gebhart/patrepeval huggingface dataset:
Identification of two epidermal growth factor-sensitive tyrosine phosphorylation sites of phospholipase C-gamma in intact HSC-1 cells. (1990)

The 145-kDa phospholipase C isozyme, PLC-gamma, is an excellent substrate for the epidermal growth factor (EGF) receptor both in vivo and in vitro. We now demonstrate that EGF treatment of HSC-1 cells, a human squamous cell carcinoma-derived cell line that expresses high levels of the EGF receptor, rapidly induces tyrosine phosphorylation of two-thirds of the total cellular PLC-gamma pool. A two-step immunoaffinity protocol was used for large-scale isolation of phosphorylated PLC-gamma from the cytosol of EGF-treated HSC-1 cells. Phosphorylated PLC-gamma was digested with trypsin, then phosphotyrosine-containing peptides were purified by phosphotyrosine affinity chromatography and reverse-phase high performance liquid chromatography. The two major phosphotyrosine-containing tryptic peptides were sequenced. Comparison of the sequence data with the bovine brain PLC-gamma amino acid sequence indicated that the major, EGF-sensitive tyrosine phosphorylation sites of human PLC-gamma correspond to the bovine brain PLC-gamma tyrosine residues 771 and 1254. The former residue is adjacent to regions of PLC-gamma that contain high homology to the non-catalytic, amino-terminal region of the src tyrosine kinase. The latter residue lies near the carboxyl terminus of the PLC-gamma molecule. The accompanying manuscript (Kim J.W., Sim, S.S., Kim, U-H., Nishibe, S., Wahl, M. I., Carpenter, G., and Rhe, S. G. (1990) J. Biol. Chem. 265, 3940-3943) identifies these same 2 residues plus 2 additional tyrosine phosphorylation sites through large-scale in vitro phosphorylation of purified bovine brain PLC-gamma by the EGF receptor.
Interstitial brachytherapy procedures for brain tumors (1997)

Promising results have been obtained using brachytherapy in the treatment of brain tumors. Very low-dose rate brachytherapy (60-100 Gy given at 0.05-0.10 Gy/h) has been used for low-grade gliomas, resulting in 5- and 10-year survival probabilities of 85% and 83% for pilocytic astrocytomas and 61% and 51% for grade II astrocytomas. Only 2.6% of patients had symptomatic radiation necrosis. For faster-growing high-grade gliomas, temporary implants delivering about 60 Gy at 0.40-0.60 Gy/h are generally used. The largest series have reported median survival times of 12-13 months after brachytherapy for recurrent malignant gliomas and 18-19 months after diagnosis of primary glioblastomas treated with external beam radiotherapy and brachytherapy boost. A recent prospective, randomized trial demonstrated significantly improved survival for high-grade glioma patients who had brachytherapy boost. However, over 50% of patients who undergo brachytherapy for malignant gliomas require reoperation for tumor progression and/or radiation necrosis. Strategies are under development to improve local control without increasing radiation toxicity.
Computer Generation of Metal Components by Simultaneous Deposition of Mould, Cores and Part (2006)

A new solid freeforming method based on co-delivery of mould powder materials and part powder materials using vibration-controlled, dry powder valves is presented in this paper. Thin layers of stainless steel powder are delivered to the forming area according to the cross-section of the CAD file to produce the component. Mould powder which has low sinterability is delivered to the non-forming areas of the same layer. All powders are delivered by computer-controlled, acoustic powder valves. The flow rate and switching of the valves provides the composition and shape control during fabrication. The stacked layers of loose powder are then sintered in a conventional furnace. The mould materials are removed after sintering. This method avoids the high thermal stress problem in selective laser sintering, avoids high capitalisation, makes use of conventional furnaces and allows for the incorporation of three dimensional function gradients. Test pieces including step wedge and Spierpinski’s cube were fabricated. Advantages, limitations and problems are discussed.
Introduction of carrier interference to spread spectrum multiple access (2003)

This paper introduces a new scheme for spread spectrum multiple access. Like MC-CDMA, this scheme accomplishes spectral spreading by transmission of identical data over N carriers simultaneously. However, unlike any existing CDMA technique to date, this method supports user orthogonality not through the use of spreading codes (based on PN sequences), but rather through multiple carrier interference. Specifically, in this novel method, aptly named CIMA (carrier interference multiple access), the interference of multiple carriers enables user orthogonality or pseudo orthogonality based on user positioning in time. It is shown that CIMA supports simplified receiver structures for AWGN channels, and offers performance benefits in AWGN and fading environments.
Microelectrode Study of Pore Size, Ion Size, and Solvent Effects on the Charge/Discharge Behavior of Microporous Carbons for Electrical Double-Layer Capacitors (2008)

International audience
Enhancement of Bioavailability of Dopamine via Nasal Route in Beagle Dogs. (1992)

Dopamine (DA), which is ineffective by oral administration due to first pass metabolism and is usually injected, was administered to dogs via rectal, dermal, buccal and nasal routes. The nasal route had the highest bioavailability and best avoided first pass metabolism. The effects of the addition of hydroxypropyl cellulose (HPC), sodium deoxycholate, POE (6) hydrogenated caster oil (HCO-60) and Azone on the nasal absorption increased bioavailability from 11.7% (control) to about 20%, 35%, 25% and 68%, respectively. Further, with a combination of 2% HPC and 5% Azone, bioavailability was increased to almost the same level as with i.v. administration. At the same time, plasma concentrations were maintained at a high level for more than 7 h. The increase in bioavailability is presumed to be caused by an enhancement in absorption and prolongation of the time DA is retained in the nasal cavity due to Azone and HPC, respectively.
Antibodies to CD44 and integrin α4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment (1999)

The role of various adhesion molecules in lymphocyte homing to the brain and in inflammatory autoimmune disease of the central nervous system (CNS) was examined in mice. Activated T cell lines and clones expressed CD44 and integrin alpha4, but not L-selectin, and entered the CNS independent of their antigen specificity. mAbs directed against CD44 and integrin alpha4 prevented the transfer of experimental autoimmune encephalomyelitis (EAE) by myelin basic protein-specific T cells. T cells preincubated with anti-CD44 or antiintegrin alpha4 were blocked only partially from entering the brain parenchyma. However, both antibodies efficiently prevented CNS inflammation and clinical expression of EAE when injected in vivo. This effect lasted as long as antibodies were administered. Antibodies specific for L-selectin had no effect on homing of encephalitogenic T cells to the brain or development of EAE. Antiintegrin alpha4 and anti-CD44 did not impair the activation and function of encephalitogenic T cells in vitro and did not deplete integrin alpha4- or CD44-positive cells in vivo. These data suggest that, in the absence of leukocyte recruitment, the entry of a reduced number of activated myelin basic protein-reactive T cells in the CNS is not sufficient for the development and expression of EAE. We propose that antibodies to integrin alpha4 and CD44 prevent clinical disease by partially targeting the primary influx of encephalitogenic T cells and by preventing the secondary influx of leukocytes to lesions initiated by the transferred T cells.
An automatic registration method for frameless stereotaxy, image guided surgery, and enhanced reality visualization (1996)

There is a need for frameless guidance systems to help surgeons plan the exact location for incisions, to define the margins of tumors, and to precisely identify locations of neighboring critical structures. The authors have developed an automatic technique for registering clinical data, such as segmented magnetic resonance imaging (MRI) or computed tomography (CT) reconstructions, with any view of the patient on the operating table. The authors demonstrate on the specific example of neurosurgery. The method enables a visual mix of live video of the patient and the segmented three-dimensional (3-D) MRI or CT model. This supports enhanced reality techniques for planning and guiding neurosurgical procedures and allows us to interactively view extracranial or intracranial structures nonintrusively. Extensions of the method include image guided biopsies, focused therapeutic procedures, and clinical studies involving change detection over time sequences of images.
Association of a cellular heat shock protein with simian virus 40 large T antigen in transformed cells (1989)

The viral oncoprotein of simian virus 40, large T antigen (T-ag), is essential for viral replication and cellular transformation. To understand the mechanisms by which T-ag mediates its multifunctional properties, it is important to identify the cellular targets with which it interacts. A cellular protein of 73 kilodaltons (p73) which specifically associates with T-ag in simian virus 40-transformed BALB/c 3T3E cells has been identified. The binding of p73 to T-ag was demonstrated by coimmunoprecipitation analyses using polyclonal and monoclonal antibodies specific for T-ag. The interaction of p73 with T-ag was independent of T-ag complex formation with the cellular protein p53. Partial V8 protease cleavage maps for p73 and the cellular heat shock protein hsp70 were identical. Immunoblot analyses indicated that p73 complexed to T-ag was antigenically related to hsp70. T-ag deletion mutants were constructed that remove internal, amino-terminal, and carboxy-terminal sequences. These mutants mapped the p73 binding domain to the amino terminus of T-ag. The specific dissociation of p73 from the p73/T-ag complex was mediated by ATP; GTP, CTP, and UTP were also utilized as substrates. These characteristics suggest that p73 may be a member of the hsp70 family of heat shock proteins. The biologic significance of p73/T-ag complex formation has yet to be determined.
Detection of MRP functional activity: Calcein AM but not BCECF AM as a multidrug resistance‐related protein (MRP1) substrate (2001)

Resistance to anticancer drugs has been attributed to an array of cellular changes. The multidrug resistance-related protein (MRP1) is an efflux pump whose overexpression confers resistance to several classes of drugs, such as the anthracyclines, epipodophyllotoxins, and vinca alkaloids. These drugs are mainstays in cancer therapy. MRP1 overexpression is hypothesized to be a causative agent of clinical treatment failure. Consistently accurate methods for detecting this protein are necessary to further understand its biology and delineate its possible clinical relevance. Flow cytometric analysis of multidrug resistance (MDR) is a valuable method to evaluate both antigen expression and function. Using flow cytometry, we assayed MRP1 functional activity in pediatric leukemic blasts and an array of MDR+ and WT cell lines. We conclude that calcein AM, when used in a retention assay with MRP1-specific modulators, is able to reliably detect MRP functional activity. 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF AM) transport is not indicative of MRP1 overexpression. .
Identification of Multiple Analytes Using an Optical Sensor Array and Pattern Recognition Neural Networks (1997)

The further development of a vapor-sensing device utilizing an array of broadly distributed optical sensors is detailed. Data from these optical sensors provided input to pattern-recognizing neural networks, which successfully identified and quantified a collection of 20 analyte vapors. The optical sensor array consisted of 19 optical fibers whose tips were coated with Nile Red immobilized in various polymer matrices. Responses consisted of the changes in fluorescence with time resulting from the presentation of a vapor to the sensor array. Numerical descriptors calculated from these responses were then used to highlight important temporal and spatial features. Learning vector quantization neural network models were constructed using subsets of these descriptors, and they accurately identified and quantified each of the presented analytes. Successful classification was achieved for both the training set data (89%) and for the external prediction set data (90%). Relative concentrations were correctly assigned for 90% of the prediction set data.
Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes (1992)

In Lewis rats, immunization with myelin basic protein induces two distinct encephalitogenic T cell populations, those responding to the immunodominant 72-89 epitope and those specific for a secondary epitope including residues 87-99. The 72-89 specific T cells were I-A restricted and preferentially expressed V beta 8.2 in their TCR. To determine the fine specificity, MHC restriction, and TCR V beta gene use in T cells reactive to the secondary epitope, we characterized 23 T cell clones from the lymph nodes (LN) and spinal cords (SC) of rats immunized with either whole basic protein or synthetic peptides S85-99 and S87-99 that were found to be functionally similar. The S85-99/S87-99 specific clones from LN and SC were all encephalitogenic despite differences in recognition of intact basic protein and class II MHC restriction. Unlike LN clones that overexpressed V beta 8 (46%+) and V beta 6 (31%+), however, SC clones were strongly biased (86%+) in their expression of V beta 6. This V gene bias raised the possibility of TCR peptide therapy using V beta 6 peptides. The V beta 6 sequence was similar to V beta 8.2 in the CDR2 region, and the corresponding peptides from this region were found to be cross-reactive in vivo. Moreover, both peptides were effective in the treatment of EAE induced with either S85-99, biased in V beta 6+ and V beta 8+ T cells, or guinea pig basic protein, biased only in V beta 8+ T cells. These data demonstrate the presence of common immunogenic epitopes among subsets of TCR V region gene families that possess important regulatory activity on effector T cell function.
Dynamic Single-Cell Network Profiles in Acute Myelogenous Leukemia Are Associated with Patient Response to Standard Induction Therapy (2010)

These data emphasize the value of performing quantitative SCNP under modulated conditions as a basis for the development of tests highly predictive for response to induction chemotherapy. SCNP provides information distinct from other known prognostic factors such as age, secondary AML, cytogenetics, and molecular alterations and is potentially combinable with the latter to improve clinical decision making. Independent validation studies are warranted.
Genetic markers associated with early cancer‐specific mortality following prostatectomy (2013)

This study identified new CNAs and genes that likely contribute to the pathogenesis of localized PCa and suggests that patients whose tumors have acquired CNAs of PTEN, MYC, or both have an increased risk of early PCa-specific mortality.
Segment Routing Part I (2016)

Over the past ten years, operators have heavily invested in network infrastructure because of exploding growth in IP traffic. Moreover, the lack of close interaction between applications and network infrastructure has made the situation even worse:Traffic engineering solutions fell short of expectations, and as a result, network infrastructures are largely underutilized. Implementation and operational complexity have led to a surge in operating expenditures, along with greater network instability. Segment Routing (SR) addresses these challenges by focusing on operational simplicity, better scale, and better application utilization of the installed infrastructure. SR achieves this by moving state from the network to the packet header. This simplifies and scales the network while putting the application in control. For the first time in the IP industry, applications program inter-domain SLA-enabled policies at scale through the Data Center, the metro/aggregation and the backbone. Segment Routing has been designed from day one for SDN and seeks the right balance between distributed intelligence, centralized optimization, and application-based policy creation. Many operators across different market segments Over-The-Top, Hyper-Scale Cloud, Service Providers, Enterprise have publicly expressed their investment into Segment Routing as the de-facto SDN architecture. This book aims at sharing and explaining the technology to a broad audience. Formal concepts are introduced together with the use-cases that lead to their definition. Doing so, the reader follows the insights and experience of the inventor of the technology and understands why it was designed this way. To further enhance the practical understanding of the technology, the authors have collected opinions from many operators who worked with them during this project. These insights help the reader to better understand the objective and benefits of the technology and its numerous deployment use-cases. This book is also available in Kindle ebook format
Site-Specific Incorporation of Novel Backbone Structures into Proteins (1992)

A number of unnatural amino acids and amino acid analogs with modified backbone structures were substituted for alanine-82 in T4 lysozyme. Replacements included alpha,alpha-disubstituted amino acids, N-alkyl amino acids, and lactic acid, an isoelectronic analog of alanine. The effects of these electronic and structural perturbations on the stability of T4 lysozyme were determined. The relatively broad substrate specificity of the Escherichia coli protein biosynthetic machinery suggests that a wide range of backbone and side-chain substitutions can be introduced, allowing a more precise definition of the factors affecting protein stability.
The active metabolite of prasugrel effectively blocks the platelet P2Y12receptor and inhibits procoagulant and pro-inflammatory platelet responses (2008)

The aim of these studies was to investigate the extent of platelet P2Y(12) receptor inhibition by the thienopyridine active metabolite of prasugrel, R-138727. Blood was taken from healthy volunteers and pre-incubated with R-138727 or cangrelor (AR-C66931MX). Platelet aggregation was assessed in platelet rich plasma (PRP) and whole blood (WB). Vasodilator stimulated phosphoprotein (VASP) phosphorylation, platelet procoagulant activity (annexin V binding and microparticle formation) and calcium mobilisation were measured by flow cytometry. Platelet-leukocyte co-aggregate formation and sCD40L release, both pro-inflammatory responses of platelets, were measured by flow cytometry and ELISA, respectively. P2Y(12) receptor antagonism was determined using a radioligand binding assay ((33)P 2-MeSADP) in resting and stimulated platelets and the effects of clopidogrel administration were also assessed. R-138727 yielded concentration-dependent inhibition of platelet aggregation, VASP phosphorylation inhibition, procoagulant activity and pro-inflammatory responses. In the presence of R-138727 or cangrelor there was increased calcium reuptake following agonist stimulation. R-138727 30 micromol/L and cangrelor 1 micromol/L completely inhibited (33)P 2-MeSADP binding, compared to partial inhibition following clopidogrel administration. Platelet activation and granule secretion did not expose an additional pool of P2Y(12) receptors. Prasugrel's active metabolite effectively blocks the P2Y(12) receptor with the highest concentrations tested yielding complete inhibition of P2Y(12)-mediated amplification of several important platelet responses.
Antimicrosporidial Activities of Fumagillin, TNP-470, Ovalicin, and Ovalicin Derivatives In Vitro and In Vivo (2006)

Therapies for microsporidiosis in humans are limited, and fumagillin, which appears to be the most broadly effective antimicrosporidial drug, is considered to be moderately toxic. The purpose of this study was to apply an in vitro drug screening assay for Encephalitozoon intestinalis and Vittaforma corneae and an in vivo athymic mouse model of V. corneae infection to assess the efficacy of TNP-470 (a semisynthetic analogue of fumagillin), ovalicin, and eight ovalicin derivatives. TNP-470, ovalicin, and three of the ovalicin derivatives inhibited both E. intestinalis and V. corneae replication by more than 70% in vitro. Another three of the ovalicin derivatives inhibited one of the two microsporidian species by more than 70%. None of the treated athymic mice survived the V. corneae infection, but they did survive statistically significantly longer than the untreated controls after daily treatment with fumagillin administered at 5, 10, and 20 mg/kg of body weight subcutaneously (s.c.), TNP-470 administered at 20 mg/kg intraperitoneally (i.p.), or ovalicin administered at 5 mg/kg s.c. Of two ovalicin derivatives that were assessed in vivo, NSC 9665 given at 10 mg/kg i.p. daily also statistically significantly prolonged survival of the mice. No lesions associated with drug toxicity were observed in the kidneys or livers of uninfected mice treated with these drugs at the highest dose of 20 mg/kg daily. These results thus support continued studies to identify more effective fumagillin-related drugs for treating microsporidiosis.
Recurrent neural network based language model (2010)

A new recurrent neural network based language model (RNN LM) with applications to speech recognition is presented. Results indicate that it is possible to obtain around 50% reduction of perplexity by using mixture of several RNN LMs, compared to a state of the art backoff language model. Speech recognition experiments show around 18% reduction of word error rate on the Wall Street Journal task when comparing models trained on the same amount of data, and around 5% on the much harder NIST RT05 task, even when the backoff model is trained on much more data than the RNN LM. We provide ample empirical evidence to suggest that connectionist language models are superior to standard n-gram techniques, except their high computational (training) complexity. Index Terms: language modeling, recurrent neural networks, speech recognition