gebhart/patrepeval huggingface dataset:
Multiple mechanisms are responsible for altered expression of ornithine decarboxylase in overproducing variant cells. (1986)

We selected and characterized a series of mouse S49 cell variants that overproduce ornithine decarboxylase (ODC). Previously, we described variants that have an amplified ODC gene and produce about 500-fold more ODC than the wild-type cells of origin (L. McConlogue and P. Coffino, J. Biol. Chem. 258:12083-12086, 1983). We examined a series of independent variants that overproduce ODC to a lesser degree and found that a number of mechanisms other than gene amplification are responsible for the increased ODC activity. Variants were selected for resistance to 0.1 mM difluoromethylornithine, an inhibitor of ODC, by either a single or a multistep process. All showed increased ODC activity and increased ODC mRNA steady-state levels. The half-life of the enzyme was not increased in any of the variants. In one class of variant the increase of ODC mRNA was sufficient to account for ODC overproduction. In a second class, the rate of synthesis of ODC polypeptide per ODC mRNA was at least four- to eightfold higher than that in wild-type cells. Therefore, these variants were altered in the translatability of ODC mRNA. Southern analysis showed that gene amplification does not account for the increased ODC mRNA levels in any of the variants. In both variant and wild-type cells, ODC activity was responsive to changes in polyamine pools; activity was reduced following augmentation of pool size. This change in activity was associated with modification of the rate of synthesis and degradation of ODC but no change in the level of ODC mRNA.
Current status of immunization against anthrax: old vaccines may be here to stay for a while (2000)

Anthrax vaccination has become a 'hot' topic. On the one hand, fears that Iraq holds secret caches of anthrax-based weaponry, that other countries may be developing or may have developed similar devices, or that hard-line groups may make their own anthrax-based devices for bioterrorist attacks have focused official attention on the need for means of protection, principally, though, for the military. On the other hand, the unsolved issues of the Gulf War illnesses have left elements of doubt in the minds of some as to the possible role of anthrax (among other) vaccines in this syndrome, and have drawn attention to the shortage of pre-clinical, clinical, pharmacological and safety data on the existing UK and US anthrax vaccines. In the middle are those hotly debating the US and Canadian policies of mandatory anthrax immunization for military personnel or, in the case of the UK policy of voluntary immunization, simply voting with their feet. Compounding matters have been the publicized failures of the US vaccine production facility and the less publicized UK problems of supply. Meanwhile, those in genuine at-risk occupations are left unsure whether, if they can get the vaccine at all, they really want it. Despite two decades of elegant science aimed at formulating alternative vaccines to overcome all the problems of efficacy, safety and supply, such an alternative is at least five years away, and the current status is that we must live with the old vaccines or not vaccinate.
INFRARED SCANNING LASER OPHTHALMOSCOPE IMAGING OF THE MACULA AND ITS CORRELATION WITH FUNCTIONAL LOSS AND STRUCTURAL CHANGES IN PATIENTS WITH STARGARDT DISEASE (2011)

Scanning laser ophthalmoscope infrared fundus images are useful for depicting retinal structural changes in patients with Stargardt disease. A spectral-domain optical coherence tomography/scanning laser ophthalmoscope microperimetry device allows for a direct correlation of structural abnormalities with functional defects that will likely be applicable for the determination of retinal areas for potential improvement of retinal function in these patients during future clinical trials and for the monitoring of the diseases' natural history.
Ctp1CtIP and Rad32Mre11 Nuclease Activity Are Required for Rec12Spo11 Removal, but Rec12Spo11 Removal Is Dispensable for Other MRN-Dependent Meiotic Functions (2009)

The evolutionarily conserved Mre11/Rad50/Nbs1 (MRN) complex is involved in various aspects of meiosis. Whereas available evidence suggests that the Mre11 nuclease activity might be responsible for Spo11 removal in Saccharomyces cerevisiae, this has not been confirmed experimentally. This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11). Furthermore, we show that the CtIP homologue Ctp1 is required for Rec12(Spo11) removal, confirming functional conservation between Ctp1(CtIP) and the more distantly related Sae2 protein from Saccharomyces cerevisiae. Finally, we show that the MRN complex is required for meiotic recombination, chromatin remodeling at the ade6-M26 recombination hot spot, and formation of linear elements (which are the equivalent of the synaptonemal complex found in other eukaryotes) but that all of these functions are proficient in a rad50S mutant, which is deficient for Rec12(Spo11) removal. These observations suggest that the conserved role of the MRN complex in these meiotic functions is independent of Rec12(Spo11) removal.
Fabrication and experimental demonstration of the first 160 Gb/s hybrid silicon-on-insulator integrated all-optical wavelength converter (2012)

We present a hybrid integrated photonic circuit on a silicon-on-insulator substrate that performs ultra high-speed all-optical wavelength conversion. The chip incorporates a 1.25 mm non-linear SOA mounted on the SOI board using gold-tin bumps as small as 14 μm. Τhe device performs chirp filtering and signal polarity inversion with two multi-mode interference (MMI) - based cascaded delay interferometers (DIs) monolithically integrated on the same SOI substrate. Full free spectral range (FSR) tuning of the DIs is accomplished by two independently tuneable on-chip thermal heaters. We demonstrate 160Gb/s all-optical wavelength conversion with power penalties of less than 4.6dB.
On the Convergence of Multiplicative Update Algorithms for Nonnegative Matrix Factorization (2007)

Nonnegative matrix factorization (NMF) is useful to find basis information of nonnegative data. Currently, multiplicative updates are a simple and popular way to find the factorization. However, for the common NMF approach of minimizing the Euclidean distance between approximate and true values, no proof has shown that multiplicative updates converge to a stationary point of the NMF optimization problem. Stationarity is important as it is a necessary condition of a local minimum. This paper discusses the difficulty of proving the convergence. We propose slight modifications of existing updates and prove their convergence. Techniques invented in this paper may be applied to prove the convergence for other bound-constrained optimization problems.
Disturbance of Nuclear and Cytoplasmic TAR DNA-binding Protein (TDP-43) Induces Disease-like Redistribution, Sequestration, and Aggregate Formation (2008)

TAR DNA-binding protein 43 (TDP-43) is the disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Although normal TDP-43 is a nuclear protein, pathological TDP-43 is redistributed and sequestered as insoluble aggregates in neuronal nuclei, perikarya, and neurites. Here we recapitulate these pathological phenotypes in cultured cells by altering endogenous TDP-43 nuclear trafficking and by expressing mutants with defective nuclear localization (TDP-43-DeltaNLS) or nuclear export signals (TDP-43-DeltaNES). Restricting endogenous cytoplasmic TDP-43 from entering the nucleus or preventing its exit out of the nucleus resulted in TDP-43 aggregate formation. TDP-43-DeltaNLS accumulates as insoluble cytoplasmic aggregates and sequesters endogenous TDP-43, thereby depleting normal nuclear TDP-43, whereas TDP-43-DeltaNES forms insoluble nuclear aggregates with endogenous TDP-43. Mutant forms of TDP-43 also replicate the biochemical profile of pathological TDP-43 in FTLD-U/ALS. Thus, FTLD-U/ALS pathogenesis may be linked mechanistically to deleterious perturbations of nuclear trafficking and solubility of TDP-43.
Fibrolamellar Hepatocellular Carcinoma (2009)

Fibrolamellar hepatocellular carcinoma (FHLCC) generally occurs in young individuals lacking a background of chronic liver disease and other risk factors for hepatocellular carcinoma. The clinical presentations of FLHCC are generally nonspecific, and the alpha-fetoprotein level is typically within the normal range in most cases. Imaging studies have a major role in clinical diagnosis, but pathology is the gold standard in confirming diagnosis. Pathological characteristics of FLHCC include the presence of tumor cells with a deeply eosinophilic cytoplasm and macronucleoli surrounded by abundant fibrous bands. The most effective treatment for FLHCC is aggressive surgical resection. This comprehensive literature review gives a full account of the clinical, pathological, and molecular features of FLHCC.
Analysis of Ligand-Dependent Recruitment of Coactivator Peptides to Estrogen Receptor Using Fluorescence Polarization (2004)

Ligand-dependent recruitment of coactivators to estrogen receptor (ER) plays an important role in transcriptional activation of target genes. Agonist-bound ER has been shown to adopt a favorable conformation for interaction with the LXXLL motifs of the coactivator proteins. To further examine the affinity and ligand dependence of the ER-coactivator interaction, several fluorescently tagged short peptides bearing an LXXLL motif (LXXLL peptide) from either natural coactivator sequences or random phage display sequences were used with purified ERalpha or ERbeta in an in vitro high-throughput fluorescence polarization assay. In the presence of saturating amounts of ligand, several LXXLL peptides bound to ERalpha and ERbeta with affinity ranging from 20-500 nm. The random phage display LXXLL peptides exhibited a higher affinity for ER than the natural single-LXXLL coactivator sequences tested. These studies indicated that ER agonists, such as 17beta-estradiol or estrone, promoted the interaction of ER with the coactivator peptides, whereas antagonists such as 4-hydroxytamoxifen or ICI-182,780 did not. Different LXXLL peptides demonstrated different affinities for ER depending on which ligand was bound to the receptor, suggesting that the peptides were recognizing different receptor conformations. Using the information obtained from direct measurement of the affinity of the ER-LXXLL peptide interaction, the dose dependency (EC50) of various ligands to either promote or disrupt this interaction was also determined. Interaction of ER with the LXXLL peptide was observed with ligands such as 17beta-estradiol, estriol, estrone, and genistein but not with ICI-182,780, 4-hydroxytamoxifen, clomiphene, or tamoxifen, resulting in distinct EC50 values for each ligand and correlating well with the ligand biological function as an agonist or antagonist. Ligand-dependent recruitment of the LXXLL peptide to ERbeta was observed in the presence of the ERbeta-selective agonist diarylpropionitrile, but not the ERalpha-selective ligand propyl pyrazole triol. This assay could be used to classify unknown ligands as agonists, antagonists, or partial modulators, based on either the receptor-coactivator peptide affinities or the dose dependency of this interaction in comparison with known compounds.
Molecular identification of PAL-E, a widely used endothelial-cell marker (2005)

The pathologische anatomie Leiden-endothelium (PAL-E) antibody has been used for almost 20 years as a specific marker for vascular endothelial cells. Due to the fact that this antibody works only in very limited applications, the molecular identity of PAL-E has remained unknown. In this work, we demonstrate by double stainings, cross-immunoprecipitations, and transfectants that the PAL-E antigen is identical with a protein designated PV-1 (plasmalemmal vesicle 1) or FELS (fenestrated endothelial-linked structure protein) and is not vimentin, as reported earlier. As the expression of this molecule is by no means restricted to fenestrated endothelium, we suggest the use of the name PLVAP for this protein. Molecular identification of PLVAP should help in the production of new tools for the identification of vascular as opposed to lymphatic endothelium and to elucidate the function of this protein.
Norbornadiene-Fused Heterocycles: Syntheses and Cycloaddition Reactions of 2-Aryl-4,7-dihydro-4,7-methano-2H-isoindoles and 4,7-Dihydro-4,7-methanoisobenzofuran (1995)

Abstract 2-Phenyl- and 2-(p-tolyl)-4,7-dihydro-4,7-methano-2H-isoindole were synthesized by treatment of 3-(diethoxymethyl)bicyclo[2.2.1]hepta-2,5-diene-2-carbaldehyde with aniline or p-toluidine, followed by reduction with sodium borohydride and acid-catalyzed cyclization. It was concluded that the previous claim of the synthesis of methanoisoindole derivatives was incorrect. 4,7-Dihydro-4,7-methanoisobenzofuran was prepared by the reduction of the norbornadiene-monocarbaldehyde with sodium borohydride and subsequent treatment with Amberlyst-15. The p-tolylmethanoisoindole reacted with dimethyl acetylenedicarboxylate to give a novel 1 : 3 adduct. On the other hand, in the reaction of the methanoisobenzofuran with N-phenylmaleimide, spontaneous oxidation of the Diels–Alder cycloadduct took place to give exclusively its epoxide.
Notch3 Gene Amplification in Ovarian Cancer (2006)

Gene amplification is one of the common mechanisms that activate oncogenes. In this study, we used single nucleotide polymorphism array to analyze genome-wide DNA copy number alterations in 31 high-grade ovarian serous carcinomas, the most lethal gynecologic neoplastic disease in women. We identified an amplicon at 19p13.12 in 6 of 31 (19.5%) ovarian high-grade serous carcinomas. This amplification was validated by digital karyotyping, quantitative real-time PCR, and dual-color fluorescence in situ hybridization (FISH) analysis. Comprehensive mRNA expression analysis of all 34 genes within the minimal amplicon identified Notch3 as the gene that showed most significant overexpression in amplified tumors compared with nonamplified tumors. Furthermore, Notch3 DNA copy number is positively correlated with Notch3 protein expression based on parallel immunohistochemistry and FISH studies in 111 high-grade tumors. Inactivation of Notch3 by both gamma-secretase inhibitor and Notch3-specific small interfering RNA suppressed cell proliferation and induced apoptosis in the cell lines that overexpressed Notch3 but not in those with minimal amount of Notch3 expression. These results indicate that Notch3 is required for proliferation and survival of Notch3-amplified tumors and inactivation of Notch3 can be a potential therapeutic approach for ovarian carcinomas.
Activated T cells can induce high levels of CTLA-4 expression on B cells (1995)

Engagement of the TCR/CD3 complex together with ligation of CD28 by its counterstructures B7-1 (CD80) and B7-2 (CD86) on APC are required for mitogenic T cell activation. After activation, T cells not only express B7-1 and B7-2 molecules, but a second receptor for the B7 ligands, CTLA-4, can be found on their surfaces. We here show that B cells can be induced to express CTLA-4 on the plasma membrane. Similar to what has been reported for T cells, CTLA-4 expression on B cells was transient. Purified B cells did not express CTLA-4 when mitogenically activated with alpha IgM and CD40 Ab, but did express the molecule when cultured in the presence of membranes from activated T cells, which suggests that induction of CTLA-4 expression on B cells was dependent on direct cell-cell contact of B lymphocytes and activated T cells. CTLA-4 molecules isolated from either T or B cells were biochemically indistinguishable. Moreover, because the ability of chimeric B7-1/Ig proteins to bind to activated B cells was correlated with CTLA-4 expression levels on these cells, we conclude that B cell-expressed CTLA-4 has ligand binding capacity. These data suggest that costimulatory receptors and their specific ligands not only play a role in T cell stimulation, but contribute in a direct fashion to the regulation of B cell responses.
Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. (1998)

Recombinant humanized anti-HER2 antibody, rhuMAb HER2, inhibits the growth of breast cancer cells overexpressing HER2 and has clinical activity. We explored in preclinical models its capacity to enhance the tumoricidal effects of paclitaxel and doxorubicin. In cultures of naturally HER2-overexpressing cancer cells, rhuMAb HER2 inhibited growth and enhanced the cytotoxic effects of paclitaxel. Treatment of well established BT-474 breast cancer xenografts overexpressing HER2 in athymic mice with rhuMAb HER2 resulted in a dose-dependent antitumor activity. In combination studies, treatment with paclitaxel and rhuMAb HER2 or doxorubicin and rhuMAb HER2 resulted in greater inhibition of growth than that observed with any agent alone. The combination of paclitaxel and rhuMAb HER2 resulted in the highest tumor growth inhibition and had a significantly superior complete tumor regression rate when compared with either paclitaxel or rhuMAb HER2 alone. Clinical trials that are built on these results are under way.
Progress in Gene Technology and Skin Gene Therapy (2004)

Significant progress has been made in gene technology and skin gene therapy in the last few years. Besides the development of suitable animal models, novel molecular technologies such as small inhibitory RNA are discussed, which enable the modification of sequence-specific gene expression. Progress is reported in the field of DNA vaccination agains
Essentials of pharmacology (1996)

General principles and pharmacokinetics autonomic nervous system central nervous system cardiovascular agents haematopoietic and clotting system agents and growth factors autocoids control of pain and inflammation anaesthetics antimicrobial chemotherapy cancer chemotherapy hormones and agents affecting endocrine and metabolic agents agents for the treatment of digestive and liver diseases nutrition and pharmacology. Appendices: toxicology drug interactions.
An object model for genome information at all levels of resolution (2002)

An object model for genome data at all levels of resolution is described. The model was derived by considering the requirements for representing genome related objects in three application domains: genome maps, large-scale DNA sequencing, and exploring functional information in gene and protein sequences. The methodology used for the object-oriented analysis is also described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Exploration of in-fiber nanostructures from capillary instability (2011)

A new class of multi-material fiber that incorporates micrometer-thickness concentric-cylindrical sheets of glass into polymer matrix has emerged. The ultimate lower limit of feature size and recent observation of interesting instability phenomenon in fiber system motivate us to examine fluid instabilities during the complicated thermal drawing fabrication processing. In this paper, from the perspective of a single instability mechanism, classical Plateau-Rayleigh instabilities in the form of radial fluctuation, we explore the stability of various microstructures (such as shells and filaments) in our composite fibers. The attained uniform structures are consistent with theoretical analysis. Furthermore, a viscous materials map is established from calculations and agrees well with various identified materials. These results not only shed insights into other forms of fluid instabilities, but also provide guidance to achieve more diverse nanostructures (such as filaments, wires, and particles) in the microstructured fibers.
A planar electroosmotic micropump (2002)

Electroosmotic (EO) micropumps use field-induced ion drag to drive liquids and achieve high pressures in a compact design with no moving parts. An analytical model applicable to planar, etched-structure micropumps has been developed. This model consists of pressure and flow relations in addition to an analytical expression that can be used to estimate the thermodynamic efficiency of planar EO pumps. The analytical model was applied to guide the design of a pump consisting of an etched EO flow chamber for near-optimal hydraulic power performance. To achieve high efficiency, the working fluid used was deionized (DI) water with a conductivity of 3.0 /spl times/ 10/sup -4/ S/m (pH = 5.7). The EO micropump was fabricated on a soda-lime glass substrate using standard microlithography and chemical wet etching techniques. The active pumping volume of the device consists of a wet-etched flow channel 1-mm long in the flow direction and 0.9 /spl mu/m by 38-mm in cross section. The pump performance agrees well with the theoretical model. The pump can produce a maximum pressure of 0.33 atm and a maximum flow rate of 15 /spl mu/L/min min at 1 kV.
Experimental allergic encephalomyelitis: successful treatment in vivo with a monoclonal antibody that recognizes T helper cells. (1984)

Monoclonal antibody W3/25, which recognizes rat T helper cells, was injected i.p. or i.v. into Lewis rats with clinical signs of experimental allergic encephalomyelitis (EAE). This treatment, which was given 12 or 13 days after inducing EAE by the injection of purified myelin basic protein, significantly affected the course of the disease in that treated animals recovered, on the average, in 2 days, whereas control animals exhibited signs of EAE for a minimum of 4 days. Two pan-T cell monoclonal antibodies given in similar dosage failed to affect the course of the disease.
How I treat heparin-induced thrombocytopenia (2012)

Heparin-induced thrombocytopenia is a prothrombotic adverse drug effect induced by platelet-activating antibodies against multimolecular complexes of platelet factor 4 and heparin. Diagnosis rests on a clinical assessment of disease probability and laboratory testing. Management involves immediate discontinuation of heparin and initiation of an alternative anticoagulant. Because of the frequency of thrombocytopenia among heparinized patients, the limited specificity of widely available immunoassays, the limited availability of more specific functional assays, and clinicians' fears of missing a case of true disease, overtesting, overdiagnosis, and overtreatment have become common. As a result, a substantial number of thrombocytopenic patients are unnecessarily exposed to costly alternative anticoagulants and their attendant risk of bleeding. In this review, we describe not only our approach to the evaluation and management of patients with heparin-induced thrombocytopenia, but also the measures we use to minimize misdiagnosis and unnecessary treatment of patients without the disease. In addition, we propose areas of investigation for improvement of the diagnosis and management of this potentially fatal disorder.