gebhart/patrepeval huggingface dataset:
Improved pairwise alignment of genomic dna (2007)

Graduate School iii Advances in DNA sequencing technology have fueled a rapid increase in the number of sequenced vertebrate genomes, and we anticipate an explosion in the number of genomes sequenced in the near future. Detecting similarities between genomes is a valuable technique in discovering functional elements, and sequence alignment is the primary tool for discovering similarities. The quality of alignments is affected by several user-specified control parameters. The parameters are so little understood that most users simply use default settings. We seek to change that, to have the program automatically infer appropriate parameter choices from statistics derived automatically from the sequences. We introduce a program, INFERZ, which addresses part of the inference problem, inferring substitution and gap scores according to a mathematically sound model. Further, we explore the usefulness of iterating inferred scores to convergence. We test this process on both simulated and actual genomic data, and show that iteration will converge in
Cooling and Control of a Cavity Optoelectromechanical System (2010)

We implement a cavity optoelectromechanical system integrating electrical actuation capabilities of nanoelectromechanical devices with ultrasensitive mechanical transduction achieved via intracavity optomechanical coupling. Electrical gradient forces as large as 0.40 microN are realized, with simultaneous mechanical transduction sensitivity of 1.5x10{-18} m Hz{-1/2} representing a 3 orders of magnitude improvement over any nanoelectromechanical system to date. Optoelectromechanical feedback cooling is demonstrated, exhibiting strong squashing of the in-loop transduction signal. Out-of-loop transduction provides accurate temperature calibration even in the critical paradigm where measurement backaction induces optomechanical correlations.
Erythropoietin Can Induce the Expression of Bcl-xLthrough Stat5 in Erythropoietin-dependent Progenitor Cell Lines (1999)

Erythropoietin (Epo) initiates its cellular response by binding to the Epo receptor, which triggers the activation of signal transducer and activator of transcription (Stat) 5 protein. Cell culture studies of erythroid progenitors have suggested that Epo functions as a survival factor by repressing apoptosis at least in part through Bcl-x(L), an anti-apoptotic protein of the Bcl-2 family. In this report, we examine whether Stat5 can induce transactivation of the bcl-x gene in response to Epo. Two Epo-responsive progenitor cell lines, HCD-57 and Bcl-2-transfected Ba/F3-Epo receptor (Ba/F3-EpoR-Bcl-2), were used in this study. After Epo stimulation, we observed a correlation between expression of bcl-x(L) and activation of Stat5 as assessed by the expression of oncostatin M, a direct target of Stat5, and the phosphorylation and nuclear translocation of Stat5. Moreover, a Stat binding element in the bcl-x promoter was found to be active in response to Epo, a finding that was further confirmed because mutagenesis of this sequence motif abrogated its promoter activity and overexpression of a dominant negative Stat5 protein blocked transactivation. When DNA-protein binding analyses were performed, we found that Stat5, not Stat1 or Stat3, was the protein bound to the bcl-x promoter in response to Epo. These data suggest that Epo-dependent activation of Stat5 is a transcriptional pathway that can be used by Epo-responsive progenitor cells to induce the expression of bcl-x(L) and consequently to inhibit apoptosis.
Editorial: Memory CD8 T cells now join “Club 21” (2010)

In this volume, Nguyen and Weng [( 1) ] show an intriguing study in which they observed an antagonizing effect by IL-21 on the IL-7- or IL-15-driven expansion of CD28(-) nonfunctional memory CD8 T cells and thereby, proposed a new role for IL-21 to keep the memory pool fresh and competent. I will summarize previous studies and discuss the recent advancement in this context.
High levels of antibodies to annexins V and VI in patients with rheumatoid arthritis. (1995)

High levels of IgG (anti-A-V and anti-A-VI) antibodies were found in sera from patients with RA. We suggest that antiannexin autoantibodies may play a role in the clinical course of RA by impairing the anti-PLA2 effect of annexins.
Green Chemistry for Sustainable Cement Production and Use (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
ER and PI3K Independently Modulate Endocrine Resistance in ER-Positive Breast Cancer (2011)

Endocrine therapy-resistant estrogen receptor-positive (ER(+)) breast cancer is the most common cause of breast cancer death. Miller and colleagues demonstrate that ligand-independent ER activity promotes the growth of breast cancer cells through CDK4/E2F. As an independent event, the phosphatidylinositol 3-kinase (PI3K) pathway is also upregulated in endocrine therapy-resistant cells. Promising preclinical evidence by several groups for the combination of an inhibitor of ligand-independent ER, fulvestrant, with PI3K inhibition, has led to the activation of trials evaluating this concept.
Automated Detection of Point Mutations by Electrophoresis in Peptide-Nucleic Acid-Containing Gels (1999)

Polymerization of electronically, essentially neutral peptide nucleic acids (PNA) into polyacrylamide gels creates a medium in which the salt-independent properties of PNA/DNA interactions are used to achieve hybridization with target DNA during affinity electrophoresis. Such physical entrapment of PNA has been used to differentiate between a retarded, complementary DNA strand and a non-retarded sequence differing by a single point mutation. Analysis of fluorescent PCR products--from both model mismatches and clinically relevant point mutations using a conventional automated DNA sequencer--allows one to follow this hybridization in real time and to distinguish homo- and heterozygous mutants visually. It has been shown that parameters affecting the resolution of these species include not only temperature and concentration (as a function of the [GC] content of the PNA), but also the position of the PNA binding sequence within the interacting DNA segment. Under conditions optimized in terms of temperature and PNA concentration, the maximum separation of retarded from non-retarded DNA single strands is obtained when the PNA binding sequence is close to either DNA terminus. Strategies of PNA and PCR primer design that permit a diagnostic application ranging over 85-451 DNA base pairs are proposed.
Molecular Rearrangements. XXIII. The Mechanism of Hydride Shift during Hydrolyses of Certain Substituted Norbornyl Tosylates (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Rearrangements. XXIII. The Mechanism of Hydride Shift during Hydrolyses of Certain Substituted Norbornyl TosylatesClair J. Collins and Ben M. BenjaminCite this: J. Am. Chem. Soc. 1967, 89, 7, 1652–1661Publication Date (Print):March 1, 1967Publication History Published online1 May 2002Published inissue 1 March 1967https://pubs.acs.org/doi/10.1021/ja00983a022https://doi.org/10.1021/ja00983a022research-articleACS PublicationsRequest reuse permissionsArticle Views112Altmetric-Citations12LEARN 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
Growth of GaN on a nanoscale-faceted Si substrate by metal-organic vapor-phase epitaxy (2004)

We demonstrate a surface morphology for growth of GaN on a Si(100) substrate by metal-organic vapor-phase epitaxy (MOVPE). The basic idea is to fabricate nanoscale periodic (111) facets on Si(100) and to restrict the initial nucleation to these (111) for better crystallinity.
Folic acid analogs. II. p-{[(2,6-Diamino-8-purinyl)methyl]amino}-benzoyl-L-glutamic acid and related compounds (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFolic acid analogs. II. p-{[(2,6-Diamino-8-purinyl)methyl]amino}-benzoyl-L-glutamic acid and related compoundsLouis T. Weinstock, Bernard F. Grabowski, and Chia-Chung ChengCite this: J. Med. Chem. 1970, 13, 5, 995–997Publication Date (Print):September 1, 1970Publication History Published online1 May 2002Published inissue 1 September 1970https://pubs.acs.org/doi/10.1021/jm00299a054https://doi.org/10.1021/jm00299a054research-articleACS PublicationsRequest reuse permissionsArticle Views100Altmetric-Citations13LEARN 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
The Recovery of Viruses from Drinking-Water by Means of an in-Line Electropositive Cartridge Filter (1985)

Efficient, fast and relatively inexpensive techniques, which will consistently give high recoveries of viruses from one hundred or more litres of water, are still sought for the monitoring of drinking-water systems. A technique using electropositive absorbent filters showed promise if sample volumes were limited to 100 ℓ. Investigation of this recovery method was warranted, as the use of an in-line cartridge filter would constitute an ideal monitoring tool if the filter could be inserted at set points in a distribution system, removed under sterile conditions after the filtration of a known volume of water, and returned to a specialized virological laboratory for elution and virus isolation. In the present study, tests were carried out to determine the efficiency of positively charged AMF-Cuno Virosorb cartridge filters in processing 100 ℓ of tap water continuously seeded with varying dosages of different viruses. Viruses were desorbed by the cycling of a 3 g/ℓ beef extract solution in 50 mM glycine - NaOH at pH 9.5 for 5 min, followed by immediate neutralization with 1 mol/ℓ HCl. In order to avoid a second concentration step, the 1 ℓ eluent was converted into growth medium by the addition of dehydrated Dulbecco's modified Eagle medium with decontamination by filtration through a 147 mm diameter 0.22 µm membrane. In eleven tests where the average poliovirus 1 seed was 22 × 106 TCID50 per 100 ℓ, virus recoveries were 75.9% ± 25.9%. In subsequent tests the virus seed was progressively reduced by one log at a time until the theoretical dosage was between one and ten TCID50 virus per 100 ℓ tap water. Virus could always be isolated from at least one to ten Nunc flasks which had been changed to the Virosorb eluent medium. Comparisons are given of the efficiency of the technique for the recovery of poliovirus types 1 and 2, reovirus type 1, the SA 11 rotavirus and coliphages.
A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. (1992)

Blood vessel growth is necessary for normal tissue homeostatis and contributes to solid tumor growth. Methods to quantitate neovascularization should be useful in testing biological factors and drugs that regulate angiogenesis or to induce a vascular supply to promote wound healing.An extract of basement membrane proteins (Matrigel) was found to reconstitute into a gel when injected subcutaneously into C57/BL mice and to support an intense vascular response when supplemented with angiogenic factors.New vessels and von Willebrand factor antigen staining were apparent in the gel 2-3 days after injection, reaching a maximum after 3-5 days. Hemoglobin content of the gels was found to parallel the increase in vessels in the gel allowing ready quantitation. Angiogenesis was obtained with both acidic and basic fibroblast growth factors and was enhanced by heparin. Several substances were tested for angiostatic activity in this assay by coinjection in Matrigel with fibroblast growth factor and heparin. Platelet-derived growth factor BB, interleukin 1-beta, interleukin-6, and transforming growth factor-beta were potent inhibitors of neovascularization induced by fibroblast growth factor. Tumor necrosis factor-alpha did not alter the response but was alone a potent inducer of neovascularization when coinjected with Matrigel and heparin. Consistent with the previously demonstrated importance of collagenase in mediating endothelial cell invasion, a tissue inhibitor of metalloproteinases that also inhibits collagenases was found to be a potent inhibitor of fibroblast growth factor-induced angiogenesis.Our assay allows the ready quantitative assessment of angiogenic and anti-angiogenic factors and should be useful in the isolation of endothelial cells from the capillaries that penetrate into the gel.
Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. (1985)

The effect of photodynamic therapy (PDT) on tumor growth as well as on tumor cell survival in vitro and in vivo was studied in the EMT-6 and RIF experimental mouse tumor systems. In vitro, RIF cells were more sensitive towards PDT than were EMT-6 cells when incubated with porphyrin (25 micrograms/ml, dihematoporphyrin ether) and subsequently given graded doses of light. In vivo, both tumor types responded to PDT (EMT-6, dihematoporphyrin ether, 7.5 mg/kg; RIF, dihematoporphyrin ether, 10 mg/kg; both followed 24 hr later by 135 J of light at 630 nm/sq cm) with severe vascular disruption and subsequent disappearance of tumor bulk. However, whereas the cure rate for EMT-6 tumors was 90%, it was 0% for RIF tumors. Raising the light dose to 200 J/sq cm resulted in 100% cures for EMT-6 tumors accompanied by damage to the surrounding tissues and 13% cures for RIF tumors. Tumor cell clonogenicity following PDT in vivo was assessed using the in vitro colony formation assay. In both tumors, it was found to be nearly unaffected by PDT if the tumor tissue was excised and explanted immediately following completion of treatment. This indicates that the effect of PDT on tumor cells directly was not sufficient to decrease tumor clonogenicity even at doses which led to total macroscopic tumor destruction. Where the tumors remained in situ following PDT and explantation was delayed for varying lengths of time (1 to 24 hr), tumor cell death occurred rapidly and progressively, indicating that tumor cell damage was expressed only if the cells remained exposed to the in situ environment after treatment. The kinetics and extent of tumor cell death were very similar for both tumor types despite their difference in cure rates. The reduction in tumor clonogenicity at 4 hr post-PDT closely matched that of tumor deprived of oxygen for the same period of time, implying that one of the major factors contributing to tumor destruction may be damage of the tumor circulation and the consequences of treatment-induced changes in tumor physiology.
Physiologic roles of interleukin-2, interleukin-4, and interleukin-7 (1996)

The use of gene targeting techniques has led to new insights into the physiologic function of lymphoid growth factors, their receptors, and associated signal transduction molecules in the formation and function of T and B cells. Mice rendered deficient for the growth factors interleukin-2 or interleukin-4 exhibit impairment in certain immune responses and in steady-state immune function, although production and expansion of lymphocyte populations is unaffected. In contrast, mice deficient for interleukin-7 show a severe lymphopenia in most lymphoid tissues. Interleukin-2, interleukin-4, and interleukin-7 all utilize the common gamma (gamma c) receptor component at the cell surface of lymphocytes and the Jak3 kinase molecule to transduce signals inside the cell. Both gamma c- and Jak3 kinase-deficient animals display a phenotype similar to interleukin-7-deficient animals in terms of lymphoid development. Collectively, these genetic experiments clearly define different in vivo roles for these lymphoid factors. Interleukin-2 and interleukin-4 function by influencing mature lymphocyte populations during immune responses, whereas interleukin-7 plays a singularly dominant role, in terms of the ligands that bind to the gamma c receptor, for the production and expansion of lymphocytes.
Functional Porous Coordination Polymers (2004)

The chemistry of the coordination polymers has in recent years advanced extensively, affording various architectures, which are constructed from a variety of molecular building blocks with different interactions between them. The next challenge is the chemical and physical functionalization of these architectures, through the porous properties of the frameworks. This review concentrates on three aspects of coordination polymers: 1). the use of crystal engineering to construct porous frameworks from connectors and linkers ("nanospace engineering"), 2). characterizing and cataloging the porous properties by functions for storage, exchange, separation, etc., and 3). the next generation of porous functions based on dynamic crystal transformations caused by guest molecules or physical stimuli. Our aim is to present the state of the art chemistry and physics of and in the micropores of porous coordination polymers.
Sequential morphologic events during apoptosis of human neutrophils. Modulation by lipoxygenase-derived eicosanoids (1996)

Dual-laser flow cytometry, based on the properties of the DNA-binding dyes Hoechst 33342 and propidium iodide, was used, with light and electron microscopy and DNA fragmentation studies, to define the influence of lipoxygenase-derived eicosanoids on apoptosis of human polymorphonuclear neutrophils (PMN) in vitro. Apoptosis was characterized by progression through an early apoptotic phase characterized by condensation of chromatin and coalescence of nuclear lobes, to a late apoptotic phase characterized by nuclear degradation and evanescence, and secondary necrosis. Prolonged exposure of PMN to leukotriene B4 (LTB4) afforded dose-dependent inhibition of constitutive PMN apoptosis (percentage of normal and apoptotic PMN, respectively, after aging for 18 h: vehicle, 30.5 +/- 2.7% and 61.8 +/- 3.2%; LTB4 10(-7) M, 57.6 +/- 1.2% and 37.6 +/- 1.0%) and apoptosis triggered by the classic peptide chemoattractant FMLP. In contrast, apoptosis was not affected by the LTB4 precursor 5(S)-hydroxyeicosatetraenoic acid (HETE), the omega-oxidation LTB4 metabolites 20-hydroxy-LTB4 and 20-carboxy-LTB4, the cysteinyl leukotriene LTC4, the 15-lipoxygenase product 15(S)-HETE, or the lipoxygenase interaction product lipoxin A4. The anti-apoptotic effect of LTB4 was mimicked by 20,20,20-trifluoro-LTB4, LTB4-dimethylamide, and 14,15-dehydro-LTB4, and was blunted by pertussis toxin and genistein, inhibitors of G alpha i GTP-binding proteins and tyrosine kinases, respectively, but not by staurosporine, 15(S)-HETE, or lipoxin A4. This unique pharmacologic profile suggested that LTB4 attenuated apoptosis through activation of cell surface receptors and signaling events distinct from those involved with PMN trafficking, degranulation, and respiratory bursts.
In vivo production and function of IL-12 p40 homodimers (1997)

The bioactivity of IL-12 is mediated by heterodimers of disulfide-linked p35 and p40 protein subunits. Homodimeric p40 competes with heterodimer for binding to the high affinity IL-12R and inhibits IL-12 bioactivity in vitro. However, the production and significance of p40 homodimer as a cytokine antagonist in vivo have not been determined. In these studies, we observed increased amounts of both IL-12 p40 monomer and homodimer in the serum of C57BL/6 mice following injection of 300 microg of Salmonella enteritidis LPS. Homodimer constituted between 20 and 40% of the total circulating p40 in endotoxemic sera, as confirmed by both Sephacryl S-100 gel filtration and p40-specific immunoprecipitation analyses. Similar relative amounts of homodimer and monomer were observed in endotoxemic BALB/c, C57BL/6, IFN-gamma-deficient C57BL/6 mice and C57BL/6 mice previously infected with bacille Calmette-Guérin. To determine whether IL-12 p40 homodimer was capable of antagonizing IL-12-dependent IFN-gamma responses in vivo, we pretreated C57BL/6 mice with purified rIL-12 p40 homodimer before i.p. challenge with endotoxin. Mice treated with 40 to 80 microg of p40 homodimer generated 80 to 82% less circulating IFN-gamma during acute endotoxemia than saline controls (p < 0.01). We conclude that p40 homodimer is produced in vivo, functions as a cytokine antagonist in the context of the mouse model of acute endotoxemia, and may represent a novel form of self-regulating cytokine response.
Regiospecific Carbonylative Annulation of Iodophenol Acetates and Acetylenes To Construct the Flavones by a New Catalyst of Palladium−Thiourea−dppp Complex (2000)

[reaction: see text] Regiospecific carbonylative annulation of o-iodophenol acetates and acetylenes mediated by palladium-thiourea-dppp complex in the presence of base at 40 degrees C under a balloon pressure of CO generates diversified flavones in high yields. This newly developed synthetic technology provides a highly efficient method for potential application to the combinatorial synthesis of those heterocycles on the solid support.
Structure-based Design of a Low Molecular Weight, Nonphosphorus, Nonpeptide, and Highly Selective Inhibitor of Protein-tyrosine Phosphatase 1B (2000)

Several protein-tyrosine phosphatases (PTPs) have been proposed to act as negative regulators of insulin signaling. Recent studies have shown increased insulin sensitivity and resistance to obesity in PTP1B knockout mice, thus pointing to this enzyme as a potential drug target in diabetes. Structure-based design, guided by PTP mutants and x-ray protein crystallography, was used to optimize a relatively weak, nonphosphorus, nonpeptide general PTP inhibitor (2-(oxalyl-amino)-benzoic acid) into a highly selective PTP1B inhibitor. This was achieved by addressing residue 48 as a selectivity determining residue. By introducing a basic nitrogen in the core structure of the inhibitor, a salt bridge was formed to Asp-48 in PTP1B. In contrast, the basic nitrogen causes repulsion in other PTPs containing an asparagine in the equivalent position resulting in a remarkable selectivity for PTP1B. Importantly, this was accomplished while retaining the molecular weight of the inhibitor below 300 g/mol.