gebhart/patrepeval huggingface dataset:
Novel Use of a Guanosine Prodrug Approach To Convert 2',3'-Didehydro-2',3'-Dideoxyguanosine into a Viable Antiviral Agent (2002)

Transient kinetic studies with human immunodeficiency virus (HIV) type 1 reverse transcriptase suggest that nucleotide analogs containing the 2',3'-didehydro-2',3'-dideoxy ribose ring structure present in D4T (stavudine) triphosphate are among the most effective alternative substrates. For unclear reasons, however, the corresponding purine nucleoside, 2',3'-didehydro-2',3'-dideoxyguanosine (D4G), was found to be inactive in cell culture. We have found that the previously reported lack of activity of D4G is primarily due to solution instability, and in this report we describe a novel use of a guanosine prodrug approach to stabilize the nucleoside. D4G was modified at the 6 position of the purine ring to contain a cyclopropylamino group yielding the prodrug, cyclo-D4G. An evaluation of cyclo-D4G revealed that the prodrug possessed anti-HIV activity. In addition, cyclo-D4G had increased stability, lipophilicity, and solubility, as well as decreased toxicity relative to D4G, suggesting that further study is warranted.
Single-dose subcutaneous administration of recombinant human parathyroid hormone [rhPTH(1–84)] in healthy postmenopausal volunteers* (1997)

Up to a dose of 5.0 micrograms.kg-1, rhPTH(1-84) was safe and well tolerated by healthy postmenopausal volunteers.
Chemistry of Nitrated Lipids: Remarkable Instability of 9-Nitrolinoleic Acid in Neutral Aqueous Medium and a Novel Nitronitrate Ester Product by Concurrent Autoxidation/Nitric Oxide-Release Pathways (2008)

Despite the mounting interest in nitrolinoleic acids and related nitrated polyunsaturated fatty acids as a novel class of bioactive signaling lipids, their chemistry and metabolic fate have remained poorly elucidated. Herein, we report an expedient nitroselenenylation/oxidation route to 9-nitrolinoleic acid (1) and 10-nitrolinoleic acid (2), which enabled comparative product studies under physiologically relevant conditions. Under biomimetic conditions, 1 decayed at an unusually fast rate to give the hydroxy-, keto-, and nitronitrate ester derivatives 3, 4, and 5 as main products, identified by ESI-MS and 2D NMR spectroscopy, including (1)H, (15)N HMBC experiments on the (15)N-labeled derivatives. The 13-nitrato functionality in 5 suggested partitioning of 1 between concurrent peroxidation and nitric oxide (NO)-release pathways. Lipid 2 decayed at a much slower rate giving only the hydroxynitro derivative 6 as an isolable product. Diphenylpicrylhydrazide (DPPH) radical quenching experiments and DFT computations concurred to support a higher H-atom donating ability of 1 versus 2, due to more effective stabilization of the resulting pentadienyl radical by the terminal nitro group. The markedly different stability of isomeric nitrolinoleic acids disclosed in the present study may provide an explanation for the previous identification of 2, but not 1, in body fluids and offers a key for future insights into the biological activities of nitrated lipids.
Amphipolar core-shell cylindrical brushes (1999)

Methacryloyl-endfunctionalized block copolymers consisting of styrene and 2-vinylpyridine were polymerized to polyblockcomacromonomers with a much higher main chain than side chain degree of polymerization. Like homopolymacromonomers these molecules exhibit the structure of cylindrical brushes. Since the vinylpyridine block is coupled to the polymerizable group, the resulting cylindrical macromolecules exhibit a core of vinylpyridine and a shell of polystyrene, thus resembling an amphipolar unimolecular micelle of cylindrical shape. The micellar character of the structure is demonstrated by loading the cylindrical brushes with tetrachloroauric acid in toluene. Subsequent reduction leads to the formation of colloidal gold, most probably within the brush in analogy to similar work on block copolymer micelles.
The involvement of NK cells in ankylosing spondylitis (2005)

A role for NK cells in the regulation of autoimmunity has been demonstrated. Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS. We studied 19 AS patients and 22 healthy volunteer donors and assessed the percentage, activity and receptor expression of peripheral blood NK cells. We also evaluated candidate-inflammatory mediators in sera. We found that AS patients have significantly higher percentages of NK cells. However, we found no differences between the ability of NK cells derived from AS and healthy controls to recognize target cells expressing HLA-B27. Remarkably, we observed that the NK-inhibitory receptor CEACAM1 (carcino-embryonic antigen-cell adhesion molecule) is highly expressed among AS-derived NK cells. Furthermore, engagement of CEACAM1 inhibited NK activity in these patients. Finally, we demonstrated that CEACAM1 expression is induced by IL-8 and SDF-1 (stromal cell derived factor), both of which are present in high levels in the sera of AS patients. These results may indicate that NK cells and CEACAM1 play a role in AS pathogenesis and implicate chemokines in the mechanism of CEACAM1 expression.
Tissue, cell type, and breast cancer stage‐specific expression of a TGF‐β inducible early transcription factor gene (1998)

This laboratory has previously identified a novel TGF-β inducible early gene (TIEG) in human osteoblasts [Subramaniam et al. (1995): Nucleic Acids Res 23:4907–4912]. Using TIEG specific polyclonal antibody and immunoprecipitation methods in normal human fetal osteoblast cells (hFOB cells), we have now demonstrated that TIEG encodes a 72-kDa protein whose levels are transiently increased at as early as 2 h of TGF-β treatment. Polarized confocal microscopic analysis of hFOB cells shows a nuclear localized TIEG protein in untreated cells under the conditions described under Methods. Interestingly, the levels of TIEG protein in the nuclei increase when the cells are treated with TGF-β1 for 2 h. In contrast, similar analyses of untreated human keratinocytes show a cytoplasmic localized TIEG protein that appears to be translocated to the nucleus after H2O2 treatment. Additional immunohistochemical studies have demonstrated that TIEG protein is expressed in epithelial cells of the placenta, breast, and pancreas, as well as in osteoblast cells of bone and selected other cells of the bone marrow and cerebellum with some cells showing a cytoplasmic localization and others a nuclear localization. All cells of the kidney display negative staining for this protein. Interestingly, a stage specific expression of TIEG protein is found in a dozen breast cancer biopsies, using immunohistochemistry. The cells in normal breast epithelium displays a high expression of TIEG protein, those in the in situ carcinoma display less than one-half of the levels, and those in the invasive carcinoma show a complete absence of the TIEG protein. TIEG has been localized to chromosome 8q22.2 locus, the same locus as the genes involved in osteopetrosis and acute myeloid leukemia and close to the c-myc gene locus and a locus of high polymorphism in cancer biopsies. The correlation between the levels of TIEG protein and the stage of breast cancer, its prime location in human chromosome 8q22.2, and past studies with pancreatic carcinoma, suggests that TIEG may play a role in tumor suppressor gene activities, apoptosis, or some other regulatory function of cell cycle regulation. J. Cell. Biochem. 68:226–236, 1998. © 1998 Wiley-Liss, Inc.
DNA large restriction fragment patterns of sporadic and epidemic nosocomial strains of Mycobacterium chelonae and Mycobacterium abscessus (1993)

Large restriction fragment (LRF) pattern analysis of genomic DNA using pulsed-field gel electrophoresis was performed on three reference strains, 32 sporadic isolates, and 92 nosocomial isolates from 12 epidemics of Mycobacterium chelonae and Mycobacterium abscessus. Only 17 of 30 (57%) unrelated strains of M. abscessus, compared with 10 of 11 (91%) of M. chelonae strains, gave satisfactory DNA extractions, with the remainder resulting in highly fragmented DNA. DraI, AsnI, XbaI, and SpeI gave satisfactory LRF patterns. Sporadic isolates of the two species had highly variable LRF patterns, except for one reference strain and one sporadic isolate of M. chelonae that differed by only two to five bands. Evaluation of repeat isolates from five patients monitored for 8 months to 13 years (mean, 5.8 years) revealed LRF patterns to be stable, with changes of not more than two bands. LRF analysis of the seven nosocomial outbreaks with evaluable DNA revealed identical patterns in most or all of the patient isolates and in three outbreaks revealed identity with environmental isolates. These outbreaks included endoscope contamination, postinjection abscesses, and surgical wound infections. LRF analysis of genomic DNA is a useful technique for epidemiologic studies of M. abscessus and M. chelonae, although improved technology is needed for the approximately 50% of strains of M. abscessus with unsatisfactory DNA extractions.
Evolution of the CRISPR-Cas adaptive immunity systems in prokaryotes: models and observations on virus–host coevolution (2014)

CRISPR-Cas is an adaptive immunity system in prokaryotes that functions via a unique mechanism which involves incorporation of foreign DNA fragments into CRISPR arrays and subsequent utilization of transcripts of these inserts (known as spacers) as guide RNAs to cleave the cognate selfish element genome. Multiple attempts have been undertaken to explore the coevolution of viruses and microbial hosts carrying CRISPR-Cas using mathematical models that employ either systems of differential equations or an agent-based approach, or combinations thereof. Analysis of these models reveals highly complex co-evolutionary dynamics that ensues from the combination of the heritability of the CRISPR-mediated adaptive immunity with the existence of different degrees of immunity depending on the number of cognate spacers and the cost of carrying a CRISPR-Cas locus. Depending on the details of the models, a variety of testable, sometimes conflicting predictions have been made on the dependence of the degree of immunity and the benefit of maintaining CRISPR-Cas on the abundance and diversity of hosts and viruses. Some of these predictions have already been directly validated experimentally. In particular, both the reality of the virus-host arms race, with viruses escaping resistance and hosts reacquiring it through the capture of new spacers, and the fitness cost of CRISPR-Cas due to the curtailment of beneficial HGT have been reproduced in the laboratory. However, to test the predictions of the models more specifically, detailed studies of coevolving populations of microbes and viruses both in nature and in the laboratory are essential. Such analyses are expected to yield disagreements with the predictions of the current, oversimplified models and to trigger a new round of theoretical developments.
Cross-correlation phase noise measurements (2003)

The noise floor of a typical two channel phase noise measurement system is set by the phase detector and amplifiers that follow the detector. If the phase noise of two oscillators is measured using two of these test systems, the output noise of the equipment is uncorrelated except for the component that is due to the phase noise between the oscillators. Examination of a system which uses matched power splitters, two phase detectors, and post amplifiers reveals that an exceptionally low noise floor is achievable. The time required to reach a given percentage of precision in the measurement at these low noise floors is lengthened due to the need to average away the uncorrelated noise. The details of the setup, including calibration procedures and confidence intervals for the measurement, are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Aberrant Nuclear p53 Expression Predicts Hemizygous 17p (TP53)Deletion in Chronic Lymphocytic Leukemia (2009)

Hemizygous TP53 gene deletion is the most important adverse risk factor in chronic lymphocytic leukemia (CLL), but its relationship with p53 protein expression is unclear. We investigated 110 CLL cases and correlated nuclear p53 protein immunoreactivity with TP53 gene deletion status and other CLL-associated genetic risk factors. Fluorescence in situ hybridization detected hemizygous TP53 deletions in 15 cases (13.6%), whereas immunohistochemical analysis detected nuclear p53 protein expression in 14 (12.7%). All cases expressing nuclear p53 protein had hemizygous TP53 deletions. Hemizygous TP53 gene deletion and p53 protein expression were strongly correlated (P < .001). There was no association between p53 expression and del(13q), del(11q) or trisomy 12 in CLL cases. Our data indicate that nuclear p53 protein expression, detected by a widely available immunohistochemical method, is strongly associated with TP53 deletion and that p53 immunohistochemical analysis may be adopted as a rapid, robust diagnostic tool for risk stratification of CLL.
Salivary Proline-rich Proteins: Biochemistry, Molecular Biology, and Regulation of Expression (1993)

The proline-rich proteins (PRPs) in mammalian salivary glands are encoded by tissue-specific multigene families whose members have diverged with respect to structure and regulation of expression. PRPs are expressed constitutively in humans, and comprise about [70%] of the total salivary proteins. Families of similar proteins are dramatically increased or induced in parotid and submandibular glands of rats, mice and hamsters by treatment with the [beta-] agonist isoproterenol. Feeding tannins to rats and mice mimics the effects of isoproterenol on the parotid glands. Salivary PRPs may constitute a defense mechanism against tannins and other polyhydroxylated phenols ingested. Putative transcriptional regulatory sequences have been identified in mouse PRP genes.
Dendrimer-platinate: a novel approach to cancer chemotherapy. (1999)

A polyamidoamine (PAMAM) dendrimer generation 3.5 with a sodium carboxylate surface was conjugated to cisplatin giving a dendrimer-platinate (dendrimer-Pt; 20-25 wt% platinum) which was highly water soluble and released platinum slowly in vitro. In vivo the dendrimer-Pt and cisplatin were equi-active i.p. against i.p. L1210, and at high dose dendrimer-Pt given i.p. showed activity against i.p. B16F10 whereas cisplatin did not. Additionally, when administered i.v. to treat a palpable s.c. B16F10 melanoma, the dendrimer-Pt displayed antitumor activity whereas cisplatin was inactive. Measurement of platinum levels in blood and tissues after i.v. injection of cisplatin (1 mg/kg) or dendrimer-Pt (15 mg/kg)-the maximum tolerated dose (MTD) of these compounds-showed selective accumulation of the dendrimer-Pt in solid tumor tissue by the EPR effect (a 50-fold increase in area under curve compared with cisplatin). The dendrimer-Pt was also less toxic (3- to 15-fold) than cisplatin and thus has potential for further investigation as a novel antitumor approach.
Species- or isozyme-specific enzyme inhibitors. 7. Selective effects in inhibitions of rat adenylate kinase isozymes by adenosine 5'-phosphate derivatives (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpecies- or isozyme-specific enzyme inhibitors. 7. Selective effects in inhibitions of rat adenylate kinase isozymes by adenosine 5'-phosphate derivativesTon T. Hai, Donald Picker, Masanobu Abo, and Alexander HamptonCite this: J. Med. Chem. 1982, 25, 7, 806–812Publication Date (Print):July 1, 1982Publication History Published online1 May 2002Published inissue 1 July 1982https://pubs.acs.org/doi/10.1021/jm00349a008https://doi.org/10.1021/jm00349a008research-articleACS PublicationsRequest reuse permissionsArticle Views169Altmetric-Citations4LEARN 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
Carboxamides Combining Favorable Olfactory Properties with Insect Repellency (2008)

By a simple methodology, we have synthesized 68 carboxamides, with structural analogy to the most efficient mosquitoes repellent DEET (N,N-diethyl-m-toluamide, 9). Eight of them have very promising olfactory profiles. In addition, 34 carboxamides have been tested for their repellency properties against three breeds of cockroach; six of them are excellent in this domain. Two of these, the 2-ethyl-N-isopropyl-N-methylbutanamide and N,N-diallyl-2-ethylbutanamide combine both the positive aspects, and are thus very good candidates for use in functional perfumery, and more particularly in home-care formulations.
Polypyrrole actuators: modeling and performance (2001)

Conducting polymer actuators generate forces that exceed those of mammalian skeletal muscle by up to two orders of magnitude for a given cross-sectional area, require only a few volts to operate, and are low in cost. However application of conducting polymer actuators is hampered by the lack of a full description of the relationship between load, displacement, voltage and current. In an effort to provide such a model, system identification techniques are employed. Stress-strain tests are performed at constant applied potential to determine polypyrrole stiffness. The admittance transfer function of polypyrrole and the associated electrolyte is measured over the potential range in which polypyrrole is highly conductive. The admittance is well described by treating the polymer as a volumetric capacitance of 8*10<SUP>7</SUP> F*m<SUP>3</SUP> whose charging rate is limited by the electrolyte resistance and by diffusion within polypyrrole. The relationship between strain and charge is investigated, showing that strain is directly proportional to charge via the strain to charge density ratio, (alpha) = 1*10+-10 m<SUP>3</SUP>*C<SUP>-1</SUP>, at loads of up to 4 MPa. Beyond 4 MPa the strain to charge ratio is time dependent. The admittance models, stress/strain relation and strain to charge relationship are combined to form a full description of polypyrrole electromechanical response. This description predicts that large increases in strain rate and power are obtained through miniaturization, yielding bandwidths in excess of 10 kHz. The model also enables motor designers to optimize polypyrrole actuator geometries for their applications.
Absolute Refractive Index Determination by Microinterferometric Backscatter Detection (2003)

Microinterferometric backscatter detection (MIBD) has previously been shown capable of measuring changes in the refractive index of liquids on the order of 10(-7). The MIBD technique is based on interference of laser light after it is reflected from different regions in a capillary. These reflections generate an interference pattern that moves upon changing refractive index of the liquid in the capillary. The small-angle interference pattern traditionally considered has a repetition frequency in the refractive index space that limits the ability to measure refractive index-to-refractive index changes causing such a repetition. Such refractive index changes are typically on the order of three decades. Recent modeling and experiments with the MIBD technique have shown that other intensity variations in the pattern are present for larger backscattered angles. By considering these variations, we have shown two methods by which it is possible to extend the dynamic measurement range to make an absolute refractive index measurement. One method utilizes variations in the Fresnel coefficients while the second approach is based on the refractive index-dependent onset of total internal reflection angles. With the second approach, we have been able to measure the absolute refractive index of a liquid with a precision of 2.5 x 10(-4).
Sequence analysis of firefly luciferase family reveals a conservative sequence motif. (1991)

A conservative sequence motif was extracted from an alignment of the firefly luciferase family. AngR derived from a pathogenic bacterium and acetyl-CoA synthetases derived from two ascomycete fungi were identified as members of the firefly luciferase family by a homology search with the motif and other sequence comparison analyses. The motif sequence shares several characteristics with the phosphate-binding sites of phosphoproteins and nucleotide-binding proteins. A multiple alignment and an unrooted phylogenetic tree were constructed for the investigation of evolutionary relationships within the firefly luciferase family.
Modulation of human dermal fibroblast extracellular matrix metabolism by the lymphokine leukoregulin. (1991)

The effect of leukoregulin, a 50-kD lymphokine with unique antitumor properties, was studied in vitro on several fibroblast functions. Leukoregulin did not inhibit fibroblast proliferation, as measured by cell enumeration and [3H]thymidine incorporation, and had no cytotoxic effect in terms of increased membrane permeability detected by trypan blue exclusion, two of the major leukoregulin actions on tumor cells. Leukoregulin induced a dose-dependent decrease in collagen synthesis, demonstrated by decreased [3H]proline incorporation into collagenase-digestible protein, as early as 6 h after the addition of the lymphokine to human fibroblasts. Leukoregulin inhibited the synthesis of both type I and type III collagen, as measured by SDS-PAGE and by specific radioimmunoassay. Neutralizing antibodies to interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma failed to alter the effect of leukoregulin on collagen synthesis, attesting that leukoregulin action was not due to contamination by these cytokines. Inhibition of collagen synthesis occurred concomitantly with increased secretion of prostaglandin E2 and a transient rise in intracellular cyclic AMP content, peaking at 6 h. However, blocking prostaglandin synthesis with indomethacin did not counteract inhibition of collagen synthesis by leukoregulin, demonstrating independence of this action of leukoregulin from cyclooxygenase metabolites. Leukoregulin also stimulated glycosaminoglycan production in a dose-dependent manner, affecting the synthesis of hyaluronic acid as the major fibroblast-derived extracellular glycosaminoglycan. In addition, secretion of neutral proteases (collagenase, elastase, caseinase) was increased. These observations indicate that leukoregulin is able to regulate synthesis of molecules critical to the deposition of the extracellular matrix by nontransformed nonmalignant fibroblasts.