gebhart/patrepeval huggingface dataset:
Impaired Autofeedback Regulation of Hypothalamic Norepinephrine Release in Experimental Uremia (2005)

Chronic renal failure (CRF) is associated with multiple hypothalamic dysfunctions, including reduced secretion of gonadotropin-releasing hormone (GnRH). Because GnRH release is tightly controlled by sympathetic neuronal input, a possible alteration of local noradrenergic neurotransmission in experimental CRF was evaluated. Basal, stimulated, and autoinhibited norepinephrine (NE) release was assessed in hypothalamic and hippocampal tissue slices obtained from 5/6-nephrectomized and control rats. Autoinhibition-free NE release from brain slices, prelabeled with [3H]NE and superfused with physiologic buffer, was stimulated by six electrical pulses, 100 Hz (pseudo-one-pulse stimulation). Autoinhibited NE release was induced by 90 pulses at 3 Hz. The release of tritiated NE was measured upon addition of increasing concentrations of unlabeled NE to exogenously activate the inhibitory alpha2-autoreceptor. Although neither basal nor stimulated NE release differed between the groups, significantly lower pIC50 and Imax estimates of the concentration-response curves of exogenous NE on [3H]NE release were observed in CRF rats, suggesting a diminished autoinhibition of hypothalamic noradrenergic terminals in CRF. Western blotting of tissue homogenates disclosed a significantly reduced abundance of alpha2-autoreceptor protein in hypothalamic tissue from CRF rats. These abnormalities were selectively observed in the hypothalamus, whereas noradrenergic autoinhibition seemed unaltered in the hippocampus. The results suggest a diminished autoinhibition of hypothalamic NE release in CRF. Although impaired hypothalamic NE autoinhibition does not explain reduced GnRH secretion in CRF, it may be involved in the pathogenesis of sympathetic hyperactivity associated with this condition.
The Bone-specific Transcriptional Regulator Cbfa1 Is a Target of Mechanical Signals in Osteoblastic Cells (2002)

A primary goal of bone research is to understand the mechanism(s) by which mechanical forces dictate the cellular and metabolic activities of osteoblasts, the bone-forming cells. Several studies indicate that osteblastic cells respond to physical loading by transducing signals that alter gene expression patterns. Accumulated data have documented the fundamental role of the osteoblast-specific transcription factor Cbfa1 (core-binding factor) in osteoblast differentiation and function. Here, we demonstrate that low level mechanical deformation (stretching) of human osteoblastic cells directly up-regulates the expression and DNA binding activity of Cbfa1. This effect seems to be fine tuned by stretch-triggered induction of distinct mitogen-activated protein kinase cascades. Our novel finding that activated extracellular signal-regulated kinase mitogen-activated protein kinase physically interacts and phosphorylates endogenous Cbfa1 in vivo (ultimately potentiating this transcription factor) provides a molecular link between mechanostressing and stimulation of osteoblast differentiation. Elucidation of the specific modifiers and cofactors that operate in this mechanotranscription circuitry will contribute to a better understanding of mechanical load-induced bone formation which may set the basis for nonpharmacological intervention in bone loss pathologies.
Requirements for the mitochondrial import and localization of dihydroorotate dehydrogenase (2000)

In animals, dihydroorotate dehydrogenase (DHODH) is a mitochondrial protein that carries out the fourth step in de novo pyrimidine biosynthesis. Because this is the only enzyme of this pathway that is localized to mitochondria and because the enzyme is cytosolic in some bacteria and fungi, we carried out studies to understand the mode of targeting of animal DHODH and its submitochondrial localization. Analysis of fractionated rat liver mitochondria revealed that DHODH is an integral membrane protein exposed to the intermembrane space. In vitro-synthesized Drosophila, rat and human DHODH proteins were efficiently imported into the intermembrane space of isolated yeast mitochondria. Import did not alter the size of the in vitro synthesized protein, nor was there a detectable size difference when compared to the DHODH protein found in vivo. Thus, there is no apparent proteolytic processing of the protein during import either in vitro or in vivo. Import of rat DHODH into isolated yeast mitochondria required inner membrane potential and was at least partially dependent upon matrix ATP, indicating that its localization uses the well described import machinery of the mitochondrial inner membrane. The DHODH proteins of animals differ from the cytosolic proteins found in some bacteria and fungi by the presence of an N-terminal segment that resembles mitochondrial-targeting presequences. Deletion of the cationic portion of this N-terminal sequence from the rat DHODH protein blocked its import into isolated yeast mitochondria, whereas deletion of the adjacent hydrophobic segment resulted in import of the protein into the matrix. Thus, the N-terminus of the DHODH protein contains a bipartite signal that governs import and correct insertion into the mitochondrial inner membrane.
Chemical reactions involved in the deep‐fat frying of foods1 (1978)

Abstract Deep‐fat frying is one of the most commonly used procedures for the preparation and manufacture of foods in the world. During deep‐fat frying, oxidative and thermal decompositions may take place with the formation of volatile and nonvolatile decomposition products, some of which in excessive amounts are harmful to human health. A limited survey of frying fats used in commercial operations indicated that some were maintained at good quality and others were overused or abused. The volatile decomposition products produced by corn oil, hydrogenated cotton‐seed oil, trilinolein, and triolein, under simulated commercial frying conditions, were collected, fractionated, and identified. A total of 211 compounds were identified. The nonvolatile decomposition products produced by trilinolein, triolein, and tristearin under simulated commercial frying conditions were collected and characterized. After being treated under deep‐fat frying conditions at 185 C for 74 hr, trilinolein yielded 26.3% non‐urea‐adduct‐forming esters, triolein yielded 10.8%, and tristearin also yielded 4.2%.
“Smart” Diblock Copolymers as Templates for Magnetic-Core Gold-Shell Nanoparticle Synthesis (2009)

We report a new strategy for synthesizing temperature-responsive gamma-Fe(2)O(3)-core/Au-shell nanoparticles (Au-mNPs) from diblock copolymer micelles. The amphiphilic diblock copolymer chains were synthesized using reversible addition-fragmentation chain-transfer (RAFT) with a thermally responsive "smart" poly(N-isopropylacrylamide) (pNIPAAm) block and an amine-containing poly(N,N-dimethylaminoethylacrylamide) (DMAEAm) block that acted as a reducing agent during gold shell formation. The Au-mNPs reversibly aggregated upon heating the solution above the transition temperature of pNIPAAm, resulting in a red-shifted localized surface plasmon resonance.
Factor VIIa for intractable blood loss in trauma: Table 8 (2002)

A short cut review was carried out to establish whether factor VIIa is indicated in patients suffering intractable blood loss after trauma. Altogether 59 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.
The natural history of claudication: risk to life and limb. (1999)

Although a patient with intermittent claudication (IC) will fear progression to severe disease and amputation, this is a relatively rare outcome of claudication, with only 1% to 3% of claudicants ever requiring major amputation over a 5-year period. Indeed, in one study, 50% of claudicants became symptom free during 5 years' follow-up. All the new evidence over the last 40 years has not altered the impression that only about one fourth of patients with IC will ever significantly deteriorate, and that deterioration is most frequent during the first year after diagnosis (6 to 9%) compared with 2% to 3% per annum thereafter. Smoking is the most important risk factor for the progression of local disease in the legs, with an amputation rate 11 times greater in smokers than nonsmokers. Diabetes, male gender, and hypertension are also important risk factors for progression. Because cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial occlusive disease (PAOD) coexist, PAOD and IC should be regarded as a marker for increased risk from fatal and nonfatal cardiovascular event, and 2% to 4% of claudicants have a nonfatal cardiovascular event every year. The risk is higher in the first year after developing IC than in a long-standing stable claudicant, and the average claudicant is more likely to have a nonfatal myocardial infarction (MI) or stroke in the next year that of ever requiring a major amputation for his leg ischemia. The mortality in claudicants is 30% at 5 years, 50% at 10 years, and 70% at 15 years, without any clear decrease in these figures over the last 30 to 40 years. The mortality of claudicants is approximately two and a half times that of an age-matched general population.
The electrical stimulation of the retina by indwelling electrodes. (1977)

Previously we proposed a transmembrane model of the FhuA receptor protein in the outer membrane of Escherichia coli. Removal of the largest loop at the cell surface converted the FhuA transport protein into an open channel and rendered cells resistant to the FhuA-specific phages T1, T5, and phi 80 and to colicin M. In the present study we employed acetylated hexapeptide amides covering the entire surface loop to investigate binding of the phages and of colicin M. Competitive peptide mapping proved to be a powerful technique to uncover three ligand binding sites within a region of 34 amino acid residues. Hexapeptides derived from three specific regions of the surface loop inhibited infection of cells by the phages and killing by colicin M. Two of these regions were common among all four FhuA ligands. Electron microscopy of phage T5 revealed that one inhibitory peptide triggered a strong conformational change leading to the release of DNA from the phage head. These results suggest that the FhuA gating loop is the target for specific binding of phages T1, T5, and phi 80 and colicin M.
Infliximab Therapy Inhibits Inflammation-Induced Angiogenesis in the Mucosa of Patients With Crohn's Disease (2011)

Administration of infliximab downregulates mucosal angiogenesis in patients with CD and restrains production of VEGF-A by mucosal fibroblasts. It is proposed that this ameliorates inflammation-driven angiogenesis in the gut mucosa and contributes to the therapeutic efficacy of blockade of TNF-α.
WHO-EORTC classification for cutaneous lymphomas (2005)

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.
Creation of a Productive, Highly Enantioselective Nitrilase through Gene Site Saturation Mutagenesis (GSSM) (2003)

Gene site saturation mutagenesis (GSSM) technology is applied for the directed evolution of a nitrilase. The nitrilase effectively catalyzes the desymmetrization of the prochiral substrate 3-hydroxyglutaronitrile to afford (R)-4-cyano-3-hydroxybutyric acid, a precursor to the valuable cholesterol-lowering drug Lipitor. The discovered wild-type enzyme effectively performs the reaction at the industrially relevant 3 M substrate concentration but affords a product enantiomeric excess of only 87.6% ee. Through GSSM, a mutagenesis technique that effects the combinatorial saturation of each amino acid in the protein to each of the other 19 amino acids, combined with a novel high-throughput mass spectroscopy assay, a number of improved variants were identified, the best of which is the Ala190His mutant that yields product enantiomeric excess of 98.5% at 3 M substrate loading and a volumetric productivity of 619 g L-1 d-1.
Inhibitors of Poly(Adenosine Diphosphate-Ribose) Synthesis: Effect on Other Metabolic Processes (1984)

3-Aminobenzamide and benzamide, purported to be specific inhibitors of the synthesis of poly(adenosine diphosphate-ribose), were used to elucidate possible functions of this biopolymer. These compounds, at frequently used experimental concentrations, not only inhibited the action of poly(adenosine diphosphate-ribose) synthetase but also affected cell viability, glucose metabolism, and DNA synthesis. Thus, the usefulness of 3-aminobenzamide and benzamide may be severely restricted by the difficulty of finding a dose small enough to inhibit the synthetase without producing additional metabolic effects.
Synthesis of 3-deazaguanine, 3-deazaguanosine, and 3-deazaguanylic acid by a novel ring closure of imidazole precursors (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 3-deazaguanine, 3-deazaguanosine, and 3-deazaguanylic acid by a novel ring closure of imidazole precursorsP. Dan Cook, Robert J. Rousseau, A. Mohsin Mian, Phoebe Dea, Rich B. Meyer Jr., and Roland K. RobinsCite this: J. Am. Chem. Soc. 1976, 98, 6, 1492–1498Publication Date (Print):March 1, 1976Publication History Published online1 May 2002Published inissue 1 March 1976https://pubs.acs.org/doi/10.1021/ja00422a036https://doi.org/10.1021/ja00422a036research-articleACS PublicationsRequest reuse permissionsArticle Views300Altmetric-Citations77LEARN 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-Alertsclose Get e-Alerts
Phospholipid-independent and -dependent interactions required for tissue factor receptor and cofactor function (1991)

Membrane anchoring of tissue factor (TF), the cell receptor for coagulation factor VIIa (VIIa), exemplifies an effective mechanism to localize proteolysis at the cell surface. A recombinant TF mutant (TF1-219), deleted of membrane spanning and intracellular domains, was used to evaluate the role of phospholipid interactions for assembly of substrate with the catalytic TF.VIIa complex. TF1-219 was secreted by cells rather than expressed as a cell membrane protein. Unlike free VIIa, TF1-219 as well as the TF1-219.VIIa complex demonstrated no stable association with phospholipid. In the absence of lipid, kinetic evaluation of substrate factor X cleavage by free VIIa, TF.VIIa, and TF1-219.VIIa suggests that the catalytic function of VIIa rather than substrate recognition is enhanced by complex formation. Furthermore, compared with free factor X, factor X on phospholipid was preferentially cleaved as a substrate by TF1-219.VIIa. TF-dependent initiation of the coagulation protease cascades thus involves an enhancement of the activation of factor X on the cell surface by a crucial role of the TF transmembrane domain to membrane anchor the reaction, by the TF extracellular domain to provide protein-protein interactions with VIIa to enhance the activity of the catalytic domain of VIIa, and the preferential presentation of factor X as a substrate when associated with phospholipid surfaces.
Wavelength-division-multiplexing add/drop multiplexer employing a novel polarisation independent acousto-optic tunable filter (1993)

A wavelength-division-multiplexing add/drop multiplexer (WDM-ADM) employing a novel polarisation independent acousto-optic tunable filter (PI-AOTF) and two optical circulators is proposed. The PI-AOTF consists of only one PBS and one acousto-optic TE-TM mode convertor. The polarisation dependent power fluctuation of the proposed PI-AOTF is less than 1 dB. A 3.2 nm spaced four-channel IM-DD transmission experiment at 622 Mbit/s is demonstrated. The power penalty due to the Doppler shift is 1 dB at a BER of 10−9.
Eukaryotic expression: developments for structural proteomics (2006)

The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe (SPINE) consortium have developed and implemented high-throughput (HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast (Pichia pastoris and Saccharomyces cerevisiae), baculovirus-infected insect cells and transient expression in mammalian cells. Suitable vectors for HTP cloning are described and results from their use in expression screening and protein-production pipelines are reported. Strategies for co-expression, selenomethionine labelling (in all three eukaryotic systems) and control of glycosylation (for secreted proteins in mammalian cells) are assessed.
A Physical Map of 30,000 Human Genes (1998)

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.
Intrinsic gettering in oxygen-free silicon (1985)

We found that a three-step high-temperature annealing leads to intrinsic gettering in oxygen-lean Czochralski silicon grown in a magnetic field as well as in oxygen-free float zone silicon. Such thermal treatment has been used thus far for achieving intrinsic gettering only in oxygen-rich Czochralski silicon. We present experimental characteristics of this new intrinsic gettering process, and we propose a phenomenological explanation involving outdiffusion and precipitation of silicon interstitials rather than oxygen which is involved in the standard intrinsic gettering.
Cover Picture: Discovery of Riociguat (BAY 63‐2521): A Potent, Oral Stimulator of Soluble Guanylate Cyclase for the Treatment of Pulmonary Hypertension (ChemMedChem 5/2009) (2009)

Abstract The cover picture shows a schematic representation of soluble guanylate cyclase (sGC). This key signal‐transduction enzyme is typically found as a heterodimer, consisting of a larger α‐subunit and a smaller haeme‐binding β‐subunit. It is activated by the ubiquitous messenger nitric oxide and catalyzes the conversion of guanosine‐5′‐triphosphate (GTP) into the second messenger cyclic guanosine‐3′,5′‐monophosphate (cGMP). The depicted compound is riociguat, which was identified as a potent, oral sGC stimulator and is currently being investigated in phase III clinical trials for the treatment of pulmonary hypertension. For more details, see the Full Paper by J. Mittendorf et al. on p. 853 ff. magnified image
Effects of graded hypothermia on outcome from brain ischemia (1996)

The effects of mild (34 degrees C) and moderate (31 degrees C) hypothermia on the electroencephalogram, cerebral blood flow and outcome from incomplete brain ischemia were compared to normothermia (37 degrees C) in the rat. Rats were anesthetized with fentanyl (25 mu g kg(-1) h(-1)) and 70 percent nitrous oxide in oxygen. Ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 25 mmHg for 30 min. CBF was measured in the right parietal cortex by laser Doppler. Neurologic outcome was measured daily for 3 days after ischemia and histopathology determined at the end of the study. Before ischemia, neither EEG nor CBF were changed by hypothermia compared to normothermic controls. Total EEG and beta EEG (12.5-32 Hz) were abolished and CBF decreased by 70 percent during ischemia. During a 2.5 h recovery period total EEG and beta EEG activity recovered better with moderate hypothermia compared to normothermia. Recovery of cerebral blood flow was not significantly different between the treatment groups. Neurologic and histopathologic outcome were improved in rats receiving moderate hypothermia compared to normothermic controls. These results show that during severe incomplete ischemia, hypothermia has a graded effect on outcome which is consistent with its effects on brain metabolism.
Vaccinia Virus GLV-1h153 Is Effective in Treating and Preventing Metastatic Triple-Negative Breast Cancer (2012)

This is the first study to demonstrate that TNBCs are killed by a novel vaccinia virus both in vitro and in vivo. Our results suggest that GLV-1h153 is a promising therapeutic agent for preventing and treating metastatic TNBC and warrants further clinical testing in patients.