gebhart/patrepeval huggingface dataset:
Calcineurin Inhibitors Synergize with Manogepix to Kill Diverse Human Fungal Pathogens (2022)

Invasive fungal infections have mortality rates of 30-90%, depending on patient co-morbidities and the causative pathogen. The frequent emergence of drug resistance reduces the efficacy of currently approved treatment options, highlighting an urgent need for antifungals with new modes of action. Addressing this need, fosmanogepix (<i>N</i>-phosphonooxymethylene prodrug of manogepix; MGX) is the first in a new class of gepix drugs, and acts as a broad-spectrum, orally bioavailable inhibitor of the essential fungal glycosylphosphatidylinositol (GPI) acyltransferase Gwt1. MGX inhibits the growth of diverse fungal pathogens and causes accumulation of immature GPI-anchored proteins in the fungal endoplasmic reticulum. Relevant to the ongoing clinical development of fosmanogepix, we report a synergistic, fungicidal interaction between MGX and inhibitors of the protein phosphatase calcineurin against important human fungal pathogens. To investigate this synergy further, we evaluated a library of 124 conditional expression mutants covering 95% of the genes encoding proteins involved in GPI-anchor biosynthesis or proteins predicted to be GPI-anchored. Strong negative chemical-genetic interactions between the calcineurin inhibitor FK506 and eleven GPI-anchor biosynthesis genes were identified, indicating that calcineurin signalling is required for fungal tolerance to not only MGX, but to inhibition of the GPI-anchor biosynthesis pathway more broadly. Depletion of these GPI-anchor biosynthesis genes, like MGX treatment, also exposed fungal cell wall (1→3)-β-D-glucans. Taken together, these findings suggest the increased risk of invasive fungal infections associated with use of calcineurin inhibitors as immunosuppressants may be mitigated by their synergistic fungicidal interaction with (fos)manogepix and its ability to enhance exposure of immunostimulatory glucans.
Review of Infrared Heating and Its Application to UHMWPE (2001)

The purpose of the cooperative research and development agreement between Smith & Nephew, Inc. (S&N) and ORNL was to explore the effects of infrared radiation heating on the physical properties of UHMWPE. Certified bars of ram extruded GUR 1050 UHMWPE were exposed to infrared heat under various conditions at ORNL. For comparison, specimens from the same bar stock were remelted using a conventional oven. The benefit to DOE was that knowledge was gained in low-temperature, vacuum heat-treating of polymers.
Dependence of Electrochemical Kinetics of Lithium Titanium Oxide Electrode on Hysteresis during a High-Rate Charge-Discharge Reaction (2009)

Abstract not Available.
Structure of ( E )-4-Hydroxy-3-methyl-but-2-enyl Diphosphate Reductase, the Terminal Enzyme of the Non-Mevalonate Pathway (2008)

Molecular evolution has evolved two metabolic routes for isoprenoid biosynthesis: the mevalonate and the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway. The MEP pathway is used by most pathogenic bacteria and some parasitic protozoa (including the malaria parasite, Plasmodium falciparum) as well as by plants, but is not present in animals. The terminal reaction of the MEP pathway is catalyzed by (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) reductase (LytB), an enzyme that converts HMBPP into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Here, we present the structure of Aquifex aeolicus LytB, at 1.65 A resolution. The protein adopts a cloverleaf or trefoil-like structure with each monomer in the dimer containing three alpha/beta domains surrounding a central [Fe3S4] cluster ligated to Cys13, Cys96, and Cys193. Two highly conserved His (His 42 and His 124) and a totally conserved Glu (Glu126) are located in the same central site and are proposed to be involved in ligand binding and catalysis. Substrate access is proposed to occur from the front-side face of the protein, with the HMBPP diphosphate binding to the two His and the 4OH of HMBPP binding to the fourth iron thought to be present in activated clusters, while Glu126 provides the protons required for IPP/DMAPP formation.
Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes (2015)

Sotagliflozin significantly improved glycemic control, without increasing the rate of hypoglycemia measurements, in diabetic mice maintained on a low insulin dose. This sotagliflozin-mediated improvement in glycemic control was comparable to that achieved by raising the insulin dose alone, but was not accompanied by the increased rate of hypoglycemia measurements observed with the higher insulin dose.
Backtracking of influenza polymerase upon consecutive incorporation of nucleoside analogue T1106 directly observed by high-resolution cryo-electron microscopy (2022)

Abstract The broad-spectrum antiviral pseudobase T705, a fluorinated pyrazinecarboxamide, is incorporated via its triphosphate form into nascent viral RNA by viral RNA-dependent RNA polymerases. Since it mimics guanine or adenine it can act as a mutagen, whereas consecutive incorporation leads to chain termination. Here we examine the structural basis for incorporation and stalling for the case of influenza polymerase, using T1106-TP, the nucleotide form of T1105, the de-fluoro analogue of T705. We used a specially designed template that allows single T1106-MP incorporation at a defined site followed by consecutive T1106-MP incorporation and stalling four nucleotides later, as demonstrated by biochemical analysis. A high-resolution cryoEM structure of influenza A/H7N9 polymerase, stalled after transcribing this template, revealed that the entire product-template duplex has backtracked by five nucleotides. Consequently, the singly incorporated T1106-MP resides at the +1 position and forms an unexpected wobble base-pair with a U in the template. The relative stability of the canonical and wobble T1106:U base-pairs in different contexts is investigated by molecular dynamics simulations. Using a different template and influenza B polymerase we also observe stalling after double incorporation of T1106-MP and structural analysis showed again that backtracking occurs, this time by four nucleotides. These results show that, at least in early elongation, consecutive T1106-MP incorporation into the product destabilises the proximal end of the product-template duplex, promoting irreversible backtracking until a more favourable overall configuration is achieved. These results give new insight into the unusual mechanism of chain termination by pyrazinecarboxamide base analogues.
Mott‐Limited Thermopower of Pascal Electron Liquid Phases at the LaAlO3/SrTiO3 Interface (2023)

The thermoelectric properties of quasi‐1D electron waveguides at the LaAlO 3 /SrTiO 3 interface at millikelvin temperatures are investigated. A highly enhanced and oscillating thermopower is found for these electron waveguides, with values exceeding 100 μV K −1 at 0.1 K in the electron‐depletion regime. The Mott relation, which governs the band‐term thermopower of noninteracting electrons, agrees well with the experimental findings in and around regimes where strongly attractive electron–electron interactions lead to a previously reported Pascal series of conductance explained by bound states of electrons. These results pave the way for quantized thermal transport studies of emergent electron liquid phases in which transport is governed by quasiparticles with charges that are integer multiples or fractions of an electron.
Role of sonography in the evaluation of carotid artery stents (2005)

Sonography allows accurate evaluation of stent placement within the vessel and visualization of stent-media distance. Stent-media separation may be an early detection sign for stent stenosis development. Velocity criteria developed for non-stented vessels, when applied to stented vessels, correlate well with angiographic findings. Doppler velocity measurements when compared with visible stent assessment may reduce false-positives.
The evolution of Big Data in neuroscience and neurology (2023)

The online version contains supplementary material available at 10.1186/s40537-023-00751-2.
Application of FTIR as a continuous emission monitoring system for cement kiln emissions (1994)

During the last several years, Entropy conducted several emissions tests using Fourier transform infrared spectrometry (FTIR) as an innovative means of measuring multicomponent mixtures of hazardous air pollutants (HAPs) and other criteria pollutants from cement kilns, and other source categories. These tests were administered and sponsored by the US Environmental Protection Agency`s Office of Air Quality Planning and Standards (OAQPS) Emission Measurement Branch (EMB) and Industrial Studies Branch (ISB). Infrared components have been employed for years in conventional continuous emission monitoring systems (CEMSs), and FTIR instruments are commonplace in the analytical laboratory. Recently, FTIR has emerged as a powerful multicomponent analyzer and a CEM because of the speed of analysis and information generated in a single infrared spectrum. The speedy analysis combined with the multicomponent capabilities of FTIR spectrometry make this an attractive instrumental choice for CEM measurements in cement kiln emissions. In addition, direct analysis of flue gas often provides a more representative emissions profile than collection of flue gas in an impinger train.
The Novel Ins(1,4,5)P3 Analog 3-Amino-3-deoxy-Ins(1,4,5)P3: A pH-Dependent Ins(1,4,5)P3 Receptor Partial Agonist in SH-SY5Y Neuroblastoma Cells (1994)

We have synthesized the first amino-substituted inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] analogue, D-3-amino-3-deoxy-myo-Ins(1,4,5)P3 (9). Although 9 is a full agonist at the Ca2+ mobilizing Ins(1,4,5)P3 receptor at pH 7.2 and 7.6, it is apparently a high intrinsic activity partial agonist at pH 6.8, releasing only 80% of the Ins(1,4,5)P3-sensitive Ca2+ stores of SH-SY5Y cells. Additionally, 9 was able to fully displace [3H]Ins(1,4,5)P3 from binding sites in rat cerebellum membranes at both pH 6.8 and 7.6, indicating a full interaction with the Ins(1,4,5)P3 receptor. The activity displayed by this amino analogue is unexpected and may be indicative of a pH-dependent conformational change in the amino acid residues comprising the Ins(1,4,5)P3 binding site.
Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host (2019)

Germ-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.
Structural and Electrochemical Properties of Layered Li[Ni[sub 1−2x]Co[sub x]Mn[sub x]]O[sub 2] (x=0.1–0.3) Positive Electrode Materials for Li-Ion Batteries (2007)

Structural and electrochemical properties of as positive electrode materials for lithium batteries were investigated. The materials were prepared via a coprecipatation process. From X-ray diffraction studies, it was found that the synthesized materials were crystallized into an layered structure . With increasing Co and Mn content in , the corresponding lattices were slightly contracted. X-ray absorption near edge spectra of also showed that the oxidation state of Ni is changed from to when tetravalent Mn is present in oxide . From Rietveld refinements of powder X-ray diffraction data, it was found that further increase in Co and Mn content also resulted in reduced cation mixing between and in Li layers. Electrochemical properties and thermal stability were also affected by the physical properties. When tetravalent Mn appeared in the structure, the corresponding cyclability was greatly improved compared to that of . Furthermore, thermal stability at highly delithiated state was also significantly enhanced by the existence of electrochemically inactive tetravalent Mn in the oxide matrix.
Estimating black‐level emissions of computer‐controlled displays (2003)

Abstract It is quite common for computer‐controlled displays to emit light in image areas set to digital values of zero, referred to as their black level. This is expected for liquid–crystal displays and also can occur for cathode‐ray tube displays when the “brightness” (gun‐amplifier offset) is set excessively high. For either display, the light emission at the black level results in color channels whose chromaticities vary with luminance level. Consequently, typical methods of colorimetric characterization result in large error. When this black‐level emission is measured and accounted for suitably, characterization accuracy is dramatically improved. Unfortunately, many instruments used to measure displays have too low a sensitivity to measure black‐level emission with sufficient precision and accuracy. A method of estimating black‐level emissions was derived and tested. Because the optimal black‐level results in channel chromaticities that are invariant to the greatest extent with luminance level, an objective function was defined as the sum of chromaticity variances of each channel over a range of measurements. Minimizing this objective function resulted is an estimate of a display's black level. The estimated black level resulted in equivalent or superior performance to direct measurements. © 2003 Wiley Periodicals, Inc. Col Res Appl, 28, 379–383, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.10181
Public-key cryptography and password protocols (1998)

We study protocols for strong authentication and key exchange in asymmetric scenarios where the authentication server possesses ~a pair of private and public keys while the client has only a weak human-memorizable password as its authentication key. We present and analyze several simple password authentication protocols in this scenario, and show that the security of these protocols can be formally proven based on standard cryptographic assumptions. Remarkably, our analysis shows optimal resistance to off-line password guessing attacks under the choice of suitable public key encryption functions. In addition to user authentication, we describe ways to enhance these protocols to provide two-way authentication, authenticated key exchange, defense against server's compromise, and user anonymity. We complement these results with a proof that strongly indicates that public key techniques are unavoidable for password protocols that resist off-line guessing attacks.As a further contribution, we introduce the notion of public passwords that enables the use of the above protocols in situations where the client's machine does not have the means to validate the server's public key. Public passwords serve as hand-held certificates that the user can carry without the need for specal computing devices.
33.1 A 16nm 32Mb Embedded STT-MRAM with a 6ns Read-Access Time, a 1M-Cycle Write Endurance, 20-Year Retention at 150°C and MTJ-OTP Solutions for Magnetic Immunity (2023)

Embedded non-volatile memory (eNVM) is an essential element for microcontrollers (MCUs) used in automotive applications. As the automotive market transitions to greater electrification and autonomy, we are seeing MCU growth in the car: including integration to simplify system design, an electrical and electronic (E/E) architectural evolution to domain/zone control, and over-the-air (OTA) updates beyond 128Mb eNVM densities. To support this transition technology nodes are migrating from 55/40nm to 28/16nm. In addition, traditional charge-based embedded Flash will be replaced by Back-end-of-line (BEOL) memories: such as STT-MRAM [1]–[3], PCRAM [4], and RRAM. Of these candidates, STT-MRAM is the most promising solution for automotive applications due to its high-temperature data retention, high write endurance, and fast write speed. However, STT-MRAM still faces several challenges from the inherent properties of magnetic tunnel junctions (MTJs) and the side effects of process integration: such as array-level variability and magnetic-field interference (MFI). In this work, several design solutions are proposed to overcome these challenges: (1) a novel merged-local-reference scheme is used to overcome the array-edge effect on the MTJs; (2) write bias segment trimming is used to mitigate the near-far effect for better write endurance; (3) an MTJ-based one-time programmable (OTP) is used to preserve critical data during the wafer-level chip-scale packaging (WLCSP) process (360°C, 3hr), and; (4) a novel sensing-reference scheme is used so that this MTJ-OTP is immune to external-magnetic-field interference. A 32-Mb STT-MRAM test chip based on these proposed solutions is successfully fabricated in a 16nm FinFET CMOS process, Measured results confirm its excellent performance and manufacturability for next generation automotive MCU application.
A Novel Dry Selective Etch of SiGe for the Enablement of High Performance Logic Stacked Gate-All-Around NanoSheet Devices (2019)

In this paper, we demonstrate a first of a kind SiGe dry etch technique for the formation of inner spacers and for channel release, enabling stacked NanoSheet (NS) gate-all-around device architectures. This novel etch involves a precisely controlled lateral SiGe etch with very high selectivity to Si. A detailed characterization of this novel process and its selectivity and tunability as a function of Ge concentration are discussed. The outstanding 150:1 selectivity for SiGe25% versus Si of this process makes it the best candidate for inner spacer shape and depth control, and enables a wide range of NS device widths on the same wafer with low Si channel thickness variability, which is critical for power/performance optimization of high performance computing stacked NS devices. As a result, very low transistor threshold voltage and subthreshold slope variations versus device width are measured. The reduced Si channel (sheet) thinning obtained with this etch process improves device performance over the standard etch method, as measured by drain current, max transconductance and bias-temperature instability.
Off-Road Glance Behavior, Response Time to a Forward Collision Hazard, and Engagement Strategy Effects in Automated Driving (2017)

Blommer et al. (2015) reported on a simulator study that investigated a driver engagement (DE) strategy designed to keep the driver-in-the-loop during automated driving in the face of two different types of secondary tasks. The method, first reported by Carsten et al. (2012), involved driving in fully automated driving mode for 6 minutes followed by 1 minute of manual driving, after which this fixed schedule was repeated several times throughout the drive. This scheduled strategy was compared to a reference condition in which different participants experienced continuous automated driving without interruptions. For each condition, some participants watched a video and others listened to the radio. All drives ended in automated driving mode with a surprise forward collision (FC) hazard to which the participant had to manually intervene. Compared to video watchers, radio listeners responded faster, looked to the road scene more, and they were more often looking forward at FC event onset. The DE strategy had no effect on radio listeners. In contrast, video watchers responded to the hazard more quickly with the scheduled strategy than without it. However, there was no reliable statistical difference between DE conditions in percent-eye-glance-time looking to the forward road scene during automated driving or in the number of drivers looking forward at FC event onset. This paper presents additional analyses of off-road eye glance behavior and finds no relationship between how long people were looking away prior to receiving a Forward Collision Warning (FCW) and driver response time (RT). About 95% of all video watching drivers glanced back to the road within 20 sec regardless of the automated driving condition. Approximately 85% of glances away from the road in the scheduled mitigation condition were 7 sec or less.
Exposure–efficacy Relationships for Vedolizumab Induction Therapy in Patients with Ulcerative Colitis or Crohn’s Disease (2017)

Higher vedolizumab serum concentrations were associated with higher remission rates after induction therapy in patients with moderately to severely active UC or CD. This relationship is affected by several factors, including previous TNFα antagonist use. Prospective studies are needed to assess vedolizumab dose individualisation and optimisation.
Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies (2021)

Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here we study the B cell response in a bnAb-producing individual, and report cooperation between two B cell lineages to drive bnAb development. We isolated an autologous virus-neutralizing antibody lineage that targeted an envelope region (loop D) and selected virus escape mutants that resulted in both enhanced bnAb lineage envelope binding and escape mutant neutralization—traits associated with increased B cell antigen drive. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. Design of vaccine immunogens that simultaneously drive both autologous and broadly neutralizing B cell lineages may be important for vaccine-induced recapitulation of events that transpire during the maturation of neutralizing antibodies in HIV-1-infected individuals.
Inositol is a constituent of detergent-solubilized immunoaffinity-purified rat liver 5′-nucleotidase (1990)

myo-Inositol analysis of detergent-solubilized immunoaffinity-purified rat liver 5'-nucleotidase showed the presence of 1 mol of myo-inositol/mol of enzyme monomer. This provides unequivocal evidence that the ectoenzyme 5'-nucleotidase is attached to liver membranes by a glycosyl-phosphatidylinositol lipid anchor.
Restoration of fertility by transplantation of mouse ovary obtained postmortem. (2001)

During the course of breeding mice, deaths sometimes occur because of sudden-onset disease or accident. In the case of valuable mutant or transgenic mice, it is of interest to know whether ovarian tissue taken after death can be grafted successfully into ovariectomized female recipients. Such a procedure would be helpful in the maintenance of rare mouse strains. In this study, we examined whether recipient mice became fertile after receiving ovaries taken from transgenic mice at various intervals after death. The transgenic mice used as donors were euthanized by cervical dislocation and left for 1, 2, 4, 6, 12, or 24 h after death at constant temperature (22 +/- 2 degrees C) and humidity (55 +/- 5%). The recipient mice were nontransgenic littermates of the donor mice, and they were mated with proven-fertile males after ovary transplantation. It was confirmed that the progeny carried the transgene by means of polymerase chain reaction analysis. Ovaries taken at 1 or 2 h after death could maintain fertility. However, mice receiving ovaries taken at 4, 6, 12, or 24 h after death failed to conceive. We have shown here that ovaries taken from dead mice within 2 h after death can be transplanted successfully.