gebhart/patrepeval huggingface dataset:
Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19 (2020)

Coronaviruses (CoVs) are a group of enveloped, single-stranded positive genomic RNA viruses and some of them are known to cause severe respiratory diseases in human, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the ongoing coronavirus disease-19 (COVID-19). One key element in viral infection is the process of viral entry into the host cells. In the last two decades, there is increasing understanding on the importance of the endocytic pathway and the autophagy process in viral entry and replication. As a result, the endocytic pathway including endosome and lysosome has become important targets for development of therapeutic strategies in combating diseases caused by CoVs. In this mini-review, we will focus on the importance of the endocytic pathway as well as the autophagy process in viral infection of several pathogenic CoVs inclusive of SARS-CoV, MERS-CoV and the new CoV named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and discuss the development of therapeutic agents by targeting these processes. Such knowledge will provide important clues for control of the ongoing epidemic of SARS-CoV-2 infection and treatment of COVID-19.
FASTDash (2007)

Software developers spend significant time gaining and maintaining awareness of fellow developers' activities. FASTDash is a new interactive visualization that seeks to improve team activity awareness using a spatial representation of the shared code base that highlights team members' current activities. With FASTDash, a developer can quickly determine which team members have source files checked out, which files are being viewed, and what methods and classes are currently being changed. The visualization can be annotated, allowing programmers to supplement activity information with additional status details. It provides immediate awareness of potential conflict situations, such as two programmers editing the same source file. FASTDash was developed through user-centered design, including surveys, team interviews, and in situ observation. Results from a field study show that FASTDash improved team awareness, reduced reliance on shared artifacts, and increased project-related communication. Additionally, the team that participated in our field study continues to use FASTDash.
Treatment of Chronic Hepatitis C With Interferon Alfa–N3: A Multicenter, Randomized, Open–Label Trial (1997)

We studied the antiviral effectiveness and safety of interferon alfa-n3, a natural alpha interferon which contains multiple interferon species, in the treatment of previously untreated patients with chronic hepatitis C. Seventy-seven patients were randomized to receive either 1.0, 2.5, 5.0, or 10.0 million units (MU) of interferon alfa-n3 three times a week for 24 weeks and were then followed for an additional 24 weeks. At the end of therapy, 67% of patients in the 10 MU group normalized serum alanine transaminase (ALT) levels and 59% had no hepatitis C virus (HCV) RNA detected by polymerase chain reaction. At the end of the follow-up period, 44% of patients in the 10 MU group maintained normal ALT, and 24% had nondetectable HCV RNA. Lower doses were much less effective. Interferon alfa-n3 was well tolerated and no patient developed neutralizing anti-interferon antibodies during or after the treatment period. Interferon alfa-n3 appears to be effective against hepatitis C virus and deserves further study in larger randomized controlled trials.
Studies of biosynthesis of waxes by developing jojoba seed: III. Biosynthesis of wax esters from Acyl‐CoA and long chain alcohols (1981)

Abstract Acyl‐CoA: alcohol transacylase activity was demonstrated in cell‐free homogenates of developing jojoba seeds. The optimal pH was 8.0–8.1. Under optimal conditions, wax formation had a nearly linear relationship with extract concentration; the time course of wax formation was also linear up to 30 min. cis ‐11‐Eicosenol was the most effective alcohol substrate whereas tetradecanol, octadecanol, dodecanol, cis ‐9‐octadecanol, and cis ‐13‐eicosenol gave progressively lower activities. Either saturated or unsaturated acyl‐CoA with 18 or 20 C‐atoms had similar activity. The enzyme was fairly stable at 0 C, less stable at RT and labile above 30 C. Differential centrifugation showed that the 12,000 × g fat pad was the most active in wax formation; to maximize the activity, a 12,000 × g supernatant appeared to be necessary. This factor in the supermatant was thermolabile and nondialyzable.
Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses (1995)

Recombinant adenoviruses are an attractive vehicle for gene therapy to the lung in the treatment of cystic fibrosis (CF). First-generation viruses deleted of E1a and E1b transduce genes into airway epithelial cells in vivo; however, expression of the transgene is transient and associated with substantial inflammatory responses, and gene transfer is significantly reduced following a second administration of the virus. In this study, we have used mice deficient in immunological effector functions in combination with adoptive and passive transfer techniques to define antigen-specific cellular and humoral immune responses that underlie these important limitations. Our studies indicate that major histocompatibility complex class I-restricted CD8+ cytotoxic T lymphocytes are activated in response to newly synthesized antigens, leading to destruction of virus infected cells and loss of transgene expression. Major histocompatibility complex class II-associated presentation of exogenous viral antigens activates CD4+ T-helper (TH) cells of the TH1 subset and, to a lesser extent, of the TH2 subset. CD4+ cell-mediated responses are insufficient in the absence of cytotoxic T cells to completely eliminate transgene containing cells; however, they contribute to the formation of neutralizing antibodies in the airway which block subsequent adenovirus-mediated gene transfer. Definition of immunological barriers to gene therapy of cystic fibrosis should facilitate the design of rational strategies to overcome them.
Virtual metrology for plasma etch processes. (2011)

Plasma processes can present dicult control challenges due to time-varying dynamics&#13;\nand a lack of relevant and/or regular measurements. Virtual metrology (VM) is the&#13;\nuse of mathematical models with accessible measurements from an operating process to&#13;\nestimate variables of interest. This thesis addresses the challenge of virtual metrology&#13;\nfor plasma processes, with a particular focus on semiconductor plasma etch.&#13;\nIntroductory material covering the essentials of plasma physics, plasma etching, plasma&#13;\nmeasurement techniques, and black-box modelling techniques is rst presented for readers&#13;\nnot familiar with these subjects. A comprehensive literature review is then completed&#13;\nto detail the state of the art in modelling and VM research for plasma etch processes.&#13;\nTo demonstrate the versatility of VM, a temperature monitoring system utilising a&#13;\nstate-space model and Luenberger observer is designed for the variable specic impulse&#13;\nmagnetoplasma rocket (VASIMR) engine, a plasma-based space propulsion system. The&#13;\ntemperature monitoring system uses optical emission spectroscopy (OES) measurements&#13;\nfrom the VASIMR engine plasma to correct temperature estimates in the presence of&#13;\nmodelling error and inaccurate initial conditions. Temperature estimates within 2% of&#13;\nthe real values are achieved using this scheme.&#13;\nAn extensive examination of the implementation of a wafer-to-wafer VM scheme to estimate&#13;\nplasma etch rate for an industrial plasma etch process is presented. The VM&#13;\nmodels estimate etch rate using measurements from the processing tool and a plasma&#13;\nimpedance monitor (PIM). A selection of modelling techniques are considered for VM&#13;\nmodelling, and Gaussian process regression (GPR) is applied for the rst time for VM&#13;\nof plasma etch rate. Models with global and local scope are compared, and modelling&#13;\nschemes that attempt to cater for the etch process dynamics are proposed. GPR-based&#13;\nwindowed models produce the most accurate estimates, achieving mean absolute percentage&#13;\nerrors (MAPEs) of approximately 1:15%. The consistency of the results presented&#13;\nsuggests that this level of accuracy represents the best accuracy achievable for&#13;\nthe plasma etch system at the current frequency of metrology.&#13;\nFinally, a real-time VM and model predictive control (MPC) scheme for control of&#13;\nplasma electron density in an industrial etch chamber is designed and tested. The VM&#13;\nscheme uses PIM measurements to estimate electron density in real time. A predictive&#13;\nfunctional control (PFC) scheme is implemented to cater for a time delay in the VM&#13;\nsystem. The controller achieves time constants of less than one second, no overshoot,&#13;\nand excellent disturbance rejection properties. The PFC scheme is further expanded by&#13;\nadapting the internal model in the controller in real time in response to changes in the&#13;\nprocess operating point.
Human Rhinoviruses Inhibit the Accessory Function of Dendritic Cells by Inducing Sialoadhesin and B7-H1 Expression (2005)

Dendritic cells (DC) are professional APCs with an unmatched ability to interact with and activate T cells. There is accumulating evidence that DC not only efficiently stimulate T cell activation but also regulate T cell responses. However, little is known about cell surface structures on DC involved in the regulation of T cell responses. We demonstrate that human rhinoviruses (HRV) can efficiently inhibit the accessory function of DC through induction of inhibitory cell surface receptors. We observed that treatment of DC with HRV14 (R-DC), a member of the major group HRV family, diminished their T cell stimulatory capacity and induced a promiscuous and deep anergic state in cocultured T cells despite high levels of MHC molecules as well as costimulatory molecules, e.g., B7-1 (CD80) and B7-2 (CD86), and independent of inhibitory soluble factors such as IL-10. In contrast, expression of inhibitory B7-H1 molecules was up-regulated and R-DC de novo expressed sialoadhesin (Sn). Most importantly, blocking of B7-H1 and Sn on R-DC with specific mAbs against both receptors reverted the inhibitory phenotype. Thus, inhibitory signals delivered from R-DC to T cells via B7-H1 and Sn were critical for the induction of anergy. These observations suggest that an altered accessory molecule repertoire on DC upon interaction with HRV down-modulates adaptive immune responses during the viral infection.
Myocardin-related Transcription Factor-A Complexes Activate Type I Collagen Expression in Lung Fibroblasts (2011)

Pulmonary fibrosis is characterized by the excessive deposition of a collagen-rich extracellular matrix. The accumulation of collagen within the lung interstitium leads to impaired respiratory function. Furthermore, smooth muscle actin-positive myofibroblasts within the fibrotic lung contribute to disease progression. Because collagen and smooth muscle cell α-actin are coordinately expressed in the setting of fibrosis, the hypothesis was tested that specific transcriptional regulators of the myocardin family might also regulate collagen gene expression in myofibroblasts. Myocardin-related transcription factors (MRTFs), through their interaction with the serum-response factor (SRF) on CArG box regulatory elements (CC(A/T)6GG), are important regulators of myofibroblast differentiation. MRTF-A transactivated type I collagen gene reporters as much as 100-fold in lung myofibroblasts. Loss of functional MRTF-A using either a dominant negative MRTF-A isoform, shRNA targeting MRTF-A, or genetic deletion of MRTF-A in lung fibroblasts significantly disrupted type I collagen synthesis relative to controls. Analysis of the COL1A2 proximal promoter revealed a noncanonical CArG box (CCAAACTTGG), flanked by several Sp1 sites important for MRTF-A activation. Chromatin immunoprecipitation experiments confirmed the co-localization of MRTF-A, SRF, and Sp1 bound to the same region of the COL1A2 promoter. Mutagenesis of either the noncanonical CArG box or the Sp1 sites significantly disrupted MRTF-A activation of COL1A2. Together, our findings show that MRTF-A is an important regulator of collagen synthesis in lung fibroblasts and exhibits a dependence on both SRF and Sp1 function to enhance collagen expression.
Efficient stackless hierarchy traversal on GPUs with backtracking in constant time (2016)

The fastest acceleration schemes for ray tracing rely on traversing a bounding volume hierarchy (BVH) for efficient culling and use backtracking, which in the worst case may expose cost proportional to the depth of the hierarchy in either time or state memory. We show that the next node in such a traversal actually can be determined in constant time and state memory. In fact, our newly proposed parallel software implementation requires only a few modifications of existing traversal methods and outperforms the fastest stack-based algorithms on GPUs. In addition, it reduces memory access during traversal, making it a very attractive building block for ray tracing hardware.
Estimation of concentration and bonding environment of water dissolved in common solvents using near infrared absorptivity (1999)

Integrated near infrared (NIR) absorbance has been used to determine the absorptivity of the upsilon(2) + upsilon(3) combination band of the asymmetric stretch (upsilon(2)) and the bending vibration (upsilon(3)) for water in several organic solvents. Absorptivity measured in this way is essentially constant across the absorption envelope and is found to be 336 L mol(-1) cm(-1) with a standard deviation of 4 L mol(-1) cm(-1) as estimated from a least squares fit of a straight line to data from water concentrations between 0.01 mol/L and 0.06 mol/L. Absorptivity measured from the peak maximum of the upsilon(2) + upsilon(3) combination band of water varies with the type of hydrogen bonding of the water molecule because the shape of the NIR absorption envelope changes with the hydrogen bonding. Because the integrated NIR absorptivity of the upsilon(2) + upsilon(3) combination band of water is essentially constant across the absorption envelope, the NIR absorption envelope reflects the distribution of hydrogen bonding of the water. The shape and location of the absorption envelope appear to be governed mostly by the number of hydrogen bonds from the water molecules to easily polarized atoms. Water that is a donor in hydrogen bonds to atoms which are not easily polarized (such as the oxygen of a typical carbonyl group) absorbs near 5240 cm(-1) to 5260 cm(-1). Water that donates one hydrogen bond to an easily polarized atom (such as a water molecule oxygen) absorbs near 5130 cm(-1) to 5175 cm(-1), and water that donates two hydrogen bonds to easily polarized atoms is estimated to absorb near 5000 cm(-1) to 5020 cm(-1). Water donating two hydrogen bonds to other water molecules may be said to be in a water-like environment. In no case does a small amount of water absorbed in a host material appear to have a water-like environment.
A computer-based bioelectrical impedance spectroscopic system for noninvasive assessment of compartmental fluid redistribution (2002)

Bioimpedance methods using fixed frequency stimulation to measure volume changes and hemodynamic parameters in body segments of human subjects under various conditions of body position and orthostatic stress are discussed. An electrical impedance spectroscopic (EIS) system has been developed to allow extension of these studies to include examination of the redistribution of fluids between the intracellular and extracellular compartments of the monitored body segments. Evaluated in studies of the human calf and thigh during 90 min of 6 degrees or 10 degrees head-down bed rest, the system promises to enable tracking of segmental and compartmental fluid redistribution in response to various environmental and physiological stresses with both temporal and anatomic resolution greater than that attainable with other methods.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Compensatory Phosphorylation and Protein-Protein Interactions Revealed by Loss of Function and Gain of Function Mutants of Multiple Serine Phosphorylation Sites in Endothelial Nitric-oxide Synthase (2003)

We examined the influence of individual serine phosphorylation sites in endothelial nitric-oxide synthase (eNOS) on basal and stimulated NO release, cooperative phosphorylation, and co-association with hsp90 and Akt. Mutation of the serine phosphorylation sites 116, 617, and 1179 to alanines affected the phospho-state of at least one other site, demonstrating cooperation between multiple phosphorylation events, whereas mutation of serine 635 to alanine did not cause compensation. Mutation of serines 116 and 617 to alanine promoted a greater protein-protein interaction with hsp90 and Akt and greater phosphorylation on serine 1179, the major site for Akt phosphorylation. More importantly, using alanine substitutions, Ser-116 is important for agonist, but not basal NO release, Ser-635 is important for basal, but not stimulated, Ser-617 negatively regulates basal and stimulated NO release, and Ser-1179 phosphorylation is stimulatory for both basal and agonist-mediated NO release. Using putative "gain of function" mutants (serine to aspartate) serines 635 and 1179 are important positive regulators of basal and stimulated NO release. S635D eNOS is the most efficacious, yielding 5-fold increases in basal and 2-fold increases in stimulated NO release from cells. However, S617A and S617D eNOS both increased NO release with opposite actions in NOS activity assays. Thus, multiple serine phosphorylation events regulate basal and stimulate NO release with Ser-635 and Ser-1179 being important positive regulatory sites and Ser-116 as a negative regulatory. Ser-617 may not be important for directly regulating NO release but is important as a modulator of phosphorylation at other sites and protein-protein interactions.
Formoterol Compared with Beclomethasone and Placebo on Allergen-induced Asthmatic Responses (1992)

Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration.
Active Efflux and Diffusion Are Involved in Transport of Pseudomonas aeruginosa Cell-to-Cell Signals (1999)

Many gram-negative bacteria communicate by N-acyl homoserine lactone signals called autoinducers (AIs). In Pseudomonas aeruginosa, cell-to-cell signaling controls expression of extracellular virulence factors, the type II secretion apparatus, a stationary-phase sigma factor (sigmas), and biofilm differentiation. The fact that a similar signal, N-(3-oxohexanoyl) homoserine lactone, freely diffuses through Vibrio fischeri and Escherichia coli cells has led to the assumption that all AIs are freely diffusible. In this work, transport of the two P. aeruginosa AIs, N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL) (formerly called PAI-1) and N-butyryl homoserine lactone (C4-HSL) (formerly called PAI-2), was studied by using tritium-labeled signals. When [3H]C4-HSL was added to cell suspensions of P. aeruginosa, the cellular concentration reached a steady state in less than 30 s and was nearly equal to the external concentration, as expected for a freely diffusible compound. In contrast, [3H]3OC12-HSL required about 5 min to reach a steady state, and the cellular concentration was 3 times higher than the external level. Addition of inhibitors of the cytoplasmic membrane proton gradient, such as azide, led to a strong increase in cellular accumulation of [3H]3OC12-HSL, suggesting the involvement of active efflux. A defined mutant lacking the mexA-mexB-oprM-encoded active-efflux pump accumulated [3H]3OC12-HSL to levels similar to those in the azide-treated wild-type cells. Efflux experiments confirmed these observations. Our results show that in contrast to the case for C4-HSL, P. aeruginosa cells are not freely permeable to 3OC12-HSL. Instead, the mexA-mexB-oprM-encoded efflux pump is involved in active efflux of 3OC12-HSL. Apparently the length and/or degree of substitution of the N-acyl side chain determines whether an AI is freely diffusible or is subject to active efflux by P. aeruginosa.
5.4 GHz Lamb Wave Resonator on LiNbO3 Thin Crystal Plate and Its Application (2011)

A cognitive radio system operating at frequencies from 400 MHz to 6 GHz requires tunable filters with a wide variable frequency range. Wide band resonators are required to realize such tunable filters consisting of resonators. However, it is difficult to fabricate a very high frequency and wide band resonator, such as 6 GHz and wider than 10%, respectively. The first antisymmetric (A 1 ) mode of a Lamb wave on a LiNbO 3 thin plate or film having a high velocity and a large electromechanical coupling factor is a suitable wave for fabricating an ultrawide band and high frequency resonator. This time, we attempted to fabricate a higher frequency Lamb wave resonator on a thin LiNbO 3 single-crystal plate instead of the LiNbO 3 film, though it has been considered difficult to form a very thin LiNbO 3 crystal plate. A new one-port Lamb wave resonator showed a high frequency in the 5 GHz range, a wide bandwidth of 12%, and a high impedance ratio of 62 dB at resonant and antiresonant frequencies. Moreover, we applied the resonator to a ladder-type tunable filter, and obtained the tunable range of 9% from 5.58 to 6.06 GHz theoretically.