gebhart/patrepeval huggingface dataset:
The pharmacokinetics of quinupristin/dalfopristin in laboratory animals and in humans (1997)

The pharmacokinetics of quinupristin/dalfopristin have been studied in rats, monkeys and humans following intravenous infusion of radiolabelled and unlabelled drug. In rats and monkeys quinupristin and dalfopristin undergo rapid elimination from the blood and wide tissue distribution. Nevertheless, they do not penetrate the central nervous system or cross the placenta to any significant degree and they do not appear to be subject to significant body retention following cessation of administration. The blood elimination half-life of quinupristin was approximately 0.6 h in rats and 0.5 h in monkeys, and that of dalfopristin was approximately 0.6 h and 0.2 h, respectively. Both compounds are primarily eliminated through the bile into the faeces; quinupristin is mainly excreted unchanged whereas dalfopristin is extensively metabolized beforehand. The metabolites include the microbiologically active pristinamycin PIIA for dalfopristin and the microbiologically active glutathione- and cysteine-conjugated derivatives for quinupristin. Quinupristin and dalfopristin appear to be handled in a similar manner by humans. Following intravenous administration both compounds are rapidly cleared from the blood with elimination half-lives of approximately 1 h for quinupristin and 0.4-0.5 h for dalfopristin. The pharmacokinetic profile of quinupristin is dose-independent and so is that of dalfopristin and RP 12536 when considered together. Extravascular diffusion of quinupristin/dalfopristin has been assessed in human non-inflammatory interstitial fluid.
Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. (1997)

This study explores the role of mevalonate inhibitors in the activation of NF-kbeta and the induction of inducible nitric oxide synthase (iNOS) and cytokines (TNF-alpha, IL-1beta, and IL-6) in rat primary astrocytes, microglia, and macrophages. Lovastatin and sodium phenylacetate (NaPA) were found to inhibit LPS- and cytokine-mediated production of NO and expression of iNOS in rat primary astrocytes; this inhibition was not due to depletion of end products of mevalonate pathway (e.g., cholesterol and ubiquinone). Reversal of the inhibitory effect of lovastatin on LPS-induced iNOS expression by mevalonate and farnesyl pyrophosphate and reversal of the inhibitory effect of NaPA on LPS-induced iNOS expression by farnesyl pyrophosphate, however, suggests a role of farnesylation in the LPS-mediated induction of iNOS. The inhibition of LPS-mediated induction of iNOS by FPT inhibitor II, an inhibitor of Ras farnesyl protein transferase, suggests that farnesylation of p21(ras) or other proteins regulates the induction of iNOS. Inhibition of LPS-mediated activation of NF-kbeta by lovastatin, NaPA, and FPT inhibitor II in astrocytes indicates that the observed inhibition of iNOS expression is mediated via inhibition of NF-kbeta activation. In addition to iNOS, lovastatin and NaPA also inhibited LPS-induced expression of TNF-alpha, IL-1beta, and IL-6 in rat primary astrocytes, microglia, and macrophages. This study delineates a novel role of the mevalonate pathway in controlling the expression of iNOS and different cytokines in rat astrocytes, microglia, and macrophages that may be important in developing therapeutics against cytokine- and NO-mediated neurodegenerative diseases.
Magnetic Resonance Imaging of the Wrist (2001)

Optimal magnetic resonance (MR) imaging of the wrist requires a high field strength magnet and a dedicated wrist coil to achieve high-resolution images. Using current MR sequences, detailed images of articular cartilage and the supporting ligaments and tendons can be obtained. Evaluation of the triangular fibrocartilage as well as the extrinsic and intrinsic ligaments of the wrist is possible with thin-slice three-dimensional volumetric gradient recalled sequences. Fast inversion recovery sequences, used to achieve fat suppression in peripheral joints such as the wrist, allow for detection of acute osseous trauma, which is often radiographically occult. Cartilage-sensitive imaging allows for evaluation of conditions in the skeletally immature patient, such as chronic physeal loading in the adolescent gymnast, as well as detection of the sequelae of altered biomechanics in the adult, as in the ulnolunate impaction syndrome. Moreover, contrast-enhanced magnetic resonance angiography permits a relatively noninvasive evaluation of peripheral vascular disease, obviating the need for an intraarticular injection.
20nm gate bulk-finFET SONOS flash (2006)

High-performance FinFET SONOS (silicon-oxide-nitride-oxide-silicon) flash cells with gate length down to 20nm have been fabricated and operated successfully on bulk-silicon substrate for the first time. A program/erase window of 2V has been achieved with high P/E speed (T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">P</sub> equiv 10mus and TE equiv 1ms), and a 1.5V window remained after 10 years at room temperature. Multi-level storage is also obtained with DeltaV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t </sub> > 4V and T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">P,E</sub> equiv 1 ms. Operation voltages are not more than 7V in the two applications. Gate disturb issues are alleviated by applying an appropriate bias on unselected bit lines
Rapid diagnostics: the detection of neuraminidase activity as a technology for high-specificity targets (2001)

The accurate detection of influenza by clinical symptoms is challenging since multiple pathogenic viruses and bacteria mimic similar symptoms in a patient. With new and more effective influenza therapeutics available, there is a growing need for highly accurate and rapid diagnosis of influenza, particularly when the window of opportunity for proper treatment is measured in hours. A parallel technology, which is also used in the treatment of influenza, was developed for the rapid diagnosis of influenza by exploiting the enzymatic activity of influenza neuraminidase. This technology, which is called Pathozyme, offers the high specificity inherent from the conservation of the neuraminidase active site. The ZstatFlu test uses a small molecule derivative of sialic acid chemically coupled to a reporter group together with simple point–of–care reagents for directly detecting influenza from a patient specimen with high specificity. A second–generation platform technology using this neuraminidase detection system coupled with a more sensitive chemiluminescent reporter has been developed and formatted for reading on high–speed instant film. This modification resulted in a platform technology many–fold more sensitive than the former while maintaining its inherent high specificity. Preliminary data from a prototype tested during the mild 2000–2001 influenza season demonstrated that an optimized chemiluminescent test system could approach the accuracy of 14 day viral culture in a convenient 10–20 min test. This platform technology is currently being explored for the rapid detection of other pathogenic organisms where sensitivity, specificity and speed are essential in a point–of–care setting.
Distributing trust with the Rampart toolkit (1996)

The Rampart group communication protocols are designed to distribute trust among a group of nodes in a distributed system-so while individual nodes need not be fully trusted, the group can be.
Formamide can dramatically improve the specificity of PCR (1990)

Journal Article Formamide can dramatically improve the specificity of PCR Get access Gobinda Sarkar, Gobinda Sarkar Department of Biochemistry and Molecular Biology, Mayo Clinic/FoundationRochester, MN 55905, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Stephen Kapelner, Stephen Kapelner Department of Biochemistry and Molecular Biology, Mayo Clinic/FoundationRochester, MN 55905, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Steve S. Sommer Steve S. Sommer * Department of Biochemistry and Molecular Biology, Mayo Clinic/FoundationRochester, MN 55905, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 24, 1 December 1990, Page 7465, https://doi.org/10.1093/nar/18.24.7465 Published: 01 January 1990 Article history Published: 01 January 1990 Accepted: 24 September 1990
Some properties and the inclusion behavior of branched cyclodextrins. (1988)

Maltosyl (G2)- and maltotriosyl (G3)-cyclodextrins (CDs), synthesized from maltose or maltotriose and α-, β- or γ-CD with Pseudomonas isoamylase or Klebsiella aerogenes pullulanase were purified by high-performance liquid chromatography, and their solubilities in water and in various concentrations of methanol in water, specific rotations, and hemolytic activities were studied. G2-and G3-CDs, as well as glucosyl (G1)-CDs, were much more soluble than each parent CD in water and methanol aqueous solutions. The hemolytic activities of the branched CDs decreased with increasing side chain length; CD>G1-CD>G2-CD>G3-CD. The inclusion behavior of the branched CDs with slightly soluble or insoluble drugs in aqueous solution and in the solid state was examined by the solubility method and the differential scanning calorimetry. The complexation abilities of G1-, G2-, G3-CD and their parent CD in a series appeared to be almost the same and the stabilities of complexes in water practically unaffected by the length of the side chain. However, the enhancement of solubility of poorly water-soluble drugs by branched CDs was much more marked than that by the parent CD.
ECOD: An Evolutionary Classification of Protein Domains (2014)

Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.
Specificity of insertion of IS91, an insertion sequence present in α‐haemolysin plasmids of Escherichia coli (1989)

We have determined the DNA sequences of eight different insertions of IS91 in a specifically engineered recipient plasmid of known DNA sequence (pSU300). The sequences at the termini of IS91 are 5'-CGAGTAGG...CCTATCGAT. IS91 inserts specifically 5' to either one of the tetranucleotides 5'-GAAC or 5'-CAAG, and always in the same relative orientation with respect to the sequence of the target. Except in one special case, no duplications of the recipient DNA were produced at the site of insertion.
MCP-1 expression in endotoxin-induced uveitis. (2002)

Data indicate that MCP-1 plays a crucial role in the induction of EIU. MCP-1 may be a new therapeutic strategy for acute anterior uveitis.
Clinical Characteristics of the West Nile Fever Outbreak, Israel, 2000 (2001)

West Nile (WN) virus is endemic in Israel. The last reported outbreak had occurred in 1981. From August to October 2000, a large-scale epidemic of WN fever occurred in Israel; 417 cases were confirmed, with 326 hospitalizations. The main clinical presentations were encephalitis (57.9%), febrile disease (24.4%), and meningitis (15.9%). Within the study group, 33 (14.1%) hospitalized patients died. Mortality was higher among patients >70 years (29.3%). On multivariate regressional analysis, independent predictors of death were age >70 years (odds ratio [OR] 7.7), change in level of consciousness (OR 9.0), and anemia (OR 2.7). In contrast to prior reports, WN fever appears to be a severe illness with high rate of central nervous system involvement and a particularly grim outcome in the elderly.
Biochemistry, Biology, and Carcinogenicity of Tobacco-Specific N-Nitrosamines (1998)

ADVERTISEMENT RETURN TO ISSUEReviewNEXTBiochemistry, Biology, and Carcinogenicity of Tobacco-Specific N-Nitrosamines†Stephen S. HechtView Author Information University of Minnesota Cancer Center, Box 806 Mayo, 420 Delaware Street S.E., Minneapolis, Minnesota 55455 Cite this: Chem. Res. Toxicol. 1998, 11, 6, 559–603Publication Date (Web):June 2, 1998Publication History Received5 January 1998Published online2 June 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/tx980005yhttps://doi.org/10.1021/tx980005yreview-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views4482Altmetric-Citations844LEARN 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:Adducts,Anatomy,Genetics,Rodent models,Tumors Get e-Alerts
A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? (2003)

During the process of oncogenic transformation, melanoma cells escape from normal growth-control mechanisms and acquire the ability to invade surrounding tissues and organs. The Ras/Raf/MEK/ERK pathway is a major pathway involved in the control of growth signals, cell survival and invasion. Melanomas are known to harbour activating mutations of both Ras and BRAF, suggesting that the downstream effector ERK may be playing a major role in the oncogenic behaviour of these tumours. The past few years have seen a growth in the understanding of the role of ERK and the MAP kinase pathway in melanoma. The aim of the current review is to assess the role of ERK in melanoma behaviour and to determine whether modulation of these kinases could offer new therapeutic opportunities.
B-1 cell (CD5+B220+) outgrowth in murine schistosomiasis is genetically restricted and is largely due to activation by polylactosamine sugars (1997)

Previously, we demonstrated that lacto-N-fucopentaose III, a sugar found on egg Ags of Schistosoma mansoni, stimulated splenic B cells from parasite-infected mice to proliferate and produce IL-10 and PGE2. The major source of B cell IL-10 is the B-1 subset (CD5+B220+). Thus we examined whether levels of peritoneal exudate B-1 cells changed as a consequence of infection. In CBA/J, BALB/c, and C3H/HeJ mice, we observed significant increases in B-1 cells at 2 to 4 wk postinfection, declining to baseline by 6 to 8 wk. In contrast, the percentage of B-1 cells remained unchanged in C57BL/6 and BALB/c X.id mice after infection. B-1 cells were not observed in the spleens of infected mice; however, coincident with peritoneal B-1 cell decline, splenic CD23+B220+ cells increased from 11% to 30%. Peritoneal B-1 cells could also be expanded by injection of soluble egg Ag, but not by its deglycosylated form, suggesting a role for carbohydrates in B-1 recruitment. In addition, these cells secreted in vitro large amounts of IL-10 in response to lacto-N-fucopentaose III. Further, this sugar induced B-1 cell outgrowth in CBA/J and C3H/HeJ mice, but not in C57BL/6 mice. Thus, early activation of polylactosamine-reactive, IL-10-producing peritoneal B-1 and splenic B cells may be related to early dominance of the Th2-type CD4+ T cell subset. The degree to which this occurs may in part explain differences in the degree of granulomatous pathology reported among various strains of mouse.
Src Utilizes Cas to Block Gap Junctional Communication Mediated by Connexin43 (2007)

The Src tyrosine kinase phosphorylates Cas (Crk-associated substrate) to confer anchorage independence and invasive growth potential to transformed cells. Gap junctional communication is often lower between aggressive tumor cells compared with normal or benign precursors. The gap junction protein connexin43 (Cx43) is a tumor suppressor that can inhibit tumor cell growth. Src can phosphorylate Cx43 to block gap junctional communication between transformed cells. However, mechanisms by which this event actually closes intercellular channels have not been clearly defined. Here, we report that Src and Cas associate with each other at intercellular junctions. In addition, Cas is required for Src to reduce dye transfer and electrical coupling between cells expressing Cx43. Thus, Src utilizes Cas to inhibit gap junctional communication mediated by Cx43. This finding introduces a novel role of the Cas focal adhesion linker protein in the gap junction complex. This observation may help explain how gap junctional communication can be suppressed between malignant and metastatic tumor cells.
S-adenosylhomocysteine hydrolase downregulation contributes to tumorigenesis (2008)

With the idea to discover novel genes involved in proliferation, we have performed a genome-wide loss-of-function genetic screen to identify additional putative tumor suppressor genes. We have previously identified five genes belonging to different biochemical families. In this report, we focused on the study of one of these genes designated S-adenosylhomocysteine hydrolase (SAHH), which has also been previously identified in an independent short hairpin RNA screening. SAHH inactivation confers resistance to both p53 and p16(INK4)-induced proliferation arrest. Interestingly, SAHH inactivation inhibits p53 transcriptional activity and impairs DNA damage-induced transcription of p21(Cip1). Given that SAHH downregulation modulates senescence in primary cells, we also studied SAHH expression in human tumors at the messenger RNA (mRNA) and protein levels. SAHH mRNA was lost in 50% of tumor tissues from 206 patients with different kinds of tumors in comparison with normal tissue counterparts. Moreover, SAHH protein was also affected in some colon cancers. Such findings may be of relevance to cancer research, suggesting that SAHH might be a largely unexplored tumor suppressor.
Photovoltaic effect in ideal carbon nanotube diodes (2005)

We demonstrate that individual single-walled carbon nanotubes (SWNTs) can form ideal p-n junction diodes. An ideal behavior is the theoretical limit of performance for any diode, a highly sought after goal in all electronic materials development. We further elaborate on their properties by examining photovoltaic effects, an application where its performance is intimately related to the quality of the diode. Under illumination, SWNT diodes show significant power conversion efficiencies owing to enhanced properties of an ideal diode.
Biotechnological and Agronomic Potential of Endophytic Pink-Pigmented MethylotrophicMethylobacteriumspp. (2015)

The genus Methylobacterium is composed of pink-pigmented facultative methylotrophic (PPFM) bacteria, which are able to synthesize carotenoids and grow on reduced organic compounds containing one carbon (C1), such as methanol and methylamine. Due to their high phenotypic plasticity, these bacteria are able to colonize different habitats, such as soil, water, and sediment, and different host plants as both endophytes and epiphytes. In plant colonization, the frequency and distribution may be influenced by plant genotype or by interactions with other associated microorganisms, which may result in increasing plant fitness. In this review, different aspects of interactions with the host plant are discussed, including their capacity to fix nitrogen, nodule the host plant, produce cytokinins, auxin and enzymes involved in the induction of systemic resistance, such as pectinase and cellulase, and therefore plant growth promotion. In addition, bacteria belonging to this group can be used to reduce environmental contamination because they are able to degrade toxic compounds, tolerate high heavy metal concentrations, and increase plant tolerance to these compounds. Moreover, genome sequencing and omics approaches have revealed genes related to plant-bacteria interactions that may be important for developing strains able to promote plant growth and protection against phytopathogens.
Tissue Distribution and Molecular Heterogeneity of Human Growth Hormone-Releasing Factor in the Transgenic Mouse (1990)

Transgenic mice expressing the human growth hormone-releasing factor (hGRF) gene linked to the metallothionein promoter exhibit high circulating levels of hGRF and GH and increased growth. We have described the distribution of GRF immunoreactivity (GRF-IR) in various tissues and characterized its molecular heterogeneity using gel filtration and high performance liquid chromatography (HPLC) and two separate RIAs that recognized mid-molecule and carboxyl-terminal epitopes of hGRF. The highest levels of GRF-IR were in the pituitary, followed by the pancreas. Intermediate levels were present in hypothalamus and liver, and lower levels in visceral organs, heart, and gonads. The pituitary and brain revealed evidence of the two mature hormone forms [hGRF(1-44)-NH2 and hGRF(1-40)-OH and in addition a more hydrophobic form that is believed to represent the hGRF precursor (proGRF) on the basis of its estimated molecular size (approximately 9,000) and selective recognition by the mid-molecule RIA. The profiles of GRF in pancreas and gut were similar except that only minimal amounts of hGRF(1-40)-OH were detected. In contrast, neither mature hormonal form was present in the liver and plasma contained primarily hGRF(3-44)-NH2, the major circulating metabolite of hGRF. The results provide evidence for variable processing of the hGRF precursor that is tissue specific and indicate that several extrahypothalamic tissues possess the necessary complement of enzymes to generate the mature hormonal forms.