gebhart/patrepeval huggingface dataset:
Oral Bioavailability of a New Class of μ-Opioid Receptor Agonists Containing 3,6-Bis[Dmt-NH(CH2)n]-2(1H)-pyrazinone with Central-Mediated Analgesia (2004)

The inability of opioid peptides to be transported through epithelial membranes in the gastrointestinal tract and pass the blood-brain barrier limits their effectiveness for oral application in an antinociceptive treatment regime. To overcome this limitation, we enhanced the hydrophobicity while maintaining the aqueous solubility properties in a class of opioid-mimetic substances by inclusion of two identical N-termini consisting of Dmt (2',6'-dimethyl-l-tyrosine) coupled to a pyrazinone ring platform by means of alkyl chains to yield the class of 3,6-bis[Dmt-NH-(CH(2))(n)]-2(1H)-pyrazinones. These compounds displayed high micro-opioid receptor affinity (K(i)micro = 0.042-0.115 nM) and selectivity (K(i)delta/K(i)micro = 204-307) and functional micro-opioid receptor agonism (guinea-pig ileum, IC(50) = 1.3-1.9 nM) with little or undetectable bioactivity toward delta-opioid receptors (mouse vas deferens) and produced analgesia in mice in a naloxone reversible manner when administered centrally (intracerebroventricular, i.c.v.) or systemically (subcutaneously and orally). Furthermore, the most potent compound, 3,6-bis(3'-Dmt-aminopropyl)-5-methyl-2(1H)-pyrazinone (7'), lacked functional delta-opioid receptor bioactivity and was 50-63-fold and 18-21-fold more active than morphine by icv administration as measured analgesia using tail-flick (spinal involvement) and hot-plate (supraspinal effect) tests, respectively; the compound ranged from 16 to 63% as potent upon systemic injection. These analgesic effects are many times greater than unmodified opioid peptides. The data open new possibilities for the rational design of potential opioid-mimetic drugs that pass through the epithelium of the gastrointestinal tract and the blood-brain barrier to target brain receptors.
Identification of a conserved self-antigen bearing the 2F5 neutralizing epitope of the HIV-1 gp41 Membrane Proximal External Region (105.2) (2011)

Abstract Accumulating evidence suggests that the efficient generation of neutralizing HIV-1 antibody may be proscribed by immunological tolerance. The majority of monoclonal human antibodies, including 2F5, that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian cells. Introduction and expression of the 2F5 VDJ rearrangement in knock-in mice results in a B-cell developmental blockade that is characteristic of immunological tolerance. If immunological tolerance does prevent regular expression of neutralizing 2F5-like antibody, then discrete autoantigens that structurally mimic the HIV-1 2F5 epitope are present in mammals. Here, we demonstrate that the 2F5 antibody precipitates a small number of proteins from mouse and human cells, including a major component with a molecular mass of about 50 kDa. We have identified this 50 kDa protein as kynureninase (KYNU), a conserved component of tryptophan metabolism. Remarkably, the conserved H3 domain of mammalian KYNU contains the core 2F5 epitope (ELDKWA), and mutation within this region greatly diminishes 2F5 binding. The 2F5 antibody and its inferred, unmutated precursor bind KYNU with high affinity and specificity. Indeed, recombinant human KYNU is an effective inhibitor of 2F5 binding to HIV-1 envelope. The nature of KYNU as autoantigen was previously unknown and our study suggests that mimicry of self-antigens may represent a general evolutionary strategy of viral pathogens.
Character articulation through profile curves (2022)

Computer animation relies heavily on rigging setups that articulate character surfaces through a broad range of poses. Although many deformation strategies have been proposed over the years, constructing character rigs is still a cumbersome process that involves repetitive authoring of point weights and corrective sculpts with limited and indirect shaping controls. This paper presents a new approach for character articulation that produces detail-preserving deformations fully controlled by 3D curves that profile the deforming surface. Our method starts with a spline-based rigging system in which artists can draw and articulate sparse curvenets that describe surface profiles. By analyzing the layout of the rigged curvenets, we quantify the deformation along each curve side independent of the mesh connectivity, thus separating the articulation controllers from the underlying surface representation. To propagate the curvenet articulation over the character surface, we formulate a deformation optimization that reconstructs surface details while conforming to the rigged curvenets. In this process, we introduce a cut-cell algorithm that binds the curvenet to the surface mesh by cutting mesh elements into smaller polygons possibly with cracks, and then derive a cut-aware numerical discretization that provides harmonic interpolations with curve discontinuities. We demonstrate the expressiveness and flexibility of our method using a series of animation clips.
Specific DNA Recognition by a Synthetic, Monomeric Cys2His2 Zinc‐Finger Peptide Conjugated to a Minor‐Groove Binder (2007)

Wrapped around the finger: Tailored Cys2His2 zinc-finger domains can specifically bind to DNA when assisted by minor-groove accessory interactions. In this way, appropriately designed hybrids containing the zinc-finger unit of the GAGA factor and a distamycin-like tripyrrole bind with high affinity to DNA sites that have a GAG triad near the 3′ side of an A-rich fragment. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z702345_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Endothelial TIE1 Restricts Angiogenic Sprouting to Coordinate Vein Assembly in Synergy With Its Homologue TIE2 (2023)

Findings from this study imply that TIE1 and TIE2, together with COUP-TFII, act in a synergistic manner to restrict sprouting angiogenesis during the development of venous system.
Electrochemical Performance of Carbon-Coated HQ-LiFePO4 Cathode (2011)

The carbon-coated LiFePO4 Li-ion cathode material was studied for its electrochemical performance. This electrode exhibited a reversible capacity corresponding to more than 86% of the theoretical capacity, when cycled between 2.5V and 4.0V. The positive electrode material displayed excellent capacity retention for prolonged cycling periods and also showed high rate capability upto 5C discharge rates. High power obtained at high discharge rates were attributed to the effects of electronic conductivity improvement enabled by carbon-coating of LiFePO4. Carbon-coating of the electrode was observed as capacitance component in the electrochemical impedance spectra (EIS). Hybrid pulse power characterization (HPPC) tests were also performed on commercial 18650 size cells, using carbon-coated LiFePO4 electrode, to observe the suitability of the positive electrode to HEV applications.
A surface micromachined silicon gyroscope using a thick polysilicon layer (1999)

A new silicon gyroscope is presented in this paper. It has a measuring range of /spl plusmn/100/spl deg//s and a resolution of 1.26/spl deg//s at 10 Hz bandwidth. The mechanical sensor structure consists of polysilicon and its lateral extension is 1600 /spl mu/m. The gyro element is 11 /spl mu/m thick and less than 19 /spl mu/g in weight. This structure is suspended in its centre of gravity with a thin tether beam. The tether beam is shaped in a way that the sensor structure can be tilted around its three axes. The gyroscope is fabricated using silicon surface micromachining technology incorporating several new process steps. These new steps are mainly thick polysilicon deposited in an epitaxy reactor, the deep silicon etching and a new stiction free release etch. The gyro structure is electrostatically driven in an in-plane torsional dithering motion. In response to an external angular rate the drive motion is coupled into an out-of-plane motion which is measured capacitively.
Charge transfer at interfaces inMoxV1−x/V superlattices (1995)

The influence of alloying and strain upon charge transfer across interfaces was investigated in ${\mathrm{Mo}}_{\mathit{x}}$${\mathrm{V}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$/V (x=0.5, 0.75, 1) superlattices. The extension of the charge transfer was measured using the relation between the hydrogen solubility and the electron density. The hydrogen concentration was measured by means of the $^{1}\mathrm{H}$${(}^{15}$N,\ensuremath{\alpha}\ensuremath{\gamma}${)}^{12}$C nuclear reaction. In Mo/V superlattices, the extension of the charge transfer was found to be 3 ML. In ${\mathrm{Mo}}_{0.75}$${\mathrm{V}}_{0.25}$/V superlattices it was found to be 2 ML whereas no charge transfer was observed in a ${\mathrm{Mo}}_{0.5}$${\mathrm{V}}_{0.5}$/V superlattice.
Impact of Phase-Change Memory Drift on Energy Efficiency and Accuracy of Analog Compute-in-Memory Deep Learning Inference (Invited) (2023)

Among the emerging approaches for deep learning acceleration, compute-in-memory (CIM) in crossbar arrays, in conjunction with optimized digital computation and communication, is attractive for achieving high execution speeds and energy efficiency. Analog phase-change memory (PCM) is particularly promising for this purpose. However, resistance typically drifts, which can degrade deep learning accuracy over time. Herein, we first discuss drift and noise mitigation by integrating projection liners into analog mushroom-type PCM devices, as well as tradeoffs with dynamic range. We then study their impact on inference accuracy for the Transformer-based language model BERT. We find that accuracy loss after extended drift can be minimal with an optimized mapping of weights to cells comprising two pairs of liner PCM devices of varying significance. Finally, we address the impact of drift on energy consumption during inference through a combination of drift, circuit, and architecture simulations. For a range of typical drift coefficients, we show that the peak vector-matrix multiplication (VMM) energy efficiency of a recently proposed heterogeneous CIM accelerator in 14 nm technology can increase by 3% to 15% over the course of one day to ten years. For convolutional neural network (CNN), long short-term memory (LSTM) and Transformer benchmarks, the increase in sustained energy efficiency remains below 10%, being greatest for models dominated by analog computation. Longer VMM integration times increase the energy impact of drift.
Measurement of the b-hadron production cross section using decays to D⁎+μ−X final states in pp collisions at s=7 TeV with the ATLAS detector (2012)

The b-hadron production cross section is measured with the ATLAS detector in pp collisions at s=7TeV, using 3.3pb−1 of integrated luminosity, collected during the 2010 LHC run. The b-hadrons are selected by partially reconstructing D⁎+μ−X final states. Differential cross sections are measured as functions of the transverse momentum and pseudorapidity. The measured production cross section for a b-hadron with pT>9GeV and |η|<2.5 is 32.7±0.8(stat.)−6.8+4.5(syst.)μb, higher than the next-to-leading-order QCD predictions but consistent within the experimental and theoretical uncertainties.
New Bioactive Natural Products from Canadian Boreal Forest (2012)

This chapter contains sections titled: Introduction Identification of New Bioactive Natural Products from Canadian Boreal Forest Chemical Modification of Bioactive Natural Products from the Canadian Boreal Forest Conclusion References
Supplementary Table 4 from Gene Expression Profiling using Nanostring Digital RNA Counting to Identify Potential Target Antigens for Melanoma Immunotherapy (2023)

&lt;p&gt;XLSX file - 64K, Supplemental Table S4. Normal Tissues: Brain Brainstem Eye Skin Trachea Salivary Artery Vein Heart Lung.&lt;/p&gt;
Red blood cell-coupled tissue plasminogen activator prevents impairment of cerebral vasodilatory responses through inhibition of c-Jun-N-terminal kinase and potentiation of p38 mitogen-activated protein kinase after cerebral photothrombosis in the newborn pig (2010)

These data indicate that in addition to restoring perfusion, red blood cells-tissue plasminogen activator prevents impairment of cerebrovasodilation after photothrombotic injury through blockade of c-Jun-N-terminal kinase and potentiation of p38 mitogen-activated protein kinase. These data suggest tissue plasminogen activator coupling to red blood cells offers a novel approach to increase the benefit/risk ratio of thrombolytic therapy to treat central nervous system ischemic disorders.
GluR2 Deficiency Accelerates Motor Neuron Degeneration in a Mouse Model of Amyotrophic Lateral Sclerosis (2005)

AMPA receptor-mediated excitotoxicity has been implicated in the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). Motor neurons in vitro are particularly vulnerable to excessive AMPA receptor stimulation and one of the factors underlying this selective vulnerability is the presence of a large proportion of Ca2+ -permeable (i.e. GluR2-lacking) AMPA receptors. However, the precise role of GluR2-lacking AMPA receptors in motor neuron degeneration remains to be defined. We therefore studied the impact of GluR2 deficiency on motor neuron death in vitro and in vivo. Cultured motor neurons from GluR2-deficient embryos displayed an increased Ca2+ influx through AMPA receptors and an increased vulnerability to AMPA receptor-mediated excitotoxicity. We deleted the GluR2 gene in mutant SOD1G93A mice by crossbreeding them with GluR2 knockout mice. GluR2 deficiency clearly accelerated the motor neuron degeneration and shortened the life span of mutant SOD1G93A mice. These findings indicate that GluR2 plays a pivotal role in the vulnerability of motor neurons in vitro and in vivo, and that therapies that limit Ca2+ entry through AMPA receptors might be beneficial in ALS patients.
Thermal-recovery of modal instability in rod fiber amplifiers (2013)

We investigate the temporal dynamics of Modal instabilities (MI) in ROD fiber amplifiers using a 100 &mu;m core rod fiber in a single-pass amplifier configuration, and we achieve ~200W of extracted output power before the onset of MI. Above the MI threshold, we investigate the temporal dynamics of beam fluctuations in both the transient and chaotic regime. We identify a set of discrete frequencies in the transient regime and a white distribution of frequencies in the chaotic regime. We test three identical rods using a multiple ramp-up procedure, where each rod is tested in three test series and thermally annealed between each test series. We find that the MI threshold degrades as it is reached multiple times, but is recovered by thermal annealing. We also find that the test history of the rods affects the temporal dynamics.
Classification of Clinically Diagnosed Alzheimer’s Disease Associated with Diabetes Based on Amyloid and Tau PET Results (2019)

Among patients with clinically diagnosed AD with DM, there are subgroups with neuronal damage independent of AD pathology. A subgroup of dementia patients suspected of having tauopathy is strongly associated with DM-related metabolic abnormalities. This study highlights the identification of a novel dementia subgroup (diabetes-related dementia), which is important for considering appropriate therapies and care in clinical practice.
<title>Multiplexed fiber optic collector for FTIR reflectance and radiance spectroscopy</title> (1993)

Recently, solar furnaces have been successfully used to harden steel, coat metals, and initiate physical and chemical vapor deposition. Successful development of this technology requires process monitoring of surface temperature, which can be in excess of 2000 degree(s)C. This severely limits the accuracy of standard devices. This paper describes the use of FT-IR spectroscopy to measure spectral reflectance and radiance of solar-heated samples in order to accurately determine their temperature. The system features a fiber optic arrangement, representative of a hemispherical mirror, to collect diffusely reflected radiation. Preliminary results are given.
PACS and multi-modality image registration (1992)

One of the main interest of PACS is to permit the matching of images coming from different sources and devoted to the same pathologic object or physiologic organ. We present here a general frame for the medical image registration methods.
Reinterpretation of ‘sperm pump’ or ‘sperm syringe’ function with notes on other male internal reproductive organs in the Asian citrus psyllid, Diaphorina citri (Hemiptera: Liviidae) (2020)

Reproduction is a critical feature in the search for means to manage the Asian citrus psyllid, vector of a devastating bacterial pathogen of citrus. The importance of accuracy in functional, anatomical descriptions and interpretations for use by other disciplines, particularly molecular genetics, cannot be overstressed. The term 'sperm pump' was coined by classical authors on observational appearance of the endoskeleton of the male reproductive apparatus. They described a thimble-shaped cuticle with smooth, cylindrical columns, interpreted as muscles, that ran longitudinally around a central cylinder. They detected transverse lines on the cylinder giving the false impression of a coiled spring. These features fostered the teleological interpretation that the device is a contractile pump. Now obsolete, the term is replaced by 'drum/spout complex'. It is a hypodermis with a sclerotized cuticle that houses the phallus which transports seminal fluid through its lumen to the female for insemination. Between the spout and the external genitalia is a spout extension, conferring flexibility to the apparatus about the abdominal apex. Approximately 21 longitudinal columns extend circumferentially around the cylinder's hemolymph-side, from the thimble's basal plate to its apical plate. These columns are correctly muscle cells, and reinterpreted to exude a lipaceous, lubricating substance for mating.
Kavalactone Pharmacophores for Major Cellular Drug Targets (2010)

A number of studies have identified differential kavalactone activity against a variety of molecular targets, including P-glycoprotein (Pgp), platelet monoamine oxidase (MAO-B), transcription factor binding domains, pregnane X (PXR) and GABA receptors, and cytochrome P450 and cyclo-oxygenase (COX) enzymes. The molecular structure of the kavalactones possesses a pharmacophore for several of these targets. In most cases, conformational stability is more significant than the substituents present. The analysis of these pharmacophores provides important insights for future medicinal chemistry-based approaches to kavalactone-type drugs.
Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders (2014)

Individuals with a family history of substance use disorder (FH+) show impaired frontal white matter as indicated by diffusion tensor imaging (DTI). This impairment may be due to impaired or delayed development of myelin in frontal regions, potentially contributing to this population's increased risk for developing substance use disorders. In this study, we examined high angular resolution DTI and proton magnetic resonance spectroscopy data from the anterior corona radiata were collected in 80 FH+ and 34 FH- youths (12.9 ± 1.0 years old). White matter integrity indices included fractional anisotropy (FA), N-acetylaspartate (NAA), and total choline (tCho). Lower FA suggests decreased myelination. Decreased NAA coupled with higher tCho suggests impaired build-up and maintenance of cerebral myelin and consequently greater breakdown of cellular membranes. We found FH+ youths had lower FA (P < 0.0001) and NAA (P = 0.017) and higher tCho (P = 0.04). FH density (number of parents and grandparents with substance use disorders) was negatively correlated with FA (P < 0.0001) and NAA (P = 0.011) and positively correlated with tCho (P = 0.001). FA was independently predicted by both FH density (P = 0.006) and NAA (P = 0.002), and NAA and tCho were both independent predictors of FH density (P < 0.001). Our finding of lower frontal FA in FH+ youths corresponding to lower NAA and increased tCho is consistent with delayed or impaired development of frontal white matter in FH+ youths. Longitudinal studies are needed to determine how these differences relate to substance use outcomes.
Structure-Guided Design and Procognitive Assessment of a Potent and Selective Phosphodiesterase 2A Inhibitor (2018)

Herein we describe the development of a series of pyrazolopyrimidinone phosphodiesterase 2A (PDE2) inhibitors using structure-guided lead identification and design. The series was derived from informed chemotype replacement based on previously identified internal leads. The initially designed compound <b>3</b>, while potent on PDE2, displayed unsatisfactory selectivity against the other PDE2 isoforms. Compound <b>3</b> was subsequently optimized for improved PDE2 activity and isoform selectivity. Insights into the origins of PDE2 selectivity are described and verified using cocrystallography. An optimized lead, <b>4</b>, demonstrated improved performance in both a rodent and a nonhuman primate cognition model.
Superconducting transition temperatures in electronic and magnetic phase diagram of a superconductor, Sr2VFeAsO3−δ (2018)

We unveil magnetic phases and superconducting transition temperatures (Tc) in an iron-based superconductor with a thick-blocking layer of a perovskite-related transition metal oxide, Sr2VFeAsO3-delta (21113V). 21113V exhibits a superconducting phase in 0.031 =< delta =< 0.145 at temperatures (T) < 37.1 K. Antiferromagnetic (AFM) iron sublattice are observed in 0.267 =< delta =< 0.664. A mixed valent vanadium exhibits a dominant AFM phase in 0.031 =< delta =< 0.088, while a partial ferrimagnetic (Ferri.) phase of the vanadium appears in 0.124 =< delta =< 0.664. The partial Ferri. phase becomes the most dominant for delta~0.267, in which the Fe shows AFM phase at T < 20 K. A volume fraction of the superconducting phase is suppressed by increasing of spontaneous magnetic moments due to the partial Ferri. vanadium; i.e the magnetic phase of the vanadium dominates superconductivity in 21113V. The Tc-delta curve shows two maxima. The lower maximum of Tc are observed for delta = 0.073. It is noted that the highest Tc of 21113V appears for delta = 0.145, which exists in a phase boundary between AFM and the partial Ferri. phases of the vanadium. 21113V is a platform to verify new mechanism for enhancing Tc in iron-based superconductors.
Texture Splicing (2009)

Abstract We propose a new texture editing operation called texture splicing. For this operation, we regard a texture as having repetitive elements (textons) seamlessly distributed in a particular pattern. Taking two textures as input, texture splicing generates a new texture by selecting the texton appearance from one texture and distribution from the other. Texture splicing involves self‐similarity search to extract the distribution, distribution warping, context‐dependent warping, and finally, texture refinement to preserve overall appearance. We show a variety of results to illustrate this operation.