gebhart/patrepeval huggingface dataset:
B-Lymphocyte Stimulator (BLyS) Is Highly Expressed in Waldenstrom’s Macroglobulinemia. (2004)

Abstract Waldenstrom’s macroglobulinemia is a serious and frequently fatal illness, however many of the mechanisms leading to this disease are not yet known. It is clear, however, that there is dysregulation of the balance between cell proliferation and programmed cell death. BLyS (B-lymphocyte stimulator) is a newly identified TNF family member expressed by monocytes, macrophages, and dendritic cells. BLyS has been shown to be critical for maintenance of normal B cell development and homeostasis, and has been found to stimulate lymphocyte growth. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B-cells. Studies of the effects of BLyS on B cell physiology have shown that it also regulates immunoglobulin secretion. To determine the relevance of the BLyS receptor-ligand system in Waldenstrom’s macroglobulinemia, we examined malignant B cells from 5 patients with Waldenstrom’s macroglobulinemia for their ability to bind soluble BLyS and for the expression of the known BLyS receptors, TACI, BAFF-R, or BCMA. The malignant B cells were found to bind BLyS and express BAFF-R and TACI. BCMA expression was undetectable. We then determined the expression of BLyS in bone marrow specimens from 5 patients with Waldenstrom’s macroglobulinemia by immunohistochemistry and compared it to the expression in 5 normal bone marrow specimens. The lymphoplasmacytic cell infiltrate in the bone marrow of patients with Waldenstrom’s macroglobulinemia showed significantly increased BLyS expression. We further determined the serum BLyS levels by ELISA in stored serum specimens from patients with Waldenstrom’s macroglobulinemia (n=20), and compared them to serum BLyS levels in other patients with lymphoplasmacytic lymphoma without elevated immunoglobulin levels (n=10) and to serum levels in normal controls (n=50). Serum BLyS levels in Waldenstrom’s patients (mean: 49.6ng/ml) as well as those in patients with lymphoplasmacytic lymphoma (mean; 46.7ng/ml) were significantly higher than normal controls (mean 12.6ng/ml). In conclusion, we have demonstrated that malignant B cells from patients with Waldenstrom’s macroglobulinemia express the receptors for BLyS and can bind soluble BLyS. Furthermore, we have found that serum BLyS levels are significantly elevated in patients with Waldenstrom’s macroglobulinemia when compared to controls. Strategies to inhibit BLyS may potentially have significant therapeutic efficacy in Waldenstrom’s macroglobulinemia.
Cellware—a multi-algorithmic software for computational systems biology (2004)

The software is available for free and can be downloaded from http://www.bii.a-star.edu.sg/sbg/cellware
Cell Membrane Lipid Composition and Distribution: Implications for Cell Function and Lessons Learned From Photoreceptors and Platelets (1997)

Photoreceptor rod cells and blood platelets are remarkably different, yet both illustrate a similar phenomenon. Both are strongly affected by membrane cholesterol, and the distribution of cholesterol in the membranes of both cell types is determined by the lipid composition within the membranes. In rod cells, cholesterol strongly inhibits rhodopsin activity. The relatively higher level of cholesterol in the plasma membrane serves to inhibit, and thereby conserve, the activity of rhodopsin, which becomes fully active in the low-cholesterol environment of the disk membranes of these same cells. This physiologically important partitioning of cholesterol between disk membranes and plasma membranes occurs because the disk membranes are enriched with phosphatidylethanolamine, thus providing a thermodynamically unfavorable environment for the sterol. Cholesterol enrichment of platelets renders these cells more responsive to stimuli of aggregation. Stimuli for platelet aggregation cause a rapid transbilayer movement of cholesterol from the outer monolayer. This stimulus-dependent redistribution of cholesterol appears to result from the concomitant movement of phosphatidylethanolamine into the outer monolayer. The attractive, yet still unproven, hypothesis is that cholesterol translocation plays an important role in the overall platelet response and is intimately related to the sensitizing actions of cholesterol on these cells.
Multiple Oncogenic Changes (K-RASV12, p53 Knockdown,Mutant EGFRs, p16Bypass, Telomerase) Are Not Sufficient to Confer a Full Malignant Phenotype on Human Bronchial Epithelial Cells (2006)

We evaluated the contribution of three genetic alterations (p53 knockdown, K-RAS(V12), and mutant EGFR) to lung tumorigenesis using human bronchial epithelial cells (HBEC) immortalized with telomerase and Cdk4-mediated p16 bypass. RNA interference p53 knockdown or oncogenic K-RAS(V12) resulted in enhanced anchorage-independent growth and increased saturation density of HBECs. The combination of p53 knockdown and K-RAS(V12) further enhanced the tumorigenic phenotype with increased growth in soft agar and an invasive phenotype in three-dimensional organotypic cultures but failed to cause HBECs to form tumors in nude mice. Growth of HBECs was highly dependent on epidermal growth factor (EGF) and completely inhibited by EGF receptor (EGFR) tyrosine kinase inhibitors, which induced G1 arrest. Introduction of EGFR mutations E746-A750 del and L858R progressed HBECs toward malignancy as measured by soft agar growth, including EGF-independent growth, but failed to induce tumor formation. Mutant EGFRs were associated with higher levels of phospho-Akt, phospho-signal transducers and activators of transcription 3 [but not phospho-extracellular signal-regulated kinase (ERK) 1/2], and increased expression of DUSP6/MKP-3 phosphatase (an inhibitor of phospho-ERK1/2). These results indicate that (a) the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis; (b) a combination of four genetic alterations, including human telomerase reverse transcriptase overexpression, bypass of p16/RB and p53 pathways, and mutant K-RAS(V12) or mutant EGFR, is still not sufficient for HBECs to completely transform to cancer; and (c) EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention.
Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model (2002)

There is increasing evidence that bacterial superantigens contribute to inflammation and T cell responses in psoriasis.Psoriatic inflammation entails a complex series of inductive and effector processes that require the regulated expression of various proinflammatory genes, many of which require NF-B for maximal trans-activation.PS-519 is a potent and selective proteasome inhibitor based upon the naturally occurring compound lactacystin, which inhibits NF-B activation by blocking the degradation of its inhibitory protein IB.We report that proteasome inhibition by PS-519 reduces superantigen-mediated T cell-activation in vitro and in vivo.Proliferation was inhibited along with the expression of very early (CD69), early (CD25), and late T cell (HLA-DR) activation molecules.Moreover, expression of E-selectin ligands relevant to dermal T cell homing was reduced, as was E-selectin binding in vitro.Finally, PS-519 proved to be therapeutically effective in a SCID-hu xenogeneic psoriasis transplantation model.We conclude that inhibition of the proteasome, e.g., by PS-519, is a promising means to treat T cell-mediated disorders such as psoriasis.
Orientation dependence of surface segregation in a dilute Ni–Au alloy (1978)

Surface segregation theory admits that the degree of surface enrichment depends on surface orientation through the anisotropy of surface properties such as surface energy. This prediction was tested by determining the surface composition of several grains of different surface orientation in a polycrystalline Ni–Au alloy foil. A scanning Auger microprobe provided Auger point analyses which were used to determine the surface segregation characteristics of individual (randomly oriented) grains, while selected area electron channeling patterns, obtained with a scanning electron microscope, allowed the surface orientation of each grain to be determined. A strong anisotropy of gold surface enrichment was observed; for example,the gold surface concentration at 700°C varied by as much as an order of magnitude over the range of surface orientations investigated. A plot of the variation in surface composition within the standard stereographic triangle showed trends that are comparable with the known anisotropy of surface energy in fcc metals. It is concluded that the coupling of the above experimental techniques provides a powerful tool for the study of such phenomena.
Nonaqueous Capillary Electrophoresis (1994)

This paper reports an investigation of performing capillary electrophoresis (CE) in formamide. Formamide has a higher dielectric constant than water and can solubilize many supporting electrolytes. It is commonly used in mixtures with water in electrophoretic buffers. It has higher viscosity than water and hence ions exhibit lower mobilities in formamide. As a result, higher electrolyte concentrations and electric field strengths can be used. The linearity between current and the applied voltage is better in formamide. The implications of using larger ionic strength and higher electric field strength on efficiency and analysis times in CE are demonstrated in this paper. Higher efficiencies and shorter analysis times were obtained using formamide, under similar conditions, as compared with aqueous media. Other possible implications of using nonaqueous media on Joule heating, extending the workable range of the capillary diameter, sample sizes, and detectability, are discussed.
Role of cancer stem cell marker CD44 in gastric cancer: a meta-analysis. (2014)

Cluster of differentiation 44 (CD44), a principal cell surface receptor for hyaluronic acid, has been implicated in tumorigenesis and metastasis. However, the relationship between CD44 expression and the patients with gastric cancer remains controversial. A meta-analysis was performed to quantitatively review the correlation of CD44 expression with the clinicopathological data of the patients with gastric cancer. We conducted a final analysis of the patients from 18 studies. Combined odds ratios (OR) suggested that CD44 expression was related with stage, tumor size, and LN metastasis of gastric cancer, and CD44v6 was related with LN metastasis, lymphatic invasion, and venous invasion. Our results suggested that CD44 and CD44v6 expression could be used to predict the metastasis of gastric cancer.
Bacterial twin-arginine signal peptide-dependent protein translocation pathway: evolution and mechanism. (2000)

The recently identified bacterial Tat pathway is capable of exporting proteins with a peculiar twin-arginine signal peptide in folded conformation independently of the Sec machinery. It is structurally and mechanistically similar to the delta pH-dependent pathway used for importing chloroplast proteins into the thylakoid. The tat genes are not ubiquitously present and are absent from half of the completely sequenced bacterial genomes. The presence of the tat genes seems to correlate with genome size and with the presence of important enzymes with a twin-arginine signal peptide. A minimal Tat system requires a copy of tatA and a copy of tatC. The composition and gene order of a tat locus are generally conserved within the same taxonomy group but vary considerably to other groups, which would exclude an acquisition of the Tat system by recent horizontal gene transfer. The tat genes are also found in the genomes of chloroplasts and plant mitochondria but are absent from animal mitochondrial genomes. The topology of evolution trees suggests a bacterial origin of the Tat system. In general, the twin-arginine signal peptide is capable of targeting any passenger protein to the Tat pathway. However, a structural signal carried by the mature part of a passenger protein can override targeting information in a signal peptide under certain circumstances. Tat systems show a substrate-Tat component specificity and a species specificity. The pore size of the Tat channel is estimated as being between 5 and 9 nm. Operational models of the Tat system are proposed.
Solid-Phase Synthesis of Peptide Thioureas and Thiazole-Containing Macrocycles through Ru-Catalyzed Ring-Closing Metathesis (2013)

N-Terminally modified α-thiourea peptides can selectively be synthesized on solid support under mild reaction conditions using N,N'-di-Boc-thiourea and Mukaiyama's reagent (2-chloro-1-methyl-pyridinium iodide). This N-terminal modification applies to the 20 proteinogenic amino acid residues on three commonly used resins for solid-phase synthesis. Complementary methods for the synthesis of α-guanidino peptides have also been developed. The thiourea products underwent quantitative reactions with α-halo ketones to form thiazoles in excellent purities and yields. When strategically installed between two alkene moieties, said thiazole core was conveniently embedded in peptide macrocycles via Ru-catalyzed ring-closing metathesis reactions. Various 15-17 membered macrocycles were easily accessible in all diastereomeric forms using this methodology. The developed "build/couple/pair" strategy is well suited for the generation of larger and stereochemically complete screening libraries of thiazole-containing peptide macrocycles.
Repairing the Injured Spinal Cord (2002)

Certain cell, molecular, and bioengineering strategies for repairing the injured spinal cord are showing encouraging results (either alone or in combination) in animal models, with limited recovery of mobility being reported in some cases.
Characterization of an adduct between CC-1065 and a defined oligodeoxynucleotide duplex (1984)

CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis. The drug binds covalently through N-3 of adenine and lies within the minor groove of DNA. Previous studies indicated that CC-1065 reacted with adenine in DNA to yield a thermally labile product that could be used to reveal its sequence specificity. These studies also provided insight into a DNA sequence (5'-CGGAGTTAGGGGCG-3') which should bind one molecule of CC-1065 in an unambiguous manner. This sequence, which contains the CC-1065 adenine binding site within the sequence 5'-TTA-3' was chemically synthesized together with the complementary strand. CC-1065 reacted with the oligoduplex to give an adduct that maintained the B-DNA form and had a final CD spectrum similar to those of the CC-1065 complexes formed with calf thymus DNA. The above 14mer was 5' end-labelled with 32P, annealed with its complementary strand, reacted with CC-1065 and heated. Drug-mediated strand breakage was evaluated on a sequencing gel. A single break occurred in the labelled strands to give a fragment that migrated as an 8.5mer; subsequent piperidine treatment produced a fragment that migrated as a 7mer, which is the size expected from the known binding of CC-1065 at adenine in 5'-TTA-3' sequences.
In Praise of Mock Food (2003)

Research Article| May 01 2003 In Praise of Mock Food Patricia Roberts Patricia Roberts Search for other works by this author on: This Site PubMed Google Scholar Gastronomica (2003) 3 (2): 17–21. https://doi.org/10.1525/gfc.2003.3.2.17 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Patricia Roberts; In Praise of Mock Food. Gastronomica 1 May 2003; 3 (2): 17–21. doi: https://doi.org/10.1525/gfc.2003.3.2.17 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search nav search search input Search input auto suggest search filter All ContentGastronomica Search This content is only available via PDF. Regents of the University of California Article PDF first page preview Close Modal You do not currently have access to this content.
Dominance of the E89G Substitution in HIV-1 Reverse Transcriptase in Regard to Increased Polymerase Processivity and Patterns of Pausing (1998)

The substitution of a glycine for glutamic acid at position 89 in human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT) (E89G) confers resistance to several nucleoside and non-nucleoside inhibitors of RT. As residue 89 contacts the template strand, it has been suggested that this mutation may modulate the conformation of the RT.template/primer complex. In addition, certain mutations in RT that confer resistance to nucleoside analogs, such as M184V, are located near the polymerase active site. To characterize further these substitutions, we performed processivity assays alongside an analysis of pausing profiles with wild-type (wt) RT and recombinant RTs containing substitutions at E89G, M184V, or both. We now show that E89G RT has higher processivity than wt enzyme as well as a different pattern of pausing sites. Similar findings were obtained with the doubly mutated RT, although enzyme containing only the M184V mutation had lower processivity than wt. Consistent with these observations, and from a mechanistic standpoint, both E89G-containing as well as doubly mutated RT had decreased dissociation constants from a complex consisting of RT and template-primer, in comparison with either wt RT or M184V-containing RT. No significant differences were observed among the various enzymes in regard to Km values for the heteropolymeric RNA template used in these studies. Viruses containing the E89G mutation synthesized longer strand DNA products than either wt viruses or viruses containing only the M184V mutation in endogenous RT assays. Thus, the E89G substitution is a dominant determinant in regard to each of the koff values from an RT.template/primer complex, RT processivity, and specific patterns of pausing during DNA polymerization.
Mechanical property and structure relationships in hard coatings for cutting tools (1988)

The trends in the use of hard protective coatings in WC–Co metal cutting inserts are reviewed in light of recent evaluations of mechanical and structure-sensitive properties such as elevated temperature microhardness, microfracture toughness, and internal stress. A better understanding of the role of hard coatings has evolved due to development of reliable methods to measure mechanical properties of thin coatings (of the order of 5 μ thick). There are intrinsic differences in the microstructure and residual stress state of chemical and physical vapor deposited (CVD and PVD) hard coatings. High compressive residual stress and fine grain size in PVD coatings contribute to increased microhardness and microfracture toughness. However, these benefits are reduced at high temperatures. Certain well-known structure/property concepts in bulk materials are shown to be applicable to hard coatings, which aid in interpretations of metal cutting wear behavior.
Intrahelical ion pairs in intermediate filaments. (1995)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress (2007)

Uric acid is considered a major antioxidant in human blood that may protect against aging and oxidative stress. Despite its proposed protective properties, elevated levels of uric acid are commonly associated with increased risk for cardiovascular disease and mortality. Furthermore, recent experimental studies suggest that uric acid may have a causal role in hypertension and metabolic syndrome. All these conditions are thought to be mediated by oxidative stress. In this study we demonstrate that differentiation of cultured mouse adipocytes is associated with increased production of reactive oxygen species (ROS) and uptake of uric acid. Soluble uric acid stimulated an increase in NADPH oxidase activity and ROS production in mature adipocytes but not in preadipocytes. The stimulation of NADPH oxidase-dependent ROS by uric acid resulted in activation of MAP kinases p38 and ERK1/2, a decrease in nitric oxide bioavailability, and an increase in protein nitrosylation and lipid oxidation. Collectively, our results suggest that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. Since oxidative stress in the adipose tissue has recently been recognized as a major cause of insulin resistance and cardiovascular disease, hyperuricemia-induced alterations in oxidative homeostasis in the adipose tissue might play an important role in these derangements.
Global Identification of Three Major Genotypes of Varicella-Zoster Virus: Longitudinal Clustering and Strategies for Genotyping (2004)

By analysis of a single, variable, and short DNA sequence of 447 bp located within open reading frame 22 (ORF22), we discriminated three major varicella-zoster virus (VZV) genotypes. VZV isolates from all six inhabited continents that showed nearly complete homology to ORF22 of the European reference strain Dumas were assigned to the European (E) genotype. All Japanese isolates, defined as the Japanese (J) genotype, were identical in the respective genomic region and proved the most divergent from the E strains, carrying four distinct variations. The remaining isolates carried a combination of E- and J-specific variations in the target sequence and thus were collectively termed the mosaic (M) genotype. Three hundred twenty-six isolates collected in 27 countries were genotyped. A distinctive longitudinal distribution of VZV genotypes supports this approach. Among 111 isolates collected from European patients, 96.4% were genotype E. Consistent with this observation, approximately 80% of the VZV strains from the United States were also genotype E. Similarly, genotype E viruses were dominant in the Asian part of Russia and in eastern Australia. M genotype viruses were strongly dominant in tropical regions of Africa, Indochina, and Central America, and they were common in western Australia. However, genotype M viruses were also identified as a minority in several countries worldwide. Two major intertypic variations of genotype M strains were identified, suggesting that the M genotype can be further differentiated into subgenotypes. These data highlight the direction for future VZV genotyping efforts. This approach provides the first simple genotyping method for VZV strains in clinical samples.
Amino Acid Composition and Betaxanthin Formation in Fruits from Opuntia ficus-indica* (1999)

In contrast to earlier reports high levels of taurine (2-aminoethanesulfonic acid) were found in fruit juices of three cultivars of Opuntia ficus-indica (L.) Mill. Whereas the occurrence of taurine in plant tissue was thought to be restricted to algae, fungi, and the endosperm of some higher plants, prickly pear proved to be a rich source of dietary taurine. Using L-taurine as the amino compound, a new betaxanthin was synthesized by partial synthesis. On the basis of chemical and spectral evidence its structure was determined to be the taurine-immonium-conjugate of betalamic acid. Also betalamic acid could be detected in yellow and orange coloured cultivars of Opuntia ficus-indica for the first time. In spite of the high levels of L-taurine accompanied by the occurrence of betalamic acid, the corresponding betaxanthin could not be detected in the fruit tissue.