Background. 46,XX disorders of sex development are rare. Approximately, 90% of XX males are SRY-positive, while testicular development in the absence of SRY takes place in a minority. Methods: A boy with 46,XX karyotype (SRY-negative; absence of SOX9 duplications) was investigated by targeted Next Generation Sequencing (NGS), Multiplex ligation-dependent probe amplification (MLPA), and Comparative Genomic Hybridization array (CGH-array). Results: The boy had normal male phenotype and normal prepubertal values of testicular hormones. He presented a heterozygous duplication of 49.626 bp, encompassing exons 2 and 3 of DMRT1. The result was arr[GRCh37] 9p24.3(845893_895518)x3. Since both breakpoints are harbored in the intronic regions, the duplication does not stop or shift the coding frame. Additional known pathogenic or uncertain variants in pro-testis gene cascade were not identified. Conclusions: This study report a boy with 46,XX testicular disorder of sex differentiation, showing a de novo partial intragenic duplication of DMRT1. This intragenic duplication may result in a gain of function, acting as primary pro-testis gene (or anti-ovary gene) in a 46,XX human foetus and permitting normal pre-pubertal endocrine testis function.

Most non-infectious diseases are associated with dysfunction of proteins or protein complexes. Аssociation between sequence and structure is analyzed since a long time, and analysis of sequence organization in domains and motifs is actual research area. A mathematical method is proposed here to identify the hierarchical organization of protein sequences. The method is based on pentapeptide as a unit of protein sequences. This method was applied on a non-homologous dataset of protein sequences. The analysis revealed 11 hierarchical levels of protein sequence organization, showing the relationship of these multiple fragments of sequences. Using different examples, we illustrated how the fragments of the spatial structure of protein correspond to the elements of the hierarchical structure of the protein sequence. A hierarchical structure is observed in the protein sequence. This methodology is an interesting basis for mathematically based classification of elements of spatial organization of proteins. Elements of the hierarchical structure of different levels of the hierarchy can be used for biotechnological and medical problems.

Paraphrase generation is an important yet challenging task in NLP. Neural network-based approaches have achieved remarkable success in sequence-to-sequence(seq2seq) learning. Previous paraphrase generation work generally ignores syntactic information regardless of its availability, with the assumption that neural nets could learn such linguistic knowledge implicitly. In this work we make an endeavor to probe into the efficacy of explicit syntactic information for the task of paraphrase generation. Syntactic information can appear in the form of dependency trees which could be easily acquired from off-the-shelf syntactic parsers. Such tree structures could be conveniently encoded via graph convolutional networks(GCNs) to obtain more meaningful sentence representations, which could improve generated paraphrases. Through extensive experiments on four paraphrase datasets with different sizes and genres, we demonstrate the utility of syntactic information in neural paraphrase generation under the framework of seq2seq modeling. Specifically, our GCN-enhanced models consistently outperform their syntax-agnostic counterparts in multiple evaluation metrics.

In this paper, we examine the performance of several classifiers in the process of searching for very negative opinions. More precisely, we do an empirical study that analyzes the influence of three types of linguistic features (n-grams, word embeddings, and polarity lexicons) and their combinations when they are used to feed different supervised machine learning classifiers: Support Vector Machine (SVM), Naive Bayes (NB), and Decision Tree (DT).

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

Road segment can be estimated from GPS trajectories by averaging. However, most existing averaging strategies suffer from high complexity or poor accuracy. For example, finding the optimal mean for a set of sequences is known to be NP-hard, while using Medoid compromises the quality. In this paper, we introduce three extremely fast and practical methods for solving the problem. The methods first analyze three descriptors and then use either a simple linear model or a more complex curvy model depending on an angle criterion. The results outperform Medoid and provide equal or better accuracy than the best existing methods while being very fast, and therefore suitable for real-time processing.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

Prosthetics have come a long way since their inception, and recent advancements in materials science have enabled the development of prosthetic devices with improved functionality and comfort. One promising area of research is the use of auxetic metamaterials in prosthetics. Auxetic materials have a negative Poisson's ratio, which means that they expand laterally when stretched, unlike conventional materials, which contract laterally. This unique property allows for the creation of prosthetic devices that can better conform to the contours of the human body and provide a more natural feel. In this review article, we provide an overview of the current state of the art in the development of prosthetics using auxetic metamaterials. We discuss the mechanical properties of these materials, including their negative Poisson's ratio and other properties that make them suitable for use in prosthetic devices. We also explore the limitations that currently exist in implementing these materials in prosthetic devices, including challenges in manufacturing and cost. Despite these challenges, the future prospects for the development of prosthetic devices using auxetic metamaterials are promising. Continued research and development in this field could lead to the creation of more comfortable, functional, and natural-feeling prosthetic devices. Overall, the use of auxetic metamaterials in prosthetics represents a promising area of research with the potential to improve the lives of millions of people around the world who rely on prosthetic devices.

The purpose of the present study is to explore the linkage between Hazardous Road Locations-based crash counts and a variety of geometric characteristics, roadway characteristics, traffic flow characteristics and spatial features in the region of Sousse, Tunisia. For this purpose, collision data was collected from at 52 hazardous road sections including 1397 crash records for a 11-year monitoring period from January 1, 2004 to December 31, 2014 obtained from National Observatory for Information, Training, Documentation and Studies on Road Safety in Tunisia (NOITDRS). The matrix of Pearson correlation was used in order to avoid inclusion of both variables, which were highly correlated. Both the Random Effects Negative Binomial model and the Negative Binomial model were estimated. To evaluate the models, the Random Effect Negative Binomial model improves the goodness-of-fit compared to the Negative Binomial model. Average Daily Traffic volume, Curved alignment, Presence of public lighting, Visibility, Number of lane, Presence of vertical/horizontal sign, Presence of rural segment, Presence of drainage system, Roadway surface condition, Presence of paved shoulder and presence of major road were found as significant variables influencing accident occurrences. Overall, the current research contributes to the literature from empirical, modeling methodological standpoints since it was the first study conducted in Tunisia to use crash prediction models for hazardous road locations, and that portrays Tunisian reality. The research findings present advantageous insights on hazardous road locations in the region of Sousse, Tunisia and present useful planning tools for public authorities in Tunisia.

Plant diseases are among the major factors affecting plant productivity. Biological control of plant diseases is preferred over chemical control as it is environment-friendly, cost-effective, and sustainable. Among many microbes capable of providing biological control of plant diseases, probiotic Bacillus species are most promising as they can survive in adverse conditions, provide plants with a wide range of benefits including protection from phytopathogens. Wheat blast caused by Magnaporthe oryzae Triticum pathotype (MoT) has emerged as a potential threat to global wheat production. Due to unreliability of fungicides and limited cultivar resistance, we aimed to screen and identify potential antagonist bacteria collected from internal tissues of rice and wheat seeds to determine their in vitro and in vivo inhibitory effects against MoT. Dual culture and seedling assays were performed to evaluate the efficacy of probiotic bacteria. Out of 170 bacterial isolates, three bacteria (BTS-3, BTS-4, and BTLK6A) were screened as potential antagonists against MoT in vitro. Artificial inoculation at the seedling stage showed that the isolates BTS-4, BTS–3, and BTLK6A reduced 89, 88, and 85% of wheat blast disease severity, respectively, compared to mock-inoculated control. The bacterial isolates were identified as Bacillus subtilis (BTS-3) and B. velezensis (BTS-4 and BTLK6A) through genome phylogeny. The whole genome sequence of these three bacterial strains decoded a number of orthologs to intrinsic genes of antimicrobial peptides, antioxidant defense enzymes, cell wall degrading enzymes, compounds involved in the induction of systemic resistance (ISR) in host plants, and volatile compounds to make them promising biologicals to control MoT in wheat. Combined data of in vitro and in vivo along with genome analysis suggest that Bacillus spp. suppress the destructive wheat blast disease likely through antibiosis and ISR in the host plants. Further field evaluation and characterization of antimicrobial compounds are needed for a better understanding of the mode of action and practical recommendation of these bacteria for wheat blast control in the farmers’ fields.

Optinalysis, as a method of symmetry detection, is a new algorithm that intrametrically (within elements or variables) or intermetrically (between elements or variables) computes and compares two or more univariate or multi-clustered or multivariate sequences as a mirror-like reflection of each other (optics-like manner), hence the name is driven. Optinalysis is based by the principles of reflection and moment about a symmetrical line which detects symmetry that reflects a similarity measurement. This proposed methodology was validated in comparison with Pearson method of skewness detection, and also with some algorithms for pairewise alignment and comparison of genomic sequences (Needle, Stretcher, Water, Matcher) on EMBL-EBI website. A results comparison shows that optinalysis is more advance, more sensitive, more inferential and simple alternative approach of skewness detection and pairewise sequence comparison.

Metabolite transport across cellular membranes is a key feature of living organisms. Specialized proteins or protein complexes mediate such transport processes and are accessible to genetic engineering approaches. This special issue will reflect on the different transport between cellular compartments. It will provide an overview about different transporter classes and metabolic engineering approaches in different organisms ranging from Bacteria to Eukarya. The transport mechanisms energetics of these compounds were thought little of, and most consideration was given to the designing of metabolic pathways. Gram-negative microbes discharge a wide scope of proteins whose capacities incorporate biogenesis of organelles, for example, pilli and flagella, supplement securing, destructiveness, and efflux of medications and different poisons. Six particular emission frameworks have been appeared to intervene protein send out through the inward and external layers of Gram-negative microbes. These pathways are exceptionally monitored all through the Gram-negative bacterial species. In Gram-positive microscopic organisms, discharged proteins are usually moved across the single layer by the Sec pathway or the two-arginine (Tat) pathway. Recently efforts focused on transporter and metabolite engineering, visualize the improvement and enhancement of microbial cell to pass such metabolites these metabolite carrier proteins are inserted into the inner membrane of mitochondria across the inner membrane, specialized carrier proteins are necessary that mediate the transport into and out of the mitochondrial matrix. Two main strategies for metabolic engineering in plants: the introduction of genes encoding new enzymes and the use of TFs controlling specialized metabolic pathways

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n=42) and European American (EA, n=33) women. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.

This study investigates the interpretability of machine learning (ML) models applied to cumulative damage prediction during a sequence of earthquakes, emphasizing the use of techniques such as SHapley Additive exPlanations (SHAP), Partial Dependence Plots (PDPs), Local Interpretable Model-agnostic Explanations (LIME), Accumulated Local Effects (ALE), Permutation and Impurity-based technique. The research explores the cumulative damage during seismic sequences, aiming to identify critical predictors and assess their influence on the cumulative damage. Moreover, the predictors contribution in respect with the range of final damage is evaluated. Nonlinear time history analyses are applied to extract the seismic response of an eight-story Reinforced Concrete (RC) frame. The regression problem’s input variables are divided into two distinct physical classes: pre-existing damage from the initial seismic event and seismic parameters representing the intensity of the subsequent earthquake, expressed by Park and Ang damage index (DIPA) and Intensity Measures (IMs), respectively. The study offers a comprehensive review of cutting-edge ML methods, hyperparameter tuning, and ML method comparisons. A LightGBM model emerges as the most efficient, among 15 different ML methods examined, with critical predictors for final damage being the initial damage caused by the first shock and the IMs of the subsequent shock: IFVF and SIH. The importance of these predictors is supported by feature importance analysis and local/global explanation methods, enhancing the interpretability and practical utility of the developed model.

Facing unprecedented global declines in the extent and integrity of ecosystems, the 15^th UN Biodiversity Conference (COP-15) in Kunming, China, presents an opportunity for transformative change. However, a lack of consensus on two key issues – resource mobilization and Access and Benefit Sharing (ABS) associated with Digital Sequence Information (DSI) – risks stalling negotiations for an ambitious ‘Post-2020 Global Biodiversity Framework’ as the next 10-year strategic plan under the Convention on Biological Diversity. We highlight systemic misconceptions concerning the financing of biodiversity and the burden this places on the ABS system. In the context of DSI, we caution that conflating ABS with resource mobilization risks disrupting modern science policy built on open access, with potentially severe ramifications for scientific research and innovation. To resolve these tensions, we call for a recalibration of discussions on ABS in order to maximize the value delivered by biodiversity for all of society, including indigenous peoples and local communities.

It is proven that the Clapeyron-Mendeleev equation, originally discovered for gases with large entropy, describes the state of dark matter and energy due to enormous self-gravitation. It is shown that the dark matter exists as compact cold neutrino stars at positive temperature with size twice the Schwarzschild radius. In contrast, the dark energy is dark matter at temperature below the absolute zero, which is locked entirely in black holes, where the pressure is negative as required for the Universe intrinsic expansion. The derived dark phase diagram predicts negative critical temperatures for the Big Bang and the Big Rip of black holes.

The simple sequence repeats (SSRs) are small 1-6bp tandem repeat elements present across diverse genomes and involved in gene regulation and evolution. Presently we analyzed SSRs in genomes of 98 species of family Polyomaviridae across four genera. The genome size ranged from 3962bp (BM87) to 7369bp (BM85) but maximum genomes were in the range of 5 to 5.5 kb. The GC% had an average of 42% and ranged between 34.69 (BM95) to 52.35 (BM81). A total of 3036 SSRs and 223 cSSRs were extracted using IMEx with incident frequency from 18 to 56 and 0 to 7 respectively. The most prevalent mono-nucleotide repeat motif was “T” (48.95%) followed by “A” (33.48%). “AT/TA” was the most prevalent dinucleotide motif closely followed by “CT/TC”. The distribution was expectedly more in coding region with 77.6% SSRs of which nearly half were in Large T Antigen (LTA) gene. Notably, most viruses with humans, apes and related species as host exhibited exclusivity of mono-nucleotide repeats in AT region, a proposed predictive marker for determination of humans as host in virus in course of its evolution. Each genome has a unique SSR signature which is pivotal for viral evolution particularly in terms of host divergence.

Reptilians or reptoids are staple characters of Hollywood cinema, science fiction literature, ufology and conspiracy theories. Despite its popularity, the reptoid has been dismissed by the scientific community as a figment of the imagination; born out of a speculation, paranoia and wanton anthropocentricism. In this paper, however, the Life Sequence Conjecture is advanced as a supportive framework for the notion of reptilian extraterrestrials. This paper is not an argument in support of the existence of extraterrestrials. Rather, it proposes that if extraterrestrials do exist, then a reptilian morphology is not untenable.

In our study we used the data set on morphimetric traits in beetles species. It has been constantly replenishing for 20 years by the samples, received from different regions of Russia and abroad. In this case we have selected data on nine species for which the left and right sides had been measured and fluctuating asymmetry (FA) could be estimated. The samples were from 6 provinces of Russia and Belarus, which ranged in 3 degrees in latitude and 57 degrees in longitude and included more than 150 plots in different types of biotopes. FA was assessed according to the standard method in 5265 specimen in one dimensional trait and one - meristic. ANOVA showed that biotope, species and their interaction affected FA in both traits, that is different species reacted differently to biotope type. In uncommon biotopes (according to accepted in carabidology classification) FA was increased. In forest species the negative relationship between FA in dimensional and meristic traits in the range in biotopes was revealed. In those species only FA values were higher in males than in females. In generalist species FA varieв similarly in both sexes and in both traits being the highest in open biotopes. In eudomonant of arable lands biotopes – Poecilus cupreus – the highest values of FA were recorded in the meadows, being about equal in all types of crops.

This review provides an overview of advancements in plant genomics, emphasizing key stages in genomics projects and addressing associated challenges. Long read sequencing enables the cost-effective sequencing of plant DNA and assembly of highly continuous genome sequences - often even separating haplophases. Incorporating external hints, such as cDNA sequences from RNA-seq or full length cDNA sequencing, enhances the identification of gene models. While these steps enable high-throughput exploration of numerous plant genomes, a significant bottleneck lies in elucidating gene functions. The classical approach based on wet lab methods is impractical when dealing with thousands of genes in a new genome sequence. To overcome this challenge, computational tools harnessing existing information for cross species knowledge transfer are essential for expediting the functional annotation process. In support of researchers entering the field of plant genomics, a collection of recommended tools has been curated and is accessible at https://github.com/bpucker/ToolOverview.

Patients diagnosed with unresectable locally advanced Triple Negative Breast Cancer (TNBC) usually have poor outcome for its aggressive clinical behaviour. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and objective responses were defined following the RECIST criteria v.1.1. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy. Our data showed patients with unresectable locally advanced TNBC and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel. For the first time, our data showed the usefulness of assessment of exosomal PD-L1 as non-invasive real-time biopsy in patients diagnosed with TNBC suggesting exosomal PD-L1 is significantly associated with outcome and response to Atezolizumab plus nab-Paclitaxel.

One-dimensional chain of core-shell pairs connected by ideal springs enables design of the metamaterial demonstrating the negative effective density and negative specific thermal capacity. We assume that the molar thermal capacity of the reported metamaterial is governed by the Dulong-Petit law in its high temperature limit. The specific thermal capacity depends of the density of the metamaterial; thus, it is expected to be negative, when the effective density of the chain is negative. The range of the frequencies enabling the effect of the negative thermal capacity is established. Dependence of the effective thermal capacity on the exciting frequency for various core/shell mass ratios is elucidated. The effective thermal capacity becomes negative in the vicinity of the local resonance frequency ω0 in the situation when the frequency ω approaches ω0 from above. The effect of the negative effective thermal capacity is expected in metals in the vicinity of the plasma frequency.

Work-related thoughts in off-job time have been studied extensively in occupational health psychology and related fields. We provide a focused review of research on overcommitment – a component within the effort-reward imbalance model – and aim to connect this line of research to the most commonly studied aspects of work-related rumination. Drawing on this integrative review, we analyze survey data on ten facets of work-related rumination, namely (1) overcommitment, (2) psychological detachment, (3) affective rumination, (4) problem-solving pondering, (5) positive work reflection, (6) negative work reflection, (7) distraction, (8) cognitive irritation, (9) emotional irritation, and (10) inability to recover. First, we leverage exploratory factor analysis to self-report survey data from 357 employees to calibrate overcommitment items and to position overcommitment within the nomological net of work-related rumination constructs. Second, we leverage confirmatory factor analysis to self-report survey data from 388 employees to provide a more specific test of uniqueness vs. overlap among these constructs. Third, we apply relative weight analysis to quantify the unique criterion-related validity of each work-related rumination facet regarding (1) physical fatigue, (2) cognitive fatigue, (3) emotional fatigue, (4) burnout, (5) psychosomatic complaints, and (6) satisfaction with life. Our results suggest that several measures of work-related rumination (e.g., overcommitment and cognitive irritation) can be used interchangeably. Emotional irritation and affective rumination emerge as the strongest unique predictors of fatigue, burnout, psychosomatic complaints, and satisfaction with life. Our study assists researchers in making informed decisions on selecting scales for their research and paves the way for integrating research on effort-reward imbalance and work-related rumination.

The determination of crack propagation velocities can provide valuable information for a better understanding of damage processes of concrete. The spatio-temporal analysis of crack patterns developing at a speed of several hundred meters per second is a rather challenging task. In the paper, a photogrammetric procedure for the determination of crack propagation velocities in concrete specimens using high-speed camera image sequences is presented. A cascaded image sequence processing which starts with the computation of displacement vector fields for a dense pattern of points on the specimen’s surface between consecutive time steps of the image sequence chain has been developed. These surface points are triangulated into a mesh, and as representations of cracks, discontinuities in the displacement vector fields are found by a deformation analysis applied to all triangles of the mesh. Connected components of the deformed triangles are computed using region-growing techniques. Then, the crack tips are determined using principal component analysis. The tips are tracked in the image sequence and the velocities between the time stamps of the images are derived. A major advantage of this method as compared to established techniques is in the fact of its allowing for spatio-temporally resolved, full-field measurements rather than point-wise measurements and that information on crack width can be obtained simultaneously. To validate the experimentation, the authors processed image sequences of tests on four compact-tension specimens performed on a split-Hopkinson tension bar. The images were taken by a high-speed camera at a frame rate of 160,000 images per second. By applying to these datasets the image sequence processing procedure as developed, crack propagation velocities of about 800 m/s were determined with a precision in the order of 50 m/s.

For any odd positive integer $x$, define $(x_n)_{n\geqslant 0} $ and $(a_n )_{n\geqslant 1} $ by setting $x_{0}=x, \,\, x_n =\cfrac{3x_{n-1} +1}{2^{a_n }}$ such that all $x_n $ are odd. The 3x+1 problem asserts that there is an $x_n =1$ for all $x$. Usually, $(x_n )_{n\geqslant 0} $ is called the trajectory of $x$. In this paper, we concentrate on $(a_n )_{n\geqslant 1} $ and call it the E-sequence of $x$. The idea is that, we consider any infinite sequence $(a_n )_{n\geqslant 1} $ of positive integers and call it an E-sequence. We then define $(a_n )_{n\geqslant 1} $ to be $\Omega-$convergent to $x$ if it is the E-sequence of $x$ and to be $\Omega-$divergent if it is not the E-sequence of any odd positive integer. We prove a remarkable fact that the $\Omega-$divergence of all non-periodic E-sequences implies the periodicity of $(x_n )_{n\geqslant 0} $ for all $x_0$. The principal results of this paper are to prove the $\Omega-$divergence of several classes of non-periodic E-sequences. Especially, we prove that all non-periodic E-sequences $(a_n )_{n\geqslant 1} $ with $\mathop {\overline {\lim } }\limits_{n\to \infty } \cfrac{b_n }{n}>\log _23$ are $\Omega-$divergent by using the Wendel's inequality and the Matthews and Watts's formula $x_n =\cfrac{3^n x_0 }{2^{b_n }}\prod\limits_{k=0}^{n-1} {(1+\cfrac{1}{3x_k })} $, where $b_n =\sum\limits_{k=1}^n {a_k } $. These results present a possible way to prove the periodicity of trajectories of all positive integers in the 3x + 1 problem and we call it the E-sequence approach.

Because imbalanced power will cause the loss of the propulsion motor of the railway vehicle, and the increase in temperature will shorten the service life of the electric vehicle. Not only this, but also increase the cost of electricity and maintenance. In the past, the industry only focused on methods to improve power quality such as load capacity, relay setting, and harmonic resolution. Now, the consider of three-phase unbalance rate (TPUR) must be applied. I propose special transformers wiring (STW) to improve the three unbalance rates and provide different transformer wiring methods. According to the IEEE Committee, in the future, power companies will need to install balanced relay stations to improve three-phase unbalance rate. the internal regulations of Taipower must be less than 4.5% (voltage unbalance rate (NPSUR)of 2.5% and motor temperature rise of 12.5%). the derivation of the transformer "three-phase unbalance rate" model is the focus of the railway system. This research is based on the model derivation of different wiring methods to improve the hot problem caused by the three-phase imbalance and improve the service life of the train. And pointed out that Scott, Le-Blanc, Modified-Woodbridge three wiring methods can be applied to future railway system routes to improve the three-phase unbalance rate, in line with the IEEE standard of less than 2%.

Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical mitochondrial carrier family SLC25, the past decade led to the discovery of additional protein families that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins and mitochondrial cation/H+ exchangers that have been linked to vital physiological functions and disease. Their structures and transport mechanisms are still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combined sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanism and structure of these novel mitochondrial carriers.

The present study investigates the reliability and validity of the Positive-Negative Relationship Quality (PN-RQ) scale in Turkey. In order to determine the validity and reliability of the scale, two studies were performed. The first was carried out with emerging adults (university students) who were in a romantic relationship (148 females, 43 males, and 2 unkown) and had the main purpose to examine the structure validity of the measurement tool in the Turkish sample with an exploratory analysis. Study 2 was performed online with 513 married adults (359 females, 149 males, and 5 unknown); confirmatory findings and criterion validity studies were added. Exploratory factor analyses revealed that relationship quality had a two-factor structure and that there was also a negative relationship between the factors. Confirmatory factor analyses on the married sample showed that the bi-factor model provided evidence for the multidimensional nature of the scale. Both studies demonstrated high internal consistency.

The aim of this paper is to discuss the relations between various notions of sequential completeness and the corresponding notions of completeness by nets or by filters in the setting of quasi-metric spaces. We propose a new definition of right $K$-Cauchy net in a quasi-metric space for which the corresponding completeness is equivalent to the sequential completeness. In this way we complete some results of R.~A. Stoltenberg, Proc. London Math. Soc. \textbf{17} (1967), 226--240, and V.~Gregori and J.~Ferrer, Proc. Lond. Math. Soc., III Ser., \textbf{49} (1984), 36. A discussion on nets defined over ordered or pre-ordered directed sets is also included.

In this article, we introduce the concept of soft intervals, soft ordering and sequences of soft real numbers, and some of their structural properties are studied. The notion of soft Lebesgue measure on the soft real numbers has been introduced. Also, a correspondence relationship has been established between the soft Lebesgue measure and the classical Lebesgue measure. Furthermore, we have studied some exciting results and relations between the soft Lebesgue measure and the Lebesgue measure of soft real sets.

The development of smart negative electrode materials with high capacitance for use in supercapacitors remains challenging. Although there have been several types of electrode materials with high capacitance used in energy storage, carbon-based materials are the most reliable electrodes due to their high conductivity, high power density and excellent stability. The most common complaint about general carbon materials is that these as-formed electrode materials can hardly ever be used as free-standing electrodes. Free-standing carbon-based electrodes are in high demand and are a passionate topic of energy storage research. Electrospun nanofibers are a potential candidate to fill this gap. However, the as-spun carbon nanofibers (ECNFs) have low capacitance and energy density on their own. To this end, several attempts have been made to improve these characteristics. In this review, we introduce negative electrode materials that have been developed. Moreover, this review places special attention to the advances of electrospun nanofiber-based negative electrode materials and their limitations. Based on the above information, we put forth a future perspective on how these limitations can be overcome to meet the demands of next-generation smart devices.

In this article, we assume that the beginning of the universe was before the Big Bang. In the beginning, all matter in the universe was combined in an infinitesimal spherical shape. This sphere was compressed to an incomprehensible value for a period, and then exploded and expanded time and space. We are referring to the negative time before the Big Bang. The evolution of the universe before the Big Bang, passing through the moment of the explosion to the end of the universe at the Big Rip, has been studied. In this article, we try to answer the questions; did the universe exist before the Big Bang? What is the origin of the universe and how did it arise? What are the stages of the evolution of the universe until the moment of the Big Rip? What is the length of time for the stages of this development?

In view of the problem of cracking easily and partial distortion of images after encryption or decryption, a novel image encryption and decryption algorithm based on Arnod Transform and fractional chaotic is proposed. To begin with, the Arnold transform is used to encrypt. So that the spatial confidence of the original image has been comprehensively disturbed. Secondly, the XOR involving the fractional order chaotic sequence is used to encrypt. The key sequence is dynamically generated to ensure the randomness and difference of key generation. When decryption is required, the first decryption is performed using the key and XOR. Then the second decryption is carried out by using the inverse Arnold transform, and finally the decrypted image is obtained. Experimental results show that the improved algorithm has achieved better performance in encryption and decryption.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

AI is extraordinarily useful technology but it is becoming increasingly powerful with rapidly growing capabilities to disrupt and harm human society. We call on international and national organizations and individuals to join forces in banning the development of superintelligent AI and introducing regulations to prevent and mitigate AI-caused harm.

The Botryosphaeriales order are best known for the diseases they cause in woody plants, as primary pathogens or latent pathogens residing in the woody tissue of asymptomatic hosts. In the first instance, Botryosphaeriales species have been identified in Venezuela using morphological de-scriptions in the 80's and 90's, and later, the mid-2000s using molecular techniques. The mor-phological descriptions of the asexual morphs were initially used for the identification of Botry-osphaeriales genera and species. Lasiodiplodia spp., (as L. theobromae) was the most isolated fungus in Venezuela within the Botryosphaeriales and has been found in more than 50% of the hosts in native and non-native plants, followed by Diplodia, Dothiorella, Fusicoccum, Lasiodiplodia, Micro-diplodia, Macrophomina, Neofusicoccum, Sphaeropsis, and Botryosphaeria, considered all of them cosmopolitan group. With molecular studies, that included DNA sequence data from multiple genes, such as the internal transcribed spacer of rDNA (ITS), translation elongation factor-1α (tef1), and β-tubulin (btub) used on the fungi isolated from woody plants, mainly trees or forest species, resulted in the presence of two families within the Botryosphaeriales order for Venezuela. Botryosphaeriaceae family with the genera: Botryosphaeria, Cophinforma, Diplodia, Lasiodiplodia and Neofusicoccum, and the Pseudofusicoccumaceae family that includes the genus Pseudofusicoccum. In Botryosphaeriaceae family was again the Lasiodiplodia genus the most predominant in most hosts, and the specie L. theobromae the most isolated in native and non-native plants; Botryosphaeria dothidea, Cophinforma atrovirens, Diplodia scrobiculata (syn. Diplodia guayanensis), Lasiodiplodia brasi-liensis, L. crassispora, L. pseudotheobromae, Neofusicoccum arbuti (syn. N. andinum), N. parvum, and N. ribis are cosmopolitan species, and they were isolated from native and non-native plants; while Pseudofusicoccum stromaticum was found in plantations non-native of Acacia mangium, E. urophylla x E. grandis, Eucalyptus urophylla, and reported exclusively in South America; Lasiodiplodia venezue-lensis has only been reported in Venezuela, from native and non-native plants. The presence, distribution, diversity, and symptoms of these fungi, mainly of the new genus, new species, and reports found in Venezuela and other parts of the world, were also reviewed.

Let $S=\left(s_1, \ldots, s_n\right)$ be a finite sequence of integers. Then $S$ is a Gilbreath sequence of length $n$, $S\in\mathbb{G}_n$, iff $s_1$ is even or odd and $s_2, \ldots, s_n$ are respectively odd or even and $\min\mathbb{K}_{\left(s_1, \ldots, s_m\right)}\leq s_{m+1}\leq\max\mathbb{K}_{\left(s_1, \ldots, s_m\right)}\forall m\in\left[\left.1, n\right)\right.$. This, applied to the order sequence of prime number $P$, defines Gilbreath polynomials and two integer sequences A347924 \cite{oeisA347924} and A347925 \cite{oeisA347925} which are used to prove that Gilbreath conjecture $GC$ is implied by $p_n-2^{n-1}\leqslant\mathcal{P}_{n-1}\left(1\right)$ where $\mathcal{P}_{n-1}\left(1\right)$ is the $n-1$-th Gilbreath polynomial at 1.

Introduction: The presence of multiple comorbidities increases the risk of all-cause mortality, but the effects of the comorbidity sequence before the baseline date on mortality remained unexplored. This study investigated the relationship between coronary heart disease (CHD), atrial fibrillation (AF) and heart failure (HF) sequence on all-cause mortality risk in type 2 diabetes mellitus. Methods: This study included patients with type 2 diabetes mellitus prescribed antidiabetic/cardiovascular medications in public hospitals of Hong Kong between January 1st, 2009 and December 31st, 2009 with follow-up until death or December 31st, 2019. Cox regression was used to identify comorbidity sequences predicting all-cause mortality in patients with different medication subgroups. Results: A total of 249291 patients (age: 66.0±12.4 years, 47.4% male) were included. At baseline, 7564, 10900 and 25589 patients had AF, HF and CHD, respectively. Over follow-up (3524±1218 days), 85870 patients died (mortality rate: 35.7 per 1000 person-years). Sulphonylurea users with CHD developed later, but insulin users with CHD developing earlier, in the disease course had lower mortality risks. Amongst insulin users with two of the three comorbidities, CHD with preceding AF (hazard ratio [HR]: 3.06, 95% CI: [2.60-3.61], p<0.001) or HF (HR: 3.84 [3.47- 4.24], p<0.001) had a higher mortality. In users of lipid-lowering agents with all three comorbidities, those with preceding AF had higher risk of mortality (AF-CHD-HF: HR: 3.22, [2.24-4.61], p<0.001; AF-HF-CHD: HR: 3.71, [2.66-5.16], p<0.001). Conclusion: The sequence of comorbidity development affects the risk of all-cause mortality to varying degrees in diabetic patients on different antidiabetic/cardiovascular medications.

Up to now, Schrödinger equation, Klein-Gordon equation (KGE) and Dirac equation are believed the fundamental equations of quantum mechanics. Schrödinger equation has a defect that there is no NKE solutions. Dirac equation has positive kinetic energy (PKE) and negative kinetic energy (NKE) branches. Both branches should have low momentum, or nonrelativistic, approximations: one is Schrödinger equation and the other is NKE Schrödinger equation. KGE has two problems: it is an equation of second time derivative, and calculated density is not definitely positive. To overcome the problems, it should be revised as PKE and NKE decoupled KGEs. The fundamental equations of quantum mechanics after the modification have at least two merits. They are of unitary in that everyone contains the first time derivative and are symmetric with respect to PKE and NKE. This reflects the symmetry of the PKE and NKE matters, as well as matter and dark matter, of our universe. The problems of one-dimensional step potentials are resolved by means of the modified fundamental equations for a nonrelativistic particle.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

The concept of using special electrical circuit design realize a "cold resistors", that is, an active resistor circuitry with lowered effective noise temperature, was first introduced about 80 years ago. Later on, various kinds of artificial resistors were applied in different research areas, such as gravitational wave detection, photo-amplifiers and quartz oscillators. Their proofs of concepts were experimentally proved. Unfortunately, the complete theory was not found even though several attempts had been published, sometimes with errors. In this paper, we describe a correct and complete circuit theoretical model of a cold resistor system. The results are confirmed by computer simulations. A design tools for this circuit is also shown.

The gravitational charge should be the energy instead of mass. This modification will lead to some different results and the experiments to test are also presented. Especially, we propose a scheme to achieve the negative energy and gravitational repulsive force in the lab.

Background: We attempted to find if there were gender differences in different types of Negative life events and Suicidal ideation among Chinese adolescents, then analyze the relationship between different types of Negative life events and Suicidal ideation among these young students. Methods: Based on the data from 6 middle-schools and 3 universities in 3 cities of Western China, the gender difference in different types of Negative life events and Suicidal ideation and their related factors were investigated and analyzed in the study. Results: Gender differences were found during different types of Negative life events and Suicidal ideation; Negative life events could predict the intensity of Suicidal ideation by gender, to some specific types. Conclusions: Negative life events were proved to be risk factors of adolescents’ Suicidal ideation regardless of different gender stereotypes, but the specific classification of negative life events which had significant impact on adolescents’ Suicidal ideation also indicated significant gender divisions. For males, negative life events of punishment and adaptation had a significant and boosting impact on their Suicidal ideation, the higher the scores of punishment and adaptation negative life events had, the greater intensity of male adolescents were to have Suicidal ideation. Thus, the above two types of negative life events may be the main stressors predicting male adolescents' Suicidal ideation; For females, in addition to punishment, other types of negative life events all had significant impacts on their Suicidal ideation, which can be treated as the main stressors to trigger female adolescents' Suicidal ideation; Additionally, parents’ marital status of remarriage and divorce were proved to be significant indicators to adolescents’ Suicidal ideation, the age variable was proved to be strongly correlated with Suicidal ideation among female adolescents.

Microalgae are a source of carotenoids, phycocyanin, phenol, amino acids, polyunsaturated fatty acids, sulfated polysaccharides, pigments, and other bioactive molecules with antimicrobial, antioxidant, antiviral, antitumor, anti-inflammatory, and fat-burning properties. The increasing incidence of infectious processes, including tuberculosis, caused by antimicrobial resistant strains of microorganisms necessitates the search for alternative sources of compounds with antimicrobial activity, including microalgae. In this study, the antimicrobial properties of marine and freshwater microalgae extracts were evaluated against Gram-positive (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa), Mycobacterium tuberculosis strain H37Rv and Mycobacterium smegmatis. Water, dimethyl sulfoxide, and ethanol were used as extractants. The obtained microalgae extract exhibited cytotoxicity against splenocytes and, to a lesser extent, against peritoneal macrophages of CBA mice. The bacteriostatic effect of the microalgae extracts against bacteria and mycobacteria was demonstrated by MTT test. In addition, activation of bacterial and mycobacterial growth was observed in a number of cases with high levels of microalgae extracts in the medium. In an expression model of tuberculosis in mice, a decrease in mycobacterial load in the lungs and spleen was observed. Thus, microalgae have moderate to weak antimicrobial activity.

In this paper, we present sums and partial sums of Horadam sequences via generating functions which extends a recent result of Prodinger.

Predictive processes and numerous cognitive, motor, and social skills depend heavily on sequence and statistical learning. The visuomotor Serial Reaction Time Task (SRTT) can measure these fundamental cognitive processes. In this review, we sought to answer whether repetitive transcranial magnetic stimulation (rTMS) is suitable for modulating visuomotor sequence learning and which factors mediate its efficacy. We systematically analyzed the eligible records (n = 17) that attempted to modulate the performance of the SRTT with rTMS. The purpose of the analysis was to determine how the following factors affected SRTT performance: (1) stimulated brain areas, (2) rTMS protocols, (3) stimulated hemisphere, (4) timing of the stimulation, (5) SRTT sequence properties, and (6) other methodological features. The primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) were found to be the most promising stimulation targets. Low-frequency protocols over the M1 usually weaken performance, but the results are less consistent for the DLPFC. These inconsistencies (at least in part) may be due to the current frequency-based heuristics of rTMS effects developed for explaining local stimulation effects in the motor cortex. Although this review cannot provide an ultimate answer about the optimal stimulation and task parameters, it comprehensively discusses the behavioral effects of six factors that are crucial for designing future studies to modulate sequence learning with rTMS. Moreover, we conclude that synergistically combining functional neuroimaging with rTMS could adequately link the rTMS-induced network effects with the behavioral findings that are crucial to develop a unified cognitive model of visuomotor sequence learning.

Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that in turn promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report, we analyzed clinical dataset of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We thus developed a new therapeutic approach to inhibit EGFR and hypoxia by combination of metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic, this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.

The Golden ratio is an irrational number that has a tendency to appear in many different scientific and artistic fields. It may be found in natural phenomena across a vast range of length scales; from galactic to atomic. In this review, the mathematical properties of the Golden ratio are discussed before exploring where in nature it has been found; beginning at astronomical scales and progressing to smaller lengths, until reaching those of atomic and quantum physics. In making such a tour across length scales, it is illustrated just how prevalent this single number is within the natural universe.

The chloroplast genome is conservative and stable, which can be employed to resolve genotypes. Currently, published nuclear sequences and molecular markers failed to differentiate the species from taxa robustly, including Machilus leptophylla, Hanceola exserta, Rubus bambusarum, and Rubus henryi. In this study, the four chloroplast genomes were characterized, and then their simple sequence repeats (SSRs) and phylogenetic positions were analyzed. The results demonstrated the four chloroplast genomes consisted of 152.624 kb, 153.296kb, 156.309 kb, and 158.953 kb in length, involving 124, 130, 129, and 131 genes, respectively. Moreover, the chloroplast genomes contained typical four regions. Six classes of SSR were identified from the four chloroplast genomes, in which mononucleotide was the class with the most members. The types of the repeats were various within individual classes of SSR. Phylogenetic trees indicated that M. leptophylla was clustered with M. yunnanensis, and H. exserta was confirmed under family Ocimeae. Additionally, R. bambusarum and R. henryi were clustered together, whereas they did not belong to the same species due to the differing SSR features. This research would provide evidence for resolving the species and contributed new genetic information for further study.

To explore the impact of parenting styles on the perception of campus non-physical bullying, 492 students in upper elementary school grades were surveyed by using the Delaware Bullying Victimization Scale, the Negative Coping Style Scale, the Negative Affect Scale, and the Egna Minnen Beträffende Uppfostran Questionnaire. The questionnaire survey was conducted in the fifth and sixth grades of eight primary schools in Zhejiang province. The results showed that cyberbullying was not significantly related to an anxious parenting style, but negative affect experiences, negative coping styles, negative family parenting styles, and the perception of campus non-physical bullying were all positively correlated with each other (p < 0.05). The refusal parenting style was shown to be an important factor that affected students’ perception of campus non-physical bullying; it was observed to directly affect students’ perception of campus non-physical bullying and indirectly affect students’ perception of campus non-physical bullying by influencing negative affect experiences and negative coping styles. In conclusion, negative affect experiences and negative coping styles had a chain-like mediating effect between the refusal parenting style and students’ perception of campus verbal bullying. Moreover, negative affect experiences had a partial mediating effect between the refusal parenting style and students’ perceptions of campus cyberbullying, relationship bullying, and non-physical bullying total scores. Implications and suggestions based on these results are also discussed.

COVID-19 may not be a ‘youth disease’ but nevertheless impacts the life of young people dramatically, loneliness and negative mood being an unexpected additional pandemic. Many young people rely on social media for their feeling of connectedness with others. However, social media are suggested to have many negative effects on people’s anxiety. Instead of self-disclosing to others, design may develop alternatives to employ social robots for self-disclosure. In a follow-up on Duan et al. (2021), we report on a lab experiment of self-disclosing negative emotions to a social-media group as compared to writing a conventional diary journal or to talk to an AI-driven social robot after negative mood induction (i.e. viewing shocking earthquake footage). Participants benefitted the most from talking to a robot rather than from writing a journal page or sharing their feelings on social media. Self-disclosure on social media or writing a journal page did not differ significantly. In the design of interventions for mental well-being, human helpers thus far took center stage. Based on our results, we propose design alternatives for an empathic smart-home, featuring social robots and chatbots for alleviating stress and anxiety: a social-media interference chatbot, smart watch plus speaker, and a mirror for self-reflection.

Despite the long history of using protein sequences to infer the tree of life the potential for different parts of protein structures to retain historical signal remains unclear. We propose that it might be possible to improve analyses of phylogenomic datasets by incorporating information about protein structure; we test this idea using the position of the root of Metazoa (animals) as a model system. We examined the distribution of “strongly decisive” sites (alignment positions that support a specific tree topology) in a dataset comprising &gt;1,500 proteins and almost 100 taxa. The proportion of each class of strongly decisive sites in different structural environments was very sensitive to the model used to analyze the data when a limited number of taxa were used but they were stable when taxa were added. As long as enough taxa were analyzed, sites in all structural environments supported the same topology (ctenophores sister to other animals) regardless of whether standard tree searches or decisive sites were used to select the optimal tree. However, the use of decisive sites revealed a difference between the support for minority topologies for sites in different structural environments; buried sites and sites in sheet and coil environments exhibited equal support for the minority topologies whereas solvent exposed and helix sites had unequal numbers of sites supporting the minority topologies. Given the plausible trees equal support for minority topologies is consistent with discordance among gene trees, making it possible the relatively slowly evolving buried (and sheet and coil) sites are giving an accurate picture of the true species tree as well as the amount of conflict among gene trees. Alternatively, the apparent support could reflect currently uncharacterized processes of molecular evolution. Regardless, it is clear that analyses of the deepest branches in the animal tree of life using sites in different structural environments are associated with a subtle data type effect that results in distinct phylogenetic signals.

Negative work behavior (NWB) threatens employee well-being. There are numerous constructs that reflect NWBs, such as bullying, aggression, and discrimination and they are often examined in isolation of each other, limiting scientific integration of these studies. We aim to contribute to this research field by developing a diagnostic tool with content validity on the full spectrum of NWBs. First, we provide a full description of how we tapped and organized content from 44 existing NWB measurement instruments and 48 studies. Second, we discussed our results with experts (N = 3) in this research field to check for missing studies and to discuss our integration results. This two-stage process yielded a questionnaire measuring physical, material, psychological, sociocultural, and digital NWB. Furthermore, the questions include a range of potential actors of NWB, namely internal (employees, managers) and external actors (clients, customers, public, family members) at work and their roles (i.e., target, perpetrator, perpetrator's assistant, target's defender, outsider, and witness of NWBs). Finally, the questionnaire measures what type of harm is experienced (i.e., bodily, material, mental, and social harm).

It is quite easy to stochastically distort an original count variable to obtain a new count variable with relatively more variability than in the original variable. Many popular overdispersion models (variance greater than mean) can indeed be obtained by mixtures, compounding or randomlystopped sums. There is no analogous stochastic mechanism for the construction of underdispersed count variables (variance less than mean), starting from an original count distribution of interest. This work proposes a generic method to stochastically distort an original count variable to obtain a new count variable with relatively less variability than in the original variable. The proposed mechanism, termed condensation, attracts probability masses from the quantiles in the tails of the original distribution and redirect them toward quantiles around the expected value. If the original distribution can be simulated, then the simulation of variates from a condensed distribution is straightforward. Moreover, condensed distributions have a simple mean-parametrization, a characteristic useful in a count regression context. An application to the negative binomial distribution resulted in a distribution allowing under, equi and overdispersion. In addition to graphical insights, fields of applications of special cases of condensed Poisson and condensed negative binomial distributions were pointed out as an indication of the potential of condensation for a flexible analysis of count data

To realize structural vibration control,a two parameters H2 optimization design was proposed to optimize the tuning ratio and damping ratio for electromagnetic tuned mass damper (EMTMD). The control effect of this two parameters optimization design is better than that of classical tuned mass damper (TMD).For this two parameters optimization,the most important thing is that the inductance of the coil can be set very small and the external load resistance can be positive ,which can avoid the use of complex negative impedance circuit. If Ref.[6] were designed according to the H2 optimization of two parameters, the EMTMD can be used for multi-modal vibration control of structures without connecting negative inductance and negative resistance spontaneously.

Because of an often complicated and difficult-to-access care system, help-seeking for people with suspected dementia can be stressful. Difficulty in help-seeking may contribute to carer burden, in addition to other known stressors in dementia care. This study examined the relationship between perceived help-seeking difficulty and carer burden, and the barriers contributing to perceived difficulty. We interviewed 110 carers accessing a community-based dementia assessment service for suspected dementia of a family member for their perceived difficulty, delays, and barriers in help-seeking, and carers burden in terms of role strain, self-criticism, and negative emotions. Linear regression models showed that perceived help-seeking difficulty is associated with carer self-criticism, while carer role strain and negative emotions are associated with symptom severity of the person with dementia but not help-seeking difficulty. Inadequate knowledge about symptoms, service accessibility, and affordability together explained more than half of the variance in perceived help-seeking difficulty (Nagelkerke R2 = .56). Public awareness about symptoms, support in navigating service, and financial support may reduce perceived difficulty in help-seeking, which in turn may reduce carer self-criticism during the early course of illness.

In 1937,German mathematician L.Collatz proposed a conjeture:for any positive integer,if it is even,divide it by 2;if it is odd,multiply it by 3 and 1 to get an even number;keep going on and on, the final result is 1.This paper gives a sequence classification of odd numbers,and gives 1-1 mapping of odd numbers and odd number sequences,and uses these results to give a proof of this conjecture.

There are unsolved problems related to inflation, gravity, dark matter, dark energy, missing antimatter, and the birth of the universe. Some of them can be better answered by assuming the existence of aether and hypoatoms. Both were created during the inflation in the very early universe. While aether forms vacuum, hypoatoms, composed of both matter and antimatter and believed to be neutrinos, form all observable matter. In vacuum, aether exists between the particle-antiparticle dark matter form and the dark energy form in a dynamic equilibrium: A + A-bar = gamma + gamma. The same reaction stabilizes hypoatoms and generates a 3-dimensional sink flow of aether that causes gravity. Based on the hypoatom structure, the singularity does not exist inside a black hole; the core of the black hole is a hypoatom star or neutrino star. By gaining enough mass, ca. 3 X 10²² M_sun, to exceed neutrino degeneracy pressure, the black hole collapses or annihilates into the singularity, thus turning itself into a white hole or a Big Bang. The universe is anisotropic. Its center, or where the Big Bang happened, is at 0.66^+0.03_-0.01 times the radius of the observable universe at Galactic coordinates (l, b) = (286⁺¹⁰_-10, -43⁺⁷_-6). If we look from the Local Group to the center of the universe, the universe is rotating clockwise.

We report on the isolation of the previously uncultured Neocallimastigomycota SK4 lineage by two independent research groups from a wild aoudad sheep rumen sample (Texas, USA) and an alpaca fecal sample (Baden-Württemberg, Germany). Isolates from both locations showed near identical morphological and microscopic features, forming medium-sized white filamentous colonies with a white center of sporangia on agar roll tubes and a heavy biofilm in liquid media. Microscopic analysis revealed monocentric thalli, and spherical polyflagellated zoospores with 7–20 flagella. Zoospore release occurred through an apical pore as well as by sporangial wall rupturing, a duality that is unique amongst described AGF strains. Isolates were capable of growing on a wide range of mono-, oligo-, and polysaccharides substrates. Phylogenetic assessment based on the D1-D2 large rRNA subunit (D1-D2 LSU) and internal transcribed spacer-1 (ITS-1) regions demonstrated high sequence identity (minimum identity of 99.07% and 96.96%, respectively) between all isolates; but low sequence identity (92.4% and 86.7%, respectively) to their closest cultured relatives. D1-D2 LSU phylogenetic trees grouped the isolates as a new monophyletic clade within the Orpinomyces-Neocallimastix-Pecoramyces-Feramyces-Ghazallamyces supragenus group. D1-D2 LSU and ITS-1 sequences from the obtained isolates were either identical, or displayed extremely high sequence similarity to sequences recovered from the same Aoudad sheep sample on which isolation was conducted, as well as several sequences recovered from domestic sheep and few other herbivores. Interestingly, members of the SK4 clade seem to be encountered in animals grazing on summer pasture. We hence propose accommodating these novel isolates in a new genus, Aestipascuomyces (derived from the Latin word for “summer pasture”), and a new species, A. dupliciliberatus. The type strain is Aestipascuomyces dupliciliberatus strain R4.

Today, air quality is one of the global concerns that governments are facing. One of the main air pollutants is the particulate matter (PM) that affects human health. This article presents the modeling of a purification system by means of negative air ions (NAIs) for air pollutant removal, using computational intelligence methods. The system uses a high voltage booster output to ionize air molecules from stainless steel electrodes; its particle-capturing efficiency reaches up to 97%. With two devices (5 x 2 x 2.5 cm), 2 trillion negative ions are produced per second, and the particulate matter (PM 2.5) can be reduced from 999 to 0 mg / m3 in a period of approximately 5 to 7 minutes (in a 40 x 40 x 40 cm acrylic chamber). This negative ion generator is a viable and sustainable alternative to reduce polluting emissions, with beneficial effects on human health.

Background: We previously found that QNBC tumors are more frequent in African Americans compared to TNBC tumors. To characterize this subtype further, we sought to determine the miRNA-mRNA profile in QNBC patients based on race. Methods: Both miRNA and mRNA expression data were analyzed from TCGA and validated using datasets from the METABRIC, TCGA proteomic, and survival analysis by KMPLOT. Results: miRNA-mRNAs which include FOXA1 and MYC (mir-17/20a targets); GATA3 and CCNG2 (mir-135b targets); CDKN2A, CDK6, and B7-H3 (mir-29c targets); and RUNX3, KLF5, IL1-β, and CTNNB1 (mir-375 targets) were correlated with basal-like and immune subtypes in QNBC patients and associated with a worse survival. Conclusion: Thus, QNBC tumors have an altered gene signature implicated in racial disparity and poor survival.

Ribosomes are macromolecular complexes important to protein translation, and thus, essential to life. Comprising an ensemble of ribosomal proteins and RNA molecules, ribosomes are conserved in structure and function across all domains of life, but recent structural studies have revealed differentiated structures of ribosomes from bacterial, archaea and eukaryotes. Additionally, unique ribosomal protein mass fingerprints have been found for individual species; thereby, indicating that ribosomes are differentiated in structure amongst different species. Given that structure defines function, differentiated function likely exists amongst ribosomes of different species, which could manifest as differences in translation efficiency that could impact on cell growth rate. But ribosomal proteins also hold phylogenetic significance in informing the evolutionary trajectory of each species. Such ribosomal proteins are thus not highly conserved and offers sufficient sequence space for the evolution of differentiated structure and function in different species. Using ribosomal proteins that hold phylogenetic significance as templates, this study sought to understand the mutational and conformational limits that define functional ribosomes. Specifically, ribosomal proteins in Bacillus subtilis that hold phylogenetic cues would be mutated through error-prone polymerase chain reaction to generate variants that are subsequently transformed into Escherichia coli. To help assess the functional properties of the heterologous ribosomal proteins, endogenous ribosomal protein genes would be inactivated by multiplex CRISPR interference. Since variants in ribosomal proteins would likely impact on ribosome function and translation efficiency, live/dead screening on LB agar would be effective as a preliminary screen for functional mutants. These mutants would subsequently be inoculated into liquid LB medium in 96 well plates to quantify relative growth rates between different strains harbouring different heterologous variants of ribosomal proteins. Plasmids containing different ribosomal protein mutants would be extracted from each functional strain and subjected to Sanger sequencing for determining the specific mutations involved. Collection of such mutations would provide a comprehensive mutational map that define the limits of ribosomal protein sequence space important to ribosome function. Furthermore, biochemical isolation of ribosomal proteins and their structural characterization by X-ray crystallography or cryo-electron microscopy would further illuminate the structural significance of each mutation on ribosome structure and function; thereby, elucidating the structural tolerance space for functional ribosomes. Overall, generating a diverse pool of mutant ribosomal proteins in viability assays followed by sequencing and structural characterization would help define the mutational and conformational limits of a functional and efficient ribosome.

In the context of all-digital radar systems, phase-modulated continuous wave (PMCW) based on pseudorandom binary sequences (PRBSs) appears a prominent candidate modulation scheme for applications such as autonomous driving. Among the reasons for that are its simplified transmitter architecture and lower linearity requirements, e.g., compared to orthogonal-frequency division multiplexing radars, as well as its high velocity unambiguity and multiple-input multiple-output operation capability that are characteristic of digital radars. For appropriate operation of a PMCW radar, choosing a PRBS whose periodic autocorrelation function (PACF) has low sidelobes and high robustness to Doppler shifts is paramount. In this sense, this article performs an analysis of Doppler shift tolerance of the PACFs of typically adopted PRBSs in PMCW radar systems supported by simulation and measurement results. To accurately measure the Doppler-shift-induced degradation of PACFs, peak power loss ratio (PPLR), peak sidelobe level ratio (PSLR), and integrated-sidelobe level ratio (ISLR) were used as metrics. Furthermore, to account for effects on targets whose ranges are not multiples of the range resolution, oversampled PACFs are analyzed.

The aim was to study alterations of bacterial communities in patients undergoing hip or knee arthroplasty to assess the impact of chlorhexidine gluconate soap decolonisation and systemic antibiotic prophylaxis. A Swedish multicentre, prospective collection of samples obtained from elective arthroplasty patients (n=83) by swabbing anterior nares, skin sites in the groin and the site of planned surgery, before and after arthroplasty surgery, was analysed by 16S rRNA (V3-V4) gene sequencing and a complementary targeted tuf gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial (p=0.04) and staphylococcal (p=0.03) groin communities after arthroplasty surgery with significant reductions in relative Corynebacterium (p=0.001) abundance and S. hominis (p=0.01) relative staphylococcal abundance. In nares, significant reductions occurred for S. hominis (p=0.02), S. haemolyticus (p=0.02), and S. pasteuri (p=0.003) relative to other staphylococci. S. aureus colonised 35% of anterior nares before and 26% after arthroplasty surgery. S. epidermidis was the most abundant staphylococcal species at all sampling sites. No bacterial genus or staphylococcal species increased significantly after arthroplasty surgery. Application of a targeted tuf gene sequencing approach provided auxiliary staphylococcal community profiles and allowed species-level characterisation directly from low biomass clinical samples.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

Foot and Mouth Disease (FMD) is a viral disease, widespread and highly contagious affecting mainly cloven-hoofed domestic and wild animals. FMD can lead to high economic losses due to reduction in animals’ production such as drop of milk production, loss of body weight and high mortality rate in young ruminants. Sixteen nasal swabs and epithelial tissues were collected from animals showing typical clinical signs of FMD during the last FMD outbreak in Libya in 2018-2019. Blood samples, swabs and epithelial tissues impressions on Flinders Technology Associates (FTA) cards were shipped to the FMD Reference laboratory in Brescia, Italy, and tested for the detection of FMD viruses. Nucleic acids were extracted from the FTA cards and molecular testing of the examined FTA cards confirmed that the FMD virus circulating in Libya was serotype O. Sequencing analysis of the FMD virus VP1 gene confirmed that FMD virus strain was serotype O/East Africa 3 (O/EA-3) topotype. The phylogenetic of the VP-1 gene of the FMD virus showed very high nucleotide identity (99.8%) between the virus circulating in Libya and the Algerian FMD virus strains isolated in Algeria on 2018 and 2019.

Fixed offshore wind turbines continue to be developed for high latitude areas where not only wind and wave loads need to be considered, but also moving sea ice. Current rules and regulations for the design of fixed offshore structures in ice-covered waters do not adequately consider effects of ice loading and its stochastic nature on fatigue life of the structure. Ice crushing on such structures results in ice-induced vibrations, which can be represented by loading the structure using a variable-amplitude loading (VAL) sequence. Typical offshore load spectra are developed for wave and wind loading. Thus, a combined VAL spectrum is developed for wind, wave, and ice action. To this goal, numerical models are used to simulate the dynamic ice-, wind-, and wave-structure interaction. The stress time-history at an exemplarily selected critical point in an offshore wind energy monopile support structure is extracted from the model and translated into a VAL sequence, which can then be used as a loading sequence for the fatigue assessment or fatigue testing of welded joints of offshore wind turbine support structures. This study presents the approach to determine combined load spectra and standardized time series for wind, wave, and ice action.

The effect of the negative effective mass emerging in the gravitating core-spring-shell system is considered. The effect appears when the entire system is exerted to the external harmonic force and the frequency of external force approaches to the critical frequency from above. The critical frequency depends on the density of the self-gravitating system only. The scaling law predicting the value of for condensed phases is derived. The generalization of the effect for the Coulomb-like forces is reported

Abstract: Discussed is an expansion of SRT to fourth-order of space-time including any velocities and possible negative kinetic energies by real rest mass in analogy of the model amplitude of enforced damped oscillation. This paper serves an introduction to developed SRT including superluminar translating velocities without tachyons or imaginary restmass. Focused is on those parts, which develop the elaborated lorentz-transformations. Discussed are the problems of this theory.

Learning programming is a complex and challenging task for many students. It in-volves both understanding theoretical concepts and acquiring practical skills. Hence, analyzing learners’ data from online learning environments alone fails to capture the full breadth of stu-dents’ actions if part of their learning process takes place elsewhere. Moreover, existing studies on learning analytics applied to programming education have mainly relied on frequency analysis to classify students according to their approach to programming or to predict academic achieve-ment. However, frequency analysis provides limited insights into the individual time-related characteristics of the learning process. The current study examines students’ strategies when learning programming, combining data from the learning management system and from an au-tomated assessment tool. To gain an in-depth understanding of students’ learning process as well as of the types of learners, we used learning analytics methods that account for the temporal order of learning actions. Our results show that students have special preferences for specific learning resources when learning programming, namely slides that support search, and copy and paste. We also found that videos are relatively less consumed by students, especially while working on programming assignments. Lastly, students resort to course forums to seek help only when they struggle.

We report the negative effective mass metamaterials based on the electro-mechanical coupling exploiting plasma oscillations of a free electron gas. The negative mass appears as a result of vibration of a metallic particle with a frequency of ω which is close the frequency of the plasma oscillations of the electron gas m_2 relatively to the ionic lattice m_1. The plasma oscillations are represented with the elastic spring k_2=ω_p^2 m_2, where ω_p is the plasma frequency. Thus, the metallic particle vibrated with the external frequency ω is described by the effective mass m_eff=m_1+(m_2 ω_p^2)/(ω_p^2-ω^2 ) , which is negative when the frequency ω approaches ω_p from above. The idea is exemplified with two conducting metals, namely Au and Li.

Due to the rapid developments in aquaculture industry, Artemia franciscana, originally an American species, has been intentionally introduced to the Eurasia, Africa and Australia. In the present study, we used a partial sequence of the mitochondrial DNA Cytochrome Oxidase subunit I (mt-DNA COI) gene and genomic fingerprinting by Inter-Simple Sequence Repeats (ISSRs) to determine the genetic variability and population structure of Artemia populations (indigenous and introduced) from 14 different geographical locations in Western Asia. Based on the haplotype spanning network, Artemia urmiana has exhibited higher genetic variation than native parthenogenetic populations. Although A. urmiana represented a completely private haplotype distribution, no apparent genetic structure was recognized among the native parthenogenetic and invasive A. franciscana populations. Our ISSR findings have documented that despite invasive populations have lower variation than source population in Great Salt Lake (Utah, USA), they have significantly revealed higher genetic variability compare to the native populations in Western Asia. According to the ISSR results, the native populations were not fully differentiated by the PCoA analysis, but the exotic A. franciscana populations were geographically divided in four genetic groups. We believe that during the colonization, invasive populations have experienced substantial genetic divergences, under new ecological conditions in the non-indigenous regions.

The negative binomial regression model (NBRM) is a generalized linear model which relaxes the restrictive assumption by the Poisson regression model when the variance is equal to the mean. The estimation of the parameters of the NBRM is obtained using the maximum likelihood (ML) method. Maximum likelihood estimator becomes unstable when the explanatory variables are linearly dependent, a situation known as multicollinearity. Based on this, we developed a new estimator called modified jackknifed Negative Binomial Kibria-Lukman (MJNBKL) estimator for the radiation of multicollinearity in NBRM using four different biasing (shrinkage) parameters. We establish superiority condition for MJNBKL estimator over the ones. The performance MJNBKL estimator was ascertained by comparing it with the existing ones through a Monte Carlo simulation study and two real life application datasets. The results of the simulation and real life application show that MJNBKL estimator outperformed the other estimators compared with by having the smallest MSE across all sample sizes and for different levels of correlation for the four biasing parameters used and the third biasing parameter is the optimal shrinkage parameter with the lowest MSE.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

Cytosine (C) to uracil (U) RNA editing is one of the most important post-transcriptional processes, however exploring C-to-U editing events efficiently within the crop mitochondrial genome remains a challenge. An improving predictive RNA editor for crop mitochondrial genomes, iPReditor-CMG, was proposed, which was based on SVM, three common crop mitochondrial genomes and self-sequenced tobacco mitochondrial ATPase. After multi-combination feature extracting, high-dimension feature screening and multi-test independent predicting, the results showed that the average accuracy of intraspecific prediction was 0.85, and the highest value even up to 0.91, which outperformed the previous reference models. While the prediction accuracies were 0.78 between dicotyledons and no more than 0.56 between dicotyledons and monocotyledons, implying a possible similarity in C-to-U editing mechanisms among close relatives. The best model was finally identified with an independent test accuracy of 0.91 and an area under the curve of 0.88, and further suggested that five unreported feature sequences TGACA, ACAAC, GTAGA, CCGTT and TAACA were closely associated with the editing phenomenon. Multiple evaluation findings supported that the iPReditor-CMG could be effectively applied to predict crop mitochondrial editing sites, which may contribute to insight into their recognition mechanisms and even other post-transcriptional events in crop mitochondria.

The Sulfur Dioxide (SO2) compound is a primary environmental pollutant worldwide, whereas elemental Sulfur (S) is a global commodity possessing a variety of industrial as well as commercial functions. The chemical relationship between poisonous SO2 and commercially viable elemental S has motivated this investigation using Density Functional Theory calculation of the relative transition state barriers for the 2-step Dehydro-sulfurization oxidation-reduction reaction. Additionally, doubly-charged nanoscale platelet Molybdenum Disulfide (MoS2), Armchair (6,6) Carbon Nanotube, 28-atom Graphene nanoflake (GR-28), and Fullerene C-60 are utilized as catalysts. The optimal heterogeneous and homogeneous catalysis pathways of the 2-step oxidation-reduction from SO2 to elemental S are further inspired by the biomimicry of the honeybee species multi-step bio-catalysis of pollen conversion to organic honey. Potential applications include environmental depollution, the mining of elemental sulfur, and the functionalization of novel technologies such as the recently patented aerial and amphibious Lynchpin TM drones.

The objective of this study is to investigate whether the sequence length of HIV-1 increases over time. A longitudinal analysis of full-length coding region sequences (FLs) in an outbreak of HIV-1 infection among patients with hemophilia and local controls identified as infected with the Korean subclade B of HIV-1 (KSB). Genes amplified by overlapping RT-PCR or nested PCR were subjected to direct sequencing. In total, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Non-KSB sequences were retrieved from the Los Alamos National Laboratory HIV Database. Phylogenetic analysis indicated that within KSB, 2 FLs from plasma donors O and P comprised two clusters together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis for the KSB of HIV-1 revealed signature nucleotide residues at 1.05%, compared with local controls. Additionally, in-depth FLs sequence analysis over 30 years in KSB indicates that the KSB FL significantly increases over time before combined antiretroviral therapy (cART) and decreases on cART. Furthermore, the increase in FLs over time significantly occurred in the subtypes B, C and G, but, there was no increase in the subtypes D, A, and F1. Consequently, subtypes F1 and D had the shortest sequence length. Our analysis was extended to compare HIV-1 with HIV-2 and SIVs. Essentially, the longer the sequence length (SIVsm > HIV-2 > SIVcpz > HIV-1), the longer the survival period. The increase in the length of the HIV-1 sequence over time suggests that it might be an evolutionary direction toward attenuated pathogenicity.

We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two variable models, where, , is Newton’s constant, and, , increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/ zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.

It is urgent to find new antibiotic classes to replenish the empty development pipeline of antibiotics. Recently, pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have been identified as a new broad spectrum antibiotic class with activity against Gram-negative bacteria. The active imine moiety of the reported lead pyrrolobenzodiazepine compounds was replaced with amide to obtain the non-DNA binding and non-cytotoxic dilactam analogues to further understand the structure activity relationship and improve the safety potential of this class. The synthesized compounds were tested against panels of multidrug resistant Gram-positive and Gram-negative bacteria, including WHO priority pathogens. Minimum inhibitory concentrations for the dilactam analogues ranged from 4 – 32 mg/L for MDR Gram-positive bacteria, compared to 0.03 to 2 mg/L for the corresponding imine analogues while they were found to be inactive against MDR Gram-negative bacteria, with an MIC &gt;32 mg/L, compared to an MIC of 0.5 to 32 mg/L. A molecular modelling study suggests the lack of imine functionality also affects the interaction of PBDs with DNA gyrase. This study suggests the presence of N10-C11 imine moiety is crucial for broad spectrum activity of pyrrolobenzodiazepines.

The genus Fusarium includes several agronomically important and toxin-producing species, that are worldwide distributed and can cause a wide range of diseases. Crown and stalk rots and grain infections are among the most severe symptoms that Fusarium spp. can cause on maize. The disease development usually occurs during germination, but it may also affect the later phases of plant growth. The purpose of this study was to investigate the diversity and the patho-genicity of 41 isolates recovered from symptomatic seedlings collected in Northern Italy, and from seeds with five different geographical origins during 2019 and 2020. The pathogenicity was tested and confirmed on 23 isolates causing rotting on maize seedlings. A multi-locus phylogeny analysis, based on four genomic loci (tef1-α, rpb2, calm and tub2), was performed for 23 repre-sentative isolates. Representative isolates were identified as species belonging to three species complexes (SC). Fusarium verticillioides and F. annulatum in the F. fujikuroi SC. Fusarium commune was identified in the F. nisikadoi SC, and three different lineages were found in the Fusarium ox-ysporum SC. This study reports F. annulatum, and two lineages of the Fusarium oxysporum SC as maize pathogens for the first time in Italy.

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs’ promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1α, IL-2, IL-4, GM-CSF, TNF-α, IFN-α and IFN-α were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO “burst” and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF – α and IFN – γ were found. Simultaneously, the decrease of pro – inflammatory cytokine IFN-α and the differentially increase of IL-1α, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

This joint experimental-theoretical work focuses on molecular and photophysical properties of the spiropyran-containing amphiphilic molecule in organic and aqueous solutions. Being dissolved in tested organic solvents, the system demonstrates positive photochromism, i.e. upon UV stimulus the colorless spiropyran form is transformed into colorful merocyanine isomer. However, aqueous solution of the amphiphile possesses a negative photochromism: the orange-red merocyanine form turns to be thermodynamically more stable in water, and both UV and vis stimuli lead to the partial or complete photobleaching of the solution. The explanation of this phenomenon is given on the basis of density functional theory calculations and classical modeling including thermodynamic integration. The simulations reveal that stabilization of merocyanine in water proceeds with the energy of ca. 70 kJ mol−1, and that the Helmholtz free energy of hydration of merocyanine form is 100 kJ mol−1 lower as compared to the behavior of SP isomer in water. The explanation of such a difference lies in the molecular properties of the merocyanine: after ring-opening reaction this molecule transforms into a zwitterionic form, as evidenced by the electrostatic potential plotted around the opened form. The presence of three charged groups on the periphery of a flat conjugated backbone stimulates the self-assembly of merocyanine molecules in water, ending up with the formation of elongated associates with stack-like building blocks, as shown in molecular dynamics simulations of the aqueous solution with the concentration above critical micelle concentration. Our quantitative evaluation of the hydrophilicity switching in spiropyran/merocyanine containing surfactants may prompt the search for new systems, including colloidal and polymeric ones, aiming at remote tuning of their morphology, which could give new promising shapes and patterns for the needs of modern nanotechnology.

Traditional dry fermented meat products are obtained artisanally in many countries, where they represent a gastronomic heritage well distinguished from industrial counterparts. This food category is most often obtained from red meat, a food commodity that is under attack because of evidences of increased risk of cancer and degenerative diseases with high consumption. However, traditional fermented meat products are intended for moderate consumption and gastronomic experience and, as such, their production must be continued also to safeguard culture and economy of the geographical areas of origin. In this review, the main risks attributed to these products are considered and how these risks are minimized by following precise production norms, respectful of the ancient manufacturing processes is described. Moreover, results obtained in studies reporting use of autochthonous microbial cultures of lactic acid bacteria (LAB), coagulase negative staphylococci (CNS), Debaryomyces hansenii and Penicillium nalgiovense to improve safety and quality of traditional fermented meats are summarized. The role of these products as a source of microorganisms that can be beneficial to the host are also considered. From the results of the studies reviewed here it appears that the development of autochthonous cultures for these foods ensure safety and stabilize sensory characteristics with possibility to be extended to the large variety of traditional productions.

The genus Vigna is penta-tropical having more than 200 species with many desirable economically important traits. The aim of study was to validate the in-silico polymorphism of whole genome sequence developed mungbean specific SSR markers and their transferability among the different Vigna species. The present study utilized a set of 200 SSR markers developed from whole genome sequence of mungbean and validated using a diversity panel of 25 accessions which belongs to 13 Vigna species. Out of 200 SSR markers, 130 markers (65%) were polymorphic across the various Vigna species and the number of alleles amplified varied between 7 to24. The SSR markers showed more than 90 percent transferability across the different Vigna species accessions. Based on allelic data, the 25 Vigna accessions grouped into three clusters based upon the unweighted pair group method with arithmetic mean (UPGMA) phylogenetic tree. The principal co-ordinates analysis (PCA) biplot graph and UPGMA based neighbor joining clustering diagram showed similar pattern of Vigna accessions distribution. The population structure assessment has grouped the cultivated and wild species accessions into two sub-population. The estimated marker parameters such as polymorphic information content (0.09 – 0.84), marker index (0.091 – 3.342) and effective multiplex ratio (1.0 – 4.0) suggested their adequacy in several genetic studies such as parental selection, hybrid testing, genetic mapping and marker aided breeding programmes for genetic enhancement of species belonging to the Vigna genus.

Quantitative polymerase chain reaction (qPCR) has emerged as an important bioanalytical method for assessing the pharmacokinetics of human cell-based medicinal products after xenotransplantation into immunodeficient mice. A particular challenge in bioanalytical qPCR studies is that the different tissues of the host organism can affect amplification efficiency and amplicon detection to varying degrees, and ignoring these matrix effects can easily cause a significant underestimation of the true number of target cells in a sample. Here we describe the development and drug regulatory-compliant validation of a TaqMan® qPCR assay for quantification of mesenchymal stromal cells in the range of 125 to 20,000 cells/200 µl lysate by amplification of a human-specific, highly repetitive αsatellite DNA sequence of the chromosome 17 centromere region HSSATA17. Assessment of matrix effects in 14 different mouse tissues and blood revealed a wide range of spike recovery rates across the different tissue types from 11 to 174%. Based on these observations, we propose to perform systematic spike-and-recovery experiments during assay validation and to correct for the effects of the different tissue matrices on cell quantification in subsequent bioanalytical studies by multiplying the back-calculated cell number by tissue-specific factors derived from the inverse of the validated percent recovery rate.

The nucleosome is a major modulator of DNA accessibility to other cellular factors. Nucleosome positioning has a critical importance in regulating cell processes such as transcription, replication, recombination or DNA repair. The DNA sequence is a major factor influencing the position of nucleosomes on genomes. Different sequence motifs can promote or inhibit the nucleosome formation, thus influencing the accessibility to the DNA. Sequence-encoded nucleosome positioning having functional consequences on cell processes can then be selected or counter-selected during evolution. We review the interplay between sequence evolution and nucleosome positioning evolution. We first focus on the different ways to encode nucleosome positions in the DNA sequence, and to which extent these mechanisms are responsible of genome-wide nucleosome positioning in vivo. Then, we discuss the findings about selection of sequences for their nucleosomal properties. Finally, we illustrate how the nucleosome can directly influence sequence evolution through its interactions with DNA damage and repair mechanisms. This review aims to provide an overview of the mutual influence of sequence evolution and nucleosome positioning evolution, possibly leading to complex evolutionary dynamics.

In the present study, piecewise integrated composite (PIC) bumper beam for passenger cars was proposed and design optimisation process for composite bumper beam against IIHS test was carried out with the help of machine learning. Several elements in IIHS bumper FE model have been assigned to be references, in order to collect training data which, allow the machine learning model to study the method of predicting loading types of each finite element. 2-D and 3-D implementations were provided by machine learning models, which determined stacking sequences of each finite element in PIC bumper beam. It was found that the PIC bumper beam, which was designed by machine learning model has direct impact on reducing the possibility of failure as well as increasing bending strength effectively than conventional composite bumper beam. Moreover, 3-D implementation produced better results compared with 2-D implementation since it was preferable to choose loading type information which was achieved from surroundings when the target elements were located either at corner or junction of planes instead of using information came from the same plane of target.

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

A new picture of the Josephson effect is devised. The radio-frequency (RF) signal, observed in a Josephson junction, is shown to stem from bound electrons, tunneling periodically through the insulating film. This holds also for the microwave mediated tunneling. The Josephson effect is found to be conditioned by the same prerequisite worked out previously for persistent currents, thermal equilibrium and occurence of superconductivity. The observed negative resistance behaviour is shown to originate from the interplay between the normal and superconducting currents.

The decapod fauna in intertidal rocky shore in continental Chile has high species diversity mainly in northern and central Chile due high productivity of these coast due influence of cold Humboldt stream. One of the abundant species in these ecosystems is decapod Cyclograpsus cinereus Dana, 1851. The aim of the present study was determine the spatial distribution pattern of C. cinereus along rocky shore in Antofagasta bay, north of Chile between spring and summer 2018-2020. Data was obtained counting individuals from random quadrants in intertidal zones, to the obtained data was applied the variance mean ratio for determine if the specimens have random, aggregate or uniform distribution, that are associated to Poisson, negative binomial or positive binomial distributions respectively. Data obtained revealed the existence of associated distribution with respective negative binomial distribution pattern in 16 observations, and uniform distribution for 3 observations. The sites corresponds to rocky shores in urban zones, and in a protected zone, and the density does not have significant differences for both kind of sites. The observed data about aggregated pattern agree with observations for decapods for rocky shore in central and southern Chile, specifically in interpretative probabilistic models.

In this paper we establish a topological framework of τ-structures to quantify the evolutionary transitions between two RNA sequence-structure pairs. τ-structures developed here consist of a pair of RNA secondary structures together with a non-crossing partial matching between the two backbones. The loop complex of a τ-structure captures the intersections of loops in both secondary structures. We compute the loop homology of τ-structures. We show that only the zeroth, first and second homology groups are free. In particular, we prove that the rank of the second homology group equals the number γ of certain arc-components in a τ-structure, and the rank of the first homology is given by γ−χ+1, where χ is the Euler characteristic of the loop complex.

This theoretical article provides a brief description of the model of living systems' functioning by defining them as resource flows patterns. It reviews the living systems growth limitation between their development cycles by the Fibonacci sequence. Besides, there are presented systems resource base criteria, necessary for accumulating the resources and their investment. The article also considers the conditions for the formation of various systems strategies. Then we reviewed the principles of elemental analysis of information by a person as a living system according to the considered model. The study also shows the possibility of forming priorities in analyzing information for 16 combinations as maximum. At that, it remains crucial to divide a human's information analysis between the two hemispheres of the brain. The described combinations of priorities in a person's information analysis are compared with the existing differential personality models, such as the big five personality traits, the Myers-Briggs type indicator, temperaments model and Honey and Mumford Learning styles.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in humans in Wuhan City at the end of December 2019. Since then, it has spread to all the countries. Therefore, global interest has been focused on discovering treatments and developing successful vaccines. This study sequenced the complete genome of the SARS-COV-2 Omicron Omicron (BA.1) and sub-variants (BA.1.1, BA.2), which were isolated from 40 individuals in Duhok, Iraq. Ninety-five different mutations were identified when the complete genome of the SARS-COV-2 virus discovered in Wuhan, China (accession number: NC 045512.2) was matched to the virus sequence using sequencing technology (Illumina, USA). Sequence analysis revealed 38 mutations in spike glycoprotein (S), 30 of which were found in ORF1a. Additionally, 11 mutations were found in ORF1b, and 7,3,2,1 mutations were found in Nucleocapsid (N), membrane protein (M), Open Reading Frames 6 (ORF6), Open Reading Frames 9 (ORF9), and Envelope (E) genes, respectively. Phylogenetic analysis and transmission further confirmed that the isolates found in Iraq had distinct infection origins and were closely related to those from other countries and states. According to the findings of this study, a new vaccine can be developed based on identifying new Omicron variant mutations and sub-variants such as BA.2, which were identified for the first time in Iraq.

Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various subtypes. Individualized therapy is recommended rather than generalized therapy, given the genetic variations among these TNBC subtypes. A precise and effective treatment for TNBC requires identifying prognostic markers. Depending on the type and stage of TNBC, patients are treated with various therapeutic interventions. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in the neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of BC in the GCC. Most of the studies reported a consistent increase in BC incidence over the past decades, which was particularly attributed to the adoption of a westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data about BC risk factors in GCC was limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50, an advanced stage at presentation, and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed towards elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

Triple-negative breast cancer (TNBC), characterized by deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotype such as tumor heterogeneity and therapy resistance remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approach, we found 55-up and 9-down regulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration, was positively correlated with status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Also, enhanced infiltration of immunosuppressive cells was positively correlated with the expression of these 5 genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expressions of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

Background: Relatively little is known and inconclusive about social inequality in human papillomavirus (HPV) vaccination among teenagers in the United States. This study aims to investigate whether there is a social disparity in HPV vaccination among teenagers and if so, whether it can differ by the source of teen vaccination information (parental reports and provider records). 
Methods: We used the data from the 2019 National Immunization Survey-Teen (NIS-Teen; 42,668 teenagers, aged 13-17) including parental reported vaccination status. Among them, 18,877 teenagers had adequate provider reported vaccination records. Two socioeconomic status (SES) measures were used: mother’s education and annual family income. Multivariate logistic analyses were conducted. 
Results: False negatives of parental reports against provider records were more than two times higher (p < 0.001) in low SES teens than in high SES teens. In both SES measures, the proportion of HPV unvaccinated teenagers were lowest in the highest SES level in analyses with parental reports. However, it was the opposite in analyses with provider records. Interestingly, regardless of vaccination information source, the HPV unvaccinated rate was highest in the middle SES teens (>12 years, non-college graduates; and above poverty level, but not > $75K). 
Conclusion: A significant social inequality in HPV vaccination among teenagers exists in the United States. The pattern of social inequality in HPV vaccination can be distorted when only parent reported vaccination information is used.

CRCMSS/pMMR contain a significantly increased fraction of TREM2+ macrophages (TAMs) and CD66+ neutrophils (TANs) together with decrease of CD4-CD8-CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of myeloid and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells display an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCMSS/pMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCMSS/pMMR.

Hepatocellular carcinoma (HCC) early diagnosis is challenging. Moreover, for patients with al-pha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profile may serve as potential HCC molecular markers. We aimed to assess plasma homo sabines (hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-199a-5p expression levels, as panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), es-pecially AFP-negative HCC cases, a step toward non-protein coding (nc) RNA precision medicine. Subjects and Methods: 79 patients enrolled with CHCV infection with LC, subclassified into LC group without HCC (n=40) and LC with HCC (n=39) in comparison with 15 apparently healthy control subjects. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n=39) when compared to LC group (n=40). Hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin re-sistance (r=0.5, p<0.001, r=0.334, p=0.01, and r=0.303, p=0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, re-spectively, vs 69% for AFP alone, with an acceptable specificity of 77.5%, 77.5%, and 80%, respec-tively, and AUC= 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC=0.76 and 0.71, respectively, with sensitivities=94% and 92%, and specifici-ties=48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR=1.198(1.063–1.329), p=0.002]. Conclusion: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made possi-ble to identify HCC development in LC patients’ cohort with higher sensitivity than using AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are poten-tial HCC molecular markers for AFP-negative HCC patients. Hsa-miR-21-5p was linked to insu-lin metabolism in HCC patients’ group as well as being an upregulated independent risk factor for the emergence of HCC from LC in CHCV patients.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.