gebhart/patrepeval huggingface dataset:
In vivo effect of prothymosin-alpha 1 on humoral and cell-mediated immune responses in the young rat (1991)

There is a large body of evidence for the role of thymosin peptides in immunogenesis and immunity. In this paper we report on the influence of prothymosin alpha 1 (ProT-alpha 1), a hormone-like peptide derived from the calf thymus, on humoral and cellular immune reactions in the rat. Young adults received intraperitoneal injections of ProT-alpha 1 in the periods before and after immunization with cellular and soluble antigens. ProT-alpha-treatment produced a dose-dependent increase of both humoral and cell-mediated immune responses. The thymus weight increased but not that of spleen. Treatment of nonimmunized rats with this polypeptide significantly elevated the number of CD4+ and decreased the number of CD8+ cells in the peripheral blood. The results suggest a potent immunostimulatory activity of ProT-alpha 1 and imply direct action of this polypeptide on T lymphocytes.
Coexpression of VEGF receptors VEGF-R2 and neuropilin-1 in proliferative diabetic retinopathy. (2000)

Coexpression of VEGF-R2 and neuropilin-1 is suggested to facilitate fibrovascular proliferation in diabetic retinopathy.
Riscos ambientais e custos de urbanização: pressupostos teórico-metodológicos (2001)

As questões ambientais estão no centro das preocupações de todos os campos do saber em nossa sociedade contemporânea. Essas questões possuem desdobramentos político-econômicos, sócioculturais e espaço-temporais, que se materializam numa gama de fenômenos, resultantes do embate da relação homem-meio/sociedade-natureza. Em especial, interessa-nos estudar a formação de riscos ambientais, na cidade de Londrina. Neste sentido, levanta-se uma problemática adjacente, que é a questão do custo de urbanização, decorrente muitas vezes, de uma política urbana inadequada, resultando em vários tipos de riscos para a população. Pretende-se traçar alguns pressupostos teórico-metodológicos, que conduzirão a pesquisa, abordando assuntos como os riscos da modernidade, a qualidade de vida, a cultura e a ética ambiental, no processo da prática da interdisciplinaridade, avançando para um “diálogo de saberes”.
Professional Sports Attendance as a Proxy for New Stadium Spillover Benefits (2001)

One of the most interesting issues in state and local public finance over the last 10-15 years has been the debate over state and local contributions to professional sports stadiums. Despite a large amount of empirical evidence indicating that state and local governments receive very little, if any economic benefit from the stadiums they help build, for some reason they keep building them (Bade, Rosentraub). Much research has gone into this issue, and essentially the same result was found each time: stadiums are poor investments for governments. This article is available in The Park Place Economist: http://digitalcommons.iwu.edu/parkplace/vol9/iss1/16
Expression of mutant human cystathionine β-synthase rescues neonatal lethality but not homocystinuria in a mouse model (2005)

Cystathionine beta-synthase (CBS) deficiency is a recessive genetic disorder in humans characterized by elevated levels of total plasma homocysteine (tHcy) and frequent thrombosis in humans. The I278T mutation is the most common mutation found in human CBS-deficient patients. The T424N mutation was identified as a mutation in human CBS that could restore function to I278T in Saccharomyces cerevisiae. In this report, we have engineered mice that express human I278T and I278T/T424N proteins from a metallotheinein-driven transgene. These transgene-containing mice were then bred to CBS knockout animals (Cbs-) to generate mice that express only human I278T or I278T/T424N protein. Both the I278T and the I278T/T424N transgenes are able to entirely rescue the previously described neonatal mortality phenotype despite the animals having a mean tHcy of 250 microm. The transgenic Cbs-/- animals exhibit facial alopecia, have moderate liver steatosis and are slightly smaller than heterozygous littermates. In contrast to human CBS deficiency, these mice do not exhibit extreme methioninemia. The mutant proteins are stable in the liver, kidney and colon, and liver extracts have only 2-3% of the CBS enzyme activity found in wild-type mice. Surprisingly, the I278T/T424N enzyme had exactly the same activity as the I278T enzyme indicating that T424N is unable to suppress I278T in mice. Our results show that elevated tHcy per se is not responsible for the neonatal lethality observed in Cbs-/- animals and suggests that CBS protein may have a function in addition to its role in homocysteine catabolism. These transgenic animals should be useful in the study of homocysteine related human disease.
Site‐Selective Protein Immobilization by Staudinger Ligation (2006)

A sticky situation: A site-specific immobilization of proteins onto a glass surface may allow the creation of protein microarrays. This approach relies on the Staudinger ligation between azide-modified proteins and a phosphane-functionalized glass surface. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z502057_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Identification of a liver growth factor as an albumin-bilirubin complex (1987)

We have reported the purification and characterization of a protein that behaves as a liver growth factor, showing activity either in vivo or in vitro [Díaz-Gil et al. (1986) Biochem. J. 235, 49-55]. In the present paper, we identify this liver growth factor (LGF) as an albumin-bilirubin complex. This conclusion is supported by the results of chemical and spectroscopic characterization of this protein as well as by experiments in vivo. Incubation of albumin isolated from normal rats with bilirubin/albumin molar ratios (r) resulted (when r = 1 or 2) in a complex with liver DNA synthesis promoter activity identical with that of LGF. The exact amount of bilirubin bound to albumin was assessed by fluorescence and c.d. spectra. This albumin-bilirubin complex showed the same dose-dependence profile as LGF either at low or high dose of protein injected per mouse. Both LGF and albumin-bilirubin complex produced similar increases in the mitotic index of mouse hepatocytes in vivo. A new mechanism for the onset of the hepatic regenerative process is proposed.
Lineage specific requirement of c-abl function in normal human hematopoiesis. Science 245: 1107-1110, 1989. IF 30,927 (1989)

Structural abnormalities of the c-abl proto-oncogene are found in hematopoietic cells of more than 90 percent of individuals with chronic myelogenous leukemia. Therefore c-abl may be important in normal as well as malignant hematopoiesis. Normal human hematopoietic progenitor cells were exposed to three different c-abl sense or antisense oligodeoxynucleotides, and the effects on myeloid and erythroid colony formation were examined. The c-abl antisense oligodeoxynucleotides inhibited myeloid, but not erythroid, colony formation. The c-abl sense oligodeoxynucleotides and bcr sense and antisense oligodeoxynucleotides were not inhibitory in this assay. These data show that c-abl is critical in normal myelopoiesis and may explain the relatively selective expansion of leukocytes in patients with chronic myelogenous leukemia.
Wild-type and E106Q mutant carbonic anhydrase complexed with acetate (1994)

The molecular structures of the acetate complexes of wild-type human carbonic anhydrase II (HCAII) and of E106Q mutant human carbonic anhydrase II were solved with high completeness (89-91%) to 2.1 and 1.9 A resolution, respectively. Both wild-type and mutant enzyme crystallize in space group P2(1) with cell dimensions a = 42.7, b = 41.7, c = 73.0 A and beta = 104.6 degrees. The altered active-site hydrogen-bond network caused by the mutation results in a different binding of the inhibitor in the two complexes. In the mutant, but not in the wild-type complex, a carboxylate O atom is within hydrogen-bond distance of Thr199 Ogamma1. In the wild-type enzyme ligand hydrogen bonding to this atom is normally only found for hydrogen-bond donors. The importance of this discrimination on catalysis by the enzyme is discussed briefly.
Transcriptional Activation of the Glut1 Gene in Response to Oxidative Stress in L6 Myotubes (1997)

Exposure of L6 myotubes to prolonged low grade oxidative stress results in increased Glut1 expression at both the protein and mRNA levels, leading to elevated glucose transport activity. To further understand the cellular mechanisms responsible for this adaptive response, the Glut1 transcription rate and mRNA stability were assessed. Nuclear run-on assays revealed 2.0- and 2.4-fold increases in Glut1 transcription rates in glucose oxidase- and xanthine/xanthine oxidase-pretreated cells, respectively. Glut1 mRNA stability was increased with both treatments compared with the control (t1/2 = 7.8 +/- 1.3, 6.0 +/- 2.0, and 2.4 +/- 0.5 h, respectively). The serum-responsive element and AP-1 (but not the cAMP-responsive element) showed increased binding capacity following oxidative stress. Both activation of AP-1 binding and elevation of Glut1 mRNA were prevented by cycloheximide. The involvement of enhancer 1 of the Glut1 gene was demonstrated using transfected 293 cells. Induction of Glut1 mRNA in response to oxidative stress differed from its activation by chronic insulin exposure as demonstrated by the ability of rapamycin to inhibit the latter without an effect on the former. In conclusion, oxidative stress increases the Glut1 transcription rate by mechanisms that may involve activation of AP-1 binding to enhancer 1 of the Glut1 gene.
Impact of epi facets on deep submicron elevated source/drain MOSFET characteristics (1998)

Deep submicron elevated source/drain (S/D) MOSFET's with epi facets, without facets, and with a second sidewall spacer covering the facets were studied using two-dimensional (2-D) process and device simulations. A slight degradation of drain-induced-barrier-lowering /spl Delta/V/sub t/ (DIBL) has been projected due to the locally deeper junction beneath the epi facets. The locally deeper junction also shortens the S/D extension length if the spacer thickness is kept the same. The shorter extension in turn leads to a smaller parasitic resistance and therefore a higher device drive current. Gate-to-drain capacitance of the elevated S/D MOSFET is decreased as a result of faceting because of the reduced overlap area.
Forensic Collection of Electronic Evidence from Infrastructure-As-a-Service Cloud Computing (2016)

As cloud computing becomes ubiquitous, the criminal targeting and criminal use of cloud computing is inevitable and imminent. Similarly, the need for civil forensic analyses of cloud computing has become more prevalent. Forensic investigation of cloud computing matters first requires an understanding of the technology and issues associated with the collection of electronically stored information (“ESI”) in the cloud. The misuse of the broad term “cloud computing” has caused some confusion and misinformation among legal and technology scholars, leading to a muddied and incomplete analysis of cloud-based discovery issues. Cases and academic analyses have dealt primarily with popular online services such as Gmail and Facebook, but they omit discussions of commercial cloud computing providers’ fundamental infrastructure offerings.
A Chemoselective Method for Site-Specific Immobilization of Peptides via Aminooxy Group (2001)

Site-specific modification of peptides and proteins is an important area of basic research for preparation of well-defined biosensors and probes. The unique properties of aminooxy group present an opportunity for chemoselective site-specific immobilization of peptides to prepare well-defined biosensors. We have prepared FLAG peptide derivatives containing L-epsilon-aminooxylysine (L-epsilon-AOLys, 1a) and L-lysine units in their sequence at the C- and N-terminals via solid-phase synthesis. Site-specific modification of peptides through aminooxy group was demonstrated in the preparation of biosensors and selective conjugation in the preparation of biotinylated probes. Effect of the incorporation of L-epsilon-AOLys (1a) into the peptide sequence and its subsequent labeling on the FLAG epitopic character was measured using a surface plasmon resonance detector. It was found that incorporation of L-epsilon-AOLys (1a) into the FLAG peptide and site-specific immobilization through aminooxy group preserved the integrity of FLAG epitope.
Antisense Myc sequences induce differentiation of F9 cells. (1988)

Down-regulation of Myc expression is the earliest documented change in gene expression in retinoic acid-induced differentiation of murine F9 teratocarcinoma cells. F9 cells transfected with plasmids expressing antisense Myc sequences under control of the simian virus 40 (SV40) early promoter exhibit a decrease in Myc protein. The result of this decrease is the spontaneous differentiation into cells that resemble retinoic acid-treated F9 cells as judged by plasminogen activator assays. In contrast, when F9 cells are transfected with a plasmid expressing Myc under control of the SV40 early promoter, resulting cell clones are resistant to differentiation by retinoic acid as shown by the lack of induction of plasminogen activator. These results suggest that down-regulation of Myc is sufficient and necessary for F9 cell differentiation.
Polyethylenimine but Not Cationic Lipid Improves Antisense Activity of 3′-Capped Phosphodiester Oligonucleotides (1999)

Lipofectin, which is a mixture of neutral lipid with a cationic lipid, has been widely used to enhance cellular delivery of phosphorothioate, 2'-sugar-modified, and chimeric antisense oligonucleotides. Phosphodiester oligonucleotides delivered with Lipofectin usually do not elicit antisense activity probably because cationic lipid formulations do not sufficiently protect unmodified oligonucleotides from nuclease degradation. We show that a cationic polymer, polyethylenimine (PEI), improves the uptake and antisense activity of 3'-capped 20-mer and 12-mer antisense phosphodiester oligonucleotides (PO-ODN) targeted to different regions of Ha-ras mRNA and to the 3'-untranslated region (3'-UTR) of C-raf kinase. In contrast, PEI, which forms a very stable complex with the 20-mer phosphorothioate oligonucleotide (PS-ODN), does not enhance its antisense activity. Using fluorescently labeled carriers and ODN, we show that PEI-PS-ODN particles are very efficiently taken up by cells but PS-ODN is not dissociated from the carrier. Our results indicate that carrier-ODN particle size and stability and ODN release kinetics vary with the chemical nature of the ODN and the carrier being transfected into the cells. The very low cost of PEI compared with cytofectins and the increased affinity for target mRNA and decreased affinity for proteins of PO-ODN compared with PS-ODN make the use of PEI-PO-ODN very attractive.
Purification and characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase from human placenta. (1986)

5'-Methylthioadenosine phosphorylase has been purified to homogeneity (30,000-fold) from human full-term placenta by a procedure involving covalent chromatography on organomercurial-agarose as the major step. The specific activity of the homogeneous enzyme is 10.2 mumol of 5'-methylthioadenosine cleaved per min per mg of protein, and the overall yield is about 20%. The enzyme has a molecular weight of 98,000, as determined by gel filtration on Sephacryl S-200 and Superose 6B, and is composed by three apparently identical subunits with a molecular weight of 32,500. The isoelectric point is 5.5, and the optimal pH ranges from 7.2 to 7.6. The resistance of the enzyme to thermal inactivation is increased remarkably by the addition of 5'-methylthioadenosine or phosphate. The homogeneous enzyme shows an absolute requirement for -SH-reducing agents and is specifically and rapidly inactivated by thiol-blocking compounds. The reaction catalyzed by the enzyme is fully reversible with a Keq of 1.39 X 10(-2) (in the direction of phosphorolysis) at 37 degrees C and pH 7.4. The Km values for 5'-methylthioadenosine, phosphate, adenine, and 5-methylthioribose 1-phosphate are 5, 320, 23, and 8 microM, respectively.
Quantitative Proteomic Analysis of Meningiomas for the Identification of Surrogate Protein Markers (2014)

Meningiomas are the most common non-glial tumors of the brain and spine. Pathophysiology and definite histological grading of meningiomas are frequently found to be deceptive due to their unusual morphological features and locations. Here for the first time we report a comprehensive serum proteomic analysis of different grades of meningiomas by using multiple quantitative proteomic and immunoassay-based approaches to obtain mechanistic insights about disease pathogenesis and identify grade specific protein signatures. In silico functional analysis revealed modulation of different vital physiological pathways including complement and coagulation cascades, metabolism of lipids and lipoproteins, immune signaling, cell growth and apoptosis and integrin signaling in meningiomas. ROC curve analysis demonstrated apolipoprotein E and A-I and hemopexin as efficient predictors for meningiomas. Identified proteins like vimentin, alpha-2-macroglobulin, apolipoprotein B and A-I and antithrombin-III, which exhibited a sequential increase in different malignancy grades of meningiomas, could serve as potential predictive markers.
TCRs Genetically Linked to CD28 and CD3ε Do Not Mispair with Endogenous TCR Chains and Mediate Enhanced T Cell Persistence and Anti-Melanoma Activity (2014)

Adoptive transfer of T cells that are gene engineered to express a defined TCR represents a feasible and promising therapy for patients with tumors. However, TCR gene therapy is hindered by the transient presence and effectiveness of transferred T cells, which are anticipated to be improved by adequate T cell costimulation. In this article, we report the identification and characterization of a novel two-chain TCR linked to CD28 and CD3ε (i.e., TCR:28ε). This modified TCR demonstrates enhanced binding of peptide-MHC and mediates enhanced T cell function following stimulation with peptide compared with wild-type TCR. Surface expression of TCR:28ε depends on the transmembrane domain of CD28, whereas T cell functions depend on the intracellular domains of both CD28 and CD3ε, with IL-2 production showing dependency on CD28:LCK binding. TCR:28ε, but not wild-type TCR, induces detectable immune synapses in primary human T cells, and such immune synapses show significantly enhanced accumulation of TCR transgenes and markers of early TCR signaling, such as phosphorylated LCK and ERK. Importantly, TCR:28ε does not show signs of off-target recognition, as evidenced by lack of TCR mispairing, as well as preserved specificity. Notably, when testing TCR:28ε in immune-competent mice, we observed a drastic increase in T cell survival, which was accompanied by regression of large melanomas with limited recurrence. Our data argue that TCR transgenes that contain CD28, and, thereby, may provide T cell costimulation in an immune-suppressive environment, represent candidate receptors to treat patients with tumors.
Major co-localization of the extracellular-matrix degradative enzymes heparanase and gelatinase in tertiary granules of human neutrophils (1997)

The expression of cell-surface adhesion proteins and the release of extracellular-matrix degradative enzymes constitute crucial processes for the attachment of neutrophils to the endothelium and for the subsequent extravasation of these cells through the endothelial layer. We have analysed in resting human neutrophils the subcellular localization of heparanase, a heparan-sulphate-degrading endoglycosidase that can degrade basement-membrane components, thereby facilitating neutrophil passage into the tissue during an inflammatory reaction. By subcellular fractionation of postnuclear supernatants from resting human neutrophils on continuous sucrose gradients, we have found that heparanase activity was mainly located in gelatinase-containing tertiary granules. Using a specific antibody, the 96-kDa heparanase protein was further located in the gelatinase-rich subcellular fractions. Following immunoblotting and immunoprecipitation analysis in the distinct subcellular fractions, we also found co-localization of heparanase and Mo1 (CD11b/CD18), a leucocyte integrin involved in the attachment of neutrophils to the endothelium, in the fractions enriched in gelatinase-containing tertiary granules. Treatment of human neutrophils with tumour necrosis factor or granulocyte/macrophage colony-stimulating factor induced an increase in the CD11b/CD18 cell-surface expression, as well as the release of both gelatinase (matrix metalloproteinase-9) and heparanase, but not of other granule markers, indicating a major co-localization of gelatinase, heparanase and CD11b/CD18 in the same organelle. Furthermore, confocal laser scanning microscopy using specific antibodies against gelatinase and heparanase revealed a major co-localization of both enzymes in intracellular cytoplasmic granules. The major localization of heparanase and CD11b/CD18 in the gelatinase-containing tertiary granule supports the notion that mobilization of this organelle can regulate extravasation of human neutrophils.
Interview with Mark Blessington (2016)

Part of the Forecaster in the Field feature--An interview with Mark Blessington concerning his writing and consulting career. Copyright International Institute of Forecasters, 2016
Mass Spectrometry–Based Proteomics: Principles, Perspectives, and Challenges (2008)

Abstract Mass spectrometry–based proteomics is a modern and rapidly developing methodology for qualitative and quantitative characterization of proteins and their posttranslational modification, subcellular localization, and interaction partners. It enables characterization of entire proteomes with unprecedented sensitivity and precision, providing platforms for identification of biomarkers and drug targets.
A New Resorbable Wrap-Around Implant as an Alternative Nerve Repair Technique (1999)

Poly-3-hydroxybutyrate (PHB), a bacterial storage product, is available as bioabsorbable sheets and has been used in this study for primary nerve repair. The aim was to assess axonal regeneration following such repair and determine the inflammatory response to PHB. In 20 adult cats, the transected superficial radial nerve was wrapped in PHB sheets, while primary epineural repair was carried out in the contralateral limb. At 6 and 12 months, the repair sites were assessed immunohistochemically for macrophage infiltration and myelinated axons were counted in the distal nerve. Mean macrophage counts across the whole width of the nerve in both groups at 6 and 12 months showed no statistically significant difference. Nor was there any significant difference between the two groups at both time-points in axon counts, axon diameter, myelin thickness and g-ratio. There was a statistically significant increase in fibre diameters at 12 months, indicating that fibres were undergoing continuous maturation.