gebhart/patrepeval huggingface dataset:
A novel bispecific antisense oligonucleotide inhibiting both bcl-2 and bcl-xL expression efficiently induces apoptosis in tumor cells. (2000)

Bcl-2 and Bcl-xL are inhibitors of apoptosis frequently overexpressed in solid tumors. The bcl-2 and bcl-xL mRNAs share a region of homology comprising nucleotides 605-624 and 687-706, respectively, which differs by only three nucleotides. This sequence does not occur in the proapoptotic splice variant bcl-xS. To test the possibility that oligonucleotides targeting this region have the potential to down-regulate bcl-2 and bcl-xL expression simultaneously, three 2'-O-methoxy-ethoxy-modified phosphorothioate oligonucleotides were designed. These oligonucleotides differed in the number of mismatches to bcl-2 and bcl-xL and in the number of nucleotides to which the modifications were made. The effects of these oligonucleotides on bcl-2 and bcl-xL expression, as well as their abilities to induce apoptosis, were assessed in small cell and non-small cell lung cancer cell lines expressing different basal levels of bcl-2 and bcl-xL. Although all oligonucleotides down-regulated bcl-2 and bcl-xL expression, oligonucleotide 4625, which has no mismatching nucleotides to bcl-2 but three to bcl-xL, two of which were modified by 2'-O-methoxy-ethoxy residues, showed the strongest bispecific activity on the transcript and protein level. In all cell lines this bispecific activity induced apoptotic cell death, as demonstrated by increased uptake of propidium iodide, a 10-100-fold increase in caspase-3-like protease activity, and nuclear condensation and fragmentation. This is the first report of a bcl-2/bcl-xL bispecific antisense oligonucleotide that deserves attention as a therapeutic compound in lung cancer and other malignancies in which bcl-2 and/or bcl-xL are overexpressed.
Changes in phenotypic expression in embryonic and adult cells treated with 5‐azacytidine (1982)

We have previously shown that 5-azacytidine (5-Aza-CR) induced the formation of biochemically differentiated myotubes, adipocytes, and chondrocytes in the mouse embryo cell line, C3H/10T1/2CL8 (10T1/2), and that the induction of the muscle phenotype was cell cycle specific. Here we show that the adipocyte phenotype is also induced maximally in cells treated during S phase. During this period, the minimum treatment time required for the subsequent formation of myotubes was 5 min and the number of myotubes formed was dependent on treatment time. The incorporation of 14C-5-Aza-CR into DNA during the cell cycle, however, was not enhanced during early S phase, suggesting that incorporation of 5-Aza-CR into specific DNA sequences synthesized during early S phase may be required for the expression of the new phenotypes. Single cells, obtained by plating cell suspensions into 16 mm wells at limiting dilution, were treated with 5-Aza-CR during S phase. The resulting clones showed a high frequency of phenotypic conversion, indicating that 5-Aza-CR did not act via a selective mechanism, and several of the clones were capable of expressing more than one phenotype. The cells required more than 2 division cycles after treatment with the analog for the expression of the muscle phenotype and the capacity to differentiate was retained for long periods of time in the absence of cell division. The adult mouse line, CVP3SC6, differentiated into functional striated muscle cells following treatment with 5-Aza-RE. The analog also caused oncogenic transformation in the adult line at the same concentration that was effective at inducing myogenic expression.
DNA VACCINES (1997)

Observations in the early 1990s that plasmid DNA could directly transfect animal cells in vivo sparked exploration of the use of DNA plasmids to induce immune responses by direct injection into animals of DNA encoding antigenic proteins. This method, termed DNA immunization, now has been used to elicit protective antibody and cell-mediated immune responses in a wide variety of preclinical animal models for viral, bacterial, and parasitic diseases. DNA vaccination is particularly useful for the induction of cytotoxic T cells. This review summarizes current knowledge on the vectors, immune responses, immunological mechanisms, safety considerations, and potential for further application of this novel method of immunization.
Concurrent up-regulation of BCL-XL and BCL2A1 induces approximately 1000-fold resistance to ABT-737 in chronic lymphocytic leukemia (2008)

ABT-737 and its orally active analog, ABT-263, are rationally designed inhibitors of BCL2 and BCL-X(L). ABT-263 shows promising activity in early phase 1 clinical trials in B-cell malignancies, particularly chronic lymphocytic leukemia (CLL). In vitro, peripheral blood CLL cells are extremely sensitive to ABT-737 (EC(50) approximately 7 nM), with rapid induction of apoptosis in all 60 patients tested, independent of parameters associated with disease progression and chemotherapy resistance. In contrast to data from cell lines, ABT-737-induced apoptosis in CLL cells was largely MCL1-independent. Because CLL cells within lymph nodes are more resistant to apoptosis than those in peripheral blood, CLL cells were cultured on CD154-expressing fibroblasts in the presence of interleukin-4 (IL-4) to mimic the lymph node microenvironment. CLL cells thus cultured developed an approximately 1000-fold resistance to ABT-737 within 24 hours. Investigations of the underlying mechanism revealed that this resistance occurred upstream of mitochondrial perturbation and involved de novo synthesis of the antiapoptotic proteins BCL-X(L) and BCL2A1, which were responsible for resistance to low and high ABT-737 concentrations, respectively. Our data indicate that after therapy with ABT-737-related inhibitors, resistant CLL cells might develop in lymph nodes in vivo and that treatment strategies targeting multiple BCL2 antiapoptotic members simultaneously may have synergistic activity.
Cloning and sequencing of the beta-lactam hydroxylase gene (cefF) from Streptomyces clavuligerus: gene duplication may have led to separate hydroxylase and expandase activities in the actinomycetes (1991)

The deacetylcephalosporin C synthetase (hydroxylase) gene from Streptomyces clavuligerus has been cloned and sequenced. The open reading frame codes for a protein with an Mr of 34,584. The hydroxylase gene (cefF) is closely linked to the epimerase gene (cefD) and the expandase gene (cefE) and is transcribed in the opposite orientation. The hydroxylase and expandase genes are 59 and 71% identical at the amino acid and DNA levels, respectively. cefE and cefF may have arisen from a gene duplication in the actinomycetes.
A Clinical and Immunological Study of Allergy to Hen's Egg White (1983)

Different subgroups of egg-allergic patients were established according to differences in allergic symptoms provoked by hen's egg white, total IgE-level, RAST (radioallergosorbent test) results to egg white, and age. In each group the pattern of specific IgE-antibodies to individual allergens in the egg white, determined by means of crossed radioimmunoelectrophoresis (CRIE), was compared with the pattern in a control group. The RAST value to egg white was found to exert the strongest influence on the CRIE results. A few statistically significant differences in CRIE results to certain allergens were also observed in other pairs of subgroups of egg-allergic patients. Possible explanations for this are discussed. It was concluded that CRIE studies of allergens in mixed protein solutions, using a series of sera from allergic patients, will most probably give the same results and the same classification of the allergens independent of the characteristics of the patients from which the sera were collected. However, it should be emphasized that the CRIE series must include a sufficient number of patients with high RAST values to the allergen in question. Otherwise some allergens may be missed and the classification of the allergens may be different.
Occurrence of the nitrosamide precursor pyrrolidin-(2)-one in food and tobacco (1994)

Pyrrolidinone was identified in food and tobacco samples by gas chromatography combined with NO-specific chemiluminescence detection (TEA). Up to 77 mg/kg pyrrolidinone were detected in cocoa powders, coffee, coffee surrogates, dried vegetables and tobacco leaves. When treated with excess nitrite under acidic conditions, N-nitrosopyrrolidinone was formed in concentrations up to 44 mg/kg. The nitrosation characteristics of pyrrolidinone indicate its possible conversion to nitrosopyrrolidinone under conditions of the gastric tract.
The low-cost packet radio (1987)

Research on packet switched radio networks requires reconfigurable testbeds with large numbers of readily deployable radios. This motivated the development of a small, low-cost packet radio (LPR) with the flexibility to support extensive network experiments, and to be amenable to tailoring to specific end-use applications. The LPR incorporates a digitally controlled direct sequence minimum shift keyed spread-spectrum radio and a microprocessor-based packet switch. Code changeable surface acoustic wave (SAW) matched filtering provides processing gain at burst symbol rates of 100k and 400k symbols per second in the presence of interference. Coherent recursive integration enhances synchronization performance, provides synchronous detection of the data, and serves the adaptive multipath accumulator. Forward error correction utilizing convolutional encoding and sequential decoding is incorporated at four different code rates for both burst symbol rates. The microprocessor runs the networking software. Requirements, design, and performance data for the LPR engineering model are presented.
Urinary oxalate determination by use of immobilized oxalate oxidase in a continuous-flow system. (1983)

In this procedure, oxalate oxidase (EC 1.2.3.4) immobilized in a continuous-flow system is used to determine oxalate in urine. The hydrogen peroxide formed from oxalate is detected by use of a color reaction with peroxidase (EC 1.11.1.7), 3-methyl-2-benzothiazoline hydrazine, and N,N-dimethylalanine. However, urine contains an oxalate oxidase inhibitor, which cannot be removed by heating, ion-exchange resins, or cellulose columns. This makes it necessary to precipitate the oxalate before assay. The overall assay system is accurate (oxalate recovery, 95.9%), sensitive (less than or equal to 5 mumol/L), precise (within-batch CV less than 1.25%, between-batch CV less than 5%), and relatively rapid (60 samples per working day). The assay system has better accuracy than an established chemical method and a gas-chromatographic method, and is considerably less arduous than and correlates well (r = 0.94) with a modified chemical method. The reference interval for urinary oxalate excretion is 0.16-0.56 mmol per day (n = 97). Only nonphysiological concentrations of ascorbate interfere with the assay, by increasing the oxalate result in the overall assay, presumably by post-micturition formation of oxalate from ascorbate in the urine samples.
Annealing and temperature coefficient study of type IA fibre Bragg gratings inscribed under strain and no strain: implications to optical fibre component reliability (2006)

The annealing properties of Type IA Bragg gratings are investigated and compared with Type I and Type IIA Bragg gratings. The transmission properties (mean and modulated wavelength components) of gratings held at predetermined temperatures are recorded from which decay characteristics are inferred. Our data show critical results concerning the high temperature stability of Type IA gratings, as they undergo a drastic initial decay at 100&deg;C, with a consequent mean index change that is severely reduced at this temperature However, the modulated index change of IA gratings remains stable at lower annealing temperatures of 80&deg;C, and the mean index change decays at a comparable rate to Type I gratings at 80&deg;C. Extending this work to include the thermal decay of Type IA gratings inscribed under strain shows that the application of strain quite dramatically transforms the temperature characteristics of the Type IA grating, modifying the temperature coefficient and annealing curves, with the grating showing a remarkable improvement in high temperature stability, leading to a robust grating that can survive temperatures exceeding 180&deg;C. Under conditions of inscription under strain it is found that the temperature coefficient increases, but is maintained at a value considerably different to the Type I grating. Therefore, the combination of Type I and IA (strained) gratings make it possible to decouple temperature and strain over larger temperature excursions.
Genetic variation in clinical varicella‐zoster virus isolates collected in Ireland between 2002 and 2003 (2004)

Analysis of genetic variation in 16 varicella-zoster virus (VZV) isolates selected at random and circulating in the Irish population between March 2002 and February 2003 was carried out. A 919 bp fragment of the glycoprotein E gene (open reading frame 68) encompassing codon 150, at which a non-synonymous mutation defines the escape mutant VZV-MSP, and including two other epitope regions e1 and c1, was sequenced. No new single nucleotide polymorphisms (SNPs) were detected, indicating stability of these epitopes in clinical isolates of VZV. However, when four informative polymorphic markers consisting of defined regions from genes 1, 21, 50, and 54 were sequenced 14 variable nucleotide positions were identified. Phylogenetic analysis showed the presence of three highly supported clades A, B, and C circulating in the Irish population. Approximately one third (6/16; 37.5%) of the Irish VZV isolates in this study belonged to genotype C, 4/16 (25%) to genotype A, and 4/16 (25%) to genotype B. A smaller number 2/16 (12.5%) belonged to genotype J1. This indicates remarkable heterogeneity in the Irish population given the small sample size. No evidence was found to suggest any of the 16 isolates was a recombinant. These findings have implications for the model of geographic isolation of VZV clades to certain regions as the circulating Irish VZV population appears to comprise approximately equal numbers of each of the main genotypes. This data is inconsistent with a model of strict geographical separation of VZV genotypes and suggests that VZV diversity is more pronounced in certain areas than had been thought previously.
Hematopoiesis from Human Embryonic Stem Cells (2007)

Human embryonic stem cells (hESCs) have the capacity to differentiate into multiple lineages, such as neural and hepatic, and include the ability to form hematopoietic cells. Efforts to develop efficient methods to induce hematopoietic differentiation effectively from hESCs, and generate primitive blood stem cells with multilineage hematopoietic repopulating function, are ongoing in several laboratories. Here, we will discuss the past and current progress of our laboratory in this area, and share our ideas to further this use of hESCs in both experimental and clinical hematology.
Lanthanum complexes of spheroidal carbon shells (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLanthanum complexes of spheroidal carbon shellsJ. R. Heath, S. C. O'Brien, Q. Zhang, Y. Liu, R. F. Curl, F. K. Tittel, and R. E. SmalleyCite this: J. Am. Chem. Soc. 1985, 107, 25, 7779–7780Publication Date (Print):December 1, 1985Publication History Published online1 May 2002Published inissue 1 December 1985https://pubs.acs.org/doi/10.1021/ja00311a102https://doi.org/10.1021/ja00311a102research-articleACS PublicationsRequest reuse permissionsArticle Views2263Altmetric-Citations1098LEARN 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
Curcumin Eliminates Leptin’s Effects on Hepatic Stellate Cell Activation via Interrupting Leptin Signaling (2009)

Nonalcoholic steatohepatitis (NASH) is commonly found in patients with obesity and is often accompanied with abnormally elevated levels of plasma leptin, i.e. hyperleptinemia. A relatively high population of NASH patients develops hepatic fibrosis, even cirrhosis. Hepatic stellate cells (HSCs) are the major effector cells during liver fibrogenesis and could be activated by leptin. The antioxidant curcumin, a phytochemical from turmeric, has been shown to suppress HSC activation in vitro and in vivo. This project is to evaluate the effect of curcumin on leptin-induced HSC activation and to elucidate the underlying mechanisms. We hypothesize that curcumin abrogates the stimulatory effect of leptin on HSC activation by interrupting leptin signaling and attenuating leptin-induced oxidative stress. Curcumin eliminates the stimulatory effects of leptin on regulating expression of genes closely relevant to HSC activation. Curcumin interrupts leptin signaling by reducing phosphorylation levels of leptin receptor (Ob-R) and its downstream intermediators. In addition, curcumin suppresses gene expression of Ob-R in HSCs, which requires the activation of endogenous peroxisome proliferator-activated receptor-gamma and de novo synthesis of glutathione. In conclusion, our results demonstrate that curcumin abrogates the stimulatory effect of leptin on HSC activation in vitro by reducing the phosphorylation level of Ob-R, stimulating peroxisome proliferator-activated receptor-gamma activity, and attenuating oxidative stress, leading to the suppression of Ob-R gene expression and interruption of leptin signaling. These results provide novel insights into therapeutic mechanisms of curcumin in inhibiting HSC activation and intervening liver fibrogenesis associated with hyperleptinemia in NASH patients.
PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis (2014)

Although aging is a known risk factor for idiopathic pulmonary fibrosis (IPF), the pathogenic mechanisms that underlie the effects of advancing age remain largely unexplained. Some age-related neurodegenerative diseases have an etiology that is related to mitochondrial dysfunction. Here, we found that alveolar type II cells (AECIIs) in the lungs of IPF patients exhibit marked accumulation of dysmorphic and dysfunctional mitochondria. These mitochondrial abnormalities in AECIIs of IPF lungs were associated with upregulation of ER stress markers and were recapitulated in normal mice with advancing age in response to stimulation of ER stress. We found that impaired mitochondria in IPF and aging lungs were associated with low expression of PTEN-induced putative kinase 1 (PINK1). Knockdown of PINK1 expression in lung epithelial cells resulted in mitochondria depolarization and expression of profibrotic factors. Moreover, young PINK1-deficient mice developed similarly dysmorphic, dysfunctional mitochondria in the AECIIs and were vulnerable to apoptosis and development of lung fibrosis. Our data indicate that PINK1 deficiency results in swollen, dysfunctional mitochondria and defective mitophagy, and promotes fibrosis in the aging lung.
Recent advances in the management of gout and hyperuricemia (2005)

The therapeutic aims in gout include termination of the acute attack as promptly and gently as possible, prevention of future attacks, prevention or reversal of complications of the, and prevention or reversal of associated features such as obesity, hypertriglyceridemia, hypertension, or alcoholism.
Further evidence for function of the Drosophila Notch protein as a transmembrane receptor. (1993)

N locus mutations associated with unusual mutant phenotypes were found to alter the structure of the encoded protein. Two mutations, NCo and N60g11, eliminate much of the cytoplasmic domain. NCo can act as a null allele or as a competitive inhibitor of N+ function, whereas N60g11 produces dominant gain of function in some cell types. This difference in function can be attributed to retention of cdc10/SWI6 repeats in the Notch60g11 protein. The results suggest a role for these repeats in intracellular signaling and are consistent with action of Notch as a receptor. nd3 and l(1)NB alter extracellular epidermal growth factor-like and lin-12/Notch elements, respectively. nd3 eliminates a conserved cysteine residue, so the mutation may result in complete loss of function for a single Notch epidermal growth factor element. N60g11 and l(1)NB produce related gain-of-function phenotypes. It is proposed that l(1)NB produces an extracellular modification of the protein that stimulates aberrant intracellular signaling by the Notch cytoplasmic domain.
Regulation of Cyclic AMP Response Element‐Binding Protein (CREB) Phosphorylation by Acute and Chronic Morphine in the Rat Locus Coeruleus (1992)

Previous studies have implicated adaptations in the cyclic AMP system in mechanisms of opiate tolerance, dependence, and withdrawal in the rat locus coeruleus. It has been speculated that such adaptations may occur at the level of gene expression. To understand better the mechanism by which opiates produce these intracellular adaptations, we studied morphine regulation of the state of phosphorylation of cyclic AMP response element-binding protein (CREB), a transcription factor that mediates some of the effects of the cyclic AMP system on gene expression. We show here, by use of a back phosphorylation and immunoprecipitation procedure, that acute morphine decreases the state of phosphorylation of CREB, an effect that becomes completely attenuated after chronic morphine administration. In contrast, acute precipitation of opiate withdrawal, via administration of an opiate receptor antagonist, increases the phosphorylation state of CREB. Such regulation of CREB phosphorylation could be part of the molecular pathway by which opiates produce changes in gene expression that lead to addiction.
Quantum computation based on Reciprocal Quantum logic (2017)

This paper gives a newfangled dimension to superconducting logic which is the successor of CMOS logic and other superconducting quantum logic. Reciprocal Quantum logic (RQL) is proposed to achieve the less memory capability. RQL is a modified version of Rapid Single Flux Quantum (RSFQ). We designed and analyzed different RQL logic like half adder, full adder, counter, and Carry Save Adder (CSA) and we achieved an increase in clock speed compared to RSFQ logic by 20%. The designs are made of AndOr and AnotB gate operation and analyzed using WRSPICE software.
Alcoholic Hepatitis (2009)

The association between alcohol intake and alcoholic liver disease has been well documented, although cirrhosis of the liver develops in only a small proportion of heavy drinkers. This review focuses on alcoholic hepatitis, a treatable form of alcoholic liver disease. Since up to 40% of patients with severe alcoholic hepatitis die within 6 months after the onset of the clinical syndrome, appropriate diagnosis and treatment are essential.
Confessions of a Part-time Baker (2015)

"But fate has a reward system. For all those rude customers, long hours, crappy managers, and painful feet, fate gives you something in return. It’s impossible to tell when, but if you do your part, log in enough hours of misery, you eventually—inevitably?—reap the benefits."