gebhart/patrepeval huggingface dataset:
Antioxidant strategies for Alzheimer's disease (2002)

Oxidative damage is present within the brains of patients with Alzheimer's disease (AD), and is observed within every class of biomolecule, including nucleic acids, proteins, lipids and carbohydrates. Oxidative injury may develop secondary to excessive oxidative stress resulting from beta-amyloid-induced free radicals, mitochondrial abnormalities, inadequate energy supply, inflammation or altered antioxidant defences. Treatment with antioxidants is a promising approach for slowing disease progression to the extent that oxidative damage may be responsible for the cognitive and functional decline observed in AD. Although not a uniformly consistent observation, a number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations. In AD clinical trials molecules with antioxidant properties such as vitamin E and Ginkgo biloba extract have shown modest benefit. A clinical trial with vitamin E is currently ongoing to determine if it can delay progression to AD in individuals with mild cognitive impairment. Combinations of antioxidants might be of even greater potential benefit for AD, especially if the agents worked in different cellular compartments or had complementary activity (e.g. vitamins E, C and ubiquinone). Naturally-occurring compounds with antioxidant capacity are available and widely marketed (e.g. vitamin C, ubiquinone, lipoic acid, beta-carotene, creatine, melatonin, curcumin) and synthetic compounds are under development by industry. Nevertheless, the clinical value of these agents for AD prevention and treatment is ambiguous, and will remain so until properly designed human trials have been performed.
Comparative expressed-sequence-tag analysis of differential gene expression profiles in PC-12 cells before and after nerve growth factor treatment. (1995)

Nerve growth factor-induced differentiation of adrenal chromaffin PC-12 cells to a neuronal phenotype involves alterations in gene expression and represents a model system to study neuronal differentiation. We have used the expressed-sequence-tag approach to identify approximately 600 differentially expressed mRNAs in untreated and nerve growth factor-treated PC-12 cells that encode proteins with diverse structural and biochemical functions. Many of these mRNAs encode proteins belonging to cellular pathways not previously known to be regulated by nerve growth factor. Comparative expressed-sequence-tag analysis provides a basis for surveying global changes in gene-expression patterns in response to biological signals at an unprecedented scale, is a powerful tool for identifying potential interactions between different cellular pathways, and allows the gene-expression profiles of individual genes belonging to a particular pathway to be followed.
Activation of interferon-regulated, dsRNA-dependent enzymes by human immunodeficiency virus-1 leader RNA (1989)

Human immunodeficiency virus-1 (HIV-1) leader RNA, which contains double-stranded regions due to inverted repeats, was shown to activate the dsRNA-dependent enzymes associated with the interferon system. HIV-1 leader RNA produced in vitro using SP6 RNA polymerase was characterized using probes for antisense and sense-strand RNA. The RNA preparation was free from significant levels of antisense RNA. HIV-1 leader RNA was shown to activate dsRNA-dependent protein kinase in a cell-free system from interferon-treated HeLa cells. Affinity resins, consisting of HIV-1 leader RNA covalently attached to cellulose, immobilized and activated dsRNA-dependent protein kinase and 2-5A-synthetase. HIV-1 leader RNA, therefore, may be a contributing factor in the mechanism by which interferon inhibits HIV replication.
Lipopolysaccharide‐sensitive serine‐protease zymogen (factor C) found in Limulus hemocytes (1986)

Bacterial endotoxin (lipopolysaccharide, LPS) induces coagulation of horseshoe crab hemolymph. Our previous studies had demonstrated that a hemolymph factor, designated factor B, was associated with the LPS-mediated activation of the Limulus clotting system [Ohki et al. (1980) FEBS Lett. 120, 318-321]. On further purification of factor B we found that an additional component, designated factor C, was required to generate factor B activity in the presence of LPS in order to activate the proclotting enzyme. To elucidate the role of factor C in the LPS-mediated reaction, factor C was isolated and characterized from the hemocyte lysate under sterile conditions. The preparation exhibited a single band on sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) in the absence of 2-mercaptoethanol, while two protein bands on SDS-PAGE were observed after reduction. Thus, factor C had a Mr of 123 000 consisting of a heavy chain of Mr = 80 000 and a light chain of Mr = 43 000. Factor C was converted to an activated form in the presence of LPS with a Mr = 123 000, designated factor C. Upon activation, cleavage of the light chain occurred resulting in the accumulation of two new fragments of Mr = 34000 and 8500 on reduced SDS-PAGE. A diisopropylfluorophosphate-sensitive active site was localized in the light chain (Mr = 34000) of factor C. The reconstitution experiments, using factor C, factor B, proclotting enzyme and LPS, demonstrated that all of these proteins are essential for the endotoxin-mediated coagulation system. On the basis of these results we propose that a cascade pathway of LPS-induced activation of the Limulus clotting system consists of three sequential activations of hemolymph serine protease zymogens.
Shaping gain of LDPC coded-QAM transmitting systems with non-uniform constellation (2007)

Shaping gains of regular (3,6) LDPC Coded-QAM transmitting systems with non-uniform QAM constellation are presented over AWGN channel. The influences of code rate, frame length, the order of non-uniform QAM constellation, and the finite fields GF(q) of LDPC codes on shaping gain are investigated. It is found that shaping gain of proposed system with non-uniform 64QAM constellation for binary LDPC codes (R=1/2) can be obviously achieved by middle frame length, and can be improved further with the increase of frame length. Meanwhile it is found that under non-uniform 16QAM constellation for binary LDPC code(R=1/2) there is no shaping gain improvement with the increase of frame length, but the shaping gains of non-uniform 16QAM and 64QAM both are increased, even the former is no less than the latter when we change the finite fields GF(q) of LDPC codes from 2 to 16. The shaping gain can disappear as the binary code rate increases to 3/4 in proposed system.
Vincristine Induces Dramatic Lysosomal Changes and Sensitizes Cancer Cells to Lysosome-Destabilizing Siramesine (2007)

Vincristine is a microtubule-destabilizing antimitotic drug that has been used in cancer therapy for over 40 years. However, the knowledge on vincristine-induced cell death pathways is still sparse. Here, we show that vincristine induces dramatic changes in the lysosomal compartment and sensitizes cells to lysosomal membrane permeabilization. In HeLa cervix carcinoma cells, vincristine induced mitotic arrest and massive cell death associated with an early increase in the lysosomal volume and lysosomal leakage followed by the activation of the intrinsic apoptosis program. In contrast, the majority of vincristine-treated MCF-7 breast carcinoma cells resisted apoptosis. Instead, they adapted to the spindle assembly checkpoint and escaped the mitotic arrest as micronucleated and senescent cells with an increase in the volume and the activity of their lysosomal compartment. Consistent with its substantial effects on the lysosomes, vincristine greatly sensitized cultured cancer cells as well as orthotopic breast cancer xenografts in mice to the cytotoxicity induced by siramesine, a sigma-2 receptor ligand that kills cancer cells by destabilizing their lysosomes. Importantly, the combination of nontoxic concentrations of vincristine and siramesine resulted in massive cell death even in MCF-7 cells that were capable of escaping vincristine-induced spindle assembly checkpoint and cell death. Similar synergism was observed when siramesine was combined with a semisynthetic vincristine analogue, vinorelbine, or with microtubule-stabilizing paclitaxel. These data strongly suggest that combination therapies consisting of microtubule-disturbing and lysosome-destabilizing drugs may prove useful in the treatment of otherwise therapy-resistant human cancers.
Relative Stability of Pertussis Vaccine Preserved with Merthiolate, Benzethonium Chloride, or the Parabens (1965)

When stored at 4 C, or heated at 22 or 35 C followed by storage at 4 C, the potency of pertussis vaccines preserved with Merthiolate was more stable than the potency of vaccines preserved with benzethonium chloride or the parabens (methyl- and propyl-p-hydroxybenzoate). Without preservative, potency was more stable than in the presence of benzethonium chloride or the parabens, but less stable than when Merthiolate was present. The histamine-sensitizing factor of the vaccines likewise decreased with the loss of potency. The deleterious effect of benzethonium chloride and the absence of the stabilizing effect of Merthiolate were contributing factors, if not the sole cause, for the instability of pertussis vaccine in quadruple antigen vaccine (diphtheria and tetanus toxoids and pertussis and poliomyelitis vaccines).
Atomic-Layer Epitaxy of Silicon on (100) Surface (2000)

Atomic-layer epitaxy (ALE) of Si on the (100) surface has been studied. The ALE temperature window for the (100) surface was as wide as that for the (111) surface, under optimum hydrogen pressure conditions. The grown film surface was smooth only within the upper half of the window. Surface roughness increased with ALE execution cycle, due to the combined dynamic effects of excess growth, etching and surface migration of adsorbates within an execution cycle, but took an extremely small value under a special set of ALE parameters.
Formation and Characterization of a Single Trp-Trp Cross-link in Indolicidin That Confers Protease Stability without Altering Antimicrobial Activity (2000)

Indolicidin is a 13-residue cationic, antimicrobial peptide-amide isolated from the cytoplasmic granules of bovine neutrophils. The unique composition of indolicidin distinguishes it from alpha-helical and beta-structured cationic peptides, because five of indolicidin's 13 residues are tryptophans: H-Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH(2). Solid phase synthesis of indolicidin gave rise to a minor byproduct that possessed unusual fluorescence and UV absorbance properties compared with authentic indolicidin. The byproduct was purified by combined ion exchange and reversed phase high pressure liquid chromatography steps and was shown be identical to authentic indolicidin in its microbicidal activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and Cryptococcus neoformans. Mass analysis of the byproduct revealed a 2-atomic mass unit reduction compared with indolicidin, suggesting the deprotonation of two indole side chains to form an intrachain delta(1),delta(1)'-ditryptophan derivative. We confirmed the nature of the cross-linked byproduct, termed X-indolicidin, by absorbance and fluorescence spectroscopy, peptide mapping, and sequence analysis. Edman degradation revealed that Trp-6 and Trp-9 were covalently cross-linked. Compared with indolicidin, X-indolicidin was partially resistant to digestion with trypsin and chymotrypsin, suggesting that the ditryptophan stabilizes a subset of molecular conformations that are protease resistant but that are absent in the native structure.
Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop (2004)

Acetyl-CoA carboxylases (ACCs) are crucial for the metabolism of fatty acids, making these enzymes important targets for the development of therapeutics against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain of ACC is the site of action of commercial herbicides, such as haloxyfop, diclofop, and sethoxydim. We have determined the crystal structures at up to 2.5-A resolution of the CT domain of yeast ACC in complex with the herbicide haloxyfop or diclofop. The inhibitors are bound in the active site, at the interface of the dimer of the CT domain. Unexpectedly, inhibitor binding requires large conformational changes for several residues in this interface, which create a highly conserved hydrophobic pocket that extends deeply into the core of the dimer. Two residues that affect herbicide sensitivity are located in this binding site, and mutation of these residues disrupts the structure of the domain. Other residues in the binding site are strictly conserved among the CT domains.
Prognostic significance of c‐myc and AIB1 amplification in hepatocellular carcinoma (2002)

The current results strongly suggest that amplifications of the c-myc and AIB1 oncogenes are late genetic alterations in the progression of HCC and are correlated with a poor prognosis.
Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems (2016)

The generation of genetic variation (somatic hypermutation) is an essential process for the adaptive immune system in vertebrates. We demonstrate the targeted single-nucleotide substitution of DNA using hybrid vertebrate and bacterial immune systems components. Nuclease-deficient type II CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated) and the activation-induced cytidine deaminase (AID) ortholog PmCDA1 were engineered to form a synthetic complex (Target-AID) that performs highly efficient target-specific mutagenesis. Specific point mutation was induced primarily at cytidines within the target range of five bases. The toxicity associated with the nuclease-based CRISPR/Cas9 system was greatly reduced. Although combination of nickase Cas9(D10A) and the deaminase was highly effective in yeasts, it also induced insertion and deletion (indel) in mammalian cells. Use of uracil DNA glycosylase inhibitor suppressed the indel formation and improved the efficiency.
Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA (2005)

Prostate-specific antigen (PSA), the tumor marker currently used for prostate cancer (PCa), is not specific enough to distinguish between PCa and benign prostate hyperplasia (BPH). Glycan processing is normally perturbed in tumors, therefore we investigated whether changes in glycosylation of PSA could be useful diagnostic indicators. Previously we determined that the glycosylation of PSA secreted by the tumor prostate cell line LNCaP differs significantly from that of PSA from seminal plasma (normal control). We therefore undertook a detailed glycan analysis of PSA derived from sera from PCa patients and, importantly, established that the glycosylation of the PCa serum PSA was significantly different from the PSA from the LNCaP cell line. In comparison with seminal plasma PSA, the fucose content of PSA from the PCa patient serum was significantly lower and there was a decrease in alpha2,3-linked sialic acid. Differences in the glycosylation of PSA derived from PCa patients' sera, seminal plasma, and LNCaP cells were further established by lectin detection, glycosylation immunosorbent assay, and two-dimensional electrophoresis. We also investigated whether the impact of glycosylation changes initiated by the tumor was reflected in the serum glycome. By comparing the glycans released from the total glycoproteins in PCa patient serum with those of normal serum we found an increase in the proportion of sialyl-Lewis x structures. Further analysis of the glycosylation of PSA from PCa and BPH sera will be required in order to determine the utility of these glycan differences to discriminate specifically between benign and malignant prostate states.
Highly Elevated Atmospheric Levels of Volatile Organic Compounds in the Uintah Basin, Utah (2014)

Oil and natural gas production in the Western United States has grown rapidly in recent years, and with this industrial expansion, growing environmental concerns have arisen regarding impacts on water supplies and air quality. Recent studies have revealed highly enhanced atmospheric levels of volatile organic compounds (VOCs) from primary emissions in regions of heavy oil and gas development and associated rapid photochemical production of ozone during winter. Here, we present surface and vertical profile observations of VOC from the Uintah Basin Winter Ozone Studies conducted in January-February of 2012 and 2013. These measurements identify highly elevated levels of atmospheric alkane hydrocarbons with enhanced rates of C2-C5 nonmethane hydrocarbon (NMHC) mean mole fractions during temperature inversion events in 2013 at 200-300 times above the regional and seasonal background. Elevated atmospheric NMHC mole fractions coincided with build-up of ambient 1-h ozone to levels exceeding 150 ppbv (parts per billion by volume). The total annual mass flux of C2-C7 VOC was estimated at 194 ± 56 × 10(6) kg yr(-1), equivalent to the annual VOC emissions of a fleet of ∼100 million automobiles. Total annual fugitive emission of the aromatic compounds benzene and toluene, considered air toxics, were estimated at 1.6 ± 0.4 × 10(6) and 2.0 ± 0.5 × 10(6) kg yr(-1), respectively. These observations reveal a strong causal link between oil and gas emissions, accumulation of air toxics, and significant production of ozone in the atmospheric surface layer.
Role of .beta.2-microglobulin in the intracellular processing of HLA antigens (1981)

The biosynthesis of HLA-A, -B, and -C antigens was examined in the two lymphoblastoid cell lines DAUDI and RAJI. In RAJI cells the HLA-A, -B, and -C antigen heavy chains become core-glycosylated in the endoplasmic reticulum as evidenced by their sensitivity to endo-H digestion and tunicamycin treatment. Beta2-Microglobulin is present in excess in the endoplasmic reticulum of the RAJI cells and associates with the heavy chain at the time of synthesis of the heavy chain. Pulse-chase experiments demonstrated that the RAJI HLA-A, -B, and -C antigen heavy chains become terminally glycosylated since their changed characteristics included resistance to endo-H digestion, sensitivity to neuraminidase treatment, and incorporation fucose. DAUDI HLA-A, -B, and -C antigen heavy chains are synthesized normally and become core-glycosylated but not terminally glycosylated. Other glycosylated cell surface proteins, like the HLA-DR antigens, display normal glycosylation in DAUDI cells. Therefore it is unlikely that the absence of terminally glycosylated HLA-A, -B, and -C antigen heavy chains is the result of a general defect in the biosynthetic machinery of DAUDI cells. However, DAUDI cells lack the ability to synthesize beta2-microglobulin, the common subunit of all HLA-A, -B, and -C antigens. Therefore, it seems reasonable to conclude that beta2-microglobulin is of importance for intracellular transport of newly synthesized HLA-A, -B, and -C antigens.
SCARF: a color vision system that tracks roads and intersections (1993)

SCARF, a color vision system that recognizes difficult roads and intersections, is presented. It has been integrated into several navigation systems that drive a robot vehicle, the Navlab, on a variety of roads in many different weather conditions. SCARF recognizes roads that have degraded surfaces and edges with no lane markings in difficult shadow conditions. It also recognizes intersections with or without predictions from the navigation system. This is the first system that detects intersections in images without a priori knowledge of the intersection shape and location. SCARF uses Bayesian classification to determine a road-surface likelihood for each pixel in a reduced color image. It then evaluates a number of road and intersection candidates by matching an ideal road-surface likelihood image with the results from the Bayesian classification. The best matching candidate is passed to a path-planning system that navigates the robot vehicle on the road or intersection. The SCARF system is described in detail, results on a variety of images are presented, and Navlab test runs using SCARF are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Host-guest complexation. 35. Spherands, the first completely preorganized ligand systems (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHost-guest complexation. 35. Spherands, the first completely preorganized ligand systemsDonald J. Cram, Takahiro Kaneda, Roger C. Helgeson, S. Bruce Brown, Carolyn B. Knobler, Emily Maverick, and Kenneth N. TruebloodCite this: J. Am. Chem. Soc. 1985, 107, 12, 3645–3657Publication Date (Print):June 1, 1985Publication History Published online1 May 2002Published inissue 1 June 1985https://pubs.acs.org/doi/10.1021/ja00298a040https://doi.org/10.1021/ja00298a040research-articleACS PublicationsRequest reuse permissionsArticle Views1504Altmetric-Citations158LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Concise Review: Mesenchymal Stem Cells and Translational Medicine: Emerging Issues (2011)

Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach of cell-based therapy for a wide range of autoimmune disorders and degenerative diseases. In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, myocardial infarction, liver cirrhosis, inflammatory bowel disease, and other disorders. The underlying therapeutic mechanisms of MSCs include their homing efficiency to the tissue injury sites, their differentiation potential, their capability to produce a large amount of trophic factors, and their immunomodulatory effect. Because tissue damage sites are complicated milieus with distinct types of inflammatory cells and factors, available data have demonstrated that the properties of MSCs could be fundamentally influenced by the inflammatory elements. Thus, an understanding of the interaction between MSCs and the inflammatory microenvironment will provide critical information in revealing the precise in vivo mechanisms of MSC-mediated therapeutic effects and designing more practical protocols for clinical use of these cells.