gebhart/patrepeval huggingface dataset:
A novel strategy for the treatment of cocaine addiction (1998)

Cocaine's addictive liability has been linked to its pharmacologic actions on mesotelencephalic dopamine (DA) reinforcement/reward pathways in the central nervous system (CNS). Dopaminergic transmission within these pathways is modulated by gamma-aminobutyric acid (GABA). With this knowledge, we examined the utility of gamma vinylGABA (GVG), a selective and irreversible inhibitor of GABA-transaminase (GABA-T) known to potentiate GABAergic inhibition, to alter cocaine's biochemical effects as well as its effects on behaviors associated with these biochemical changes. GVG significantly attenuated cocaine-induced increases in neostriatal synaptic DA in the non-human primate (baboon) brain as assessed by positron emission tomography (PET) and abolished both the expression and acquisition of cocaine-induced conditioned place preference (CPP). It had no effect on CPP for a food reward, the delivery of cocaine to the brain or locomotor activity. These findings suggest the possible therapeutic utility in cocaine addiction of a pharmacologic strategy targeted at the GABAergic neurotransmitter system, a system distinct from but functionally linked to the DA mesotelencephalic reward/reinforcement system. However, rather than targeting the GABA receptor complex with a direct GABA agonist, this novel approach with GVG takes advantage of the prolonged effects of an irreversible enzyme inhibitor that raises endogenous GABA levels without the addictive liability associated with GABA agonists acting directly at the receptor itself. Human trials with GVG are currently being developed to directly examine the utility of this novel strategy for the treatment of cocaine addiction.
ENZYME LINKED IMMUNOSORBENT ASSAY FOR MILK PROGESTERONE (2010)

A direct antigen heterologous enzyme linked immunosorbent assay (ELISA) for milk progesterone has been developed using progesterone-3-O-carboxymethyloxime-bovine serum albumin (P-3-O-CMO-BSA) antiserum and 17-α-hydroxy-progesterone-3-O-carboxymethyloxime-horseradish peroxidase (17-α-OH-P-3-O-CMO-HRP) enzyme conjugate. The data of the present study reveal that the homologous assay, which employed P-3-O-CMO-HRP as the label, showed no displacement. On the contrary, replacement of P-3-O-CMO-HRP with 17-α-OH-P-3-O-CMO-HRP as the label showed significant displacement and led to the development of a sensitive and specific assay. The recovery of the exogenously spiked progesterone from milk pools was in the range of 94.3-97.88% for toned milk and 97.6-101% for full-cream milk. The intra-assay and interassay coefficients of variation (CVs) ranged from 4.1-7.8% and 4.4-7.0%, respectively. A high ionic strength buffer was used to obtain released progesterone from binding protein/fat. The progesterone values measured in toned and full-cream milk ranged from 1.198-9.745 ng/mL and 6.949-14.923 ng/mL, respectively. The milk progesterone values obtained by this method correlated well with those obtained by radioimmunoassay; r = 0.95 (n = 65).
Polarization-maintaining amplifier employing double-clad bow-tie fiber (2001)

We report a polarization-maintaining double-clad Yb-doped fiber amplifier employing bow-tie fiber. Borosilicate stress elements were incorporated into the inner cladding of the fiber, yielding a beat length of 5.1 mm at 633 nm. When the fiber was pumped at 975 nm and seeded with linearly polarized light, the polarization extinction ratio was >15 dB , independent of pump power, and the output power was as high as 3.5 W.
Early Biomarkers of Stroke (2003)

Abstract Background: The diagnosis and management of acute ischemic stroke are limited by the lack of rapid diagnostic assays for use in an emergency setting. Computed tomography (CT) scanning is used to diagnose hemorrhagic stroke but is relatively ineffective (&amp;lt;33% sensitive) in detecting ischemic stroke. The ability to correlate blood-borne protein biomarkers with stroke phenotypes would aid in the development of such rapid tests. Methods: ELISAs for &amp;gt;50 protein biomarkers were developed for use on a high-throughput robotic workstation. These assays were used to screen plasma samples from 214 healthy donors and 223 patients diagnosed with stroke, including 82 patients diagnosed with acute ischemic stroke. Marker assay values were first compared by univariate analysis, and then the top markers were subjected to multivariate analysis to derive a marker panel algorithm for the prediction of stroke. Results: The top markers from this analysis were S-100b (a marker of astrocytic activation), B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. In a panel algorithm in which three or more marker values above their respective cutoffs were scored as positive, these five markers provided a sensitivity of 92% at 93% specificity for ischemic stroke samples taken within 6 h from symptom onset. Conclusion: A marker panel approach to the diagnosis of stroke may provide a useful adjunct to CT scanning in the emergency setting.
Etch rate dependence on crystal orientation of lithium niobate (2010)

This paper presents the etch rate of lithium niobate (LiNbO(3)) as a function of crystal orientation. Etching is a fundamental technology needed for the fabrication of new sensors, actuators, and other new devices. In this study, LiNbO(3) spheres 30 mm in diameter were etched in hydrofluoric acid and a mixture of hydrofluoric and nitric acids at different temperatures and different times. The measured data of the etched sphere shape were processed and plotted, giving etch rate diagrams over the entire spheres. Based on the etch rate data obtained, the Wulff-Jaccodine method was used to predict the etched shape of 128° Y-cut and 155° Y-cut LiNbO(3). The predicted etching profiles were compared with those obtained by experiments. A least-square polynomial fit for the data was also developed and was found to be useful in removing some of the variation in the measurements.
Interferon‐β therapy reduces CD4+ and CD8+ T‐cell reactivity in multiple sclerosis (2006)

Therapy with interferon-beta (IFN-beta) has well-established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN-beta-treated MS patients, in response to myelin oligodendrocyte glycoprotein (MOG). The proportion of CD45RO+ memory T cells was higher in MS patients than in healthy donors, but returned to normal values upon therapy with IFN-beta. While CD45RO+ CD4+ T cells from all three groups responded to MOG in vitro, untreated patients showed augmented proliferative responses compared to healthy individuals and IFN-beta treatment reduced this elevated reactivity back to the values observed in healthy donors. Similarly, the response of CD45RO+ CD8+ T cells to MOG was strongest in untreated patients and decreased to normal values upon immunotherapy. Overall, the frequency of peripheral CD45RO+ memory T cells ex vivo correlated with the strength of the cellular in vitro response to MOG in untreated patients but not in healthy donors or IFN-beta-treated patients. Compared with healthy individuals, responding CD4+ and CD8+ cells were skewed towards a type 1 cytokine phenotype in untreated patients, but towards a type 2 phenotype under IFN-beta therapy. Our data suggest that the beneficial effect of IFN-beta in MS might be the result of the suppression or depletion of autoreactive, pro-inflammatory memory T cells in the periphery. Assessment of T-cell subsets and their reactivity to MOG may represent an important diagnostic tool for monitoring successful immunotherapy in MS.
Structure and expression of germline epsilon transcripts in human B cells induced by interleukin 4 to switch to IgE production. (1990)

Interleukin 4 (IL-4)-induced IgE production coincides with the appearance of the 2.2-kb productive epsilon-mRNA, but is preceded by synthesis of a 1.7-kb epsilon-RNA. Analysis of cDNA copies of the 5' end of this RNA indicated that the 1.7-kb epsilon-RNA is a germline epsilon immunoglobulin heavy chain transcript with an exon mapping 5' to the switch region. Transcription through switch regions has been implicated in the control of class switching. However, IL-4 or cloned CD4+ T cells were able to induce germline epsilon transcripts without inducing IgE synthesis, for which both signals were required. These results indicate that induction of human germline epsilon-RNA does not necessarily result in IgE synthesis, and that additional regulatory mechanisms are involved in class switching.
Catalysts for CO2/epoxide copolymerisation (2010)

The article reviews recent developments (mostly since 2004 until June 2010) in catalysts for CO(2)/epoxide copolymerisation and in the properties of the polycarbonates.
Mathematical Model Identifies Blood Biomarker–Based Early Cancer Detection Strategies and Limitations (2011)

Most clinical blood biomarkers lack the necessary sensitivity and specificity to reliably detect cancer at an early stage, when it is best treatable. It is not yet clear how early a clinical blood assay can be used to detect cancer or how biomarker-based strategies can be improved to enable earlier detection of smaller tumors. To address these issues, we developed a mathematical model describing dynamic plasma biomarker kinetics in relation to the growth of a tumor, beginning with a single cancer cell. To exemplify a realistic scenario in which biomarker is shed by both cancerous and noncancerous cells, we primed the model on ovarian tumor growth and CA125 shedding data, for which tumor growth parameters and shedding rates are readily available in published literature. We found that a tumor could grow unnoticed for more than 10.1 years and reach a volume of about π/6(25.36 mm)(3), corresponding to a spherical diameter of about 25.36 mm, before becoming detectable by current clinical blood assays. Model parameters were perturbed over log orders of magnitude to quantify ideal shedding rates and identify other blood-based strategies required for early submillimeter tumor detectability. The detection times we estimated are consistent with recently published tumor progression time lines based on clinical genomic sequencing data for several cancers. Here, we rigorously showed that shedding rates of current clinical blood biomarkers are likely 10(4)-fold too low to enable detection of a developing tumor within the first decade of tumor growth. The model presented here can be extended to virtually any solid cancer and associated biomarkers.
Architecture of a coprocessor module for image compositing (2002)

This paper proposes the architecture of a coprocesssor module for image compositing. The emerging MPEG-4 standard for multimedia applications allows script-based compositing of audiovisual scenes from multiple audio and visual objects. This involves the composition of the output frame by alpha-blending of Video Object Planes (VOPs). A coprocessor architecture is presented, that works in parallel to an MPEG-4 video- and audio-decoder, and performs computation and bandwidth intensive low-level algorithms for image compositing. The processor has on-chip memories that allow preload of data before it is accessed. VHDL implementation and synthesis for a 0.5/spl mu/ process show an estimate of 100 MHz achievable clock-frequency and 10 k gates for arithmetic and control circuitry which results in roughly 5 mm/sup 2/ silicon area. Overall performance is sufficient to compose more than 5 full-screen VOPs with a background of size 704/spl times/576 each at 30 Hz.
Acylation of the Lipooligosaccharide ofHaemophilus influenzaeand Colonization: anhtrBMutation Diminishes the Colonization of Human Airway Epithelial Cells (2002)

Haemophilus influenzae is a commensal and opportunistic pathogen of the human airways. A number of surface molecules contribute to colonization of the airways by H. influenzae, such as adhesins, including structures found in the lipooligosaccharide (LOS). A human bronchiolar xenograft model was employed to investigate the host-bacterial interactions involved in the colonization of the airway by H. influenzae. Differential display was used to identify H. influenzae mRNA that reflect genes which were preferentially expressed in the xenograft compared to growth. Eleven mRNA fragments had consistent increased expression when the bacteria grew in xenografts. On sequencing these fragments, eight open reading frames were identified. Three of these had no match in the NCBI or the TIGR database, while an additional three were homologous to genes involved in heme or iron acquisition and utilization: two of the mRNAs encoded proteins homologous to enzymes involved in LOS biosynthesis: a heptosyl transferase (rfaF) involved in the synthesis of the LOS core and a ketodeoxyoctonate phosphate-dependent acyltransferase (htrB) that performs one of the late acylation reactions in lipid A synthesis. Inoculation of human bronchiolar xenografts revealed a significant reduction in colonization capacity by htrB mutants. In vitro, htrB mutants elicited lesser degrees of cytoskeletal rearrangement and less stimulation of host cell signaling with 16HBE14o(-) cells and decreased intracellular survival. These results implicate acylation of H. influenzae lipid A as playing a key role in the organisms' colonization of the normal airway.
The Shape of the Lateral Edge of the First Metatarsal Head as a Risk Factor for Recurrence of Hallux Valgus (2007)

There is a significant relationship between a round-shaped lateral edge of the first metatarsal head and hallux valgus, and a positive round sign after a proximal first metatarsal osteotomy can be a risk factor for the recurrence of hallux valgus.
Transcription Start Regions in the Human Genome Are Favored Targets for MLV Integration (2003)

Factors contributing to retroviral integration have been intractable because past studies have not precisely located genomic sites of proviruses in sufficient numbers for significant analysis. In this study, 903 murine leukemia virus (MLV) and 379 human immunodeficiency virus-1 (HIV-1) integrations in the human genome were mapped. The data showed that MLV preferred integration near the start of transcriptional units (either upstream or downstream) whereas HIV-1 preferred integration anywhere in the transcriptional unit but not upstream of the transcriptional start. Defining different integration site preferences for retroviruses will have important ramifications for gene therapy and may aid in our understanding of the factors directing the integration process.
Health-related quality of life of unrelated bone marrow donors in Japan (2002)

To promote bone marrow donation, both the safety and well-being of healthy unrelated volunteer donors must be protected. This prospective cohort study evaluated donors' health-related quality of life (HRQOL) and identified factors associated with it. Using the Medical Outcomes Study Short Form 36 Health Survey (SF-36) before bone marrow harvesting (BMH), and again 1 week and 3 months after the donors' discharge, we evaluated HRQOL of 565 donors (329 men, 236 women) registered with the Japan Marrow Donor Program (JMDP). We also examined the data routinely collected by the JMDP, such as BMH-related problems and other demographic and medical variables, to determine whether such data could be used to predict donors' HRQOL after discharge. Mean scores of all pre-BMH SF-36 subscales showed better functioning than the national norm. One week after discharge, mean scores on physical functioning (PF) and role-physical (RP) subscales, indicative of physical states, and bodily pain (BP) were approximately 1 SD lower than the national norm; however, mental health (MH) and general health perception (GH) remained above normal; the most frequent BMH-related problems were pain at the donation site and lower back pain, which were associated with lower PF, RP, and BP scores. Female gender and duration of procedure predicted lower PF, RP, and BP. Three months after discharge, mean scores of all SF-36 subscales had returned to baseline levels. These data show that the adverse effects of BMH on donors' HRQOL are transient and can be minimized by better management of pain.
Intraparticle‐forced convection effect in catalyst diffusivity measurements and reactor design (1982)

Abstract Intraparticle forced convection was considered in order to explain experimentally observed changes in effective diffusivity (apparent) with flowrate, when measures are carried out in fixed beds. A complete model taking into account intraparticle diffusion and forced convection together with film diffusion is derived in order to analyze diffusivity measurements by physical methods, both in perfectly mixed reactors and fixed beds. The experiments were carried out with hydrogen tracer in a partial oxydation catalyst. Implications of the use of such “apparent” effective diffusivities in reactor design are discussed, showing that errors of 100% can be made.
Randomised sham-controlled trial of transcutaneous electrical stimulation in obstructive sleep apnoea (2016)

NCT01661712.
Secure file transfer over TCP/IP (2003)

With the spread of internetworks able to link LANs, and the availability of network hardware to monitor network traffic, the need to add additional security to traditional network utilities is becoming imperative. The development of security extensions to the FTP file transfer utility/protocol in the TCP/IP communications suite in order to provide authentication of the user and encryption of the files transferred is described. Specific security issues, including some alternatives for providing these security extensions, are given, and the final choice is explained. Initial trials of the implementation are presented. These show that on a single LAN link there is a performance penalty in providing encryption, but that over a wide area internetwork this is masked by the network delays.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mouse α1(I)‐collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast (2002)

Cell- and time-specific gene inactivation should enhance our knowledge of bone biology. Implementation of this technique requires construction of transgenic mouse lines expressing Cre recombinase in osteoblasts, the bone forming cell. We tested several promoter fragments for their ability to drive efficient Cre expression in osteoblasts. In the first mouse transgenic line, the Cre gene was placed under the control of the 2.3-kb proximal fragment of the alpha1(I)-collagen promoter, which is expressed at high levels in osteoblasts throughout their differentiation. Transgenic mice expressing this transgene in bone were bred with the ROSA26 reporter (R26R) strain in which the ROSA26 locus is targeted with a conditional LacZ reporter cassette. In R26R mice, Cre expression and subsequent Cre-mediated recombination lead to expression of the LacZ reporter gene, an event that can be monitored by LacZ staining. LacZ staining was detected in virtually all osteoblasts of alpha1(I)-Cre;R26R mice indicating that homologous recombination occurred in these cells. No other cell type stained blue. In the second line studied, the 1.3-kb fragment of osteocalcin gene 2 (OG2) promoter, which is active in differentiated osteoblasts, was used to drive Cre expression. OG2-Cre mice expressed Cre specifically in bone. However, cross of OG2-Cre mice with R26R mice did not lead to any detectable LacZ staining in osteoblasts. Lastly, we tested a more active artificial promoter derived from the OG2 promoter. The artificial OG2-Cre transgene was expressed by reverse transcriptase-polymerase chain reaction in cartilage and bone samples. After cross of the artificial OG2-Cre mice with R26R mice, we detected a LacZ staining in articular chondrocytes but not in osteoblasts. Our data suggest that the only promoter able to drive Cre expression at a level sufficient to induce recombination in osteoblasts is the alpha1(I)-collagen promoter.
Structures, Alternative Splicing, and Neurexin Binding of Multiple Neuroligins (1996)

Neuroligin 1 is a neuronal cell surface protein that binds to a subset of neurexins, polymorphic cell surface proteins that are also localized on neurons (Ichtchenko, K., Hata, Y., Nguyen, T., Ullrich, B., Missler, M., Moomaw, C., and Südhof, T. C. (1995) Cell 81, 435-443). We now describe two novel neuroligins called neuroligins 2 and 3 that are similar in structure and sequence to neuroligin 1. All neuroligins contain an N-terminal hydrophobic sequence with the characteristics of a cleaved signal peptide followed by a large esterase homology domain, a highly conserved single transmembrane region, and a short cytoplasmic domain. The three neuroligins are alternatively spliced at the same position and are expressed at high levels only in brain. Binding studies demonstrate that all three neuroligins bind to beta-neurexins both as native brain proteins and as recombinant proteins. Tight binding of the three neuroligins to beta-neurexins is observed only for beta-neurexins lacking an insert in splice site 4. Thus, neuroligins constitute a multigene family of brain-specific proteins with distinct isoforms that may have overlapping functions in mediating recognition processes between neurons.
The Design, Structure, and Clinical Update of Small Molecular Weight Matrix Metalloproteinase Inhibitors (2004)

Matrix metalloproteinases (MMPs) are a family of zinc-containing enzymes involved in the degradation and remodeling of extracellular matrix proteins. Under normal physiological conditions, the activities of these enzymes are well-regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Chronic stimulation of MMP activities due to an imbalance in the levels of MMPs and TIMPs has been implicated in the pathogenesis of a variety of diseases such as cancer, osteoarthritis, and rheumatoid arthritis. Thus, MMP inhibitors are expected to be useful for the treatment of these disorders. Because of their importance in a variety of pathological conditions, a number of small molecular weight MMP inhibitors have entered clinical trials in humans. However, the results of these trials have been extremely disappointing and have led many investigators to conclude that MMP inhibitors have no therapeutic benefit in human cancer. To date, the first generation MMP inhibitors exhibited poor bioavailability while second-generation compounds revealed that prolonged treatment caused musculoskeletal pain and inflammation or had a lack of efficacy. This article describes the design of small molecular weight MMP inhibitors, a brief description of available three-dimensional MMP structures, a review of the proposed therapeutic utility of MMP inhibitors, and a clinical update of compounds that have entered clinical trials in humans. The experimentally determined structures used in the structure-based design of MMP inhibitors are thoroughly covered. Major emphasis is on recently published and/or patented potent MMP inhibitors, from approximately January 2000 to April 2003, and their pharmacological properties. Protein inhibitors of these proteolytic enzymes, i.e. TIMPs, will not be discussed.
Automatic DNA sequencer: Computer-programmed microchemical manipulator for the Maxam–Gilbert sequencing method (1983)

A computer controlled microchemical robot which carries out a series of chemical reaction steps in DNA sequence analysis of Maxam and Gilbert’s scheme is described. Within a 2-h operation of this apparatus, one of the four types of solutions for G, A+C, C+T, or C analysis for a DNA restriction fragment is prepared and is ready for subsequent electrophoretic analysis. It is proven that the chemical robot operated by a computer command is capable of speedily accomplishing the fragmentation reaction for DNA sequencing with accuracy similar to that of a well-trained technician.