gebhart/patrepeval huggingface dataset:
Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976)

The biosynthesis of carnitine in the rat was studied by following the metabolism of two radioactive derivatives of asialo-fetuin. The first contained 14C-labelled methyl groups covalently bound to the 6-N-amino fraction of its lysine residues as 6-N-monomethyl- and dimethyl-lysine. By treating this protein with iodomethane, a second derivative was produced in which the radioactivity was preferentially incorporated as 6-N-[Me-14C]-trimethyl-lysine. These desialylated glycoproteins, like other asialo-proteins, were immediately cleared from the blood by rat liver. Within hepatocyte lysosomes, the 14C-labelled proteins were rapidly hydrolysed, producing free amino acids containing the various 6-N-[Me-14C]methylated lysine residues. The radioactive amino acids crossed the lysosomal membrane and were further metabolized in the cytosol. Carnitine was the major radioactive metabolite detected in extracts of the rat carcass and liver after intravenous injection of 6-N-[Me-14C]trimethyl-lysine-labelled asialo-fetuin. Within 3h, at least 34.6% of the trimethyl-lysine in the administered protein was converted into carnitine. Similarly, an isolated perfused rat liver converted 30% of the added peptide-bound trimethyl-lysine into carnitine within 90 min. On the other hand, in numerous attempts we failed to detect radioactive carnitine in both rat liver and carcass between 20 min and 22 h after injection of 6-N-[Me-14C]-monomethyl- and -dimethyl-lysine-labelled asialo-fetuin. These data provide evidence for a pathway of carnitine biosynthesis that involves trimethyl-lysine as a peptide-bound precursor as proposed by R.A. Cox &amp; C.L. Hoppel [(1973) Biochem. J. 136, 1083-1090] and V. Tanphaichitr &amp; H.P. Broquist [(1973) J. Biol. Chem. 248, 2176-2181]. The findings also show that rat liver can synthesize carnitine without the aid of other tissues, but cannot convert free partially methylated lysines into trimethyl-lysine.
Autonomous exploration and mapping of abandoned mines (2004)

This article discusses the software architecture of an autonomous robotic system designed to explore and map abandoned mines. A new set of software tools is presented, enabling robots to acquire maps of unprecedented size and accuracy. On 30 May 2003, the robot "Groundhog" successfully explored and mapped a main corridor of the abandoned Mathies mine near Courtney, Pennsylvania. This article also discusses some of the challenges that arise in the subterranean environments and some the difficulties of building truly autonomous robots.
Homologous expression and characterization of Cel61A (EG IV) of Trichoderma reesei (2001)

There are currently four proteins in family 61 of the glycoside hydrolases, from Trichoderma reesei , Agaricus bisporus , Cryptococcus neoformans and Neurospora crassa . The enzymatic activity of these proteins has not been studied thoroughly. We report here the homologous expression and purification of T. reesei Cel61A [previously named endoglucanase (EG) IV]. The enzyme was expressed in high amounts with a histidine tag on the C‐terminus and purified by metal affinity chromatography. This is the first time that a histidine tag has been used as a purification aid in the T. reesei expression system. The enzyme activity was studied on a series of carbohydrate polymers. The only activity exhibited by Cel61A was an endoglucanase activity observed on substrates containing β‐1,4 glycosidic bonds, e.g. carboxymethylcellulose (CMC), hydroxyethylcellulose (HEC) and β‐glucan. The endoglucanase activity on CMC and β‐glucan was determined by viscosity analysis, by measuring the production of reducing ends and by following the degradation of the polymer on a size exclusion chromatography system. The formation of soluble sugars by Cel61A from microcrystalline cellulose (Avicel; Merck), phosphoric acid swollen cellulose (PASC), and CMC were analysed on a HPLC system. Cel61A produced small amounts of oligosaccharides from these substrates. Furthermore, Cel61A showed activity against cellotetraose and cellopentaose. The activity of Cel61A was several orders of magnitude lower compared to Cel7B (previously EG I) of T. reesei on all substrates. One significant difference between Cel61A and Cel7B was that cellotriose was a poor substrate for Cel61A but was readily hydrolysed by Cel7B. The enzyme activity for Cel61A was further studied on a large number of carbohydrate substrates but the enzyme showed no activity towards any of these substrates.
Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis. (1988)

The presence of amyloid P-component (AP) within cerebral amyloid deposits was investigated by means of biochemical and immunocytochemical methods. Immunoperoxidase on formalin-fixed, paraffin-embedded tissue sections from Alzheimer's Disease, Down's Syndrome, asymptomatic age-related cerebral amyloidosis, sporadic cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis-Icelandic type, and hereditary cerebral hemorrhage with amyloidosis-Dutch type revealed the presence of AP in the affected vessel walls in all cases, and in parenchymal deposits resembling neuritic plaques of Alzheimer's disease, sporadic cerebral amyloid angiopathy, and hereditary cerebral hemorrhage with amyloidosis-Dutch type. A short digestion of tissue sections with pepsin was required for immunodetection of AP in these latter structures. After extraction of leptomeningeal amyloid fibrils, AP was characterized by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis, Western blot, gel chromatography, and partial amino acid sequencing. Our results indicate that: (a) AP from cerebral amyloidosis has similar biochemical properties and homologous amino terminal sequence to AP from systemic amyloidosis; (b) AP is associated to a variety of brain amyloid deposits regardless of their chemical nature. The presence of AP, a serum protein, within the brain parenchyma points to an impairment of the blood-brain barrier in these diseases.
Hemagglutinating Virus of Japan (HVJ) Envelope Vector as a Versatile Gene Delivery System (2002)

We have developed a simple method for converting the lipid envelope of an inactivated virus to a gene transfer vector. Hemagglutinating virus of Japan (HVJ; Sendai virus) envelope vector was constructed by incorporating plasmid DNA into inactivated HVJ particles. This HVJ envelope vector introduced plasmid DNA efficiently and rapidly into various cell lines, including cancer cells and several types of primary cell culture. Efficiency of gene transfer was greatly enhanced by protamine sulfate and centrifugation. Fluorescein isothiocyanate-labeled oligodeoxynucleotides (FITC-ODN) were also delivered to cells at > 95% efficiency. When HVJ envelope vector was injected into organs directly, reporter gene expression was observed in organs including liver, brain, skin, uterus, tumor masses, lung, and eye. When HVJ envelope vector containing luciferase gene was injected into mouse tail vein, luciferase gene expression was detected primarily in spleen. FITC-ODN were also delivered to spleen cells by intravenous injection of HVJ envelope. These results suggest that HVJ envelope vector will be useful for both ex vivo and in vivo gene therapy experiments.
SpeechActs: a spoken-language framework (1996)

SpeechActs is a prototype testbed for developing spoken natural language applications. In developing SpeechActs, our primary goal was to enable software developers without special expertise in speech or natural language to create effective conversational speech applications-that is, applications with which users can speak naturally, as if they were conversing with a personal assistant. We also wanted SpeechActs applications to work with one another without requiring that each have specific knowledge of other applications running in the same suite. A discourse management component is necessary to embody the information that allows such a natural conversational flow. Because technology changes so rapidly, we also did not want to tie developers to specific speech recognizers or synthesizers. We wanted them to be able to use these speech technologies as plug-in components.
Gaps in structurally similar proteins: Towards improvement of multiple sequence alignment (2003)

An algorithm was developed to locally optimize gaps from the FSSP database. Over 2 million gaps were identified from all versus all FSSP structure comparisons, and datasets of non-identical gaps and flanking regions comprising between 90,000 and 135,000 sequence fragments were extracted for statistical analysis. Relative to background frequencies, gaps were enriched in residue types with small side chains and high turn propensity (D, G, N, P, S), and were depleted in residue types with hydrophobic side chains (C, F, I, L, V, W, Y). In contrast, regions flanking a gap exhibited opposite trends in amino acid frequencies, i.e., enrichment in hydrophobic residues and a high degree of secondary structure. Log-odds scores of residue type as a function of position in or around a gap were derived from the statistics. Three simple experiments demonstrated that these scores contained significant predictive information. First, regions where gaps were observed in single sequences taken from HOMSTRAD structure-based multiple sequence alignments generally scored higher than regions where gaps were not observed. Second, given the correct pairwise-aligned cores, the actual positions of gaps could be reproduced from sequence more accurately using the structurally-derived statistics than by using random pairwise alignments. Finally, revision of the Clustal-W residue-specific gap opening parameters with this new information improved the agreement of Clustal-W alignments with the structure-based alignments. At least three applications for these results are envisioned: improvement of gap penalties in pairwise (or multiple) sequence alignment, prediction of regions of single sequences likely (or unlikely) to contain indels, and more accurate placement of gaps in automated pairwise structure alignment.
Regulation of hypoxia-inducible factor-1α by nitric oxide through mitochondria-dependent and -independent pathways (2003)

Nitric oxide (NO) has been reported both to promote and to inhibit the activity of the transcription factor hypoxia-inducible factor-1 (HIF-1). In order to avoid the pitfalls associated with the use of NO donors, we have developed a human cell line (Tet-iNOS 293) that expresses the inducible NO synthase (iNOS) under the control of a tetracycline-inducible promoter. Using this system to generate finely controlled amounts of NO, we have demonstrated that the stability of the alpha-subunit of HIF-1 is regulated by NO through two separate mechanisms, only one of which is dependent on a functional respiratory chain. HIF-1alpha is unstable in cells maintained at 21% O(2), but is progressively stabilized as the O(2) concentration decreases, resulting in augmented HIF-1 DNA-binding activity. High concentrations of NO (>1 microM) stabilize HIF-1alpha at all O(2) concentrations tested. This effect does not involve the respiratory chain, since it is preserved in cells lacking functional mitochondria (rho(0)-cells) and is not reproduced by other inhibitors of the cytochrome c oxidase. By contrast, lower concentrations of NO (<400 nM) cause a rapid decrease in HIF-1alpha stabilized by exposure of the cells to 3% O(2). This effect of NO is dependent on the inhibition of mitochondrial respiration, since it is mimicked by other inhibitors of mitochondrial respiration, including those not acting at cytochrome c oxidase. We suggest that, although stabilization of HIF-1alpha by high concentrations of NO might have implications in pathophysiological processes, the inhibitory effect of lower NO concentrations is likely to be of physiological relevance.
Zika Virus Structure, Maturation, and Receptors (2017)

The emergence of Zika virus (ZIKV) as a major public health threat has focused research on understanding virus biology and developing a suite of strategies for disease intervention. Recent advances in cryoelectron microscopy have accelerated structure-function studies of flaviviruses and of ZIKV in particular. Structures of the mature and immature ZIKV have demonstrated its similarity with other known flaviviruses such as dengue and West Nile viruses. However, ZIKV's unique pathobiology demands an explanation of how its structure, although similar to its flavivirus relatives, is sufficiently unique to address questions of receptor specificity, transmission, and antigenicity. Progress in defining the immunodominant epitopes and how neutralizing antibodies bind to them will provide great insight as vaccines progress through clinical trials. Identification of host receptors will substantially illuminate the interesting ZIKV tropism and provide insights into pathogenesis. Although the answers to all of these questions are not yet available, rapid progress in combining structural biology with other techniques is revealing the similarities and the differences in virion structure and function between ZIKV and related flaviviruses.
Antishock and endothelial protective actions of a NO donor in mesenteric ischemia and reperfusion. (1992)

Splanchnic artery occlusion (SAO) of the celiac, superior mesenteric, and inferior mesenteric arteries for 2 hr, followed by a 2-hr reperfusion period in cats produces a severe form of circulatory shock characterized by endothelial dysfunction, increased lysosomal leakage, and severe hypotension resulting from release of proteases, oxygen-derived free radicals, and other humoral mediators into the circulation. Administration of 0.75 mg/kg/hr of C873754, a nitric oxide (NO) donor, 10 min prior to reperfusion, significantly attenuated the accumulation of plasma cathepsin D from 12 +/- 3 U/ml in the SAO + vehicle group to 5 +/- 1 U/ml (P < 0.05) in the C87-3754 treated SAO group. A similar attenuation of plasma myocardial depressant factor (MDF) activity was observed in the C87-3754 treated cats (P < 0.02). Administration of C87-3754 significantly increased short term (i.e., 2-hr) survival rate (P < 0.05, compared to the vehicle group). Moreover, C87-3754 attenuated the SAO shock induced decline in release of endothelium-derived relaxing factor (EDRF) from isolated superior mesenteric artery (SMA) rings stimulated by acetylcholine and A23187. Additionally, C87-3754 significantly decreased PMN adherence to the superior mesenteric venous endothelium in vitro. Thus, treatment with the NO donor, C87-3754 reduced the accumulation of humoral mediators into the plasma while significantly attenuating endothelial dysfunction and improving short term survival.
Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro (1999)

Oxidized LDL is implicated in atherosclerosis; however, the pathways that convert LDL into an atherogenic form in vivo are not established. Production of reactive nitrogen species may be one important pathway, since LDL recovered from human atherosclerotic aorta is enriched in nitrotyrosine. We now report that reactive nitrogen species generated by the MPO-H2O2-NO2- system of monocytes convert LDL into a form (NO2-LDL) that is avidly taken up and degraded by macrophages, leading to massive cholesterol deposition and foam cell formation, essential steps in lesion development. Incubation of LDL with isolated MPO, an H2O2-generating system, and nitrite (NO2-)-- a major end-product of NO metabolism--resulted in nitration of apolipoprotein B 100 tyrosyl residues and initiation of LDL lipid peroxidation. The time course of LDL protein nitration and lipid peroxidation paralleled the acquisition of high-affinity, concentration-dependent, and saturable binding of NO2-LDL to human monocyte-derived macrophages and mouse peritoneal macrophages. LDL modification and conversion into a high-uptake form occurred in the absence of free metal ions, required NO2-, occurred at physiological levels of Cl-, and was inhibited by heme poisons, catalase, and BHT. Macrophage binding of NO2-LDL was specific and mediated by neither the LDL receptor nor the scavenger receptor class A type I. Exposure of macrophages to NO2-LDL promoted cholesteryl ester synthesis, intracellular cholesterol and cholesteryl ester accumulation, and foam cell formation. Collectively, these results identify MPO-generated reactive nitrogen species as a physiologically plausible pathway for converting LDL into an atherogenic form.
Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer. (1992)

Hepatocyte growth factor (HGF) is a heterodimeric protein consisting of a heavy chain and a light chain held by a disulfide bond. These chains are produced by endoproteolytic processing from a single chain precursor. In this study, we examined whether the processing is a prerequisite for the mitogenic activity of HGF on hepatocytes in primary culture. Single chain HGF was proteolytically converted to the heterodimeric form during incubation with hepatocytes and was as mitogenic as the heterodimeric form. When the conversion was inhibited by serine-protease inhibitors, the mitogenic activity of single chain HGF was markedly reduced. Furthermore, a mutant resistant to the proteolytic processing, which was prepared by in vitro mutagenesis, completely lost the mitogenic activity. From these results, we concluded that the single chain form of HGF is endoproteolytically processed by a serine-protease and that this processing is a prerequisite for the mitogenic activity of HGF.
The cytokine storm in multiple sclerosis (1998)

MS is associated with a cytokine storm characterized by the parallel upregulation of proinflammatory (IFN-gamma, TNF-alpha, and beta, and IL-12) and immune response-down-regulating (TGF-beta, IL-10) cytokines. Also IL-6 and the cytolytic molecule perforin are upregulated. Even when evaluated in individual MS patients over the disease course, no Th1/Th2 dichotomy is obvious but, instead, upregulation of Th1 + Th2 + Th3 cytokines simultaneously, probably reflecting the complex pathology of MS in lesion size, time and distribution in the individual patient. Few correlations have been observed between cytokines and clinical MS variables, though upregulation of TGF-beta seems to correlate with benign course and minor disability. Both pro- and antiinflammatory cytokines are also produced by microglia and astrocytes, constituting a CNS-cytokine network that interacts with the cytokine network of the immune system. This complexity is to be kept in mind when searching for cytokine abnormalities in MS.
FastUniq: A Fast De Novo Duplicates Removal Tool for Paired Short Reads (2012)

The presence of duplicates introduced by PCR amplification is a major issue in paired short reads from next-generation sequencing platforms. These duplicates might have a serious impact on research applications, such as scaffolding in whole-genome sequencing and discovering large-scale genome variations, and are usually removed. We present FastUniq as a fast de novo tool for removal of duplicates in paired short reads. FastUniq identifies duplicates by comparing sequences between read pairs and does not require complete genome sequences as prerequisites. FastUniq is capable of simultaneously handling reads with different lengths and results in highly efficient running time, which increases linearly at an average speed of 87 million reads per 10 minutes. FastUniq is freely available at http://sourceforge.net/projects/fastuniq/.
Neutrophil Gelatinase-Associated Lipocalin: A Novel Early Urinary Biomarker for Cisplatin Nephrotoxicity (2004)

The results indicate that NGAL represents an early and quantitative urinary biomarker for cisplatin nephrotoxicity.
Apatinib is effective as third-line and more treatment of advanced metastatic non-small-cell lung cancer (2019)

No standard methods are recommended for patients with advanced metastatic non-small-cell lung cancer (NSCLC) experiencing progression after 2 or more lines treatment now. The aim of this retrospective study was to assess the efficacy and safety of apatinib in metastatic NSCLC patients after second-line or more treatments failure in a real-world setting.A total of 52 advanced NSCLC patients who experienced progression after second-line and more treatments and received apatinib from March 2016 to February 2018 were retrospectively reviewed. Patients were treated with oral apatinib 500 mg QD (take the medicine once a day), every 4 weeks for a cycle. Responding and stable patients continued the treatment until progression or intolerable toxicity. The overall survival (OS), progression-free survival (PFS), objective remission rate (ORR) and disease control rate (DCR), and side effects of the drug were collected and reviewed.The ORR and the DCR were 6.9% and 67.4%. The median PFS and median OS of all patients were 3.8 months and 5.8 months, respectively. The Eastern Cooperative Oncology Group score was the independent influencing factor of PFS and OS for the advanced NSCLC patients who were treated with apatinib after second-line and above standard regimens (PFS: hazard ratio [HR] = 4.446, 95% confidence interval [CI]: 1.185-16.678, P = .027 and OS: HR = 8.149, 95% CI: 1.173-56.596, P = .034). The most common adverse events apatinib-related included hypertension (19.2%), hand-foot syndrome (11.5%), and mucous membrane reaction (17.3%). And treatment-related grade 3/4 toxicities were low.Apatinib showed favorable efficacy and safety and could be a treatment option in patients with advanced NSCLC experiencing progression after second-line and more treatment.
A Selective and Sensitive Fluoroionophore for HgII, AgI, and CuIIwith Virtually Decoupled Fluorophore and Receptor Units (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Selective and Sensitive Fluoroionophore for HgII, AgI, and CuII with Virtually Decoupled Fluorophore and Receptor UnitsKnut Rurack, Matthias Kollmannsberger, Ute Resch-Genger, and Jörg DaubView Author Information Federal Institute for Materials Research and Testing (BAM) Richard-Willstaetter Str. 11 D-12489 Berlin, Germany Institute of Organic Chemistry University of Regensburg D-93040 Regensburg, Germany Cite this: J. Am. Chem. Soc. 2000, 122, 5, 968–969Publication Date (Web):January 25, 2000Publication History Received26 July 1999Revised18 October 1999Published online25 January 2000Published inissue 1 February 2000https://doi.org/10.1021/ja992630aCopyright © 2000 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views4277Altmetric-Citations636LEARN 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 InReddit Read OnlinePDF (42 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Cations,Fluorescence,Ions,Mercury,Solvents Get e-Alerts