Ag micro-alloyed Sn58Bi solder joints produced utilising a surface-mount technology (SMT) process, were assessed under accelerated temperature cycling (ATC) conditions. Results reveal that micro-alloyed Sn57.6Bi0.4Ag has a higher characteristic lifetime with a narrower failure distribution. This enhanced reliability corresponds with improved bulk mechanical properties. It is postulated that Ag3Sn IMCs are located at the Sn-Bi phase boundaries and suppress the solder microstructure from coarsening during the temperature cycling, hereby extending the time to failure.

Manipulation of micro- and nano-sized objects with optical tweezers is a well established, albeit still evolving technique. While many objects can be trapped directly with focused laser beam(s), for some applications indirect manipulation with tweezers-operated tools is preferred. We introduce a simple, versatile micro-tool operated with holographic optical tweezers. The 40 µm long dumbbell-shaped tool, fabricated with two-photon laser 3D photolithography has two beads for efficient optical trapping and a probing spike on one end. We demonstrate fluids viscosity measurements and vibration detection as examples of possible applications.

Micro channel tube (MCT) is widely employed in industry due to its excellent efficiency in heat transfer. An MCT is commonly produced through extrusion within a porthole die, where severe plastic deformation is inevitably involved. Moreover, the plastic deformation, which dramatically affects the final property of the MCT, varies significantly from location to location. In order to understand the development of the microstructure and its effect on the final property of the MCT, the viscoplastic self-consistent (VPSC) model, together with the finite element analysis and the flow line model, is employed in the current study. The flow line model is used to reproduce the local velocity gradient within the complex porthole die, while VPSC model is employed to predict the evolution of the microstructure accordingly. In addition, electron backscatter diffraction (EBSD) measurement and mechanical tests are used to characterize the evolution of the microstructure and the property of the MCT. The simulation results agree well with the corresponding experimental ones. The influence of the material’s flow line on the evolution of the orientation and morphology of the grains, and the property of the produced MCT are discussed in detail.

Background: The demand in the development of cancer nanomedicine has increased due to various limitations in conventional cancer therapy. This study assessed the mRNA transcriptomic profiling of human HepG2 cells exposed to C. roseus-AgNPs. Methods: The proliferative activity of hepatocellular carcinoma (HepG2) and normal human liver (THLE3) cells treated with C. roseus‑AgNPs were measured using MTT assay. The RNA samples were extracted and sequenced using BGIseq500 platform. This is followed by data filtering, mapping, gene expression analysis, DEG analysis, GO analysis, and pathway analysis. Results: The mean IC₅₀ values of C. roseus‑AgNPs on HepG2 was 4.38±1.59 µg/mL while on THLE3 cells was 800±1.55 µg/mL. Transciptomic profiling revealed an alteration of 296 genes. C. roseus‑AgNPs induced the expression of stress-associated genes such as MT, HSP and HMOX-1. Cellular signaling pathways were potentially activated through MAPK, TNF and TGF pathways that responsible for apoptosis and cell cycle arrest. The alteration of ARF6, EHD2, FGFR3, RhoA, EEA1, VPS28, VPS25, TSG101 indicated the uptake of C. roseus-AgNPs via both clathrin-dependent and clathrin-independent endocytosis. Conclusions: This study provides the new insights on gene expression study of biosynthesized AgNPs on cancer cells. The cytotoxicity effect is mediated by the aberrant gene alteration, and more interestingly the unique selective antiproliferative properties indicates the C. roseus‑AgNPs as an ideal anticancer candidate.

This study deals with vibrational and crystallographic aspects of the thermally induced transformation of serpentine-like garnierite into quartz, forsterite, and enstatite occurring at about 620 °C. Powder specimens of garnierite have been annealed in static air between room temperature and 1000 °C. The resulting products from the transformations detected based on thermogravimetric and differential thermal analysis, have been extensively characterized via microRaman spectroscopy, and X-ray diffraction. Our study shows that serpentine-like garnierite consists of a mixture of different mineral species. Furthermore, these garnierites and their composition can provide details based on the mineralogy and the crystalline phases resulting from the thermal treatment.

Titanium micro-scale topography results in excellent osteoconductivity and bone-implant integration. However, the biological effects of sub-micron topography are unknown. We compared osteoblastic phenotypes and in vivo bone and implant integration abilities between titanium surfaces with micro- (1–5 µm) and sub-micro-scale (0.1–0.5 µm) topographies and machined titanium. Average roughness was 12.5 ± 0.65 nm, 123 ± 6.15 nm, and 24 ± 1.2 nm for machined, micro-rough, and sub-micro-rough surfaces, respectively. The micro-rough surface showed the fewest cells attaching during the initial stage and the lowest proliferation. Calcium deposition and expression of osteoblastic genes were highest on the sub-micro-rough surface and lowest on the machined surface. Bone-to-implant integration was strongest for the micro-rough surface, consistent with it having the greatest ability to retain cells in vitro. Thus, the biological effects of titanium surfaces are not necessarily proportional to the degree of roughness in osteoblastic cultures or in vivo. Sub-micro-rough titanium ameliorates the disadvantage of micro-rough titanium by restoring cell attachment and proliferation and enhances the rate of osteoblastic differentiation over that of micro-rough titanium; however, bone integration and the ability to retain cells are compromised due to its lower interfacial mechanical locking compared to that of micro-rough titanium.

ST-elevation myocardial infarction (STEMI) remains one of the leading causes of morbidity and mortality worldwide. The identification of novel metabolic and imaging biomarkers could unveil key pathophysiological mechanisms at the molecular level and promote personalized care in patients with acute coronary syndromes. We studied 38 patients with STEMI who underwent primary percutaneous coronary intervention and thrombus aspiration. We sought to correlate serum ceramide levels with micro-CT quantified aspirated thrombus volume and relevant angiographic outcomes, including modified TIMI thrombus grade and pre- or post-procedural TIMI flow. Higher ceramide C16:0 levels were significantly, but weakly correlated with larger aspirated thrombus volume (Spearman r=0.326, p=0.046), larger intracoronary thrombus burden (Nagelkerke R2=0.236, p=0.030) and worse pre- and post-procedural TIMI flow (Nagelkerke R2=0.210; p=0.049 and Nagelkerke R2=0.277; p=0.039, respectively). Ceramides C24:0 and C24:1 were also significantly associated with larger intracoronary thrombus burden (Nagelkerke R2=0.311; p=0.008 and Nagelkerke R2=0.423; p=0.001, respectively). In conclusion, serum ceramide levels (mainly C16:0 and C24:1) were higher among patients with larger intracoronary and aspirated thrombus burden. This suggests that quantification of serum ceramides might improve risk-stratification of patients with STEMI and facilitate a more individualized approach in everyday clinical practice.

The size of TiO2 (either nanometric or micrometric) can significantly affect both its photocatalytic and photoelectrochemical properties, thus altering the photooxidation of organic pollutants in air or water. The purpose of this work is to give an account of the photoelectrochemical and photocatalytic features of some nano- and micro-sized TiO2 commercial powders towards a model reaction, the photooxidation of acetone. Cyclic voltammograms (CV) of TiO2 particulated electrodes under UV illumination experiments were carried out in either saturated O2 or N2 solutions for a direct correlation with the photocatalytic process. In addition, the effect of different reaction conditions on the photocatalytic efficiency under UV light in both aqueous and gaseous phases was also investigated. CV curves with the addition of acetone under UV light showed a negative shift of the photocurrent onset, confirming the efficient transfer of photoproduced reactive oxygen species (ROSs), e.g., hydroxyl radicals, or holes to acetone molecules. The photocatalytic experiments showed that the two nano-sized samples exhibit the best photocatalytic performance. The different photoactivity of the micro-sized samples is probably attributed to their morphological differences, affecting both the amount and distribution of free ROSs involved in the photooxidation reaction.

Nonwoven fabrics have been widely used in textile manufacturing industry as a sheet or web structure because of soft, water-repellent, recycle, ecological and resilient functions. Ultrasonic welding method has been applied for bonding nonwoven fabrics due to clean, fast and reliable approach. In this work, the ultrasonic stepped horn is designed to generate uniform amplitudes on the working surface by using finite element analysis (FEA) simulation. Chromium carbon steels are utilized to produce ultrasonic horns due to high wear resistant and hardness. Isotactic polypropylene nonwoven fabrics fabricated by spunbond process were bonded by continuous ultrasonic sewing machine. Ultrasonic horn with 70 mm in diameter working at 20 kHz, polypropylene (PP) nonwoven density of 80 gsm and various design of welding joints were applied. A typical image in the case of number one was investigated by the scanning electron microscope (SEM) images of inter-facial micro-structure. However, welding joints of totally eight roller patterns was test the tensile strength of the ultrasonic welding joints on PP nonwoven fabrics. The tensile strength of the welding joints is proportional to the area ratio between the welding area and cycling area. The results showed that the melted zone without welding defects such as crack or blowhole can be seen. Furthermore, the tensile strength of welding joints in eight cases of roller patterns (No.1-No.8) was described in details. The ultrasonic welding joints with brick structures give higher tensile strength while the solid line in the pattern gave less strength.

Cancer cells are adept at reprogramming energy metabolism and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism and ROS detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

Gene expression data is key for the functional annotation of single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS). Expression and splicing quantitative trait loci (e/sQTLs) in normal colon tissue, such as those from the University of Barcelona and University of Virginia RNA sequencing project (BarcUVa-Seq) and the Genotype-Tissue Expression project (GTEx), are required to gain biological insight of colon-related diseases risk loci. Moreover, transcriptome-wide association studies (TWAS) rely on reference gene expression imputation panels in the tissue of interest to nominate susceptibility genes. Also, it is of high interest to study the relationships between genes in a network framework. For facilitating these analyses, we have updated and expanded the scope of the Colon Transcriptome Explorer (CoTrEx) to the version 2.0. This web-based resource provides exhaustive visualization and analysis of transcriptome-wide gene expression profiles of normal colon tissue from BarcUVa-Seq and GTEx. In addition to the integration of new datasets, CoTrEx 2.0 provides additional e/sQTLs sets, as well as gene expression prediction models and regulatory and co-expression networks. It is freely available at https://barcuvaseq.org/cotrex/. Overall, it is of high interest for researchers aiming to investigate the genetic susceptibility to colon-related complex traits and diseases.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Metazoans have an elaborate and functionally segmented body. It evolves from a single cell by systematic divisions. Metazoans attain structural complexity with exquisite precision, which is a molecular mystery. The indispensable role of centrioles in cell division and ciliogenesis can shed insight into this riddle. Cell division helps in growth of the body and is a highly regulated and integrated process. Its errors cause malignancies. The cell mass is organized during organogenesis. Prior to it, the centrioles are retrieved from the cell cycle to initiate ciliogenesis. The cilia-modulated developmental signaling pathways elaborate the body plan. The secluded compartment of the cilium reduces noise during signaling and is essential for a precise body plan development. The dysfunctional centrioles and cilia can distort body plan. Thus, centriole has a dual role in growth and cellular organization. This concept review analyses the comprehensive interactome and the key domain features (like C2 domain) of molecules which connect and disarm the centriole from the cell cycle and ciliogenesis by switching on or off the essential regulators of the pathways. The concentration of these signaling pathways at the centriole reinforces the hypothesis that centriole is the molecular workstation to carve out structural design and complexity in metazoans.

Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse Foot and Mouth Disease (FMD) Virus (FMDV) strains. Among seven distinct serotypes, only serotype O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse subtypes of FMDV serotype O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for FMDV serotypes O and A circulating in Bangladesh and surrounding territories.

Aedes aegypti (L.) is the primary vector of chikungunya, dengue, yellow fever and Zika viruses. The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in invertebrates and vertebrates, as well as plants. We focused on the AaeLRIM1 and AaeAPL1 gene expressions in response to Zika virus (ZIKV) and Chikungunya virus (CHIKV) infection using a time course study, as well as the developmental expressions in the eggs, larvae, pupae, and adults. RNA-seq analysis data provided 60 leucine-rich repeat related transcriptions in Ae. aegypti in response to Zika virus (Accession number: GSE118858, https://www.ncbi.nlm.nih.gov/gds/?term=GSE118858). RNA-seq analysis data showed that AaeLRIM1 (AAEL012086-RA) and AaeAPL1 (AAEL009520-RA) were significantly upregulated 2.5 and 3-fold during infection by ZIKV 7-days post infection (dpi) of an Ae. aegypti Key West strain compared to an Orlando strain. The qPCR data showed that LRR-containing proteins AaeLRIM1, AaeAPL1 and five paralogues were expressed 100-fold lower than other nuclear genes, such as defensin, during all developmental stages examined. Together, these data provide insights into transcription profiles of LRR proteins of Ae. aegypti during its development and in response to infection with emergent arboviruses.

MicroRNA (miRNA) is a typical class of small RNAs that could modulate gene expression in trans at the post-transcriptional level. miRNAs bind to the miRNA binding sites (MBSs) in target mRNAs by sequence complementarity. Alternative splicing (AS) is another commonly occurred process in pre-mRNAs that changes the isoforms of a gene. It is hypothesized that there should be an interaction for gene regulation that involves both AS and miRNA targeting. Studies have verified this hypothesis in the model organism Arabidopsis thaliana. High-throughput sequencing data suggested that in Arabidopsis a considerably large fraction of MBSs are affected by AS events. The overlapping between MBS and AS exceeds the randomly simulated number. Functional experiments have indicated that the AS events are required for the gene expression changes of miRNA targets. Therefore, AS and MBS are mutually favored. The observed expression changes caused by miRNAs could also be contributed by AS events. In the present perspective article, we propose that the AS analysis should be incorporated in the differential-expression analysis of miRNA studies. When defining a differentially-expressed gene, it should be clarified whether the change in gene expression is caused by AS events or solely by miRNA targeting.

Prostate cancer is a leading cause of death among men but its genomic characterization and best therapeutic strategy are still under debate. The Genomic Fabric Paradigm (GFP) considers the transcriptome as a multi-dimensional mathematical object subjected to a dynamic set of expression correlations among the genes. Here, GFP is applied to gene expression profiles of three (one primary, and two secondary) cancer nodules and the surrounding normal tissue from a surgically removed prostate tumor. GFP was used to determine the regulation and rewiring of the P53 signaling, apoptosis, prostate cancer and several other pathways involved in survival and proliferation of the cancer cells. Genes responsible for the block of differentiation, evading apoptosis, immortality, insensitivity to anti-growth signals, proliferation, resistance to chemotherapy and sustained angiogenesis were found as differently regulated in the three cancer nodules with respect to the normal tissue. The analysis indicates that even histo-pathologically equally graded cancer nodules from the same tumor have substantially different transcriptomic organizations, raising legitimate questions about the validity of meta-analyses comparing large populations of healthy and cancer humans. The study suggests that GFP may provide a personalized alternative to the biomarkers’ approach of cancer genomics.

Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The present study examines the expression of previously-described genes that may influence resistance to bortezomib treatment at the mRNA level (ABCB1, CXCR4, MAF, MARCKS, POMP, PSMB5, RPL5, TXN and XBP1). mRNA expression was determined in 73 MM patients treated with bortezomib-based regimens (30 bortzomib-sensitive and 43 bortezomib-refractory patients) and 11 healthy controls. RPL5 was significantly down-regulated in multiple myeloma patients as compared with healthy controls. Moreover, POMP was significantly up-regulated in MM patients refractory to bortezomib-based treatment. In multivariate analysis, high expression of PSMB5 and CXCR and autologous stem cell transplantation were independent predictors of progression-free survival, and high expression of POMP and RPL5 was associated with shorter overall survival.

Leishmania species are parasitic protozoans which cause leishmaniasis affecting millions of people worldwide. Sterols are important components of plasma and organellar membranes and serve as precursors for the synthesis of signaling molecules. In contrast to animals, Leishmania do not produce cholesterol but instead synthesize ergostane-based sterols. C14-demethylase is a key enzyme involved in the biosynthesis of sterols in Leishmania parasites and an important drug target. Its inactivation leads to multiple defects including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis plays an unexpected role in global gene regulation in Leishmania parasites.

Genes that affect adaptive traits have been identified, but our knowledge of the genetic basis of adaptation in a more general sense (across multiple traits) remains limited. We combined population-genomic analyses of evolve and resequence experiments, genome-wide association mapping of performance traits, and analyses of gene expression to fill this knowledge gap, and shed light on the genomics of adaptation to a marginal host (lentil) by the seed beetle Callosobruchus maculatus. Using population-genomic approaches, we detected modest parallelism in allele frequency change across replicate lines during adaptation to lentil. Mapping populations derived from each lentil-adapted line revealed a polygenic basis for two host-specific performance traits (weight and development time), which had low to modest heritabilities. We found less evidence of parallelism in genotype-phenotype associations across these lines than in allele frequency changes during the experiments. Differential gene expression caused by differences in recent evolutionary history exceeded that caused by immediate rearing host. Together, the three genomic data sets suggest that genes affecting traits other than weight and development time are likely to be the main causes of parallel evolution, and that detoxification genes (especially cytochrome P450s and beta-glucosidase) could be especially important for colonization of lentil by C. maculatus.

Deep learning is based on matrix computing with a large amount of hidden parameters that is not visible outside the computing module. Deep learning is a non-linear system and a linear approach is not possible. It is natural for people to visualize the algorithm and to follow some hidden parameters. In this paper, we propose a simple graphical programming of a nonlinear system based on drawing the simplest unit, such as a single neuron model. A more complex scheme of a classical neural network is obtained by commands copy-move-place of one neuron. The number of neurons and layers can be chosen arbitrarily. Once the scheme is complete, the implementation code is evaluated with symbolic parameters and nonlinear activation functions. This cannot be done manually. With the symbolic expression of outputs in terms of inputs and symbolic parameters, including symbolic activation pure functions, some other properties can be derived in closed form. This unique original approach can help scientists and developers and design numerical algorithms for machine learning and to understand how deep learning algorithms work.

This research paper is part of the wider project concerning the very first detailed mapping of the overall Taiwanese hydro-power plants that took place from 2013 up to 2015 and it is currently in evaluation and finalization stage. The case of Shanping hydro-power plant has been carefully studied, photographed, documented and mapped in situ. It was one of the isolated hydro-power plant projects originally built to supply the remote area with the specific designation. Shanping hydro-power plant, as well as the other units from the early hydro-power generation era in Taiwan, are considered to be the technological heritage of civil and mechanical engineering that reflects later in all the further projects up to nowadays modern Taiwanese hydro-power plants. Unfortunately, most of the hydro-power houses from the older periods were severely damaged or destroyed by natural causes which were also the case of Shanping unit. The research is trying to reconstruct the original location of the powerhouse and its supporting structures based on available historical documents, previous studies, comparative methodology, and the current on-site observation.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and similarly to the other cetaceans represent the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary and expression study of Tursiops truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3’ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged TRA and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the CDR-IMGT of the dolphin variable V alpha and beta domains were identified. According to comparative modelisation, the atome pair contact sites analysis between the human MH1 grove (G) domains and the TR V domains confirms conservation of the structure of the dolphin TR/pMH.

The cellular cytoskeleton provides the cell with a mechanical rigidity which allows mechanical interaction between cells and the extracellular environment. The actin structure plays a key role in mechanical events like motility, or establishment of cell polarity. From the earliest stages of development, as represented by ex vivo expansion of naïve embryonic stem cells (ESCs), the critical mechanical role of the actin structure is becoming recognized as a vital cue for correct segregation and lineage control of cells and as a regulatory structure that controls several transcription factors. Naïve ESCs have a characteristic morphology and the ultrastructure that underlies this condition remains to be further investigated. Here, we investigate the 3D actin cytoskeleton of naïve mouse ESCs using super resolution optical reconstruction microscopy (STORM). We investigate the morphological, cytoskeletal and mechanical changes in cells cultured in 2i or Serum/LIF media reflecting a homogenous preimplantation cell state and a state that is closer to embarking on differentiation. STORM imaging showed that the peripheral actin structure undergoes a dramatic change between the two media conditions. We also detected micro-rheological differences in the cell periphery between the cells cultured in these two media correlating well with the observed nano-architecture of the ESCs in the two different culture conditions. These results pave the way for linking physical properties and cytoskeletal architecture to cell morphology during early development.

Whole-genome DNA sequencing of Lactobacillus D75 and D76 strains (Vitaflor, Russia) was performed using the PacBio RS II platform, followed by de novo assembly with SMRT Portal 2.3.0. The average nucleotide identity (ANI) test showed that both strains belong to the Lactobacillus helveticus, but not the L. acidophilus as previously assumed. 31 exopolysaccharide (EPS) production genes (nine of which form a single genetic cluster), 13 adhesion genes, 38 milk protein and 11 milk sugar utilization genes, 13 genes for and against specific antagonistic activity, aight antibiotic resistance genes, and also three CRISPR blocks and eight Cas I-B system genes were identified in the genomes of the both strains. The expression of some genes was confirmed. In fact, the presence of identified genes suggests that L. helveticus D75 and D76 are able to form biofilms on the outer mucin layer, inhibit the growth of pathogens and pathobionts, utilize milk substrates with the formation of digestible milk sugars and bioactive peptides, resist bacteriophages and show some genome-determined resistance to antibiotics, stimulate the host’s immune system. Pathogenicity genes have not been identified. The study results confirm the safety and high probiotic potential of the strains.

Promoter choice is an essential consideration for transgene expression in gene therapy. The expression of multiple genes requires ribosomal entry or skip sites, or the use of multiple promoters. Promoters systems comprised of two separate, divergent promoters may significantly increase the size of genetic cassettes intended for use in gene therapy. However, an alternative approach is to use a single, compact bidirectional promoter. We identified strong and stable bidirectional activity of the RPBSA synthetic promoter comprised of a fragment of the human Rpl13a promoter, together with additional intron / exon structures. The Rpl13a-based promoter drove long-term bidirectional activity of fluorescent proteins. Similar results were obtained for the EF1-α and LMP2/TAP1 promoters. However, in a lentiviral vector, the divergent bidirectional systems failed to produce sufficient titres to translate into an expression system for dual chimeric antigen receptors (CAR) expression. Although bidirectional promoters show excellent applicability to drive short RNA in Sleeping Beauty transposon systems, their possible use in the lentiviral applications requiring longer and more complex RNA, such as dual CAR cassettes, is limited.

A technique for fabrication of bacterial cellulose-based films with CeO₂ nanofiller has been developed. The structural and morphological characteristics of the materials have been studied, their thermal and mechanical properties in dry and swollen states having been determined. The preparation methodology makes it possible to obtain composites with a uniform distribution of nanoparticles. The catalytic effect of ceria regarding the thermal oxidative destruction of cellulose has been confirmed by TGA and DTA methods. An increase in CeO₂ content led to an increase in the elastic modulus (a 1.27-fold increase caused by the introduction of 5 wt.% of the nanofiller into the polymer) and strength of the films. This effect is explained by the formation of additional links between polymer macro-chains via the nanoparticles’ surface. The materials fabricated were characterised by a limited ability to swell in water. Swelling caused a 20- to 30-fold reduction in the stiffness of the material, the mechanical properties of the films in a swollen state remaining germane to their practical use. The application of the composite films in cell engineering as substrates for the stem cells’ proliferation has been studied. The increase in CeO₂ content in the films enhanced the proliferative activity of embryonic mouse stem cells. The cells cultured on the scaffold containing 5 wt.% of ceria demonstrated increased cell survival and migration activity. An analysis of gene expression confirmed improved cultivation conditions on CeO₂-containing scaffolds.

Few-layer graphene oxide (GO) has shown none or very weak cytotoxicity and anti-proliferative effects in a wide range of cell lines such as glyoma cells and human skin HaCaT cells, in concentrations up to 100 µg/mL However, multi-layer GO has been hardly explored in the biomedical field. Thus, multi-layer GO was examined here in human keratinocyte HaCaT cells treated with different concentrations ranging from 0.01 to 150 µg/mL during different periods of times (3, 12 and 24 hours). The results of this study showed a time-concentration dependence with two non-cytotoxic concentrations (0.01 and 0.05 µg/mL) and a median effective concentration value of 4.087 µg/mL at 24 hours of GO exposure. Contrary to what has been reported for few-layer GO, cell proliferation of the HaCaT cells in contact with the multi-layer GO at 0.01 μg/mL showed identical proliferative activity compared to an epidermal growth factor (1.6-fold greater than the control group) after 96 hours. The effects of the multi-layer GO on the expression of 13 genes (SOD1, CAT, MMP1, TGFB1, GPX1, FN1, HAS2, LAMB1, LUM, CDH1, COL4A1, FBN and VCAN) at the non-cytotoxic concentrations of GO in the HaCaT cells were analyzed after 24 hours. Thus, the lowest non-cytotoxic GO concentration was able to up-regulate the CAT, TGFB1, FN1 and CDH1 genes, which confirms the great potential of multi-layer GO in the biomedical field.

Appropriate estimation of soil settlement is of significant importance since it directly influences the performance of building and infrastructures that are built on soil. In particular, the settlement of fine-grained soils is critical because of low permeability and continuous settlement with time. Coefficient of consolidation (C_c) is a key parameter to estimate settlement of fine-grained soil layers. However, estimation of this parameter is time consuming, needs skilled technicians, and specific equipment. In this study, C_c was estimated using several soil parameters such as liquid limit (LL), plastic limit (PL), and initial void ratio (e₀). Estimating such parameters in laboratory is straight forward and needs substantially less time and cost compared to conventional tests to estimate C_c such as oedometer test. This study presents a novel prediction model for C_c of fine-grained soils using gene-expression programming (GEP). GEP is a biologically inspired technique capable of offering closed-form solution for the optimal solution. A database consisted of 108 different data points was used to develop the model. A closed-form equation solution was derived to estimate C_c based on LL, PL, and e₀. The performance of developed GEP-based model was evaluated through coefficient of determination (R²), root mean squared error (RMSE), and mean average error (MAE). High R² and low error values indicated the descent performance of the model. Furthermore, the model was evaluated using the additional performance measures and met all the suggested criteria. Furthermore, the model had a better performance in terms of R², RMSE, and MAE compared to most of existing models. It is expected that the developed model will decrease the time and cost associate with determining C_c of fine-grained soils.Keywords: evolutionary model, gene-expression programming (GEP), prediction, soil compression index, estimation, soil engineering, soil informatics, civil engineering, machine learning, data science, big data, soft computing, deep learning, forecasting, subject classification codes, construction informatics, computational intelligence (CI), artificial intelligence (AI), estimation

The study purpose was to train and validate a deep-learning approach to detect micro-scale streetscape features related to pedestrian physical activity. This work innovates by combining computer vision techniques with Google Street View (GSV) images to overcome impediments to conducting audits (e.g., time, safety, and expert labor cost). The EfficientNETB5 architecture was used to build deep-learning models for eight micro-scale features guided by the Microscale Audit of Pedestrian Streetscapes-Mini tool: sidewalks, sidewalk buffers, curb cuts, zebra and line crosswalks, walk signals, bike symbols, and streetlights. We used a train--correct loop, whereby images were trained on a training dataset, evaluated using a separate validation dataset, and trained further until acceptable performance metrics were achieved. Further, we used trained models to audit participant (N=512) neighborhoods in the WalkIT Arizona trial. Correlations were explored between micro-scale features and GIS-measured- and participant reported-macro-scale walkability. Classifier precision, recall, and overall accuracy were all >84%. Total micro-scale was associated with overall macro-scale walkability (r=0.300,p<.001). Positive associations were found between model-detected and self-reported sidewalks (r=0.41,p<.001) and sidewalk buffers (r=0.26,p<.001). Computer vision model results suggest an alternative to trained human raters, allowing for audits of hundreds or thousands of neighborhoods for population surveillance or hypothesis testing.

The tissue micro environment or milieu consists of a highly dynamic population of cellular and non-cellular components which constitute a complex regulatory network aimed at maintaining the organ homeostasis. In the modern medicine the discovery of miRNAs is undoubtedly a promising field of research and they are essential in orchestrating immune system logic and their release in the gut micro milieu can directly affect bacterial gene expression. Here, we briefly review the role of microRNAs, focuses on their role on immune system components in physiological and pathophysiological gut micro milieu.

Identification of the differentially-expressed genes is important for clarification of the complex molecular mechanisms under drought conditions. In this experiment, transcriptome profiles of sensitive and tolerant tomato genotypes under drought stress were analyzed. Three up-regulated genes were selected, included CAB3 (Chlorophyll a-b binding protein3), SAMDC (S-adenosylmethionine decarboxylase proenzyme), and ACS9 (1-aminocyclopropane-1-carboxylate synthase 9). After bioinformatics analysis, tomato genotypes were subjected to drought stress and gene expression was determined using Real-Time-PCR. Physiological parameters of genotypes were also measured by spectrophotometer-based methods. According to the results, these three genes play a key role in stress tolerance. Expression of the CAB3 gene in both sensitive and tolerant genotypes was not significantly different compared to the control, but the SAMDC gene decreased in both genotypes and the ACS9 gene decreased in sensitive genotype and increased in tolerant genotype. The physiological analysis also showed that under stress conditions, the photosynthetic system of the plant was disrupted and the chlorophyll content was reduced, but, proline content and antioxidant enzymes activity increased, in which their quantity in the tolerant genotype was significantly higher than sensitive. Under drought stress, due to damage to the lipid membrane, Malondialdehyde content also increased, in which the sensitive genotype was more affected.

Studies on the influence of dietary components and their effects are fundamental for nutrigenomics, or the study of how nutrients can be cellular sensors, how they affect biological processes and gene expression in different tissues. Lipids are an important source of fatty acids (FA) and energy and are fundamental to biological processes and influence the regulation of transcription. Pigs are excellent model to study nutrigenomics, particularly lipid metabolism because the deposition and composition of FA in their tissues reflect the composition of FA in their diet. Recent studies show that FA supplementation is important in production systems, such as growing and finishing pigs, as it can improve the energy value of the feed, help reduce costs, improve animal welfare, and influence the nutritional value of the meat. Studies show that oleic (OA), linoleic (LA), docosahexaenoic (DHA), and eicosapentaenoic (EPA) acids are associated with the regulation of transcription in tissues such as muscle, liver, adipose tissue, and brain. Other studies indicate that EPA and DHA are associated with changes in specific signaling pathways, altering gene expression and biophysical properties of membranes. This review, therefore, focuses on the current knowledge of the effects of dietary FA on production traits and gene expression.

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons on amygdala gene expression to analyze the specific transcriptional pathways involved in adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and in strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

The upregulated expression of thyrosine kinase AXL has been reported in several hematologic and solid human tumors including gastric, breast, colorectal, prostate, and ovarian cancers. Thus, AXL can potentially serve as a diagnostic and prognostic biomarker for various cancers. This paper reports the first-ever use of loop-mediated isothermal amplification (LAMP) of the AXL gene as a diagnostic method for ovarian cancer. We demonstrated simple instrumentation toward a point-of-care device to perform LAMP. This paper also reports the first-ever use of core-shell beads as a microreactor to perform LAMP as an attempt to promote environmentally friendly laboratory practices.

The study of pain requires a balance between subjective methods that rely on self-reports and complementary objective biometrics that ascertain physical signals associated with subjective accounts. There are at present no objective scales that enable the personalized assessment of pain, as most work involving electrophysiology rely on summary statistics from a priori theoretical population assumptions. Along these lines, recent work has provided evidence of differences in pain sensations between participants with Sensory Over Responsivity (SOR) and controls. While these analyses are useful to understand pain across groups, there remains a need to quantify individual differences more precisely in a personalized manner. Here we offer new methods to characterize pain using the moment-by-moment standardized fluctuations in EEG brain activity centrally reflecting the person’s experiencing temperature-based stimulation at the periphery. This type of gross data is often disregarded as noise, yet here we show its utility to characterize the lingering sensation of discomfort raising to the level of pain, individually, for each participant. We show fundamental differences between the SOR group in relation to controls and provide an objective account of pain congruent with the subjective self-reported data. This offers the potential to build a standardized scale useful to profile pain levels in a personalized manner across the general population.

Escherichia coli and Shigella are common diarrhea-causing pathogens in children and adults. Enteroinvasive Escherichia coli (EIEC) shares a similar pathogenic mechanism with Shigella. However, EIEC are less virulent than Shigella. The aim of this work was to get a better understanding of the virulence differences between EIEC and S. flexneri. We investigated i) the bacterial gene co-expression networks (GCNs) and ii) the the transcriptional modules (WGCNA) of Caco-2 cells infected with EIEC or with S. flexneri during a three-hour period of bacterial infection. The GCN analysis showed that EIEC and S. flexneri networks presented different topologies. Additionally, the EIEC network revealed that pINV genes are not connected with chromosomal genes. WGCNA and eigengene analysis showed enterocyte gene expression variation along the three-hour bacterial post-infection period. Additionally, at one-hour post-infection EIEC induced a higher number of gene expression changes in Caco-2 cells than S. flexneri. Several of these genes are involved in autophagy. This study showed that the lower virulence of EIEC is associated with a lack of functional cooperation between pINV and chromosomal genes, differently from what was observed in S. flexneri. Consequently, EIEC becomes less efficient in subverting host-cell bacterial recognition as well as defense mechanisms such as autophagy.

Two types of trenches cross-section in conventional vertical and brand new reverse-V-shape have fabricated on SCD substrate by micro-jet water-assist laser, the epitaxial lateral overgrowth technique has applied by microwave plasma chemical vapor deposition system in forming multiple micrometer-size channels. Raman and SEM techniques have applied in analyze both types growth layer characterization. Optical microscope has used to test microchannels hollowness. As a result, with the brand new reverse-V-shape trench, epitaxial lateral overgrowth layer reaches higher SCD surface morphology and crystal quality.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cells, B cell, and NF-kB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

A pilot study on laser 3D printing of inorganic free-form micro-optics is experimentally validated. Ultrafast laser nanolithography is employed for structuring hybrid organic-inorganic material SZ2080TM followed by high-temperature calcination post-processing. The combination allows production of 3D architectures and the heat-treatment results in converting the material to inorganic substance. The produced miniature optical elements are characterized and their optical performance demonstrated. Finally, the concept is validated for manufacturing compound optical components such as stacked lenses. This is opening for new directions and applications of laser made microoptics under harsh conditions such as high intensity radiation, temperature, acidic environment, pressure variations, which include open space, astrophotonics, and remote sensing.

Magnesium (Mg) is a vital element, which involves in various key cellular processes in plants. Mg transporter (MGT) genes play an important role in magnesium distribution and ionic balance maintenance. Here, MGT family members were identified and characterized in three species of the plant family Malvaceae, including Theobroma cacao, Corchorus capsularis, and Gossypium hirsutum to improve our understanding of their structure, regulatory systems, functions, and possible interactions. We identified 18, 41, and 16 putative non-redundant MGT genes from the genome of T. cacao, G. hirsutum, and C. capsularis, respectively, which were clustered into five groups within maximum likelihood tree. Several segmental/tandem duplication events were determined between MGTs genes. It seems that MGTs were slowly evolving and have been evolved under a purifying selection. Analysis of gene promoter regions showed that MGTs have a high potential to respond to biotic/abiotic stresses as well as hormones. The expression patterns of MGT genes revealed their possible T. cacaorole in response to P. megakarya fungi in T. cacao, whereas MGT genes showed differential expression in various tissues and respond to several abiotic stresses, including cold, salt, drought, and heat stress in G. hirsutum. Besides, the co-expressions network of MGTs indicated that genes involved in auxin responsive, lipid metabolism, cell wall organization, and photoprotection can interact with MGTs.

Recent improvements within the fields of high-throughput screening and 3D tissue culture have provided the possibility of developing in vitro micro-tissue models that can be used to study diseases and screen potential new therapies. This paper reports a proof of concept study on the use of microvalve-based bioprinting to create laminar MSC-chondrocyte co-cultures as an in vitro model of autologous chondrocyte implantation (ACI), an established cellular therapy for osteoarthritis. Microvalve-based bioprinting uses microvalves to deposit cells suspended in a liquid in a consistent and repeatable manner. In this case MSCs and chondrocytes have been sequentially deposited into an insert based transwell system in order to create a laminar co-culture, with variations in the ratios of the cell types used to investigate the potential for MSCs to stimulate improved repair. Histological and indirect immunofluorescence staining revealed the formation of dense tissue structures within the chondrocyte and MSC-chondrocyte cell co-cultures, alongside the establishment of a proliferative region at the base of the tissue. No stimulatory or inhibitory effect in terms of ECM production was observed through the introduction of MSCs, although the potential for an immunomodulatory benefit remains. This proof-of-concept study therefore provides a novel method to enable the scalable production of therapeutically relevant micro-tissue models that can be used for in vitro research to optimise ACI procedures.

This paper presents an improved droop control strategy for grid-connected inverter power stability and power quality under distorted with consideration of grid fluctuation and inter-harmonics. An instantaneous frequency without PLL and amplitude of capacitor voltage feed-forward control strategy is given to power stability control, meanwhile a grid current feedback control is given by an incomplete derivation with a high-pass filter, so that the harmonics and inter-harmonics current can be suppressed. These approaches can provide both good active and reactive power dynamic response under fluctuation of frequency, and rejection ability against harmonic and inter-harmonic voltage. Based on model of inverter, the proposed control strategies are designed in detail. Simulations and experiments are present to validate the effectiveness of proposed method.

Methylenetetrahydrofolate reductase (MTHFR), an enzyme expressed in mammalian testes exerts direct effect on spermatogenesis; however, its protein characteristics in bovine testes remain unknown. Here, we analysed bovine testicular structure, MTHFR bioinformatics profile, mRNA, and protein expression characteristics in yellow-cattle (y-c) and yak testis using histological procedures, bioinformatics analysis, qRT-PCR, and western blot. Testes from 13 bovines, ≤ 2 years juvenile (y-c, n = 3; yak, n=3) and ≥ 3 years adult (y-c, n = 3; yak, n = 4) were collected and analysed. Anatomical characteristics of testis in y-c and yak were similar except the weight or size for which that of y-c was significantly higher or greater than yak. In y-c, an open reading frame (ORF) for 2600 nucleotides sequence, encoding 655 amino acids showed high homology with zebu cattle (99.51%) and wild yak (98.68%). Secondary and 3D protein structures were similar to that of humans with differences in number of nucleotides, amino acids, and some physico-chemical characteristics. MTHFR mRNA expression in y-c and yak were significantly higher in adult testes compared with juvenile ones. However, its protein expression was higher but not statistically significant in adult y-c and yak compared to the juvenile ones. The highlights and inferences of these and other findings are discussed.

The investigation of membrane proteins, key constituents of cells, is hampered by the difficulty and complexity of their in vitro synthesis, of unpredictable yield. Cell-free synthesis is herein employed to unravel the impact of the expression construct on gene transcription and translation, without the complex regulatory mechanisms of cellular systems. Through the systematic design of plasmids in the immediacy of the start of the target gene, it was possible to identify translation initiation and the conformation of mRNA as the main factors governing the cell-free expression efficiency of the human voltage dependent anion channel (VDAC), a relevant membrane protein in drug-based therapy. A simple translation initiation model was developed to quantitatively assess the expression potential for the designed constructs. A scoring function is proposed that quantifies the feasibility of formation of the translation initiation complex through the ribosome-mRNA hybridization energy and the accessibility of the mRNA segment binding to the ribosome. The scoring function enables to optimize plasmid sequences and semi-quantitatively predict protein expression efficiencies. This scoring function is publicly available as webservice XenoExpressO at rna.tbi.univie.ac.at.

Individual plant cells are the building blocks for all plantae and artificially constructed plant biomaterials, like biocomposites. Secondary cell walls (SCWs) are a key component for mediating mechanical strength and stiffness in both living vascular plants and biocomposite materials. In this paper, we study the structure and biomechanics of cultured plant cells during the cellular developmental stages associated with SCW formation. We use a model culture system that induces transdifferentiation of Arabidopsis thaliana cells to xylem vessel elements, upon treatment with dexamethasone (DEX). We group the transdifferentiation process into three distinct stages, based on morphological observations of the cell walls. The first stage includes cells with only a primary cell wall (PCW), the second covers cells that have formed a SCW, and the third stage includes cells with a ruptured tonoplast and partially or fully degraded PCW. We adopt a multi-scale approach to study the mechanical properties of cells in these three stages. We perform large-scale indentations with a micro-compression system and nanoscale indentations through atomic force microscopy (AFM), in three different osmotic conditions. We introduce a spring-based model to deconvolve the competing stiffness contributions from turgor pressure, PCW, SCW and cytoplasm in the stiffness of differentiating cells. Prior to triggering differentiation, cells in hypotonic pressure conditions are significantly stiffer than cells in isotonic or hypertonic conditions, highlighting the dominant role of turgor pressure. Plasmolyzed cells with a SCW reach similar levels of stiffness as cells with maximum turgor pressure. The stiffness of the PCW in all of these conditions is lower than the stiffness of the fully-formed SCW. Our results provide the first experimental characterization of the mechanics of SCW formation at single cell level.

Appropriate estimation of soil settlement is of significant importance since it directly influences the performance of building and infrastructures that are built on soil. In particular, the settlement of fine-grained soils is critical because of low permeability and continuous settlement with time. Coefficient of consolidation (Cc) is a key parameter to estimate settlement of fine-grained soil layers. However, estimation of this parameter is time consuming, needs skilled technicians, and specific equipment. In this study, Cc was estimated using several soil parameters such as liquid limit (LL), plastic limit (PL), and initial void ratio (e0). Estimating such parameters in laboratory is straight forward and needs substantially less time and cost compared to conventional tests to estimate Cc such as Oedometer test. This study presents a novel prediction model for Cc of fine-grained soils using gene-expression programming (GEP). GEP is a biologically inspired technique capable of offering closed-form solution for the optimal solution. A database consisted of 108 different data points was used to develop the model. A closed-form equation solution was derived to estimate Cc based on LL, PL, and e0. The performance of developed GEP-based model was evaluated through coefficient of determination (R2), root mean squared error (RMSE), and mean average error (MAE). High R2 and low error values indicated the descent performance of the model. Furthermore, the model was evaluated using the additional performance measures and met all the suggested criteria. Furthermore, the model had a better performance in terms of R2, RMSE, and MAE compared to most of existing models. It is expected that the developed model will decrease the time and cost associate with determining Cc of fine-grained soils.

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

We report on the application of femtosecond laser micromachining to the fabrication of complex glass microdevices, for high-order harmonic generation in gas. The three-dimensional capabilities and extreme flexibility of femtosecond laser micromachining allow us to achieve accurate control of gas density inside the micrometer interaction channel. This device gives a considerable increase in harmonics generation efficiency if compared with traditional harmonic generation in gas jets. We propose different chip geometries that allow to control the gas density and driving field intensity inside the interaction channel to achieve quasi-phase matching conditions in the harmonic generation process. We believe that these glass micro-devices will pave the way to future downscaling of High-order Harmonic Generation beamlines.

Leishmania major is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus Leishmania. The objective was successfully attained in 2005, and this represented a milestone for Leishmania molecular biology studies around the world. Although the LmjF genome sequence was done following a shotgun strategy and using classical Sanger sequencing, the results were excellent and this genome assembly served as the reference for subsequent genome assemblies in other Leishmania species. Here, we present a new assembly for the genome of this strain (named LMJFC for clarity), generated by the combination of two high throughput sequencing platforms, Illumina short-read sequencing and PacBio Single Molecular Real-Time (SMRT) sequencing, which provides long-read sequences. Apart from resolving uncertain nucleotide positions, several genomic regions have been reorganized and a more precise composition of tandemly repeated gene loci was attained. Additionally, the genome annotation has been improved by adding 542 genes and more accurate coding-sequences defined for around two hundred genes, based on the transcriptome delimitation also carried out in this work. As a result, we are providing gene models (including untranslated regions and introns) for 11,238 genes. Genomic information ultimately determines the biology of every organism; therefore, our understanding of molecular mechanisms will depend on the availability of precise genome sequences and accurate gene annotations. In this regards, this work is providing an improved genome sequence and updated transcriptome annotations for the reference L. major Friedlin strain.

This paper presents a novel architecture for detecting mathematical formulas in document images, which is an important step for reliable information extraction in several domains. Recently, Cascade Mask R-CNN networks have been introduced to solve object detection in computer vision. In this paper, we suggest a couple of modifications to the existing Cascade Mask R-CNN architecture: First, the proposed network uses deformable convolutions instead of conventional convolutions in the backbone network to spot areas of interest better. Second, it uses a dual backbone of ResNeXt-101, having composite connections at the parallel stages. Finally, our proposed network is end-to-end trainable. We evaluate the proposed approach on the ICDAR-2017 POD and Marmot datasets. The proposed approach demonstrates state-of-the-art performance on ICDAR-2017 POD at a higher IoU threshold with an f1-score of 0.917, reducing the relative error by 7.8%. Moreover, we accomplished correct detection accuracy of 81.3% on embedded formulas on the Marmot dataset, which results in a relative error reduction of 30%.

The Brassica family contains several economically important crops, including rapeseed (Brassica napus, 2n = 38, AACC), the second largest source of seed oil and protein meal worldwide. However, research in rapeseed is hampered because it is complicated and time-consuming for researchers to access different types of expression data. We therefore developed the Brassica Expression Database (BrassicaEDB, https://biodb.swu.edu.cn/brassica/) for the research community. We conducted RNA sequencing (RNA-Seq) of 103 tissues from rapeseed cultivar ZhongShuang11 (ZS11) at seven developmental stages (seed germination, seedling, bolting, initial flowering, full-bloom, podding, and maturation). We determined the expression patterns of 101,040 genes via FPKM analysis and displayed the results using the eFP browser. We also analyzed transcriptome data for rapeseed from 70 BioProjects in the SRA database and obtained three types of expression level data (FPKM, TPM, and read counts). We used this information to develop the BrassicaEDB, including eFP, Treatment, Coexpression, and SRA Project modules based on gene expression profiles and Gene Feature, qPCR Primer, and BLAST modules based on gene sequences. The BrassicaEDB provides comprehensive gene expression profile information and a user-friendly visualization interface for Brassica crop researchers. Using this database, researchers can quickly retrieve the expression level data for target genes in different tissues and in response to different treatments to elucidate gene functions and explore the biology of rapeseed at the transcriptome level.

Until recently, research on the molecular signatures of HPV-associated head and neck cancers mainly focused on their differences with respect to HPV-negative HNSCCs. However, given the continuing high incidence level of HPV-related HNSCC, the time is ripe to characterize the heterogeneity that exists within these cancers. Here, we review research thus far on HPV-positive HNSCC molecular subtypes, and their relationship with clinical characteristics and HPV integration into the host genome. Different omics data including host transcriptomics and epigenomics, as well as HPV characteristics, can provide complementary viewpoints. Keratinization, mesenchymal differentiation, immune signatures, stromal cells, and oxidoreductive processes all play important roles.

The aim of present study was to link the gene expression profile of selected candidate genes with blood profile, growth performance and carcass traits of Barki lambs. Thirty-eight Barki lambs were divided into 3 groups (fast, intermediate and slow growing) according to growth perfor-mance. Body tissues (muscle, liver and fat) were taken from for RNA isolation and Real-time PCR. The results indicated that, the final body weight hot carcass weight were heavier (P ≤ 0.05) in fast (49.9 Kg and 24.57) than intermediate (40.7 and 19.07 Kg) and slow (30.8 and 15.10 Kg) growing animals. The blood profile of total protein, total lipids, calcium, T3 and T4 hormones did not differ among sheep groups. Genes involved in protein biosynthesis (RPL7), fatty acid oxidation (CPT1) and lipolysis (FABP4) were up regulated in fast and intermediate growing lambs in all studied tissues. While, gene-regulating lipogenesis (ADIPOQ) was expressed simi-larly in fat and liver tissues, but increased its expression in muscle of fast and intermediate growing lambs. Expression of CAPN3 was increased in fast and intermediate growing compared to slow growing lambs. In conclusion, the current study providing an evidence for the im-portance of co-expression of these genes in main body tissues linked with growth performance of Barki lambs.

Classical models of gene expression were built using genetics and biochemistry. Although these approaches are powerful, they have very limited consideration of the spatial and temporal organization of gene expression. Although the spatial organization and dynamics of RNA polymerase II (RNAPII) transcription machinery has fundamental functional consequences for gene expression, its detailed studies have been for long time abrogated by the limits of classical light microscopy. The advent of super-resolution microscopy (SRM) techniques allowed for the visualization of the RNAPII transcription machinery with nanometer resolution and millisecond precision. In this review, we summarize the recent methodological advances in SRM, focus on its application for studies of the nanoscale organization in space and time of RNAPII transcription, and discuss its consequences for the mechanistic understanding of gene expression.