gebhart/patrepeval huggingface dataset:
The c-Jun N-Terminal Protein Kinase Signaling Pathway Mediates Bax Activation and Subsequent Neuronal Apoptosis through Interaction with Bim after Transient Focal Cerebral Ischemia (2004)

The c-Jun N-terminal protein kinase (JNK) signaling pathway is implicated in neuronal apoptosis. The mechanism by which activated JNK induces neuronal apoptosis is strongly linked to mitochondrial apoptogenic proteins, although the molecular machinery downstream of JNK has not been precisely elucidated. Our study examined the relevance of proapoptotic Bcl-2 family members in JNK-mediated apoptosis after transient focal cerebral ischemia (tFCI), which, when induced by 60 min of middle cerebral artery (MCA) occlusion, elevated levels of JNK activity and phospho-JNK in the MCA territory. Phospho-JNK was primarily expressed in neurons and colocalized with terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-positive cells. Inhibition of JNK activity by anthra[1,9-cd]pyrazol-6(2H)-one (SP600125), a selective JNK inhibitor, protected neurons from ischemia-induced apoptosis detected by TUNEL staining and an apoptotic-related DNA fragmentation assay. SP600125 blocked translocation of the cell death effector Bax from the cytosol to the mitochondria after tFCI. BimL (Bim long) was induced and phosphorylated parallel to JNK activity. Coimmunoprecipitation studies consistently revealed increased interaction of JNK with BimL, as well as BimL with Bax, after tFCI. SP600125 blocked these interactions at a dose that significantly inhibited JNK-induced neuronal apoptosis. These results suggest that the JNK signaling pathway is involved in ischemia-induced neuronal apoptosis by stimulation, at least in part, of Bax translocation to the mitochondria, in which BimL is likely regulated by JNK as a downstream substrate for transmission of apoptotic signals to Bax.
Pharmacokinetic, pharmacodynamic and clinical effects of a humanized IgG1 anti‐CD4 monoclonal antibody in the peripheral blood and synovial fluid of rheumatoid arthritis patients (2000)

Background. CD4(+) T cells are important mediators in the pathogenesis of rheumatoid arthritis (RA). Tn this open-label, dose-escalating study, we examined the pharmacokinetic (PK), clinical, biological and immunological effects of a humanized IgG1 anti-CD4 monoclonal antibody (mAb), 4162W94, in the peripheral blood (PB) and synovial fluid (SF) of RA patients. Method. Twenty-four patients in four cohorts (six patients in each cohort) were allocated to be treated with five consecutive daily doses of 4162W94 (10, 30, 100 or 300 mg i.v.). Disease activity was measured by the American College of Rheumatology (ACR) criteria and disease activity score (DAS). We also measured 4162W94 concentration, the percentage of 4162W94-coated CD4(+) lymphocytes, percentage down-modulation of CD4, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha) levels in the PB and SF. Results. A direct relationship between 4162W94 dose, biological response and clinical outcome was seen. Treatment with 10 and 30 mg of 4162W94 for 5 consecutive days resulted in transient coating and down-modulation of CD4(+) lymphocytes, with little effect observed beyond the final dose. However, treatment with 100 and 300 mg resulted in sustained coating and/or down-modulation for 3 weeks and 4 weeks, respectively, in PB and &gt;4 weeks in SF in one patient from the 300 mg cohort. There was a dose-related moderate but transient depression in the CD4(+) lymphocyte count in most patients, with all but three returning to &gt;0.40 x 10(9)/1 or &gt; 75% baseline by the end of the study period. Significant clinical improvement (ACR 20%) was seen in only 1/6 patients in each of the 10- and 30-mg cohorts; however, 3/6 and 5/5 patients in the 100 and 300-mg cohorts, respectively, were ACR 20% responders. In addition, there were significant reductions in PB acute phase reactants as well as SF IL-6 and TNF alpha concentrations in parallel to clinical improvement. Conclusion. Data from this pilot study suggest that 4162W94 is a clinically active novel immunotherapeutic agent that may suppress inflammation in RA.
PHASE-I STUDY OF SYNTHETIC MUC1 PEPTIDES IN BREAST-CANCER (1995)

Exposed peptides in the repeat (VNTR) protein core of human mucin 1 (MUC1) could be a target for immunotherapy, as it is highly immunogenic in mice and a human cytotoxic T lymphocytes to MUC1 recognise the peptide. On this basis 13 patients were immunised with a MUC1 peptide - a 20 amino acids dimer conjugated with diphtheria toroid as carrier. In patients with established breast cancer increasing doses (0.15 mg, 0.25 mg, 0.5 mg, 1.0 mg) were used at 2 week intervals (3 injections). No toxicity was found, other than for DTH reaction to the diphtheria carrier; weak antibody and T cell proliferative responses were seen and weak DTH reaction in proportion of patients. The MUC1 peptide appears to be safe but in the form used was not highly immunogenic.
Novel Helicobacter pylori α1,2-fucosyltransferase, a key enzyme in the synthesis of Lewis antigens (1999)

Helicobacter pylori lipopolysaccharides (LPS) contain complex carbohydrates known as Lewis antigens which may contribute to the pathogenesis and adaptation of the bacterium. Involved in the biosynthesis of Lewis antigens is an alpha1,2-fucosyltransferase (FucT) that adds fucose to the terminal betaGal unit of the O-chain of LPS. Recently, the H. pylori (Hp) alpha1,2-FucT-encoding gene (fucT2) was cloned and analysed in detail. However, due to the low level of expression and instability of the protein, its enzymic activity was not demonstrated. In this study, the Hp fucT2 gene was successfully overexpressed in Escherichia coli. Sufficient amounts of the protein were obtained which revealed alpha1,2-fucosyltransferase activity to be associated with the protein. A series of substrates were chosen to examine the acceptor specificity of Hp alpha1,2-FucT, and the enzyme reaction products were identified by capillary electrophoresis. In contrast to the normal mammalian alpha,2-FucT (H or Se enzyme), Hp alpha1,2-FucT prefers to use Lewis X [betaGal1-4(alphaFuc1-3)betaGlcNAc] rather than LacNAc [betaGal1-4betaGIcNAc] as a substrate, suggesting that H. pylori uses a novel pathway (via Lewis X) to synthesize Lewis Y. Hp alpha1,2-FucT also acts on type 1 acceptor [betaGal1-3betaGlcNAc] and Lewis a [betaGal1-3(alphaFuc1-4)betaGIcNAc], which provides H. pylori with the potential to synthesize H type 1 and Lewis b epitopes. The ability to transfer fucose to a monofucosylated substrate (Lewis X or Lewis a) makes Hp alpha1,2-FucT distinct from normal mammalian alpha1,2-FucT.
Measurement of the Relative Motion Between an Implant and Bone under Cyclic Loading (2004)

Abstract: The measurement of the relative motion between a prosthesis and the surrounding bone is important for the pre‐clinical testing of prostheses and implants. A technique that allows measurements to be made over several million loading cycles was developed by Maher et al. ( Clin. Biomech. 2001; 16: 307–314). However, the measurement of implant/bone motion is fraught with difficulties because: (i) testing over millions of cycles can take several days and errors because of diurnal temperature variations can occur, (ii) elastic deformations of the stem could have a dominant effect on ‘inducible displacements’, the rate of change of which is hypothesised to be a measure of loosening, and (iii) the use of this method for the analysis of cementless prostheses has yet to be demonstrated. This paper addresses these methodological issues with respect to testing hip prostheses, and concludes with a comparative evaluation of pre‐clinical testing methods.
Molecular Topology Fractionation of Polystyrene Stars and Long Chain Branched Polyethylene Fractions (2007)

This chapter contains sections titled: Control of long chain branching (LCB) architecture is an area of considerable interest in materials science because LCB can have a dominating effect on polymer rheology and properties. Currently no analytical technique provides a quantitative description of the LCB topologies in these materials beyond a basic estimation of the average number of branch points per molecule. Neither the molecular weight of the branch, nor the shape of the branched molecule (e. g. star, comb, “H” or other) can be determined using current state of the art methodology such as size exclusion chromatography (SEC) with molecular weight sensitive detectors or nuclear magnetic resonance spectroscopy. In our laboratory, we have developed a fractionation method that sorts polymer solutes based on LCB topology. The approach, which we term molecular topology fractionation (MTF), utilizes a separating medium comprising channels having dimensions similar in size to the dimensions of the macromolecules being analyzed. An applied flow field provides the driving force for the separation. Although the details of the separation mechanism are not well understood at this time, two possible mechanisms are being considered. In one, dissolved solute molecules are restricted by the channels such that the relaxation modes for reorientation determine the rate of transport. In the second, pinning (or entanglement) of molecules on the stationary phase determines the rate of transport. Both mechanisms result in the largest molecules eluting latest (opposite to the sequencing in SEC), and produce significant additional retardation for LCB chains above that of linear chains. This additional retardation leads to fractionation of an LCB distribution even if the hydrodynamic radii of the components are the same. In this paper, an overview of the MTF experiment will be provided. MTF fractionation of PS stars is presented to demonstrate the separation of LCB chains from linear chains and LCB chains based on topology. The application of MTF for characterizing LCB polyolefin fractions will be shown. The paper will also include a brief discussion of the coupling of MTF and SEC in an on line two dimensional approach for determination of LCB distributions.
Prenatal Tobacco Smoke Exposure Affects Global and Gene-specific DNA Methylation (2009)

Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.
A capacitor cross-coupled common-gate low-noise amplifier (2005)

The conventional common-gate low-noise amplifier (CGLNA) exhibits a relatively high noise figure (NF) at low operating frequencies relative to the MOSFET f/sub T/, which has limited its adoption notwithstanding its superior linearity, input matching, and stability compared to the inductively degenerated common-source LNA (CSLNA). A capacitor cross-coupled g/sub m/-boosting scheme is described that improves the NF and retains the advantages of the CGLNA topology. The technique also enables a significant reduction in current consumption. A fully integrated capacitor cross-coupled CGLNA implemented in 180-nm CMOS validates the g/sub m/-boosting technique. It achieves a measured NF of 3.0 dB at 6.0 GHz and consumes only 3.6 mA from 1.8 V; the measured input-referred third-order intercept ( IIP3) value is 11.4 dBm. The capacitor cross-coupled g/sub m/-boosted CGLNA is attractive for low-power fully integrated applications in fine-line CMOS technologies.
NSAIDs induce both necrosis and apoptosis in guinea pig gastric mucosal cells in primary culture (2001)

A major clinical problem encountered with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin is gastropathy. In this study, we examined, using guinea pig gastric mucosal cells in primary culture, how NSAIDs damage gastric mucosal cells. The short-term treatment of cells with high concentrations of indomethacin decreased cell viability in the absence of apoptotic DNA fragmentation, chromatin condensation, or caspase activation. Cells lost membrane integrity with this short-term indomethacin treatment, suggesting that indomethacin induced necrosis under these conditions. In contrast, the long-term treatment of cells with low concentrations of indomethacin decreased cell viability and was accompanied by apoptotic DNA fragmentation, chromatin condensation, and caspase activation. Pretreatment of cells with inhibitors of caspases or protein synthesis suppressed cell death caused by long-term indomethacin treatment, suggesting that apoptosis was induced when the inhibitors were not present. These results imply that NSAIDs cause gastric mucosal damage through both necrosis and apoptosis of gastric mucosal cells.
Polymer Photovoltaic Cells: Enhanced Efficiencies via a Network of Internal Donor-Acceptor Heterojunctions (1995)

The carrier collection efficiency (η c ) and energy conversion efficiency (η e ) of polymer photovoltaic cells were improved by blending of the semiconducting polymer with C 60 or its functionalized derivatives. Composite films of poly(2-methoxy-5-(2′-ethyl-hexyloxy)-1,4-phenylene vinylene) (MEH-PPV) and fullerenes exhibit η c of about 29 percent of electrons per photon and η e of about 2.9 percent, efficiencies that are better by more than two orders of magnitude than those that have been achieved with devices made with pure MEH-PPV. The efficient charge separation results from photoinduced electron transfer from the MEH-PPV (as donor) to C 60 (as acceptor); the high collection efficiency results from a bicontinuous network of internal donor-acceptor heterojunctions.
c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release (1999)

Expression of c-Myc sensitizes cells to a wide range of pro-apoptotic stimuli. We here show that this pro-apoptotic effect is mediated through release of mitochondrial holocytochrome c into the cytosol. First, activation of c-Myc triggers release of cytochrome c from mitochondria. This release is caspase-independent and blocked by the survival factor IGF-1. Second, c-Myc-induced apoptosis is blocked by microinjection of anticytochrome c antibody. In addition, we show that microinjection of holocytochrome c mimics the effect of c-Myc activation, sensitizing cells to DNA damage and to the CD95 pathway. Both p53 and CD95/Fas signaling have been implicated in c-Myc-induced apoptosis but neither was required for c-Myc-induced cytochrome c release. Nonetheless, inhibition of CD95 signaling in fibroblasts did prevent c-Myc-induced apoptosis, apparently by obstructing the ability of cytosolic cytochrome c to activate caspases. We conclude that c-Myc promotes apoptosis by causing the release of cytochrome c, but the ability of cytochrome c to activate apoptosis is critically dependent upon other signals.
From Pixels to Torques: Policy Learning with Deep Dynamical Models (2015)

Data-efficient learning in continuous state-action spaces using very high-dimensional observations remains a key challenge in developing fully autonomous systems. In this paper, we consider one instance of this challenge, the pixels to torques problem, where an agent must learn a closed-loop control policy from pixel information only. We introduce a data-efficient, model-based reinforcement learning algorithm that learns such a closed-loop policy directly from pixel information. The key ingredient is a deep dynamical model that uses deep auto-encoders to learn a low-dimensional embedding of images jointly with a predictive model in this low-dimensional feature space. Joint learning ensures that not only static but also dynamic properties of the data are accounted for. This is crucial for long-term predictions, which lie at the core of the adaptive model predictive control strategy that we use for closed-loop control. Compared to state-of-the-art reinforcement learning methods for continuous states and actions, our approach learns quickly, scales to high-dimensional state spaces and is an important step toward fully autonomous learning from pixels to torques.
Atopic Dermatitis: Skin-Directed Management (2014)

Atopic dermatitis is a common inflammatory skin condition characterized by relapsing eczematous lesions in a typical distribution. It can be frustrating for pediatric patients, parents, and health care providers alike. The pediatrician will treat the majority of children with atopic dermatitis as many patients will not have access to a pediatric medical subspecialist, such as a pediatric dermatologist or pediatric allergist. This report provides up-to-date information regarding the disease and its impact, pathogenesis, treatment options, and potential complications. The goal of this report is to assist pediatricians with accurate and useful information that will improve the care of patients with atopic dermatitis.
A Phase 1-2 Clinical Trial of Gene Therapy for Recurrent Glioblastoma Multiforme by Tumor Transduction with the Herpes Simplex Thymidine Kinase Gene Followed by Ganciclovir (1999)

This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies.
On A Version of The Banach's Fixed Point Theorem 1 (2008)

Banach in 1922 proved the celebrated result which is well-known in the literature as the Banach’s Fixed Point Theorem or the Con-traction Mapping Principle. This result of Banach also known as the Theorem of Picard-Banach-Cacciopoli is contained in several mono-graphs including Agarwal et al [1], Berinde [3, 4, 5] and Zeidler [17]. In this paper, we shall establish the error estimates as well as the rate of convergence for a version of the Banach’s Fixed Point The-orem by employing a certain form of ϕ−contraction different from that of Berinde [5]. Our results are generalizations of those of Banach [2] and Berinde
Gene Transfer by DNA/Glycosylated Polylysine Complexes into Human Blood Monocyte-Derived Macrophages (1996)

Macrophages are putative target cells for expressing an exogenous gene with therapeutical effects. Knowing that macrophages express membrane lectins mediating endocytosis of their ligands, DNA/glycosylated polylysine complexes were used to transfect human blood monocyte-derived macrophages. Monocytes from human peripheral blood were matured in culture for 7 days to differentiate into macrophage-like cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Adherent cells, which displayed characteristic macrophage markers, CD 14, CD 11b, HLA-DR, and HLA-ABC antigens and mannose receptor, were transfected by DNA/glycosylated polylysine complexes in the presence of chloroquine. The luciferase reporter gene expression was maximal 24 hr after transfection with a DNA/mannosylated polylysine complex and by using plasmids in which the promoters (either the long terminal repeat of the human immunodeficiency virus or the human cytomegalovirus) drove the luciferase gene expression. Luciferase gene expression was lower when the promoter was the early region of the large T antigen of SV40 virus. Transfection mediated by DNA/mannosylated polylysine complexes was much more efficient than with DEAE-dextran or lipofectin. The possibility of transferring and expressing an exogenous gene into macrophage-like cells by using a nonimmunogenic synthetic vector as a DNA carrier opens new ways to develop nonviral gene therapy strategies.
DNA barcoding the floras of biodiversity hotspots (2008)

DNA barcoding is a technique in which species identification is performed by using DNA sequences from a small fragment of the genome, with the aim of contributing to a wide range of ecological and conservation studies in which traditional taxonomic identification is not practical. DNA barcoding is well established in animals, but there is not yet any universally accepted barcode for plants. Here, we undertook intensive field collections in two biodiversity hotspots (Mesoamerica and southern Africa). Using >1,600 samples, we compared eight potential barcodes. Going beyond previous plant studies, we assessed to what extent a "DNA barcoding gap" is present between intra- and interspecific variations, using multiple accessions per species. Given its adequate rate of variation, easy amplification, and alignment, we identified a portion of the plastid matK gene as a universal DNA barcode for flowering plants. Critically, we further demonstrate the applicability of DNA barcoding for biodiversity inventories. In addition, analyzing >1,000 species of Mesoamerican orchids, DNA barcoding with matK alone reveals cryptic species and proves useful in identifying species listed in Convention on International Trade of Endangered Species (CITES) appendixes.
Waste Cooking OilAn Economical Source for Biodiesel:  A Review (2006)

Biodiesel (fatty acid methyl ester) is a nontoxic and biodegradable alternative fuel that is obtained from renewable sources. A major hurdle in the commercialization of biodiesel from virgin oil, in comparison to petroleum-based diesel fuel, is its cost of manufacturing, primarily the raw material cost. Used cooking oil is one of the economical sources for biodiesel production. However, the products formed during frying, such as free fatty acid and some polymerized triglycerides, can affect the transesterification reaction and the biodiesel properties. Apart from this phenomenon, the biodiesel obtained from waste cooking oil gives better engine performance and less emissions when tested on commercial diesel engines. The present paper attempts to review methods for the transesterification of waste cooking oil and the performance of biodiesel obtained from waste cooking oil in a commercial diesel engine. The paper also examines the basic chemistry involved during frying and the effects of the products formed in the frying process on biodiesel quality.