gebhart/patrepeval huggingface dataset:
Ultrastructural localization of beta-amyloid, tau, and ubiquitin epitopes in extracellular neurofibrillary tangles. (1991)

Neurofibrillary tangles (NFTs), a hallmark of Alzheimer disease, are commonly located in perikarya of neurons. In advanced cases of Alzheimer disease, however, NFTs are observed also in the extracellular space. As extracellular NFTs (E-NFTs), and occasionally intracellular NFTs (I-NFTs), are recognized by antibodies to beta-amyloid protein (beta AP), beta AP may be present not only in amyloid deposits but also in paired helical filaments (PHFs), the primary components of NFTs. We compared the antigenic characteristics of I-NFTs and E-NFTs with light- and electron-microscopic immunocytochemistry by using several antibodies to noncontiguous epitopes of the microtubule-associated protein tau and of ubiquitin (Ub) as well as an antiserum to beta AP. At variance with I-NFTs, E-NFTs were made predominantly of straight filaments (SFs), rather than PHFs, that were often separated by astroglial processes and in close association with small beta AP deposits. Occasionally, E-NFTs were made of bundles of amorphous material, which showed no resemblance to SFs, PHFs, or amyloid fibrils. The antigenic changes in E-NFTs suggest that when NFTs become extracellular they lose the N and, possibly, the C termini of tau while maintaining the intermediate region of the molecule; they also lose the N-terminal two-thirds of Ub while the C-terminal conjugation site of Ub is preserved. A small subset of E-NFTs reacted with antibodies to both beta AP and tau. Although in most E-NFTs, the epitopes recognized by tau and Ub antibodies were located in typical PHFs and SFs, the epitopes recognized in this subset of anti-beta AP and anti-tau-positive E-NFTs were located exclusively in the bundles of amorphous material. It is suggested that either beta AP epitopes are present but inaccessible in PHFs and SFs and become exposed after conformational changes occurring in the extracellular space or PHFs and SFs become closely associated with beta AP in the extracellular space.
Performance evaluation of a sequential minimal radial basis function (RBF) neural network learning algorithm (1998)

This paper presents a detailed performance analysis of the minimal resource allocation network (M-RAN) learning algorithm, M-RAN is a sequential learning radial basis function neural network which combines the growth criterion of the resource allocating network (RAN) of Platt (1991) with a pruning strategy based on the relative contribution of each hidden unit to the overall network output. The resulting network leads toward a minimal topology for the RAN. The performance of this algorithm is compared with the multilayer feedforward networks (MFNs) trained with 1) a variant of the standard backpropagation algorithm, known as RPROP and 2) the dependence identification (DI) algorithm of Moody and Antsaklis on several benchmark problems in the function approximation and pattern classification areas. For all these problems, the M-RAN algorithm is shown to realize networks with far fewer hidden neurons with better or same approximation/classification accuracy. Further, the time taken for learning (training) is also considerably shorter as M-RAN does not require repeated presentation of the training data.
Echoplanar chemical shift imaging (1999)

A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degree refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 microl and signal-to-noise ratio approximately 7:1 in less than 13 min.
p53 from basic research to clinical applications. (1992)

Mutations on the TP53 tumor suppressor gene and allele loss on chromosome 17p, where this gene has been located, are among the most frequent alterations yet identified in human malignancies. The p53 protein is highly conserved through evolution and expressed in most normal tissues. Wild-type p53 has been shown to control normal cell proliferation possibly through transcriptional regulation. The wild-type TP53 gene can suppress cell transformation and neoplastic cell growth. In contrast, mutant TP53 has lost the tumor suppressing ability and, in most cases, has gained a transformation promoting ability. Many different TP53 mutations have common conformational and functional consequences on the p53 protein. However, all the TP53 mutants are not necessarily equivalent in terms of biological activity: some mutations confer a strong transforming ability, while others lead to truncated products with probably no biological function. Some mutants may exhibit a dominant behavior over wild-type TP53, others may be recessive. Point mutations of TP53 tend to occur on evolutionary conserved positions. However, the TP53 mutational spectrum differs among cancer types, and this fact may reflect different exogenous mutagens and endogenous factors contributing to human carcinogenesis. In defined types of malignancies, the tumors with TP53 alteration or tumors with allele loss on 17p are associated with more aggressive phenotypes than those without these alterations. For these malignancies, the monitoring of TP53 alteration should now be included in therapeutic trials. Germ line mutations on TP53 may also occur. Individuals with constitutional TP53 mutation have a predisposition to a wide variety of neoplasms. Further characterization of this predisposition will enable the definition of the best follow-up for these at-risk patients.
CXCR4 Inhibitors Selectively Eliminate CXCR4 Expressing Human Acute Myeloid Leukemia Cells in NOG Mouse Model (2012)

Abstract Abstract 1881 The chemokine receptor CXCR4 favors the interaction of acute myeloid leukemia (AML) cells with their niche but the extent to which it participates to pathogenesis is unclear. Here we show that CXCR4 expression at the surface of leukemic cells allowed distinguishing CXCR4high (25/47; 53%) from CXCR4neg/low (22/47, 47%) AML patients. Leukemic engraftment in NOD/Shi-scid/IL-2Rnull (NOG) mice was observed for both the CXCR4high and CXCR4neg/low groups. When high levels of CXCR4 are expressed at the surface of AML cells, blocking the receptor function with small molecule inhibitors could promote leukemic cell death and reduce NOG leukemia-initiating cells (LICs). Conversely, these drugs had no efficacy when AML cells do not express CXCR4 or when they do not respond to CXCL12. Mechanisms of this anti-leukemic effect included interference with the retention of LICs with their supportive bone marrow microenvironment niches, as indicated by a mobilization of LICs in response to drugs, and increased apoptosis of leukemic cells in vitro and in vivo. CXCR4 expression level on AML blast cells and their migratory response to CXCL12 are therefore predictive of the response to the inhibitors and could be used as biomarkers to select patients that could potentially benefit from the drugs. Disclosures: No relevant conflicts of interest to declare.
CONTINUOUS FLOW BIODIESEL PRODUCTION (2002)

Biodiesel, which consists of the fatty acid esters of simple alcohols, is a potential replacement for a portion of thediesel fuel used in transportation. It is produced from both used (oil that has been utilized for frying and discarded) and newvegetable and animal fats and oils. It has several advantages. Among these advantages are its classification as a renewableresource, its ability to reduce HC, CO, and CO2 exhaust emissions, its nontoxic character, and its biodegradability. One ofthe keys to making biodiesel a viable and profitable energy source is the use of a continuous flow transesterification processto reduce time and cost, thereby increasing production and profit.<br><br>A continuous flow esterification process for producing biodiesel from rapeseed oil and ethanol was investigated. Theequipment consisted of an oil metering pump, centrifugal mixing pump, ethanol and catalyst metering pump, static mixers,laddertype retention reactor, water injection system, and continuous flow centrifugal separating system. The oil feed ratewas 0.38 L/min that yields about three times the weekly production of the existing batch type transesterification system thatproduces 945 L (250 gal) per batch. It was anticipated that if methanol were used instead of ethanol that the flow rate couldbe considerably increased.<br><br>The system in its present configuration has met ASTM PS12199 standard for free and total glycerol. The centrifugalseparation resulted in release of excessive alcohol vapors. A vapor recovery and condensing system should be installed. Thislatter system could help further reduce costs of the biodiesel produced by recycling some of the alcohol used.
BioConductor: Microarray versus Next-Generation Sequencing toolsets (2014)

B oth microarray and next generation sequencing platforms generate copious amounts of data for each experiment. Thus, computational tools are required to handle and process such experiments. For microarray analysis, many open-source R packages have been developed, most of which are available through the BioConductor project. With certain microarray platforms, it is now possible to perform the entire analysis chain using only BioConductor tools. A comprehensive next-generation sequencing toolchain in pure R/BioConductor has until so far not been possible. Next-generation sequencing analysis still requires the use of disparate tools on disparate platforms: only some of them in R. This literature review reviewed the existing BioConductor toolsets for both approaches, and highlights key differences and similarities.
Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities (1989)

In view of the possible effects of the sphingoid base on protein kinases, and the fact that the sphingoid bases used in previous studies were not chemically well-defined, we have studied the effects of chemically well-defined sphingosines and their derivatives on kinase activity. Both (4E)-D- and (4E)-L-erythro-sphingenine showed a weak inhibitory effect, and (4E)-L-threo-sphingenine had a moderate inhibitory effect. In contrast, (4E)-N,N-dimethyl-D-erythro-sphingenine and the sphingosine preparation from a commercial source showed a strong inhibitory effect on PK-C in A431 cells as well as on purified PK-C. Synthetic (4E)-D-erythro-sphingenine and several samples of natural sphingosine inhibited v-src or c-src tyrosine kinase activity measured with polyglutamate-tyrosine (4:1) as substrate. N-Acetylated or N-methylated sphingosines did not inhibit src kinase activity, but rather produced a consistent 1.5-2-fold stimulation of such activity.
Human physiological responses to cold exposure. (2004)

Thermal energy is transferred within and between bodies via several avenues, but for most unprotected human cold exposures, particularly during immersion, convective heat loss dominates. Lower tissue temperatures stimulate thermoreceptors, and the resultant afferent flow elicits autonomic homoeostatic responses (thermogenesis and vasoconstriction) that regulate body temperature within a narrow range. The most powerful effector responses occur when both superficial and deep thermoreceptors are cooled simultaneously, but thermoeffector activation can also occur as a result of peripheral cooling alone. The responses to cold, and the hazards associated with cold exposure, are moderated by factors which influence heat production and heat loss, including the severity and duration of cold stimuli, accompanying exercise, the magnitude of the metabolic response, and individual characteristics such as body composition, age, and gender. Cold stress can quickly overwhelm human thermoregulation with consequences ranging from impaired performance to death. This review provides a comprehensive overview of the human physiological responses to acute cold exposure.
Free Radicals and Hearing: Cause, Consequence, and Criteria (1999)

Reactive oxygen and nitrogen species, including free radicals, are produced in the human body in both health and disease. In health, they may arise as regulatory mechanisms, intercellular signaling species, or as bacteriocidal agents. Their production is normally controlled by the antioxidant defense mechanisms that include intracellular enzymes--for example, glutathione peroxidase and superoxide dismutase--and low molecular-mass compounds such as vitamin E or ascorbic acid. Although repair mechanisms exist, some steady-state basal oxidative damage occurs in all individuals. Oxidative stress arises when there is a marked imbalance between the production and removal of reactive oxygen and nitrogen species. This may originate from an overproduction of these substances or from a depletion in the antioxidant defenses. Certain drugs may induce oxidative stress by forming drug-derived radicals that can not only deplete the antioxidant defenses but can also react directly with biomolecules. To be able to assess whether oxidative stress is occurring in a particular tissue, reliable biomarkers of oxidative damage are required. Since oxidative stress can damage all major biomolecules in vitro and probably in vivo, biomarkers for DNA, protein, and lipid damage are being developed which, when taken with an assessment of the antioxidant status of the individual, will allow evaluation of the involvement of oxidative stress in the etiology of disease and in the side effects of drugs. There is some evidence to suggest that free radical-mediated damage may be involved in the ototoxicity of aminoglycosides and cisplatin derivatives. Whether this is a cause or consequence of the toxic insult to the sensory hair cells of the inner ear remains to be determined.
Mitochondria are a direct site of Aβ accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression (2006)

Alzheimer's disease (AD) is a complex, neurodegenerative disease characterized by the impairment of cognitive function in elderly individuals. In a recent global gene expression study of APP transgenic mice, we found elevated expression of mitochondrial genes, which we hypothesize represents a compensatory response because of mitochondrial oxidative damage caused by the over-expression of mutant APP and/or amyloid beta (Abeta). We investigated this hypothesis in a series of experiments examining what forms of APP and Abeta localize to the mitochondria, and whether the presence of these species is associated with mitochondrial dysfunction and oxidative damage. Using immunoblotting, digitonin fractionation, immunofluorescence, and electron microscopy techniques, we found a relationship between mutant APP derivatives and mitochondria in brain slices from Tg2576 mice and in mouse neuroblastoma cells expressing mutant human APP. Further, to determine the functional relationship between mutant APP/Abeta and oxidative damage, we quantified Abeta levels, hydrogen peroxide production, cytochrome oxidase activity and carbonyl proteins in Tg2576 mice and age-matched wild-type (WT) littermates. Hydrogen peroxide levels were found to be significantly increased in Tg2576 mice when compared with age-matched WT littermates and directly correlated with levels of soluble Abeta in Tg2576 mice, suggesting that soluble Abeta may be responsible for the production of hydrogen peroxide in AD progression in Tg2576 mice. Cytochrome c oxidase activity was found to be decreased in Tg2576 mice when compared with age-matched WT littermates, suggesting that mutant APP and soluble Abeta impair mitochondrial metabolism in AD development and progression. An increase in hydrogen peroxide and a decrease in cytochrome oxidase activity were found in young Tg2576 mice, prior to the appearance of Abeta plaques. These findings suggest that early mitochondrially targeted therapeutic interventions may be effective in delaying AD progression in elderly individuals and in treating AD patients.
Coprinus comatus: A basidiomycete fungus forms novel spiny structures and infects nematode (2004)

Nematophagous basidiomycete fungi kill nematodes by trapping, endoparasitizing and producing toxin. In our studies Coprinus comatus (O.F.Müll. : Fr.) Pers. is found to be a nematode-destroying fungus; this fungus immobilizes, kills and uses free-living nematode Panagrellus redivivus Goodey and root-knot nematode Meloidogyne arenaria Neal. C. comatus produces an unusual structure designated spiny ball. Set on a sporophore-like branch, the spiny ball is a burr-like structure assembled with a large number of tiny tubes. Purified spiny balls exhibit moderate nematicidal activity. Experiments show that spiny balls are not chlamydospores because of the absence of nuclei in the structures and quick formation within 3 d in a young colony. Nematodes added to C. comatus cultures on potato-dextrose agar (PDA) and cornmeal agar (CMA) become inactive in hours. Infection of nematodes by the fungus occurs only after the nematodes are immobilized (feeble or dead), probably by a toxin. Electron micrographs illustrate that C. comatus infect P. redivivus by producing penetration pegs with which hyphae colonize nematode bodies. An infected nematode is digested and consumed within days and hyphae grow out of the nematode.
Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis. (1990)

Eicosanoids are modulators of defensive and inflammatory processes in the gut mucosa, and may be involved in the pathogenesis of chronic inflammatory lesions of the bowel. As omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower (source of omega-6) or cod liver (source of omega-3) oil on the development of chronic granulomatous lesions in the rat colon. After four weeks on the supplemented diets, plasma omega-6 fatty acid content was significantly higher in the sunflower group, while omega-3 fatty acids predominated in the cod liver group. Inflammatory colitis was then induced by intracolonic administration of trinitrobenzene sulphonic acid. Luminal eicosanoid release, as measured by radioimmunoassay of intracolonic dialysis fluid, increased significantly after the challenge in both groups. Generation of prostaglandin E2 (PGE2) and leucotriene B4 (LTB4) peaked by day 3 and thereafter declined; thromboxane B2 (TXB2), instead, continued to increase from day 3 to 20 in sunflower fed rats, whereas this change was blunted in cod liver animals. The rats were killed 20, 30, or 50 days after the induction of colitis, and the colonic lesions were scored macroscopically (adhesions to surrounding tissues, strictures, ulcerations, and wall thickness) and histologically (ulceration, inflammation, depth of the lesions, and fibrosis). In cod liver animals, the damage score was markedly reduced by day 30, and inflammation and ulceration were almost absent by day 50. In conclusion, a fish oil diet prevents the increase in thromboxane in the chronic state of inflammation and shortens the course of the colonic disease by diminishing both the severity of the lesions and their progression to chronicity.
Establishment and Characterization of Japanese Encephalitis Virus-Specific, Human CD4 + T-Cell Clones: Flavivirus Cross-Reactivity, Protein Recognition, and Cytotoxic Activity (1998)

We analyzed the CD4(+) T-lymphocyte responses of two donors who had received Japanese encephalitis virus (JEV) vaccine 6 or 12 months earlier. Bulk culture proliferation assays showed that peripheral blood mononuclear cells (PBMC) responded to JEV antigens (Ag) but also responded at lower levels to West Nile virus (WNV) and dengue virus type 1, 2, and 4 (D1V, D2V, and D4V, respectively) Ag. Five JEV-specific CD4(+) human T-cell clones and one subclone were established from PBMC of these two donors. Two clones responded to WNV Ag as well as to JEV Ag, whereas the others responded only to JEV Ag. Three of five CD4(+) T-cell clones had JEV-specific cytotoxic activity and recognized E protein. The HLA restriction of the JEV-specific T-cell clones was examined. Three clones were HLA-DR4 restricted, one was HLA-DQ3 restricted, and the HLA restriction of one clone was not determined. T-cell receptor analysis showed that these clones expressed different T-cell receptors, suggesting that they originated from different T lymphocytes. These results indicate that JEV vaccine induces JEV-specific and flavivirus-cross-reactive CD4(+) T lymphocytes and that these T lymphocytes recognize E protein. The functions and HLA restriction patterns of these T lymphocytes are, however, heterogeneous.
Altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non‐lymphoid human tissues (2008)

The endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 contribute to generate HLA class I binding peptides. Recently, we have shown that the expression of these enzymes is high and coordinated (with each other and with HLA class I molecules) in immortalized B cells, but variable and imbalanced in human tumour cell lines of various non-lymphoid lineages. Herein, this issue was investigated in vivo by testing ERAP1 and ERAP2 expression in normal non-lymphoid tissues and their malignant counterparts. ERAP1 and ERAP2 were detected exclusively in the epithelial cells of over half of the tested normal tissues. Four ERAP1/ERAP2 phenotypes (+/+, -/-, +/- and -/+) were detected, and the presence of either or both enzymes was not necessarily associated with HLA class I expression. In more than 160 neoplastic lesions, the expression of either or both aminopeptidases was retained, lost (most frequently, particularly ERAP1) or acquired as compared to the normal counterparts, depending on the tumour histotype. The double-negative (-/-) phenotype was the most frequent, and significantly (P = 0.013) associated with a lack of detectable HLA class I antigens. In selected neoplastic lesions, ERAP1 and ERAP2 were also tested for their enzymatic (peptide-trimming) activities. Expression and function were found to correlate, indicating that immunohistochemistry detects active enzymes in vivo. Thus, dissociation in the expression of ERAP1, ERAP2 and HLA class I may already be present in some normal tissues, but malignant transformation causes additional losses, gains and imbalances in specific tumour histotypes, and these alter the peptide-trimming ability of tumour cells in vivo.