gebhart/patrepeval huggingface dataset:
Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization. (1997)

A series of novel tricyclic pyrido-phthalazine-dione derivatives was tested for antagonistic effects at the strychnine-insensitive modulatory site of the N-methyl-D-aspartate (NMDA) receptor (glycineB). All compounds displaced [3H]MDL-105,519 binding to rat cortical membranes with IC50 values of between 90 nM and 3.6 microM. In patch-clamp experiments, steady-state inward current responses of cultured hippocampal neurons to NMDA (200 microM, glycine 1 microM) were antagonized by these same compounds with IC50 values of 0.14 to 13.8 microM. The antagonism observed was typical for glycineB antagonists, i.e., they induced desensitization and their effects were not use or voltage dependent. Moreover, increasing concentrations of glycine were able to decrease their apparent potency. Much higher concentrations (>100 microM) were required to antagonize alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced currents. They were potent, systemically active NMDA receptor antagonists in vivo against responses of single neurons in the rat spinal cord to microelectrophoretic application of NMDA with ID50 values in the low milligram per kilogram i.v. range. They also inhibited pentylenetetrazol-, NMDA- and maximal electroshock-induced convulsions in mice with ED50 values ranging from 8 to 100 mg/kg i.p. The duration of anticonvulsive action was rather short but was prolonged by the organic acid transport inhibitor probenecid (200 mg/kg). The agents tested represent a novel class of systemically active glycineB antagonists with greatly improved bioavailability.
Antinociceptive action of GLYX-13: an N-methyl-D-aspartate receptor glycine site partial agonist (2008)

Inhibition of N-methyl-D-aspartate (NMDA)-mediated neurotransmission has been demonstrated to provide antinociceptive actions in a number of animal models of tonic and neuropathic pain. However, both competitive and noncompetitive NMDA receptor antagonists are ataxic at analgesic doses. Partial agonists and antagonists of the NMDA-associated glycine site have demonstrated antinociceptive actions at doses that are not ataxic. In this study, we present data showing that GLYX-13, an NMDA receptor, glycine-site, partial agonist, also is antinociceptive in the rat formalin model of tonic pain and in the rat constriction nerve injury model of neuropathic pain at doses not inducing ataxia.
Analysis of blood vessel maturation processes during cyclic ovarian angiogenesis. (1998)

Cyclic angiogenic processes in the ovarian corpus luteum (CL) of monovulatory species are characterized by distinct phases of blood vessel growth, vessel maturation, and vessel regression. To characterize molecular and cellular systems that may play a role in regulating blood vessel maturation, we have (a) analyzed the spatiotemporal expression of vascular endothelial growth factor (VEGF) and its receptors VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1) throughout the ovarian cycle, (b) examined the recruitment of pericytes during vessel maturation, and (c) quantitatively measured the ratio of angiopoietin-2 (Ang-2) to angiopoietin-1 (Ang-1) throughout the ovarian cycle. The data indicate that the VEGF/VEGF-receptor system is expressed not only during ovarian angiogenesis, but also with similar intensity in the nonangiogenic midstage CL. In fact, VEGF is expressed through most of the ovarian cycle, only being down-regulated during luteolysis, which leads to regression of the CL neovasculature. Pericytes are recruited soon after the induction of CL angiogenesis following the front of invading endothelial cells. Based on a double-staining immunohistochemistry technique, we developed a microvessel maturation index (MMI) that reflects the percentage of the capillary neovasculature that is associated with pericytes. The MMI in the angiogenic corpus rubrum is approximately 0.60. This value is not significantly higher in the nonangiogenic midstage CL but increases to close to 0.90 during CL regression. Lastly, an RT-PCR analysis of Ang-1 and Ang-2 expression revealed that both molecules are expressed throughout the ovarian cycle. The quantitative Ang-2/Ang-1 ratio does, however, change from 1.34 in the angiogenic CL and 1.07 in the midstage CL to 7.59 during CL regression, reflecting the strong overexpression of Ang-2 over Ang-1 during blood vessel regression. Taken together, the data support a model of a transiently maturated vasculature in the midstage CL, which is characterized by VEGF and pericyte contact-mediated endothelial cell survival and an induction of blood vessel regression during luteolysis that is characterized by the down-regulation of VEGF and the up-regulation of Ang-2.
Dexmedetomidine-induced ocular hypotension in rabbits with normal or elevated intraocular pressures. (1992)

This study covered the ocular hypotensive effects of the stereoisomers of the alpha 2-adrenoceptor agonist medetomidine. The dextro-isomer, dexmedetomidine, is known from pharmacologic experiments to be a specific, potent, and selective full agonist at alpha 2-adrenoceptors, whereas the levo-enantiomer seems to be almost inactive. Thus, the levo-isomer (0.5 mg/ml, 25 microliters) had no significant effect on intraocular pressure. After unilateral topical administration, dexmedetomidine (0.5 mg/ml, 25 microliters) lowered intraocular pressure bilaterally in normal rabbits and in rabbits with intraocular pressure elevated after laser irradiation of the pigmented trabecular band of the anterior chamber angle. In the treated (ipsilateral) eye of normal rabbits, a maximum decrease of 4.6 +/- 0.6 mmHg was observed at 2 hr post treatment. In the contralateral eye, the maximum decrease was 4.1 +/- 0.5 mmHg at 1 hr after treatment. In rabbits with laser-induced elevation of intraocular pressure, the maximum decrease in treated hypertensive eyes was 13.5 +/- 0.3 mmHg 1 hr after dexmedetomidine administration. These results indicate that the selective alpha 2-adrenoceptor agonist, dexmedetomidine, is a potent and effective drug for decreasing intraocular pressure in rabbits.
Gastric Acid Antisecretory Effect of Two Different Dosage Forms of Omeprazole during Prolonged Oral Treatment in the Gastric Fistula Dog (1988)

Two series of experiments have been performed in gastric fistula dogs to test the antisecretory effect of two different oral dosage forms of omeprazole: 2 mumol x kg-1 x day-1 as a methylcellulose suspension for 8 weeks and 0.5 mumol x kg-1 x day-1 in enteric-coated granules (ECG) for 3 weeks. There was an increasing inhibitory effect during the first days of repeated administration of omeprazole, which is in accordance with its long duration of action. The steady-state inhibitory level was reached after five doses. During the 8-week treatment with the omeprazole suspension (2 mumol x kg-1) the mean maximal inhibitory level (3 h after dose) was 82%, and the mean minimal inhibitory level (24 h after dose) was 35%. With omeprazole in ECG (0.5 mumol x kg-1) the steady-state maximal inhibition (4th h) was 60%, whereas 40% inhibition remained after 24 h. Thus, a more even inhibitory level over day and night seems to be obtained with the ECG formulation than with the suspension. Basal and food-stimulated plasma gastrin levels were not significantly affected by the treatment with 0.5 mumol x kg-1, whereas food-stimulated gastrin levels were slightly increased during treatment with 2 mumol x kg-1. Control levels of acid secretion were reached within 4 days of stopping treatment. In the present studies, in which the inhibition of acid secretion varied over 24 h between approximately 80% and 35% (maximum and minimum), no rebound effects could be detected as measured up to 1 month after cessation of treatment.
Complementation of adenovirus E4 mutants by transient expression of E4 cDNA and deletion plasmids (1989)

Human adenovirus mutants that carry a large deletion in early region 4 (E4) are severely defective in the synthesis of viral late proteins. Plasmids that carry intact E4 sequences can complement the late protein synthetic defect of such mutants when introduced into infected cells by transfection, presumably due to the transient expression of E4 products. Cells transfected with cDNA clones capable of expressing E4 open reading frame (ORF) 6, or deletion mutant clones expected to express either E4 ORF 6 or E4 ORF 3, also complement the mutants' defects. Thus, these E4 ORFs can individually satisfy the requirement for E4 products in viral late gene expression, and function effectively in the absence of other E4 products. Some E4 deletion mutants also exhibit a defect in the production of viral DNA. All of the clones that stimulate late gene expression also enhance one such mutant's ability to accumulate viral DNA. Thus, the ORF 3 and ORF 6 products are also individually sufficient to provide an E4 function necessary for normal viral DNA replication in the absence of other E4 products.
Immunogenic duplex nucleic acids are nuclease resistant. (1988)

Several derivatives of the synthetic duplex DNA poly(d(GC] were prepared. These analogs contained ribo- and phosphorothioate substitutions, namely, poly(r(GC], poly(rGdC), poly(d(sGC], poly(d(GsC], and poly(d(sGsC]. The nucleic acids were complexed to methylated BSA and injected into C57BL/6 mice. Poly(d(GC] was not immunogenic, whereas the analogs gave a strong response. Analysis of the sera revealed that antibody populations were present, which recognized A, B, and Z form nucleic acids. In particular, immunization with poly(d(sGC] and poly(d(GsC] produced antibodies that bound poly(d(GC] and poly(d(IC]. The nuclease sensitivity of these polymers also was investigated. Poly(d(GC] was rapidly degraded by pancreatic DNase I, whereas the phosphorothioate derivatives were resistant, and the ribo-substituted polymers were resistant to both RNases and DNase I. Similarly, the nucleases present in mouse serum digested calf thymus DNA and ribosomal rRNA while both types of analog persisted indefinitely. These results suggest the hypothesis that duplex DNAs are generally not immunogenic because they are rapidly degraded by serum nucleases. Therefore, they escape immune detection.
Near-optimal hashing algorithms for approximate nearest neighbor in high dimensions (2008)

In this article, we give an overview of efficient algorithms for the approximate and exact nearest neighbor problem. The goal is to preprocess a dataset of objects (e.g., images) so that later, given a new query object, one can quickly return the dataset object that is most similar to the query. The problem is of significant interest in a wide variety of areas.
BH3 Domain of BAD Is Required for Heterodimerization with BCL-XL and Pro-apoptotic Activity (1997)

BAD interacts with anti-apoptotic molecules BCL-2 and BCL-XL and promotes apoptosis. BAD is phosphorylated on serine residues in response to a survival factor, interleukin-3. Phosphorylated BAD cannot bind to BCL-XL or BCL-2 at membrane sites and is found in the cytosol bound to 14-3-3. We report here that deletion mapping and site-directed mutagenesis identified a BH3 domain within BAD that proved necessary for both its heterodimerization with BCL-XL and its death agonist activity. Substitution of the conserved Leu151 with Ala in the BH3 amphipathic alpha-helix abrogated both functions. The BAD Leu151 mutant was predominantly in the cytosol bound to 14-3-3. The BH3 domain of BCL-2 also proved important for BCL-2/BAD interaction. These results establish a critical role for a BH3 domain within BAD and provide evidence that BAD may function as a death ligand whose pro-apoptotic activity requires heterodimerization with BCL-XL.
Towards Oracle Knowledge Distillation with Neural Architecture Search (2019)

We present a novel framework of knowledge distillation that is capable of learning powerful and efficient student models from ensemble teacher networks. Our approach addresses the inherent model capacity issue between teacher and student and aims to maximize benefit from teacher models during distillation by reducing their capacity gap. Specifically, we employ a neural architecture search technique to augment useful structures and operations, where the searched network is appropriate for knowledge distillation towards student models and free from sacrificing its performance by fixing the network capacity. We also introduce an oracle knowledge distillation loss to facilitate model search and distillation using an ensemble-based teacher model, where a student network is learned to imitate oracle performance of the teacher. We perform extensive experiments on the image classification datasets---CIFAR-100 and TinyImageNet---using various networks. We also show that searching for a new student model is effective in both accuracy and memory size and that the searched models often outperform their teacher models thanks to neural architecture search with oracle knowledge distillation.
Vibration arthrography as a diagnostic aid in diseases of the knee. A preliminary report (1987)

The detection and recording of vibration emission from human joints, a technique which we have termed "vibration arthrography", is a sensitive, non-invasive method for the objective study of the locomotor system. Using vibration sensors attached to bony prominences around the knee, we studied the joints of both normal and symptomatic subjects. Normal subjects produced three signal types--physiological patellofemoral crepitus, patellar clicks, and the lateral band signal. In symptomatic subjects we identified and categorised many signal types and related them to pathology. Lesions of the menisci produced distinctive signals, and it was possible not only to lateralise the tear, but in many cases to determine the type of meniscal injury present. Vibration arthrography promises to be a useful tool in the non-invasive diagnosis of knee disorders.
Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy (2014)

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.
In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques (2004)

Antiviral resistance is a significant obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Because nonnucleoside reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus (SIV) RT, the development of animal models to study the evolution of antiviral resistance has been problematic. To facilitate in vivo studies of NNRTI resistance, we examined whether a SIV that causes immunopathogenesis in pigtail macaques could be made sensitive to NNRTIs. Two simian-human immunodeficiency viruses (SHIVs) were derived from the genetic background of SIV(mne): SIV-RT-YY contains RT substitutions intended to confer NNRTI susceptibility (V181Y and L188Y), and RT-SHIV(mne) contains the entire HIV-1 RT coding region. Both mutant viruses grew to high titers in vitro but had reduced fitness relative to wild-type SIV(mne). Although the HIV-1 RT was properly processed into p66 and p51 subunits in RT-SHIV(mne) particles, the RT-SHIV(mne) virions had lower levels of RT per viral genomic RNA than HIV-1. Correspondingly, there was decreased RT activity in RT-SHIV(mne) and SIV-RT-YY particles. HIV-1 and RT-SHIV(mne) were similarly susceptible to the NNRTIs efavirenz, nevirapine, and UC781. However, SIV-RT-YY was less sensitive to NNRTIs than HIV-1 or RT-SHIV(mne). Classical NNRTI resistance mutations were selected in RT-SHIV(mne) after in vitro drug treatment and were monitored in a sensitive allele-specific real-time RT-PCR assay. Collectively, these results indicate that RT-SHIV(mne) may be a useful model in macaques for the preclinical evaluation of NNRTIs and for studies of the development of drug resistance in vivo.
MicroRNAs: new players in acute myeloid leukaemia (2009)

MicroRNAs (miRNAs) are short non-coding RNAs that have key functions in a wide array of critical cell processes, including haematopoiesis by regulating the expression of multiple genes. Aberrant miRNA expression has been described in acute myeloid leukaemia suggesting a role in leukaemogenesis. In this review we summarise the current knowledge.
Topography Driven Spreading (2004)

Roughening a hydrophobic surface enhances its nonwetting properties into superhydrophobicity. For liquids other than water, roughness can induce a complete rollup of a droplet. However, topographic effects can also enhance partial wetting by a given liquid into complete wetting to create superwetting. In this work, a model system of spreading droplets of a nonvolatile liquid on surfaces having lithographically produced pillars is used to show that superwetting also modifies the dynamics of spreading. The edge speed-dynamic contact angle relation is shown to obey a simple power law, and such power laws are shown to apply to naturally occurring surfaces.
Expression of scatter factor and c‐ met receptor in benign and malignant breast tissue (1997)

SF and c-met are overexpressed in breast carcinoma as compared with benign breast tissue, and they tend to be coexpressed in cancerous tissue. These findings are consistent with the idea that the SF:c-met ligand:receptor pair may have a role in breast carcinoma progression.
Broad-area high-power semiconductor optical amplifier (1991)

Operating characteristics of a high-power 400-μm-wide, 500-μm-long double-pass near-traveling-wave GaAlAs amplifier are described. In pulsed operation, 2.5 W of diffraction-limited emission at 820 nm was obtained with an external power gain of 10 dB and 24% electrical to optical conversion efficiency.
Evidence for classic complement activity in neuromyelitis optica (2014)

Abstract not available.
Vascular endothelial growth factor gene expression in patients' ischemic skeletal muscle with diabetic foot. (2002)

The endogenous VEGF gene expression in ischemic lower extremity of DLASO is obviously lower than that of ASO. It is the important endogenic cause of the genesis and development of diabetic foot ulcer.
Microcontact Printing of Proteins on Mixed Self-Assembled Monolayers (2001)

Microcontact printing of proteins from an elastomeric stamp has been demonstrated on a limited number of substrates. This work explores the generality of this method of patterning proteins by examining the role of surface wettability of both the substrate and the stamp in microcontact printing. The substrates used in this study consisted of two-component, mixed self-assembled monolayers (SAMs) of alkanethiols on gold presenting −CH3 and polar groups −COOH, −OH, or −(OCH2CH2)6OH. We found that protein adsorbed on a stamp successfully transfers onto a mixed SAM only when the mole fraction of polar functionality on the SAM exceeded a particular threshold. Although the mole fraction of polar groups required was different for each of the three types of mixed SAMs, the advancing water contact angles on these surfaces nearly coincided. Moreover, the minimum wettability of the SAM needed for the transfer of proteins decreased when the wettability of the stamp was decreased. Our findings suggest that the difference in wettability between the surfaces of the stamp and substrate is the dominant parameter that determines the successful microcontact printing of proteins.
The Value of Transaction Cost Forecasts: Another Source of Alpha (2007)

This article examines the impact of transaction costs on portfolio performance. Previous research on this topic has focused largely on post-trade considerations, i.e., the impact of realized transaction costs on investment performance. By contrast, we focus on pre-trade considerations, namely the impact of transaction costs on portfolio breadth, turnover, and expected returns. Although costs reduce the information ratio, improvements in transaction cost modeling can mitigate these effects by increasing skill and breadth. Transactions cost considerations also affect the choice of portfolio turnover. Greater turnover allows for more active bets, increasing breadth, but magnifies the impact of trading costs. Balancing these considerations yields an optimal turnover level. The analysis provides insights into the determinants of optimal fund capacity. We show that capacity problems are manifested gradually in the form of higher expected costs, reduced breadth, and lower turnover. Capacity is an elastic concept that is surprisingly responsive to even relatively modest gains in transaction cost control or forecasting ability. This suggests that fund managers can influence their capacity through investments in better execution research and technology.
Effect of carbon nanofibre structure on the binding of antibodies (2005)

Potential biomedical applications for carbon nanofibres include, but are not limited to, biosensors and drug delivery vehicles. For such applications, it is essential to know how carbon nanotubes interact with antibodies and proteins. We report on the successful adsorption of monoclonal CD3 antibodies on two types of carbon nanofibre produced by the same method and having the same average size and shape, but differing in surface structure and chemistry due to dissimilar post-treatments. Binding of proteins to nanofibres is enhanced by poly (L-lysine) (PLL) and improves with increasing disorder and hydrophilicity of the nanofibres' surface. Oxidized and disordered surfaces of pyrolytically stripped nanofibres show improved wetting and attachment of PLL and proteins compared to hydrophobic and well-ordered surfaces of heat-treated nanofibres. These results show that the surface of carbon nanofibres can be tailored for their use in biomedical applications.