gebhart/patrepeval huggingface dataset:
α 2 -macroglobulin associates with β-amyloid peptide and prevents fibril formation (1998)

We have used the yeast two-hybrid system to isolate cDNAs encoding proteins that specifically interact with the 42-aa beta-amyloid peptide (Abeta), a major constituent of senile plaques in Alzheimer's disease. The carboxy terminus of alpha2-macroglobulin (alpha2M), a proteinase inhibitor released in response to inflammatory stimuli, was identified as a strong and specific interactor of Abeta, utilizing this system. Direct evidence for this interaction was obtained by co-immunoprecipitation of alpha2M with Abeta from the yeast cell, and by formation of SDS-resistant Abeta complexes in polyacrylamide gels by using synthetic Abeta and purified alpha2M. The association of Abeta with alpha2M and various purified amyloid binding proteins was assessed by employing a method measuring protein-protein interactions in liquid phase. The dissociation constant by this technique for the alpha2M-Abeta association using labeled purified proteins was measured (Kd = 350 nM). Electron microscopy showed that a 1:8 ratio of alpha2M to Abeta prevented fibril formation in solution; the same ratio to Abeta of another acute phase protein, alpha1-antichymotrypsin, was not active in preventing fibril formation in vitro. These results were corroborated by data obtained from an in vitro aggregation assay employing Thioflavine T. The interaction of alpha2M with Abeta suggests new pathway(s) for the clearance of the soluble amyloid peptide.
Automatic abstracting and indexing—survey and recommendations (1961)

In preparation for the widespread use of automatic scanners which will read documents and transmit their contents to other machines for analysis, this report presents a new concept in automatic analysis: the relative-frequency approach to measuring the significance of words, word groups, and sentences. The relative-frequency approach is discussed in detail, as is its application to problems of automatic indexing and automatic abstracting. Included in the report is a summary of automatic analysis studies published as of the date of writing. Conclusions are drawn that point toward more sophisticated mathematical and linguistic techniques for the solution of problems of automatic analysis.
A distributed, parallel, interactive volume rendering package (1994)

This paper presents a parallel ray-casting volume rendering algorithm and its implementation on the massively parallel IBM SP-1 computer using the Chameleon message passing library. Though this algorithm takes advantage of many of the unique features of the SP-1 (e.g. high-speed switch, large memory per node, high-speed disk array, HIPPI display, et al.), the use of Chameleon allows the code to be executed on any collection of workstations. The algorithm is image-ordered and distributes the data and the computational load to individual processors. After the volume data is distributed, all processors then perform local ray tracing of their respective subvolumes concurrently. No interprocess communication takes place during the ray tracing process. After a subimage is generated by each processor, the final image is obtained by composing subimages between all the processors. The program itself is implemented as an interactive process through a GUI residing on a graphics workstation which is coupled to the parallel rendering algorithm via sockets. The paper highlights the Chameleon implementation, the GUI, some optimization improvements, static load balancing, and direct parallel display to a HIPPI framebuffer. >
Metabolism of retinoic acid and retinol during differentiation of F9 embryonal carcinoma cells. (1985)

Retinol and retinoic acid dose-response curves were obtained for promotion of the differentiation of F9 murine embryonal carcinoma cells with an enzyme-linked immunoadsorbent assay for laminin, a product of differentiated F9 cells. Retinoic acid produced a half-maximum response at 1.3 nM and a maximum response at about 30 nM; retinol was 1/175th as potent. Maximum differentiation required 48 hr of continuous exposure to retinoic acid, whereas retinol required 72 hr of exposure. The half-time of retinoic acid conversion into polar metabolites was 3.5 hr; metabolism was accelerated by pretreating F9 cells with retinoic acid. An inhibitor of oxidative metabolism, ketoconazole, decreased the rate of retinoic acid metabolism and decreased the concentration of retinoic acid required to produce a half-maximum response. Unchanged retinoic acid was the sole compound isolated from nuclei of F9 cells incubated with retinoic acid. Retinol had a half-life approximately 5-fold longer than retinoic acid, attained greater cell concentrations, and was converted into retinoic acid by F9 cells. These data indicate that retinoic acid itself directs the differentiation of F9 cells and may mediate differentiation induced by retinol.
CXCR4 Inhibition Synergizes with Cytotoxic Chemotherapy in Gliomas (2006)

These studies support testing CXCR4 inhibitors in patients with glioblastoma multiforme and establish that inhibition of CXCR4 synergizes with conventional cytotoxic therapies in a clinically relevant combinatorial strategy.
High H 2 Uptake by Alkali-Doped Carbon Nanotubes Under Ambient Pressure and Moderate Temperatures (1999)

Lithium- or potassium-doped carbon nanotubes can absorb approximately 20 or approximately 14 weight percent of hydrogen at moderate (200 degrees to 400 degrees C) or room temperatures, respectively, under ambient pressure. These values are greater than those of metal hydride and cryoadsorption systems. The hydrogen stored in the lithium- or potassium-doped carbon nanotubes can be released at higher temperatures, and the sorption-desorption cycle can be repeated with little decrease in the sorption capacity. The high hydrogen-uptake capacity of these systems may be derived from the special open-edged, layered structure of the carbon nanotubes made from methane, as well as the catalytic effect of alkali metals.
Lymphatic endothelium‐specific hyaluronan receptor LYVE‐1 is expressed by stabilin‐1+, F4/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis (2006)

Lymphangiogenesis is a novel prognostic parameter for several cancers that is preferentially quantified by immunohistochemistry of the lymphatic endothelium-specific hyaluronan receptor LYVE-1. Recently, the specificity of LYVE-1 was challenged by serendipitous observations of LYVE-1 expression in rare tissue macrophages. As expression of the hyaluronan receptor-like molecule stabilin-1 is shared by sinusoidal endothelium and macrophages, a thorough analysis of LYVE-1 expression was performed using macrophage-specific markers in vivo and in vitro. In murine tumour models and excisional wound healing, LYVE-1 expression occurred in a subset of CD11b(+), F4/80(+) tissue macrophages that preferentially co-expressed stabilin-1. Upon comparison of single- and double-labelling immunofluorescence, it became apparent that LYVE-1(+) macrophages mimic sprouting and collapsed lymphatic vessels. In vitro, LYVE-1 expression was induced in 25-40% of murine bone marrow-derived macrophages upon exposure to B16F1 melanoma-conditioned medium and IL-4/dexamethasone. By FACS analysis, 11.5% of bone marrow-derived macrophages were LYVE-1(+), stabilin-1(+) double-positive, while 9.9% were LYVE-1(+), stabilin-1(-) and 33.5% were LYVE-1(-), stabilin-1(+). Northern and western analyses confirmed expression of LYVE-1 mRNA and protein in bone marrow-derived macrophages. In the light of the current debate about true endothelial trans-differentiation versus endothelial mimicry of monocytes/macrophages, LYVE-1(+), stabilin-1(+) non-continuous endothelial-like macrophages will require further developmental and functional analyses. In conclusion, the findings imply that LYVE-1 staining must be supplemented by double labelling with macrophage markers in order to differentiate clearly between LYVE-1(+) lymphatics and LYVE-1(+) tumour-infiltrating macrophages. This improved approach will help to clarify the prognostic significance of lymphangiogenesis in malignant tumours.
Gaussian Process Dynamical Models for Human Motion (2007)

We introduce Gaussian process dynamical models (GPDM) for nonlinear time series analysis, with applications to learning models of human pose and motion from high-dimensionalmotion capture data. A GPDM is a latent variable model. It comprises a low-dimensional latent space with associated dynamics, and a map from the latent space to an observation space. We marginalize out the model parameters in closed-form, using Gaussian process priors for both the dynamics and the observation mappings. This results in a non-parametric model for dynamical systems that accounts for uncertainty in the model. We demonstrate the approach, and compare four learning algorithms on human motion capture data in which each pose is 50-dimensional. Despite the use of small data sets, the GPDM learns an effective representation of the nonlinear dynamics in these spaces.
The sites of thyroid hormone formation in rabbit thyroglobulin. (1987)

Rabbit thyroglobulin (Tg) was labeled in vivo with 125I and purified by gel filtration. Separation by high performance liquid chromatography (HPLC) of tryptic digests of S-cyanoethylated Tg yielded four major iodothyronine-containing peaks, designated A, B, C, and D. These were further purified on HPLC and sequenced for identification of amino acid residues and for location of the iodothyronine by 125I counting. The published primary structure for bovine Tg, derived from cDNA sequencing of the Tg gene (Mercken, L., Simons, M.J., Swillens, S., Massaer, M., and Vassart, G. (1985) Nature 316, 647-651), permitted tentative location of the rabbit hormonogenic peptides within the Tg polypeptide chain. Site A, corresponding to bovine residue 5, contained 44% of Tgs [125I]T4 (thyroxine) and 25% of its [125I]T3 (triiodothyronine); its specific activity of iodine was higher than that for other sites, indicating priority of iodination. Site B, containing 24% of Tgs [125I]T4 and 18% of its [125I]T3, corresponded to bovine residue 2555. Site C, at the third residue from the C terminus (bovine residue 2748), was the major T3 site, accounting for over 50% of Tgs [125I]T3. The amino acid sequence around this site shows less homology among different animal species than do those flanking the other hormonogenic sites. Site D accounted for 17% of Tgs [125I]T4 and corresponded to bovine Tyr-1291, in the midportion of Tgs polypeptide chain. The three major T4-forming sites had the sequence Asp-Tyr (sites B and D) or Glu-Tyr (site A), while the sequence Ser-Tyr-Ser appeared to favor T3 synthesis (site C), suggesting an important influence of primary structure on hormonogenesis. We conclude that site A is the major T4-forming site and site C the major T3-forming one, but others are available and offer the opportunity for flexibility in meeting different demands for hormone formation.
Neoexpression of the c-met/Hepatocyte Growth Factor-Scatter Factor Receptor Gene in Activated Monocytes (1997)

Hepatocyte growth factor-scatter factor (HGF-SF ) mediates mito-, moto-, and morphogenic effects through the MET receptor, a membrane bound tyrosine kinase. HGF-SF/MET signaling is mitogenic for a large number of epithelial and endothelial cells and activates organ regeneration. HGF-SF transcripts have been detected in various myeloid cell lines. Therefore, the potential role of HGF-SF/MET signaling for circulating cells of the immune system, especially under conditions of inflammation, was evaluated. Several B-lymphoid and myeloid cell lines were found to express HGF-SF or c-met transcripts, while activity of both genes was mutually exclusive with the exception of low level coexpression in two B-cell lines. HGF-SF transcripts were present in low quantities in freshly isolated peripheral blood mononuclear cells (PBMNCs). In contrast, c-met expression was not detected in freshly isolated cells from peripheral blood, but was induced in monocytes by activation of monocytic or T-cell function. HGF-SF incubation led to an increased c-fos steady state transcript level in myeloblastic K562 cells and moderately promoted cell viability of freshly isolated preactivated monocytes. c-met expression is thus established in activated monocytes, in particular under conditions resembling inflammation, making these cells accessible to functional effects of HGF-SF.
Quantification of the variation in percentage identity for protein sequence alignments (2006)

Although it is well known amongst expert sequence analysts that PID is a poor score for discriminating between protein sequences, the apparent simplicity of the percentage identity score encourages its widespread use in establishing cutoffs for structural similarity. This paper illustrates that not only is PID a poor measure of sequence similarity when compared to the Z-score, but that there is also a large uncertainty in reported PID values. Since better alternatives to PID exist to quantify sequence similarity, these should be quoted where possible in preference to PID. The findings presented here should prove helpful to those new to sequence analysis, and in warning those who seek to interpret the value of a PID reported in the literature.
Genome-wide differentially methylated genes in prostate cancer tissues from African-American and Caucasian men (2015)

Increasing evidence suggests that aberrant DNA methylation changes may contribute to prostate cancer (PCa) ethnic disparity. To comprehensively identify DNA methylation alterations in PCa disparity, we used the Illumina 450K methylation platform to interrogate the methylation status of 485,577 CpG sites focusing on gene-associated regions of the human genome. Genomic DNA from African-American (AA; 7 normal and 3 cancers) and Caucasian (Cau; 8 normal and 3 cancers) was used in the analysis. Hierarchical clustering analysis identified probe-sets unique to AA and Cau samples, as well as common to both. We selected 25 promoter-associated novel CpG sites most differentially methylated by race (fold change > 1.5-fold; adjusted P < 0.05) and compared the β-value of these sites provided by the Illumina, Inc. array with quantitative methylation obtained by pyrosequencing in 7 prostate cell lines. We found very good concordance of the methylation levels between β-value and pyrosequencing. Gene expression analysis using qRT-PCR in a subset of 8 genes after treatment with 5-aza-2'-deoxycytidine and/or trichostatin showed up-regulation of gene expression in PCa cells. Quantitative analysis of 4 genes, SNRPN, SHANK2, MST1R, and ABCG5, in matched normal and PCa tissues derived from AA and Cau PCa patients demonstrated differential promoter methylation and concomitant differences in mRNA expression in prostate tissues from AA vs. Cau. Regression analysis in normal and PCa tissues as a function of race showed significantly higher methylation prevalence for SNRPN (P = 0.012), MST1R (P = 0.038), and ABCG5 (P < 0.0002) for AA vs. Cau samples. We selected the ABCG5 and SNRPN genes and verified their biological functions by Western blot analysis and siRNA gene knockout effects on cell proliferation and invasion in 4 PCa cell lines (2 AA and 2 Cau patients-derived lines). Knockdown of either ABCG5 or SNRPN resulted in a significant decrease in both invasion and proliferation in Cau PCa cell lines but we did not observe these remarkable loss-of-function effects in AA PCa cell lines. Our study demonstrates how differential genome-wide DNA methylation levels influence gene expression and biological functions in AA and Cau PCa.
Atomically Thin Molybdenum Disulfide Nanopores with High Sensitivity for DNA Translocation (2014)

Atomically thin nanopore membranes are considered to be a promising approach to achieve single base resolution with the ultimate aim of rapid and cheap DNA sequencing. Molybdenum disulfide (MoS2) is newly emerging as a material complementary to graphene due to its semiconductive nature and other interesting physical properties that can enable a wide range of potential sensing and nanoelectronics applications. Here, we demonstrate that monolayer or few-layer thick exfoliated MoS2 with subnanometer thickness can be transferred and suspended on a predesigned location on the 20 nm thick SiNx membranes. Nanopores in MoS2 are further sculpted with variable sizes using a transmission electron microscope (TEM) to drill through suspended portions of the MoS2 membrane. Various types of double-stranded (ds) DNA with different lengths and conformations are translocated through such a novel architecture, showing improved sensitivity (signal-to-noise ratio>10) compared to the conventional silicon nitride (SiNx) nanopores with tens of nanometers thickness. Unlike graphene nanopores, no special surface treatment is needed to avoid hydrophobic interaction between DNA and the surface. Our results imply that MoS2 membranes with nanopore can complement graphene nanopore membranes and offer potentially better performance in transverse detection.
Surfactant−Semiconductor Interfaces:  Perturbation of the Photoluminescence of Bulk Cadmium Selenide by Adsorption of Tri-n-octylphosphine Oxide as a Probe of Solution Aggregation with Relevance to Nanocrystal Stabilization (1998)

The band edge photoluminescence (PL) of bulk single-crystal n-CdSe is perturbed by adsorption of tri-n-octylphosphine oxide (TOPO) from toluene solution onto the crystal's 0001, 0001̄, and 112̄0 faces. These are three of the crystal faces observed in studies of CdSe nanocrystals, which are commonly capped with TOPO surfactant molecules to control their properties. At low concentration, where monomeric TOPO dominates the toluene solution composition, reversible PL enhancements are observed, indicating that the adsorbate is acting as a labile Lewis base toward the surface. However, above ∼10 mM concentration, there is an abrupt reversal in the PL signature, such that net quenching of PL is observed relative to the PL intensity in the toluene reference ambient. The PL changes at concentrations above 10 mM are not reversible with toluene rinsing, and are associated with a strongly bound species of Lewis acidic character that requires exposure to a strong base such as pyridine for desorption. XPS data are consistent with PL measurements in identifying experimental conditions associated with strong and weak binding of TOPO to CdSe. The PL changes can be fit to a dead-layer model in both the low and high concentration regimes, permitting an estimate for TOPO-induced contractions and expansions of the dead-layer thickness of about 100−300 Å, for the 0001 face, which generally yielded the largest PL changes. Equilibrium binding constants were estimated from the Langmuir adsorption isotherm model as being ∼104 M-1 and at least 102 M-1 in the low and high concentration regimes, respectively. The concentration at which the PL signature reversal occurs corresponds to incipient aggregate formation in solution based on both 31P NMR and IR spectral changes. MacroModel calculations indicate that TOPO dimer formation is energetically favorable and that a surface adduct formed from the dimer could be stabilized by multiple surface interactions.
Synthesis of 5-Fluorouracil Derivatives Containing an Inhibitor of 5-Fluorouracil Degradation. (1993)

The reactivities of 5-fluorouracil (5-FUra) degradation inhibitors, 2, 4- (2) and 2, 6-dihydroxypyridines (3), were investigated. Acylation of 2 and 2, 4-bis(trimethylsilyloxy)pyridines with equimolar amounts of acid chlorides preferentially occurred at the 4-OH and 2-OH positions, respectively, and the structure of monobenzoylated 5-chloro-2, 4-dihydroxypyridine (2b) was determined as 4-benzoyloxy-5-chloro-2-pyridone (5b) by X-ray crystallo-graphic analysis. Compounds 2 and 3, as well as the N-2-tetrahydrofuryl (11), N-alkyl (12), and N-carbamoyl (14) derivatives of 2, exhibit dynamic keto-enol tautomerism. The acyl derivatives of these pyridines are labile and are thought to be active esters. Monoacyl ester derivatives of these pyridines were combined with 5-FUra analogs to develop novel antitumor agents containing an inhibitor of 5-FUra degradation. One of them, 3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1-ethoxymethyl-5-fluorouracil (BOF-A2) (22b), was the most effective and is currently undergoing late phase-II clinical trials.
Synthesis of 2‐(3‐Indolyl)‐1H‐benzimidazoles from 2‐Acylmethyl‐1H‐benzimidazoles. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Development of cell surface linkage complexes in cultured fibroblasts. (1985)

The possible role of a 140K membrane-associated protein complex (140K) in fibronectin-cytoskeleton associations has been examined. The 140K was identified by the monoclonal antibody JG22E. Monoclonal and polyclonal antibodies to the 140K showed identical patterns of binding to the cell membranes of fixed and permeabilized chicken embryonic fibroblasts; localization was diffuse, but with marked concentration in cell-to-extracellular matrix contact sites. Correlative localization with interference reflection microscopy and double-label or triple-label immunofluorescence showed that 140K co-distributed with extracellular fibronectin fibrils and intracellular alpha-actinin in microfilament bundles at extracellular matrix contact sites but tended not to co-localize with tropomyosin present in bundles at sites farther from adhesion sites. In addition, binding of antibodies to 140K, alpha-actinin, and fibronectin was excluded from vinculin-rich focal adhesion sites at the cellular periphery. A progressive development of cell surface alpha-actinin-140K-fibronectin associations was observed in early spreading cells. The anti-140K monoclonal antibody JG22E inhibited the attachment and spreading of both normal and Rous sarcoma virus-transformed chicken embryonic fibroblasts to a fibronectin substratum. However, the anti-140K monoclonal antibody became a positive mediator of cell attachment and spreading if it was adsorbed or cross-linked to the substratum. Our results provide the first description of a membrane-associated protein complex that co-localizes with fibronectin and microfilament bundles, and they suggest that the 140K complex may be part of a cell surface linkage between fibronectin and the cytoskeleton.
Functional Dissociation Between Local and Systemic Immune Response During Anti-Melanoma Peptide Vaccination (1998)

Peptide vaccination against tumor Ags can induce powerful systemic CTL responses. However, in the majority of patients, no tumor regression is noted. To study this discrepancy, we analyzed CTL reactivity in a melanoma patient (F001) vaccinated with g209-2M peptide, a single residue variant of gp100(209-217). G209/g209-2M-reactive CTL were identified in post- but not prevaccination PBL. Limiting dilution analysis identified one predominant CTL clone (C1-35), with TCR Vbeta6s2, recognizing g209/HLA-A*0201-expressing targets. Additionally, two autologous melanoma lines (F001TU-3 and -4) and 20 separate tumor-infiltrating lymphocyte cultures were generated from a fine needle aspirate of a metastatic lesion progressing after initial response to vaccination. Both F001TU did not express gp100 and were not recognized by C1-35. Loss of gp100 by F001TU correlated with a marked reduction of gp100 expression in the same metastatic lesion compared with prevaccination. Thus, ineffectiveness of C1-35 and tumor progression could be best explained by loss of target Ag expression. Interestingly, 12 of 20 tumor-infiltrating lymphocyte cultures recognized F001TU, but none demonstrated g209/g209-2M reactivity, suggesting a functional dissociation between systemic and local immune response. This study suggests that vaccination effects must be analyzed in the target tissue, rather than in the systemic circulation alone.
Assessment of the two Helicobacter pylori α-1,3-fucosyltransferase ortholog genes for the large-scale synthesis of LewisX human milk oligosaccharides by metabolically engineered Escherichia coli (2004)

International audience