gebhart/patrepeval huggingface dataset:
Solution structure of the N‐terminal amphitropic domain of Escherichia coli glucose‐specific enzyme IIA in membrane‐mimetic micelles (2003)

The N-terminal domain of enzyme IIA(Glc) of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system confers amphitropism to the protein, allowing IIA(Glc) to shuttle between the cytoplasm and the membrane. To further understand this amphitropic protein, we have elucidated, by NMR spectroscopy, the solution structure of a synthetic peptide corresponding to the N-terminal domain of IIA(Glc). In water, this peptide is predominantly disordered, consistent with previous data obtained in the absence of membranes. In detergent micelles of dihexanoylphosphatidylglycerol (DHPG) or sodium dodecylsulfate (SDS), however, residues Phe 3-Val 10 of the peptide adopt a helical conformation in the ensemble of structures calculated on the basis of NOE-derived distance restraints. The root mean square deviations for superimposing the backbone atoms of the helical region are 0.18 A in DHPG and 0.22 A in SDS. The structure, chemical shifts, and spin-spin coupling constants all indicate that, of the four lysines in the N-terminal domain of IIA(Glc), only Lys 5 and Lys 7 in the amphipathic helical region interact with DHPG. In addition, the peptide-detergent interactions were investigated using intermolecular NOESY experiments. The aliphatic chains of anionic detergents DHPG, SDS, and 2,2-dimethyl-2-silapentane-5-sulfonate sodium salt (DSS) all showed intermolecular NOE cross-peaks to the peptide, providing direct evidence for the putative membrane anchor of IIA(Glc) in binding to the membrane-mimicking micelles.
Thrombocytopenia in c-mpl-deficient mice (1994)

Thrombopoietin (TPO) is a cytokine that is involved in the regulation of platelet production. The receptor for TPO is c-Mpl. To further investigate the role and specificity of this receptor in regulating megakaryocytopoiesis, c-mpl-deficient mice were generated by gene targeting. The c-mpl-/- mice had an 85 percent decrease in their number of platelets and megakaryocytes but had normal amounts of other hematopoietic cell types. These mice also had increased concentrations of circulating TPO. These results show that c-mpl specifically regulates megakaryocytopoiesis and thrombopoiesis through activation by its ligand TPO.
ALLPATHS 2: small genomes assembled accurately and with high continuity from short paired reads (2009)

We demonstrate that genome sequences approaching finished quality can be generated from short paired reads. Using 36 base (fragment) and 26 base (jumping) reads from five microbial genomes of varied GC composition and sizes up to 40 Mb, ALLPATHS2 generated assemblies with long, accurate contigs and scaffolds. Velvet and EULER-SR were less accurate. For example, for Escherichia coli, the fraction of 10-kb stretches that were perfect was 99.8% (ALLPATHS2), 68.7% (Velvet), and 42.1% (EULER-SR).
Triple Antihypertensive Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide (2009)

Many patients with hypertension require > or =3 agents to achieve target blood pressure (BP). The efficacy/safety of the dual combinations of valsartan (Val)/hydrochlorothiazide (HCTZ) and amlodipine (Aml)/Val in hypertension are well established. This randomized, double-blind study evaluated the efficacy/safety of triple therapy with Aml/Val/HCTZ for moderate or severe hypertension (mean sitting systolic BP: > or =145 mm Hg; mean sitting diastolic BP: > or =100 mm Hg). The study included a single-blind, placebo run-in period, followed by double-blind treatment for 8 weeks; patients were randomly assigned to 1 of 4 groups titrated to Aml/Val/HCTZ 10/320/25 mg, Val/HCTZ 320/25 mg, Aml/Val 10/320 mg, or Aml/HCTZ 10/25 mg once daily. Dual-therapy recipients received half of the target doses of both agents for the first 2 weeks, titrating to target doses during week 3. Those on triple therapy received Val/HCTZ 160.0/12.5 mg during week 1, Aml/Val/HCTZ 5.0/160.0/12.5 mg during week 2, and target doses of all 3 of the agents during week 3. Of the 4285 patients enrolled, 2271 were randomly assigned to treatment, and 2060 completed the study. Triple therapy was significantly superior to all of the dual therapies in reducing mean sitting systolic BP and mean sitting diastolic BP from baseline to end point (all P<0.0001). Significantly more patients on triple therapy achieved overall BP control (<140/90 mm Hg; P<0.0001) and systolic and diastolic control (P< or =0.0002) compared with each dual therapy. Aml/Val/HCTZ was well tolerated. The benefits of triple therapy over dual therapy were observed regardless of age, sex, race, ethnicity, or baseline mean sitting systolic BP. In conclusion, this study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg.
Determination of chemically reduced pyrrolobenzodiazepine SJG‐136 in human plasma by HPLC‐MS/MS: application to an anticancer phase I dose escalation study (2007)

SJG-136 1,1'-[[(propane-1,3-diyl)dioxy]bis[(11aS)-7-methoxy-2-methylidene-1,2,3,11a-tetrahydro-5H-pyr- rolo[2,1-c][1,4]benzodiazepin-5-one]] (NSC 694501), is a bifunctional pyrrolobenzodiazepine (PBD) dimer that forms selective, irreversible, interstrand DNA cross-links via exocyclic N2 atoms of two guanine bases, with a preference for 5'PuGATCPy binding sites. SJG-136 is highly cytotoxic in human tumor cells in vitro and in human tumor xenograft models in vivo at subnanomolar concentrations and is currently in anticancer phase I clinical trials in the United Kingdom and United States. To support correlative pharmacokinetics studies, a highly sensitive HPLC-MS/MS assay was developed and validated for the reliable quantitation of SJG-136 in human plasma, using the structurally similar PBD dimer DSB-120 as an internal standard. Chemical reduction of SJG-136 to its corresponding amine (SJG-136-H(4), [M + H](+)m/z 561) improved HPLC peak resolution and sensitivity by minimizing complications that arose from the reactivity of the labile imine moieties. Plasma samples were processed by protein precipitation and centrifugal membrane dialysis; components were separated by HPLC using an Agilent Rapid Resolution HT 1.8 mm (2.1 mm x 50 mm) analytical column. The total analysis time from injection to injection was 11 min. Electrospray MS/MS detection of SJG-136-H(4) was based on the selected reaction monitoring (SRM) transition [M + H](+)m/z 561 --> 301. The analytical response ratio was linearly proportional to the plasma concentration of SJG-136 over the nominal concentration range of 25 pg/ml to 250 ng/ml, with a coefficient of determination of r > or = 0.999. The intrarun absolute %RE was < or =19.6, 14.2, and 14.0% at 0.056, 2.83, and 56.3 ng/ml, respectively. The corresponding %RSD was < or =14.9%, 9.01, and 4.59%. The interday %RSD was < or =2.72, 3.46, and 5.20%. The lower and upper limits of quantitation were 0.056 and 56 ng/ml, respectively; recovery of SJG-136 from plasma was > or = 62% across the validated concentration range. The sensitivity of the validated assay was sufficient to detect SJG-136 in human subjects for up to 6 h after intravenous administration of 6 microg/m(2), the starting dose of an NCI-sponsored dose escalation study.
Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. (1997)

These preliminary findings suggest that possession of an APOE epsilon4 allele may be associated with increased severity of chronic neurologic deficits in high-exposure boxers.
Contraception (1999)

The UK still has the highest rate of teenage pregnancy in western Europe. Annabel Bennett discusses the benefits, side effects and contraindications of contraception, and the key role of practice nurses in educating this client group
Effect of short-chain fatty acids on pancreatic exocrine secretion in calves aged 2 weeks and 13 weeks. (1989)

Effects of short-chain fatty acids on pancreatic exocrine secretion were studied under anesthesia in calves within 2 weeks of age (2-wks calves) given only whole milk and milk replacement and in which rumen fermentation has not begun yet, and in calves at 13 weeks of age (13-wks calves) weaned at 40 days of age and in which rumen fermentation has already begun. Basal rate of juice flow and protein concentration and amylase activity in pancreatic juice under basal condition were significantly lower in the 2-wks calves than those in the 13-wks calves. Intravenous administrations of acetate, propionate and butyrate stimulated pancreatic juice secretion and protein and amylase output in both groups of calves. Those responses were increased with increasing carbon number in the molecule of fatty acids. Although the response of amylase output (/kg of body weight) in the 2-wks calves was significantly less than that in the 13-wks calves, the response of juice flow and protein output (/kg of body weight) in the 2-wks calves were equivalent to or greater than those in the 13-wks calves. These results indicate that the characteristic of pancreas, being stimulated by short-chain fatty acids, in calves and probably in other ruminants is not generated on the process of postnatal development, but has been already acquired before rumen fermentation begins.
Carbocycles from Carbohydrates via Free Radical Cyclizations: Synthesis and Manipulation of Annulated Furanoses (1998)

Tributyltin hydride plus AIBN mediated free radical cyclization of chiral precursors derived from O-glycosylated carbohydrates is an efficient method for the asymmetric synthesis of carbocycles (cyclitols, aminocyclitols and pseudosugars) of biological and pharmacological interest. Starting from simple aldoses and after a series of trivial synthetic steps for hydroxyl protection and functionalization, it is possible to prepare the required radical precursor in the furanose form with a radical donor and acceptor at the appropriate positions. Under typical free radical cyclization conditions the desired annulated furanoses were obtained in good chemical yield and excellent acyclic diastereoselection at "off-template" sites. A large number of precursors have been synthesized and cyclized in order to analyze the scope and extent of this new synthetic methodology.
Absorption Spectrum and Some Chemical Reactions of Colloidal Platinum in Aqueous Solution (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAbsorption Spectrum and Some Chemical Reactions of Colloidal Platinum in Aqueous SolutionA. Henglein, B. G. Ershov, and M. MalowCite this: J. Phys. Chem. 1995, 99, 38, 14129–14136Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/j100038a053https://doi.org/10.1021/j100038a053research-articleACS PublicationsRequest reuse permissionsArticle Views2606Altmetric-Citations293LEARN 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 options Get e-Alerts
Pancreatic stellate cells: new kids become mature (2005)

Vitamin A and its metabolites can reverse activation of culture activated pancreatic stellate cells and prevent ethanol induced pancreatic stellate cell activation
Tissue response to single-polymer fibers of varying diameters: Evaluation of fibrous encapsulation and macrophage density (2000)

An in vivo study was conducted to assess the sensitivity of fibrous capsule thickness and macrophage density to polymer fiber diameter. Single polypropylene fibers of diameters ranging from 2.1 to 26.7 microm were implanted in the subcutaneous dorsum of Sprague-Dawley rats. Results at 5 weeks demonstrated reduced fibrous capsule thickness for small fibers. Capsule thickness was 0.6 (+/-1.8) microm, 11.7 (+/-12.0) microm, 20.3 (+/-11.6) microm, and 25.5 (+/-10.0) microm for fibers in the ranges of 2.1 to 5.9, 6.5 to 10.6, 11.1 to 15.8, and 16.7 to 26.7 microm, respectively. Fibers very near to blood vessels had smaller capsules than did those with local vasculature further away. The macrophage density in tissue with fiber diameters 2.1 to 5.9 microm (23.03 +/- 8.67%) was comparable to that of unoperated contralateral control skin (18.72+/-10.06%). For fibers with diameters in the ranges of 6.5 to 10.6, 11.1 to 15.8, and 16.7 to 26.7 microm, macrophage densities were 33.90+/-13.08%, 34.40+/-15.77%, and 41.68+/-13.98%, respectively, all of which were significantly larger (p<0.002) than that for the control. The reduced fibrous capsule thickness and macrophage density for small fibers (<6 microm) compared with large fibers could be due to the reduced cell-material contact surface area or to a curvature threshold effect that triggers cell signaling. A next step will be to extend the analysis to meshes to evaluate fiber-spacing effects on small-fiber biomaterials.
Identifying differences in mRNA expression by representational difference analysis of cDNA (1994)

Detection of differentially regulated genes has been severely hampered by technical limitations. In an effort to overcome these problems, the PCR-coupled subtractive process of representational difference analysis (RDA) [Lisitsyn, N. et al. (1993) Science 259, 946-951] has been adapted for use with cDNA. In a model system, RAG-1 and RAG-2, the genes responsible for activating V(D)J recombination, were identified in a genomic transfectant by cDNA RDA in a small fraction of the time taken by conventional means. The system was also modified to eliminate expected difference products to facilitate the identification of novel genes. Additional alterations to the conditions allowed isolation of differentially expressed fragments. Several caffeine up-regulated clones were obtained from the pre-B cell line 1-8, including IGF-1B, and a predicted homologue of the natural killer cell antigen, NKR-P1. The approach was found to be fast, extremely sensitive, reproducible, and predominantly lacked false positives. cDNA RDA has the capacity and adaptability to be applied to a wide range of biological problems, including the study of single gene disorders, characterization of mutant and complemented cell types, developmental or post-event expression time courses, and examination of pathogen-host interactions.
[Strain differences related to Ebola virus reproduction in peritoneal macrophages and in aorta explants of guinea pigs]. (2004)

Reproduction of the Ebola strains (ES) virus causing lethality in guinea pigs as well as in peritoneal macrophages and aorta explants of animals was investigated in vitro and in vivo; besides, production of interferon-gamma (IFN-gamma) and of tumor necrosis factor-alpha (TNF-alpha) by macrophages and endotheliocytes of guinea pigs was also studied. The interplay "macrophage--ES" by the example of 2 models of susceptibility to ES demonstrates that the ES lethality is not unambiguously related only with a level of virus reproduction in macrophages. The interplay "endotheliocyte--ES" is indicative of that the ES lethality is inversely dependent on a level of production of the IFN-gamma and of TNF-alpha by endotheliocytes. In general, the Eboly fever lethality is not conditioned only by the ability or inability of ES to reproduce in macrophages and endotheliocytes; it also depends on a variety of pathogenetic factors, one of which could be the cytotoxic action of immune complexes shaping in the process of infection progression.
FAILURE OF DEXAMETHASONE TO PROVIDE ADEQUATE CHRONIC IMMUNOSUPPRESSION FOR RENAL TRANSPLANTATION (1979)

Departments of Medicine and Urology University of Oregon Health Sciences Center Portland, Oregon 97201
The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells (2015)

Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.
Modelo de autoevaluación integrado entre la norma ISO 9004 y el sistema único de acreditación en salud (2012)

&lt;p&gt;Todo proceso de mejora permanente en las organizaciones requiere de una reflexión periódica sobre el camino recorrido, los avances, los tropiezos y los retos que se presentan, para el logro de los propósitos organizacionales. La autoevaluación, como proceso interno de valoración, se constituye en una herramienta valiosa para llevar a cabo dicha reflexión.&lt;/p&gt;&lt;p&gt;El modelo de gestión de la calidad ISO 9004:2009 contiene una herramienta para llevar a cabo una autoevaluación, la cual permite identificar oportunidades para la mejora, mostrar fortalezas y debilidades para lograr el éxito sostenido, establecer el nivel de madurez de la organización y, si se repite, determinar el progreso de la organización en el tiempo. Dado el enfoque generalista de la norma ISO 9004, esta herramienta es aplicable a cualquier tipo de organizaciones.&lt;/p&gt;&lt;p&gt;Por otra parte, el sistema único de acréditación para las instituciones de salud en Colombia incluye también una herramienta de autoevaluación con una especifidad muy alta para el sector salud, pero que no tiene el enfoque sistémico de ISO 9004: no permite determinar un nivel de madurez y, según los usuarios resulta complejo de aplicar.&lt;/p&gt;&lt;p&gt;Se percibe entonces la posibilidad de crear un instrumento metodológico que integre lo mejor de ambas herramientas y resulte práctico en su aplicación.&lt;/p&gt;&lt;p&gt;Este documento presenta los resultados de la aplicacíón de la herramienta de autoevaluación del modelo ISO 9004:2009 en una institución prestadora de servicios de salud de alto nivel de complejidad y su comparación con el resultado de la autoevaluación del sistema único de acreditación.&lt;/p&gt;&lt;p&gt;Este ejercicio permitió identificar las similitudes, diferencias, fortalezas y debilidades de los dos instrumentos, lo cual condujo a la vez, dentro de una orientación de complementariedad e integración de modelos de gestión de la calidad, a desarrollar y presentar una nueva propuesta de instrumento de autoevaluación, enriquecido y fortalecido, aplicable a cualquier institución de salud que desee optar por la acreditación. &lt;/p&gt;
Extracellular Matrix Molecules that Influence Neural Development (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Response properties of ganglion cells in the isolated mouse retina (1993)

We have studied the organization of receptive fields of ganglion cells in the isolated mouse retina and have shown that the organization is similar to that of the cat. Based upon responses to circular and annular stimuli, most ganglion cells (90%; N = 83) had receptive fields with concentric center-surround organization, either ON or OFF center. The plot of response amplitude vs. stimulus area for these cells increased to a maximum (corresponding to a diameter of 10.0 +/- 2.8 deg S.E.M.; N = 13) and then decreased for larger stimuli, demonstrating the presence of an antagonistic surround. The dark-adapted sensitivity (205 +/- 43.8 impulses quantum-1 rod-1; mean +/- S.E.M.) did not differ from that measured for the intact preparation. We found a subset of OFF-center cells for which the dark discharge was very regular (mean coefficient of variation = 0.30). Using sinusoidal grating stimuli, we classified ganglion cells as X-like (87%) and Y-like (13%) based on spatial summation properties and the presence of subunit activity in the receptive-field center. We found no difference in the spatial-frequency preference between X-like and Y-like cells in the central retina (high cutoff frequency, 0.20 +/- 0.014 cycle/deg, mean +/- S.E.M.), in contrast to the marked difference between X cells and Y cells in the cat. Thus, ganglion cell receptive fields in the mouse retina resemble those of the cat, although the spatial characteristics of the receptive fields in the central retina are more homogeneous. This homogeneity would simplify the comparison of retinas from normal and mutant strains of the mouse.
Relation Between Excreted Lipopolysaccharide Complexes and Surface Structures of a Lysine-Limited Culture of Escherichia coli (1966)

Knox, K. W. (Twyford Laboratories, London, England), Maret Vesk, and Elizabeth Work. Relation between excreted lipopolysaccharide complexes and surface structures of a lysine-limited culture of Escherichia coli. J. Bacteriol. 92:1206-1217. 1966.-The lysine-requiring mutant Escherichia coli 12408, when grown in 15 liters of defined medium containing a suboptimal amount of lysine, showed a biphasic type of growth. During a long stationary phase of 15 hr, there was a steady accumulation of diaminopimelic acid (DAP) and an antigenic complex of lipopolysaccharide (LPS) and lipoprotein; the accumulation continued unchanged until the end of the second growth phase. The rapid rate of DAP excretion suggested that it was the result of a derepressed state of a biosynthetic pathway. LPS excretion was such that the amount in the culture fluid was doubled during a period corresponding to the normal generation time for the organism; this suggested that the LPS-lipoprotein complex was a product of unbalanced growth. Surface defects were suggested by the action of lysozyme, which, in low concentrations (10 mug/ml), lysed the lysine-limited cells even in the absence of ethylenediaminetetraacetic acid, but had no effect at 10 mug/ml on cells grown with adequate lysine. Electron microscopy of cells excreting the LPS complex showed them to be surrounded by a mass of stacked leaflets and globules, some of which were bounded by triple membranes. Sections showed no lysis but changes in cell surfaces; outer layers of the walls had numerous blebs whose outer membranes were sometimes continuous with the outer triple membrane of the wall. LPS-lipoprotein probably originates from these blebs.