A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.

Background: Barleria lupulina Lindl. (Hop-headed) is a small shrub, possess potent anti-inflammatory, analgesic, anti-leukemic, antitumor, anti-hyperglycemic, anti-amoebic, virucidal, diuretic, bactericidal and antibiotic properties. Methods: Cytotoxicity, bioactive assay and genetic analysis of B. lupulina were investigated in the present communication. The leaf extract was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Neutral red uptake (NRU), DNA fragment, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) assay, gene expression analysis and cDNA synthesis to evaluate anti-cancerous potency using cancerous THP-1 cell lines in vitro and in vivo. Results: HPTLC analysis reveals four spots and GC-MS analysis displayed the presence of eleven bioactive compounds among which benzofuranon, hexadecanoic acid, ethyl 9,12,15-octadecatrienoate, and 3,7,11,15-tetramethyl-2-hexadecanoic acid were the most prominent compounds. The ethanolic extract showed significant cytotoxicity (P<0.5) against THP-1 cell line at a concentration of 1mg/mL. The cells were also observed for apoptosis through DNA fragmentation in B. lupulina treated cells. Conclusions: It can be concluded that if the dose range was further refined within the range of 100-1000 µg/mL there could be dose at which the entire population of the THP-1 cell line would be apoptosis induced. The extract induced ROS in the cells after 30 minutes of exposure displaying cytotoxic effects and DNA fragmentation assay.

Sentinel-1A/B radar remote sensing data were applied for the first time to determine the sixth nuclear test, its underground explosion h-bomb location and affected zone in North Korea, on September 3, 2017. Location of epicenters nuclear test were found according to line-of-sight displacement images via its maximum value. Line-of-sight displacement images were obtained by processing in the GMTSAR package in the VirtualBox virtual machine of the Linux Ubuntu 16.04 operation system. In this research, three scenes Sentinel-B data with descending orbits were considered, one after and two before the event (the nuclear test date) scene were used.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

Two X chromosomes of female mammals randomly inactivate one of paternal or maternal X chromosome in early embryonic development and all the daughter cells produced from these cells retain the same feature of X chromosome inactivation, which is called X chromosome inactivation (XCI). Studying the mechanisms of XCI is important for understanding epigenetic that plays an important role in age-associated diseases. The previous studies have demonstrated that binding of RNAs and DNAs may play a role in activating gene expression. In this paper, our study aims to explore whether the mechanisms of XCI involve the RNA binding strength to X chromosome DNAs. The bioinformatics analyses based on big data were used to analyze the simulated binding strength of RNAs (RNA binding strength) to 23 chromosomes (including X chromosome and 22 human autosomes) and the characteristics of repetitive sequences in the X-inactivation centre. The results revealed that RNA binding strength of the long arm of the X chromosome that is almost entirely inactivated in XCI was significantly lower than that of all autosomes and the short arm of X chromosome, meanwhile the RNA binding strengths of inactivation regions in X chromosome were significantly lower than that of regions escaping from XCI. Different repetitive sequence clusters within the center of XCI presented a cross distribution characteristic. To further prove whether the repetitive sequences in human X chromosome involve in XCI, we cloned long interspersed element (LINE-1, L1) and short interspersed element (Alu) from human Xq13, the center of XCI, and constructed expression vectors carrying sense-antisense combination repetitive sequences (L1s or Alus). Effects of combined L1 or combined Alu sequences on expression of EGFP reporter gene were examined in stably transfected HeLa cells, which simulates the effects of repetitive sequences located on chromosomes. The results of experiments revealed transcribed L1 repetitive sequences activated EGFP reporter gene expression, so did the Alus. The experiment results suggested repetitive sequences activated genes by interaction of transcribed RNAs and DNAs. Since the binding of RNAs and DNAs can activate gene, so the low RNA binding strength of human X chromosome may be one of reasons of XCI. The cross distribution characteristics of different repetitive sequence clusters leading to a cascade of gene activation or gene inactivation may be the reason of transcriptional silencing one of the X chromosomes in female mammals.

This study is designed to assess and improve apparel sewing section efficiency and productivity throughout line balancing. Apparel industry is one of the oldest and among the most global industry, being primarily concerned with the design and production of cloth and their supply. The central process in apparel manufacturing is the joining together of components which is known as the sewing process , which is the most labour intensive type of manufacturing process .Proper utilization of resources in garment sewing section is more critical to enhance the performance of the apparel industry by reducing production cost and minimizing wastage. For effective utilization of resources in the sewing section, good line balancing is important to increase productivity and production efficiency. This research was a design to analyse and improve the assembling line in the case of Telaje garment manufacturing and sales plc. The study was first conduct observations in the production floor and start work with the selection of sewing line in the garment production process. Among the nine lines of the factory select one on the production floor and one garment ordered product known as five pocket men’s jeans trousers are selected. For this study, both qualitative and quantitative research approaches were employed. Both primary and secondary data sources are used to detail the collected relevant data to understand the current efficiency scenario of the factory. The main challenges to minimizing line efficiency and productivity with the expected performance measurement are improper utilization of resources and improper implementation of line balancing in sewing section, therefore this thesis work shows that the bottleneck process and consequence solution will be searched, and finally significantly improving the productivity by 418 unit products/ day and, hence the efficiency will increase from 28.83% to 50.04% of the line

Salinity is considered as one of the most important abiotic challenges that affect crop productivity. Plant hormones, including salicylic acid (SA), are key factors in the defence signalling output triggered during plant responses against environmental stresses. We have previously reported in peach a new SA biosynthetic pathway from mandelonitrile (MD), the molecule at the hub of the cyanogenic glucoside turnover in Prunus sp. In this work, we have studied whether this new SA biosynthetic pathway is also present in plum and the possible role this pathway plays in plant plasticity under salinity, focusing on the transgenic plum line J8-1, which displays stress tolerance via an enhanced antioxidant capacity. The SA biosynthesis from MD in non-transgenic and J8-1 micropropagated plum shoots was studied by metabolomics. Then the response of J8-1 to salt stress in presence of MD or Phe (MD precursor) was assayed by measuring: chlorophyll content and fluorescence parameters, stress related hormones, levels of non-enzymatic antioxidants, the expression of two genes coding redox-related proteins, and the content of soluble nutrients. The results from in vitro assays suggest that the SA synthesis from the MD pathway demonstrated in peach is not clearly present in plum, at least under in vitro conditions. Nevertheless, in J8-1 NaCl-stressed seedlings, an increase in SA was recorded as a result of the MD treatment, suggesting that MD could be involved in the SA biosynthesis under NaCl stress conditions in plum plants. We have also shown that the plum line J8-1 was tolerant to NaCl under greenhouse conditions, and this response was somewhat different in MD-treated plants. In that regards, the MD treatment produced an increase in SA, jasmonic acid (JA) and reduced ascorbate (ASC) contents as well as in the coefficient of non-photochemical quenching (qN) and the gene expression of Non-Expressor of Pathogenesis-Related 1 (NPR1) and thioredoxin H (TrxH) under salinity conditions, suggesting a crosstalk between different signalling pathways (NPR1/Trx and SA/JA) leading to salinity tolerance in the transgenic plum line J8-1.

A methodology for both accurate and smooth contour line generation from Light Detection and Ranging (LiDAR) point clouds is proposed in this paper. In order to improve the accuracy of contour lines in the area of forests, constrained triangulation networks with break lines are then constructed to generate contour lines. In break line extraction, a bi-threshold method for edge line detection is used to extract both complete and reliable break lines. A point clouds elevation adjustment with constrain of break lines and an interpolator considering a contour interval is proposed to improve the smoothness of contour lines. The proposed interpotator is also can avoid contour line intersection when contour lines are interpolated. Statistical parameters and shape index are then used to evaluate quantitatively the accuracy and smoothness of the resultant contour lines, which fill in the blank of contour lines evaluation in theory. The experiments show that high-quality contours in terms of smoothness and accuracy can be generated from LiDAR point clouds.

This research concerns the virtual reconstruction and technical constructive analysis of the emblematic and disappeared Matriz church of Ambato city, whose structure was demolished after the collapse of its vaults in the 1949 earthquake, about which it was said to have had deficiencies in its construction. Through an exhaustive historical review of documents and images, its constructive hypothesis was achieved, and using photogrammetry technique, its virtual reconstruction was obtained, where, through the interpretation and understanding of the generated plans, the verification of its technical and constructive characteristics associated with its hypothetical mechanical behavior inherent to its stone construction was carried out. For the structural study, the principle of the Limit Analysis of Structures was used, where through a graphic static approach, the technical stability conditions of a masonry structure are established, in this case, to give an interpretation to the possible poor execution of the church's work, and eventual cause that could have contributed to the collapse of its vaults.

In the paper, the author discusses and computes bounds of the sine and cosine along straight lines on the complex plane.

For a given set of plasma parameters, along a single series (Lyman, Balmer etc) the lines with higher principal quantum number(n) lines get progressively wider, closer to each other, and start merging for a certain critical n. In the present work four different codes(with further options) are used to calculate the entire Balmer series for moderate and high electron densities. Particular attention is paid to the relevant physics, such as the cutoff criteria, strong and penetrating electron collisions.

HIV-1 transcribes only one kind of transcript – the full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must splice but not completely. Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all. HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full length genomic RNA and has a dramatic fitness cost. Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 has to circumvent this cell policing mechanism to allow some splicing while suppressing most. Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev. There is still much work to be done to clarify the combinatorial effects of these splicing regulators. These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and also present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

A closed form solution for the common and differential modal currents induced on a pair of infinitely long parallel conductors by a voltage source was derived. For lossy conductors the current consists of a continuous spectrum of radiation modes and (for the common mode) a modified low loss Sommerfeld-Goubau mode and (for the differential mode) a quasi-TEM mode. This model is used to investigate the influence of a parallel conductor on microwave power line communication systems. For typical parameters, it is shown that the performance of these systems can be enhanced.

Stark widths for 23 transitions in Al IV have been calculated employing modified semiempirical method. The results are obtained for an electron density of 10^17 cm−3 and temperatures from 10,000 K up to 160,000 K. The results obtained in this investigation are used for the examination of the influence of Stark broadening in Al IV stellar spectra, as well as to check Stark width regular behavior and similarites within Al IV spectrum.

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

The research in neuroscience links alexithymia, the difficulty of identifying and describing feelings and emotions, with a left hemisphere preference and/or a right hemisphere deficit. To provide a neuropsychological support to this finding, we explored the relationship between alexithymia and the performance in a line bisection task, a standard method to evaluate spatial attention in relation with the functioning of the right hemisphere. 222 healthy participants completed a version of the TAS-20 scale, which measures alexithymia, and were asked to mark (bisect) the center of a 10 cm horizontal segment. The results document a significant rightward shift of the line center in borderline and manifest alexithymic participants, as compared to non-alexithymic individuals. Moreover, the higher the TAS-20 score the greater the rightward shift in the line bisection task. This result supports the right-hemisphere deficit hypothesis in alexithymia and suggests that visuospatial abnormalities may be an inner component of their profile.

Overhead power transmission line icing (PTLI) disasters are one of the most severe dangers to power grid safety. Automatic iced transmission line identification is critical in various fields. However, existing methods primarily focus on the linear characteristics of transmission lines, employing a two-step process involving edge and line detection for PTLI identification. Nonetheless, these traditional methods are often difficult when confronted with challenges such as background noise or variations in illumination, leading to incomplete identification of the target area, missed target regions, or misclassification of background pixels as foreground. We propose a new iced transmission line identification scheme to overcome this limitation. In the initial stage, we integrate the image restoration method with image filter enhancement to restore the image's color information. This combined approach effectively retains valuable information and preserves the original image quality, thereby mitigating noise presented during the image acquisition. Subsequently, in the second stage, we introduce an enhanced multi-threshold algorithm to separate background and target pixels. After image segmentation, we enhance the image and obtain the region of interest (ROI) through connected component labeling modification and mathematical morphology operations, eliminating background regions. Our proposed scheme achieves an accuracy value of 97.72%, a precision value of 96.24%, a recall value of 86.22%, and the specificity value of 99.48% based on the average value of test images. Through object segmentation and location, the proposed method can avoid background interference, effectively solve the problem of transmission line icing identification, and achieve 90% measurement accuracy compared to manual measurement on the collected PTLI dataset.

Diagnosis of kidney diseases has recently become more comprehensive and accurate by using new renal markers. Despite the fact that creatinine and cystatin c have been sufficient in determining kidney function, they did not indicate the exact site of the damage and they were often insufficient in predicting the course of the disease. Aim of the study was to evaluate the potential correlations and differences in levels of six factors related to kidney function and injury: kidney injury molecule-1 (KIM-1), ncalbindin (CALB), glutathione S-transferase Pi (GST-Pi), calbindin and monocyte chemoattractant protein-1 (MCP-1), between renal patients with diabetic nephropathy (DM), congenital defects (CD) of the kidney and glomerulonephritis (GN). Study involved 75 patients: 49 with diabetic nephropathy, 12 with congenital defects and 14 with glomerulonephritis. Levels of renalase was measured using immunoenzymatic tests. Levels of other markers: calbindin, glutathione-S-transferase (GST-pi), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were analyzed using Kidney Toxicity-1 Panel and BioPlex system, designed for analyses in urine and optimized by us for serum.From all analyzed markers, only levels of KIM-1 differed significantly between any subgroups, and that was for CD and DM. Renalase correlated significantly negatively with creatinine and positively with all other markers, apart from MCP-1. Obtained results indicate, that serum renalase, KIM-1, calbindin and GST-pi are related to kidney function, with KIM-1 being the most exact, while MCP-1 levels are unrelated to creatinine and glucose levels, does not differ between patients with diabetic nephropathy and other subgroups, and therefore seem to be independent of diabetes. Also, serum-optimized Kidney Toxicity Panel 1 kit for determination of selected markers gave results similar to previous ones and therefore the method can be valuable in determination of analyzed factors.

This study compares the action of different handpieces (turbine, high-speed electric handpiece and piezoelectric device) on surface roughness of enamel and dentin when using diamond-coated working tips and burs of the same grit size. Experiment was conducted on 15 extracted first molars from patients aged 45 to 60 years. The occlusal portion was removed using a diamond-coated water wheel and then refined with a 120-130 μm grit bur in order to obtain a flat surface with an adequate exposition of the dentin core. Each surface was divided into three portions and every portion was finished with one of the three tested instruments. Rotary burs and piezoelectric tips had the same grit size (60 μm) and load on handpiece during preparation never exceeded 150 g. Surface roughness parameters (Ra, Rsk, Rku) were recorded with an optical profilometer and SEM analysis of treated surfaces and working tips was conducted. Ra and Rsk differed significantly between enamel and dentin only after using turbine (p=0.004 and p=0.007, respectively). No significant differences were observed in Ra, Rsk, and Rku between enamel and dentin when using high-speed electric handpiece or piezoelectric device. Turbine produced higher Ra and Rsk values on dentin than the other devices, while no significant differences were found between piezoelectric handpiece and high-speed electric contra-angle on both substrates. Summarizing, the findings of the present study demonstrated that turbine generated rougher surfaces on dentin compared to the other handpieces. Moreover, the turbine produced more asymmetrical surface profiles on both enamel and dentin. However, it should be considered that these differences in roughness (Ra) were within the range of 0.25-0.30 μm: it is still unclear if these variations, although statistically significant, will influence final clinical outcomes.

Herbs and Plants have been the most important form of medicine in India since ancient times. the plant kingdom is a goldmine of potential drugs and active molecules. Medicinal plants played a vital role in manufacturing human health and improving the quality of human life for thousands of years. During the last decade, the use of traditional medicine has expanded globally and gained popularity. Medicinal plants have healing properties due to the presence of various complex chemical substances of different compositions. Medicinal plants have served humans well as valuable components of medicines, flavorings, beverages, cosmetics, and dyes. Ficus religiosa is one of the medically important plants belonging to the family of Moraceae. It has been used broadly by Ayurvedic practitioners in India to treat various diseases. The present work is an endeavor to improve the effectiveness of synthetic drugs in combination with plant extracts.

Accordingly, the present study is aimed at investigating quaternary climate changes in Binalod Heights. To identify glacial effects, Morphic indices, field evidence and effects, climatic evidence, and (laboratory) experimental analysis were employed. Determining the permanent snow line in the region was conducted using the Right Method and 65 cirques which are considered as much enriched feeding resources for the formation an ice cover in the region. The expansion of settlements in the region are lower than the permanent snow life is more accumulated than above the border of the permanent snow line. This issue indicates that refrigeration cells do not have the ability to create civil nuclear. Regarding quaternary climate changes and the gradual warming of the climate, the initial core of the City of Mashhad ranges from the center of the Kashf rood River to northeastern heights of Binalod. In addition, the existence of glacial cirques in heights as an important factor in feeding refrigerating conditions has been effective on the expansion of urbanization of Mashhad in the past time. Our new geomorphological mapping and landsystem reconstructions provide an important insight into the response of temperate Binalod glaciers to rapidly-warming climate

Chilli leaf curl virus (ChiLCV) is a severe threat to the successful cultivation of the chilli peppers. Besides, the genetics and heterosis for important traits under the influence of ChiLCV infestation is not well studied. Therefore here, were crossed seven genotypes (lines) with high yield and quality attributes with four highly resistant genotypes (testers) in a line (L) × tester (T) mating design to produce 28 F1 hybrids. Parents and their hybrids were evaluated for yield attributes and ChiLCV resistance. All the four testers were symptomless and among seven lines, two were moderately resistant and five were moderately susceptible to the ChiLCV. Among 28 F1 hybrids, 12 showed a moderate resistant reaction, 11 were moderately susceptible and five susceptible to the ChiLCV disease. Based on per se performance, most promising hybrid combinations were L3 × T2, L6 × T1, and L3 × T1 for yield attributes. Whereas the superior crosses for ChiLCV resistance based on heterobeltosis, standard heterosis and specific combining ability test (SCA) effects were L6 × T1 and L7 × T3. Lines and testers showed significant differences for all the characters except for the plant height. The general combining ability (GCA) effects for testers were significant for all the traits except for days to first harvest. The ratio of σ2GCA/σ2SCA indicated the predominance of non-additive gene effects in the inheritance of traits studied in this experiment. The contribution of lines was more compared to testers for all the characters except for primary branches plant-1. Overall, this study provides valuable information regarding the genetics and heterosis in chilli with respect to ChiLCV infestation

When the distance between an obstacle and a power line is less than the discharge distance, a discharge arc can be generated, resulting in interruption of power supplies. Therefore, regular safety inspections are necessary to ensure safe operations of power grids. Tall vegetation and buildings are the key factors threatening the safe operation of extra high voltage transmission lines within a power line corridor. Manual or LiDAR based-inspections are time consuming and expensive. To make safety inspections more efficient and flexible, a low-altitude unmanned aerial vehicle remote-sensing platform equipped with optical digital camera was used to inspect power line corridors. We propose a semi-patch matching algorithm based on epipolar constraints using both correlation coefficient and the shape of its curve to extract three dimensional (3D) point clouds for a power line corridor. Virtual photography was used to transform the power line direction from approximately parallel to the epipolar line to approximately perpendicular to epipolar line to improve power line measurement accuracy. The distance between the power lines and the 3D point cloud is taken as a criterion for locating obstacles within the power line corridor automatically. Experimental results show that our proposed method is a reliable, cost effective and applicable way for practical power line inspection, and can locate obstacles within the power line corridor with measurement accuracies better than ±0.5 m.

Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

To supply stable and high-quality power according to the advancement of industrial growth, electric power companies have performed maintenance of power facilities using various meth-ods. In the case of domestic power distribution facilities, there are limitations in performing di-agnostic management on all facilities owing to the large number of facilities; therefore, old fa-cilities are managed by the health index assessment method. The health index assessment com-prises only facility operation data and external environmental data and is managed only for four types of distribution facilities, including overhead/underground transformers and switchgear. In the case of extra high–voltage overhead wires, there is no standard for old replacement, despite the large number of wires, such as transformers and switchgear, and the large ripple effect of power failure in the event of a power outage. Therefore, in this paper, a health index assessment methodology for extra-high voltage overhead cables was developed. In this paper, we devel-oped an economic health index assessment methodology that additionally considers risk cost, which is different from the existing health index assessment method that uses only operational data and external environmental data to determine facility performance evaluation and aging replacement criteria. Using the health index assessment methodology developed in this paper, it is possible to expect a reduction in facility operating costs and investment costs from the per-spective of electric power companies through the replacement of old extra-high voltage over-head cables. In addition, from the perspective of consumers, it is expected to increase power re-liability and reduce the ripple effect of failure by preferentially replacing equipment with a high probability of failure.

Transposable elements (TEs) ubiquitously exist in the human genome, and some have the ability to copy and paste themselves to other locations, resulting in new insertions. Organisms have evolved with mechanisms and machineries to repress such activity. TEs are also co-opted for beneficial functions by the host and are thus maintained in the genome. During the lifetime of humans, aberrant TE activity might cause or contribute towards diseases including neurological conditions such as Alzheimers Disease (AD) and cancer. While inflammatory pathways linked to TEs may be a part of the disease pathology, on the other hand altered TE activity involving inflammatory pathways could be recognised by disease suppression mechanisms. For this reason, TEs could be targeted for therapeutic applications aiming to prevent TE activity or reduce initial inflammatory pathways as well as to activate disease suppression mechanisms. In this review, we describe the contributory and potential preventative roles of TEs in neurological conditions and cancer from a molecular and evolutionary perspective. Evolutionary paradigms both at the unicellular and organismal level aid understanding the role of TEs in disease. These observations could pave the way for the development of novel therapeutic approaches targeting TEs.

Efficient quality evaluation provides support for the timely and good maintenance of the lane line marking. This paper searches and optimizes the back propagation(BP) network model which referred to the analytic hierarchy process(AHP) model structure, as well as the number of nodes in the middle layer network. Based on this, a comprehensive evaluation method of multi-dimensional lane line quality such as shape, color and contrast is established. The experimental results show that the parameters of the model are more simplified, and the scoring and classification results of lane lines are more accurate.

Background: The front-line treatment of advanced NeuroEndocrine Neoplasms (NENs) depends on clinical and pathological factors but there are no standard second-line therapies. Methods: Metastatic NENs patients were treated at the ENETS (European NeuroEndocrine Tumor Society) center of excellence of Naples (Italy), from 2014 to 2017 with second-line metronomic temozolomide, 75 mg/m2 per os “one week on/one week off”. Toxicity was graded with NCI-CTC criteria v4.0; objective responses with RECIST v1.1 and performance status (PS) according to ECOG. Results: Twenty-six consecutive patients were treated. Median age was 65.5 years. The predominant primary organs were pancreas and lung. Grading was G2 in 11 patients, G3 in 15. Eleven patients presented with PS 1 and 15 with PS 2. The median time-on-temozolomide therapy was 12.2 months (95% CI: 11.4-19.6). No G3/G4 toxicities were registered. Complete response was obtained in 1 patient, partial response in 4, stable disease in 19 (disease control rate: 92.3%), and progressive disease in 2. The median overall survival from temozolomide start was 28.3 months. PS improved in 73% of patients. Conclusions: Metronomic temozolomide is a safe and active treatment for G2 and G3 NENs. Prospective and larger trials are needed to confirm these results.

The key issue in the post-genomic era is how to systematically describe the association between small molecule transcripts or translations inside cells. With the rapid development of high-throughput “omics” technologies, the achieved ability to detect and characterize molecules with other molecule targets opens up the possibility of investigating the relationships between different molecules from a global perspective. In this article, a Molecular Associations Network(MAN) is constructed and comprehensively analyzed by integrating the associations among miRNA, lncRNA, protein, drug, and disease, in which any kind of potential associations can be predicted. More specifically, each node in MAN can be represented as a vector by combining two kinds of information including the attributes of the node itself (e.g. sequences of ncRNAs and proteins, semantics of diseases and molecular fingerprints of drugs) and the manner of the node in the complex network (associations with other nodes). Random Forest classifier is trained to classify and predict new interactions or associations between biomolecules. In the experiment, the proposed method achieves a superb performance with 0.9735 AUC in 5-fold cross-validation, which show that the proposed method can provide new insight for exploration of the molecular mechanisms of disease and valuable clues for disease treatment.

Based on the kinematic approach of the limit analysis and slip-line theories, this paper proposes a new 2D analytical model to evaluate the collapse support pressure to ensure the face stability of a circular tunnel in purely cohesive soils driven by a shield. The normality conditions, the yield criterion and the vertical soil arching effect are considered in the analytical model. Two upper bound solutions corresponding to the ratio of the cover to the diameter (C/D) are derived from considering the mechanisms based on the motion of rigid multi-blocks. Comparisons are made with existing upper and lower bound solutions published in previous articles. The results are close to the solutions of practical engineering. The failure mechanisms proposed in this study provide a better explanation for the failure process in the heading of the tunnel face.

Atomic structure of N-electron atoms is often determined using the Hartree-Fock method, which is an integro-differential equation. The exchange term of the Hartree-Fock equations is usually treated as an inhomogeneous term of a differential equation, or with a local density approximation. This work uses matrix methods to solve for the Hartree-Fock equations, rather than the more commonly-used shooting method to integrate an inhomogeneous differential equation. It is well known that a derivative operator can be expressed as a matrix made of finite-difference coefficients; energy eigenvalues and eigenvectors can be obtained by using computer linear-algebra packages. We extend the same technique to integro-differential equations, where a discretized integral can be written as a sum in matrix form. This method is compared against experiment and standard atomic structure calculations. We also can use this method for free-electron wavefunctions. This technique is important for spectral line broadening in two ways: improving the atomic structure calculations, and improving the motion of the plasma electrons that collide with the atom.

Synthesis of new series of 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea derivatives and its in vitro antiproliferative activities against NCI-60 human cancer cell lines of nine different cancer types are described. Fourteen compounds 5a-n have been synthesized with three different hydrogen bondable moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea. Different substituents with different π and σ values were added on the terminal phenyl group. Compounds with 4-hydroxymethylpiperidine moiety showed higher mean percentage inhibition values over the 60-cell line panel at 10-µM concentration. They showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 5a elicited some lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line by 146.1, 108.7, 136.2, 134.8, 116.6 % at 10 µM, respectively. Compounds 5a-e exhibited superior antiproliferative activity than Paclitaxel and Gefitinib against the most sensitive cell lines. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC₅₀ values. The data revealed that 5a and 5d urea compounds are the most active derivatives with significant efficacies and superior potencies than Paclitaxel in 21 different cancer cell lines, belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than Gefitinib in 38 and 34 cancer cell lines, respectively; belonging particularly to colon cancer, breast cancer and melanoma cell lines.

Computational fluid dynamics is used to study the impact of the support structure of a tidal turbine on performance and the downstream wake characteristics. A high-fidelity computational model of a dual rotor, contra-rotating tidal turbine in a large channel domain is presented, with turbulence modelled using large eddy simulation. Actuator lines represent the turbine blades, permitting the analysis of transient flow features and turbine diagnostics. The following four cases are considered: the flow in an unexploited, empty channel; flow in a channel containing the rotors; flow in a channel containing the support structure; and flow in a channel with both rotors and support structure. The results indicate that the support structure contributes significantly to the behaviour of the turbine and to turbulence levels downstream, even when the rotors are upstream. This implies that inclusion of the turbine structure, or some parametrisation thereof, is a prerequisite for the realistic prediction of turbine performance and reliability, particularly for array layouts where wake effects become significant.

The study aimed to explore the correlation among Angiopoietin-1, (Ang-1) and Angiopoietin-2, (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio, (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 COVID-19 adult patients, with 30 hospitalized in intensive care and 30 in ward units and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured, and statistical analysis was performed using IBM SPSS Statistics software, version 29. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU -ICU groups) for the Ang-1 and Ang-2 indexes. The Ang-2/Ang-1 ratio has differed significantly among all individual patient groups. A ROC analysis was conducted to find an optimal threshold for distinguishing (outpatients – non-ICU) and (non-ICU –ICU) groups. It was based on Youden's Index and was 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analysed as indicators for severity in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated more excellent prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies for improved outcomes.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

Cognitive linguistics is founded on the assumption that language is a reflection of universal cognitive principles, implying that all cognitive processes share a common origin. This assumption is known as the 'Cognitive Commitment.' The present article examines the sensory schema hypothesis, which traces all forms of expression back to sensations. This theoretical framework integrates the physicality of the body with sensations that underlie human experiences and their linguistic and non-linguistic expressions. By challenging the traditional dichotomy between mind and body, it provides a more integrated understanding.

Campylobacter jejuni is a zoonotic bacterium, causing intestinal infection in humans. One characteristic feature of the pathogenicity process is the ability of this bacterium invading the epithelial cells. Several factors have been identified to contribute to this process and some recent analyses revealed changes in the bacterium cell on molecular level. However, our knowledge is still limited about responses of the host that accompany the bacterial internalisation and survival process. This study focused on molecular events on transcriptomic level detected between the 1st and the 3rd hour of internalisation in INT407 epithelial cells. From the 41.769 human genes tested, altogether 19,060 genes and 22,734 pseudogenes and introns were shown by whole transcriptome analysis to be affected in different extent. Most affected functions regulate transcription (28%), signal transduction (21%), apoptosis (15%), immune responses (9%), transmembrane transport (6%), cell-cell signaling (3%), cell-cell adhesions (3%) and carbohydrate metabolism (3%) and to a lesser extent other functions. Our results provide insight into a scenario where, the invaded cell focuses on survival, but, at the same time, flashing the possibility of pushing the process toward the death of the invaded and metabolically disrupted cell.

Influence lines are indispensable tools for visualizing and analyzing the dynamic variations in force factors induced by external loads within structural systems. Among these methods, the energetic approach stands as a widely employed technique, rooted in the fundamental principle of work done by changing forces. It enables engineers to transform intricate structural analysis problems into manageable ones by exploring the first derivatives of the radius vector, which represent infinitesimal velocity or displacement. This methodology seamlessly interweaves concepts such as carrier motion, relative motion, and the construction of mechanisms, bringing fresh perspectives to the analysis of influence lines. In this article, we explore the nuances of these novel methods within the domain of mechanism theory. Through comprehensive elaboration and analysis, we elucidate the underlying principles and practical applications of Jacobian contours. Crucially, we introduce a straightforward, rapid, and programmable approach, promising to revolutionize influence line determination in structural engineering. This method bridges the gap between theory and practice, offering the potential to elevate the accuracy, efficiency, and adaptability of influence line analysis. As such, it represents a significant advancement in the field of structural and applied mechanics, with broad-reaching implications for engineering practice.

To avoid the endless accumulation of QTL effects during pyramiding breeding, QTL epistasis plays a role of homeostasis. Four single-segment substitution lines with heading date QTLs were utilized to construct pyramiding materials with dual QTLs and triple QTLs, allowing for the estimation of QTL epistatic effects on heading date in rice. The epistatic components of dual QTL and triple QTL interactions were analyzed using data from three seasons of two years. All four QTLs can be considered as dominant loci, demonstrating superdominance. 75% of dual QTL interactions and 81.25% of triple QTL interactions obtained statistically significant results, reaffirming the prevalence of epistasis. Interactions of four QTLs with three positive effects and one negative effect generated 62.5% negative dual QTL epistatic effects and 57.7% positive triple QTL epistatic effects, forming the balance relationship “positive-negative-positive”. In fact, QTL effects were consistently partially neutralized by mixed QTL epistatic effects so as to control the infinite accumulation of QTL effects. QTL epistasis plays a role of homeostasis on heading date in rice. However, there were two exceptions. The directions of OsMADS50 and Hd3a-2 effects were consistently aligned with those of their mixed epistases, suggesting that the QTL or gene could be employed in pyramiding breeding with different objectives. This study elucidated the mechanism of epistatic interactions among four QTLs and provided valuable genetic resources for improving heading date in rice.

Influenced by the quasi-stationary Mei-yu front and the development of mesoscale low vortices on the Mei-yu front, a torrential rain event occurred in Suzhou on July 6, 2020. The 24-hour rainfall recorded by the automatic station exceeded 200 millimeters, with the highest hourly intensity surpassing 70 millimeters, accompanied by thunderstorms and strong winds. This heavy precipitation process was characterized by suddenness, extremity, long duration, high precipitation efficiency, and backward propagation. Using various data sources such as the European ERA5 reanalysis data, ground-based automatic stations, sounding, Doppler weather radar, and wind profile radar, this paper analyzed in detail the circulation characteristics and radar echo structures of this torrential rain event, and further studied the triggering, feature evolution, and maintenance mechanisms of the heavy precipitation.The results show: (1) The continuously strengthening low-level jet stream propagates downward forming an ultra-low-level jet stream. Heavy precipitation is located on the left front side of the jet exit area, where strong convergence and lifting in the boundary layer overlap with the ascending branch of the secondary circulation above the shear line, resulting in heavy precipitation. (2) A supercell storm with intense precipitation produced this heavy rainfall event, characterized by a low centroid of strong echo; echo-free vault, bounded weak echo region, and other supercell structural features. During this event, the high reflectivity factor areas corresponded to high KDP value areas, indicating a large amount of liquid water content. Vertically, the KDP column can track the rainwater mixing ratio well, and its location corresponds to the vicinity of the short-term heavy precipitation occurrence. The high KDP value area mainly consists of numerous precipitation particles, and the vertical vortex wind field structure causes rapid growth of precipitation particles through continuous rolling. Furthermore, it can be found through correlation coefficients (CC) that there are always high-value areas for CC since they correspond to areas of intense precipitation. (3) Continuous triggering of mesoscale convective cloud clusters on the east-west ground convergence line leads to new development and forms a "train effect." Strong frontogenesis in both horizontal and vertical directions triggers and sustains this heavy precipitation event. The significant increase in liquid water and water vapor density has indicative significance for the occurrence of heavy precipitation.

This paper presents a new algorithm for semi-supervised action recognition using adaptive feature analysis. We model the samples of the same action as the same manifold and those of different actions as different manifolds, and integrate feature correlation mining and visual similarity mining into a joint framework. By maximizing the separability between different classes based on the labeled data, the proposed algorithm learns multiple features from labeled data and utilizes the intrinsic geometric structure of the data distribution between labeled and unlabeled data to boost the recognition. We introduce Projected Barzilai-Borwein (PBB) to train a subspace projection matrix as classifier. Extensive experiments on three benchmark datasets demonstrate that our algorithm outperforms the existing semi-supervised action recognition algorithms when there are a few labeled training samples.

High blood cholesterol levels are one of the main risks for atherosclerotic disease. A purified aqueous extract of Fucus vesiculosus, characterized as rich in phlorotannins and peptides, was described as having the capacity to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells metabolites and proteins was analysed, aiming to expand the knowledge about its mode of action targeting cholesterol metabolism, in particular exogenous cholesterol absorption and transport. Caco-2 cells differentiated into enterocytes were exposed to the purified aqueous extract of F. vesiculosus and analysed by undirected metabolomics and proteomics. The results of the metabolomic analysis showed only statistically significant differences in glutathione content of the cells exposed to the extract relatively to the control cells, with a decreased glutathione expression in exposed cells. The proteomic analysis showed an increased expression for cells exposed to the extract of NPC1, an important protein known to be involved in cholesterol transport. To extent of our knowledge this is the first study using untargeted metabolomics and proteomic analysis to study the effect of F. vesiculosus on differentiated Caco-2 cells, which aims to provide some insight about the molecular mechanism of extract compounds on intestinal cells.

Ovarian cancers are curable by surgical resection when discovered early enough. Unfortunately, most ovarian cancers are diagnosed in the later stages. One strategy to identify early ovarian tumors is to screen women who have the highest risk scores. This mini review summarizes the accuracy of different methods used to assess the risk of developing ovarian cancer, including family history, BRCA genetic tests, and polygenic risk scores. The accuracy of these is compared to the maximum theoretical accuracy, revealing a substantial gap. We suggest that this gap, or missing heritability, could be caused by epistatic interactions between genes. An alternative approach to computing genetic risk scores, using chromosomal-scale length variation should incorporate epistatic interactions. Future research in this area should focus on this and other alternative methods of characterizing genomes.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

Shipbreaking research has not been in the forefront until the last decade in which environmental and occupational hazards have been highlighted while economic sustainability and contextual conditions were not equally considered. The adoption of a triple bottom line approach across core business issues (environmental impacts, workplace safety ) as well as peripheral stakeholders expectation (environmental sustainability focus) has been retarded due to the less attention on the latter. Based on the findings of the 128 review papers, the study suggests that organizational learning and economic sustainability needs to prioritize through the formation of strange alliance among the stakeholders. The study argues that the dialogue and discussion on the peripheral stakeholders (NGOs, yard managers, national and international policy organizations) would lead to a more sustainable shipbreaking industry in the south Asian regions.

Sports video analysis is an interesting and emerging field in the domain of computer vision. It has become a very popular subject among scholars all over the world in the last decade due to the need of automated classification of events such as offsides, in/out situations, goals and so on. The most important problem in sports video analysis is detection and tracking of ball and players. Extraction of court lines is also another important problem since it is necessary in the classification of aforementioned events. In this study, considering some of the previous work on the subject, we develop a method for tracking the ball and players in tennis videos where the camera position and orientation is supposed fixed.

Gene electrotransfer is one of the main non-viral methods for intracellular delivery of plasmid DNA, wherein pulsed electric fields are used to transiently permeabilize the cell membrane allowing enhanced transmembrane transport. By localizing the electric field over small portions of the cell membrane using nanostructured substrates, it is possible to increase considerably the gene electrotransfer efficiency while preserving cell viability. In this study, we design an electrotransfer approach based on commercially available cell culture inserts with polyethylene-terephthalate (PET) porous substrate. We first use multiscale numerical modelling to determine the pulse parameters, substrate pore size, and other factors that are expected to result in successful gene electrotransfer. Based on numerical results we design a simple device combining an insert with substrates containing pores with 0.4 um and 1.0 um diameter, a multiwell plate, and a pair of wire electrodes. We test the device in three mammalian cell lines and obtain transfection efficiencies similar to those achieved with bulk electroporation, but with low-voltage pulses that do not require the use of expensive electroporators. Our combined theoretical and experimental analysis calls for further systematic studies that will investigate the influence of substrate pore size and porosity on gene electrotransfer efficiency and cell viability.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Brazil, Russia, China, India, and the Republic of South Africa (BRICS) represent developing economies facing different energy and economic development challenges. The current study aims to forecast energy consumption in BRICS at aggregate and disaggregate levels using the annual time series data set from 1992 to 2019 and to compare results obtained from a set of models. The time-series data are from the British Petroleum (BP-2019) Statistical Review of World Energy. The forecasting methodology bases on a novel Fractional-order Grey Model (FGM) with different order parameters. This study contributes to the literature by comparing the forecasting accuracy and the forecasting ability of the FGM(1,1) with traditional ones, like standard GM(1,1) and ARIMA(1,1,1) models. Also, it illustrates the view of BRICS's nexus of energy consumption at aggregate and disaggregates levels using the latest available data set, which will provide a reliable and broader perspective. The Diebold-Mariano test results confirmed the equal predictive ability of FGM(1,1) for a specific range of order parameters and the ARIMA(1,1,1) model and the usefulness of both approaches for energy consumption efficient forecasting.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

Purpose: The aim of the study is an approach to a nanocomposite with copper nanoparticles, constituting a bacteriostatic surface for maintaining the human lung cells' function. Methods: The polyelectrolyte layer coating with copper nanoparticles incorporated was designed. As a bacteriostatic factor, copper nanoparticles were applied as a colloidal solution of copper nanoparticles (ColloidCuNPs) and solution of copper nanoparticles (CuNPs). The influence of polyelectrolytes on selected Gram(+) and Gram(-) strains was examined. The function of the human adenocarcinoma A549 cell line of epithelial human lung cells cultured in the presence of nanocomposite layer coatings was analyzed, as well as their morphology using flow cytometry, fluorescence microscopy, and scanning electron microscopy. In addition, the material of layer coating was assessed using AFM and SEM-EDX characterization. Results: It was observed that polyelectrolytes polyethylenimine and poly-L-lysine do not induce proliferation of E.coli strain. On the other hand, it induces the proliferation of S. aureus strain. Due to CuNPs effectiveness against E.coli strain, CuNPs were selected for further research. The designed coatings at proper NPs share sustained the function of human lung cells cultured within 10 days of culture. The AFM and EDX characterization confirmed copper presence in the layer coating nanomaterial. The presence of CuNPs in polyethyleneimine-based nanocomposite deepens the bacteriostatic effect on E. coli compared with PEI alone. Meanwhile, incorporating CuNPs in PLL at share allowed A549 cell maintenance, did not exert a bacteriostatic influence on the examined strain.Conclusion: The platform based on polyelectrolytes incorporated with copper nanoparticles ensuring the growth and morphology of the human lung epithelial cells can be considered an element of the system components for medical devices for maintaining the human lung cells' function.

In this study, we propose an efficient field-free line (FFL) generator for mechanically driven FFL-magnetic particle imaging (MPI) applications. The novel FFL generator comprises pairs of Halbach arrays and bar magnets. The proposed design generates high-gradient FFLs with low-mass permanent magnets, realizing fine spatial resolutions in MPI. We investigate the generated magnetic field using simulations and experiments. Our results show that the FFL generator yields a high gradient of 4.76 T/m at a cylindrical field of view of 30 mm diameter and a 70 mm open bore. A spatial resolution of less than 3.5 mm was obtained in the mechanically driven FFL-MPI.

The short-lived positron-emitter carbon-11 (t1/2 = 20.4 min; b+, 99.8%) is prominent for labeling tracers for use in biomedical research with positron emission tomography (PET). Carbon-11 is produced for this purpose with a cyclotron, nowadays almost exclusively by the 14N(p,a)11C nuclear reaction, either on nitrogen containing a low concentration of oxygen (0.1–0.5%) or hydrogen (~ 5%) to produce [11C]carbon dioxide or [11C]methane, respectively. These primary radioactive products can be produced in high yields and with high molar activities. However, only [11C]carbon dioxide has some utility for directly labeling PET tracers. Primary products are required to be converted rapidly and efficiently into secondary labeling synthons to provide versatile radiochemistry for labeling diverse tracer chemotypes at molecular positions of choice. This review surveys known gas phase transformations of carbon-11 and summarizes the important roles that many of these transformations now play for producing a broad range of labeling synthons in carbon-11 chemistry.

With the global warming and the frequent occurrences of harsh environments, mooring line failures are frequent. Response analysis of the platform structure and its residual mooring system under multiple mooring line failures is needed. Therefore, it is necessary to investigate the change law of platform motion response after mooring line failure to find out the reasons for the change. Studies for different failure combinations of mooring lines show that the variation of the steady-state equilibrium position of the platform is closely related to the stiffness, with a clear functional. The duration and amplitude of the transient response are mainly influenced by the Morison drag force. And it was found that the suspended mooring line reduced the motion responses. It is also found that the mooring line failure increased the effective tension and suspension length of the riser. Based on the improved Dezert-Smarandache theory (DSmT), it is calculated that mooring line failure has little effect on the failure probability in different zones of the riser.

Sustainable Forest Management (SFM) can fully use forest resources and improve the economic, environmental and social sustainability of forest areas. Forestry enterprises play a crucial role in the implementation of SFM. To better play the role of forestry enterprises in implementing SFM, it is necessary to establish a comprehensive and reasonable performance evaluation model for SFM in forestry enterprises. However, the previous literature pays little attention to this research question. Taking the Triple Bottom Line (TBL) as a theoretical framework and the Montreal Process Criteria and Indicators (MP C&I) as a basis, this paper constructs an indicator system to evaluate the performance of SFM of forest enterprises from economic, social and environmental aspects. This paper applies the integrated MCDM method, i.e. the BWM method and the VIKOR method, to construct the methodological system for SFM performance evaluation of forestry enterprises. The effectiveness of this SFM performance evaluation model is then demonstrated through its application to a case study of forestry enterprises in China. Through the application of the model, this paper evaluates the enterprise's SFM performance over the five-year period 2017-2021 and proposes appropriate policy recommendations and improvements.

In the modern world, all manufacturers strive for the optimal design of their products. This general trend is recently also observed in the corrugated board packaging industry. Colorful prints on displays, perforations in shelf-ready-packaging and various types of ventilation holes in trays, although extremely important for ergonomic or functional reasons, weaken the strength of the box. To meet the requirements of customers and recipients, packaging manufacturers outdo each other in new ideas for the construction of their products. Often the aesthetic qualities of the product become more important than the attention to maintaining the standards of the load capacity of the packaging (which, apart from their attention-grabbing functions, are also intended to protect transported products). The particular flaps design (both top and bottom) and their influence on the strength of the box is investigated in this study. The updated analytical-numerical approach is used here to predict the strength of the packaging with various flap’s offsets. Experimental results indicated a significant decrease in the static load-bearing capacity of packaging in the case of shifted flap creases. The simulation model proposed in our previous work has been modified and updated to take into account also this effect. The results obtained by the model presented in the paper are in satisfactory agreement with the experimental data.

Typhonium flagelliforme is an Indonesian herbal plant used and applied traditionally to treat cancer diseases. Gamma rays have irradiated rodent tuber mutant plant at six doses gray to in-crease the chemical compounds of anticancer activity. The effect of isolated compounds from ro-dent tuber mutant plants has never been studied and published yet. Our study unveiled the poten-tial of stigmasterol as a remarkable cytotoxic agent and the significant contribution of NMR spectroscopy, IR, Mass spectra, QTOF MS towards the isolation and identification of this anti-cancer agent. Stigmasterol was isolated from T. flagelliforme mutant plant. Stigmasterol was more effective against MCF-7 cells with an IC50 value of 0.1623 µM than Cisplatin with IC50 value 13.2 µM. It is the most potential and active fraction in the human breast cancer cell line. The mo-lecular docking study analyzed the chemical profile of stigmasterol to confirm the receptor in agonist binding sites. The prediction of the toxicity of stigmasterol compounds using in silico and analysis of its interaction with the receptor can act as a competitive regulator with a high-affinity binding site on FXR. Stigmasterol has potential as a candidate for an anticancer drug that pro-moting further clinical action.

Nowadays, the wasting of resources is one of the fundamental challenges of the industrial sector. The rectangle packing problem can be very effective in this context. Practical applications of this issue in the timing and designing of the industries and businesses are very remarkable. The purpose of this issue is to arrange a set of rectangles with specific dimensions in a rectangular page with a specific width and unlimited height without overlapping. The fundamental challenge in this issue is that this is an NP-complete issue. Therefore, it is difficult to achieve the best arrangement, which has the maximum rate of resource utilization and also has a linear running time. Many algorithms have been presented to estimate a practical solution for this issue. In the past decades, the best fit method has been one of the most useful methods for this purpose. This study presents a combinatorial algorithm based on two algorithms, including the lowest front-line strategy and the best-fit algorithm. The running results indicate that the suggested algorithm performs well, despite its simplicity. The time complexity of the suggested algorithm is O(nm), in which n is the number of input rectangles and m is the number of the created front lines.

Prostate cancer (PCa) has become the most common tumor among males in Europe and the USA. Adoptive immunotherapy appears as a promising strategy to control the advanced stages of the disease by specific targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy.

The current study sets out to develop an empirical line method (ELM) radiometric calibration framework for reducing atmospheric contributions in UAS imagery and for producing scaled remote sensing reflectance imagery. Using a MicaSense RedEdge camera flown on a custom-built octocopter, the research reported herein finds that atmospheric contributions have an important impact on UAS imagery. Data collected over the Lower Pearl River Estuary in Mississippi during five week-long missions covering a wide range of environmental conditions was used to develop and test a simplified ELM radiometric calibration framework designed specifically for the reduction of atmospheric contributions to UAS imagery in studies with limited site accessibility or data acquisition time constraints. The framework was effective in reducing atmospheric and other external contributions to UAS imagery. Unique to the proposed radiometric calibration framework is the radiance to reflectance conversion conducted externally from the calibration equations which allows for the normalization of illumination independent from the time of UAS image acquisition and from the time of calibration equations development. This paper presents the simplified ELM radiometric calibration framework that can be used as a time-effective calibration technique to reduce errors in the UAS imagery.

Background: Breast cancer is the leading cause of cancer mortality and morbidity among Indonesian women. Identification of biological pathways leading into therapeutic resistance through in vitro model is an important step to develop alternative effective therapy in breast cancer. Loss of PTEN expression has been associated with resistance to chemotherapy by involving PI3K/PTEN- dependent apoptosis pathway. We conducted in vitro experiment to investigate the association of hsa-miR-21 and PTEN expression in Doxorubicin-resistant MCF-7 cell line. Methods: Parental MCF-7 cells were periodically incubated with Doxorubicin to obtain specific Dox-resistant variant determined by IC50 using MTT assay. PTEN protein expression was analyzed using immunocytochemistry. Expression of mature has-miR-21 was measured using qRT-PCR. Results: The IC50 of Doxorubicin in parental MCF-7 and Doxorubicin-resistant MCF-7 cells (MCF-7/Dox) was 0.68 and 5.78 µg/ml, respectively. Hsa-miR-21 was significantly overexpressed in MCF-7/Dox cells compared to parental MCF cells (7.94 fold changes). Conclusion: PTEN and hsa-miR-21 expression levels were negatively correlated in Doxorubicin resistant-MCF cells. Further study to confirm the causal relationship of miR-21 overexpression and PTEN downregulation in MCF-7/Dox is required.

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

The notion of the three-phase (line) tension remains one of the most disputable notions in the surface science. A very broad range of its values has been reported. Experts even do not agree on the sign of the line tension. The polymer-chain-like model of the three-phase (triple) line enables the rough estimation of the entropic input into the value of the line tension, estimated as Γ_en≅(k_B T)/d_m ≅〖10〗^(-11) N, where d_m is the diameter of the liquid molecule. The introducing of the polymer-chain-like model of the triple line is justified by the “water string” model of the liquid state, predicting strong orientation effects for liquid molecules located in the vicinity of hydrophobic moieties. The estimated value of the entropic input into the line tension is close to experimental findings, reported by various groups.

This paper proposes a crack recognition method based on high-resolution line array cameras and adaptive lifting algorithm. By defining the crack rate, this algorithm calculates the ratio of the crack area to the area of the entire collected image to characterize the damage extent of the current section. The algorithm first uses image preprocessing to reduce the image noise, then uses histogram equalization to enhance the feature of the crack region, divides the whole image into multiple sub-blocks, and extracts region features in the sub-block. At the same time, this algorithm defines related feature descriptors, and constructs weak classifiers according to each feature descriptor, and converts the weak classifiers into strong classifiers by using an adaptive lifting algorithm. Finally, this algorithm realizes the division of the crack regions. Experimental results show that the proposed algorithm can meet the actual needs and is better than other classical algorithms.

Dislocation is one of the major challenges in unmanned aerial vehicle (UAV) image stitching. In this paper, we propose a new dynamic programming for seamlessly stitching UAV images using optical flow. Our solution consists of two steps: Firstly, an image-matching algorithm is used to correct the images so that they are in the same coordinate system. Secondly, a new dynamic programming algorithm is develop based on the concept of a stereo dual-channel energy accumulation using optical flow. A new energy aggregation and traversal strategy is adopted in our solution, which can find a more optimal seam line for adjacent image stitching. Our algorithm overcomes the theoretical limitation of the classical Duplaquet algorithm. Experiments show that the algorithm can effectively solve the dislocation problem in UAV image stitching. Beyond that, our solution is also direction-independent, which has more adaptability and robustness for UAV images.

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

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Typhoons bring great damages to transmission line systems located in coastal areas. Strong wind and extreme precipitation are the main sources of damaging effects. Transmission lines suffered from wind-driven rain exhibit more susceptibility to damage due to the coupled effect of wind and rain water. This paper presents an integrated numerical simulation framework based on mesoscale WRF model, multiphase CFD model and FEM model to analyze the motions of a transmission line subjected to coupled wind and rain loads during typhoon events. A full-scale transmission line in Zhoushan island is employed to demonstrate the effectiveness of the proposed framework by simulating typhoon evolution in terms of wind fields and rainfall, solving the coupled wind and rain fields around the conductor and predicting the dynamic responses of the transmission line during Super Typhoon Lekima (2019). The results show that the horizontal displacements of the transmission line under the joint actions of wind and rain increases approximately 17%~18% compared to those of wind loads only. It is important to consider the coupled effects of wind-driven rain on conductors in the design of transmission lines under typhoon conditions.

A novel compressible real gas 1D finite volume thermofluid network modelling methodology is proposed that can be applied in the analysis of supercritical CO₂ (sCO2) power cycles. It is applied to simulate centrifugal compressor performance via a mean line approach that directly solves the mass, energy, and momentum balance equations for the discretized flow channels within the machine along with the associated loss models, component characteristics, and applicable compressible real gas equation of state. This can be integrated seamlessly with the rest of the power cycle components like pipes, valves, heat exchangers, etc., thereby eliminating the need for static performance maps and the associated difficulties to ensure similarity over the whole range of operation. This direct simulation of the internal flows also makes it possible to do integrated cycle design optimization that includes the geometry of the compressors, and to simulate fast transients for dynamic analysis. The methodology was applied to simulate well-documented air and sCO2 centrifugal compressors and compared the generated results with that of conventional thermofluid network incompressible and compressible ideal gas approaches. The results indicate that the proposed compressible real gas approach can capture the stagnation pressure changes and isentropic efficiencies with good accuracy for both cases over the whole range of mass flow rates and shaft rotational speeds. In contrast, the conventional thermofluid network incompressible and compressible ideal gas approaches are only applicable in selected regions of the fluid property regime and suffer from discretization errors and inappropriate treatment of the relationship between stagnation and static pressures. Furthermore, comparative analyses between the newly proposed approach and the traditional mechanical energy balance method are performed, showing that the latter approach needs to be discretized more finely through the compression process to correctly capture the polytropic compression path shape, whereas the former more accurately captures the stagnation pressure changes through the analyzed compressors with only a single increment per compressor component.

Many corporations have now revised their value statements to showcase their commitment to sustainable development and green business due to the pressing issues of climate and environmental damage. Despite the importance of value statements that can direct companies to achieve sustainable goals, what kind of values can be perceived as organizational orientations to sustainability remains unknown. This study explores how the general public views the inclusion of sustainable components in value statements from the listed companies in Hong Kong by using Q-sort methodology (n = 30). Analyzing the final sample of 40 value statements extracted from 27 listed companies, we identified three factors related to sustainability, namely, Empowering business process management, Empowering customer-centric excellence, and Empowering sustainable progress. This study provides an additional component to the traditional triple bottom line by suggesting that internal operation of a company is an emerging idea to understand corporate sustainability.

The extraction of roof feature lines is an important foundation for realizing large-scale and batch 3D modeling. However, the current traditional point cloud segmentation algorithms do not have satisfactory results in extracting roof feature lines of Chinese traditional residential buildings. In this paper, taking Jingping Village in Western Hunan as an example, we propose a method that combines multiple algorithms based on slope segmentation of roof patches to extract feature lines. Firstly, VDVI and CSF algorithms are used to extract the building and roof point cloud based on the MVS point cloud. Secondly, according to roof features, village buildings are classified, and 3D roof point cloud is projected into 2D regular grid data. Finally, the roof slope is segmented via slope direction, and internal and external feature lines are obtained after refinement through Canny edge detection and Hough straight line detection. Results reveal that this method effectively extracts feature lines of low-building roofs in traditional villages, with slope-based roof surface segmentation accuracy surpassing 99.6%. This method significantly outperforms the RANSAC algorithm and region segmentation algorithm.

Colorectal cancer is the third most common disease and the second most common cause of death in the world. The drug for second-line treatment depends on the drugs used in first-line treatment and biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers are established for selecting angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be hopeful biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

This work focused on proposing a plan for improvement and control of the customer service process in a customer service center, based on a waiting line analysis where it describes all the elements that interact in the system and a statistical analysis of processes to define the state in which it operates. Subsequently, the simulation of processes is applied to represent the system studied, and with it, to be able to evaluate different strategies for improvement and increase in productivity. The following strategies were evaluated: correction of the instability of customer service processes, establishment of new specification limits according to the promise of value to be fulfilled to customers, human resource management, administrative technical support. Finally, with the results obtained from the simulation of the system, the improvement and productivity increase plan is planned according to the DMAMC (Define, Measure, Analyze, Improve, Control, or DMAIC) continuous improvement cycle established in six sigma

Globally, gastric cancer is a major cause of cancer mortality, with a 5-year survival rate of 32% for locally advanced and metastatic gastric cancer. This systematic literature review summarized the clinical, safety, and humanistic outcomes associated with systemic regimens given as first line therapy for locally advanced and metastatic gastric cancer. The search included articles published in English in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and the American Society of Clinical Oncology meeting library, from inception to April 2022. Phase II and III randomized controlled trials conducted among western populations diagnosed with stage III and IV locally advanced and metastatic gastric cancer were included. Two investigators independently reviewed the studies, conducted data extraction, and assessed risk of bias in accordance with PRISMA guidelines. Twenty-four randomized controlled trials totaling 8,705 patients were included. Median overall survival ranged from 5.0-13.1 months, median progression-free survival ranged from 2.0-7.7 months, and objective response ranged from 13.0-64.1%. Two studies reported higher quality of life outcomes. Grade 3 and 4 adverse events were reported in most studies. Improvement in clinical outcomes can be seen in recently published randomized controlled trials for locally advanced and metastatic gastric cancer.

The images captured by UAVs during inspection often contain numerous small targets related to transmission lines, which are critical and vulnerable elements for ensuring the safe operation of these lines. However, due to various factors such as the small size of the targets, low resolution, complex background, and potential line aggregation, achieving accurate and real-time detection becomes challenging. To address these issues, this paper proposes a detection algorithm called P2-ECA-EIOU-YOLOv5 (P2E-YOLOv5). Firstly, in order to address the challenges posed by the complex background and environmental interference that impact small targets, an ECA attention module is integrated into the network. This module effectively enhances the network's focus on small targets while concurrently mitigating the influence of environmental interference. Secondly, considering the characteristics of small target size and low resolution, a new high-resolution detection head is introduced, which is more sensitive to small targets. Lastly, the network utilizes the EIOU-Loss as the regression Loss function to improve the positioning accuracy of small targets, as they tend to aggregate. Experimental results demonstrate that the proposed P2E-YOLOv5 detection algorithm achieves an accuracy P of 96.0% and an average accuracy (mAP) of 97.0% for small target detection in transmission lines.

Interference on Power Line Communication (PLC), which is a wired communication technology that provides communication and data transmission over the existing electrical network, is examined in this paper. Many applications employ PLC technologies, which have the benefit of leveraging existing power connections for both power and data transfer, reducing cost and complexity. These interactions may be observed in contemporary smart grids and automobile power networks, where lengthy cables, switching power supplies, and communication links all work together but exacerbate electromagnetic interference problems. This research examines the effects of Spread Spectrum methods used to reduce EMI from power converters on PLC systems. Spread spectrum modulation and its three variants Sine, Random and Triangle are frequently employed to meet the requirements of electromagnetic compatibility, however there are some repercussions, that might be detrimental to the converter or the rest of the electrical network. These outcomes occur for various modulation algorithm settings and at various frequencies. Measurements are made utilising the Frame Error Rate value provided by the PLC link system to ascertain the interference produced by a SiC-based DC-DC converter in order to investigate these concerns and standardise an assessment approach.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to determine the therapeutic potential of these compounds by testing them in A375 cell-line derived xenograft in nu/nu mice. Animals were randomized into four groups (n=12/group) to receive subcutaneous administration of vehicle, 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 three times per week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results suggest a therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.

In this paper, new N-way Wilkinson power dividers (WPDs) are represented by using slow-wave structures such as narrow slits loaded and meandered transmission lines. The slit loaded and meandered lines are used to represent the quarter wavelength transmission lines of a conventional WPD for size reduction. Based on the proposed approaches, 2-, 4- and 8-way power dividers are designed, simulated and fabricated. The fabricated -, 4- and 8-way circuits have been measured at the center frequencies of 2.03, 1.77, and 1.73 GHz in an excellent agreement with the predicted ones. The meandered transmission lines are also used to design new types of WPDs having novel input/output port arrangements. For this purpose, two 3-way WPDs are located at both sides of the same board so as to have different power splitting ratios at different inputs and outputs to provide alternative solutions for antenna arrays. Furthermore, a 5-way dual layer WPD is introduced by locating the meandered transmission lines to two layers. The proposed 3- and 5-way WPDs allow halving the input power at the next output port in the order of P/2, P/4, P/8, P/16, and P/16. All of the designed power halving WPDs have been simulated, fabricated and successfully tested.

The extrusion of food for human and animal consumption is a unit operation that includes mixing, shearing and force to the materials related to the rheological properties of the materials in the extruder. The present work aims to study the rheological behavior of an extruded fish diet incorporating hydrolyzed protein flour processed by extrusion. The measurement was carried out online with a slit die rheometer, defining the rheological models and parameters that fit the process. During the extrusion process, the raw materials used were hydrolyzed protein meal, fish meal and cassava starch. For the results, the evaluated treatments were adjusted to the Power Law, where an increase in the shear rate decreases the viscosity of the material, corresponding to a pseudoplastic behavior. The incorporation of hydrolyzed protein flour presented a significant effect on the value of n and Klp, increasing the viscosity with the increase in the percentage of inclusion of HPH. The models obtained for the prediction of the viscosity are adjusted to the changes in shear rate, temperature and humidity of the system.

Wolbachia are intracellular endosymbionts of several invertebrate taxa, including insects and nematodes. Although Wolbachia DNA has been detected in ticks, its presence is generally associated with parasitism by insects. To determine whether or not Wolbachia can infect and grow in tick cells, cell lines from three tick species, Ixodes scapularis, Ixodes ricinus and Rhipicephalus microplus, were inoculated with Wolbachia strains wStri and wAlbB isolated from mosquito cell lines. Homogenates prepared from fleas collected from cats in Malaysia were inoculated into an I. scapularis cell line. Bacterial growth and identity were monitored by microscopy and PCR amplification and sequencing of fragments of Wolbachia genes. The wStri strain infected Ixodes spp. cells and was maintained through 29 passages. The wAlbB strain successfully infected Ixodes spp. and R. microplus cells and was maintained through 2-5 passages. A novel strain of Wolbachia belonging to the supergroup F, designated wCfeF, was isolated in I. scapularis cells from a pool of Ctenocephalides sp. cat fleas and maintained in vitro through two passages over nine months. This is the first confirmed isolation of a Wolbachia strain from a flea and the first isolation of any Wolbachia strain outside the “pandemic” A and B supergroups. The study demonstrates that tick cells can host multiple Wolbachia strains, and can be added to panels of insect cell lines to improve success rates in isolation of field strains of Wolbachia.

Marine mortar was the goal material and its multi-scale physical-chemical-mechanical characteristics were the principal interest in this study. The on-line multi-scale damage detection experiments art was designed to quantify the characteristics mathematically and graphically. The normal cylinder specimen with 70-day age was produced and investigated by dynamically global MSHCT scan and local detection of EDS, SEM and XRD. The experiments results indicated that the marine mortar offered the appreciable strength at the early age at least, although some saline minerals were generated during the preparation. The micro-interfacial behavior and the parental foci controlled the damage development of the marine mortar the performance of which was still the adjustable one by the composition optimization.

Flushing tap water is often promoted as a simple and low cost approach to reducing water lead exposures. This study evaluated lead reduction when prevailing flush guidelines (30 seconds-2 minutes) are implemented in a city compliant with lead-associated water regulations (New Orleans, LA). Water samples (n=1,497) collected from a convenience sample of 376 residential sites (2015-2017) were analyzed for lead in samples collected: at 1) first draw (n=375), and after incremental flushes of 2) 30-45 seconds (n=375), 3) 2.5-3 minutes (n=373), and 4) 5.5-6 minutes (n=218). There was no significant reduction when compared to the first draw lead level, until the 6 minute flush (p<0.05); but most sites (52%) still had detectable lead (≥1 ppb) after 6 minutes. Older homes (pre-1950) and low occupancy sites had significantly higher WLLs (p<0.05).Each sample type had health-based standard exceedances at over 50% of sites sampled (max: 58 ppb). While flushing is an effective short-term approach to remediate high lead, prevailing flush recommendations are an inconsistently effective exposure prevention measure that can often inadvertently increase exposures. Public health messages should be modified to ensure appropriate application of flushing for specific cities, while acknowledging its short-comings and practical limitations.

In this study, a matched-mode autoregressive source depth estimation method (MMAR) based on autoregressive (AR) wavenumber estimation is proposed for a moving source in shallow water waveguides. The signal original frequency and the environmental parameters, namely, the sound speed profile and bottom properties are known as a prior knowledge. The mode wavenumbers are estimated by the AR modal wavenumber spectrum. On the basis of the mode wavenumber estimation, the mode amplitudes can be estimated by the wavenumber spectrum that is obtained by generalized Hankel transform. The source depth estimation is determined by the peak of source depth function wherein the data mode best matches the replica mode that is calculated using a propagation model. Compared with other methods of moving source depth estimation, the proposed method exhibits a better performance in source depth estimation under low signal-to-noise ratio or the small range span. The selection of horizontal line array depth is illustrated by simulation and normal mode theory in details.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.

Background High Mobility Group Box-1 (HMGB-1) is implicated in the pathogenesis of thrombosis and cancer. In the present study, we aimed to evaluate its potential role as a diagnostic biomarker of portal vein thrombosis (PVT) among patients with hepatocellular carcinoma (HCC). Methods The study population included N=100 prospectively recruited patients with a novel diagnosis of HCC. We compared circulating HMGB-1 levels between 34 healthy controls, HCC patients with PVT (N=22), and HCC patients without PVT (N=78). Results HCC patients without PVT showed significantly higher median HMGB-1 serum levels (8.2 [5.5-13.1] ng/ml) than those observed in the case of HCC with PVT (5.5 [4.4-8.5] ng/ml; p=0.012) and in healthy controls (4.1 [3.1-8.2] ng/ml; p&lt;0.001). Among HCC patients, at univariate analysis, the presence of PVT was associated with higher median age (p=0.036), larger major cancer node diameter (p&lt;0.001), and lower HMGB-1 serum level (p=0.012). At multivariate analysis, the presence of PVT maintained a positive association with major node diameter p=0.001) and an inverse association with serum HMGB-1 levels (p=0.003). Conclusions These findings indicate that serum HMGB-1 bears an inverse association with PVT complicating HCC at the time of diagnosis and suggest that serum HMGB-1 depletion may mark PVT development in cirrhotic patients with HCC.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii has occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019 the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high resistant proportion of ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.