gebhart/patrepeval huggingface dataset:
Loquacious Modulates Flaviviral RNA Replication in Mosquito Cells (2021)

Abstract Arthropod-borne viruses infect both mosquito and mammalian hosts. While much is known about virus-host interactions that modulate viral gene expression in their mammalian host, much less is known about the interactions that involve inhibition, subversion or avoidance strategies in the mosquito host. A novel RNA-Protein interaction detection assay was used to detect proteins that directly or indirectly bind to dengue viral genomes in infected mosquito cells. Membrane-associated mosquito proteins SEC61A1 and Loquacious (Loqs) were found to be in complex with the viral RNA. Depletion analysis demonstrated that both SEC61A1 and Loqs have pro-viral functions in the dengue viral infectious cycle. Co-localization and pull-down assays showed that Loqs interacts with viral protein NS3 and both full-length and subgenomic viral RNAs. While Loqs coats the entire positive-stranded viral RNA, it binds selectively to the 3’ end of the negative-strand of the viral genome. In-depth analyses showed that the absence of Loqs did not affect translation or turnover of the viral RNA but modulated viral replication. Loqs also displayed pro-viral functions for several flaviviruses in infected mosquito cells, suggesting a conserved role for Loqs in flavivirus-infected mosquito cells. Author Summary There is a wealth of information that dictates virus-host interactions in flavivirus-infected mammalian cells, yet there is only sparse information on the mechanisms that modulate viral gene expression in the mosquito host. Using a novel RNA-protein detection assay, the interactions of SEC61A1 and Loqs with the dengue viral genome were found to have proviral functions in infected mosquito cells. In particular, Loqs forms complexes with the positive-strand of the viral RNA and the very 3’ end of the negative-strand viral RNA. Further analyses showed that Loqs modulates viral RNA replication of dengue virus and gene amplification of several other flaviviral genomes. These findings argue that Loqs is an essential proviral host factor in mosquitos.
Supplementary Figure 1 from Higher Frequencies of GARP<sup>+</sup>CTLA-4<sup>+</sup>Foxp3<sup>+</sup> T Regulatory Cells and Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Are Associated with Impaired T-Cell Functionality (2023)

&lt;p&gt;PDF file - 81K, Supplementary Figure 1. (A) q-PCR analysis of Foxp3 gene expression from PBMCs of HCC patients (n=10) and healthy donors (n=10). Lines represent mean values of Foxp3 mRNA copies normalized to GAPDH control (**P = 0.005). (B) Correlation between Foxp3 mRNA copies and CD4+FoxP3+ Treg frequency (Spearman correlation = 0.49; P = 0.005).&lt;/p&gt;
Synthesis and expression in E. coli of the gene for human tumor necrosis factor (h alpha TNF). (1991)

A gene coding for human tumor necrosis factor (h alpha TNF) has been assembled by ligating short oligodeoxyribonucleotides and cloning into plasmid vectors. These oligonucleotides were prepared by the modified phosphoramidite methodology using isopropoxyacetyl (IPA) as a protecting group for exoamino- functions of nucleosides. Gene was expressed in E. coli and the protein product was purified to homogeneity by ion-exchange chromatography.
Inter‐ and intra‐fractional stability of rectal gas in pelvic cancer patients during MRIgRT (2020)

Rectal gas in pelvic cancer patients is likely to remain stable over the course of an MRIgRT fraction, and also likely to reappear in the same location in multiple fractions, and can therefore result in clinically relevant over-dosage in the rectal wall. The over-dosage is reduced when accounting for gas in the daily adaption.
High-Resolution NMR and Computer Modeling Studies of the Cannabimimetic Aminoalkylindole Prototype WIN-55212-2 (1999)

Aminoalkylindoles (AAIs), although structurally dissimilar from the classical cannabinoids (CCs), are known to be capable of binding to cannabinoid receptors and of evoking cannabimimetic responses. However, their mode of binding remains unknown. In this communication, we have carried out further studies on the AAI prototype (R)-[2, 3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1, 4-benzoxazin-6-yl](1-naphthalenyl)methanone (WIN-55212-2, 1) by the combined use of high-resolution 2D NMR and computer modeling. Our results suggest that the minimum energy conformations of the molecule 1 have distinct pharmacophoric features: (i) The naphthyl ring is oriented off the plane of the benzoxazine ring by approximately 59 degrees with the carbonyl C=O group pointing toward the C2-CH(3) group. (ii) At the C10-position the axial morpholinomethyl conformation is preferred over the equatorial in order to relieve a steric interaction with the C2-methyl group. The preferred conformer as defined by the three key pharmacophores, naphthyl, morpholino, and 3-keto groups, shows that the morpholinyl ring of the molecule 1 deviates from the plane of the benzoxazine ring by about 32 degrees and orients in the left molecular quadrant. This model supports the hypothesis that a certain deviation of the morpholino group from the plane of the indole ring in compound 1 is essential for cannabimimetic activity. We postulate that such an alignment by the respective pharmacophores allows them to interact optimally with the receptor. The results should help us to better understand the pharmacophoric requirements of the AAIs and serve as a basis for future SAR studies and drug design.
Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity (2018)

Here, the group of Jerrold Olefsky identified adipose tissue macrophages as important sources of microRNAs regulating metabolic processes not only within the adipose tissue depot, but also in an endocrine way in other distant tissues. The application of exosomes derived from ATMs isolated from obese mice caused insulin resistance both in vitro and in vivo. In obese mice, the exosomes of lean mice attenuated obesity-induced insulin resistance. Finally, these results confirmed the causal effect of miR-155 from macrophages in mediating systemic insulin resistance. By this comprehensive work, the authors revealed exosomes as the possible missing link between obesity-induced chronic tissue inflammation and insulin resistance. Therefore, exosomal miRNAs are potential treatment strategies or biomarkers for metabolic and other diseases.
Abstract 2612: BluePrint Luminal subtype predicts non-response to HER2-targeted therapies in HR+/HER2+ I-SPY 2 breast cancer patients (2018)

Abstract Background: Previous studies suggest that within the triple positive HR+HER2+ subtype, patients classified as BluePrint (BP) Luminal subtype are more responsive to pertuzumab and trastuzumab (P/H) as opposed to trastuzumab (H) alone. In the I-SPY2 TRIAL, HER2-targeted treatment arms include H, P/H, neratinib (N), and T-DM1/Pertuzumab (T-DM1/P); and patients were classified by BP molecular subtyping in addition to conventional receptors. We evaluated BP subtype as a predictor of response in HR+HER2+ patients and assessed pathway differences between BP molecular subtypes. Methods: 125 HR+HER2+ patients (N: 42; P/H: 29, T-DM1/P: 35; H: 19) with pre-treatment Agilent microarrays and BP subtype assignments were considered. We assess association between BP subtypes and pCR using Fisher's exact test. To identify genes associated with BP Luminal vs. BP HER2 subtype, we (1) apply a Wilcoxon rank sum test and (2) fit a logistic model, with the Benjamini-Hochberg (BH) multiple testing correction (BH p&amp;lt;0.05 from both tests). We then perform pathway enrichment analysis using DAVID. Our study is exploratory and does not adjust for multiplicities of other biomarkers in the trial outside this study. Results: Of the 125 HR+HER2+ patients, 71 were BP HER2-type and 50 were BP Luminal-type. The distribution of pCR rates in BP Luminal/ HER2 subtypes are as follows: Distribution of pCR rates in BP Luminal/ HER2 subtypes by treatment armN (n = 40)P/H (n = 29)T-DM1/P (n = 34)H (n = 18)All arms (n = 121)BP Luminal (n = 50)0 / 9 (0%)1 / 12 (8.3%)2 / 16 (12.5%)1 / 13 (7.7%)4 / 50 (8%)BP HER2 (n = 71)12 / 31 (38.7%)13 / 17 (76.5%)15 / 18 (83.3%)1 / 5 (20%)41 / 71 (57.7%)Odds Ratio6.1; p = 0.12730.2; p = 0.00048429.6; p = 8.60E-052.8; p = 0.49015.3; p = 1.04E-08 In a whole transcriptome analysis, 1725 genes were differentially expressed. By DAVID enrichment analysis, the most significantly enriched pathways were related to immune function, with the BP HER2 subgroup showing higher expression. Conclusion: Our analysis suggests that HR+HER2+ BP Luminal subtype is associated with lower response rates to HER2-targeted agents, including P/H, and may need an alternative strategy. BP HER2 subtype appears associated with higher expression of immune-related genes, relative to BP Luminal; and suggests that immune signaling may contribute to HER2-targeted therapy sensitivity. Citation Format: Pei Rong Evelyn Lee, Zelos Zhu, Denise Wolf, Christina Yau, William Audeh, Annuska Glas, Lamorna Brown-Swigart, Gillian Hirst, Angela DeMichele, I-SPY 2 TRIAL Investigators, Laura Esserman, Laura van 't Veer. BluePrint Luminal subtype predicts non-response to HER2-targeted therapies in HR+/HER2+ I-SPY 2 breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2612.
Solving Inverse Problems with Piecewise Linear Estimators: From Gaussian Mixture Models to Structured Sparsity (2010)

A general framework for solving image inverse problems is introduced in this paper.The approach is based on Gaussian mixture models, estimated via a computationally efficient MAP-EM algorithm.A dual mathematical interpretation of the proposed framework with structured sparse estimation is described, which shows that the resulting piecewise linear estimate stabilizes the estimation when compared to traditional sparse inverse problem techniques.This interpretation also suggests an effective dictionary motivated initialization for the MAP-EM algorithm.We demonstrate that in a number of image inverse problems, including inpainting, zooming, and deblurring, the same algorithm produces either equal, often significantly better, or very small margin worse results than the best published ones, at a lower computational cost.
Canines in the emergency department: a novel approach to stress reduction in emergency medicine providers (2018)

Background and Hypothesis: Cognitive stress during shiftwork contributes to burnout in emergency care. We hypothesize that if emergency care providers (physicians and nurses) were to interact with a therapy dog, their stress levels will decrease. Experimental Design or Project Methods: Consenting emergency medicine physicians and nurses provided three self-reported assessments of stress as well as saliva samples near the beginning of their shift. During peak hours in the emergency department at Eskenazi Hospital participants are randomized to interact with either a therapy dog or perform a mindfulness exercise via art therapy for five minutes. Self-perceived stress and saliva samples are obtained 30 minutes later and again near the end of shift. To assess potential change in participant behavior, patients of providers in either group receive a validated questionnaire assessing perceived empathy of the provider. Salivary cortisol will be measured at the end of the study by a vendor (Salimetrics). The sample size of 40 per group is predicated on a 25% decrease in self-reported stress in the dog group on the emergency care worker stress scale (ECWSS). Results: From June 1 to July 10, 24 participants have been randomized (12 in each group). Seven participants (58%) exposed to dogs had a mean decrease in the ECWSS of -5 (+/-1.8) compared with four participants (33%) who had a mean decrease of -2 (+/-0.8) after art therapy. The mean overall change in ECWSS after dog was -2 (+/-1.5) vs. +3 (+/-1.5) after art therapy. Current data suggest a greater decrease of self-reported stress after interaction with a therapy dog, compared to art therapy. Conclusion and Potential Impact: Interim analysis suggests that exposure to a therapy dog decreases stress in a subset of emergency care workers. This work will help determine if human-animal interaction can modulate stress biology imposed by providing emergency medical care.
Thermally reversible polymeric sorbents for acid gases: CO2, SO2, and NOx (1994)

Abstract Weakly acidic gases such as CO 2 , SO 2 , NO 2 , and NO discharged directly into the atmosphere have been suggested to contribute to the formation of acid rain and to global climate changes. In an effort to develop an effective process by which to remove these pollutants from gas streams, we synthesized polymeric sorbents that bind acid gases. In an earlier work, we reported that polymers carrying pendant amine groups are capable of absorbing carbon dioxide to form thermally reversible amine/CO 2 addition products. In this study, we investigated the effects of amine structure on acid gas sorption and the thermal reversibility of the sorption–desorption reactions of various acid gases including CO 2 , SO 2 , NO, and NO 2 with both linear and cross‐linked polymers using thermogravimetric analysis. © 1994 John Wiley &amp; Sons, Inc.
Himbacine-Derived Thrombin Receptor Antagonists: C7-Spirocyclic Analogues of Vorapaxar (2014)

We have synthesized several C7-spirocyclic analogues of vorapaxar and evaluated their in vitro activities against PAR-1 receptor. Some of these analogues showed activities and rat plasma levels comparable to vorapaxar. Compound 5c from this series showed excellent PAR-1 activity (K i = 5.1 nM). We also present a model of these spirocyclic compounds docked to the PAR-1 receptor based on the X-ray crystal structure of vorapaxar bound to PAR-1 receptor. This model explains some of the structure-activity relationships in this series.
Compatibility of N-Methyl-N-propylpyrrolidinium Cation Room-Temperature Ionic Liquid Electrolytes and Graphite Electrodes (2008)

To realize high-safety, high-performance lithium ion secondary batteries using room-temperature ionic liquids, we examined [graphite electrode|room-temperature ionic liquid−lithium salt binary electrolyte|lithium metal electrode] cells by varying the cation structure of the room-temperature ionic liquid. In particular, a bis(fluorosulfonyl)imide anion based room-temperature ionic liquid cell showed high charge/discharge capacity and reversibility. By application of electrochemical calorimetric measurements during charge/discharge operation, the formation of a suitable interfacial layer, such as a solid electrolyte interphase between the graphite electrode and the room-temperature ionic liquid−lithium salt binary electrolyte was indicated. Moreover, we found that not only the anion structure but also the cation structure was important for the suitable charge/discharge of the graphite electrode.
Identification of a nonameric H-2Kk-restricted CD8+ cytotoxic T lymphocyte epitope on the Plasmodium falciparum circumsporozoite protein (1995)

Class I-restricted CD8+ cytotoxic T lymphocytes (CTL) against the circumsporozoite protein (CSP) protect mice against the rodent malaria parasite, Plasmodium yoelii, and vaccines designed to produce protective CTL against the P. falciparum CSP (PfCSP) are under development. Humans and B10.BR (H-2k) mice have been shown to have CD8+ CTL activity against a 23-amino-acid region of the PfCSP (residues 368 to 390 from the PfCSP 7G8 sequence) that is too long to bind directly to class I major histocompatibility complex molecules. To identify within this 23-amino-acid peptide a shorter peptide that binds to an H-2k class I major histocompatibility molecule, a primarily CD8+ (97.8%) T-cell line (PfCSP TCL.1) was produced by immunizing B10.BR mice with recombinant vaccinia virus expressing the PfCSP and stimulating in vitro spleen cells from these immunized mice with L cells transfected with the PfCSP gene (LPF cells). PfCSP TCL.1 lysed LPF cells and L cells pulsed with peptide PfCSP 7G8 368-390. When 15 overlapping nonamer peptides spanning the 368 to 390 sequence were tested, only one peptide, PfCSP 7G8 375-383 (Y E N D I E K K I), which includes an H-2Kk-binding motif, E at amino acid residue 2, and I at residue 9, sensitized targets for lysis by PfCSP TCL.1. Furthermore, a 10(3)- to 10(4)-fold lower concentration of the nonamer than that of the 23-amino-acid peptide was required to sensitize target cells for lysis by PfCSP TCL.1. Presentation by H-2Kk was demonstrated by using 3T3 fibroblast cells transfected with the murine H-2Kk or H-2Dk genes, and only the H-2Kk transfectants were lysed by PfCSP TCL.1 after incubation with peptide PfCSP 7G8 375-383. Binding to H-2Kk was confirmed by competitive inhibition of binding of labelled peptides to affinity-purified Kk molecules. Substitution of the anchor amino acid residue, E, at position 2 with A dramatically reduced binding to Kk and eliminated the capacity of the peptide to sensitize target cells for killing. Variation of non-anchor residues did not markedly reduce binding to Kk but in some cases eliminated the capacity of the peptide to sensitize targets for cytolysis by PfCSP TCL.1, presumably by eliminating T-cell receptor-binding sites. These data suggest that similar studies with human T cells will be required for optimal development of peptide-based vaccines designed to produce protective class I-restricted CD8+ CTL against the PfCSP in humans.
Experimental Evaluation and Quasi-dimensional Modeling of Hydrogen Combustion for Sustainable Maritime Applications (2020)

Paper to 4th South East European Conference on Sustainable Development of Energy, Water and Environment Systems, 28 June - 2 July 2020, virtual
Trust in AutoML (2020)

We explore trust in a relatively new area of data science: Automated Machine Learning (AutoML). In AutoML, AI methods are used to generate and optimize machine learning models by automatically engineering features, selecting models, and optimizing hyperparameters. In this paper, we seek to understand what kinds of information influence data scientists' trust in the models produced by AutoML? We operationalize trust as a willingness to deploy a model produced using automated methods. We report results from three studies - qualitative interviews, a controlled experiment, and a card-sorting task - to understand the information needs of data scientists for establishing trust in AutoML systems. We find that including transparency features in an AutoML tool increased user trust and understandability in the tool; and out of all proposed features, model performance metrics and visualizations are the most important information to data scientists when establishing their trust with an AutoML tool.
Abstract 315: Human metabotropic glutamate receptor 1 (GRM1) may be essential for melanoma cell survival and activation of angiogenic signaling (2011)

Abstract Our group has demonstrated that ectopic expression of murine GRM1 results in transformation of mouse melanocyte cells, and we have found that human GRM1 is ectopically expressed in more than 60% human melanomas. We recently reported on the results of a Phase 0 preclinical trial targeting GRM1 signaling using a glutamate release-inhibitor, Riluzole. We demonstrated inhibition of signaling through the PI3K/AKT and MAPK pathways and a reduction in tumor size in 40% of patients treated. To better examine the mechanisms of Riluzole treatment effect and to begin to understand the function of GRM1 signal transduction in melanoma, cell lines that over-express GRM1 (UACC903 G2 and UACC903G4) were constructed using the native, low GRM1-expressing, UACC903 human melanoma cell line. We found that UACC903G2 and G4 cells produce elevated levels of GRM1 and were much more sensitive to treatment with 25uM Riluzole than the vector transfected control cell line UACC903V1. We also found that UACC903G2 and G4 cells produced much larger tumors in nude mice than the vector control cells. Tumors formed by UACC903G2 and G4 xenografts also do not demonstrate areas of hemorrhage necrosis as is found in UACC903V1 xenografts, and there are significantly more tumor blood vessels in the GRM1-overexpressing xenograft tumors. To confirm the angiogenic effect of GRM1 over-expression in UACC903 cells, an endothelial cell migration assay was performed. We found that culturing UACC903G2 and G4 cells in serum-free basic medium stimulated HMVECnd endothelial cell migration, an effect not seen with the vector control UACC903V1 cells. We next examined whether increased GRM1 expression in UACC903 cells resulted in the release of angiogenesis factor(s) from these cells. An angiogenesis antibody array (from Affymetrix) experiment was performed and we found that the conditioned medium from UACC903G2 and G4 cells had significantly higher levels of IL8 and VEGF (angiogenesis promoters), but decreased level of TIMP-2 and TIMP-1 (angiogenesis inhibitors) as compared to the conditioned medium from the UACC903V1 vector control cells. We conclude that over-expression of human GRM1 promotes proliferation, activates angiogenesis signaling, and renders cells more susceptible to the inhibitory effects of the glutamate-release inhibitor Riluzole. Further experiments examining the molecular mechanism of GRM1 in cell survival and angiogenesis are need to better understand the mechanisms at work. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 315. doi:10.1158/1538-7445.AM2011-315
The Ultimate Noise Limit for Hall Plates in Voltage, Current, and Hybrid Operating Modes (2020)

If Hall plates are used as magnetic field sensors they are usually powered up by a current source connected to a pair of non-neighboring contacts. The output voltage is tapped at another pair of non-neighboring contacts. In this paper we study more general operating conditions of Hall plates with an arbitrary number of contacts. In such hybrid operating modes current sources are connected to a first set of contacts and voltage sources to a second set of contacts. Output voltages are tapped at the first set of contacts and output currents are measured at the second set of contacts. All these output signals are multiplied by coefficients and added up. The purpose of this work is to figure out which operating mode and which Hall plate achieve maximum signal at minimum thermal noise and power dissipation. To this end we develop a theory, which gives the ratio of signal over noise and power as a function of the resistance matrix of Hall plates, of the supply voltages and currents, and of the coefficients. Optimization is done analytically in closed form and numerically for specific examples. The results are: 1) all operating modes have identical noise performance if their parameters are optimized; 2) for any Hall plate one can measure its resistance matrix and insert its values into our formulae to obtain the optimum supply currents and coefficients for optimum noise performance.
A 10Gb/s Mach-Zehnder silicon evanescent modulator (2008)

We demonstrate a 10 Gb/s Mach-Zehnder silicon evanescent modulator utilizing coplanar waveguide design. The device has a modulation efficiency of 1.5V-mm and modulation bandwidth of 8 GHz.
Boundary Layer Analysis (2014)

This chapter contains sections titled: 4.1 Boundary Layer Flow Features and Overview, 4.2 Defect Integrals and Thicknesses, 4.3 Boundary Layer Governing Equations, 4.4 Boundary Layer Response to Pressure and Shear Gradients, 4.5 Integral Boundary Layer Relations, 4.6 Self-Similar Laminar Boundary Layers, 4.7 Self-Similar Turbulent Boundary Layers, 4.8 Axisymmetric Boundary Layers, 4.9 3D Boundary Layers, 4.10 2D Boundary Layer Solution Methods - Overview, 4.11 Integral Boundary Layer Solution, 4.12 Coupling of Potential Flow and Boundary Layers, 4.13 Profile Drag Prediction, 4.14 Transition