gebhart/patrepeval huggingface dataset:
Platelet derived growth factor/tyrosine kinase receptor mediated proliferation. (1993)

PDGF heterodimer of A and B chains, a complete mitogen for 3T3 mouse fibroblasts, exemplifies those growth factors interacting with membrane associated tyrosine kinase receptors. Its binding to the PDGF-receptors results in receptor dimerization and subsequent activation of tyrosine kinase activity in the cytoplasmic protein domain, autophosphorylation of the receptor being the first event in the transduction cascade. Before the ligand-receptor complex is internalized and degraded, receptor stimulation is transmitted to the general transduction network, in which several tyrosine kinase substrates are activated by phosphorylation and changes the cytoplasmic biochemistry. These changes include cytoplasmic alkalinization, increases in the intracellular concentration of cyclic-AMP and Ca2+ and activation of protein kinase C through the degradation of phosphoinositides. The known substrates recruited by the PDGF-receptor association are phosphatidylinositol-3'-kinase, ras-GTPase-activating protein, phospholipase C-gamma, serine-threonine kinase Raf-1 and src and src-related tyrosine kinases. Upon binding of PDGF to its receptor, transactivation of transcriptional and nuclear factors such as c-fos and c-myc genes and dephosphorylation of c-jun occurs, V-sis, the oncogen of the simian sarcoma virus (SSV), is highly homologous to the c-sis/PDGF-B gene that encodes the homodimer of the B-chain of the PDGF receptor. Cells transformed by SSV have been studied as a model system for the autocrine stimulation of the PDGF receptor.
Uracil-DNA glycosylase inhibitor of bacteriophage PBS2: cloning and effects of expression of the inhibitor gene in Escherichia coli (1988)

The uracil-DNA glycosylase inhibitor gene of bacteriophage PBS2 was cloned, and the effects of this inhibitor on Escherichia coli cells that contain uracil-DNA glycosylase activity were determined. A PBS2 genomic library was constructed by inserting EcoRI restriction fragments of PBS2 DNA into a plasmid pUC19 vector. The library was used to transform wild-type (ung+) E. coli, and the presence of the functional inhibitor gene was determined by screening for colonies that supported growth of M13mp19 phage containing uracil-DNA. A clone was identified that carried a 4.1-kilobase EcoRI DNA insert in the vector plasmid. Extracts of cells transformed with this recombinant plasmid lacked detectable uracil-DNA glycosylase activity and contained a protein that inhibited the activity of purified E. coli uracil-DNA glycosylase in vitro. The uracil-DNA glycosylase inhibitor expressed in these E. coli was partially purified and characterized as a heat-stable protein with a native molecular weight of about 18,000. Hence, we conclude that the PBS2 uracil-DNA glycosylase inhibitor gene was cloned and that the gene product has properties similar to those from PBS2-infected Bacillus subtilis cells. Inhibitor gene expression in E. coli resulted in (i) a weak mutator phenotype, (ii) a growth rate similar to that of E. coli containing pUC19 alone, (iii) a sensitivity to the antifolate drug aminopterin similar to that of cells lacking the inhibitor gene, and (iv) an increased resistance to the lethal effects of 5-fluoro-2'-deoxyuridine. These physiological properties are consistent with the phenotypes of other ung mutants.
Practical and economical method for using biotinylated DNA probes with bacterial colony blots to identify diarrhea-causing Escherichia coli (1990)

A simple and economical method was developed for using biotinylated DNA probes to hybridize with bacterial colonies belonging to the various categories of diarrhea-causing Escherichia coli. Simplification and cost containment were achieved by using Whatman no. 541 filter papers instead of nitrocellulose, by minimizing the concentration of proteinase K (an expensive but necessary reagent used to pretreat the colony blots prior to hybridization with biotin-labeled DNA probes) and by reusing hybridization solution containing labeled probe DNA. After exposing the colony blots to lysing solution and steam, followed by lysozyme (1.5 mg/ml), sucrose (25%), and proteinase K (10 micrograms/ml) treatments, biotinylated probes were used to detect enterotoxigenic, enteropathogenic, enterohemorrhagic, diffuse adherence, and enteroinvasive categories of diarrhea-causing E. coli with a high level of sensitivity and specificity. Three independent observers who were experienced in reading DNA blots recorded remarkably similar results, while less satisfactory results were obtained when the blots were read by an inexperienced observer. This technique will be useful in laboratories in which radioactive isotopes are unavailable or impractical and in which budgets are restricted.
SYNTHESIS AND ANTIMICROBIAL EVALUATION OF OXAZOLE-1,4-NAPHTHQUINONES (2002)

Several routes for preparing oxazole nucleus fused to 1,4-naphthoquinone moiety were studied. Three new oxazole-l,4-naphthoquinone derivatives (4a-c) were prepared and evaluated against phatogenic bacteria. The use of ortho-ester methodology was found to be the best synthetic method for preparing these oxazoles, which showed very low antibacterial activity. The intermediate 2 showed a broad spectrum of activity comparable with oxacillin and vancomycin.
Density functional study of Ag in Ge<sub>2</sub>Se<sub>3</sub> (2009)

We present density functional calculations of isolated Ag atoms in a crystalline model for Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Se <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> . We present defect levels for interstitial and substitutional sites. Absent other defects, we show that interstitial Ag donates an electron to the conduction band of Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Se <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> because the highest occupied atomic level is well above the Kohn-Sham conduction band edge. Thus, we predict that Ag is always positively charged, although its charge state is fractional and significantly below +1. This results accounts for both the conductive properties of Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Se <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> :Ag and the persistence of field-driven Ag motion. The presence of three fold-coordinated Ge alters the physics considerably. The midgap Ge states are electron sinks for the conduction electrons donated by Ag. Finally, we present evidence that Ag will displace Ge into interstitial sites, creating both dangling Ge orbitals and substitutional Ag with a strong Ag-Ge bond.
Fucose: biosynthesis and biological function in mammals (2003)

Fucose is a deoxyhexose that is present in a wide variety of organisms. In mammals, fucose-containing glycans have important roles in blood transfusion reactions, selectin-mediated leukocyte-endothelial adhesion, host–microbe interactions, and numerous ontogenic events, including signaling events by the Notch receptor family. Alterations in the expression of fucosylated oligosaccharides have also been observed in several pathological processes, including cancer and atherosclerosis. Fucose deficiency is accompanied by a complex set of phenotypes both in humans with leukocyte adhesion deficiency type II (LAD II; also known as congenital disorder of glycosylation type IIc) and in a recently generated strain of mice with a conditional defect in fucosylated glycan expression. Fucosylated glycans are constructed by fucosyltransferases, which require the substrate GDP-fucose. Two pathways for the synthesis of GDP-fucose operate in mammalian cells, the GDP-mannose-dependent de novo pathway and the free fucose-dependent salvage pathway. In this review, we focus on the biological functions of mammalian fucosylated glycans and the biosynthetic processes leading to formation of the fucosylated glycan precursor GDP-fucose.
A frequency-division multiple-access system concept for 30/20 GHz high-capacity domestic satellite service (1983)

Covers advancements in spacecraft and tactical and strategic missile systems, including subsystem design and application, mission design and analysis, materials and structures, developments in space sciences, space processing and manufacturing, space operations, and applications of space technologies to other fields.
HMGB1 as a cytokine and therapeutic target (2002)

HMGB1 is an abundant nuclear and cytoplasmic protein present in mammalian cells. It is traditionally known as a DNA binding protein involved in maintenance of nucleosome structure and regulation of gene transcription. Beyond these intracellular roles, we recently discovered that HMGB1 is released from activated macrophages and functions as a late mediator of lethal endotoxemia. Addition of HMGB1 to macrophage cultures activates cytokine release. When released into the extracellular milieu, HMGB1 causes systemic inflammatory responses including acute lung injury, epithelial barrier dysfunction, and death. Passive immunization with anti-HMGB1 antibodies confers significant protection against lethality induced by LPS administration and sepsis caused by cecal perforation in mice. Truncation of HMGB1 into individual structural domains revealed that the HMGB1 A box, a DNA-binding motif, specifically antagonizes the activity of HMGB1 and rescues mice from lethal sepsis caused by cecal perforation. Thus, strategies that target HMGB1 with specific antibodies or antagonists have potential for treating lethal systemic inflammatory diseases characterized by excessive HMGB1 release.
TNF-α-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1—Relevance for Concanavalin A-Induced Hepatitis (2001)

TNF-alpha has been clearly identified as central mediator of T cell activation-induced acute hepatic injury in mice, e.g., Con A hepatitis. In this model, liver injury depends on both TNFRs, i.e., the 55-kDa TNFR1 as well as the 75-kDa TNFR2. We show in this report that the hepatic TNFRs are not transcriptionally regulated, but are regulated by receptor shedding. TNF directly mediates hepatocellular death by activation of TNFR1 but also induces the expression of inflammatory proteins, such as cytokines and adhesion molecules. Here we provide evidence that resistance of TNFR1(-/-) and TNFR2(-/-) mice against Con A hepatitis is not due to an impaired production of the central mediators TNF and IFN-gamma. Con A injection results in a massive induction of ICAM-1, VCAM-1, and E-selectin in the liver. Lack of either one of both TNFRs did not change adhesion molecule expression in the livers of Con A-treated mice, presumably reflecting the fact that other endothelial cell-activating cytokines up-regulated adhesion molecule expression. However, treatment of TNFR1(-/-) and TNFR2(-/-) mice with murine rTNF revealed a predominant role for TNFR1 for the induction of hepatic adhesion molecule expression. Pretreatment with blocking Abs against E- and P-selectin or of ICAM(-/-) mice with anti-VCAM-1 Abs failed to prevent Con A hepatitis, although accumulation of the critical cell population, i.e., CD4(+) T cells was significantly inhibited. Hence, up-regulation of adhesion molecules during acute hepatitis unlikely contributes to organ injury but rather represents a defense mechanism.
Developmental Expression of Wnt Signaling Factors in Mouse Brain (2002)

The Wnt signaling pathway has been implicated in a variety of biological events inducing neurogenesis. In this study, we aim to investigate the expression pattern of various components of the Wnt pathway including b-catenin and its partners LEF-1/TCF-4, GSK-3beta and their nuclear target genes such as c-myc and cyclin D1 during mouse brain development. We performed a series of Western blot and immunohistochemistry of brain cortex, brainstem, and cerebellum which revealed differential accumulation of these proteins in different types of brain cells including neurons, astrocytes, and oligodendrocytes at different developmental stages. Intense cytoplasmic immunolabeling of beta-catenin in 5 day old neurons throughout the cortex and brainstem significantly decreased as the brain developed, whereas the level of GSK-3beta, the protein that phosphorylates beta-catenin and causes its destabilization, increased during brain maturation. On the other hand, high level accumulation of LEF-1 and TCF-4 in neurons and astrocytes at the early stage of brain development diminished at the later stages. Interestingly, while the majority of LEF-1 and TCF-4 immunoreactivity was detected in the cytoplasm of neurons, it was evident that both proteins accumulated in the nuclei of astrocytes. Examination of cyclin D1, a protein that controls the cell cycle and proliferation, exhibited an intense staining in the nuclei of astrocytes throughout brain parenchyma during development. Interestingly, cyclin D was found in the cytoplasm of neurons from cortex, brainstem, and cerebellum during brain development. These data provide compelling evidence for the differential expression of the Wnt signaling pathway during brain development, and suggest that these signaling pathways may function differently in various brain regions and cell types.
Pyruvat-Produktion durch acetatauxotrophe Escherichia coli - Stämme (2003)

Pyruvate is a central intermediate of cellular metabolism, which is also used industrially in the synthesis of a variety of compounds, e.g. L-Dopa, L-ephedrine or L-tryptophane. The aim of this work was to establish a biotechnological process for the production of pyruvate based on acetate-auxotrophic Escherichia coli strains. For this purpose, E. coli YYC202 was choosen, a strain which lacks the aceEF genes for the pyruvate dehydrogenase complex and contains mutations in the genes encoding pyruvate oxidase (poxB), pyruvate formate lyase (pfB) and PEP synthetase (pps). Due to this genotype, strain YYC202 is unable to convert pyruvate to acetyl-CoA, acetate or PEP and requires acetate for growth in glucose minimal medium. In contrast to the E. coli wild-type strain MG1655, YYC202 converted glucose and acetate simultaneously and possessed a very high acetate resistance. The acetate auxotrophy of YYC202 could be complemented in this work by transformation with plasmid pGS87, a pBR322 derivative encoding the genes of the pyruvate dehydrogenase complex. When cultivated aerobically in glucose/acetate minimal medium, E. coli YYC202 produced up to 1.7 mol pyruvate/mol glucose, depending on the concentrations of glucose and acetate and on the pH. This yield is significantly higher than the yield of 1.2 mol pyruvate/mol glucose obtained in an alternative pyruvate production process using vitamine auxotrophic microorganisms. With resting cells of E. coli YYC202, an almost complete conversion of glucose to pyruvate was obtained (&gt;1.9 mol/mol). Formation of the by-product lactate, which occurred at higher cell densities, was entirely prevented by disruption of the ldhA gene encoding NAD$^{+}$-dependent D-lactate dehydrogenase, leading to increased yields and productivity. Transriptional profiling using whole-genome DNA microarrays revealed that pyruvate production by E. coli YYC202/pBR322 is associated with acid stress. Several genes involved in the acid stress response, e.g. gadA and gadB encoding glutamate decarboxylases, had increased mRNA levels in the pyruvate producer when compared with the non-producer YYC202/pGS87. Since the external pH was 7 in these experiments, the results suggest a cytoplasmic acidification. Besides acid stress genes, the genes for the Na$^{+}$/serine symporter SstT and for the not yet characterised transporter YbgH showed increasedmRNA levels in the pyruvate producer. Whether these secondary transporters are involved in pyruvate import or export remains to be shown.
Current understanding of the inflammatory process in cystic fibrosis: Onset and etiology (1997)

Although airway obstruction and chronic endobronchial infection have long been recognized as major factors in the pathogenesis of lung disease in cystic fibrosis (CF), only recently has it been recognized that the inflammatory process itself may be responsible in a major way for destroying the lungs. The most characteristic feature of inflammation in the CF lung is the persistent infiltration of massive numbers of neutrophils into the airways. Although neutrophils help to control infection, when present in great excess, they cause more harm than good. Major advances in our understanding of the inflammatory process in the CF lung have come from the use of bronchoscopy and bronchoalveolar lavage (BAL) to analyze the inflammatory process in patients who are relatively symptom free and/or do not regularly produce sputum. Recent BAL studies suggest that neutrophil-rich inflammation begins very early, even in infants without clinically apparent lung disease. A number of chemoattractants from epithelial cells, macrophages, neutrophils themselves, and bacterial products contribute to the neutrophil influx. Surprisingly, some infants have inflammation even in the apparent absence of infection, leading to the speculation that inflammation may precede infection. Links between the basic defect in CF and inflammation have been postulated, with dysregulation of cytokine production and abnormal epithelial host defenses being implicated as causal factors of sustained inflammation. Regardless of the details of how this process is initiated and/or perpetuated, it has become clear that inflammation begins at a very early stage and progresses throughout life, gradually worsening and destroying the lungs. For these reasons, anti-inflammatory therapy should be initiated in early life. Additional studies are necessary to define the optimal antiinflammatory drugs and regimens, and to confirm their long-term safety and efficacy.
Agelastatin A (AgA), a Marine Sponge Derived Alkaloid, Inhibits Wnt/Beta-Catenin Signaling and Selectively Induces Apoptosis in Chronic Lymphocytic Leukemia Independently of p53 (2011)

Abstract Abstract 1786 The Wnt/beta-catenin pathway is highly active in chronic lymphocytic leukemia (CLL) and confers an anti-apoptotic effect in vitro and possibly also in vivo. As such, inhibition of this pathway represents a potential therapeutic target. Here we report preclinical studies using agelastatin A (AgA), a naturally occurring alkaloid extracted from the marine sponges Agelas dendromorpha and Cymbastella sp. We tested AgA using SW480 cells transfected with a beta-catenin dependent reporter gene expression system. Using this assay, we found that AgA is a potent Wnt signaling inhibitor with IC50 of 12nM. AgA also inhibits the expression of reporter genes in HEK293 cells cotransfected with either Wnt1 or mutated (dominant-active) beta-catenin, suggesting that its mechanism of action is independent of the beta-catenin degradation complex. Moreover, real time-PCR results show that Lef1, a classic Wnt/beta-catenin target gene highly expressed in CLL, is down-regulated in primary CLL cells incubated with AgA at nanomolar concentrations. AgA, but not structurally related compounds agelastatin C and agelastatin D, selectively induces apoptosis in CLL B-cells (mean IC50 = 56nM) compared with peripheral blood mononuclear cells from healthy volunteers (mean IC50 = 250nM). Interestingly, AgA induces apoptosis at nanomolar concentrations even in samples from CLL patients who had no clinical response to fludarabine, samples with 17p deletion or TP53 gene mutations, and samples in which p53 deficiency was determined by in vitro chemoresistance and absence of inducible p21, CD95, and DR5 after irradiation (Figure 1). In addition, AgA induces apoptosis on CLL cells that are maintained in co-culture conditions with stromal cells, which typically increases leukemia cell viability. This suggests that AgA is capable of disrupting pro-survival signals derived from the microenvironment, including Wnt mediated activation. In conclusion, AgA has potent activity against CLL cells in vitro. Our studies show that AgA inhibits Wnt/beta-catenin signaling at nanomolar concentrations, induces apoptosis in CLL cells independently of p53, and is able to disrupt pro-survival signaling derived from stromal cell support. AgA warrants further studies and clinical development for the treatment of CLL and potentially other malignancies associated with Wnt/beta-catenin signaling. Disclosures: No relevant conflicts of interest to declare.
Antifungal Activities of Rapamycin and Its Derivatives, Prolylrapamycin, 32-Desmethylrapamycin, and 32-Desmethoxyrapamycin. (1998)

The antifungal agent rapamycin is highly effective in inhibiting growth of yeast and mold strains. This study demonstrates that in liquid medium, rapamycin is more active than its derivatives (prolylrapamycin, 32-desmethylrapamycin, 32-desmethoxyrapamycin) against Candida albicans, Saccharomyces cerevisiae, and Fusarium oxysporum. All the rapamycins were more active than amphotericin B. Although four other molds were not inhibited in liquid medium, they were very sensitive to rapamycin and its derivatives when tested on agar. The latter assay showed that rapamycin is the most active and 32-desmethylrapamycin is more active than prolylrapamycin and 32-desmethoxyrapamycin. The conclusion of this study is that rapamycin is the most active antifungal agent of the compounds examined. The unexpected finding of high activity of rapamycin and its derivatives against filamentous fungi when assayed by the agar diffusion assay suggests that rapamycin or a derivative may hold promise for chemotherapy against pathogenic molds as well as yeasts.
Sequence-selective DNA recognition by synthetic ligands (1991)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTSequence-selective DNA recognition by synthetic ligandsPeter E. NielsenCite this: Bioconjugate Chem. 1991, 2, 1, 1–12Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/bc00007a001https://doi.org/10.1021/bc00007a001research-articleACS PublicationsRequest reuse permissionsArticle Views384Altmetric-Citations85LEARN 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
Color‐Saturated Green‐Emitting QD‐LEDs (2006)

Green to the core: CdxZn1−xSe alloy core nanocrystals are synthesized and overcoated with CdyZn1−yS to create core–shell nanocrystals with the ideal wavelength of emission for quantum dot light-emitting device (QD-LED) displays. These (CdxZn1−xSe)CdyZn1−yS core–shell nanocrystals are used to fabricate color-saturated green-emitting QD-LEDs (see picture), which are suitable for display applications.