gebhart/patrepeval huggingface dataset:
Control of Proton Sensitivity of the NMDA Receptor by RNA Splicing and Polyamines (1995)

The function of the N-methyl-D-aspartate (NMDA)-preferring glutamate receptor can be regulated by extracellular pH, a process that may be important during ischemia in the brain or during seizures. Protons inhibit NMDA receptor function by 50 percent at pH 7.3 through interactions with the NR1 subunit, and both polyamines and NR1 exon 5 potentiate receptor function through relief of the tonic proton inhibition present at physiological pH. A single amino acid (lysine 211) was identified that mediates the effects of exon 5 in the rat brain. Electroneutral substitutions at this position restored pH sensitivity and, consequently, polyamine relief of tonic inhibition. This effect, together with the structural similarities between polyamines and the surface loop encoded by exon 5, suggest that exon 5 may act as a tethered pH-sensitive constitutive modulator of NMDA receptor function.
Partial Synthetic Glucan Sulfates as Potential New Antithrombotics:  A Review (2001)

Structurally defined sulfated polysaccharides were produced by partial synthesis to develop new antithrombotics as potential heparin alternatives. Glucans of different natural origins were used as starting polymers. The resulting glucan sulfates display pronounced anticoagulant effects; some of them are as active as heparin. According to studies on the structure-activity relationships, besides the molecular weight (MW) and the degree of sulfation (DS), the sulfation pattern and the polysaccharide basic structure are crucial parameters for their anticoagulant potency. Their mode of action differs from that of heparin. Depending on their individual structure, they specifically interfere with various stages of the coagulation process. In vivo, they partly exhibit antithrombotic activity similar to that of heparin. But the in vivo efficacy is not just based on their anticoagulant activity. Their profibrinolytic actions and their strong TFPI-releasing effect may considerably contribute to this overall effect. Due to their manifold interactions with the system of hemostasis, each glucan sulfate shows a structure-dependent, individual action profile. From the investigated glucan sulfates, mainly C2- and C4-sulfated, linear beta-1,3-glucan sulfates with DS > 1.0 and MW between 18 and 50 kDa proved to be most suitable for a potential use as heparin alternatives. The results of this study demonstrate the impact of the various structural parameters on the antithrombotic activity of sulfated polysaccharides. However, the biological actions of sulfated polysaccharides are not limited to hemostasis, but they also show manifold modulating effects on other biological systems. Therefore, the approach of using highly sophisticated carbohydrate drug design might be a possibility to obtain new drugs with specific action profiles.
Textbook of Biochemistry (2002)

Textbook of biochemistry , Textbook of biochemistry , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی
Ultra-sensitive chemical vapor detection using micro-cavity photothermal spectroscopy (2010)

In this paper, I systematically investigated Micro-Cavity PhotoThermal Spectroscopy (MC-PTS), a novel technique for ultra-sensitive detection of chemical molecular species. I first derive the photothermal enhancement factor and noise characteristics of the technique using a generic theoretical model, followed by numerical analysis of a design example using chalcogenide glass micro-disk cavities. Guidelines for sensor material selection and device design are formulated based on the theoretical insight. The numerical analysis shows that this technique features a record photothermal enhancement factor of 10(4) with respect to conventional cavity-enhanced (multi-pass) infrared absorption spectroscopy, and is capable of detecting non-preconcentrated chemical vapor molecules down to the ppt level with a moderate cavity quality factor of 10(5) and a pump laser power of 0.1 W. Such performance qualifies this technique as one of the most sensitive methods for chemical vapor spectroscopic analysis.
Ordered Nanoporous Polymers from Polystyrene−Polylactide Block Copolymers (2002)

Nanoporous polystyrene monoliths were prepared from polystyrene-polylactide (PS-PLA) block copolymers that form hexagonally packed nanocylinders of PLA in a PS matrix. A morphology diagram was developed to determine the range in composition and molecular weight over which this morphology existed. Macroscopic alignment of these materials gave anisotropic monoliths that were subjected to mild degradation conditions leading to the chemical etching of the PLA. The resulting nanoporous monoliths consisted of a polystyrene matrix containing hexagonally close-packed, oriented, and continuous nanoscopic channels (pore size was tunable through synthesis or blending) lined with chemically accessible hydroxyl functional groups. Both the precursors and the porous materials were analyzed moleculary (size-exclusion chromatography and proton nuclear magnetic resonance spectroscopy) and structurally (small-angle X-ray scattering, scanning electron microscopy, and differential scanning calorimetry). In addition, the surface area and pore size distribution of the nanoporous monoliths were characterized (N2 adsorption measurements). These nanoporous materials have remarkable potential as hosts for nanomaterial synthesis, size-selective catalyst supports, and advanced separations.
Methods to Increase the Percentage of Free Fetal DNA Recovered From the Maternal Circulation (2004)

Addition of formaldehyde to maternal blood samples, coupled with careful processing protocols, increases the relative percentage of free fetal DNA, providing a foundation for development of noninvasive prenatal diagnostic tests to distinguish fetal DNA from maternal DNA in the maternal circulation.
Microbicidal spermicide or spermicidal microbicide? (2005)

Vaginal contraception, the oldest method of fertility regulation that remained virtually forgotten for a few decades has recently come under focal review due to an increase in STDs and HIV infections worldwide. Today it is being considered very strongly that a conceptual microbicidal spermicide can tender protection against pregnancy as well as STDs (including AIDS), simultaneously. However the two activities (spermicidal and microbicidal) need to be integrated in vaginal preparations, as many women across the world may be concerned more about the unwanted pregnancy rather than the STI during a coital act. A strong detergent like nonoxynol-9 (N-9) has been used as a spermicide in many local contraceptive preparations and studies have shown that it also exhibits significant microbicidal activity in vitro. However, recent clinical trials have shown that detergent spermicides do not provide any protection against STDs and AIDS but may in fact even promote their transmission. This anomaly has largely been attributed to their surfactant nature that irritates the vagina and kills the normal vaginal flora making it more susceptible to STD infections. An urgent need for a suitable non-detergent spermicide has thus emerged to replace N-9 in local contraceptive preparations. Anticipating the potential of spermicide-based vaginal contraceptives in the reproductive health of women, a large number of synthetic, non-detergent molecules were designed and evaluated at this Institute over recent years. Simultaneously, a number of natural products from terrestrial plants and marine flora/fauna were also evaluated for spermicidal activity. A local contraceptive preparation incorporating the active ingredient from the fruit pericarp of Sapindus mukorossi has successfully completed Phase III clinical trials in India and is ready for marketing. Recent studies have indicated that in comparison to N-9, this ingredient is much less toxic to Lactobacillus spp. and effectively inhibits the growth of Trichomonas vaginalis in vitro. Other candidate spermicides/microbicides under development worldwide have been reviewed briefly.
Regions of the Bacillus subtilis ilv-leu operon involved in regulation by leucine (1993)

The ilv-leu operon of Bacillus subtilis is regulated in part by transcription attenuation. The cis-acting elements required for regulation by leucine lie within a 683-bp fragment of DNA from the region upstream of ilvB, the first gene of the operon. This fragment contains the ilv-leu promoter and 482 bp of the ilv-leu leader region. Spontaneous mutations that lead to increased expression of the operon were shown to lie in an imperfect inverted repeat encoding the terminator stem within the leader region. Mutations within the inverted repeat of the terminator destroyed most of the leucine-mediated repression. The remaining leucine-mediated repression probably resulted from a decrease in transcription initiation. A systematic analysis of other deletions within the ilv-leu leader region identified a 40-bp region required for the derepression that occurred during leucine limitation. This region lies within a potential RNA stem-and-loop structure that is probably required for leucine-dependent control. Deletion analysis also suggested that alternate secondary structures proximal to the terminator are involved in allowing transcription to proceed beyond the terminator. Additional experiments suggested that attenuation of the ilv-leu operon is not dependent on coupling translation to transcription of the leader region. Our data support a model proposed by Grundy and Henkin (F. J. Grundy and T. M. Henkin, Cell 74:475-482, 1993) in which uncharged tRNA acts as a positive regulatory factor to increase gene expression during amino acid limitation.
Cigarette smoking causes biochemical changes in blood that are suggestive of oxidative stress: a case-control study. (1995)

Cigarette smoking has been shown to be a major risk factor for cardiovascular disease, lung cancer, and respiratory diseases. Due to its high content of oxidants, the cigarette smoke is bound to cause a prooxidant/antioxidant imbalance in the blood plasma and tissues of smokers. The study groups were selected from an apparently healthy population living in urban areas, comprising 200 subjects aged 18 to 80 years, half of whom were smokers. In smokers aged 18 to 45 years, the changes of the plasma prooxidant parameters (i.e., lipid peroxides, leukocyte activation, and the antioxidant ones [thiol concentration, total antioxidant capacity]) were not significantly different from those of the age-matched controls, whereas in the 46 to 80 age group they were. In smokers, both antioxidant erythrocyte enzymes, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), exhibited increased activity in the 18 to 45 age group and decreased activity in the 46 to 80 age group. The differences in enzyme activity between the smoking and nonsmoking groups were highly significant for SOD in all ages, whereas for GSH-Px the difference in activity was significant only in the case of older smokers. These findings would suggest that a process of adaptation takes place in younger smokers, in whom the antioxidant systems are able to counteract the oxidant factors, while in older smokers this process is no longer occurring and the plasma and tissues are under permanent oxidative stress. Our results clearly demonstrated that a prooxidant/antioxidant imbalance exists in the blood of smokers, and the determination of leukocytes stimulation index may be a useful and simple way of assessing the oxidative stress status of these individuals. A hypothesis regarding a possible mechanism linking cigarette smoking to the development of coronary heart disease is presented.
Cyclooxygenase inhibitors block uterine tumorigenesis in HMGA1a transgenic mice and human xenografts (2008)

Uterine cancer is a common cause for cancer death in women and there is no effective therapy for metastatic disease. Thus, research is urgently needed to identify new therapeutic agents. We showed previously that all female HMGA1a transgenic mice develop malignant uterine tumors, indicating that HMGA1a causes uterine cancer in vivo. We also demonstrated that HMGA1a up-regulates cyclooxygenase-2 (COX-2) during tumorigenesis in this model. Similarly, we found that HMGA1a and COX-2 are overexpressed in human leiomyosarcomas, a highly malignant uterine cancer. Although epidemiologic studies indicate that individuals who take COX inhibitors have a lower incidence of some tumors, these inhibitors have not been evaluated in uterine cancer. Here, we show that HMGA1a mice on sulindac (a COX-1/COX-2 inhibitor) have significantly smaller uterine tumors than controls. To determine if COX inhibitors are active in human uterine cancers that overexpress HMGA1a, we treated cultured cells with sulindac sulfide or celecoxib (a specific COX-2 inhibitor). Both drugs block anchorage-independent growth in high-grade human uterine cancer cells that overexpress HMGA1a (MES-SA cells). In contrast, neither inhibitor blocked transformation in cells that do not overexpress HMGA1a. Moreover, xenograft tumors from MES-SA cells were significantly inhibited in mice on sulindac. More strikingly, no tumors formed in mice on celecoxib. These preclinical studies suggest that COX inhibitors could play a role in preventing tumor onset or progression in uterine cancers with dysregulation of the HMGA1a-COX-2 pathway. Importantly, these drugs have lower toxicity than chemotherapeutic agents used to treat advanced-stage uterine cancers.
Recombinant Tissue-Type Plasminogen Activator Use for Ischemic Stroke in the United States (2011)

In 2009, 3.4% to 5.2% of AIS patients in the United States received thrombolytics, approximately double the rate of treatment in 2005. Rapid recognition and transport and quick treatment in the emergency department remain goals for further improving treatment rates.
Activation of Transcription by IFN-γ: Tyrosine Phosphorylation of a 91-kD DNA Binding Protein (1992)

Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites.
Heterogeneity of subcellular localization of p53 protein in human glioblastomas. (1994)

Immunohistochemical analysis of the p53 protein in human glioblastomas with known genetic profiles of p53 mutations and allele losses on chromosome 17p demonstrated a heterogeneous pattern of subcellular compartmentalization of the p53 protein. Tumors with a single wild type copy of the p53 gene but with allelic deletions on chromosome 17p exhibit nuclear and/or cytoplasmic accumulation of p53, whereas tumors with both copies of the wild type gene and no allele losses on chromosome 17 do not accumulate p53. Glioblastomas with one normal and one mutated copy of the p53 gene and allelic deletions on 17p distal to p53, on the other hand, show predominantly cytoplasmic staining, probably originating from the wild type p53 protein. Furthermore, tumors with mutations in the same codon of p53 display quite different intracellular distribution suggesting that, in addition to the genotype of p53, the intracellular microenvironment of a particular tumor is important in determining the subcellular localization of the p53 protein.
Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2 (2012)

The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.
Oxidation of 1,2-diaminobenzimidazoles to 3-amino-1,2,4-benzotriazines (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of 1,2-diaminobenzimidazoles to 3-amino-1,2,4-benzotriazinesAlice V. Zeiger and Madeleine M. JoullieCite this: J. Org. Chem. 1977, 42, 3, 542–545Publication Date (Print):February 1, 1977Publication History Published online1 May 2002Published inissue 1 February 1977https://pubs.acs.org/doi/10.1021/jo00423a032https://doi.org/10.1021/jo00423a032research-articleACS PublicationsRequest reuse permissionsArticle Views766Altmetric-Citations42LEARN 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
Involvement of Notch-1 in mammalian retinal neurogenesis: association of Notch-1 activity with both immature and terminally differentiated cells (1995)

The Notch pathway is thought to define an evolutionarily conserved signaling mechanism that regulates the differentiation of immature cells through cells interactions. We have examined the expression of the Notch-1 receptor, the central element of this pathway, in the developing rat retina, where cell-fate choices depend upon a series of local cell interactions. Notch-1 immunoreactivity is associated with differentiating cells at different stages of retinal neurogenesis, suggesting that Notch-1 may play a role in the successive cell-fate determination which governs retinal development. In addition, the Notch-1 immunoreactivity is detected in nuclei of postmitotic, differentiated neurons of the adult retina. Our observations raise the possibility that besides its role in the differentiation of immature cell populations Notch-1 activity may also be involved in the maintenance of the differentiated state.
Development of a Spelling List (1982)

The word list used by the UNIX spelling checker, SPELL, was developed from many sources over several years. As the spelling checker may be used on minicomputers, it is important to make the list as compact as possible. Stripping prefixes and suffixes reduces the list below one third of its original size, hashing discards 60 percent of the bits that remain, and data compression halves it once again. This paper tells how the spelling checker works, how the words were chosen, how the spelling checker was used to improve itself, and how the (reduced) list of 30000 English words was squeezed into 26000 16-bit machine words.
Histone Deacetylase 3 (HDAC3) and Other Class I HDACs Regulate Colon Cell Maturation and p21 Expression and Are Deregulated in Human Colon Cancer (2006)

Inhibitors of histone deacetylases (HDACs) induce growth arrest, differentiation, and apoptosis of colon cancer cell lines in vitro and have demonstrated anti-cancer efficacy in clinical trials. Whereas a role for HDAC1 and -2 in mediating components of the HDAC inhibitor response has been reported, the role of HDAC3 is unknown. Here we demonstrate increased protein expression of HDAC3 in human colon tumors and in duodenal adenomas from Apc1638(N/+) mice. HDAC3 was also maximally expressed in proliferating crypt cells in normal intestine. Silencing of HDAC3 expression in colon cancer cell lines resulted in growth inhibition, a decrease in cell survival, and increased apoptosis. Similar effects were observed for HDAC2 and, to a lesser extent, for HDAC1. HDAC3 silencing also selectively induced expression of alkaline phosphatase, a marker of colon cell maturation. Concurrent with its effect on cell growth, overexpression of HDAC3 and other Class I HDACs inhibited basal and butyrate-induced p21 transcription in a Sp1/Sp3-dependent manner, whereas silencing of HDAC3 stimulated p21 promoter activity and expression. However, the magnitude of the effects elicited by silencing of individual Class I HDACs was significantly less than that induced by HDAC inhibitors. These findings identify HDAC3 as a gene deregulated in human colon cancer and as a novel regulator of colon cell maturation and p21 expression. These findings also demonstrate that multiple Class I HDACs are involved in repressing p21 and suggest that the growth-inhibitory and apoptotic effects induced by HDAC inhibitors are probably mediated through the inhibition of multiple HDACs.
Group III Materials: New Phases and Nano-Particles with Applications in Electronics and Optoelectronics (1999)

Abstract : Objectives: 1. Demonstrate molecular control for the MOCVD growth of gallium and indium chalcogenides. 2. Demonstrate a molecular model approach to the prediction of suitable binding groups to semiconductor surfaces. 3. Demonstrate the application of surface coordination chemistry to the control over the electronic properties of semiconductor nanoparticles.
Purification and characterization of a human T-lymphocyte-derived granulocyte-macrophage colony-stimulating factor (1981)

We have examined the biologic and physical properties of a human T-lymphocyte granulocyte-macrophage colony-stimulating factor (CSF). The source of the factor is a T-lymphoblast cell line (Mo) that was derived from a patient with a T-cell variant of hairy-cell leukemia. The Mo line constitutively produces a number of lymphokines that are normally produced by mitogen-stimulated T lymphocytes. Medium conditioned by Mo cells grown in the absence of serum is especially rich in CSF activity, and using this source we have purified the CSF to a specific activity of about 3.5 x 10(6) colonies per 10(5) Ficoll-Hypaque-separated human bone marrow cells plated per mg protein. The Mo CSF stimulates the formation of both granulocyte and macrophage colonies in vitro (in about equal numbers) and it has a relatively steep dose-response curve. Both the crude and purified preparations stimulated the formation of eosinophil as well as neutrophil colonies; it is unclear whether this is due to the presence of multiple factors with similar physical properties or a single factor with multiple activities. The CSF has little stimulating activity for mouse bone marrow progenitors. Physically, the Mo CSF is an acidic glycoprotein of molecular weight about 34,000. It binds to concanavalin A-Sepharose, is unusually resistant to denaturing agents and heat treatment, and is not inactivated in the presence of sulfhydryl reagents. The Mo CSF is distinct from factors stimulating erythroid colony formation and inhibiting neutrophil migration that are also produced by Mo cells. It differs in several physical and biologic properties from other human CSFs that have been characterized.