gebhart/patrepeval huggingface dataset:
Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer (2012)

Our aim was to comprehensively analyze promoter hypermethylation of a panel of novel and known methylation markers for thyroid neoplasms and to establish their relationship with BRAF mutation and clinicopathologic parameters of thyroid cancer. A cohort of thyroid tumors, consisting of 44 cancers and 44 benign thyroid lesions, as well as 15 samples of adjacent normal thyroid tissue, was evaluated for BRAF mutation and promoter hypermethylation. Genes for quantitative methylation specific PCR (QMSP) were selected by a candidate gene approach. Twenty-two genes were tested: TSHR, RASSF1A, RARβ2, DAPK, hMLH1, ATM, S100, p16, CTNNB1, GSTP1, CALCA, TIMP3, TGFßR2, THBS1, MINT1, CTNNB1, MT1G, PAK3, NISCH, DCC, AIM1 and KIF1A. The PCR-based "mutector assay" was used to detect BRAF mutation. All p values reported are two sided. Considerable overlap was seen in the methylation markers among the different tissue groups. Significantly higher methylation frequency and level were observed for KIF1A and RARß2 in cancer samples compared with benign tumors. A negative correlation between BRAF mutation and RASSF1A methylation, and a positive correlation with RARß2 methylation were observed in accordance with previous results. In addition, positive correlation with TIMP3 and a marginal correlation with DCC methylation were observed. The present study constitutes a comprehensive promoter methylation profile of thyroid neoplasia and shows that results must be analyzed in a tissue-specific manner to identify clinically useful methylation markers. Integration of genetic and epigenetic changes in thyroid cancer will help identify relevant biologic pathways that drive its development.
Nucleotide sequence of the bovine parainfluenza 3 virus genome: the genes of the F and HN glycoproteins (1987)

By analysing complementary DNA clones constructed from genomic RNA of bovine parainfluenza 3 virus (BPIV3), we determined the nucleotide sequence of the region containing the entire F and HN genes. Their deduced amino acid sequences showed about 80% homologies with those of human parainfluenza 3 virus (HPIV3), about 45% with those of Sendai virus, and about 20% with those of SV5 and Newcastle disease virus (NDV), indicating, together with the results described in the preceding paper on the NP, P, C and M proteins of BPIV3, that BPIV3, HPIV3 and Sendai virus constitute a paramyxovirus subgroup, and that BPIV3 and HPIV3 are very closely related. The F and HN proteins of all these viruses, including SV5 and NDV, however, were shown to have protein-specific structures as well as short but well-conserved amino acid sequences, suggesting that these structures and sequences are related to the activities of these glycoproteins.
Novel Dual Inhibitors of AChE and MAO Derived from Hydroxy Aminoindan and Phenethylamine as Potential Treatment for Alzheimer's Disease (2002)

Carbamate derivatives of N-propargylaminoindans (Series I) and N-propargylphenethylamines (Series II) were synthesized via multistep procedures from the corresponding hydroxy precursors. The respective rasagiline- and selegiline-related series were designed to combine inhibitory activities of both acetylcholine esterase (AChE) and monoamine oxidase (MAO) by virtue of their carbamoyl and propargylamine pharmacophores. Each compound was tested for these activities in vitro in order to find molecules with similar potencies against each enzyme. Compounds with such dual AChE and MAO inhibitory activities are expected to have potential for the treatment of Alzheimer's disease. The observed SAR also offers insight into the requirements of the active sites on these enzymes. A carbamate moiety was found to be essential for AChE inhibition, which was absent in the corresponding hydroxy precursors. The propargyl group caused 2-70-fold decrease in AChE inhibitory activity (depending on the position of the carbamoyl group) of Series I, but had little or no effect in Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were either equipotent to, or slightly (2- to 5-fold) less active as AChE inhibitors than, the corresponding compounds in Series II, while the 4-carbamyloxyphenyls were more potent. The presence of the carbamate moiety in 6- and 7-carbamyloxyphenyls of Series I, considerably decreased MAO-A and -B inhibitory activity, compared to that of the parent hydroxy analogues, while the opposite was true for Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were 2-3 orders of magnitude weaker MAO inhibitors while the 4- carbamyloxyphenyls were equipotent with the corresponding compounds in Series II. In both series, N-methylation of the propargylamine enhanced the MAO (A and B equally) inhibitory activities and decreased the AChE inhibitory activity. Two candidates belonging to the indan and tetralin ring systems (24c, 27b) and one phenethylamine (53d) were identified as possible leads for further development based on the following criteria: (a) comparable AChE and MAO-B inhibitory activities, (b) good to moderate AChE inhibitory activity, and (c) lack of strong MAO-A selectivity. However, it is likely that these compounds will be metabolized to the corresponding phenols, with inhibitory activities against AChE and/or MAO-A or -B, different from those of the parent carbamates. Thus, the apparent enzyme inhibition will be a result of the combined inhibition of all of these individual metabolites. The results of our ongoing in vivo screening programs will be published elsewhere.
Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) (2016)

In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months.
Graphite powder derivatised with poly-l-cysteine using “building-block” chemistry—a novel material for the extraction of heavy metal ions (2005)

Graphite powder derivatised with 4-nitrophenyl moieties (NPcarbon) can be used to successively attach other chemical species to the graphite surface in a controlled and selective manner. Characterisation of these novel materials was undertaken using electrochemical and X-ray photoelectron spectroscopic (XPS) techniques. We demonstrate the proof of concept of this “building-block” chemistry by first reducing the nitro groups on the NPcarbon using a Sn–HCl reduction to the corresponding aniline-like moieties, and then coupling p-nitrobenzoic acid to these via an amide-linkage. Next we demonstrate the utility of this novel derivatisation method by coupling poly-S-benzyl-L-cysteine to the reduced NPcarbon in an analogous manner. After deprotection of the thiol groups using Na in liquid ammonia, the poly-L-cysteine derivatised carbon (PCcarbon) was found to complex cadmium(II) ions. Quantitative analysis of the uptake of Cd2+ from aqueous solutions at pH 5.0 by PCcarbon was carried out using stripping-voltammetry at a boron doped diamond (BDD) electrode and revealed that PCcarbon complexed 137 ± 20 mg of Cd2+ per gram of modified PCcarbon.
Three genes for the human high affinity Fc receptor for IgG (Fc gamma RI) encode four distinct transcription products. (1992)

Three distinct but closely related classes of receptors that bind the Fc portion of immunoglobulin G (Fc gamma RI, -II, and -III) have been identified in humans. Only Fc gamma RI has high affinity for ligand and has a unique third extracellular domain (EC3). We have characterized three genes for human Fc gamma RI (A, B, and C). Each gene consists of six exons, spans 9.4 kilobase pairs, and localizes to chromosome 1. Although they are remarkably similar, genes B and C are notably different from A; in-frame stop codons are present in the EC3 domain of genes B and C, and deletions occur in a splice donor sequence of gene B. Four distinct Fc gamma RI transcripts were analyzed. One transcript, from gene A, would encode a transmembrane receptor with three external domains. A second transcript, an alternatively spliced product of gene B, would encode a two-external domain transmembrane receptor. Two transcripts, from genes B and C, have stop codons in EC3 and would be predicted to generate secreted receptors.
Gold Nanosphere Gated Mesoporous Silica Nanoparticle Responsive to Near-Infrared Light and Redox Potential as a Theranostic Platform for Cancer Therapy (2016)

A gold/mesoporous silica hybrid nanoparticle (GoMe), which possesses the best of both conventional gold nanoparticles and mesoporous silica nanoparticles, such as excellent photothermal converting ability as well as high drug loading capacity and triggerable drug release, has been developed. In contrast to gold nanorod and other heat generating gold nanoparticles, GoMe is photothermal stable and can be repetitively activated through NIR irradiation. Doxorubicin loaded GoMe (DOX@GoMe) is sensitive to both NIR irradiation and intracellularly elevated redox potential. DOX@GoMe coupled with NIR irradiation exhibits a synergistic effect of photothermal therapy and chemotherapy in killing cancer cells. Furthermore, 64Cu-labeled GoMe can successfully detect the existence of clinically relevant spontaneous lung tumors in a urethane-induced lung cancer mouse model through PET imaging. Altogether, GoMe can be utilized as an effective theranostic platform for cancer therapy.
Synergy between A2B Adenosine Receptors and Hypoxia in Activating Human Lung Fibroblasts (2004)

Chronic inflammatory airway diseases, such as asthma, chronic obstructive pulmonary disease and pulmonary fibrosis, are associated with subepithelial fibroblast activation, myofibroblast hyperplasia, hypoxia, and increase in interstitial adenosine concentrations. The goal of this study was to determine the effect of adenosine and its receptors on activation of human lung fibroblasts under normoxia (21% O2) and hypoxia (5% O2). Under the normoxic condition, adenosine and its stable analog, 5'-(N-ethylcarboxamido)-adenosine, via activation of A2B adenosine receptors, increased the release of interleukin (IL)-6 by 14-fold and induced the differentiation of human lung fibroblasts to myofibroblasts. This latter effect of 5'-(N-ethylcarboxamido)-adenosine was abolished by an IL-6-neutralizing antibody. Hypoxia increased the release of IL-6 by 2.8-fold, and there was a synergy between hypoxia and activation of A2B adenosine receptors to increase the release of IL-6 and to induce differentiation of fibroblasts into myofibroblasts. Hypoxia increased the expression of A2B adenosine receptors by 3.4-fold. Altogether, these data suggest that hypoxia amplifies the effect of adenosine on the release of IL-6 and cell differentiation by upregulating the expression of A2B adenosine receptors. Our findings provide a novel mechanism whereby adenosine participates in the remodeling process of inflammatory lung diseases.
Monoclonal anti-idiotypic antibody mimicking the principal neutralization site in HIV-1 GP120 induces HIV-1 neutralizing antibodies in rabbits. (1990)

A murine mAb BAT123 (Ab1) directing to the principal neutralization site of human T cell leukemia virus (HTLV)-IIIB gp120 (amino acid residue 308-322) was used to generate syngeneic anti-Id mAb (Ab2). Among the Ab2, a mAb AB19-4 was characterized by both serologic and biologic methods to be paratope-specific (Ab2 beta), bearing the internal image of the neutralization site. AB19-4 was found to bind specifically to BAT123 and also to its mouse-human chimeric form in ELISA. The binding of AB19-4 to BAT123 was specifically inhibited by HTLV-IIIB gp120 and the synthetic epitope peptides of HTLV-IIIB and HTLV-IIIMN defined by BAT123. AB19-4 also inhibited the binding of BAT123 to HTLV-IIIB-infected H9 cells in flow cytometric studies. Polyclonal goat and sheep antisera against HTLV-IIIB gp120 reacted specifically with AB19-4, suggesting that AB19-4 may recognize cross-species idiotopes. Rabbits immunized with purified AB19-4 generated anti-anti-Id antibodies (Ab3) that reacted specifically with HTLV-IIIB gp120 and the BAT123-binding epitope peptides of HTLV-IIIB and HTLV-IIIMN. The Ab3 bound to H9 cells infected by HTLV-IIIB or HTLV-IIIMN and inhibited the infection of CEM cells by HTLV-IIIB or HTLV-IIIMN, whereas BAT123 also bound H9 cells infected by HTLV-IIIB or HTLV-IIIMN but neutralized only HTLV-IIIB. Our data suggest that AB19-4 mimics the neutralization site on HIV-1 gp120 defined by BAT123. The induction of immunity to HIV using internal-image Ab2 to HIV-neutralizing antibodies may provide a viable approach for developing effective vaccines for AIDS.
Learning with progressive transductive Support Vector Machine (2003)

Support Vector Machine (SVM) is a new learning method developed in recent years based on the foundations of statistical learning theory. By taking a transductive approach instead of an inductive one in support vector classifiers, the test set can be used as an additional source of information about margins. Intuitively, we would expect transductive learning to yield improvements when the training sets are small or when there is a significant deviation between the training and working set subsamples of the total population. In this paper, a progressive transductive support vector machine is addressed to extend Joachims' Transductive SVM to handle different class distributions. It solves the problem of having to estimate the ratio of positive/negative examples from the working set. The experimental results show that the algorithm is very promising.
Analysis of HPV16, 18, 31, and 35 DNA in pre-invasive and invasive lesions of the uterine cervix. (1997)

The results suggest that in advanced cervical intraepithelial neoplasia lesions, a subset of lesions can be identified in which the viral genome is integrated and there is a greater risk of malignant progression. In addition, HPV16 DNA was not present in the integrated form in 26% of tumours, suggesting that integration and subsequent inactivation of the transcriptional regulator, E2, are not essential steps for the development of HPV16 associated carcinoma. In this respect, the behaviour of HPV16 associated tumours is different from HPV18, 31, and 35 associated tumours, where the viral genome is always present in the integrated form.
Fluoroimmunoassay: present status and key problems. (1979)

Fluorescence immunoassay of biological fluids (for example, blood samples) is discussed. We attempt to chart present methods of assay as well as new possibilities. Different fluorescent probes, their detection limit, and methods for reduction of background are discussed; methods for separating the free and bound fraction are also reviewed. Special consideration is given to the possibilities of enhancing sensitivity by developing both instruments and chemical methods, and in particular to the possibilities inherent in time-resolved fluorometric applications and to the use of metal chelates in this application.
Glycogen synthase kinase-3beta suppression eliminates tumor necrosis factor-related apoptosis-inducing ligand resistance in prostate cancer. (2003)

Prostate cancer is a major health threat for American men. Therefore, the development of effective therapeutic options is an urgent issue for prostate cancer treatment. In this study, we evaluated the effect of glycogen synthase kinase-3beta (GSK-3beta) suppression on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human prostate cancer cell lines. In the presence of lithium chloride (LiCl) or SB216763, the GSK-3beta inhibitors, TRAIL-induced cell death was dramatically enhanced, and the enhanced cell death was an augmented apoptotic response evidenced by increased Annexin V labeling and caspase-3 activation. GSK-3beta gene silencing mediated by a small interference RNA (siRNA) duplex also sensitized the cells to TRAIL, confirming the specificity of GSK-3beta suppression. Importantly, TRAIL stimulation increased GSK-3beta tyrosine phosphorylation at Y216, suggesting that GSK-3beta is activated by TRAIL. Furthermore, TRAIL sensitization was associated with increased proteolytic procession of caspase-8 and its downstream target BID, and z-IETD-FMK, the inhibitor specific to active caspase-8 totally blocked LiCl-induced TRAIL sensitization. Finally, Trichodion, a potent nuclear factor-kappaB (NF-kappaB) inhibitor, could not affect LiCl-induced TRAIL sensitization, although GSK-3beta inhibitors significantly blocked TRAIL-reduced NF-kappaB activity in prostate cancer cells. These results indicate that GSK-3beta suppression sensitizes prostate cancer cells to TRAIL-induced apoptosis that is dependent on caspase-8 activities but independent of NF-kappaB activation, and suggest that a mechanism involving GSK-3beta activation may be responsible for TRAIL resistance in prostate cancer cells.
First synthesis of L-ascorbic acid (vitamin C) from a non-carbohydrate source (1998)

M. Banwell, S. Blakey, G. Harfoot and R. Longmore, J. Chem. Soc., Perkin Trans. 1, 1998, 3141 DOI: 10.1039/A806062B
Comparison of Three Lumbar Orthoses Using Motion Assessment During Task Performance (2003)

The Lordosimeter is useful for measuring lumbar motion during orthosis wear. The Aspen and the Boston orthoses provided significant flexion-extension motion restriction compared with no orthosis, but for almost all of the motion measures did not differ from each other. The Cybertech did not differ significantly from the no orthosis condition. The Aspen orthosis was rated significantly more comfortable than the Boston or the Cybertech.
Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials (2014)

NCT01644188 ( NCT01644188).
Band Gap Variation of Size- and Shape-Controlled Colloidal CdSe Quantum Rods (2001)

No abstract prepared.
CD31 − but Not CD31 + Cardiac Side Population Cells Exhibit Functional Cardiomyogenic Differentiation (2005)

Heart failure remains a leading cause of morbidity and mortality. The cellular mechanism underlying the development of cardiac dysfunction is a decrease in the number of viable cardiomyocytes. Recent observations have suggested that the adult heart may contain a progenitor cell population. Side population (SP) cells, characterized by a distinct Hoechst dye efflux pattern, have been shown to exist in multiple tissues and are capable of tissue-specific differentiation. In this report, we confirm the existence of a cardiac SP cell population, immunophenotypically distinct from bone marrow SP cells. Moreover, we demonstrate that among cardiac SP cells, the greatest potential for cardiomyogenic differentiation is restricted to cells negative for CD31 expression and positive for stem cell antigen 1 (Sca1) expression (CD31-/Sca1+). Furthermore, we determine that CD31-/Sca1+ cardiac SP cells are capable of both biochemical and functional cardiomyogenic differentiation into mature cardiomyocytes, with expression of cardiomyocyte-specific transcription factors and contractile proteins, as well as stimulated cellular contraction and intracellular calcium transients indistinguishable from adult cardiomyocytes. We also determine the necessity of cell-extrinsic signaling through coupling, although not fusion, with adult cardiomyocytes in regulating cardiomyogenic differentiation of cardiac SP cells. We, therefore, conclude that CD31-/Sca1+ cardiac SP cells represent a distinct cardiac progenitor cell population, capable of cardiomyogenic differentiation into mature cardiomyocytes through a process mediated by cellular coupling with adult cardiomyocytes.
Aminoimidazoles as Potent and Selective Human β-Secretase (BACE1) Inhibitors (2009)

The identification of small molecule aminoimidazoles as potent and selective human beta-secretase inhibitors is reported. These analogues demonstrate low nannomolar potency for BACE1 in a FRET assay, exhibit comparable activity in a cell-based (ELISA) assay, and show >100x selectivity for the other structurally related aspartyl proteases BACE2, cathepsin D, renin, and pepsin. Our design strategy was supported by molecular modeling studies based on the cocrystal structure of the HTS-hit 3 in the BACE1 active site. These strategies enabled us to integrate pyridine and pyrimidine groups on 3 extending deep into the S3 region of the BACE1 binding pocket and enhancing the ligand's potency. Compound (R)-37 displayed an IC50 value for BACE1 of 20 nM, cellular activity of 90 nM, and >100-fold selectivity over related aspartyl proteases. Acute oral administration of (R)-37 at 30 mg/kg resulted in a significant 71% reduction of plasma Abeta40 measured at the 6 h time point in a Tg2576 mouse model (p < 0.001).
Dexamethasone regulation of plasminogen activator in embryonic and tumor-derived human cells. (1980)

Plasminogen activator (PA) activity in human polymorphonuclear leukocytes and embryonic lung cell cultures is reduced substantially following treatment with glucocorticoids such as dexamethasone. To determine whether tumor-derived cells responded similarly, we compared the effect of dexamethasone on the PA activity of a variety of tumor-derived and embryonic cell cultures. These cultures produced either exclusively M.W. 55,000 to 60,000 urokinase-like PA, exclusively M.W. 73,000 anti-urokinase immunoglobulin-resistant PA, or a mixture of both types of enzyme. Treatment of embryonic human lung, kidney, and uveal melanocyte cell cultures with 10-7 m dexamethasone strongly inhibited both extracellular and cell-associated PA activity. One lung adenocarcinoma-derived and two renal carcinoma-derived cell cultures also showed substantial inhibition of PA activity under these conditions. In contrast, treatment of six independently isolated, melanoma-derived cultures with 10-7 m dexamethasone produced no detectable inhibition of either extracellular or cell-associated PA activity. All six melanoma-derived cultures produced exclusively or principally the M.W. 73,000-type PA. [3H]Dexamethasone-binding assays indicated that the content and size of the cytoplasmic dexamethasone-binding protein were similar in both melanoma-derived and embryonic lung cultures. Our in vitro results suggest that, in vivo , physiological concentrations of glucocorticoids will inhibit the PA activity expressed by many embryonic and several tumor-derived cell types but not that expressed by the melanoma-derived cells.
Nonlinear Absorption Microscopy† (2009)

For the past two decades, nonlinear microscopy has been developed to overcome the scattering problem in thick tissue imaging. Owing to its increased imaging depth and high spatial resolution, nonlinear microscopy becomes the first choice for imaging living tissues. The use of nonlinear optical effects not only facilitates the signal originating from an extremely small volume defined by light focusing but also provides novel contrast mechanisms with molecular specificity. Nonlinear absorption is a nonlinear optical effect in which the absorption coefficient depends on excitation intensity. As a commonly used spectroscopy tool, nonlinear absorption measurement uncovers many photophysical and photochemical processes correlated with electronic states of molecules. Recently we have been focusing on adapting this spectroscopy method to a microscopy imaging technique. The effort leads to a novel modality in nonlinear microscopy-nonlinear absorption microscopy. This article summarizes the principles and instrumentation of this imaging technique and highlights some of the recent progress in applying it to imaging skin pigmentation and microvasculature under ex vivo or in vivo conditions.