gebhart/patrepeval huggingface dataset:
Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection (2021)

SUMMARY SARS-CoV-2 can cause a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of the host factors mediating viral infection or restriction is critical to elucidate SARS-CoV-2 host-pathogen interactions and the progression of COVID-19. To this end, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. These screens uncovered proviral and antiviral host factors across highly interconnected host pathways, including components implicated in clathrin transport, inflammatory signaling, cell cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high-molecular weight glycoproteins, as a prominent viral restriction network. We demonstrate that multiple membrane-anchored mucins are critical inhibitors of SARS-CoV-2 entry and are upregulated in response to viral infection. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and suggests interactions between SARS-CoV-2 and airway mucins of COVID-19 patients as a host defense mechanism.
A Comparison of Atomistic and Continuum Approaches to the Study of Bonding Dynamics in Electrocatalysis: Microcantilever Stress andin SituEXAFS Observations of Platinum Bond Expansion Due to Oxygen Adsorption during the Oxygen Reduction Reaction (2014)

Microcantilever stress measurements are examined to contrast and compare their attributes with those from in situ X-ray absorption spectroscopy to elucidate bonding dynamics during the oxygen reduction reaction (ORR) on a Pt catalyst. The present work explores multiple atomistic catalyst properties that notably include features of the Pt-Pt bonding and changes in bond strains that occur upon exposure to O2 in the electrochemical environment. The alteration of the Pt electronic and physical structures due to O2 exposure occurs over a wide potential range (1.2 to 0.4 V vs normal hydrogen electrode), a range spanning potentials where Pt catalyzes the ORR to those where Pt-oxide forms and all ORR activity ceases. We show that Pt-Pt surface bond strains due to oxygen interactions with Pt-Pt bonds are discernible at macroscopic scales in cantilever-based bending measurements of Pt thin films under O2 and Ar. Complementary extended X-ray absorption fine structure (EXAFS) measurements of nanoscale Pt clusters supported on carbon provide an estimate of the magnitude and direction of the in-operando bond strains. The data show that under O2 the M-M bonds elongate as compared to an N2 atmosphere across a broad range of potentials and ORR rates, an interfacial bond expansion that falls within a range of 0.23 (±0.15)% to 0.40 (±0.20)%. The EXAFS-measured Pt-Pt bond strains correspond to a stress thickness and magnitude that is well matched to the predictions of a mechanics mode applied to experimentally determined data obtained via the cantilever bending method. The data provide new quantitative understandings of bonding dynamics that will need to be considered in theoretical treatments of ORR catalysis and substantiate the subpicometer resolution of electrochemically mediated bond strains detected on the macroscale.
Nanoscale Optical Sensors Based on Surface Plasmon Resonance (2017)

The development of nanodevices, including nanosensors that are highly sensitive and selective (give low false positives, low false negatives) have the potential to provide a major improvement over current technologies for disease understanding, treatment, and monitoring. Nanoscale sensors consume less sample volume than conventional instruments because their inherently small size scale in comparison to standard macroscale devices permits straightforward integration with microfluidic devices. Additionally, nanoscale systems often exhibit behavior that is markedly different from their macroscale counterparts, thereby providing alternative pathways for obtaining new information.
Targeting Uptake Receptors on Human Plasmacytoid Dendritic Cells Triggers Antigen Cross-Presentation and Robust Type I IFN Secretion (2013)

Plasmacytoid dendritic cells (pDCs) play a crucial role in initiating immune responses by secreting large amounts of type I IFNs. Currently, the role for human pDCs as professional APCs in the cross-presentation of exogenous Ags is being re-evaluated. Human pDCs are equipped with a broad repertoire of Ag uptake receptors and an efficient Ag-processing machinery. In this study, we set out to investigate which receptor can best be deployed to deliver Ag to pDCs for Ag (cross-)presentation. We show that targeting nanoparticles to pDCs via the C-type lectins DEC-205, DC immunoreceptor, blood DC Ag-2, or the FcR CD32 led to uptake, processing, and (cross-) presentation of encapsulated Ag to both CD4(+) and CD8(+) T cells. This makes these receptors good candidates for potential in vivo targeting of pDCs by nanocarriers. Notably, the coencapsulated TLR7 agonist R848 efficiently activated pDCs, resulting in phenotypical maturation as well as robust IFN-α and TNF-α production. Taken together, their cross-presentation capacity and type I IFN production to further activate components of both the innate and adaptive immune system mark pDCs as inducers of potent antitumor responses. These findings pave the way to actively recruit human pDCs for cellular cancer immunotherapy.
Direct Synthetic Strategies to Hydrophilic Starlike Polymers by MADIX (2006)

Three direct synthetic routes to branched polymers based on poly(acrylic acid) (PAA) are proposed. Three-arm PAA stars were obtained by the "core-first" approach using trifunctional O-alkyl xanthates as reversible chain transfer agents for MADIX solution polymerization of acrylic acid (AA). Chain extension of PAA star precursors with acrylamide afforded double hydrophilic star-block copolymers. Star-like structures consisting of a microgel core were also prepared by the "arm-first" approach using linear chains derived by MADIX and N,N'-methylene-bis(acrylamide) (MBA) as the linking agent. Finally, polymeric nanogels were synthesized by radical solution radical crosslinking copolymerization of AA and MBA in the presence of a O-ethyl xanthate as a MADIX agent. Up to 15% mol. of MBA could be incorporated without macrogel formation. Core-shell star structures were obtained by chain extension from the xanthate chain-ends present in these polymeric precursors.
Kinetic and crystallographic studies of glucopyranose spirohydantoin and glucopyranosylamine analogs inhibitors of glycogen phosphorylase (2005)

Glycogen phosphorylase (GP) is currently exploited as a target for inhibition of hepatic glycogenolysis under high glucose conditions. Spirohydantoin of glucopyranose and N-acetyl-beta-D-glucopyranosylamine have been identified as the most potent inhibitors of GP that bind at the catalytic site. Four spirohydantoin and three beta-D-glucopyranosylamine analogs have been designed, synthesized and tested for inhibition of GP in kinetic experiments. Depending on the functional group introduced, the K(i) values varied from 16.5 microM to 1200 microM. In order to rationalize the kinetic results, we determined the crystal structures of the analogs in complex with GP. All the inhibitors bound at the catalytic site of the enzyme, by making direct and water-mediated hydrogen bonds with the protein and by inducing minor movements of the side chains of Asp283 and Asn284, of the 280s loop that blocks access of the substrate glycogen to the catalytic site, and changes in the water structure in the vicinity of the site. The differences observed in the Ki values of the analogs can be interpreted in terms of variations in hydrogen bonding and van der Waals interactions, desolvation effects, ligand conformational entropy, and displacement of water molecules on ligand binding to the catalytic site.
Krill-eye: Superposition Compound Eye for Wide-Angle Imaging via GRIN Lenses (2010)

We propose a novel wide angle imaging system inspired by compound eyes of animals. Instead of using a single lens, well compensated for aberration, we used a number of simple lenses to form a compound eye which produces practically distortion-free, uniform images with angular variation. The images formed by the multiple lenses are superposed on a single surface for increased light efficiency. We use GRIN (gradient refractive index) lenses to create sharply focused images without the artifacts seen when using reflection based methods for X-ray astronomy. We show the theoretical constraints for forming a blur-free image on the image sensor, and derive a continuum between 1 : 1 flat optics for document scanners and curved sensors focused at infinity. Finally, we show a practical application of the proposed optics in a beacon to measure the relative rotation angle between the light source and the camera with ID information.
Flow‐level performance analysis of a multi‐rate system supporting stream and elastic services (2012)

SUMMARY We consider a multi‐rate system where stream and elastic flows receive service. Both the stream and the elastic classes are associated with peak rate limitation. In contrast to the constant bit rate stream flows, the elastic flows tolerate bandwidth compression while in service. Because of the occasional bandwidth compression, the holding time of elastic flows depends on their perceived throughput. Although this model is Markovian under quite non‐restrictive assumptions, the model's state space grows exponentially with the number of traffic classes. The model is not quasi‐reversible, and therefore, it cannot be evaluated by efficient recursive formulae. We propose a method whereby the original state space is mapped to a two‐dimensional one, independently of the number of the stream and the elastic traffic classes. The special structure of the two‐dimensional model allows us to develop an efficient method that approximates the average throughputs of elastic flows. The state space reduction together with the proposed approximation provides a powerful tool for the performance analysis of this model as it allows the approximation of the average throughputs of elastic flows reasonably accurately in large models as well. Copyright © 2012 John Wiley &amp; Sons, Ltd.
58.5L: Late‐News Paper : Engineering a Retinal Scanning Laser Display with Integrated Accommodative Depth Cues (2003)

Abstract A deformable membrane mirror (DMM) dynamically varies image focus in a retinal scanning laser display. The display presents variable accommodation cues with the goal of matching the vergence cues generated by stereo images. This study examines the effects of the DMM on beam diameter and power at the exit pupil of the display.
Chip-scale wavelength-division multiplexed integrated sensor arrays (2010)

We demonstrate a wavelength-division multiplexing (WDM) technique for interrogating multiple sensors on a single chip. While wavelength- and frequency-division multiplexing (FDM) has previously been demonstrated in micro-electro mechanical (MEMS) sensors, numerous off-chip components were required thereby increasing the system size and limiting the number of sensors. In contrast, our approach enables all components to be developed on-chip. The high Q-factor afforded by optical microcavities enables a large number of sensor elements to be interrogated using WDM. First, we demonstrate wavelength-enabled addressing of individual sensors. Next, we show how two sensors can be individually interrogated in a sensor network. Finally, we illustrate how such "sensor-networks on a chip" are fabricated. The ability to develop large-scale arrays, where each sensor has been functionalized to respond to a different analyte, enables increased selectivity for MEMS resonant chemical sensors.
Tumor cell total mRNA expression shapes the molecular and clinical phenotype of cancer (2020)

Abstract Cancers can vary greatly in their transcriptomes. In contrast to alterations in specific genes or pathways, differences in tumor cell total mRNA content have not been comprehensively assessed. Technical and analytical challenges have impeded examination of total mRNA expression at scale across cancers. To address this, we developed a model for quantifying tumor-specific total mRNA expression (TmS) from bulk sequencing data, which performs transcriptomic deconvolution while adjusting for mixed genomes. We used single-cell RNA sequencing data to demonstrate total mRNA expression as a feature of tumor phenotype. We estimated and validated TmS in 5,015 patients across 15 cancer types identifying significant inter-individual variability. At a pan-cancer level, high TmS is associated with increased risk of disease progression and death. Cancer type-specific patterns of genetic alterations, intra-tumor genetic heterogeneity, as well as pan-cancer trends in metabolic dysregulation and hypoxia contribute to TmS. Taken together, our results suggest that measuring cell-type specific total mRNA expression offers a broader perspective of tracking cancer transcriptomes, which has important biological and clinical implications.
Glucocorticoids induce retinal toxicity through mechanisms mainly associated with paraptosis. (2007)

These observations suggest that corticosteroid-induced retinal cell death may be carried out mainly through a paraptosis pathway.
Puzzling Transcutaneous Access Flow Measurements before and after Hemodialysis (2003)

Letters| August 29 2003 Puzzling Transcutaneous Access Flow Measurements before and after Hemodialysis Subject Area: Nephrology Nikolai Krivitski; Nikolai Krivitski Transonic Systems, Inc., Ithaca, N.Y., USA Search for other works by this author on: This Site PubMed Google Scholar Swaroop Gantela Swaroop Gantela Transonic Systems, Inc., Ithaca, N.Y., USA Search for other works by this author on: This Site PubMed Google Scholar Blood Purif (2003) 21 (4-5): 301. https://doi.org/10.1159/000072549 Article history Published Online: August 29 2003 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Nikolai Krivitski, Swaroop Gantela; Puzzling Transcutaneous Access Flow Measurements before and after Hemodialysis. Blood Purif 1 July 2003; 21 (4-5): 301. https://doi.org/10.1159/000072549 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Purification Search Advanced Search This content is only available via PDF. 2003Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Article PDF first page preview Close Modal You do not currently have access to this content.
A Simple and Scalable Strategy for Analysis of Endogenous Protein Dynamics (2020)

The ability to analyze protein function in a native context is central to understanding cellular physiology. This study explores whether tagging endogenous proteins with a reporter is a scalable strategy for generating cell models that accurately quantitate protein dynamics. Specifically, it investigates whether CRISPR-mediated integration of the HiBiT luminescent peptide tag can easily be accomplished on a large-scale and whether integrated reporter faithfully represents target biology. For this purpose, a large set of proteins representing diverse structures and functions, some of which are known or potential drug targets, were targeted for tagging with HiBiT in multiple cell lines. Successful insertion was detected for 86% of the targets, as determined by luminescence-based plate assays, blotting, and imaging. In order to determine whether endogenously tagged proteins yield more representative models, cells expressing HiBiT protein fusions either from endogenous loci or plasmids were directly compared in functional assays. In the tested cases, only the edited lines were capable of accurately reproducing the anticipated biology. This study provides evidence that cell lines expressing HiBiT fusions from endogenous loci can be rapidly generated for many different proteins and that these cellular models provide insight into protein function that may be unobtainable using overexpression-based approaches.
The whale shark genome reveals how genomic and physiological properties scale with body size (2018)

Abstract The endangered whale shark ( Rhincodon typus ) is the largest fish on Earth and is a long-lived member of the ancient Elasmobranchii clade. To characterize the relationship between genome features and biological traits, we sequenced and assembled the genome of the whale shark and compared its genomic and physiological features to those of 81 animals and yeast. We examined scaling relationships between body size, temperature, metabolic rates, and genomic features and found both general correlations across the animal kingdom and features specific to the whale shark genome. Among animals, increased lifespan is positively correlated to body size and metabolic rate. Several genomic features also significantly correlated with body size, including intron and gene length. Our large-scale comparative genomic analysis uncovered general features of metazoan genome architecture: GC content and codon adaptation index are negatively correlated, and neural connectivity genes are longer than average genes in most genomes. Focusing on the whale shark genome, we identified multiple features that significantly correlate with lifespan. Among these were very long gene length, due to large introns highly enriched in repetitive elements such as CR1-like LINEs, and considerably longer neural genes of several types, including connectivity, activity, and neurodegeneration genes. The whale shark’s genome had an expansion of gene families related to fatty acid metabolism and neurogenesis, with the slowest evolutionary rate observed in vertebrates to date. Our comparative genomics approach uncovered multiple genetic features associated with body size, metabolic rate, and lifespan, and showed that the whale shark is a promising model for studies of neural architecture and lifespan.
Retrotransposon overdose and genome integrity (2009)

Yeast and mammalian genomes are replete with nearly identical copies of long dispersed repeats in the form of retrotransposons. Mechanisms clearly exist to maintain genome structure in the face of potential rearrangement between the dispersed repeats, but the nature of this machinery is poorly understood. Here we describe a series of distinct "retrotransposon overdose" (RO) lineages in which the number of Ty1 elements in the Saccharomyces cerevisiae genome has been increased by as much as 10 fold. Although these RO strains are remarkably normal in growth rate, they demonstrate an intrinsic supersensitivity to DNA-damaging agents. We describe the identification of mutants in the DNA replication pathway that enhance this RO-specific DNA damage supersensitivity by promoting ectopic recombination between Ty1 elements. Abrogation of normal DNA replication leads to rampant genome instability primarily in the form of chromosomal aberrations and confirms the central role of DNA replication accuracy in the stabilization of repetitive DNA.
Patterns of opioid use in older people diagnosed with cancer in New South Wales, Australia (2020)

Our study suggests that many older cancer patients were dispensed opioids before their cancer diagnosis. Previously opioid-treated people had more intense opioid use patterns after diagnosis than opioid-naïve people. Acknowledging the history of opioid use is important as it may complicate pain treatment in clinical practice.
Analysis of Tarnished Copper Foil (2008)

Tarnished copper foil was investigated before surface treatment. Its surface color changed to band strips (streaks) of soft reddish-brown, dark blue, purple, dark blue, and soft reddish-brown. Its surface morphology was related to the color change. Actually, this surface oxide film formation caused the color change. Surfaces of all samples were composed of CuO and Cu2O. The fractions of these oxides differed. The soft reddish-brown out-end sample has the lowest CuO content ; all other samples show almost identical CuO contents. The oxygen contents of the out-end sample show the lowest value. Its degree of oxidation was the lowest of all samples. The out-end and center samples show an almost constant CuO content region. In contrast, the CuO content of the middle of the samples decreased gradually with increasing depth from the surface. The color samples, out-ends, and center samples have similar depth profiles of CuO contents, but they have different surface contents of CuO. However, the other color samples, the middle two samples, show almost identical CuO depth profiles and contents. Therefore, it is concluded that the main factor of color change is the CuO depth profile.
Glial cells of the human fovea. (2020)

This study showed that in humans, astrocytic glial cells cover the foveal pit. Their roles in macula homeostasis and mechanisms of macular diseases disease remain to be determined.
Optimizing Memory Translation Emulation in Full System Emulators (2015)

The emulation speed of a full system emulator (FSE) determines its usefulness. This work quantitatively measures where time is spent in QEMU [Bellard 2005], an industrial-strength FSE. The analysis finds that memory emulation is one of the most heavily exercised emulator components. For workloads studied, 38.1% of the emulation time is spent in memory emulation on average, even though QEMU implements a software translation lookaside buffer (STLB) to accelerate dynamic address translation. Despite the amount of time spent in memory emulation, there has been no study on how to further improve its speed. This work analyzes where time is spent in memory emulation and studies the performance impact of a number of STLB optimizations. Although there are several performance optimization techniques for hardware TLBs, this work finds that the trade-offs with an STLB are quite different compared to those with hardware TLBs. As a result, not all hardware TLB performance optimization techniques are applicable to STLBs and vice versa. The evaluated STLB optimizations target STLB lookups, as well as refills, and result in an average emulator performance improvement of 24.4% over the baseline.