gebhart/patrepeval huggingface dataset:
Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy (2010)

Inhibitory antibodies to factor VIII (FVIII) are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of patients. Current treatment for inhibitors is based on long-term, daily injections of large amounts of FVIII protein. Liver-directed gene therapy has been used to induce antigen-specific tolerance, but there are no data in hemophilic animals with pre-existing inhibitors. To determine whether sustained endogenous expression of FVIII could eradicate inhibitors, we injected adeno-associated viral vectors encoding canine FVIII (cFVIII) in 2 strains of inhibitor hemophilia A dogs. In 3 dogs, a transient increase in inhibitor titers (up to 7 Bethesda Units [BU]) at 2 weeks was followed by continuous decline to complete disappearance within 4-5 weeks. Subsequently, an increase in cFVIII levels (1.5%-8%), a shortening of clotting times, and a reduction (> 90%) of bleeding episodes were observed. Immune tolerance was confirmed by lack of antibody formation after repeated challenges with cFVIII protein and normal protein half-life. A fourth dog exhibited a strong early anamnestic response (216 BU), with slow decline to 0.8 BU and cFVIII antigen detection by 18 months after vector delivery. These data suggest that liver gene therapy has the potential to eradicate inhibitors and could improve the outcomes of hemophilia A patients.
The Calicheamicin Gene Cluster and Its Iterative Type I Enediyne PKS (2002)

The enediynes exemplify nature's ingenuity. We have cloned and characterized the biosynthetic locus coding for perhaps the most notorious member of the nonchromoprotein enediyne family, calicheamicin. This gene cluster contains an unusual polyketide synthase (PKS) that is demonstrated to be essential for enediyne biosynthesis. Comparison of the calicheamicin locus with the locus encoding the chromoprotein enediyne C-1027 reveals that the enediyne PKS is highly conserved among these distinct enediyne families. Contrary to previous hypotheses, this suggests that the chromoprotein and nonchromoprotein enediynes are generated by similar biosynthetic pathways.
Career Counseling (2015)

Abstract Career counseling helps individuals arrive at decisions about their careers. Organization‐based counseling includes career planning workshops, individual counseling, and outplacement. Some evidence shows that those who received counseling from trained counselors and followed the advice reported better outcomes than those in similar circumstances who did not receive counseling.
Diet and oxidative stress in breast, colon and prostate cancer patients: a case-control study. (1994)

Oxidative stress may be associated with malignant diseases, suggesting the importance of simultaneous analysis of pro- and antioxidation in the search of mechanistic parameters leading to the tumour formation.
Microtubule release from the centrosome (1997)

Although microtubules (MTs) are generally thought to originate at the centrosome, a number of cell types have significant populations of MTs with no apparent centrosomal connection. The origin of these noncentrosomal MTs has been unclear. We applied kinetic analysis of MT formation in vivo to establish their mode of origin. Time-lapse fluorescence microscopy demonstrated that noncentrosomal MTs in cultured epithelial cells arise primarily by constitutive nucleation at, and release from, the centrosome. After release, MTs moved away from the centrosome and tended to depolymerize. Laser-marking experiments demonstrated that released MTs moved individually with their plus ends leading, suggesting that they were transported by minus end-directed motors. Released MTs were dynamic. The laser marking experiments demonstrated that plus ends of released MTs grew, paused, or shortened while the minus ends were stable or shortened. Microtubule release may serve two kinds of cellular function. Release and transport could generate the noncentrosomal MT arrays observed in epithelial cells, neurons, and other asymmetric, differentiated cells. Release would also contribute to polymer turnover by exposing MT minus ends, thereby providing additional sites for loss of subunits. The noncentrosomal population of MTs may reflect a steady-state of centrosomal nucleation, release, and dynamics.
Thromboxane Biosynthesis and Platelet Function in Type II Diabetes Mellitus (1990)

It has been suggested that platelet hyperreactivity in patients with diabetes mellitus is associated with increased platelet production of thromboxane. We therefore compared the excretion of a thromboxane metabolite and platelet function in 50 patients with Type II diabetes mellitus who had normal renal function and clinical evidence of macrovascular disease and in 32 healthy controls. The mean (+/- SD) excretion rate of urinary 11-dehydro-thromboxane B2 was significantly higher in the patients than in the controls (5.94 +/- 3.68 vs. 1.50 +/- 0.79 nmol per day; P less than 0.001), irrespective of the type of macrovascular complication. Tight metabolic control achieved with insulin therapy reduced the levels of 11-dehydro-thromboxane B2 by approximately 50 percent. The fractional conversion of exogenous thromboxane B2 (infused at a rate of 4.5, 45.3, or 226.4 fmol per kilogram of body weight per second) to urinary 11-dehydro-thromboxane B2 was assessed in four patients, in whom it averaged 5.4 +/- 0.1 percent; this value did not differ from that measured in healthy subjects. Aspirin in low doses (50 mg per day for seven days) reduced urinary excretion of the metabolite by approximately 80 percent in four patients. The fact that thromboxane biosynthesis recovered over the following 10 days was consistent with a platelet origin of the urinary metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)
Binding of beta-amyloid to the p75 neurotrophin receptor induces apoptosis. A possible mechanism for Alzheimer's disease. (1997)

Alzheimer's disease is a neurodegenerative disorder characterized by the extracellular deposition in the brain of aggregated beta-amyloid peptide, presumed to play a pathogenic role, and by preferential loss of neurons that express the 75-kD neurotrophin receptor (p75NTR). Using rat cortical neurons and NIH-3T3 cell line engineered to stably express p75NTR, we find that the beta-amyloid peptide specifically binds the p75NTR. Furthermore, 3T3 cells expressing p75NTR, but not wild-type control cells lacking the receptor, undergo apoptosis in the presence of aggregated beta-amyloid. Normal neural crest-derived melanocytes that express physiologic levels of p75NTR undergo apoptosis in the presence of aggregated beta-amyloid, but not in the presence of control peptide synthesized in reverse. These data imply that neuronal death in Alzheimer's disease is mediated, at least in part, by the interaction of beta-amyloid with p75NTR, and suggest new targets for therapeutic intervention.
Anticipation in familial leukemia. (1996)

Anticipation refers to worsening severity or earlier age at onset with each generation for an inherited disease and primarily has been described for neurodegenerative illnesses resulting from expansion of trinucleotide repeats. We have tested for evidence of anticipation in familial leukemia. Of 49 affected individuals in nine families transmitting autosomal dominant acute myelogenous leukemia (AML), the mean age at onset is 57 years in the grandparental generation, 32 years in the parental generation, and 13 years in the youngest generation (P < .001). Of 21 parent-child pairs with AML, 19 show younger ages at onset in the child and demonstrate a mean decline in age at onset of 28 years (P < .001). Of 18 affected individuals from seven pedigrees with autosomal dominant chronic lymphocytic leukemia (CLL), the mean age at onset in the parental generation is 66 years versus 51 years in the youngest generation (P = .008). Of nine parent-child pairs with CLL, eight show younger ages at onset in the child and reveal a mean decline in age at onset of 21 years (P = .001). Inspection of rare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types of leukemia, and lymphoma is also compatible with anticipation. Sampling bias is unlikely to explain these findings. This suggests that dynamic mutation of unstable DNA sequence repeats could be a common mechanism of inherited hematopoietic malignancy with implications for the role of somatic mutation in the more frequent sporadic cases. We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22.
FDTD simulation of photonic devices and circuits based on circular and fan-shaped microdisks (1999)

This paper proposes novel photonic devices and circuits composed of circular and fan-shaped microdisks. Using the finite difference time domain (FDTD) method, we investigated propagation characteristics of light in fundamental elements, the coupler of closely placed disks and the butt-joint of disks. The coupler can be used for extracting the light from a disk laser. It was shown that the efficiency of the light extraction can be over 70% by the coupler. A mode size converter and a tunable filter combined with couplers were numerically demonstrated. The joint can be applied to a compact and sophisticate optical wiring in a large scale circuit, since the joint loss estimated was as low as 0.1 dB.
Suppression of Prostaglandin Synthesis by Arachidonic Acid or Eicosapentaenoic Acid in a Macrophage-Like Cell Line, RAW 264.7, Treated with LPS. (1999)

In a mouse macrophage-like cell line, RAW 264.7, increasing the arachidonic acid (AA) content, by culturing cells with AA, caused profound AA release, irrespective of the lipopolysaccharide (LPS)-treatment, while lowering the AA content, by culturing cells with eicosapentaenoic acid (EPA), decreased it compared with the level in non-modified control cells. However, the release of prostaglandin D2 (PGD2), which had been generated from AA in response to LPS-treatment, was significantly decreased in both AA- and EPA-treated cells. Furthermore, although the amount of PG endoperoxide synthase-2 (PGHS-2) increased following LPS-treatment in all cases, both AA- and EPA-treatment caused a reduction of PGHS activity in LPS-treated cell lysates. Also, the addition of EPA or preincubation with AA in an in vitro PGHS assay system involving an LPS-treated, un-modified macrophage lysate, resulted in rapid inhibition of PGHS activity. These results suggest that both AA- and EPA-treatment inhibit PGD2 synthesis by inactivating PGHS-2 without affecting induction of the protein, and that the increase or decrease in AA content following AA- or EPA-treatment correlates simply with the level of AA release but not with that of PGD2 formation.
Development of Thermal and Photochemical Strategies for Thiol−Ene Click Polymer Functionalization (2008)

A series of alkene-functional polymers were synthesized by controlled polymerization techniques in order to investigate and compare the efficiency and orthogonality of both photochemically and thermally initiated thiol−ene click coupling reactions. The copolymers were designed to have single or multiple alkene-functional groups along the backbone, and to evaluate the robustness of these procedures, functionalization reactions with a library of mercaptans were studied. In comparing the photoinitiated reaction to its thermal counterpart, the thiol−ene photocoupling was found to proceed with higher efficiency, require shorter reaction times for complete conversion, and displayed a higher tolerance to various backbones and functional groups. To examine the orthogonality of the thiol−ene click reaction, an asymmetric telechelic polymer based on PS was designed with alkene functionality at one end and an azide at the other. The thermally initiated thiol−ene coupling was found to be completely orthogonal with the traditional azide/alkyne click reaction allowing the individual chain ends to be quantitatively functionalized without the need for protection/deprotection strategies. From these studies, the demonstrated efficiency and orthogonality of thiol−ene chemistry shows it to be a practical addition to the family of click reactions that are suitable for polymer functionalization.
Molecular insights into renal interstitial fibrosis. (1996)

Progressive interstitial fibrosis accompanied by loss of renal tubules and interstitial capillaries typifies all progressive renal diseases. Dynamic and complex, the process evidently overlaps with matrix remodeling; it may even be reversible. The interstitial fibrous tissue comprises several normal and novel matrix proteins, proteoglycans, and glycoproteins. Interstitial myofibroblasts are a major site of matrix protein overproduction, although resident fibroblasts, tubular cells, and inflammatory cells may contribute. Inadequate matrix degradation also appears to contribute to the fibrogenic process. Two protease cascades, the metalloproteinases and the plasminogen activator/ plasmin family of serine proteases, are implicated in the turnover of interstitial matrix proteins; upregulated expression of protease inhibitors has been observed in each. Increased tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 levels suggest that the intrinsic renal activity of the metalloproteinases and serine proteases are inhibited while matrix proteins accumulate in the interstitium. Several signals that may direct the interstitial fibrogenic process have been identified, but not yet proved to cause it. Upregulated expression of transforming growth factor beta-1, the proteotypic fibrogenic cytokine, has been observed in experimental and human models; it probably does not act alone. There may be supportive roles for platelet-derived growth factor, interleukin-1, basic fibroblast growth factor, angiotensin II, and endothelin-1. Although it is not known why interstitial fibrosis compromises renal function, atrophy of renal tubules may be pivotal. Ischemic necrosis and/or apoptosis may generate nonfunctioning atubular and sclerotic glomeruli. Future studies must delineate the molecular basis of the differences between renal repair and renal destruction by fibrosis, two processes that share many common features.
GI-5005, a yeast vector vaccine expressing an NS3-core fusion protein for chronic HCV infection. (2009)

The HCV nonstructural protein 3 (NS3) and core protein are highly conserved among various HCV genotypes, and several B- and T-cell epitopes have been characterized with these antigens. The immunotherapeutic vaccine GI-5005, being developed by GlobeImmune Inc, is a Tarmogen (targeted molecular immunogen) consisting of recombinant Saccharomyces cerevisiae yeast expressing an HCV NS3-core fusion protein designed to elicit antigen-specific host CD4+ and CD8+ T-cell responses for the treatment of chronic HCV infection. GI-5005 has demonstrated robust immunogenicity in preclinical in vitro and in vivo models. In a phase Ib clinical trial, GI-5005 monotherapy was well tolerated and displayed efficacy in patients with chronic HCV infection. At the time of publication, interim data were available from a completed phase II trial that evaluated a triple therapy of GI-5005 in combination with the standard-of-care (SOC; PEGylated-IFNalpha and ribavirin) regimen, compared with the SOC regimen alone. Triple therapy resulted in improved early virological responses in all treatment-naïve patients. End-of-trial results, including data of sustained virological responses, are required to better evaluate the efficacy of GI-5005 for the improvement of viral clearance and to compare the efficacy of the agent with other approaches such as NS3 protease inhibitors.
Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019 (2020)

Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
Image denoising with multi-layer perceptrons, part 1: comparison with existing algorithms and with bounds (2012)

Image denoising can be described as the problem of mapping from a noisy image to a noise-free image. The best currently available denoising methods approximate this mapping with cleverly engineered algorithms. In this work we attempt to learn this mapping directly with plain multi layer perceptrons (MLP) applied to image patches. We will show that by training on large image databases we are able to outperform the current state-of-the-art image denoising methods. In addition, our method achieves results that are superior to one type of theoretical bound and goes a large way toward closing the gap with a second type of theoretical bound. Our approach is easily adapted to less extensively studied types of noise, such as mixed Poisson-Gaussian noise, JPEG artifacts, salt-and-pepper noise and noise resembling stripes, for which we achieve excellent results as well. We will show that combining a block-matching procedure with MLPs can further improve the results on certain images. In a second paper, we detail the training trade-offs and the inner mechanisms of our MLPs.
Cancer and Altered Metabolism: Potential Importance of Hypoxia-Inducible Factor and 2-Oxoglutarate-Dependent Dioxygenases (2011)

Hypoxia-inducible factor (HIF) deregulation contributes to the Warburg effect. HIF consists of an unstable α subunit and a stable β subunit. In the presence of oxygen, HIFα becomes prolyl hydroxylated by members of the EglN (also called PHD) family, leading to its proteasomal degradation. Under hypoxic conditions, EglN activity is diminished and HIF levels rise. EglN1 is the primary HIF prolyl hydroxylase with EglN2 and EglN3 playing compensatory roles under certain conditions. EglN2 and EglN3 also appear to play HIF-independent roles in regulating cell proliferation and apoptosis, respectively. The EglNs belong to a large family of 2-oxoglutarate-dependent dioxygenases that includes the TET DNA hydroxymethylases and JmjC-containing histone demethylases. Members of this superfamily can be inhibited by endogenous metabolites, including fumarate and succinate, which accumulate in tumors that have fumarate hydratase (FH) or succinate dehydrogenase (SDH) mutations, respectively, as well as by the 2-hydroxyglutarate detected in isocitrate dehydrogenase (IDH) mutant tumors. 2-Oxoglutarate-dependent dioxygenases therefore provide a link between altered metabolism and cancer.
Ternary I−III−VI Quantum Dots Luminescent in the Red to Near-Infrared (2008)

We report the synthesis of a size series of copper indium selenide quantum dots (QDs) of various stoichiometries exhibiting photoluminescence (PL) from the red to near-infrared (NIR). The synthetic method is modular, and we have extended it to the synthesis of luminescent silver indium diselenide QDs. Previous reports on QDs luminescent in the NIR region have been primarily restricted to binary semiconductor systems, such as InAs, PbS, and CdTe. This work seeks to expand the availability of luminescent QD materials to ternary I-III-VI semiconductor systems.
Photoelectrolysis of water in cells with SrTiO3 anodes (1976)

The photoelectrolysis of water in cells with SrTiO3 anodes has been confirmed. The maximum external quantum efficiency at zero bias voltage is 10% (at hν=3.8 eV), about an order of magnitude higher than the maximum value obtained with anodes of TiO2, the only other material so far known to catalyze photoelectrolysis. In agreement with the energy-level model proposed previously, the efficiency is increased because the band bending at the anode surface is about 0.2 eV larger for SrTiO3 than for TiO2, as a result of the smaller electron affinity of SrTiO3.
Substituent effects in the photochemistry of 5-aryl-3,3-diphenyl-2(3H)-furanones. Steady-state and laser flash photolysis studies (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstituent effects in the photochemistry of 5-aryl-3,3-diphenyl-2(3H)-furanones. Steady-state and laser flash photolysis studiesS. Pratapan, K. Ashok, D. R. Cyr, P. K. Das, and M. V. GeorgeCite this: J. Org. Chem. 1988, 53, 25, 5826–5831Publication Date (Print):December 1, 1988Publication History Published online1 May 2002Published inissue 1 December 1988https://pubs.acs.org/doi/10.1021/jo00260a006https://doi.org/10.1021/jo00260a006research-articleACS PublicationsRequest reuse permissionsArticle Views101Altmetric-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
BIAcore Analysis to Test Phosphopeptide-SH2 Domain Interactions (2003)

The elucidation of intracytoplasmic signaling pathways is a ctriical step in the precise understanding of cell biology. In this regard, the identification of intracytoplasmic domains, which are specialized in the transmission of biological messages, has been an enormous breakthrough (). Among these transducing domains, the src homology 2 (SH2) domains are specialized in the interaction with the phosphorylated forms of tyrosine residues (). SH2 domains are classically 100 amino acids long and the three-dimensional structure of several SH2-containing molecules has been resolved. As it is precisely controlled by a subtle balance between protein tyrosine kinases (which phosphorylate) and protein tyrosine phosphatases (which dephosphorylate), the phosphorylation on tyrosine residues is a highly versatile way of dictating the interaction between a given protein and an SH2-containing partner (). The inhibitory receptors (IRs) for major histocompatibility complex (MHC) class Ia and Ib molecules expressed on NK cells, such as the killer cell inhibitory receptors (KIRs) and the CD94-NKG2A heterodimers, respectively, mediate their inhibitory function via intracytoplasmic motifs (IVLS)xYxx(LV), the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) (, ). Upon engagement of these IRs, the tyrosine residue present in ITIMs is phosphorylated, and is therefore capable of interacting with two distinct SH2-containing proteins: the protein tyrosine phosphatases SHP-1 and SHP-2 . In this chapter, we provide protocols (1) to investigate the direct binding of recombinant soluble SH2 domains to phosphorylated peptides using surface plasmon reso-nance (SPR) technology, as well as (2) to measure the affinity constant that characterizes this interaction (, , , , , , ).
Curability of Tumors Bearing Herpes Thymidine Kinase Genes Transfered by Retroviral Vectors (1990)

Retroviral vectors constructed to contain the herpes simplex virus thymidine kinase (HSV-TK) gene were used for transduction of this gene into murine sarcoma and lymphoma cells to yield sublines susceptible in vitro to the cytotoxicity of ganciclovir, a drug specifically activated by HSV-TK. In vivo, ganciclovir induced complete, durable regressions in most mice bearing transplanted HSV-TK-positive sarcomas; its efficacy against lymphomas was only marginal, possibly because of their greater instability of gene expression. The results imply the potential value of an anticancer strategy entailing the prophylactic use of retroviral vectors to create tissue mosaicism for drug sensitivity.