gebhart/patrepeval huggingface dataset:
Local Algorithms for Pattern Recognition and Dependencies Estimation (1993)

In previous publications (Bottou and Vapnik 1992; Vapnik 1992) we described local learning algorithms, which result in performance improvements for real problems. We present here the theoretical framework on which these algorithms are based. First, we present a new statement of certain learning problems, namely the local risk minimization. We review the basic results of the uniform convergence theory of learning, and extend these results to local risk minimization. We also extend the structural risk minimization principle for both pattern recognition problems and regression problems. This extended induction principle is the basis for a new class of algorithms.
Titanium pyridyl-phosphinimide complexes Synthesis, structure, and ethylene polymerization catalysis (2006)

A series of Tipyridyl-phosphinimide complexes of the form Cp′TiX 2 [NPR 2 (2-CH 2 Py)] (Cp′ = Cp, Cp*, R = i-Pr, t-Bu, X = Cl, Me) have been prepared and characterized. These complexes generate ethylene polymerization catalysts upon activation with MAO or B(C 6 F 5 ) 3 . The resulting polymers exhibit broad molecular weight distributions. The role of the pyridyl group is discussed in light of stoichiometric reactions of CpTiCl 2 [NPR 2 (2-CH 2 Py)] with B(C 6 F 5 ) 3 .Key words: phosphinimide complexes, pyridyl-phosphinimides, olefin polymerization.
Severe clinical outcome is uncommon in Clostridium difficile infection in children: a retrospective cohort study (2014)

Severe outcomes due to CDI are uncommon in children compared to adults. Further prospective pediatric studies on CDI in community and hospital settings are required to better understand risk factors, optimal treatment and the significance of NAP4 in pediatric CDI.
Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth, and susceptibility to IL-2 therapy of a murine melanoma (1992)

Tumor-derived chemotactic factors have been identified and suggested to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of a tumor-derived chemotactic factor molecularly identified as monocyte chemotactic protein (MCP; alternative designations are JE and MCAF) by gene transfer in a murine melanoma. After gene transfer, MCP-producing melanoma clones showed a marked (twofold) increase in the percentage of tumor-associated macrophages compared with control clones and with the parent line: for instance, the percentage of tumor-associated macrophages was 20.9 +/- 1.5, 29.4 +/- 2.3, and 47.6 +/- 2.5 for the parent line, the control V14 clone, and the MCP-producing L12 clone, respectively. MCP-producing cells were tumorigenic but exhibited a slower growth rate in vivo (e.g., doubling time of 2.9 and 6.6 days for the control V14 and the MCP-producing L12 clone, respectively) with a prolongation of survival time. The in vitro growth rate of melanoma clones was unaffected by MCP gene transfer. The same difference between MCP-producing and control cells, in terms of macrophage infiltration and growth rate, was detected after implantation in athymic mice. Whereas the in vivo growth rate of MCP-expressing tumors was slower, after i.m. inoculation of small cell numbers (10(2) cells) MCP-producing cells were slightly, but significantly, more tumorigenic. Local administration of IL-2 had modest, but definite, antitumor activity in this model; MCP-producing cells were less susceptible to local IL-2 immunotherapy. These results demonstrate that a tumor-derived chemotactic cytokine can indeed play a role in the regulation of mononuclear phagocyte recruitment in neoplastic tissues and emphasize how tumor-associated macrophages can exert a dual influence in tumor-host interactions.
A Biochemical Analysis of the Interaction of Porphyromonas gingivalis HU PG0121 Protein with DNA (2014)

K-antigen capsule, a key virulence determinant of the oral pathogen Porphyromonas gingivalis, is synthesized by proteins encoded in a series of genes transcribed as a large polycistronic message. Previously, we identified a 77-base pair inverted repeat region with the potential to form a large stem-loop structure at the 5' end of this locus. PG0121, one of two genes flanking the capsule operon, was found to be co-transcribed with the operon and to share high similarity to the DNA binding protein HU from Escherichia coli. A null mutation in PG0121 results in down-regulation of transcription of the capsule synthesis genes and production of capsule. Furthermore, we have also shown that PG0121 gene can complement multiple deficiencies in a strain of E. coli that is deficient for both the alpha and beta subunits of HU. Here, we examined the biochemical properties of the interaction of PG0121 to DNA with the emphasis on the kinds of nucleic acid architectures that may be encountered at the 77-bp inverted repeat. We have concluded that although some DNA binding characteristics are shared with E. coli HU, HU PG0121 also shows some distinct characteristics that set it apart from other HU-like proteins tested to date. We discuss our results in the context of how PG0121 may affect the regulation of the K-antigen capsule expression.
Corticocortical inhibition in human motor cortex. (1993)

1. In ten normal volunteers, a transcranial magnetic or electric stimulus that was subthreshold for evoking an EMG response in relaxed muscles was used to condition responses evoked by a later, suprathreshold magnetic or electric test shock. In most experiments the test stimulus was given to the lateral part of the motor strip in order to evoke EMG responses in the first dorsal interosseous muscle (FDI). 2. A magnetic conditioning stimulus over the hand area of cortex could suppress responses produced in the relaxed FDI by a suprathreshold magnetic test stimulus at interstimulus intervals of 1-6 ms. At interstimulus intervals of 10 and 15 ms, the test response was facilitated. 3. Using a focal magnetic stimulus we explored the effects of moving the conditioning stimulus to different scalp locations while maintaining the magnetic test coil at one site. If the conditioning coil was moved anterior or posterior to the motor strip there was less suppression of test responses in the FDI. In contrast, stimulation at the vertex could suppress FDI responses by an amount comparable to that seen with stimulation over the hand area. With the positions of the two coils reversed, conditioning stimuli over the hand area suppressed responses evoked in leg muscles by vertex test shocks. 4. The intensity of both conditioning and test shocks influenced the amount of suppression. Small test responses were more readily suppressed than large responses. The best suppression was seen with small conditioning stimuli (0.7-0.9 times motor threshold in relaxed muscle); increasing the intensity to motor threshold or above resulted in less suppression or even facilitation. 5. Two experiments suggested that the suppression was produced by an action on cortical, rather than spinal excitability. First, a magnetic conditioning stimulus over the hand area failed to produce any suppression of responses evoked in active hand muscles by a small (approximately 200 V, 50 microsecond time constant) anodal electric test shock. Second, a vertex conditioning shock had no effect on forearm flexor H reflexes even though responses in the same muscles produced by magnetic cortical test shocks were readily suppressed at appropriate interstimulus intervals. 6. Small anodal electric conditioning stimuli were much less effective in suppressing magnetic test responses than either magnetic or cathodal electric conditioning shocks.(ABSTRACT TRUNCATED AT 400 WORDS)
Identification of nicotinic acetylcholine receptors on lymphocytes in the periphery as well as thymus in mice (1997)

The existence of nicotinic acetylcholine receptors (nAChR) on lymphocytes remains controversial. We attempted to show the existence of nAChR on murine lymphocytes. The intraperitoneal injection of nicotine induced the lymphocytosis in the spleen on day 3. Although freshly isolated lymphocytes bound small quantities of fluorescein isothiocyanate (FITC)-conjugated alpha-bungarotoxin (alpha BuTx), they began to bind alpha BuTx after incubation in medium. In contrast to granulocytes, various lymphocyte subsets obtained from various lymphoid organs were found to bind alpha BuTx. Affinity purification of alpha BuTx-binding protein revealed that lymphocytes expressed the same nAChR molecules as those of muscle. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that lymphocytes expressed the alpha-subunit mRNA of nAChR. These results suggest that lymphocytes carry nAChR on the surface and are stimulated directly via their nAChR by parasympathetic nerve stimuli.
Real‐time refinement of subthalamic nucleus targeting using Bayesian decision‐making on the root mean square measure (2006)

The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders.
Lipid Lowering by Diet Reduces Matrix Metalloproteinase Activity and Increases Collagen Content of Rabbit Atheroma (1998)

These results establish a mechanism by which lipid lowering may stabilize vulnerable plaques by reduced expression and activity of enzymes that degrade the arterial extracellular matrix and render atheroma less susceptible to disruption and thrombosis by favoring collagen accumulation in the fibrous cap.
Development of a Real-Time Reverse Transcriptase PCR Assay for Type A Influenza Virus and the Avian H5 and H7 Hemagglutinin Subtypes (2002)

A real-time reverse transcriptase PCR (RRT-PCR) assay based on the avian influenza virus matrix gene was developed for the rapid detection of type A influenza virus. Additionally, H5 and H7 hemagglutinin subtype-specific probe sets were developed based on North American avian influenza virus sequences. The RRT-PCR assay utilizes a one-step RT-PCR protocol and fluorogenic hydrolysis type probes. The matrix gene RRT-PCR assay has a detection limit of 10 fg or approximately 1,000 copies of target RNA and can detect 0.1 50% egg infective dose of virus. The H5- and H7-specific probe sets each have a detection limit of 100 fg of target RNA or approximately 10(3) to 10(4) gene copies. The sensitivity and specificity of the real-time PCR assay were directly compared with those of the current standard for detection of influenza virus: virus isolation (VI) in embryonated chicken eggs and hemagglutinin subtyping by hemagglutination inhibition (HI) assay. The comparison was performed with 1,550 tracheal and cloacal swabs from various avian species and environmental swabs obtained from live-bird markets in New York and New Jersey. Influenza virus-specific RRT-PCR results correlated with VI results for 89% of the samples. The remaining samples were positive with only one detection method. Overall the sensitivity and specificity of the H7- and H5-specific RRT-PCR were similar to those of VI and HI.
Review of frovatriptan in the treatment of migraine (2008)

Triptans are recommended for the acute treatment of moderate to severe migraine or failure to respond to other acute migraine treatments. Seven triptans are available providing a wide range of choices. These triptans are more similar than dissimilar but patients do note differences in effectiveness and in tolerance. Also migraine situations may differ from attack to attack, providing the opportunity to exploit the uniqueness of a particular triptan. Frovatriptan has a uniquely long-half life, five times that of other triptans. This provides the opportunity to use frovatriptan in mini-prophylaxis such as in menstrual-related migraine and other situations, as well as use in long-lasting or recurrent migraine.
Measured performance of data transmission over cellular telephone networks (1994)

Recent developments in mobile communication and personal computer technology have laid a new foundation for mobile computing. Performance of the data communication system as seen by an application program is a fundamental factor when communication infrastructure at the application layer is designed. This paper provides results of performance measurements of data transmission over two different cellular telephone networks, a digital GSM-network and an analogue NMT-network. Since our emphasis is on performance as seen by application programs, we use the standard TCP/IP protocols in the measurements. The performance is measured using three basic operations: establishment of a wireless dial-up connection, exchange of request-reply messages, and bulk data transfer. The external conditions under which the measurements were carried out present a normal office environment when the field strength of the cellular link is good or fairly good.
A new selective substrate for cathepsin E based on the cleavage site sequence of α2-macroglobulin (2005)

Cathepsin E is an intracellular aspartic proteinase of the pepsin family predominantly expressed in cells of the immune system and believed to contribute to homeostasis by participating in host defense mechanisms. Studies on its enzymatic properties, however, have been limited by a lack of sensitive and selective substrates. For a better understanding of the importance of this enzyme in vivo, we designed and synthesized a highly sensitive peptide substrate for cathepsin E based on the sequence of the specific cleavage site of alpha2-macroglobulin. The substrate constructed, MOCAc-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2 [where MOCAc is (7-methoxycoumarin-4-yl)acetyl and Dnp is dinitrophenyl], derived from the cleavage site sequence of human alpha2-macroglobulin, was the most sensitive and selective for cathepsin E, with k(cat)/K(m) values of 8-11 microM(-1) s(-1), whereas it was resistant to hydrolysis by the analogous aspartic proteinases cathepsin D and pepsin, as well as the lysosomal cysteine proteinases cathepsins B, L, and H. The assay allows the detection of a few fmol of cathepsin E, even in the presence of plasma and cell lysate, and gives accurate results over a wide enzyme concentration range. This substrate might represent a useful tool for monitoring and accurately quantifying cathepsin E, even in crude enzyme preparations.
Small Molecule Binding Sites on the Ras:SOS Complex Can Be Exploited for Inhibition of Ras Activation (2015)

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras.
Prostaglandin Extraction and Analysis in <em>Caenorhabditis elegans</em> (2013)

Caenorhabditis elegans is emerging as a powerful animal model to study the biology of lipids(1-9). Prostaglandins are an important class of eicosanoids, which are lipid signals derived from polyunsaturated fatty acids (PUFAs)(10-14). These signalling molecules are difficult to study because of their low abundance and reactive nature. The characteristic feature of prostaglandins is a cyclopentane ring structure located within the fatty acid backbone. In mammals, prostaglandins can be formed through cyclooxygenase enzyme-dependent and -independent pathways(10,15). C. elegans synthesizes a wide array of prostaglandins independent of cyclooxygenases(6,16,17). A large class of F-series prostaglandins has been identified, but the study of eicosanoids is at an early stage with ample room for new discoveries. Here we describe a procedure for extracting and analyzing prostaglandins and other eicosanoids. Charged lipids are extracted from mass worm cultures using a liquid-liquid extraction technique and analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The inclusion of deuterated analogs of prostaglandins, such as PGF2 α-d4 as an internal standard is recommended for quantitative analysis. Multiple reaction monitoring or MRM can be used to quantify and compare specific prostaglandin types between wild-type and mutant animals. Collision-induced decomposition or MS/MS can be used to obtain information on important structural features. Liquid chromatography mass spectrometry (LC-MS) survey scans of a selected mass range, such as m/z 315-360 can be used to evaluate global changes in prostaglandin levels. We provide examples of all three analyses. These methods will provide researchers with a toolset for discovering novel eicosanoids and delineating their metabolic pathways.
Phosphorylation-dependent Regnase-1 release from endoplasmic reticulum is critical in IL-17 response (2019)

Regnase-1 (also known as Zc3h12a or MCPIP-1) is an endoribonuclease involved in mRNA degradation of inflammation-associated genes. Regnase-1 is inactivated in response to external stimuli through post-translational modifications including phosphorylation, yet the precise role of phosphorylation remains unknown. Here, we demonstrate that interleukin (IL)-17 induces phosphorylation of Regnase-1 in an Act1-TBK1/IKKi-dependent manner, especially in nonhematopoietic cells. Phosphorylated Regnase-1 is released from the endoplasmic reticulum (ER) into the cytosol, thereby losing its mRNA degradation function, which leads to expression of IL-17 target genes. By using CRISPR/Cas-9 technology, we generated Regnase-1 mutant mice, in which IL-17-induced Regnase-1 phosphorylation is completely blocked. Mutant mice (<i>Regnase-1<sup>AA/AA</sup></i> and <i>Regnase-1<sup>ΔCTD/ΔCTD</sup></i> ) were resistant to the IL-17-mediated inflammation caused by T helper 17 (Th17) cells in vivo. Thus, Regnase-1 plays a critical role in the development of IL-17-mediated inflammatory diseases via the Act1-TBK1-IKKi axis, and blockade of Regnase-1 phosphorylation sites may be promising for treatment of Th17-associated diseases.
3D-QSAR Analysis on ATR Protein Kinase Inhibitors Using CoMFA and CoMSIA (2015)

Ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase is an attractive anticancer target. In this study, comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) were performed on a series of aminopyrazine ATR inhibitors. The models generated by CoMFA had a cross-validated coefficient (q(2)) of 0.752 and a regression coefficient (r(2)) of 0.947. The CoMSIA models had a q(2) of 0.728 and an r(2) of 0.936. The reasonable quantitative structure-activity relationship model showed robust predictive ability. The contour map provided guidelines for building novel virtual compounds based on compound NO.40. In addition, the 3D structure of ATR was modeled by homology modeling. Molecular dynamic simulations were employed to optimize the structure. The docking results offered insights into the interactions between the inhibitors and the active site for potent analysis. This study provides useful guidance for the discovery of more potent compounds.
Silver-Enhanced Colloidal Gold Electrochemical Stripping Detection of DNA Hybridization (2001)

We report on a novel method for detecting DNA hybridization, based on the precipitation of silver on gold nanoparticle tags and a subsequent electrochemical stripping detection of the dissolved silver. Such coupling of a nanoparticle-promoted silver precipitation with the remarkable sensitivity of stripping metal analysis offers a dramatic enhancement of the hybridization response. An efficient magnetic isolation of the duplex is used for discriminating against nonhybridized DNA, including an excess of mismatched oligonucleotides. The new silver-enhanced colloidal gold stripping detection strategy holds great promise for the detection of DNA hybridization and represents an attractive alternative to indirect optical affinity assays of nucleic acids and other biomolecules.
[Helicobacter pylori and skin diseases--a (still) intact myth?]. (2000)

Helicobacter pylori plays a key role in the aetiology of peptic ulcer, gastric cancer and gastric MALT-lymphoma. Based on a number of reports, a possible relationship of Helicobacter pylori infection to a variety of different dermatoses has been suggested, including urticaria, rosacea, acne-rosacea, atopic dermatitis, alopecia areata, Sjögren's syndrome, Schönlein-Henoch purpura, and Sweet syndrome. Larger case-control studies, however, do not confirm this relationship. Therefore, Helicobacter pylori eradication therapy cannot be generally recommended in these dermatoses.
CHOLESTASIS AS A PRESENTING FEATURE OF ACUTE EPSTEIN-BARR VIRUS INFECTION (2001)

Biochemical evidence of hepatic involvement in Epstein-Barr virus disease is common but clinical features of cholestasis are rare in children. We present three children with cholestasis as a presenting feature of Epstein-Barr virus disease.
Cell-surface-antigen mutants of haematopoietic cells. Tools to study differentiation, biosynthesis and function (1985)

Rationale for and limitations of a somatic genetic approach for studying cell-surface-antigen biosyn- thesis and function Serological heterogeneity of haematopoietic cells One of the major concepts of developmental biology is that diverse cell lineages arise from a common progenitor cell. Important among the objectives of developmental biology is to under- stand the lineage relationships of those cells that descend from a single progenitor, to understand the events that lead to commitment of a progenitor cell to a specific developmental pathway, and to understand how the steps of differentiation along a particular pathway are regulated.