gebhart/patrepeval huggingface dataset:
Quantum interference and manipulation of entanglement in silicon wire waveguide quantum circuits (2012)

Integrated quantum photonic waveguide circuits are a promising approach to realizing future photonic quantum technologies. Here, we present an integrated photonic quantum technology platform utilizing the silicon-oninsulator material system, where quantum interference and the manipulation of quantum states of light are demonstrated in components orders of magnitude smaller than previous implementations. Two-photon quantum interference is presented in a multi-mode interference coupler, and the manipulation of entanglement is demonstrated in a Mach–Zehnder interferometer, opening the way to an all-silicon photonic quantum technology platform.
Evidence for a major gene accounting for mild elevation in LDL cholesterol: The NHLBI Family Heart Study (1999)

Studies of rare Mendelian disorders of low density lipoprotein cholesterol (LDL-C) metabolism have identified specific genetic mutations in the LDL receptor and apolipoprotein B. Although these rare mutations account for a small proportion of LDL-C variation, twin and adoption studies indicate that at least 50% of the overall LDL-C observed variation is genetically determined. In a heterogeneous sample of 3227 subjects from the NHLBI Family Heart Study collected from four US centres, we find evidence for a common major gene accounting for mild elevations (1.25 standard deviations) in LDL-C. The analysis favored a recessive model with a frequency of 0.52 for the gene influencing elevated LDL-C, phenotypic means of 113 mg/dl for the normal genotypes and 146 mg/dl for the abnormal genotype, and a significant polygenic heritability. This statistically-inferred major gene accounted for 24% of the variation in LDL-C, with polygenes accounting for another 28% of the variation. Using parameters for major gene transmission estimated in the segregation analysis, LDL-C showed no linkage to the LDL receptor gene (LDLR), nor to the apolipoprotein E gene (APOE), nor to the cholesterol 7alpha-hydroxylase gene (CYP7A1), indicating the major gene effect influencing mild elevation in LDL-C is not explained by any of these candidate loci.
E3 ubiquitin ligase Cbl-b in innate and adaptive immunity (2014)

Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING finger E3 ubiquitin-protein ligase, has been demonstrated to play a crucial role in establishing the threshold for T-cell activation and controlling peripheral T-cell tolerance via multiple mechanisms. Accumulating evidence suggests that Cbl-b also regulates innate immune responses and plays an important role in host defense to pathogens. Understanding the signaling pathways regulated by Cbl-b in innate and adaptive immune cells is therefore essential for efficient manipulation of Cbl-b in emerging immunotherapies for human disorders such as autoimmune diseases, allergic inflammation, infections, and cancer. In this article, we review the latest developments in the molecular structural basis of Cbl-b function, the regulation of Cbl-b expression, the signaling mechanisms of Cbl-b in immune cells, as well as the biological function of Cbl-b in physiological and pathological immune responses in animal models and human diseases.
RIG-E, a human homolog of the murine Ly-6 family, is induced by retinoic acid during the differentiation of acute promyelocytic leukemia cell. (1996)

In vivo all-trans-retinoic acid (ATRA), a differentiation inducer, is capable of causing clinical remission in about 90% of patients with acute promyelocytic leukemia (APL). The molecular basis for the differentiation of APL cells after treatment with ATRA remains obscure and may involve genes other than the known retinoid nuclear transcription factors. We report here the ATRA-induced gene expression in a cell line (NB4) derived from a patient with APL. By differential display-PCR, we isolated and characterized a novel gene (RIG-E) whose expression is up-regulated by ATRA. The gene is 4.0 kb long, consisting of four exons and three introns, and is localized on human chromosome region 8q24. The deduced amino acid sequence predicts a cell surface protein containing 20 amino acids at the N-terminal end corresponding to a signal peptide and an extracellular sequence containing 111 amino acids. The RIG-E coded protein shares some homology with CD59 and with a number of growth factor receptors. It shares high sequence homology with the murine LY-6 multigene family, whose members are small cysteine-rich proteins differentially expressed in several hematopoietic cell lines and appear to function in signal transduction. It seems that so far RIG-E is the closest human homolog of the LY-6 family. Expression of RIG-E is not restricted to myeloid differentiation, because it is also present in thymocytes and in a number of other tissues at different levels.
Dimethylmethylene blue-based spectrophotometry of glycosaminoglycans in untreated urine: a rapid screening procedure for mucopolysaccharidoses. (1989)

Glycosaminoglycans (GAGs) are measured in urine to screen for mucopolysaccharidoses. Other assay procedures are only qualitative (spot tests), can give false-negative results (spot tests, turbidity tests), or are relatively laborious (uronic acid-carbazole test). The present spectrophotometric procedure, based on the color reaction with dimethylmethylene blue (DMB), can be performed directly on untimed urine samples without prior precipitation. Reference values were age dependent. We tested urines of 27 patients with various mucopolysaccharidoses and compared results by three other procedures (cetylpyridinium chloride turbidity tests at pH 4.8 and at pH 7.0, and the uronic acid-carbazole test). In the DMB assay, GAGs were increased in 26 of the 27 patients. The exception was a Morquio A patient, whose activity of the defective enzyme was higher than in classical Morquio patients. Uronic acid, measured in precipitated GAG by the carbazole test, was increased in 23 of the 25 patients so tested. In the turbidity test at pH 7.0, values were increased in 24 of the 27 patients. In contrast, with the citrate-buffered (pH 4.8) turbidity measurement, GAG content was increased in only 19 of the 27 patients. This rapid and easy DMB method is a reliable screening procedure for mucopolysaccharidoses and compares well with procedures used hitherto.
Evaluation of Quinacrine Treatment for Prion Diseases (2003)

Based on in vitro observations in scrapie-infected neuroblastoma cells, quinacrine has recently been proposed as a treatment for Creutzfeldt-Jakob disease (CJD), including a new variant CJD which is linked to contamination of food by the bovine spongiform encephalopathy (BSE) agent. The present study investigated possible mechanisms of action of quinacrine on prions. The ability of quinacrine to interact with and to reduce the protease resistance of PrP peptide aggregates and PrPres of human and animal origin were analyzed, together with its ability to inhibit the in vitro conversion of the normal prion protein (PrPc) to the abnormal form (PrPres). Furthermore, the efficiencies of quinacrine and chlorpromazine, another tricyclic compound, were examined in different in vitro models and in an experimental murine model of BSE. Quinacrine efficiently hampered de novo generation of fibrillogenic prion protein and PrPres accumulation in ScN2a cells. However, it was unable to affect the protease resistance of preexisting PrP fibrils and PrPres from brain homogenates, and a "curing" effect was obtained in ScGT1 cells only after lengthy treatment. In vivo, no detectable effect was observed in the animal model used, consistent with other recent studies and preliminary observations in humans. Despite its ability to cross the blood-brain barrier, the use of quinacrine for the treatment of CJD is questionable, at least as a monotherapy. The multistep experimental approach employed here could be used to test new therapeutic regimes before their use in human trials.
Mast cells are required for experimental oral allergen–induced diarrhea (2003)

Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.
Production of pea lectin in Escherichia coli. (1986)

In order to explore the molecular basis for the glycopeptide specificity of legume lectins, we have developed an experimental system in which specific amino acid alterations can be introduced into the carbohydrate binding site of pea lectin. This system is based on the production of pea lectin in Escherichia coli. The plasmid coding for the lectin was constructed from two lectin cDNA sequences isolated from Pisum sativum seeds (Higgins, T. J. V., Chandler, P. M., Zurawski, G., Button, S. C., and Spencer, D. (1983) J. Biol. Chem. 258, 9544-9549) and an expression vector based on the gene for the outer membrane lipoprotein of E. coli (Nakamura, K., and Inouye, M. (1982) EMBO J. 1, 771-775). The lectin is produced as a single polypeptide chain and forms insoluble aggregates in E. coli cells (2-5 mg/liter). Functional lectin is recovered by solubilization of the aggregates in guanidinium hydrochloride, renaturation in the presence of MnCl2 and CaCl2, and affinity purification on Sephadex. This procedure yields a homogeneous 28,000-dalton protein. Comparison of the recombinant lectin with natural pea lectin in an inhibition of hemagglutination assay demonstrated that there is no detectable difference in the carbohydrate binding properties of the two lectins.
Role of T Lymphocyte Subsets in Protection and Recovery from Hantaan Virus Infection in Mice (1987)

Adult athymic nude (BALB/c background) mice or inbred BALB/c mice were inoculated intraperitoneally with Hantaan virus (HV), and attempts were made to isolate the virus from brain, lung and spleen. Virus was isolated from the organs of BALB/c mice for only a short time after infection but was isolated from various organs of nude mice consistently for at least 84 days after infection. Viral antigen was also detected in various organs of nude mice for a long time after infection. The effects of adoptive transfer of immune serum or immune T cells from BALB/c to nude mice before or after virus inoculation were examined. Before transfer, the T cell fraction was treated with complement (C') (group 1), anti-L3T4 + C' (group 2), anti-Lyt1.2 + C' (group 3) or anti-Lyt2.2 + C' (group 4). When transferred before virus inoculation to test the effects on protection against infection, immune serum and T cells of groups 1, 2 and 4 were effective. When transferred after HV inoculation to test the effects on clearance of virus, group 1 was the most effective followed by group 2. These results suggest that humoral and cellular immunity both have roles in protection against HV infection, and that T cells possessing L3T4- Lyt2+ markers on the cell-surface are especially important for elimination of infectious virus in vivo.
Two adjacent residues in staphylococcal enterotoxins A and E determine T cell receptor V beta specificity. (1993)

The T cell receptor (TCR) V beta-determining region of two bacterial superantigens, staphylococcal enterotoxin A (SEA) and SEE, has been mapped to the COOH-terminal region of SEA and SEE using a panel of recombinant SEA/SEE hybrids. Total TCR V beta mRNA enrichment in human peripheral blood T cell cultures was determined by a novel single-tube amplification technique using a redundant V beta-specific primer. SEA routinely enriched mRNA coding for hV beta 1.1, 5.3, 6.3, 6.4, 6.9, 7.3, 7.4, and 9.1, while SEE, which is 83% homologous to SEA, enriched hV beta 5.1, 6.3, 6.4, 6.9, and 8.1 mRNA. Exchanging residues 206 and 207 was sufficient to convert in toto the TCR V beta response of human peripheral T lymphocytes. In addition, an SEA-reactive murine T cell line, SO3 (mV beta 17), unresponsive to wild-type SEE responded to SEE-S206N207, while an SEE-specific human T cell line, Jurkat (hV beta 8.1), unresponsive to SEA was stimulated strongly by SEA-P206D207. Exchanging all other regions of SEA and SEE except residues 206 and 207 did little to change the V beta response. Thus, the V beta binding region appears to be a stable, discrete domain localized within the COOH-terminal region that is largely unaffected by the considerable amino acid variability between SEA and SEE. This region may interact directly with TCR V beta.
Hematologic Improvement, Transfusion Independence, and Safety Assessed Using Three Alternative Dosing Schedules of Azacitidine in Patients with Myelodysplastic Syndromes. (2006)

Abstract Efficacy and safety of azacitidine (Vidaza®), at the FDA-approved dosing schedule of 75 mg/m2/day x 7 days every 28 days, was demonstrated in a phase III CALGB study by Silverman et al (JCO2002; 20:2429) for the treatment of myelodysplastic syndromes (MDS). The objective of this phase II, multicenter, randomized, open-label study in all FAB subtypes of MDS was to study the treatment response and safety of 3 alternative subcutaneous azacitidine dosing schedules, eliminating the need for weekend azacitidine injections. Patients were randomized to either AZA 5-2-2 (75 mg/m2 day x 5 days, followed by 2 days no treatment, followed by 75 mg/m2/day x 2 days), AZA 5-2-5 (50 mg/m2/day x 5 days, followed by 2 days no treatment, followed by 50 mg/m2/day x 5 days) or AZA 5 (75 mg/m2/day x 5 days). After 6 cycles of azacitidine, patients meeting International Working Group MDS response/improvement criteria (Blood2000; 96:3671), defined as complete remission, partial remission, stable disease, or hematologic improvement, were eligible to receive an additional 12 cycles. As of July 1st, a total of 106 patients have been randomized in the AZA 5-2-2 (n=33), AZA 5-2-5 (n=35), and AZA 5 (n=38) treatment arms. Based on FAB classification, most patients have RA (42%, 45/106) or RAEB (30%, 32/106). Of 80 patients who have received ≥2 cycles of treatment, hematologic improvement (major or minor in at least 1 cell line) occurred in 58% (46/80) of the patients (Table). Median time to improvement in the 3 arms ranged between 1 and 3 cycles (AZA 5-2-2: 1.1, AZA 5-2-5: 3.0, AZA 5: 2.6). Of 38 patients who were RBC transfusion dependent at baseline, 27 (71%) became independent (AZA 5-2-2: 59%, 10/17, AZA 5-2-5: 89%, 8/9; AZA 5: 75%, 9/12). The most common grade 3 or 4 events included neutropenia 29%, 28/98 (AZA 5-2-2: 44%, 14/32; AZA 5-2-5: 20%, 6/30, and AZA 5: 22%, 8/36), thrombocytopenia 15%, 15/98 (AZA 5-2-2: 28%, 9/32; AZA 5-2-5: 10%, 3/30, and AZA 5: 8%, 3/36) and anemia 12%, 12/98 (AZA 5-2-2: 16%, 5/32; AZA 5-2-5: 17%, 5/30, and AZA 5: 6%, 2/36). The frequency of patients with a grade 3 or 4 infection was 15%, 15/98 (AZA 5-2-2: 19%, 6/32; AZA 5-2-5: 23%, 7/30; AZA 5: 6%, 2/36) or hemorrhage was 4%, 4/98 (AZA 5-2-2: 6%, 2/32; AZA 5-2-5: 7%, 2/30; AZA 5: 0/36). Updated data will be available at the time of the meeting. Based on preliminary results, these data indicate that the 3 alternative dosing schedules provide clinical benefit (i.e., transfusion independence and hematologic improvement) and are consistent with the FDA-approved 75 mg/m2/day x 7 days dosing results from previous CALGB studies. Table: Hematologic Improvement Response Rates
Keto-enol tautomerism in the thiophene analogs of naphthacen-5-one (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKeto-enol tautomerism in the thiophene analogs of naphthacen-5-oneWilliam A. Lindley and Denis W. H. MacDowellCite this: J. Org. Chem. 1982, 47, 4, 705–709Publication Date (Print):February 1, 1982Publication History Published online1 May 2002Published inissue 1 February 1982https://pubs.acs.org/doi/10.1021/jo00343a021https://doi.org/10.1021/jo00343a021research-articleACS PublicationsRequest reuse permissionsArticle Views905Altmetric-Citations22LEARN 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
Achieving 550 MHz in an ASIC methodology (2001)

Typically, good automated ASIC designs may be two to five times slower than handcrafted custom designs. At last year's DAC this was examined and causes of the speed gap between custom circuits and ASICs were identified. In particular, faster custom speeds are achieved by a combination of factors: good architecture with well-balanced pipelines; compact logic design; timing overhead minimization; careful floorplanning, partitioning and placement; dynamic logic; post-layout transistor and wire sizing; and speed binning of chips. Closing the speed gap requires improving these same factors in ASICs, as far as possible. In this paper we examine a practical example of how these factors may be improved in ASICs. In particular we show how techniques commonly found in custom design were applied to design a high-speed 550 MHz disk drive read channel in an ASIC design flow.
Glutathione: A Vital Lens Antioxidant (2000)

The reducing compound glutathione (GSH) exists in an unusually high concentration in the lens where it functions as an essential antioxidant vital for maintenance of the tissue's transparency. In conjunction with an active glutathione redox cycle located in the lens epithelium and superficial cortex, GSH detoxifies potentially damaging oxidants such as H2O2 and dehydroascorbic acid. Recent studies have indicated an important hydroxyl radical-scavenging function for GSH in lens epithelial cells, independent of the cells' ability to detoxify H2O2. Depletion of GSH or inhibition of the redox cycle allows low levels of oxidant to damage lens epithelial targets such as Na/K-ATPase, certain cytoskeletal proteins and proteins associated with normal membrane permeability. The level of GSH in the nucleus of the lens is relatively low, particularly in the aging lens, and exactly how the compound travels from the epithelium to the central region of the organ is not known. Recently, a cortical/nuclear barrier to GSH migration in older human lenses was demonstrated by Sweeney et al. The relatively low ratio of GSH to protein -SH in the nucleus of the lens, combined with low activity of the glutathione redox cycle in this region, makes the nucleus especially vulnerable to oxidative stress, as has been demonstrated with use of in vivo experimental animal models such as hyperbaric oxygen, UVA light and the glutathione peroxidase knockout mouse. Effects observed in these models, which are currently being utilized to investigate the mechanism of formation of human senile nuclear cataract, include an increase in lens nuclear disulfide, damage to nuclear membranes and an increase in nuclear light scattering. A need exists for development of therapeutic agents to slow age-related loss of antioxidant activity in the nucleus of the human lens to delay the onset of cataract.
Tumor cell targeting with antibody-avidin complexes and biotinylated tumor necrosis factor alpha. (1997)

Tumor pretargeting with biotinylated antibodies and avidin, followed by a delayed delivery of radioactive-labeled biotin, is currently used for in vivo diagnosis and therapy in cancer patients. Herein, we describe the use of a three-step antibody/avidin targeting approach to increase the local concentration and the persistence of biotinylated human tumor necrosis factor alpha (bio-TNF) on a mouse tumor. Mouse RMA lymphoma cells were transfected with the Thy 1.1 allele (RMA-Thy 1.1) to generate a unique tumor-associated antigen. In vitro pretargeting of RMA-Thy 1.1 cells with the biotinylated anti-Thy 1.1 monoclonal antibody 19E12 (bio-19E12) and NeutrAvidin increased the amount of bio-TNF that bound to the cell (10-20 times in comparison with non-pretargeted cells), as well as its half-life on the surface (>30 times). Furthermore, cell pretargeting reduced by more than 2 orders of magnitude the LD50 of bio-TNF in a cytolytic assay with actinomycin D. Finally, RMA-Thy 1.1 cells, pretreated in vitro with bio-TNF according to the three-step procedure and injected into syngeneic C57/BL6 mice, were less tumorigenic than controls. These results indicate that the three-step targeting approach markedly increases the amount and the persistence of bio-TNF on the cell surface and that cell-bound bio-TNF can trigger cytolytic effects in vitro and antitumor effects in vivo. Tumor pretargeting with biotinylated antibodies and avidin could be a novel strategy for increasing the therapeutic index of TNF.
From Palliation to Epigenetic Therapy in Myelofibrosis (2008)

Myelofibrosis shows a progressive clinical course and usually a poor, lethal prognosis. The molecular pathogenesis of this disease largely remains to be fully understood but the identification of the JAK2V617F mutation in more than half of patients was a major improvement in our understanding of the disease biology and may represent the first biologic marker useful for risk stratification, independently from conventional clinical predictors. After many elusive efforts, new effective treatment strategies are becoming available for this disease. Allogeneic transplantation following reduced-intensity conditioning programs, at least in some patients, may induce not only a hematologic response but also a molecular remission, thus supporting the hope of a possible, definitive eradication of the disease. Moreover, new innovative drugs, targeting either the JAK2V617F mutation or more general oncogenic mechanisms, may provide widely applicable, effective treatments to many patients for whom allogeneic transplantation is not feasible.