gebhart/patrepeval huggingface dataset:
Performance analysis of decimal floating-point libraries and its impact on decimal hardware and software solutions (2009)

The IEEE Standards Committee recently approved the IEEE 754-2008 Standard for Floating-point Arithmetic, which includes specifications for decimal floating-point (DFP) arithmetic. A growing number of DFP solutions have emerged, and developers now have many DFP design choices including arbitrary or fixed precision, binary or decimal significand encodings, 64-bit or 128-bit DFP operands, and software or hardware implementations. There is a need for accurate analysis of these solutions on representative DFP benchmarks. In this paper, we expand previous DFP benchmark and performance analysis research. We employ a DFP benchmark suite that currently supports several DFP solutions and is easily extendable. We also present performance analysis that (1) provides execution profiles for various DFP encodings and types, (2) gives the average number cycles for common DFP operations and the total number of each DFP operation in each benchmark, and (3) highlights the tradeoffs between using 64-bit and 128-bit DFP operands for both binary and decimal significand encodings. This analysis can help guide the design of future DFP hardware and software solutions.
Venc Design and Velocity Estimation for Phase Contrast MRI (2022)

In phase-contrast magnetic resonance imaging (PC-MRI), spin velocity contributes to the phase measured at each voxel. Therefore, estimating velocity from potentially wrapped phase measurements is the task of solving a system of noisy congruence equations. We propose Phase Recovery from Multiple Wrapped Measurements (PRoM) as a fast, approximate maximum likelihood estimator of velocity from multi-coil data with possible amplitude attenuation due to dephasing. The estimator can recover the fullest possible extent of unambiguous velocities, which can greatly exceed twice the highest venc. The estimator uses all pairwise phase differences and the inherent correlations among them to minimize the estimation error. Correlations are directly estimated from multi-coil data without requiring knowledge of coil sensitivity maps, dephasing factors, or the actual per-voxel signal-to-noise ratio. Derivation of the estimator yields explicit probabilities of unwrapping errors and the probability distribution for the velocity estimate; this, in turn, allows for optimized design of the phase-encoded acquisition. These probabilities are also incorporated into spatial post-processing to further mitigate wrapping errors. Simulation, phantom, and in vivo results for three-point PC-MRI acquisitions validate the benefits of reduced estimation error, increased recovered velocity range, optimized acquisition, and fast computation. A phantom study at 1.5T demonstrates 48.5% decrease in root mean squared error using PRoM with post-processing versus a conventional "dual-venc" technique. Simulation and 3T in vivo results likewise demonstrate the proposed benefits.
Mission Planning for Synthetic Aperture Radar Surveillance (1999)

The Microwave Radar Division of the Defence Sciences and Technology Organisation employs synthetic aperture radar to obtain high-resolution images of selected ground targets. It uses this device, mounted on an aircraft, to scan up to 20 rectangular regions called swaths to obtain images with resolutions down to one meter. Missions consisting of a designated sequence of swaths and flight paths are planned using mapping software. Previously DSTO had been determining the best tours for missions by visually tracking possible swath sequences from a starting base to an ending base. This method was time consuming and did not guarantee optimality in terms of distance traveled. We developed optimization software tools to plan mission tours more efficiently. DSTO can now plan missions with up to 20 swaths in a few seconds, rather than the hour it took using the visual approach. Proposed tour lengths show an average improvement of 15 percent over those manually produced. The software incorporates methods for dealing with the operational problems of no-fly zones and shadowing associated with images.
AC Impedance Measurements on Chara corallina.I. Characterisation of the Static Cytoplasm (1991)

Measurements of impedance (or admittance) of Chara corallina at frequencies of 1-102 Hz have revealed conduction, dielectric, geometrical and phenomenological properties of the plasmalemma and tonoplast. At much higher frequencies, 102-104 Hz, the impedance of these membranes is mainly capacitative and small. Thus, measurements of the overall impedance of these frequencies largely reflect the electrical properties of regions in series with the membranes. The data and arguments presented indicate impedance measurements at these frequencies derive substantially from the static cytoplasm. Results indicated the conductance of the static cytoplasm ranged from 0.5 to 300 S m-2. Conductance was strongly dependent on temperature; a 10�C rise in temperature produced more than a 2-fold increase in conductance.
Quantitative, directional measurement of electric field heterogeneity in the active site of ketosteroid isomerase (2012)

Understanding the electrostatic forces and features within highly heterogeneous, anisotropic, and chemically complex enzyme active sites and their connection to biological catalysis remains a longstanding challenge, in part due to the paucity of incisive experimental probes of electrostatic properties within proteins. To quantitatively assess the landscape of electrostatic fields at discrete locations and orientations within an enzyme active site, we have incorporated site-specific thiocyanate vibrational probes into multiple positions within bacterial ketosteroid isomerase. A battery of X-ray crystallographic, vibrational Stark spectroscopy, and NMR studies revealed electrostatic field heterogeneity of 8 MV/cm between active site probe locations and widely differing sensitivities of discrete probes to common electrostatic perturbations from mutation, ligand binding, and pH changes. Electrostatic calculations based on active site ionization states assigned by literature precedent and computational pK(a) prediction were unable to quantitatively account for the observed vibrational band shifts. However, electrostatic models of the D40N mutant gave qualitative agreement with the observed vibrational effects when an unusual ionization of an active site tyrosine with a pK(a) near 7 was included. UV-absorbance and (13)C NMR experiments confirmed the presence of a tyrosinate in the active site, in agreement with electrostatic models. This work provides the most direct measure of the heterogeneous and anisotropic nature of the electrostatic environment within an enzyme active site, and these measurements provide incisive benchmarks for further developing accurate computational models and a foundation for future tests of electrostatics in enzymatic catalysis.
Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila (2011)

Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insights into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG-repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified 160 genes that are differentially expressed specifically in CAG100 flies. Functional annotation clustering analysis revealed several broad ontologies enriched in the CAG100 gene list, including iron ion binding and nucleotide binding. Intriguingly, transcripts for the Hsp70 genes, a powerful suppressor of polyQ and other human neurodegenerative diseases, were also upregulated. We therefore tested and showed that upregulation of heat shock protein 70 mitigates CAG-repeat RNA toxicity. We then assessed whether other modifiers of the pathogenic, expanded Ataxin-3 polyQ protein could also modify the CAG-repeat RNA toxicity. This approach identified the co-chaperone Tpr2, the transcriptional regulator Dpld, and the RNA-binding protein Orb2 as modifiers of both polyQ protein toxicity and CAG-repeat RNA-based toxicity. These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease.
Nocturnal Blood Pressure Fall on Ambulatory Monitoring in a Large International Database (1997)

A wide range of definitions is used to distinguish subjects in whom blood pressure (BP) falls at night (dippers) from their counterparts (nondippers). In an attempt to standardize the definition of nondipping, we determined the nocturnal BP fall and night-day BP ratio by 24-hour ambulatory monitoring in 4765 normotensive and 2555 hypertensive subjects from 10 to 99 years old. In all subjects combined, the systolic/diastolic nocturnal fall and corresponding ratio averaged (+/- SD) -16.7 +/- 11.0/ -13.6 +/- 8.1 mm Hg and 87.2 +/- 8.0%/83.1 +/- 9.6%, respectively. In normotensive subjects, the 95th percentiles were -0.3/-1.1 mm Hg for the nocturnal fall and 99.7%/98.3% for the night-day ratio. Both the fall and ratio showed a curvilinear correlation with age. The smallest fall and largest ratio were observed in older (> or = 70 years) subjects. A higher BP on conventional sphygmomanometry was associated with a larger systolic (partial r = .11) and diastolic (r = .12) nocturnal BP fall. The diastolic (r = .08) but not the systolic night-day ratio increased with higher conventional BP. The nocturnal BP fall was larger and the corresponding night-day ratio smaller in oscillometric (n = 5884) than in auscultatory (n = 1436) recordings, in males (n = 3730) than in females (n = 3590), and in Europe (n = 4556) than in the other continents (n = 2764). The distributions of the nocturnal BP fall and night-day ratio showed considerable overlap among normotensive and hypertensive subjects, but the overlap tended to be larger for the ratio than for the fall. Of all subjects, 3.2% had systolic and diastolic ratios of 100% or more. With adjustments applied for confounders, the probability of being a nondipper increased 2.8 times (95% confidence interval, 2.0-4.0) from 30 to 60 years and 5.7 times (4.4-7.4) from 60 to 80 years. The odds ratios were 1.0 (0.8-1.4) for males versus females. 1.6 (1.2-2.1) for subjects with definite hypertension versus normotensive subjects, 2.4 (1.2-4.7) for Asians (n = 2213, 96% Japanese) versus inhabitants of the other continents, and 2.4 (1.5-3.8) for subjects examined with auscultatory versus oscillometric devices. In conclusion, the mathematical definition of nondipping, ie, having a night-day ratio of 100% or more for systolic and diastolic BPs, closely approximated the 95th percentiles of the night-day ratio in normotensive subjects. The ratio depends less on BP level than the nocturnal BP fall and is therefore to be preferred in the definition of dipping status. Notwithstanding the present findings, the reproducibility of nondipping and its prognostic significance need further clarification.
Liquid-Crystalline Properties of Thioesters (2018)

An extension of a new method for forming thioesters with mesomorphic properties has been described, whereby the treatment of aryl tert-butylthioethers with long-chain acid chlorides in the presence of bismuth triflate afforded simple derivatives in good yields. This method in the case of 1-cyanoazulenes was, however, complicated by a competitive Friedel–Crafts-type acylation side reaction at the 3-position. Long-chain derivatives of cyanobiphenyl attached through a thioester linkage exhibited mesophases comparable with their ester analogues. The use of shorter chains to decorate the cyanobiphenyl moiety did not produce mesophasic behaviour, unlike their ester analogues. The cyanobiphenyl derivatives showing mesophasic behaviour were studied by small-angle X-ray diffraction, showing alignment for molecules possessing a smectic A phase. It was found that the layer spacing in the smectic A phase was ~1.5 times the length of the molecule, owing to antiparallel pairing arising from p-stacking between neighbouring units. Calculations suggest these derivatives should exhibit large dielectric anisotropy; however, instability made an exact value difficult to determine. For potential use in a liquid crystal display (LCD), the thioester holds some promise, although this may be limited by the relative stability of the thioester functionality.
MAL Inhibits the Production of HIV-1 Particles by Sequestering Gag to Intracellular Endosomal Compartments (2022)

The host innate immune response is the first line of defense against human immunodeficiency virus (HIV) infection. The type I interferon (IFN) response is a robust anti-viral response that induces the transcription of several IFN-stimulated genes (ISGs). However, the effects of ISGs, particularly on the HIV-1 Gag protein, remain largely unknown. Hence, we screened ISG-encoded proteins by bioluminescence resonance energy transfer to identify the crucial host effectors that suppressed Gag function. Consequently, we identified the transmembrane protein MAL as a Gag-interacting ISG product. In fact, ectopic expression of MAL substantially inhibited the production of HIV-1 particles, leading to the translocation, accumulation, and eventual lysosomal degradation of Gag in the host endosomal compartments. Owing to the conserved N-terminal region of MAL, which specifically interacts with HIV-1 Gag, this particular antiviral function of MAL targeting Gag is also conserved among orthologs of various animal species. Notably, the antiviral activity of MAL was partially antagonized by the viral accessory protein Nef, as it interfered with the interaction between MAL and Gag. Therefore, this study reveals a previously unidentified antiviral function of MAL and its viral counteraction. It also sheds new light on therapeutic strategies against HIV-1 infection based on the intrinsic antiviral immunity of host cells.
Highly Stable Low-Strain Flexible Sensors Based on Gold Nanoparticles/Silica Nanohelices (2023)

Flexible strain sensors based on nanoparticle (NP) arrays show great potential for future applications such as electronic skin, flexible touchscreens, healthcare sensors, and robotics. However, even though these sensors can exhibit high sensitivity, they are usually not very stable under mechanical cycling and often exhibit large hysteresis, making them unsuitable for practical applications. In this work, strain sensors based on silica nanohelix (NH) arrays grafted with gold nanoparticles (AuNPs) can overcome these critical aspects. These 10 nm AuNPs are functionalized with mercaptopropionic acid (MPA) and different ratios of thiol-polyethylene glycol-carboxylic acid (HS-PEG7-COOH) to optimize the colloidal stability of the resulting NH@AuNPs nanocomposite suspensions, control their aggregation state, and tune the thickness of the insulating layer. They are then grafted covalently onto the surface of the NHs by chemical coupling. These nanomaterials exhibit a well-defined arrangement of AuNPs, which follows the helicity of the silica template. The modified NHs are then aligned by dielectrophoresis (DEP) between interdigitated electrodes on a flexible substrate. The flexibility, stability, and especially sensitivity of these sensors are then characterized by electromechanical measurements and scanning electron microscopy observations. These strain sensors based on NH@AuNPs nanocomposites are much more stable than those containing only nanoparticles and exhibit significantly reduced hysteresis and high sensitivity at very slight strains. They can retain their sensitivity even after 2 million consecutive cycles with virtually unchanged responsiveness. These improved performances come from their mechanical stability and the use of nanohelices as stable mechanical templates.
Down regulation of the high-affinity IgE receptor associated with successful treatment of chronic idiopathic urticaria with omalizumab (2011)

Chronic idiopathic urticaria is a condition that is often controllable with antihistamine therapy. However, some patients have disease burden that is difficult to manage, non-responsive to antihistamines and often requires immunosuppressive medications such as corticosteroids or cyclosporine. We present here a study that demonstrates the effectiveness of omalizumab in treating this condition and the temporal relationship between improvement and down regulation of the high affinity IgE receptor (FcεRI). For this, blood samples were obtained from a symptomatic patient before each treatment and processed for flow cytometric analysis of FcεRI levels on the surface of blood basophils. Down regulation of FcεRI was observed in association with significant clinical improvement and discontinuation of immunosuppressive medications.
The electrostatic potential of B‐DNA (1989)

Electrostatic potentials around DNA are obtained by solving the nonlinear Poisson-Boltzmann (PB) equation. The detailed charge distribution of the DNA and the different polarizabilities of the macromolecule and solvent are included explicitly in the calculations. The PB equation is solved using extensions of a finite difference approach applied previously to proteins. Electrical potentials and ion concentrations are compared to those obtained with simpler models. It is found that the shape of the dielectric boundary between the macromolecule and solvent has significant effects on the calculated potentials near the surface, particularly in the grooves. Sequence-specific patterns are found, the most surprising result being the existence of positive regions of potential near the bases in both the major and minor grooves. The effect of solvent and ionic atmosphere screening of phosphate-phosphate repulsions is studied, and an effective dielectric function, appropriate for molecular mechanics simulations, is derived.
Sensitization of Cutaneous Nociceptors after Nerve Transection and Regeneration: Possible Role of Target-Derived Neurotrophic Factor Signaling (2009)

Damage to peripheral nerves is known to contribute to chronic pain states, including mechanical and thermal hyperalgesia and allodynia. It is unknown whether the establishment of these states is attributable to peripheral changes, central modifications, or both. In this study, we used several different approaches to assess the changes in myelinated (A) and unmyelinated (C) cutaneous nociceptors after transection and regeneration of the saphenous nerve. An ex vivo recording preparation was used to examine response characteristics and neurochemical phenotype of different types of functionally defined neurons. We found that myelinated nociceptors had significantly lower mechanical and thermal thresholds after regeneration, whereas C-polymodal nociceptors (CPMs) had lower heat thresholds. There was a significant increase in the percentage of mechanically insensitive C-fibers that responded to heat (CHs) after regeneration. Immunocytochemical analysis of identified afferents revealed that most CPMs were isolectin B4 (IB4) positive and transient receptor potential vanilloid 1 (TRPV1) negative, whereas CHs were always TRPV1 positive and IB4 negative in naive animals (Lawson et al., 2008). However, after regeneration, some identified CPMs and CHs stained positively for both markers, which was apparently attributable to an increase in the total number of IB4-positive neurons. Real-time PCR analysis of L2/L3 DRGs and hairy hindpaw skin at various times after saphenous nerve axotomy suggested multiple changes in neurotrophic factor signaling that correlated with either denervation or reinnervation of the cutaneous target. These changes may underlie the functional alterations observed after nerve regeneration and may explain how nerve damage leads to chronic pain conditions.
A New Peptidic Ligand and Its Receptor Regulating Adrenal Function in Rats (2003)

We searched for peptidic ligands for orphan G protein-coupled receptors utilizing a human genome data base and identified a new gene encoding a preproprotein that could generate a peptide. This peptide consisted of 43 amino acid residues starting from N-terminal pyroglutamic acid and ending at C-terminal arginine-phenylalanine-amide. We therefore named it QRFP after pyroglutamylated arginine-phenylalanine-amide peptide. We subsequently searched for its receptor and found that Chinese hamster ovary cells expressing an orphan G protein-coupled receptor, AQ27, specifically responded to QRFP. We analyzed tissue distributions of QRFP and its receptor mRNAs in rats utilizing quantitative reverse transcription-polymerase chain reaction and in situ hybridization. QRFP mRNA was highly expressed in the hypothalamus, whereas its receptor mRNA was highly expressed in the adrenal gland. The intravenous administration of QRFP caused the release of aldosterone, suggesting that QRFP and its receptor have a regulatory function in the rat adrenal gland.
A novel long non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia. (2020)

Abstract Background Microglia are resident immunocompetent and phagocytic cells in the CNS. Pro-inflammatory microglia, stimulated by environmental microbial signals such as bacterial lipopolysaccharide (LPS), viral RNAs, or inflammatory cytokines, are neurotoxic and associated with pathogenesis of several neurodegenerative diseases. Long non-coding RNA (lncRNA) are emerging as important tissue-specific regulators directing cell differentiation and functional states and may help direct proinflammatory responses of microglia. Methods Microglial gene expression array analyses and qRT-PCR was used to identify a novel intergenic long-noncoding RNA that was upregulated in LPS-stimulated microglial cell lines, LPS-stimulated primary microglia, and LPS-injected mouse cortical tissue. Silencing and overexpression studies, RNA immunoprecipitation, chromatin immunoprecipitation, chromatin RNA immunoprecipitation assays, and qRT-PCR were used to study the function of this long-noncoding RNA in microglia. In vitro cytotoxicity assays were used to examine the effects of silencing the novel long-noncoding RNA in LPS-stimulated microglia on neurotoxicity. Results We report here that the previously uncharacterized intergenic lncRNA we termed Nostrill is induced by LPS stimulation in both BV2 cells and primary murine microglia, as well as in cortical tissue of LPS-injected mice. Induction of Nostrill is NF-κB dependent and silencing of Nostrill decreased inducible nitric oxide synthase (iNOS) expression and nitric oxide production in BV2 and primary microglial cells. Overexpression of Nostrill increased iNOS expression and nitric oxide production. RNA immunoprecipitation assays demonstrated that Nostrill is physically associated with NF-κB subunit p65 following LPS stimulation. Silencing of Nostrill significantly reduced NF-κB p65 and RNA polymerase II recruitment to the iNOS promoter and decreased H3K4me3 activating histone modifications at iNOS gene loci. In vitro studies demonstrate that silencing of Nostrill in microglia reduced LPS-stimulated microglia neurotoxicity. Conclusions Our data indicate a new regulatory role of NF-κB-induced Nostrill and suggest that Nostrill acts as a co-activator of transcription of iNOS resulting in the production of nitric oxide in microglia through modulation of epigenetic chromatin remodeling. Nostrill may be a target for reducing the neurotoxicity associated with iNOS-mediated inflammatory processes in microglia during neurodegeneration.