gebhart/patrepeval huggingface dataset:
A Genomic Virulence Reference Map of Enterococcus faecalis Reveals an Important Contribution of Phage03-Like Elements in Nosocomial Genetic Lineages to Pathogenicity in a Caenorhabditis elegans Infection Model (2015)

In the present study, the commensal and pathogenic host-microbe interaction of Enterococcus faecalis was explored using a Caenorhabditis elegans model system. The virulence of 28 E. faecalis isolates representing 24 multilocus sequence types (MLSTs), including human commensal and clinical isolates as well as isolates from animals and of insect origin, was investigated using C. elegans strain glp-4 (bn2ts); sek-1 (km4). This revealed that 6 E. faecalis isolates behaved in a commensal manner with no nematocidal effect, while the remaining strains showed a time to 50% lethality ranging from 47 to 120 h. Principal component analysis showed that the difference in nematocidal activity explained 94% of the variance in the data. Assessment of known virulence traits revealed that gelatinase and cytolysin production accounted for 40.8% and 36.5% of the observed pathogenicity, respectively. However, coproduction of gelatinase and cytolysin did not increase virulence additively, accounting for 50.6% of the pathogenicity and therefore indicating a significant (26.7%) saturation effect. We employed a comparative genomic analysis approach using the 28 isolates comprising a collection of 82,356 annotated coding sequences (CDS) to identify 2,325 patterns of presence or absence among the investigated strains. Univariate statistical analysis of variance (ANOVA) established that individual patterns positively correlated (n = 61) with virulence. The patterns were investigated to identify potential new virulence traits, among which we found five patterns consisting of the phage03-like gene clusters. Strains harboring phage03 showed, on average, 17% higher killing of C. elegans (P = 4.4e(-6)). The phage03 gene cluster was also present in gelatinase-and-cytolysin-negative strain E. faecalis JH2-2. Deletion of this phage element from the JH2-2 clinical strain rendered the mutant apathogenic in C. elegans, and a similar mutant of the nosocomial V583 isolate showed significantly attenuated virulence. Bioinformatics investigation indicated that, unlike other E. faecalis virulence traits, phage03-like elements were found at a higher frequency among nosocomial isolates. In conclusion, our report provides a valuable virulence map that explains enhancement in E. faecalis virulence and contributes to a deeper comprehension of the genetic mechanism leading to the transition from commensalism to a pathogenic lifestyle.
Untargeted Metabolomic Profile for the Detection of Prostate Carcinoma—Preliminary Results from PARAFAC2 and PLS–DA Models (2019)

Prostate-specific antigen (PSA) is the main biomarker for the screening of prostate cancer (PCa), which has a high sensibility (higher than 80%) that is negatively offset by its poor specificity (only 30%, with the European cut-off of 4 ng/mL). This generates a large number of useless biopsies, involving both risks for the patients and costs for the national healthcare systems. Consequently, efforts were recently made to discover new biomarkers useful for PCa screening, including our proposal of interpreting a multi-parametric urinary steroidal profile with multivariate statistics. This approach has been expanded to investigate new alleged biomarkers by the application of untargeted urinary metabolomics. Urine samples from 91 patients (43 affected by PCa; 48 by benign hyperplasia) were deconjugated, extracted in both basic and acidic conditions, derivatized with different reagents, and analyzed with different gas chromatographic columns. Three-dimensional data were obtained from full-scan electron impact mass spectra. The PARADISe software, coupled with NIST libraries, was employed for the computation of PARAFAC2 models, the extraction of the significative components (alleged biomarkers), and the generation of a semiquantitative dataset. After variables selection, a partial least squares-discriminant analysis classification model was built, yielding promising performances. The selected biomarkers need further validation, possibly involving, yet again, a targeted approach.
Combining confocal microscopy and optical coherence tomography for imaging in developmental biology (2008)

<i>In-vivo</i> Optical Coherence Tomography (OCT) imaging of the fruit fly <i>Drosophila melanogaster</i> larval heart allows non invasive visualizations and assesment of its cardiac functions. To image <i>Drosophila melanogaster</i> heart, we have developed a dedicated imaging instrument able to provide simultaneous Optical Coherence Tomography (OCT) and Laser Confocal Scanning Microscopy (LCSM) or Laser Scanning Fluorescence Microscopy (LSFM) images and can be used to produce B-scan OCT images. With this dual imaging system, the image of heart can be easily located in the specimen and the change of the heart shape in a cardiac cycle monitored. This technique therefore provides an excellent tool for large scale screen of candidate genes responsible for the contractility of the <i>Drosophila</i> heart. As this technique can also image the dynamic process of the heartbeat in a non-invasive fashion, it provides a new avenue to study the physiology of the heart function. <i>En-face</i> and B-scan OCT images of the <i>Drosophila melanogaster</i> heart showing its chambers have been obtained with our imaging instruments. Our results are consistent with detailed anatomical studies from the literature.
Neuron‐specific age‐related decreases in dopamine receptor subtype mRNAs (2002)

Age-related decline in dopamine receptor levels has been observed in regional studies of animal and human brains; however, identifying specific cellular substrates and/or alterations in distinct neuronal populations remains elusive. To evaluate whether age-related decreases in dopamine receptor subtypes are associated with specific cell populations in the hippocampus and entorhinal cortex, antisense RNA amplification was combined with cDNA array analysis to examine effects of aging on D1-D5 dopamine receptor mRNA expression levels in hippocampal CA1 pyramidal neurons and entorhinal cortex layer II stellate cells from post-mortem human brains (19-92 years). In CA1 pyramidal neurons, significant age-related decline was observed for dopamine receptor mRNAs (D1-D4, P < 0.001; D5, P < 0.05) but not for the cytoskeletal elements beta-actin, three-repeat (3R) tau, and four-repeat (4R) tau. In contrast, no significant changes were observed in stellate cells across the same cohort. Thus, senescence may be a factor responsible for cell-specific decrements in dopamine receptor gene expression in one population of neurons within a circuit that is critical for learning and memory. Furthermore, these results support the hypothesis that alterations in dopaminergic function may also be related to behavioral abnormalities, such as psychosis, that occur with aging.
Engineering of an Avidity-Optimized CD19-Specific Parallel Chimeric Antigen Receptor That Delivers Dual CD28 and 4-1BB Co-Stimulation (2022)

Co-stimulation is critical to the function of chimeric antigen receptor (CAR) T-cells. Previously, we demonstrated that dual co-stimulation can be effectively harnessed by a parallel (p)CAR architecture in which a CD28-containing second generation CAR is co-expressed with a 4-1BB containing chimeric co-stimulatory receptor (CCR). When compared to linear CARs, pCAR-engineered T-cells elicit superior anti-tumor activity in a range of pre-clinical models. Since CD19 is the best validated clinical target for cellular immunotherapy, we evaluated a panel of CD19-specific CAR and pCAR T-cells in this study. First, we generated a panel of single chain antibody fragments (scFvs) by alanine scanning mutagenesis of the CD19-specific FMC63 scFv (V<sub>H</sub> domain) and these were incorporated into second generation CD28+CD3ζ CARs. The resulting panel of CAR T-cells demonstrated a broad range of CD19 binding ability and avidity for CD19-expressing tumor cells. Each scFv-modified CAR was then converted into a pCAR by co-expression of an FMC63 scFv-targeted CCR with a 4-1BB endodomain. When compared to second generation CARs that contained an unmodified or mutated FMC63 scFv, each pCAR demonstrated a significant enhancement of tumor re-stimulation potential and IL-2 release, reduced exhaustion marker expression and enhanced therapeutic efficacy in mice with established Nalm-6 leukemic xenografts. These data reinforce the evidence that the pCAR platform delivers enhanced anti-tumor activity through effective provision of dual co-stimulation. Greatest anti-tumor activity was noted for intermediate avidity CAR T-cells and derived pCARs, raising the possibility that effector to target cell avidity is an important determinant of efficacy.
Photosynthetic Characteristics of a Photoautotrophic Cell Suspension Culture of Soybean (1987)

A soybean suspension culture (SB-P) which can grow photoautotrophically in 5% CO(2) will not grow in ambient CO(2) levels. This elevated CO(2) requirement seems to be due to the additive effects of a number of factors. The in vivo activity of ribulose-1,5-bisphosphate carboxylase (RuBPcase) is much lower in the SB-P cells, compared to soybean plants. This may be due to the low light intensity used to culture the cells, which has been shown to decrease both the amount and activity in whole plants, resulting in a low rate of net photosynthesis. The RuBPcase activation level is also lowered in air CO(2) levels. The presence of the liquid medium raises the cells CO(2) compensation concentration (the CO(2) concentration reached when the rates of CO(2) fixed by photosynthesis and the CO(2) respired by the cells are equal). These factors, coupled with the high respiratory loss of CO(2) all contribute to reduced net photosynthesis in air, resulting in a photosynthetic capacity that is inadequate for cell survival. Active cell division, low photosynthetic capacity, elevated respiration, and a low ratio of RuBPcase(initial)/phosphoenolpyruvate carboxylase are traits that SB-P cells share with young leaf cells, indicating SB-P cell physiology may be comparable to that of young expanding leaves rather than to that of mature leaves.
An Undergraduate Research Experience: Wireless Propagation And Position Location In A Forest Environment (2020)

At Virginia Tech
Data from Immune-Related Gene Expression Profiling After PD-1 Blockade in Non–Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma (2023)

&lt;div&gt;Abstract&lt;p&gt;Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor specimens from 65 patients with melanoma, lung nonsquamous, squamous cell lung or head and neck cancers who were treated with the approved PD1-targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS). In addition, we evaluated intra- and interbiopsy variability of PD1, PD-L1, CD8A, and CD4 mRNAs and their relationship with tumor-infiltrating lymphocytes (TIL) and PD-L1 IHC expression. Among the biomarkers examined, PD1 gene expression along with 12 signatures tracking CD8 and CD4 T-cell activation, natural killer cells, and IFN activation associated significantly with nonprogressive disease and PFS. These associations were independent of sample timing, drug used, or cancer type. TIL correlated moderately (∼0.50) with PD1 and CD8A mRNA levels and weakly (∼0.35) with CD4 and PD-L1. IHC expression of PD-L1 correlated strongly with PD-L1 (0.90), moderately with CD4 and CD8A, and weakly with PD1. Reproducibility of gene expression in intra- and interbiopsy specimens was very high (total SD &lt;3%). Overall, our results support the hypothesis that identification of a preexisting and stable adaptive immune response as defined by mRNA expression pattern is reproducible and sufficient to predict clinical outcome, regardless of the type of cancer or the PD1 therapeutic antibody administered to patients. &lt;i&gt;Cancer Res; 77(13); 3540–50. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Die Expression der Moleküle HLA-G und HLA-E moduliert die Zytokinproduktion monozytengenerierter dendritischer Zellen (2002)

These results show that DC react with an increased cytokine release upon contact with cells lacking HLA class I and II antigens. The suppressive effect of HLA-G and HLA-E on the secretion of TNF-alpha (Th1 cytokine), IL-10 (Th2 cytokine) and IL-8 (chemokine) by immature DC could be interpreted as further evidence for the central immunotolerance role of HLA-G and HLA-E during early pregnancy.
Serine 970 of RNA helicase MOV10 is phosphorylated and controls unfolding activity and fate of mRNAs targeted for AGO2-mediated silencing (2023)

MOV10 is an RNA helicase required for organismal development and is highly expressed in postnatal brain. MOV10 is an AGO2-associated protein that is also necessary for AGO2-mediated silencing. AGO2 is the primary effector of the miRNA pathway. MOV10 has been shown to be ubiquitinated, leading to its degradation and release from bound mRNAs, but no other posttranslational modifications with functional implications have been described. Using mass spectrometry, we show that MOV10 is phosphorylated in cells at the C-terminus, specifically at serine 970 (S970). Substitution of S970 to phospho-mimic aspartic acid (S970D) blocked unfolding of an RNA G-quadruplex, similar to when the helicase domain was mutated (K531A). In contrast, the alanine substitution (S970A) of MOV10 unfolded the model RNA G-quadruplex. To examine its role in cells, our RNA-seq analysis showed that the expression of S970D causes decreased expression of MOV10 enhanced Cross-Linking Immunoprecipitation targets compared to WT. Introduction of S970A had an intermediate effect, suggesting that S970 was protective of mRNAs. In whole-cell extracts, MOV10 and its substitutions bound AGO2 comparably; however, knockdown of AGO2 abrogated the S970D-induced mRNA degradation. Thus, MOV10 activity protects mRNA from AGO2; phosphorylation of S970 restricts this activity resulting in AGO2-mediated mRNA degradation. S970 is positioned C-terminal to the defined MOV10-AGO2 interaction site and is proximal to a disordered region that likely modulates AGO2 interaction with target mRNAs upon phosphorylation. In summary, we provide evidence whereby MOV10 phosphorylation facilitates AGO2 association with the 3'UTR of translating mRNAs that leads to their degradation.
O2‐10‐04: MITOCHONDRIAL VARIANTS AND HAPLOGROUPS ASSOCIATED WITH LATE‐ONSET ALZHEIMER'S DISEASE IDENTIFIED BY WHOLE EXOME SEQUENCING (2019)

Numerous studies suggest that mitochondrial (MT) dysfunction is involved in Alzheimer disease (AD) pathogenesis. The Alzheimer's Disease Sequencing Project (ADSP) performed whole-exome sequencing (WES) of 5,519 AD cases and 4,917 cognitively normal elderly controls of European ancestry (EA) and 218 cases and 177 controls of Caribbean Hispanic (CH) heritage. After mapping to the reference MT genome (NC_012920), MT variants were called using the haploid mode of GATK HaplotypeCaller. Low-quality, multi-allelic and monomorphic variants were excluded using a QC metric based on comparison with MT variants called in the Alzheimer Disease Neuroimaging Initiative WGS dataset and the 1000 Genomes project. Haplogrep 2 software was used to classify mtDNA hapogroups with Phylotree 17. The association of AD with MT single nucleotide variants (SNVs) with minor allele count (MAC) ≥10 and call rate≥ 0.80 (802 SNVs in EA, 135 SNVs in CH) and with mtDNA haplogroups was evaluated in EAs and CHs separately. In gene-based tests, only genes with ≥2 rare SNVs (minor allele frequency <0.05) and cumulative MAC≥10 were tested. Analyses were performed using single variant SCORE tests and gene-based (SKAT-O) tests in seqMeta R package, controlling for age, sex, and principal components of ancestry. Results were meta-analyzed across ethnicities. Bonferroni-corrected thresholds were used to determine study-wide significance (SWS) for single variant (P=6.2×10−5) and gene-based (P=3.8×10−3) associations. In EAs, association of AD with 47 mtDNA haplogroups was tested using logistic regression. After variant-level and sample-level QC, 4,220 variants and 10,610 samples remained for analyses. A missense SNV in MT-ND4L which encodes NADH dehydrogenase subunit 4L involved in ubiquinone and oxidoreductase activity (26:10733:C:T, rs28709356, Asp88Glu, MAF=0.002) was associated with AD risk in EAs at nearly the SWS level (OR=7.52; P=7.3×10−5). One SWS gene-based finding was identified with MT-TI (P = 3.0×10−3). None of the mtDNA haplogroups were associated with AD. A set of high quality MT variants and mtDNA haplogroups were called from the large ADSP sequencing data. We identified significant association of AD risk with a rare SNV in MT-NDL4 and the MT-TI gene. A replication study using WGS data in independent cohorts from the ADSP extension phase is currently underway.
An Efficient Requirement-Aware Attachment Policy for Future Millimeter\n Wave Vehicular Networks (2019)

The automotive industry is rapidly evolving towards connected and autonomous\nvehicles, whose ever more stringent data traffic requirements might exceed the\ncapacity of traditional technologies for vehicular networks. In this scenario,\ndensely deploying millimeter wave (mmWave) base stations is a promising\napproach to provide very high transmission speeds to the vehicles. However,\nmmWave signals suffer from high path and penetration losses which might render\nthe communication unreliable and discontinuous. Coexistence between mmWave and\nLong Term Evolution (LTE) communication systems has therefore been considered\nto guarantee increased capacity and robustness through heterogeneous\nnetworking. Following this rationale, we face the challenge of designing fair\nand efficient attachment policies in heterogeneous vehicular networks.\nTraditional methods based on received signal quality criteria lack\nconsideration of the vehicle's individual requirements and traffic demands, and\nlead to suboptimal resource allocation across the network. In this paper we\npropose a Quality-of-Service (QoS) aware attachment scheme which biases the\ncell selection as a function of the vehicular service requirements, preventing\nthe overload of transmission links. Our simulations demonstrate that the\nproposed strategy significantly improves the percentage of vehicles satisfying\napplication requirements and delivers efficient and fair association compared\nto state-of-the-art schemes.\n
COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of digestion1 (2015)

The digestive systems of all species have been shaped by environmental pressures over long evolutionary time spans. Nevertheless, all digestive systems must achieve the same end points, the ingestion of biological material and its conversion to molecules that serve as energy substrates and structural components of tissues. A range of strategies to extract nutrients, including for animals reliant primarily on foregut fermentation, hindgut fermentation, and enzymatic degradation, have evolved. Moreover, animals have adapted to different foodstuffs as herbivores (including frugivores, folivores, granivores, etc.), carnivores, and omnivores. We present evidence that humans have diverged from other omnivores because of the long history of consumption of cooked or otherwise prepared food. We consider them to be cucinivores. We present examples to illustrate that the range of foodstuffs that can be efficiently assimilated by each group or species is limited and is different from that of other groups or species. Differences are reflected in alimentary tract morphology. The digestive systems of each group and of species within the groups are adaptable, with constraints determined by individual digestive physiology. Although overall digestive strategies and systems differ, the building blocks for digestion are remarkably similar. All vertebrates have muscular tubular tracts lined with a single layer of epithelial cells for most of the length, use closely related digestive enzymes and transporters, and control the digestive process through similar hormones and similarly organized nerve pathways. Extrapolations among species that are widely separated in their digestive physiologies are possible when the basis for extrapolation is carefully considered. Divergence is greatest at organ or organismal levels, and similarities are greatest at the cell and molecular level.
Photoacoustic image synthesis with generative adversarial networks (2022)

Photoacoustic tomography (PAT) has the potential to recover morphological and functional tissue properties with high spatial resolution. However, previous attempts to solve the optical inverse problem with supervised machine learning were hampered by the absence of labeled reference data. While this bottleneck has been tackled by simulating training data, the domain gap between real and simulated images remains an unsolved challenge. We propose a novel approach to PAT image synthesis that involves subdividing the challenge of generating plausible simulations into two disjoint problems: (1) Probabilistic generation of realistic tissue morphology, and (2) pixel-wise assignment of corresponding optical and acoustic properties. The former is achieved with Generative Adversarial Networks (GANs) trained on semantically annotated medical imaging data. According to a validation study on a downstream task our approach yields more realistic synthetic images than the traditional model-based approach and could therefore become a fundamental step for deep learning-based quantitative PAT (qPAT).
A one-step conversion of cholest-4-en-3-one to 24-hydroxychol-4-en-3-one (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA one-step conversion of cholest-4-en-3-one to 24-hydroxychol-4-en-3-oneRonald P. Manley, Kenneth W. Curry, Norman C. Deno, and Michael D. MeyerCite this: J. Org. Chem. 1980, 45, 22, 4385–4387Publication Date (Print):October 1, 1980Publication History Published online1 May 2002Published inissue 1 October 1980https://pubs.acs.org/doi/10.1021/jo01310a024https://doi.org/10.1021/jo01310a024research-articleACS PublicationsRequest reuse permissionsArticle Views143Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts