gebhart/patrepeval huggingface dataset:
Modulation of Interferon-γ-induced Macrophage Activation by Phosphotyrosine Phosphatases Inhibition (1998)

Phagocyte functions are markedly inhibited after infection with the intracellular protozoan parasite Leishmania. This situation strongly favors the installation and propagation of this pathogen within its mammalian host. Previous findings by us and others have established that alteration of several signaling pathways (protein kinase C-, Ca2+- and protein-tyrosine kinases-dependent signaling events) were directly responsible for Leishmania-induced macrophage (MO) dysfunctions. Here we report that modulation of phosphotyrosine-dependent events with a protein tyrosine phosphatases (PTP) inhibitor, the peroxovanadium (pV) compound bpV(phen) (potassium bisperoxo(1,10-phenanthroline)oxovanadate(Vi)), can control host-pathogen interactions by different mechanisms. We observed that the inhibition of parasite PTP resulted in an arrest of proliferation and death of the latter in coincidence with cyclin-dependent kinase (CDK1) tyrosine 15 phosphorylation. Moreover the treatment of MO with bpV(phen) resulted in an increased sensitivity to interferon-gamma stimulation, which was reflected by enhanced nitric oxide (NO) production. This enhanced IFN-gamma-induced NO generation was accompanied by a marked increase of inducible nitric oxide synthase (iNOS) mRNA gene and protein expression. Finally we have verified the in vivo potency of bpV(phen) over a 6-week period of daily administration of a sub-toxic dose. The results revealed its effectiveness in controlling the progression of visceral and cutaneous leishmaniasis. Therefore PTP inhibition of Leishmania and MO by the pV compound bpV(phen) can differentially affect these eukaryotic cells. This strongly suggests that PTP plays an important role in the progression of Leishmania infection and pathogenesis. The apparent potency of pV compounds along with their relatively simple and versatile structure render them attractive pharmacological agents for the management of parasitic infections.
Self-Assembled, Deterministic Carbon Nanotube Wiring Networks (2002)

Nanonetze: Aus einer Suspension von einwandigen Kohlenstoff-Nanoröhren (single-walled carbon nanotubes; SWNTs) wurden elektrisch leitende Gitter mit 8 bis 14 Knotenpunkten (siehe Bild) erhalten. Die entscheidenden Strukturparameter dieser „Miniaturschaltkreise“ wurden hauptsächlich durch chemisch gesteuerte Selbstorganisation, nicht so sehr durch lithographische Musterbildung, erreicht. Alle Arbeitsschritte wurden unter Normalbedingungen ausgeführt. Supporting information for this article is available on the WWW under http://www.angewandte.com 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.
Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy (2018)

Abnormally <i>O</i>-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three <i>O</i>-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five <i>O</i>-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed.
Time Warner cable's full service network-program management of the FSN virtual organization (2002)

When Time Warner chose to pursue its vision of the information superhighway, it was well recognized that this endeavor was a technological undertaking of dramatic proportions. Acknowledging that no one company could solely deliver the multitude of required technologies, Time Warner created a "virtual organization" of key technology providers. This paper analyzes the challenges and rewards of program management within this virtual organization, and presents innovatively adapted program management techniques that enabled this program's success.
Conformational Studies of Copper Proteins (1968)

Abstract Optical rotatory dispersion and circular dichroism spectra of the Pseudomonas blue protein and laccase B from Polyporus versicolor are presented from 190 to 700 mµ. Circular dichroism spectra of both proteins show six ellipticity bands above 300 mµ associated with the copper chromophore, indicating more transitions to be present in these copper protein complexes than the three parity-forbidden d-d transitions associated with Cu(II) in its common symmetries. A Gaussian analysis of the visible spectra of these proteins is presented. The same set of bands generates both the absorption and the circular dichroism spectra by the adjustment of the signs and the heights of the bands, while keeping the positions and the band widths constant. Below 1.8 x 104 cm-1, both proteins show three bands in the circular dichroism spectrum with signs (+, +, -) for the blue protein and (+, -, +) for laccase B. The uniqueness of the analysis has been established by using the Kronig-Kramers transform to generate the optical rotatory dispersion spectrum of the blue protein. Comparisons are made to the circular dichroism spectra of a Cu(II) complex of known donor atoms and geometry, [Cu(II)(glycyl-l-valine)]. Each protein creates a unique chemical environment for the aromatic residues. The Pseudomonas blue protein shows at least seven aromatic ellipticity bands, both positive and negative ([θ] ∼ ±6 x 103 deg cm2 per decimole), whereas laccase B shows three large positive aromatic bands ([θ] = 1 to 2.7 x 104 deg cm2 per decimole). In the region of the absorption bands of the peptide bonds, the blue protein shows a negative ellipticity band at 222 mµ ([θ] = 4.9 x 103 on a mean residue basis) and a positive band at 196 mµ ([θ] = 1.28 x 104 on a mean residue basis). A prominent negative band is not present at 206 mµ, and the circular dichroism spectrum exhibits a crossover point at 206 mµ. A preliminary analysis based on the computed contours of both the optical rotatory dispersion and circular dichroism spectra indicates a mixture of approximately 40% α-helix, 37% β structure, and 23% random coil. Laccase B shows a negative ellipticity band at 216 mµ ([θ] ∼ 4.1 x 103 on a mean residue basis) and a positive band at 196 mµ ([θ] ∼ 5.5 x 103 on a mean residue basis). Both features fit a β structure; however, the crossover occurs at 204 mµ and the computed curves indicate a mixture of β structure and random coil. The chemical interactions leading to the three-dimensional structure of the blue protein are apparently inherent in the primary chain. Acid denaturation, pH 1.5, destroys the ellipticity bands associated with the peptide bonds, the aromatic residues, and the copper chromophore. All are restored by return of the protein to neutral pH.
Gene expression profiles in thyroid carcinomas (2000)

The gene expression profiles of human thyroid carcinomas were analysed by serial analysis of gene expression (SAGE) which allows quantitative and simultaneous analysis of a large number of transcripts. More than 29,000 transcripts derived from a normal thyroid tissue and four thyroid tumours were analysed. While extensive similarity was noted between the expression profiles of the normal thyroid tissue and three differentiated thyroid tumours, many transcripts, such as osteonectin, a-tubulin, glyceraldehyde-3-phosphate dehydrogenase, glutathione peroxidase, and thyroglobulin, were expressed at extremely different levels in differentiated and undifferentiated carcinomas. These data provide new information that might be used to identify genes useful for the diagnosis and treatment of thyroid carcinomas.
Molecular Characterization of the Hemin Uptake Locus ( hmu ) from Yersinia pestis and Analysis of hmu Mutants for Hemin and Hemoprotein Utilization (1999)

Sequence analysis of the hemin uptake locus (hmu) of Yersinia pestis revealed five genes, hmuRSTUV, required for use of hemin and hemoproteins as iron sources. The translated gene products have homologies with proteins of the hemin transport genes of several gram-negative bacteria. Promoters were identified upstream of hmuP'R (p1) and upstream of hmuS (p2); p1, which contains a Fur box, is regulated by iron and Fur, while p2 exhibits weak, but constitutive, activity. HmuR, which has homology with TonB-dependent outer membrane (OM) receptors, is localized to the OM of Y. pestis and is required for utilizing hemin and all hemoproteins under iron-depleted conditions. The proposed ABC transporter, HmuTUV, is necessary for use of hemin, hemin-albumin, and myoglobin, but not hemoglobin, hemoglobin-haptoglobin, or heme-hemopexin, as iron sources. In the absence of HmuTUV, HmuS, a cytoplasmic protein, is involved in use of hemoglobin and heme-hemopexin. In mice, the 50% lethal doses of Y. pestis DeltahmuP'RSTUV mutants injected subcutaneously or retro-orbitally did not differ from that of the Hmu(+) parent strain. Thus, the hmu system is not essential for infection in mice via these routes. Growth studies showed that a DeltahmuP'RSTUV mutant could grow in iron-depleted medium containing high concentrations of hemoglobin, suggesting that an Hmu-independent, lower-affinity hemoglobin uptake system may exist.
Nomenclature of monocytes and dendritic cells in blood (2010)

Monocytes and cells of the dendritic cell lineage circulate in blood and eventually migrate into tissue where they further mature and serve various functions, most notably in immune defense. Over recent years these cells have been characterized in detail with the use of cell surface markers and flow cytometry, and subpopulations have been described. The present document proposes a nomenclature for these cells and defines 3 types of monocytes (classical, intermediate, and nonclassical monocytes) and 3 types of dendritic cells (plasmacytoid and 2 types of myeloid dendritic cells) in human and in mouse blood. This classification has been approved by the Nomenclature Committee of the International Union of Immunological Societies, and we are convinced that it will facilitate communication among experts and in the wider scientific community.
Two Arginine Repressors Regulate Arginine Biosynthesis inLactobacillus plantarum (2004)

The repression of the carAB operon encoding carbamoyl phosphate synthase leads to Lactobacillus plantarum FB331 growth inhibition in the presence of arginine. This phenotype was used in a positive screening to select spontaneous mutants deregulated in the arginine biosynthesis pathway. Fourteen mutants were genetically characterized for constitutive arginine production. Mutations were located either in one of the arginine repressor genes (argR1 or argR2) present in L. plantarum or in a putative ARG operator in the intergenic region of the bipolar carAB-argCJBDF operons involved in arginine biosynthesis. Although the presence of two ArgR regulators is commonly found in gram-positive bacteria, only single arginine repressors have so far been well studied in Escherichia coli or Bacillus subtilis. In L. plantarum, arginine repression was abolished when ArgR1 or ArgR2 was mutated in the DNA binding domain, or in the oligomerization domain or when an A123D mutation occurred in ArgR1. A123, equivalent to the conserved residue A124 in E. coli ArgR involved in arginine binding, was different in the wild-type ArgR2. Thus, corepressor binding sites may be different in ArgR1 and ArgR2, which have only 35% identical residues. Other mutants harbored wild-type argR genes, and 20 mutants have lost their ability to grow in normal air without carbon dioxide enrichment; this revealed a link between arginine biosynthesis and a still-unknown CO2-dependent metabolic pathway. In many gram-positive bacteria, the expression and interaction of different ArgR-like proteins may imply a complex regulatory network in response to environmental stimuli.
StereoCut: Consistent interactive object selection in stereo image pairs (2011)

Methods of interacting with stereo image pairs are important for handling the increasing amount of stereoscopic 3D data now being produced. In this paper, we introduce a framework for interactively selecting objects in two stereo images simultaneously using graph cut. A key contribution of our method is the use of stereo correspondence probability distributions to govern the strength of the connection between the two images. This allows information from arbitrary stereo matching algorithms to be utilized by our method. We show how to enforce consistency in these distributions to improve the results. For comparisons, we introduce a new dataset of stereo images and ground truth selections. We evaluate different correspondence distributions and show that our method is effective in selecting objects from stereo pairs.
Role of interleukin-6 in macrophage function (1996)

Interleukin-6 is a multifunctional cytokine important for host defense. Macrophages are potent producers of interleukin-6. Conversely, interleukin-6 acts on monocytes to induce their differentiation to macrophages. This paper reviews the in vivo roles of interleukin-6 and nuclear factor for interleukin-6 expression that have been revealed by gene targeting as well as recent progress in understanding the interleukin-6 gene regulation and signaling pathway in macrophages.
A Putative Selectivity Filter in the G-protein-coupled Receptors for Parathyroid Hormone and Secretin (1996)

The seven transmembrane segments (TMs) of many G-protein-coupled receptors (GPCRs) are thought to form a cavity into which cognate ligands insert, leading to receptor activation. Residues lining the cavity are often essential for optimal ligand binding and/or signal transduction. The present studies evaluated whether residues lining the cavity also contribute to specificity, using GPCRs for the polypeptides parathyroid hormone (PTH) and secretin as models. These ligands display no sequence homology with one another, and neither ligand cross-reacts with the other's receptor. However, mutation of a single amino acid in the second TM of the secretin receptor to the corresponding residue in the PTH receptor (N192I) resulted in a receptor that binds and signals in response to PTH. The reciprocal mutation in the PTH receptor (I234N) likewise unmasked responsiveness to secretin. Neither mutation significantly altered the response of the receptors to their own ligands. The results suggest a model of specificity wherein TM residues near the extracellular surface of the receptor function as a selectivity filter that restricts access of inappropriate ligands to an activation site in the transmembrane cavity.
The Canon Group's Effort: Working Toward a Merged Model (1995)

The Canon Group's modeling effort focused on a collaborative approach to developing a representational schema for clinical concepts, using chest radiography reports as the initial experiment. This effort resulted in a core model that represents a consensus. Further efforts in modeling will extend the representational coverage and will also address issues such as scalability, automation, evaluation, and support of the collaborative effort.
Near-Infrared Studies of the Structure of Water. II. Ionic Solutions (1963)

The infrared absorption bands of water in the 1.1- to 1.3-μ region have been studied. Variations in intensities of three bands have been used to calculate for ionic solutions the mole fractions of water molecules in which zero, one, and two of the hydrogens are involved in hydrogen bonding. The average sizes of water clusters in HCl, HBr, HNO3, HClO4, H2O2, NaOH, KOH, NaNO3, and NaClO4 solutions were calculated. From this and from qualitative evaluations for other solution systems, it was possible to assign the following effect on the water structure to the ions: cations:order−producing: La3+&amp;gt;Mg2+&amp;gt;H+&amp;gt;Ca2+,order−destroying:K+&amp;gt;Na+&amp;gt;Li+&amp;gt;Cs+=Ag+;anions:order−producing:OH−&amp;gt;F−,order−destroying:ClO4−&amp;gt;I−&amp;gt;Br−&amp;gt;NO3−&amp;gt;Cl−&amp;gt;SCN−.
Aβ(25–35) and its C‐ and/or N‐blocked derivatives: Copper driven structural features and neurotoxicity (2006)

The toxic properties of beta-amyloid protein, Abeta(1-42), the major component of senile plaques in Alzheimer's disease, depend on nucleation-dependent oligomerization and aggregation. In addition, Abeta(1-42) toxicity is favored by the presence of trace metals, which affect the secondary structure of the peptide. A peptide comprising 11 residues within Abeta(1-42) [Abeta(25-35)] aggregates and retains the neurotoxic activity of Abeta(1-42). We have used both Abeta(25-35) and its C-amidated or N-acetylated/C-amidated derivatives to investigate the role of copper(II) in modulating the conformation and aggregation state as well as the neurotoxic properties of amyloid peptides. Electrospray ionization mass spectrometry (ESI-MS) and electron paramagnetic resonance (EPR) measurements were performed to verify the formation of copper(II)/Abeta(25-35) complexes and to determine the coordination mode, respectively. Abeta(25-35) and its derivatives were analyzed by circular dichroism spectroscopy to assess their secondary structure, subjected to thioflavine-T (Th-T) binding assay to reveal beta-sheet structured aggregates formation, and imaged by scanning force microscopy. Toxicity was assessed on mature cultures of rat cortical neurons. We found that beta-sheet-structured species of Abeta(25-35) were neurotoxic, whereas the random-coil-structured derivatives were devoid of effect. Interestingly, copper promoted the random-coil/beta-sheet transition of Abeta(25-35), with ensuing peptide toxicity, but it induced the toxicity of the N-acetylated/C-amidated derivative without affecting peptide folding. Moreover, copper did not influence either the folding or the activity of the C-amidated Abeta(25-35), suggesting that blockade of the C-terminus of Abeta peptides might be sufficient to prevent Abeta toxicity.
Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer (2003)

The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
[In vivo distribution and pharmacokinetics of dexamethasone sodium phosphate thermosensitive in situ gel following intratympanic injection]. (2006)

DSP thermosensitive in situ gel following IT has significant cochlea-oriented and sustained-release effect.
Introduction (2003)

Although James I declared duelling illegal in 1613, his edict failed to lessen the popularity of the custom. The English duel of honor had arisen in the 1580s, when Italian weaponry and customs had reshaped the single combat. Unlike the more traditionally "English" broadsword, the rapier gave no advantage to superior strength but, on the contrary, rewarded superior expertise. Its lightness made the rapier popular; ease and popularity altered the nature of its use.KeywordsGender IdentitySocial RankPersonal SpaceEarly Modern PeriodSingle CombatThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Tests of Independence for a $2 \times 2$ Contingency Table with Random Margins (2017)

Fisher's exact test is commonly used for testing the hypothesis of independence between the row and column variables in a $r \times c$ contingency table. It is a ``small-sample'' test since it is used when the sample size is not large enough for the Pearsonian chi-square test to be valid. Fisher's exact test conditions on both margins of a $2 \times 2$ table leading to a hypergeometric distribution of the cell counts under independence. Moreover, it is conservative in the sense that its actual significance level falls short of the nominal level. In this paper, we modify Fisher's exact test by lifting the restriction of fixed margins and allow the margins to be random. In doing so, we propose two new tests - a likelihood ratio test in a frequentist framework and a Bayes factor test in a Bayesian framework, both of which are based on a new multinomial distributional framework. We apply the three tests on data from the Worcester Heart Attack study and compare their power functions in assessing gender difference in the therapeutic management of patients with acute myocardial infarction (AMI).
Serum CD4, CD8, and interleukin-2 receptor levels in childhood acute myeloid leukemia. (1991)

Leukemic cell expression and serum levels of CD4, CD8, and interleukin-2 receptor (IL-2R) were determined at diagnosis for children or adolescents with acute myeloid leukemia (AML). Cellular expression of CD4 was detected in 18 of 62 cases, CD8 in none of 60 cases, and IL-2R in one of 33 cases tested. Myeloblasts of the M4 and M5 subtypes expressed CD4 significantly more frequently than other FAB subtypes (p = 0.0001). Serum levels of the three soluble factors (tested for 91 patients) were positively correlated with each other. Increased serum CD4 levels were significantly associated with cellular CD4 expression, high leukocyte count, M5 leukemia, spleen enlargement, and age less than 1 year. High serum CD8 levels correlated significantly with splenomegaly, extramedullary disease, absence of Auer rods, and high leukocyte count. Cases with high serum IL-2R levels were less likely to have Auer rods and more likely to have splenomegaly and M5 leukemia; serum levels greater than 750 U/ml were associated with a higher probability of treatment failure (p = 0.05), even after adjustment for other potential prognostic factors. Further studies of serum CD4, CD8, and IL-2R levels may help to clarify the immunoregulatory role of T-cells in patients with AML.
An extra-uterine system to physiologically support the extreme premature lamb (2017)

In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed 'amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.