gebhart/patrepeval huggingface dataset:
Mortality and bacteriology of sepsis following cecal ligation and puncture in aged mice (1990)

Epidemiologic data suggest that elderly adults are more susceptible to invasive bacterial infection by indigenous gut flora than are younger adults. The purpose of this investigation was to characterize a murine model of clinically encountered peritonitis in the aged. We subjected three different age groups (young, 16 weeks; mature, 12 months; senescent, 24 months) of C57BL/6NNia mice to surgically induced peritonitis by the cecal ligation and puncture procedure. Senescent mice died in a significantly shorter time following surgery than mature mice (median time to death, 24.4 versus 38.5 h, respectively; P less than or equal to 0.001). Blood, liver, spleen and occasionally, ceca were obtained at 2 and 12 h after the cecal ligation and puncture procedure and immediately following death, to characterize the bacterial kinetics of the model. Qualitative and quantitative aerobic, anaerobic, and coliform cultures were performed. No age-related differences were found in the types of bacteria isolated throughout the time course of progressive sepsis. In mice in the mature and senescent age groups, at 2 and 12 h postsurgery, gram-negative anaerobes and gram-positive aerobes predominated in all tissues that were cultured. At the time of death, however, blood and tissue isolates consisted predominantly of coliform bacteria. The shift from mixed infection during sepsis to predominantly gram-negative bacterial infection reflected a similar progressive shift in bacterial types found in the cecum. At death, senescent mice had 100-fold fewer coliform bacteria in the bloodstream than those found in mature mice (2.5 x 10(9) versus 4.6 x 10(11), respectively). The increased sensitivity of aged mice to invasive bacterial infection documented in this series of experiments accords well with human epidemiologic experience and demonstrates the appropriateness of the model for continued investigations of sepsis in the aged.
ChemInform Abstract: Antirheumatic Agents. Part 1. Novel Methotrexate Derivatives Bearing an Indoline Moiety. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A core–BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes (2002)

BRAF35, a structural DNA-binding protein, initially was identified as a component of a large BRCA2-containing complex. Biochemical analysis revealed the presence of a smaller core-BRAF35 complex devoid of BRCA2. Here we report the isolation of a six-subunit core-BRAF35 complex with the capacity to deacetylate histones, termed the BRAF-histone deacetylase complex (BHC), from human cells. BHC contains polypeptides reminiscent of the chromatin-remodeling complexes SWI/SNF and NuRD (nucleosome remodeling and deacetylating). Similar to NuRD, BHC contains an Mi2-like subunit, BHC80, and a PHD zinc-finger subunit as well as histone deacetylases 1/2 and an MTA-like subunit, the transcriptional corepressor CoREST. We show that BHC mediates repression of neuron-specific genes through the cis-regulatory element known as the repressor element 1 or neural restrictive silencer (RE1/NRS). Chromatin-immunoprecipitation experiments demonstrate the recruitment of BHC by the neuronal repressor REST. Expression of BRAF35 containing a single point mutation in the HMG domain of the protein abrogated REST-mediated transcriptional repression. These results demonstrate a role for core-BRAF35-containing complex in the regulation of neuron-specific genes through modulation of the chromatin structure.
Introduction to Parallel Algorithms and Architectures: Arrays, Trees, Hypercubes (1991)

Introduction to Parallel Algorithms and Architectures: Arrays Trees Hypercubes provides an introduction to the expanding field of parallel algorithms and architectures. This book focuses on parallel computation involving the most popular network architectures, namely, arrays, trees, hypercubes, and some closely related networks.Organized into three chapters, this book begins with an overview of the simplest architectures of arrays and trees. This text then presents the structures and relationships between the dominant network architectures, as well as the most efficient parallel algorithms for
Ribosomal Protein S5 Interacts with the Internal Ribosomal Entry Site of Hepatitis C Virus (2001)

Translational initiation of hepatitis C virus (HCV) genome RNA occurs via its highly structured 5' noncoding region called the internal ribosome entry site (IRES). Recent studies indicate that HCV IRES and 40 S ribosomal subunit form a stable binary complex that is believed to be important for the subsequent assembly of the 48 S initiation complex. Ribosomal protein (rp) S9 has been suggested as the prime candidate protein for binding of the HCV IRES to the 40 S subunit. RpS9 has a molecular mass of approximately 25 kDa in UV cross-linking experiments. In the present study, we examined the approximately 25-kDa proteins of the 40 S ribosome that form complexes with the HCV IRES upon UV cross-linking. Immunoprecipitation with specific antibodies against two 25-kDa 40 S proteins, rpS5 and rpS9, clearly identified rpS5 as the protein bound to the IRES. Thus, our results support rpS5 as the critical element in positioning the HCV RNA on the 40 S ribosomal subunit during translation initiation.
Monocyte Chemoattractant Protein-1 Deficiency is Protective in a Murine Stroke Model (2002)

Inflammatory processes have been implicated in the pathogenesis of brain damage after stroke. In rodent stroke models, focal ischemia induces several proinflammatory chemokines, including monocyte chemoattractant protein-1 (MCP-1). The individual contribution to ischemic tissue damage, however, is largely unknown. To address this question, the authors subjected MCP-1-deficient mice (MCP-1-/-) to permanent middle cerebral artery occlusion (MCAO). Measurement of basal blood pressure, cerebral blood flow, and blood volume revealed no differences between wild-type (wt) and MCP-1-/- mice. MCAO led to similar cerebral perfusion deficits in wt and MCP-1-/- mice, excluding differences in the MCA supply territory and collaterals. However, compared with wt mice, the mean infarct volume was 29% smaller in MCP-1-/- mice 24 hours after MCAO (P = 0.022). Immunostaining showed a reduction of phagocytic macrophage accumulation within infarcts and the infarct border in MCP-1-/- mice 2 weeks after MCAO. At the same time point, the authors found an attenuation of astrocytic hypertrophy in the infarct border and thalamus in MCP-1-/- mice. However, these effects on macrophages and astrocytes in MCP-1-/- mice occurred too late to suggest a protective role in acute infarct growth. Of note: at 6 hours after MCAO, MCP-1-/- mice produced significantly less interleukin-1beta in ischemic tissue; this might be related to tissue protection. The results of this study indicate that inhibition of MCP-1 signaling could be a new acute treatment approach to limit infarct size after stroke.
Induction of mutant dynamin specifically blocks endocytic coated vesicle formation. (1994)

Dynamin is the mammalian homologue to the Drosophila shibire gene product. Mutations in this 100-kD GTPase cause a pleiotropic defect in endocytosis. To further investigate its role, we generated stable HeLa cell lines expressing either wild-type dynamin or a mutant defective in GTP binding and hydrolysis driven by a tightly controlled, tetracycline-inducible promoter. Overexpression of wild-type dynamin had no effect. In contrast, coated pits failed to become constricted and coated vesicles failed to bud in cells overexpressing mutant dynamin so that endocytosis via both transferrin (Tfn) and EGF receptors was potently inhibited. Coated pit assembly, invagination, and the recruitment of receptors into coated pits were unaffected. Other vesicular transport pathways, including Tfn receptor recycling, Tfn receptor biosynthesis, and cathepsin D transport to lysosomes via Golgi-derived coated vesicles, were unaffected. Bulk fluid-phase uptake also continued at the same initial rates as wild type. EM immunolocalization showed that membrane-bound dynamin was specifically associated with clathrin-coated pits on the plasma membrane. Dynamin was also associated with isolated coated vesicles, suggesting that it plays a role in vesicle budding. Like the Drosophila shibire mutant, HeLa cells overexpressing mutant dynamin accumulated long tubules, many of which remained connected to the plasma membrane. We conclude that dynamin is specifically required for endocytic coated vesicle formation, and that its GTP binding and hydrolysis activities are required to form constricted coated pits and, subsequently, for coated vesicle budding.
Log-Domain Speech Feature Enhancement Using Sequential MAP Noise Estimation and a Phase-sensitive Model of the Acoustic Environment (2002)

In this paper we present an MMSE (minimum mean square error) speech feature enhancement algorithm, capitalizing on a new probabilistic, nonlinear environment model that effectively incorporates the phase relationship between the clean speech and the corrupting noise in acoustic distortion. The MMSE estimator based on this phase-sensitive model is derived and it achieves high efficiency by exploiting single-point Taylor series expansion to approximate the joint probability of clean and noisy speech as a multivariate Gaussian. As an integral component of the enhancement algorithm, we also present a new sequential MAP-based nonstationary noise estimator. Experimental results on the Aurora2 task demonstrate the importance of exploiting the phase relationship in the speech corruption process captured by the MMSE estimator. The phasesensitive MMSE estimator reported in this paper performs significantly better than phase-insensitive spectral subtraction (54 % error rate reduction), and also noticeably better than a phase-insensitive MMSE estimator as our previous state-of-the-art technique reported in [2] (7 % error rate reduction), under otherwise identical experimental conditions of speech recognition. 1.
Alopecia areata: an autoimmune disease? (1999)

Abstract: A wide range of hypotheses such as focal infection, trophoneur‐ oses, and endocrine dysfunction, have been previously proposed to explain the pathogenesis of alopecia areata (AA). Currently, the most widely held belief is that AA is an autoimmune disease with cellular and/or humoral immunity directed against anagen hair follicle antigen(s). However, until recently evidence in support of an autoimmune mechanism of AA has been largely circumstantial. More fundamental evidence has recently been amassed in support of AA as an autoimmune disease by using animal models. These data include: 1) identification of cross‐species hair follicle specific IgG autoantibodies, 2) The ability to induce AA in an animal model with transfer of skin from affected to naive individuals, and 3) the induction of disease by transfer of lymphocytes to human skin grafted to severe combined immunodeficiency mutant mice. A review of the pre‐ vious and current data related to the autoimmune basis of AA is provided to put into perspective the future studies needed to definitively determine whether AA is an autoimmune disease.
Periaxin mutations cause a broad spectrum of demyelinating neuropathies (2002)

Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal recessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a homozygous C715X mutation had much worse sensory impairment than motor impairment. Despite early disease onset, these siblings with the C715X mutation had relatively slow disease progression and adult motor impairment typical of classic demyelinating Charcot-Marie-Tooth neuropathy. In contrast, a patient with the homozygous R82fsX96 mutation had a disease course consistent with Dejerine-Sottas neuropathy. The neuropathology of patients in both families was remarkable for demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal loops and axon. Our study indicates a prominent sensory neuropathy resulting from periaxin gene mutations and suggests a role for the carboxyl terminal domain of the periaxin protein.
Discovery of Pyrrolopyridine−Pyridone Based Inhibitors of Met Kinase: Synthesis, X-ray Crystallographic Analysis, and Biological Activities (2008)

Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC50 value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-pyridone and pyridine N-oxide inhibitors such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent antiproliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC50 values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model.
York University Enterprise (1989)

In the academic year 1988–9, York University's silver jubilee year, the university decided to improve its links with industry. Concentrating on local business, the university promoted the idea of the university as a regional resource. This report details the success of their enterprise.
ANTIOXIDANT AND ANTIHEPATOMA ACTIVITIES OF PALM OIL EXTRACT (2007)

ABSTRACT Palm oil extract (POE) at different concentrations (0.1–500 µg/mL) was evaluated for antioxidant and antihepatoma activities. Results showed that POE exhibited a greater antioxidant activity than α‐tocopherol in all model systems tested. At concentrations of 0.1–100 µg/mL, POE showed a superoxide radical scavenging activity ranging from 50.6 to 100%, with an IC 50 value (0.09 µg/mL) lower than α‐tocopherol (0.51 µg/mL). In the xanthine oxidase inhibition test, POE (IC 50 = 0.67 µg/mL) also exhibited a stronger inhibitory effect on xanthine oxidase activity than α‐tocopherol (IC 50 = 0.83 µg/mL). At concentrations of 0.1 µg/mL and above, POE showed significant ability in inhibiting the oxidative damage to lipids induced by ascorbate‐Fe 2+ than α‐tocopherol in rat liver (IC 50 = 0.53 µg/mL versus 0.94 µg/mL), brain (IC 50 = 0.10 µg/mL versus 52.52 µg/mL) and plasma (IC 50 = 77.17 µg/mL versus 190.81 µg/mL). In the antihepatoma studies, POE showed a greater potency than α‐tocopherol in inhibiting Hep G2, Hep 3B and PLC/PRF/5 cells. The antiproliferative effect of POE against these human hepatoma cells was dose‐dependent, with IC 50 values varying from 4.86 to 68.44 µg/mL. The present results demonstrate that POE is an effective natural antioxidant supplement for protecting cellular membranes against oxidative damage and inhibiting hepatoma cell proliferation.
The PTEN/PI3K/AKT Signalling Pathway in Cancer, Therapeutic Implications (2008)

PTEN/PI3K/AKT constitutes an important pathway regulating the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation and cell growth. PTEN is a dual protein/lipid phosphatase which main substrate is the phosphatidyl-inositol,3,4,5 triphosphate (PIP3), the product of PI3K. Increase in PIP3 recruits AKT to the membrane where it is activated by other kinases also dependent on PIP3. Many components of this pathway have been described as causal forces in cancer. PTEN activity is lost by mutations, deletions or promoter methylation silencing at high frequency in many primary and metastatic human cancers. Germ line mutations of PTEN are found in several familial cancer predisposition syndromes. Activating mutations which have been reported for PI3K and AKT, in tumours are able to confer tumourigenic properties in several cellular systems. Additionally, the binding of PI3K to oncogenic ras is essential for the transforming properties of ras. In summary, the data strongly support the view of the PTEN/PI3K/AKT pathway as an important target for drug discovery.
CD4(+) cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner. (1998)

Although it is well known that CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the suppression of cancer cell growth, the significance of CD4(+) CTLs in resistance to cancer is obscure. In an attempt to elucidate the role of CD4(+) CTLs in immunosurveillance of chronic myelogenous leukemia (CML), we examined the immunologic functions of bcr-abl b3a2 fusion peptide-specific CD4(+) CTL clones. Seven CD4(+) T-cell clones that responded to stimulation with b3a2 peptide, but not with b2a2 peptide or physiological counterparts bcr b3b4 and abl 1A-a2 peptides, were established from two healthy individuals. Restriction elements of these clones were HLA-DRB1*0901. These CD4(+) T-cell clones exhibited b3a2 peptide-specific and HLA-DRB1*0901-restricted cytotoxicity and produced interleukin-3 (IL-3), IL-4, IL-10, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in response to bcr-abl peptide stimulation, indicating they were Th0 clones. The numbers of HLA-DRB1*0901-positive b3a2, but not those of b2a2-positive or HLA-DRB1*0901-negative CML cell colonies increased when CML cells were cultured with b3a2-specific CD4(+) CTL clones. These data suggest that bcr-abl-specific CD4(+) CTLs recognize CML cells in an antigen-specific and HLA-DR-restricted manner, and that they do not inhibit, but in fact augment, CML cell growth.
Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology (2009)

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations. Converging concepts were identified: enhanced knowledge of interferon-related pathways was found to be central to the understanding of immune-mediated tissue-specific destruction (TSD) of which tumor rejection is a representative facet. Although the expression of interferon-stimulated genes (ISGs) likely mediates the inflammatory process leading to tumor rejection, it is insufficient by itself and the associated mechanisms need to be identified. It is likely that adaptive immune responses play a broader role in tumor rejection than those strictly related to their antigen-specificity; likely, their primary role is to trigger an acute and tissue-specific inflammatory response at the tumor site that leads to rejection upon recruitment of additional innate and adaptive immune mechanisms. Other candidate systemic and/or tissue-specific biomarkers were recognized that might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions.
MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) Software Version 4.0 (2007)

We announce the release of the fourth version of MEGA software, which expands on the existing facilities for editing DNA sequence data from autosequencers, mining Web-databases, performing automatic and manual sequence alignment, analyzing sequence alignments to estimate evolutionary distances, inferring phylogenetic trees, and testing evolutionary hypotheses. Version 4 includes a unique facility to generate captions, written in figure legend format, in order to provide natural language descriptions of the models and methods used in the analyses. This facility aims to promote a better understanding of the underlying assumptions used in analyses, and of the results generated. Another new feature is the Maximum Composite Likelihood (MCL) method for estimating evolutionary distances between all pairs of sequences simultaneously, with and without incorporating rate variation among sites and substitution pattern heterogeneities among lineages. This MCL method also can be used to estimate transition/transversion bias and nucleotide substitution pattern without knowledge of the phylogenetic tree. This new version is a native 32-bit Windows application with multi-threading and multi-user supports, and it is also available to run in a Linux desktop environment (via the Wine compatibility layer) and on Intel-based Macintosh computers under the Parallels program. The current version of MEGA is available free of charge at (http://www.megasoftware.net).
A Robotic System to Scan and Reproduce Object (2011)

An application of a robotic system integrated with a vision system is presented. The robot is a 3-axis revolute prototype, while the vision system essentially consists in a laser scanner made up of a camera and a linear laser projector. Both the robotic and the video system were designed and built at DIME (Department of Mechanical Engineering for Energetics), University of Naples Federico II. The presented application essentially consists of a laser scanner that is installed on the robot arm; the scanner scans a 3D surface, and the data are converted in a cloud of points in the robot’s workspace. Then, starting from those points, the end-effector trajectories adopted to replicate the scanned surface are calculated; so, the same robot, by using a tool, can reproduce the scanned object. The software was developed also at the DIME. The adopted tool was a high-speed drill, installed on the last link of the robot arm, with a spherical milling cutter in order to obtain enough accurate surfaces by the data represented by the cloud of points. An algorithm to interpolate the paths and to plan the trajectories was also developed and successfully tested.