gebhart/patrepeval huggingface dataset:
Synthesis of antimicrobial nitroimidazolyl 2-sulfides, -sulfoxides, and -sulfones (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of antimicrobial nitroimidazolyl 2-sulfides, -sulfoxides, and -sulfonesRobert C. Tweit, E. M. Kreider, and R. D. MuirCite this: J. Med. Chem. 1973, 16, 10, 1161–1169Publication Date (Print):October 1, 1973Publication History Published online1 May 2002Published inissue 1 October 1973https://pubs.acs.org/doi/10.1021/jm00268a021https://doi.org/10.1021/jm00268a021research-articleACS PublicationsRequest reuse permissionsArticle Views223Altmetric-Citations22LEARN 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
ChIA-PET tool for comprehensive chromatin interaction analysis with paired-end tag sequencing (2010)

Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. Here we present ChIA-PET Tool, a software package for automatic processing of ChIA-PET sequence data, including linker filtering, mapping tags to reference genomes, identifying protein binding sites and chromatin interactions, and displaying the results on a graphical genome browser. ChIA-PET Tool is fast, accurate, comprehensive, user-friendly, and open source (available at http://chiapet.gis.a-star.edu.sg).
Regulation of extracellular matrix synthesis by mechanical stress (1996)

The extracellular matrix (ECM) provides mechanical support to tissues and is a substrate for cell adhesion and differentiation. Cells bind to ECM via specific cell surface receptors such as integrins. When engaging with ECM ligands, these receptors can activate signal transduction pathways within the cells and may act as mechanochemical transducers. Thus, interaction of cells with ECM can modulate gene expression although the exact mechanisms are not known. Among the genes that are, in part, controlled by cell-ECM interactions are those for certain ECM components themselves. Bone cells, for example, remodel their matrix and reorient bone trabeculae in response to mechanical strain. Recently, we found that fibroblasts attached to a strained collagen matrix produce more of the ECM glycoproteins tenascin and collagen XII than cells in a relaxed matrix. In vivo, these two proteins are specifically expressed in places where mechanical strain is high. We also showed that the chick tenascin gene promoter contains a novel cis-acting, "strain-responsive" element that causes enhanced transcription in cells attached to a strained collagen matrix. Similar enhancer elements might be present in the promoters of other genes induced by mechanical stress. It can be speculated that connective tissue cells sense force vectors in their ECM environment and react to altered mechanical needs by regulating the transcription of specific ECM genes; this process is a prerequisite for matrix remodeling.
Characterization of Protein Glycosylation in Francisella tularensis subsp. holarctica (2012)

FTH_0069 is a previously uncharacterized strongly immunoreactive protein that has been proposed to be a novel virulence factor in Francisella tularensis. Here, the glycan structure modifying two C-terminal peptides of FTH_0069 was identified utilizing high resolution, high mass accuracy mass spectrometry, combined with in-source CID tandem MS experiments. The glycan observed at m/z 1156 was determined to be a hexasaccharide, consisting of two hexoses, three N-acetylhexosamines, and an unknown monosaccharide containing a phosphate group. The monosaccharide sequence of the glycan is tentatively proposed as X-P-HexNAc-HexNAc-Hex-Hex-HexNAc, where X denotes the unknown monosaccharide. The glycan is identical to that of DsbA glycoprotein, as well as to one of the multiple glycan structures modifying the type IV pilin PilA, suggesting a common biosynthetic pathway for the protein modification. Here, we demonstrate that the glycosylation of FTH_0069, DsbA, and PilA was affected in an isogenic mutant with a disrupted wbtDEF gene cluster encoding O-antigen synthesis and in a mutant with a deleted pglA gene encoding pilin oligosaccharyltransferase PglA. Based on our findings, we propose that PglA is involved in both pilin and general F. tularensis protein glycosylation, and we further suggest an inter-relationship between the O-antigen and the glycan synthesis in the early steps in their biosynthetic pathways.
Ion Microprobe Mass Analyzer (1967)

This paper describes the development of an instrument which is analogous to an electron microprobe x-ray analyzer, whereby the electron microprobe is replaced by an ion microprobe, and the x-ray spectrometer by a mass spectrometer. A duoplasmatron is the primary ion source. The primary ion beam is mass separated to eliminate impurity ions. A probe diameter of less than 2 μ at 2×10−10 A is realized for 12-kV Ar+ ions. A new mass spectrometer was developed with the emphasis on high transmission, yet simple construction. It is stigmatic imaging, double focusing, has a mass-resolving power of 300 with a solid acceptance angle of 1.5×10−2 sr (4° half-angle) and a transmitted-energy bandwidth of 10%. It consists of an axially symmetrical electrostatic Einzel lens, a 45° spherical condenser sector, and a magnetic field with plane but inclined pole faces, which deflects the beam by 90°. No entrance slit is used. Experimental results are presented.
A Nearly Four-Year Longitudinal Study of Search-Engine Poisoning (2014)

We investigate the evolution of search-engine poisoning using data on over 5 million search results collected over nearly 4 years. We build on prior work investigating search-redirection attacks, where criminals compromise high-ranking websites and direct search traffic to the websites of paying customers, such as unlicensed pharmacies who lack access to traditional search-based advertisements. We overcome several obstacles to longitudinal studies by amalgamating different resources and adapting our measurement infrastructure to changes brought by adaptations by both legitimate operators and attackers. Our goal is to empirically characterize how strategies for carrying out and combating search poisoning have evolved over a relatively long time period. We investigate how the composition of search results themselves has changed. For instance, we find that search-redirection attacks have steadily grown to take over a larger share of results (rising from around 30% in late 2010 to a peak of nearly 60% in late 2012), despite efforts by search engines and browsers to combat their effectiveness. We also study the efforts of hosts to remedy search-redirection attacks. We find that the median time to clean up source infections has fallen from around 30 days in 2010 to around 15 days by late 2013, yet the number of distinct infections has increased considerably over the same period. Finally, we show that the concentration of traffic to the most successful brokers has persisted over time. Further, these brokers have been mostly hosted on a few autonomous systems, which indicates a possible intervention strategy.
PCR-based site-specific mutagenesis of peptide antibiotics FALL-39 and its biologic activities. (2004)

PCR-based mutagenesis is a useful model system for studying the structure and function relationship of antimicrobial peptides. Keeping a-helical conformation of FALL-39 and increasing net positive charge can increase the antibacterial activity of FALL-39 without increasing hemolysis at the antibacterial concentrations.
Emerging influenza viruses and the prospect of a universal influenza virus vaccine (2015)

Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses.
Interaction of a Simian Papovavirus and Adenoviruses I. Induction of Adenovirus Tumor Antigen During Abortive Infection of Simian Cells (1966)

Feldman, Lawrence A. (Baylor University College of Medicine, Houston, Tex.), Janet S. Butel, and Fred Rapp. Interaction of a simian papovavirus and adenoviruses. I. Induction of adenovirus tumor antigen during abortive infection of simian cells. J. Bacteriol. 91:813-818. 1966.-Adenovirus types 2, 7, and 12 undergo an abortive growth cycle in green monkey kidney cells; they induce the formation of adenovirus tumor antigen, but synthesis of adeno capsid antigen and infectious adenovirus was observed only when cultures were concomitantly infected with a simian papovavirus (SV40). Several other viruses, including herpes simplex and measles which replicate in monkey cells, and rabbit papilloma and human wart papovaviruses which do not, failed to stimulate adenovirus replication in the monkey cells. Adenovirus tumor antigen was detected 8 to 10 hr postinfection by immunofluorescent techniques. The antigen induced by adenovirus types 2 and 7 appeared as intranuclear masses; adenovirus type 12 tumor antigen also appeared as cytoplasmic and nuclear flecks. Sera from hamsters bearing tumors induced by adenovirus type 12 cross-reacted with tumor antigens induced by types 2 and 7 but not with antigens induced by SV40.
Detection of secreted peptides by using hypothesis-driven multistage mass spectrometry (2003)

A method is presented for the rapid detection and characterization of trace amounts of peptides secreted from microorganisms, including pheromones, virulence factors, and quorum-sensing peptides. The procedure, based on targeted multistage MS, uses a novel matrix-assisted laser desorptionionization-ion trap mass spectrometer to overcome limitations of current MS methods (limited dynamic range, signal suppression effects, and chemical noise) that impair observation of low abundance peptides from complex biological matrixes. Here, secreted peptides that are hypothesized to be present in the supernatant, but that may not be sufficiently abundant to be observed in single-stage mass spectra, are subjected to multistage MS. Highly specific fragmentation signatures enable unambiguous identification of the peptides of interest and differentiation of the signals from the background. As examples, we demonstrate the rapid (<1 min) determination of the mating type of cells in colonies of Saccharomyces cerevisiae and the elucidation of autoinducing peptides (AIPs) from supernatants of pathogenic Staphylococci. We confirm the primary structures of the agrD encoded cyclic AIPs of Staphylococcus aureus for groups I, II, and IV and provide direct evidence that the native group-III AIP is a heptapeptide (INCDFLL). We also show that the homologous peptide from Staphylococcus intermedius is a nonapeptide (RIPTSTGFF) with a lactone ring formed through condensation of the serine side chain with the C terminus of the peptide. This is the first demonstration of cyclization in a staphylococcal AIP that occurs via lactone formation. These examples demonstrate the analytical power of the present procedure for characterizing secreted peptides and its potential utility for identifying microorganisms.
Strategies for dielectrophoretic separation in laboratory-on-a-chip systems (2002)

Dielectrophoresis – the induced motion of polarizable particles in nonuniform fields – has proven to be an effective method for the separation of bioparticles such as cells, viruses and proteins. In this paper, the application of dielectrophoresis in miniaturized laboratories-on-a-chip is discussed, and strategies are described for using dielectrophoresis both for the binary separation of bioparticles and for the fractionation of many populations in such devices.
Rat kidney glutamyl aminopeptidase (aminopeptidase A): molecular identity and cellular localization (1994)

Glutamyl aminopeptidase [aminopeptidase A (EAP), EC 3.4.11.7] is an ectoenzyme that selectively hydrolyzes acidic amino acid residues from the amino terminus of oligopeptides. EAP activity is highest within the kidney and small intestine. The murine pre-B cell BP-1/6C3 and the human kidney glycoprotein gp160 differentiation antigens have been reported to have biochemical properties indistinguishable from EAP. It is not known, however, if rat kidney EAP is a homologue of these antigens or molecularly distinct. Using the reverse transcription-polymerase chain reaction method with oligonucleotide primers based on the BP-1/6C3 nucleotide sequence, we isolated a 450-bp partial cDNA from rat kidney poly(A)+ RNA. The partial cDNA encoded a predicted protein that was 92% and 86% identical to the murine BP-1/6C3 and human gp160 antigens, respectively; the amino acid sequence within the zinc-binding domain was completely conserved. Purification of EAP from rat kidney and microsequence analysis of a tryptic digest peptide fragment (18-mer) indicated that the fragment was highly similar to a region within the BP-1/6C3 and gp160 proteins. Northern blot hybridization and immunoblot analyses were also consistent with labeling of products the same size as reported for the BP-1/6C3 and gp160 antigens. There was a good correlation between the cellular distribution of EAP mRNA and EAP immunoreactivity, with proximal tubules and glomerular mesangial cells having the highest densities. These results indicate that rat kidney EAP is a species homologue of the murine BP-1/6C3 and human gp160 antigens. Furthermore, on the basis of its cellular localization, rat kidney EAP is likely to be involved in degradation of oligopeptides within the glomerulus and the glomerular filtrate. Since cells that express EAP also express receptors for angiotensin II, an intrarenal vasoactive hormone that is a substrate for EAP, these results further suggest that EAP may play a role in modulating the activity of intrarenal angiotensin II.
Survival during exposure to the electrophilic reagent N-ethylmaleimide in Escherichia coli: role of KefB and KefC potassium channels (1997)

The role of the KefB and KefC potassium efflux systems in protecting Escherichia coli cells against the toxic effects of the electrophile N-ethylmaleimide has been investigated. Activation of KefB and KefC aids the survival of cells exposed to high concentrations (> 100 microM) of NEM. High potassium concentrations reduce the protection afforded by activation of KefB and KefC, but the possession of these systems is still important under these conditions. The Kdp system, which confers sensitivity to the electrophile methylglyoxal, did not affect the survival of cells exposed to NEM. Survival is correlated with the reduction of the cytoplasmic pH upon activation of the channels. In particular, the kinetics of the intracellular pH (pHi) change are crucial to the retention of viability of cells exposed to NEM; slow acidification does not protect cells as effectively as rapid lowering of pHi. Cells treated with low levels of NEM (10 microM) recover faster if they activate KefB and KefC, and this correlates with changes in pHi. The pHi does not significantly alter the rate of NEM metabolism. The possible mechanisms by which protection against the electrophile is mediated are discussed.
Renewable Acrylic Acid (2012)

Acrylic acid is an important industrial chemical, used as a raw material in a wide variety of consumer end products. The present predominant source of acrylic acid is from the partial oxygenation of propene, produced as a by-product in the industrial production of ethylene and gasoline. Both processes depend heavily on the processing of petrochemicals as the base raw material. The purpose of this process is to produce acrylic acid from renewable carbon sources (such as corn or sugarcane) in an economically preferential manner. Our process has used genetically recombinant Escherichia coli (E. coli) to ferment the carbohydrate content of the proposed feedstock to 3-hydroxypropionic acid (3-HP) which is then dehydrated in the presence of strong acid catalyst (phosphoric acid) to form acrylic acid. The acrylic acid is then purified to the standard required for use as a polymer raw material (99.98% by mass) with total capacity of 160,000 MT/year of product.\nThis design analyzes two proposed locations, the US Midwest or Brazil, and their associated renewable feedstocks, corn or sugarcane juice, respectively. This report investigates the relative economic attractiveness of each option. The US case requires location near an existing industrial ethanol fermentation plant to give easy access to dry-ground corn as a carbohydrate source. This case yields an IRR of 17.56% and an overall NPV of $35.2 million at a 15% discount rate. The Brazil case has comparatively cheaper feedstock, however because of seasonality and total usable carbohydrate content, it requires a greater mass of feedstock and increased capital investment relative to the US case. The NPV difference of the two cases is extremely sensitive to the assumed price of sugarcane juice which has recently shown extraordinary volatility. Based on this analysis, the US location seems most promising; however, detailed laboratory level studies are needed to confirm the profitability and assumptions made.
Maturation of the gut microbiome and risk of asthma in childhood (2018)

The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children.
Sitagliptin with metformin: Profile of a combination for thetreatment of type 2 diabetes (2007)

Sitagliptin, a novel orally-active dipeptidyl-peptidase (DPP-4) inhibitor has been introduced into type 2 diabetes therapy. Sitagliptin inhibits the degradation of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), as well as that of other regulatory peptides important for glucose homeostasis. It reduces haemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose- dependent stimulation of insulin secretion and inhibition of glucagon secretion. Sitagliptin is weight neutral. Indirect measures show a possible improvement of beta-cell function. Sitagliptin does not cause hypoglycemia when compared to metformin or placebo. Metformin, which has a different unique mechanism, has been used in type 2 diabetes for approximately 50 years. Metformin improves insulin resistance and is the first-line antidiabetic drug in use today. The combination of a DPP-4 inhibitor with metformin allows a broad and complementary spectrum of antidiabetic actions. This combination does not increase the risk of hypoglycaemia nor does it promote weight gain, an adverse effect of various other oral antidiabetic combinations. This article gives an overview of the data available on the combined antidiabetic effects of metformin and sitagliptin.
The relative densities of pharmaceutical powders, blends, dry granulations, and immediate-release tablets (2003)

The absolute and relative densities of pharmaceutical solids play an important role in determining their performance (e.g., flow and compaction properties) in both tablet and capsule dosage forms. In this article, the authors report the densities of a wide variety of solid pharmaceutical formulations and intermediates. The variance of density with chemical structure, processing history, and dosage-form type is significant.This study shows that density can be used as an equipment-independent scaling parameter for several common drug-product manufacturing operations.
Formation of Pmel17 Amyloid Is Regulated by Juxtamembrane Metalloproteinase Cleavage, and the Resulting C-terminal Fragment Is a Substrate for γ-Secretase (2008)

The formation of insoluble cross beta-sheet amyloid is pathologically associated with disorders such as Alzheimer, Parkinson, and Huntington diseases. One exception is the nonpathological amyloid derived from the protein Pmel17 within melanosomes to generate melanin pigment. Here we show that the formation of insoluble MalphaC intracellular fragments of Pmel17, which are the direct precursors to Pmel17 amyloid, depends on a novel juxtamembrane cleavage at amino acid position 583 between the furin-like proprotein convertase cleavage site and the transmembrane domain. The resulting Pmel17 C-terminal fragment is then processed by the gamma-secretase complex to release a short-lived intracellular domain fragment. Thus, by analogy to the Notch receptor, we designate this cleavage the S2 cleavage site, whereas gamma-secretase mediates proteolysis at the intramembrane S3 site. Substitutions or deletions at this S2 cleavage site, the use of the metalloproteinase inhibitor TAPI-2, as well as small interfering RNA-mediated knock-down of the metalloproteinases ADAM10 and 17 reduced the formation of insoluble Pmel17 fragments. These results demonstrate that the release of the Pmel17 ectodomain, which is critical for melanin amyloidogenesis, is initiated by S2 cleavage at a juxtamembrane position.
Development of a diphtheria toxin mutant conjugate directed against antigen-specific B cells expressing high affinity surface Ig. (1990)

Modification of a mutant diphtheria toxin, possessing reduced binding capacity, with TNP groups resulted in an Ag-toxin conjugate capable of eliminating TNP-specific B cells. Previous experimental approaches to the elimination of Ag-specific B cells have involved the conjugation of Ag to holoricin molecules or ricin A chain. Holoricin conjugates possess efficacy, but display high nonspecific toxicity. A chain conjugates, which appear specific, lack high potency. In developing the diphtheria toxin-based conjugate, we found high potency for target anti-TNP hybridoma cells and for spleen cells isolated from TNP-immunized mice. The similar intoxication of nontarget cells required concentrations approximately three orders of magnitude higher. Additionally, it was found that the TNP-specific agent may have selectively depleted B cells producing high affinity IgG anti-TNP antibodies.