gebhart/patrepeval huggingface dataset:
Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. (1993)

We have utilized the polymerase chain reaction technique to selectively amplify a G protein-coupled receptor cDNA from rat kidney proximal convoluted tubule mRNA, which exhibits high homology with previously cloned serotonin receptors. Sequencing of a full-length clone isolated from a rat hippocampal cDNA library revealed an open reading frame of 1,212 base pairs encoding a 404-residue protein with seven hydrophobic regions predicted to represent transmembrane-spanning domains. Within the transmembrane regions, this receptor was found to be 44-50% identical with various members of the 5-HT1, 5-HT5, and 5-HT6 subfamilies with lower (37-40%) homology to the 5-HT2-like receptors. Northern blots revealed a approximately 3.6-kilobase transcript localized in various brain regions with the following rank order of abundance: hypothalamus > hippocampus = mesencephalon > cerebral cortex = olfactory bulb > olfactory tubercle. Expression of this clone in COS-7 cells resulted in the appearance of high affinity, saturable binding of [3H]lysergic acid diethylamide ([3H]LSD; KD = 5 nM) and [3H]serotonin ([3H]5-HT; KD = 1 nM). Among endogenous biogenic amines, only 5-HT completely inhibited radioligand binding. The inhibition of radioligand binding by other serotonergic agents revealed a pharmacological profile that does not correlate with any previously described serotonin receptor subtype. In addition, this receptor exhibits high affinity for a number of tricyclic antipsychotic and antidepressant drugs including clozapine, loxapine, and amitriptyline. In HEK-293 cells stably transfected with this receptor, serotonin elicits a potent stimulation of adenylylcyclase activity. The distinct structural and pharmacological properties of this receptor suggests that it represents a completely novel serotonin receptor subtype, which we propose to designate 5-HT7. Based on its pharmacology and its localization to limbic and cortical regions of the brain, it is likely that this receptor may play a role in several neuropsychiatric disorders that involve serotonergic systems.
Hydrophilic/Hydrophobic Patterned Surfaces as Templates for DNA Arrays (2000)

Addressable DNA arrays are created by photopatterning self-assembled monolayers to form hydrophilic and hydrophobic regions on a gold surface. The hydrophilic regions aid to contain small volumes of different DNA solutions placed on them using an automated pin-tool loading strategy. The method allows for efficient attachment, manipulation, and hybridization of pure DNA strands on the surface.
Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. (1985)

Human peripheral blood mononuclear cells (PBMC) were induced by recombinant interleukin 2 and mitogens to secrete two distinct cytotoxic polypeptides, tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta), previously called lymphotoxin. Treatment of PBMC with recombinant human interleukin 2 (rIL 2) or mitogens in combination with recombinant human interferon-gamma (rIFN-gamma) resulted in augmented production of both TNF-alpha and TNF-beta. rIFN-gamma alone had no effect on production of either cytotoxic polypeptide. TNF-alpha was produced within 2 to 3 hr after induction and was the major cytotoxin produced by PBMC during the first 48 hr of culture, after which time TNF-beta became the predominant species. TNF-beta was first secreted into the media after 8 hr of induction. Enhanced levels of both TNF-alpha and TNF-beta were seen when the PBMC were separated into adherent and nonadherent cells. Both TNF-alpha and TNF-beta were induced in different tumor cell lines of hematopoietic origin. The results demonstrate that the production of TNF-alpha and TNF-beta can be enhanced by two lymphokines, IL 2 and IFN-gamma.
Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function. (1990)

Regions of the hamster alpha 1-adrenergic receptor (alpha 1 AR) that are important in GTP-binding protein (G protein)-mediated activation of phospholipase C were determined by studying the biological functions of mutant receptors constructed by recombinant DNA techniques. A chimeric receptor consisting of the beta 2-adrenergic receptor (beta 2AR) into which the putative third cytoplasmic loop of the alpha 1AR had been placed activated phosphatidylinositol metabolism as effectively as the native alpha 1AR, as did a truncated alpha 1AR lacking the last 47 residues in its cytoplasmic tail. Substitutions of beta 2AR amino acid sequence in the intermediate portions of the third cytoplasmic loop of the alpha 1AR or at the N-terminal portion of the cytoplasmic tail caused marked decreases in receptor coupling to phospholipase C. Conservative substitutions of two residues in the C terminus of the third cytoplasmic loop (Ala293----Leu, Lys290----His) increased the potency of agonists for stimulating phosphatidylinositol metabolism by up to 2 orders of magnitude. These data indicate (i) that the regions of the alpha 1AR that determine coupling to phosphatidylinositol metabolism are similar to those previously shown to be involved in coupling of beta 2AR to adenylate cyclase stimulation and (ii) that point mutations of a G-protein-coupled receptor can cause remarkable increases in sensitivity of biological response.
Effect of a Monoclonal Antibody to PCSK9 on Low-Density Lipoprotein Cholesterol Levels in Statin-Intolerant Patients (2012)

In this phase 2 study in statin-intolerant patients, subcutaneous administration of a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels and was associated with short-term tolerability. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01375764.
Circulating microRNAs as stable blood-based markers for cancer detection (2008)

Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small ( approximately 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
Reconstitution of native human hemoglobin from separated globin chains and alloplex intermediates. (1977)

A complete experimental format is given for the reconstitution of human hemoglobin from the separated heme-free alpha- and beta-globin chains (alpha degrees, beta degrees) and hemin, by two alternative routes. Based on their oxygen binding properties, the reaction of the ferri-forms with reducing agent, and the response of the oxygen binding curves to pH variation and to the addition of the allosteric effector 2,3-diphosphoglycerate, the molecules are native. One reconstitution route uses direct addition of hemin to the separated globin chains with production of the separated subunits, which can then be recombined and reduced. This procedure occasions losses by precipitation in the heme-addition step except at high dilutions, and the yields are low. In the second pathway, either globin chain is mixed with the complementary untreated subunit to form the half-filled (with heme) intermediates, which combine stoichiometrically with hemin. No precipitation accompanies these reactions. For alpha-globin, the yield is about 50% because of incomplete combination with the heme-containing beta chain. For beta-globin, the yield is better than 70%. It is suggested that experiments intended to test either globin chain should use the second route in preparation for structural or functional comparisons with native hemoglobin.
Statistics of « starburst » polymers (1983)

We discuss the growth of completely branched polymer, based on tertiary amine branch points conected by flexible linear portions (« spacers ») each of P monomers. The method is a modified version of the Edwards self consistent fields. We find that ideal « starburst » growth (without any residual secondary amine functions) is restricted to a number of generations m ≤ m1 where m1 ≅ 2.88(ln P + 1.5). This corresponds in space to a limiting radius R1 which increases linearly with P. Well below this limit, the polymer radius R(M), plotted as a function of molecular weight M, should increase like M0.2. Above the limit (R > R 1) we expect compact structures (R ∼ M0.33).
[Inhibition of neovascularization and tumor growth by dexamethasone]. (1992)

It has been proposed that angiogenesis inhibitors should be used for the treatment of diseases accompanied by an uncontrolled angiogenic response, particularly such disease occurring during progressive growth of solid tumors. In this study, the antiangiogenic effect of dexamethasone (DEX) was studied in a system using chorioallantoic membranes (CAM) of fertilized eggs and rabbit corneas. First, DEX was examined for its effect on embryonic angiogenesis using 4, 5 day old CAMs of chick embryos. After the shell and shell membrane was removed, an EV pellet with or without DEX was placed within a silicon ring. Two days later, the antiangiogenic response was evaluated by measuring the avascular zone of the CAM beneath the pellet. When the CAM showed an avascular zone of 3 mm or more in diameter, the response was scored as positive. DEX showed potent antiangiogenic activity and produced an avascular zone in 100% of CAMs at the highest dose tested. (250 ng/egg). Next, inhibitory effect of vascularization and tumor growth by local implant of DEX was observed in a rabbit cornea assay. An intra-corneal pocket extending to within 1 mm of the limbus was used to house a 1-mm3 piece of glioma. In the treatment group, DEX-containing EV pellet was inserted between the limbus and glioma. Ten days after the implantation of glioma and EV pellet, vascular response and tumor growth was evaluated. For morphologic studies, the excised corneas were fixed with formaldehyde fixative and sectioned for light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)
Antimicrobial Studies Using the Therapeutic Tissue Cross-Linking Agent, Sodium Hydroxymethylglycinate: Implication for Treating Infectious Keratitis (2018)

SMG solution exhibits a dose-dependent bactericidal effect on MSSA, MRSA, and PA, with milder effects on VRE and CA. These studies raise the possibility of using SMG TXL for the treatment of infectious keratitis.
Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards (2016)

Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research.
[Construction and screening of SARS-CoV S protein-specific phage displayed antigen library]. (2013)

The aim of this study is to construct a SARS-CoV S protein-specific phage displayed antigen library for the epitope characterization of anti-S monoclonal antibodies (mAbs). First, the full-length gene of SARS-S protein was PCR amplified, purified and then digested with DNase I to obtain DNA fragments in the size range of 50-500 bp. The resulting fragments were blunt-end ligated to the modified phage display vector pComb3XSS. The reactions were electrotransformed into XL1-Blue and infected with VCSM13 helper phage. The SARS-CoV S protein-specific phage displayed antigen library was biopanned and screened against two anti-S mAbs, S-M1 and S-M2. The results showed that we successfully constructed the phage displayed antigen library with a size of 5.7 x 10(6). After three-rounds of biopanning, 14 positive phage clones for S-M1 and 15 for S-M2 were respectively identified. Sequence analyses revealed the possible epitopes of two mAbs. Therefore, the S protein-specific phage displayed antigen library provides a crucial platform for the epitope characterization of anti-S antibodies and it is highly valuable for development of SARS vaccines and diagnostics.
Wavelet domain adaptive visible watermarking (2001)

Pixel based scaling of a watermark image is of paramount importance to make the degree of marking applied variable according to the features of host images. Here, a wavelet domain visible watermarking is proposed. The scaling factors for the pixel based method are adaptively determined by the effect of luminance and local spatial characteristics.
Synthesis and Voltage-Clamp Studies of Methyl 1,4-Dihydro-2,6-dimethyl-5-nitro-4-(benzofurazanyl)pyridine-3-carboxylate Racemates and Enantiomers and of Their Benzofuroxanyl Analogues (1999)

Racemic methyl 1,4-dihydro-2, 6-dimethyl-5-nitro-4-(benzofurazanyl)pyridine-3-carboxylates (+/-)-10 and (+/-)-11 and their benzofuroxanyl analogues (+/-)-12 and (+/-)-13 were prepared using a modified Hantzsch reaction that involved the condensation of nitroacetone with methyl 3-aminocrotonate and the appropriate aldehydes. The racemic mixtures were resolved into the corresponding enantiomers. Whole-cell voltage-clamp studies on L-type Ca2+ channels expressed in a rat insulinoma cell line (RINm5F) showed that all the dextrorotatory antipodes were effective agonists of L-type Ca2+ currents, while the levorotatory ones were weak Ca2+ entry blockers. The (+)-enantiomer of benzofurazan-5'-yl derivative 11 demonstrated unusual activity in that, in addition to producing a potentiation of L-type currents, it interfered with the voltage-dependent gating of L-type channels by producing a net delay of their activation at low voltages. This compound represents an interesting tool to probe L-type Ca2+ channel structure and function.
Diazo group as a new chemical reporter for bioorthogonal labelling of biomolecules (2014)

Diazoacetyl groups undergo spontaneous cycloaddition with strained alkenes and alkynes and can be bioorthogonal reporter groups labelling proteins and glycans.
Adamantyl analogs of 2'-(3-dimethylaminopropylthio)cinnamanilide (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdamantyl analogs of 2'-(3-dimethylaminopropylthio)cinnamanilideV. L. NarayananCite this: J. Med. Chem. 1972, 15, 11, 1180–1182Publication Date (Print):November 1, 1972Publication History Published online1 May 2002Published inissue 1 November 1972https://pubs.acs.org/doi/10.1021/jm00281a024https://doi.org/10.1021/jm00281a024research-articleACS PublicationsRequest reuse permissionsArticle Views45Altmetric-Citations5LEARN 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
Sparse aperiodic arrays for optical beam forming and LIDAR (2017)

We analyze optical phased arrays with aperiodic pitch and element-to-element spacing greater than one wavelength at channel counts exceeding hundreds of elements. We optimize the spacing between waveguides for highest side-mode suppression providing grating lobe free steering in full visible space while preserving the narrow beamwidth. Optimum waveguide placement strategies are derived and design guidelines for sparse (> 1.5 λ and > 3 λ average element spacing) optical phased arrays are given. Scaling to larger array areas by means of tiling is considered.
Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin. (1997)

N901-bR is an immunotoxin with potential clinical activity in SCLC. N901-bR is well tolerated when given by 7-day continuous infusion at the dose of 30 microg/kg(LBW)/d. Neurologic and cardiac toxicity were acceptable when given to patients with refractory SCLC. A second study to evaluate this agent after induction chemoradiotherapy in both limited- and extensive-stage disease was started following completion of this study.
Progressive Transforming Growth Factor β1–induced Lung Fibrosis Is Blocked by an Orally Active ALK5 Kinase Inhibitor (2004)

Pulmonary fibrosis is characterized by chronic scar formation and deposition of extracellular matrix, resulting in impaired lung function and respiratory failure. Idiopathic pulmonary fibrosis (IPF) is associated with pronounced morbidity and mortality and responds poorly to known therapeutic interventions; there are no known drugs that effectively block or reverse progressive fibrosis. Transforming growth factor beta (TGF-beta) is known to mediate extracellular matrix gene regulation and appears to be a major player in both the initiation and progression of IPF. TGF-beta mediates its biological effects through members of a family of activin receptor-like kinases (ALK). We have used a gene transfer model of progressive TGF-beta1-induced pulmonary fibrosis in rats to study a newly described orally active small molecular weight drug that is a potent and selective inhibitor of the kinase activity of ALK5, the specific TGF-beta receptor. We show that the drug inhibits the induction of fibrosis when administered at the time of initiation of fibrogenesis and, most important, blocks progressive fibrosis when administered transiently to animals with established fibrosis. These data show promise of the development of an effective therapeutic intervention for IPF and that inhibition of chronic progressive fibrosis may be achieved by blocking TGF-beta receptor activation.
RECRUITMENT, DISTRIBUTION AND PHENOTYPES OF MAST CELLS IN INTERSTITIAL CYSTITIS (2000)

Redistribution of MC into the epithelium and a high bladder wall MC density distinguish classic IC from nonulcer IC. Our findings suggest an SCF/IL-6-driven MC response in IC. They also indicate a downregulation of the SCF receptor in IC.
4 W single-transverse mode VECSEL utilising intra-cavity diamond heat spreader (2006)

An optically pumped semiconductor vertical external cavity surface emitting laser, with high output power and excellent beam quality operating at a wavelength near 1.05 µm, is reported. A transparent diamond heat spreader was used for thermal management of the laser. The gain structure grown by molecular beam epitaxy includes 13 compressively strained InGaAs quantum wells. Maximum output power of 4 W with diffraction-limited beam (M2≤1.15) was achieved using a 2% output coupler and incident pump power of 20 W. It is shown that power scalability is feasible with the presented laser geometry.
An alternative approach to somatic cell gene therapy. (1988)

Mouse primary skin fibroblasts were infected with a recombinant retrovirus containing human factor IX cDNA. Bulk infected cells capable of synthesizing and secreting biologically active human factor IX protein were embedded in collagen, and the implant was grafted under the epidermis. Sera from the transplanted mice contain human factor IX protein for at least 10-12 days. Loss of immunoreactive human factor IX protein in the mouse serum is not due to graft rejection. Instead, the mouse serum contains anti-human factor IX antibodies, which react with the protein. We suggest that retroviral-infected primary skin fibroblasts offer an alternative approach to somatic cell gene therapy.
Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFκB (2007)

The dietary antioxidant Curcumin has been proposed for cancer chemoprevention since it induces apoptosis and inhibits the formation of breast cancer metastases. Curcumin acts through the inhibition of phosphorylation of the inhibitor of kappa B (IkappaB), which in turn reduces the nuclear translocation of nuclear factor kappa B (NFkappaB), an inflammation- and cell survival-related transcription factor. However, it is not clear whether the strong antimetastatic effect can exclusively be explained by inhibition of NFkappaB. Here, we addressed the effects of Curcumin (IC(50) = 17 muM) in MDA-MB-231 breast cancer cells using microarray gene expression analyses. Among the 62 genes whose expression was significantly altered, we found the two inflammatory cytokines CXCL1 and -2 (Groalpha and -beta) that were downregulated. Further validation of the microarray results by quantitative real-time reverse transcription-polymerase chain reaction, western blots and enzyme-linked immunosorbent assay revealed that Curcumin impairs transcription of CXCL1 and -2 >24 h and reduces the corresponding proteins. Using small interfering RNA techniques, we elucidated the underlying molecular mechanism revealing that reduction of CXCL1 and -2 messenger RNA levels is NFkappaB dependent and requires intact IkappaBalpha expression. Moreover, CXCL1 and -2 silencing leads to downregulation of several metastasis-promoting genes among which we found the cytokine receptor CXCR4. We therefore suggest that the decrease of CXCL1 and -2 mediated by Curcumin is involved in the inhibition of metastasis.
How do inositol phosphates regulate calcium signaling? (1989)

Activation of a variety of cell surface receptors results in the phospholipase C-catalyzed hydrolysis of the minor plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate, with concomitant formation of inositol 1,4,5-trisphosphate and diacylglycerol. There is strong evidence that inositol 1,4,5-trisphosphate stimulates Ca2+ release from intracellular stores. The Ca2+-releasing actions of inositol 1,4,5-trisphosphate are terminated by its metabolism through two distinct pathways. Inositol 1,4,5-trisphosphate is dephosphorylated by a 5-phosphatase to inositol 1,4-bisphosphate; alternatively, inositol 1,4,5-trisphosphate can also be phosphorylated to inositol 1,3,4,5-tetrakisphosphate by a 3-kinase. Although the mechanism of Ca2+ mobilization is understood, the precise mechanisms involved in Ca2+ entry are not known; the proposal that inositol 1,4,5-trisphosphate secondarily elicits Ca2+ entry by emptying an intracellular Ca2+ pool is considered.