gebhart/patrepeval huggingface dataset:
Facile Conversion of Cysteine and Alkyl Cysteines to Dehydroalanine on Protein Surfaces: Versatile and Switchable Access to Functionalized Proteins (2008)

An efficient and robust oxidative elimination of cysteine to dehydroalanine has been discovered. The reaction is induced by O-mesitylenesulfonylhydroxylamine (MSH) and is compatible with methionine. The key elimination has been executed on protein surfaces and allows ready access to different post-translationally modified proteins through conjugate addition of sulfur nucleophiles to dehydroalanine. Treatment of the resulting thioether with MSH results in regeneration of dehydroalanine, allowing a "functional switch" by subsequent addition of a different thiol.
C2‐Symmetrical Thiodigalactoside Bis‐Benzamido Derivatives as High‐Affinity Inhibitors of Galectin‐3: Efficient Lectin Inhibition through Double Arginine–Arene Interactions (2005)

Inhibitoren von Galectin-3, das mit Krebs und Immunität in Zusammenhang gebracht wird, können aus Thiodigalactosid-Derivaten mit aromatischen Amidsubstituenten an beiden C3-Positionen (siehe Formel) erhalten werden. Dissoziationskonstanten Kd bis herunter zu 33 nM wurden bestimmt. Modeling-Studien legten nahe, dass diese hohe Affinität ihren Grund in doppelten Arginin-Aren-Stapelwechselwirkungen hat. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2005/z500627_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Coexpression of keratin- and vimentin-type intermediate filaments in human metastatic carcinoma cells. (1983)

Metastatic tumor cells of epithelial origin present in effusions from human serous cavity fluids (ascites or pleural fluid) were examined for their intermediate-sized filament types by using antibodies to keratin, vimentin, and desmin in the indirect immunofluorescence technique. Solid epithelial tumors (both primary carcinomas and their metastases) contain keratin intermediate-sized filaments exclusively. However, when these cells are present in ascitic or pleural fluid, they also express vimentin, which occurs in a fibrillar organization. The possible effects of this additional, but temporary, cytoskeleton on metastatic growth or aggressiveness (or both) are discussed.
Hepatocyte Growth Factor Suppresses the Onset of Liver Cirrhosis and Abrogates Lethal Hepatic Dysfunction in Rats1 (1995)

Heptic fibrosis/cirrhosis is a common hepatic disease characterized by the hyper-accumulation of connective tissue components, and hepatic necrosis. Chronic alcohol ingestion, viral infection, and metabolic disorders are contributing factors and there has been no effective treatment. Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is a long-sought hepatotrophic factor for liver regeneration. Administration of human recombinant HGF into rats with hepatic fibrosis/cirrhosis caused by dimethylnitrosamine (DMN) elicited mitogenic action for hepatocytes, stimulated hepatic collagenase activity, and prevented the onset and progression of hepatic fibrosis/cirrhosis. Accumulation of fibrous tissue components in the liver due to DMN-treatment were markedly decreased in HGF-injected rats. Moreover, HGF completely abrogated death caused by severe hepatic cirrhosis and dysfunction. We postulate that HGF may prove to be an effective treatment for human liver fibrosis/cirrhosis and for chronic hepatic failure.
Floating-point division algorithms for an x86 microprocessor with a rectangular multiplier (2007)

Floating-point division is an important operation in scientific computing and multimedia applications. This paper presents and compares two division algorithms for an times86 microprocessor, which utilizes a rectangular multiplier that is optimized for multimedia applications. The proposed division algorithms are based on Goldschmidt's division algorithm and provide correctly rounded results for IEEE 754 single, double, and extended precision floating-point numbers. Compared to a previous Goldschmidt division algorithm, the fastest proposed algorithm requires 25% to 37% fewer cycles, while utilizing a multiplier that is roughly 2.5 times smaller.
Microarrays as a tool to identify untagged deletions in rice. (2007)

The rice lesion mimic mutant spl1, which spontaneously exhibits necrotic lesions, shows enhanced resistance to important rice pathogens, including Magnaporthe grisea (rice blast) and Xanthomonas oryzae pv. oryzae (bacterial blight). Many lesion mimic mutants, which have been discovered in plant species including Arabidopsis, Zea mays, Hordeum vulgare and Triticum sp., show enhanced resistance to pathogen invasion. To study the molecular basis for the broad spectrum resistance exhibited by the rice spl1 mutant, we examined changes in gene expression and initiated work to identify the gene causing the phenotype.
The Lapidus Procedure: A Prospective Cohort Outcome Study (2004)

The Lapidus procedure obviously is not the answer to all bunion deformities, but with proper technique and attention to detail it is an excellent alternative treatment for moderate to severe metatarsus primus varus and hallux valgus deformities.
Hypercholesterolaemia, atherosclerosis and release of endothelium-derived relaxing factor by aggregating platelets (1991)

In pig coronary arteries atherosclerosis developed progressively after an experimental mechanical injury to the endothelium, despite its regeneration. The atherosclerotic process can be considerably accelerated by a high cholesterol diet. In arteries with regenerated endothelium, there is a reduction of endothelium-dependent relaxations mediated by (a) pertussis toxin-sensitive G protein(s). As this includes the response to platelet-derived serotonin, the ability of the regenerated endothelium to prevent abnormal vasoconstrictions (and presumably to feedback on platelet aggregation) in response to aggregating platelets is seriously curtailed. These changes are exacerbated in atherosclerotic arteries. Bioassay studies demonstrate that reduced endothelium-dependent relaxations are due mainly to a reduced release of endothelium-derived relaxing factor. Thus, endothelial dysfunction, in particular the reduced ability to release endothelium-derived relaxing factor, is a key factor in determining the abnormal responsiveness of the atherosclerotic blood vessel wall.
Modulation of serum cytokine levels by a novel superoxide dismutase mimetic, M40401, in an Escherichia coli model of septic shock: Correlation with preserved circulating catecholamines* (2003)

Postinfection treatment with the superoxide dismutase mimetic M40401 protects against hypotension, vascular hyporeactivity to catecholamines, and mortality associated with septic shock. Such beneficial effects correlate with both reduced oxidative inactivation of serum catecholamines and a reduction in canonical cytokine mediators of inflammation.
Modes of action and inhibitory activities of new siderophore-beta-lactam conjugates that use specific iron uptake pathways for entry into bacteria (1992)

We describe here the mechanism of inhibition of two new siderophore-beta-lactam conjugates against Escherichia coli X580. One conjugate is a spermidine-based catechol siderophore-carbacephalosporin (JAM-2-263), and the other is an N5-acetyl-N5-hydroxy-L-ornithine tripeptide hydroxamate siderophore-carbacephalosporin (EKD-3-88). In an agar diffusion test, both conjugates produced large inhibitory zones against strain X580. Resistant strains (i.e., JAMR and EKDR) could be isolated after exposure of X580 to the conjugates JAM-2-263 and EKD-3-88, respectively. No cross-resistance was observed in these individual isolates. JAMR and EKDR were studied further to elucidate the mechanism of inhibition of each conjugated drug. The affinities of JAM-2-263 and EKD-3-88 for penicillin-binding proteins (PBPs) of isolated inner membranes were determined by a competition assay with 125I-penicillin V. JAM-2-263 targeted primarily PBPs 1A/B and 5/6, while EKD-3-88 targeted PBPs 1A/B and 3. Strains X580, JAMR, and EKDR showed similar PBP affinities for the conjugates. However, marked changes were observed in the iron-regulated outer membrane proteins of resistant isolates grown on agar plates depleted of iron. EKDR lost the expression of FhuA (78 kDa) and its sensitivity to phages T1 and T5, whereas JAMR lost the expression of Cir (74 kDa) and its sensitivity to colicin Ia. These results revealed the requirement of FhuA and Cir for the inhibitory activities of EKD-3-88 and JAM-2-263, respectively. In an antibiotic diffusion assay, ferrichrome (1 microM) strongly antagonized the activities of both conjugates against X580 and JAMR, including the residual activity of JAM-2-263 against JAMR. However, the susceptibility of strain EKDR lacking the ferrichrome receptor (FhuA-) to the two conjugates remained the same in the presence of ferrichrome. The antagonistic effect of ferrichrome on the activity of JAM-2-263 may also indicate a role for FhuA in the activity of this beta-lactam conjugate. A FhuA- Cir- double mutant confirmed this hypothesis, since it showed a higher level of resistance to JAM-2-263. To reproduce iron-restricted in vivo growth conditions, we grew X580 and EKDR cells in diffusion chambers implanted in the peritoneal cavities of rats. Strain EKDR showed impaired growth in such a cultivation system. This is the first report of beta-lactam drug transport into E. coli cells that involves the FhuA outer membrane protein.
Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses (2017)

The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC<sub>50</sub> = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.
The Intercellular Adhesion ( ica ) Locus Is Present in Staphylococcus aureus and Is Required for Biofilm Formation (1999)

Nosocomial infections that result in the formation of biofilms on the surfaces of biomedical implants are a leading cause of sepsis and are often associated with colonization of the implants by Staphylococcus epidermidis. Biofilm formation is thought to require two sequential steps: adhesion of cells to a solid substrate followed by cell-cell adhesion, creating multiple layers of cells. Intercellular adhesion requires the polysaccharide intercellular adhesin (PIA), which is composed of linear beta-1,6-linked glucosaminylglycans and can be synthesized in vitro from UDP-N-acetylglucosamine by products of the intercellular adhesion (ica) locus. We have investigated a variety of Staphylococcus aureus strains and find that all strains tested contain the ica locus and that several can form biofilms in vitro. Sequence comparison with the S. epidermidis ica genes revealed 59 to 78% amino acid identity. Deletion of the ica locus results in a loss of the ability to form biofilms, produce PIA, or mediate N-acetylglucosaminyltransferase activity in vitro. Cross-species hybridization experiments revealed the presence of icaA in several other Staphylococcus species, suggesting that cell-cell adhesion and the potential to form biofilms is conserved within this genus.
Localization of heparanase in normal and pathological human placenta (2002)

Degradation of extracellular matrix (ECM) components is critical for invasion. Heparan sulphate proteoglycans are abundant in the ECM of the placenta and the decidua, hence their degradation may disassemble the matrix and facilitate placentation and trophoblast invasion. This study investigates the expression of heparanase in normal and pathological placentation using RT-PCR, in-situ hybridization and immunohistochemistry analysis to detect heparanase in specific cells of the placenta and at the fetal-maternal interface throughout pregnancy. Heparanase was observed in villous cytotrophoblasts (CT), syncytial trophoblasts (ST) and in intermediate trophoblast cell columns in normal first trimester, molar and ectopic pregnancies. The heparanase protein was preferentially expressed in the endothelium of fetal capillaries, and to a much lesser extent in larger fetal vessels. Extravillous trophoblasts (EVT) invading the decidua and the maternal vessels were also heparanase positive. In the second and third trimesters, villous CT remained heparanase positive whereas ST showed variable heparanase expression. EVT invading the placental implantation site were also positively stained. A similar pattern was observed in samples obtained from pre-eclamptic placentae and from placenta accreta. Our results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials.
Development and comparison of SYBR Green quantitative real-time PCR assays for detection and enumeration of sulfate-reducing bacteria in stored swine manure (2008)

The PCR assays described here provide improved and efficient molecular tools for quantitative detection of SRB populations. This is the first study to show population shifts of SRB in swine manure, which are a result of either the effects of swine diets or the maturity of the manure ecosystem.
Emergence of the Ehrlichioses as Human Health Problems (1996)

Ehrlichiae are small, gram-negative, obligately intracellular bacteria that reside within a phagosome. The first human ehrlichial infection was recognized in the United States in 1987. It was later shown to be caused by a new species, Ehrlichia chaffeensis. In 1994, an ehrlichial pathogen within neutrophils that is closely related to the known veterinary pathogens E. equi and E. phagocytophila was found to infect humans. Molecular methods were required to detect, characterize, and identify these fastidious and uncultivated bacteria. Subsequently, E. chaffeensis infection was documented in more than 400 patients in 30 states, Europe, and Africa. Likewise, approximately 170 cases of human granulocytic ehrlichiosis have been diagnosed, most since 1994, predominantly in the upper midwestern and northeastern states, but also in northern California. The disease caused by ehrlichiae is generally undifferentiated but is often associated with leukopenia, thrombocytopenia, and elevated serum hepatic transaminase levels in tick-exposed patients. Infection ranges from subclinical to fatal; tetracycline appears to be an effective therapy. The emergence of these two newly recognized tickborne infections as threats to human health is probably due to increased clinical cognizance, but as in other emerging tickborne infections, it is likely that the rapid increase in identified cases signals a true emergence of disease associated with a changing vector-host ecology.
Scheduling Cluster Tools With Ready Time Constraints for Consecutive Small Lots (2012)

In the semiconductor manufacturing industry, the lot size currently tends to be extremely small, even being only 5-8 wafers, whereas conventional lots have 25 identical wafers. The smaller lot size is made because customers demand extremely small lots, and the number of chips in a large 300 mm wafer has increased. Cyclic scheduling is not applicable for such small lot production because the number of identical work cycles accounts for a small proportion of scheduling as compared to the lengths of the starting and closing transient periods. We therefore examine a new noncyclic scheduling problem of cluster tools for small lot production that considers ready time constraints on the chambers and the robot. The ready times are the epochs when the resources are freed from processing the preceding lot. To solve the scheduling problem, we develop a Petri net model which is a graphical and mathematical method for discrete event dynamic systems. Based on the Petri net model, we also develop a mixed integer programming (MIP) model and a branch and bound (B&B) algorithm for determining an optimal schedule. The B&B algorithm solves lots with up to 25 wafers and eight wafers within 500 s for a single-armed cluster tool and a dual-armed cluster tool, respectively, when three process steps are considered. Therefore, we propose an approximation method for the dual-armed cluster tool that schedules only the first few wafers with the B&B algorithm and the succeeding wafers with a well-known cyclic sequence. From experiments, we conclude that the difference between the approximation method and an optimal makespan is less than 1%. The methods we propose can be used for general noncyclic scheduling problems that can be modeled by Petri nets.
Curing of R plasmids present in gram negative bacteria isolated from poultry in Karachi by ethidium bromide. (1997)

R plasmids of Gram negative bacteria isolated from poultry in Karachi were studied for their curing by ethidium bromide (EBr) in E. coli AB 712. Of 12 R plasmids studied, 3 were lost by treatment with ethidium bromide.
Defining Desirable Central Nervous System Drug Space through the Alignment of Molecular Properties, in Vitro ADME, and Safety Attributes (2010)

As part of our effort to increase survival of drug candidates and to move our medicinal chemistry design to higher probability space for success in the Neuroscience therapeutic area, we embarked on a detailed study of the property space for a collection of central nervous system (CNS) molecules. We carried out a thorough analysis of properties for 119 marketed CNS drugs and a set of 108 Pfizer CNS candidates. In particular, we focused on understanding the relationships between physicochemical properties, in vitro ADME (absorption, distribution, metabolism, and elimination) attributes, primary pharmacology binding efficiencies, and in vitro safety data for these two sets of compounds. This scholarship provides guidance for the design of CNS molecules in a property space with increased probability of success and may lead to the identification of druglike candidates with favorable safety profiles that can successfully test hypotheses in the clinic.
A Critical Threshold of Rehabilitation Involving Brain-Derived Neurotrophic Factor Is Required for Poststroke Recovery (2011)

Data suggest that there is a critical threshold of rehabilitation, below which recovery will not occur, and that BDNF mediates functional recovery. The use of intensive rehabilitation therapies for stroke patients is strongly supported.
Solid-Supported Synthesis of Imidazoles:  A Strategy for Direct Resin-Attachment to the Imidazole Core (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSolid-Supported Synthesis of Imidazoles: A Strategy for Direct Resin-Attachment to the Imidazole CoreMark T. Bilodeau and April M. CunninghamView Author Information Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486 Cite this: J. Org. Chem. 1998, 63, 9, 2800–2801Publication Date (Web):April 7, 1998Publication History Received9 January 1998Published online7 April 1998Published inissue 1 May 1998https://pubs.acs.org/doi/10.1021/jo980027phttps://doi.org/10.1021/jo980027prapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1254Altmetric-Citations78LEARN 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 SUBJECTS:Alcohols,Imidazoles,Organic polymers,Phenyls,Substituents Get e-Alerts
Methionyl-tRNA synthetase gene from an extreme thermophile, Thermus thermophilus HB8. Molecular cloning, primary-structure analysis, expression in Escherichia coli, and site-directed mutagenesis. (1991)

The gene for the methionyl-tRNA synthetase (MetRS) from an extreme thermophile, Thermus thermophilus HB8, was cloned and sequenced. By expression of the T. thermophilus MetRS gene in Escherichia coli cells, thermostable MetRS was overproduced and purified to homogeneity by heat treatment and one-step column chromatography. The amino acid sequence of T. thermophilus MetRS showed low identities (approximately 25%) with those of MetRSs from E. coli, and cytoplasm and mitochondria of Saccharomyces cerevisiae. However, the amino acid residues in the binding sites for ATP and the anticodon and the 3' terminus of tRNA(Met) are highly conserved among the four MetRSs. T. thermophilus MetRS has a zinc finger-like sequence with all the three cysteine residues and a histidine residue. By site-directed mutagenesis of one of the cysteine residues (Cys127) of T. thermophilus MetRS, the SH group was found to be important for methionyl-tRNA synthesis. Just upstream of the structural gene for T. thermophilus MetRS there is a short open reading frame which codes for a methionine-rich peptide and is partly overlapped with an alternative terminator/antiterminator structure, suggesting that transcription of this gene is regulated by attenuation. Further upstream a region contains a nucleotide sequence homologous to that of the 5' half of T. thermophilus initiator tRNA(Met).
Robust anisotropic diffusion (1998)

Relations between anisotropic diffusion and robust statistics are described in this paper. Specifically, we show that anisotropic diffusion can be seen as a robust estimation procedure that estimates a piecewise smooth image from a noisy input image. The "edge-stopping" function in the anisotropic diffusion equation is closely related to the error norm and influence function in the robust estimation framework. This connection leads to a new "edge-stopping" function based on Tukey's biweight robust estimator that preserves sharper boundaries than previous formulations and improves the automatic stopping of the diffusion. The robust statistical interpretation also provides a means for detecting the boundaries (edges) between the piecewise smooth regions in an image that has been smoothed with anisotropic diffusion. Additionally, we derive a relationship between anisotropic diffusion and regularization with line processes. Adding constraints on the spatial organization of the line processes allows us to develop new anisotropic diffusion equations that result in a qualitative improvement in the continuity of edges.