gebhart/patrepeval huggingface dataset:
Genetic Linkage of Exotoxin Alleles andemmGene Markers for Tissue Tropism in Group A Streptococci (1999)

In group A streptococci, genetic markers for principal tissue reservoir are located within emm genes, which encode surface proteins that have a role in virulence. A worldwide collection of 160 isolates was evaluated for two traits: chromosomal emm gene markers for tissue tropism (designated patterns A-E), and bacteriophage-associated genes (speA and speC) encoding pyrogenic exotoxins. The speA and speC alleles of organisms harboring the emm marker for a pharyngeal reservoir (pattern A-C) differ from spe alleles that predominate in organisms with the emm marker for impetigo (pattern D). However, organisms that display the emm marker for both tissue sites (pattern E) are not intermediate for the distribution of either speA or speC alleles, but instead resemble pattern A-C isolates for speA and pattern D strains for speC. Statistically significant nonrandom associations between exotoxin alleles and emm patterns were observed but cannot be readily explained by niche separation alone.
mRNA display selection and solid‐phase synthesis of Fc‐binding cyclic peptide affinity ligands (2012)

Cyclic peptides are attractive candidates for synthetic affinity ligands due to their favorable properties, such as resistance to proteolysis, and higher affinity and specificity relative to linear peptides. Here we describe the discovery, synthesis and characterization of novel cyclic peptide affinity ligands that bind the Fc portion of human Immunoglobulin G (IgG; hFc). We generated an mRNA display library of cyclic pentapeptides wherein peptide cyclization was achieved with high yield and selectivity, using a solid-phase crosslinking reaction between two primary amine groups, mediated by a homobifunctional linker. Subsequently, a pool of cyclic peptide binders to hFc was isolated from this library and chromatographic resins incorporating the selected cyclic peptides were prepared by on-resin solid-phase peptide synthesis and cyclization. Significantly, this approach results in resins that are resistant to harsh basic conditions of column cleaning and regeneration. Further studies identified a specific cyclic peptide--cyclo[Link-M-WFRHY-K]--as a robust affinity ligand for purification of IgG from complex mixtures. The cyclo[Link-M-WFRHY-K] resin bound selectively to the Fc fragment of IgG, with no binding to the Fab fragment, and also bound immunoglobulins from a variety of mammalian species. Notably, while the recovery of IgG using the cyclo[Link-M-WFRHY-K] resin was comparable to a Protein A resin, elution of IgG could be achieved under milder conditions (pH 4 vs. pH 2.5). Thus, cyclo[Link-M-WFRHY-K] is an attractive candidate for developing a cost-effective and robust chromatographic resin to purify monoclonal antibodies (mAbs). Finally, our approach can be extended to efficiently generate and evaluate cyclic peptide affinity ligands for other targets of interest.
Clinical significance of mannose‐binding lectin‐associated serine protease‐2 expression in esophageal squamous cell carcinoma (2006)

Mannan-binding lectin-associated serine protease-2 (MASP-2) is a serine protease involved in the activation of lectin complement pathway. The differential expression of MASP-2 in human esophageal squamous cell carcinoma (ESCC) was recently reported from our laboratory using differential display. To determine the expression of MASP-2 protein, we raised a polyclonal antibody to human MASP-2 and used it for immunohistochemical analysis of MASP-2 in ESCCs. The antibody showed a single band of predicted molecular weight by western blotting. In normal human liver tissue, the cytoplasm was distinctly labeled by the antibody. Intriguingly, besides the cytoplasm, the nuclei of esophageal tumor cells were also labeled. To investigate the association of MASP-2 expression with esophageal tumorigenesis, its expression was analyzed in 51 primary ESCCs, 32 dysplasias, 21 histologically normal esophageal tissues and 6 adenocarcinomas by immunohistochemistry. Increased MASP-2 expression was observed in ESCCs (p = 0.001, Odd's ratio (OR) = 3.662) and in premalignant condition, dysplasia (p = 0.000, OR = 5.091) in comparison with the normal tissues. MASP-2 expression in ESCCs was associated with late clinical stage (p = 0.009, O.R. = 3.430) and nodal metastasis (p = 0.001, O.R. = 4.520). In conclusion, our antibody was demonstrated to be useful in recognizing MASP-2 expression on paraffin embedded tissue sections. To our knowledge, this is the first report showing MASP-2 expression in a solid tumor. MASP-2 expression in premalignant stage (dysplasia) as well as in ESCCs and its association with late clinical stage and nodal metastasis suggest that alteration in its expression is maintained during disease progression and is associated with aggressive tumor behavior.
Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice (1989)

Protective immunity to lethal Candida albicans challenge in vivo and activation of splenic macrophages with highly candidacidal activity in vitro were detected in mice infected with low-virulence agerminative yeast cells of the variant strain PCA-2, at a time when a strong delayed-type hypersensitivity (DTH) reaction to C. albicans occurred in the footpads of PCA-2-treated mice. The DTH reaction was transferable with spleen cell populations from these animals, and enrichment of splenic lymphocytes in L3T4+ cells significantly increased the footpad swelling. The reactivity transferred by L3T4+ cells was a radiosensitive (2,500 rads in vitro) phenomenon that required collaboration with radioresistant, silica-sensitive syngeneic cells in the host and was inhibited by treatment of recipient mice with antibodies to the L3T4 antigen or murine gamma interferon. In vitro, the PCA-2-immune L3T4+ cells produced various lymphokine activities upon incubation with C. albicans, including gamma interferon and granulocyte-macrophage colony-stimulating factor. Anti-L3T4 monoclonal antibody treatment of PCA-2-infected mice significantly impaired their footpad reaction and resistance to C. albicans, as shown by increased recovery of yeast cells from the kidneys of anti-L3T4-treated mice. These results suggested that the mechanisms of anti-Candida resistance induced by PCA-2 may involve specific induction of a DTH response mediated by inflammatory L3T4+ T cells and lymphokine-activated phagocytic effectors. However, the survival rate of the PCA-2-immune mice challenged with C. albicans was not significantly modified by administration of the anti-L3T4 antibody, thus allowing for the conclusion that compensatory mechanisms lead to considerable anti-Candida resistance when the activity of L3T4+ cells is deficient.
Structure of the cobalt-dependent methionine aminopeptidase from Escherichia coli: a new type of proteolytic enzyme (1993)

The X-ray structure of Escherichia coli methionine aminopeptidase (MAP) has been determined to 2.4-A resolution and refined to a crystallographic R-factor of 18.2%. The fold is novel and displays internal pseudo-2-fold symmetry which structurally relates the first and second halves of the polypeptide chain. The topology consists of a central antiparallel beta-sheet covered on one side by two pairs of alpha-helices and by a C-terminal loop. The other face of the beta-sheet, together with some irregular loops, forms the active site, which contains two cobalt ions 2.9 A apart. These metal ions are liganded by the side chains of Asp 97, Asp 108, Glu 204, Glu 235, and His 171 with approximate octahedral coordination. In terms of both the novel backbone fold and the constitution of the active site, MAP appears to represent a new class of proteolytic enzyme.
Euclidean shape-encoded combinatorial chemical libraries (2000)

A method for the encoding of split/mix combinatorial chemical libraries based on Euclidean shapes is described. The shapes are fashioned from a polymeric matrix designed to swell in common organic solvents while retaining their unique forms, and exhibit good mechanical strength. The lightly crosslinked gel-type polymer was processed into an array of Euclidean forms that serve as encoding elements in the synthesis of combinatorial chemical libraries by using the split/pool methodology. To assess the viability of this approach, a library of compounds based on a urea scaffold was prepared. The validity of this methodology was demonstrated through correct deconvolution of the library mixture by shape discrimination. Furthermore, because the shapes used have a large surface area to volume ratio, each monolith can act as an independent chemical reactor. This simplifies the analytical identification process because each compound can be prepared in significant quantities and isolated as single entities. Given the high loading capacity of the monoliths and the conceptually simple encoding strategy, it is envisioned that these Euclidean forms will find significant application in combinatorial and high-throughput synthetic chemistry.
Generation of Lymphohematopoietic Cells from Embryonic Stem Cells in Culture (1994)

An efficient system was developed that induced the differentiation of embryonic stem (ES) cells into blood cells of erythroid, myeloid, and B cell lineages by coculture with the stromal cell line OP9. This cell line does not express functional macrophage colony-stimulating factor (M-CSF). The presence of M-CSF had inhibitory effects on the differentiation of ES cells to blood cells other than macrophages. Embryoid body formation or addition of exogenous growth factors was not required, and differentiation was highly reproducible even after the selection of ES cells with the antibiotic G418. Combined with the ability to genetically manipulate ES cells, this system will facilitate the study of molecular mechanisms involved in development and differentiation of hematopoietic cells.
Conclusion (2001)

This book has argued that Marcel Proust's philosophy of perspectivism finds its most appropriate expression in fiction. It is no surprise that Friedrich Nietzsche's philosophy should have been, and should continue to be, a potent force in spurring the literary creativity of novelists, poets, and dramatists since his time. Proust was certainly no Nietzschean in this sense, but perhaps this book, by setting up its own dialogue between the two writers, will have established that a comparative reading of Nietzsche and Proust can be more productive than either might themselves have conceded.
Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy (2015)

Interleukins as immunomodulators are promising therapeutic agents for cancer therapy. Previous studies showed that there was an improved antitumor immunity in tumor-bearing mice using recombinant Newcastle disease virus carrying for interleukin-2. Interleukin-12 is a promising antitumor cytokine too. So we investigated and compared the antitumor effect of genetically engineered Newcastle disease virus strains expressing both interleukin-12 and/or interleukin-2 (rClone30-interleukin-2, rClone30-interleukin-12, and rClone30-interleukin-12-interleukin-2). In vitro studies showed that rClone30s could efficiently infect tumor cells and express interleukin-12 and/or interleukin-2. 3-(4,5-Dimethylthiazol-2-y)-2,5-diphenyl-tetrazolium bromide results showed rClone30s possessed strong cytotoxic activities against multiple tumor cell lines (U251, HepG2, A549, and Hela). Animal studies showed that rClone30-interleukin-12-interleukin-2 was more effective in inhibition of murine hepatoma carcinoma tumors, with the mean tumor volume (day 14) of 141.70 mm(3) comparing 165.67 mm(3) of rClone30-interleukin-12 group, 210.47 mm(3) of rClone30-interleukin-2 group, 574.70 mm(3) of rClone30 group, and 1206.83 mm(3) of phosphate-buffered saline group. Moreover, the rClone30-interleukin-12-interleukin-2 treated mice secreted more interferon γ (333.518 pg/mL) and its downstream cytokine interferon-γ induced protein 10 (16.006 pg/mL) in tumor than the rClone30-interleukin-12 group (interferon γ: 257.548 pg/mL; interferon-γ induced protein 10: 13.601 pg/mL), rClone30-interleukin2 group (interferon γ: 124.601 pg/mL; interferon-γ induced protein 10: 9.779 pg/mL), or rClone30 group (interferon γ: 48.630 pg/mL; interferon-γ induced protein 10:1.650 pg/mL). For the survival study, rClone30-interleukin12-interleukin2 increased the survival rate (12 of 16) of the tumor-bearing mice versus 11 of 16 in rClone30-interleukin-12 group, 10 of 16 in rClone30-interleukin-2 group, 7 of 16 in Clone30 group, and 0/16 in phosphate-buffered saline group, respectively. To determine whether the mice treated with recombinant virus developed protective immune response, the mice were rechallenged with the same tumor cells. The results showed that viral-treated mice were significantly protected from rechallenge. These results suggest that expressing both interleukin-2 and/or interleukin-12 could be ideal approaches to enhance the antitumor ability of Newcastle disease virus, and rClone30-interleukin-12-interleukin-2 is slightly superior over rClone30-interleukin-12 and rClone30-interleukin-2 alone.
Crystal structure of nickel-containing superoxide dismutase reveals another type of active site (2004)

Superoxide dismutases (SODs, EC 1.15.1.1) are ubiquitous enzymes that efficiently catalyze the dismutation of superoxide radical anions to protect biological molecules from oxidative damage. The crystal structure of nickel-containing SOD (NiSOD) from Streptomyces seoulensis was determined for the resting, x-ray-reduced, and thiosulfate-reduced enzyme state. NiSOD is a homohexamer consisting of four-helix-bundle subunits. The catalytic center resides in the N-terminal active-site loop, where a Ni(III) ion is coordinated by the amino group of His-1, the amide group of Cys-2, two thiolate groups of Cys-2 and Cys-6, and the imidazolate of His-1 as axial ligand that is lost in the chemically reduced state as well as after x-ray-induced reduction. This structure represents a third class of SODs concerning the catalytic metal species, subunit structure, and oligomeric organization. It adds a member to the small number of Ni-metalloenzymes and contributes with its Ni(III) active site to the general understanding of Ni-related biochemistry. NiSOD is shown to occur also in bacteria other than Streptomyces and is predicted to be present in some cyanobacteria.
Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene. (1990)

Matrix Gla protein (MGP) is an 84-residue vitamin K-dependent protein initially isolated from bovine bone. MGP is also expressed at high levels in heart, kidney, and lung and is up-regulated by vitamin D in bone cells. To characterize the genomic sequences responsible for the regulated expression of this gene, we screened a human genomic library using a MGP cDNA probe and obtained two clones containing the MGP locus. The human MGP gene spans 3.9 kilobases of chromosomal DNA and consists of four exons separated by three large intervening sequences which account for more than 80% of the gene. Southern analysis of total human genomic DNA indicated the presence of a single copy of the MGP gene. Hybridization of the hMGP cDNA to a series of Chinese Hamster x human hybrid clones assigned this gene to the short arm of the human chromosome 12 (12p). The N-terminal sequences of the known vitamin K-dependent vertebrate proteins reveal a transmembrane signal peptide, followed by a putative gamma-carboxylation recognition site and a Gla-containing domain. Each of these regions correspond to a separate exon in MGP. MGP also contains a fourth exon of unknown function which codes for 11 residues and lies between the transmembrane signal peptide and the putative recognition site for the gamma-carboxylase. This four-exon organization is essentially identical to that of bone Gla protein and is quite different from the two exon organization encoding this region in the other known vitamin K-dependent proteins. Analysis of the MGP gene promoter revealed, in addition to the typical TATA and CAT boxes, the presence of a number of putative regulatory sequences homologous to previously identified hormone and transcription factor responsive elements. In particular, two regions of the promoter were delineated containing possible binding sites for retinoic acid and vitamin D receptors.
Transaction Network, Telephones, and Terminals: Overview (1978)

Short inquiry and response messages, called transactions, are becoming increasingly important in the conduct of business affairs. These messages are moved electronically through data communications networks. To meet the need, a family of Transaction telephones, terminals, and associated networks, adjuncts, and arrangements has been developed.
Inhibition of the transport function of membrane proteins by some substituted phenothiazines in E. coli and multidrug resistant tumor cells. (1997)

Efflux-pumps mediated by P-glycoprotein increase the level of resistance to antibiotics in bacteria and to cytostatics in tumor cells due to decreased drug accumulation, and are also involved in the operation of blood brain barrier. Different compounds are able to enhance drug retention in the cells by inhibiting the efflux-pump mechanism of multidrug resistant (mdr) cancer cells and bacteria. The effects of substituted chlorpromazines were studied on a hemolysin producing and antibiotic resistant plasmid carrying E coli, and rhodamine uptake of multidrug resistant (mdr 1 gene expressing) mouse lymphoma cells. Hemolysin transporter protein encoding plasmids were eliminated from E. coli by a representative phenothiazine namely promethazine. Minimal inhibitory concentrations of tetracyclin and promethazine were lower for plasmidless bacteria as compared to the parent, plasmid carrying strains. The antibiotic resistance plasmid was cured of the R-plasmid of E. coli JE 2571, however, the ring substituted derivatives were less effective then parent compounds. The effect of some substituted phenothiazines on P-glycoprotein efflux-pump of mouse lymphoma cells were studied. The majority of ring substituted derivatives reversed the mdr of tumor cells. The 3,7,8-trihydroxy- and 7,8-dihydroxy derivatives of chlorpromazine were effective as P-glycoprotein blockers, however, 7,8-diacetoxy-, 7,8dimetoxy-, 7-semicarbazone-, and 5-oxo-chlorpromazine derivatives had only moderate effect. A tomato lectin, specific for blood brain capillary endothelium was able to modify the activity of P-glycoprotein in tumor cells. Phenothiazine and tomato lectin had some antagonism in tumor cells. Our results suggest that the inhibition of P-glycoprotein function in murine tumor cells and inhibition of transporter protein in E. coli bacteria may depend on pi-electron superdelocalizibility and electrophile binding of the compounds to the transporter proteins. The intracellular accumulation of antibiotics or chemotherapeutics increased as a consequence of decreased drug efflux in both bacterial and tumor cell systems. The inhibition of the drug effux-pump is the same for all individual cells of the population. These results can be realized by combination chemotherapy, however, antiplasmid effect itself cannot be exploited in this respect because the resistance was reversed in a part of the population only. The similarity with mdr P-glycoprotein in tumor cells and brain capillary endothels provides a good model for molecules opening the blood brain barrier.
Agglomerative clustering of a search engine query log (2000)

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Aligned carbon nanotubes in a thin polymer film (1995)

Carbon nanotubes (see figure) constitute one of the smallest one‐dimensional and nearly perfect structures available and these materials should exhibit a wide range of interesting properties. Most of these properties, however, will only be of use if te structures can be manipulated into a controlled configuration here the alignment of nanotubes in thin polymer films is discussed. magnified image
Cap ribose methylation of c-mos mRNA stimulates translation and oocyte maturation in Xenopus laevis (1998)

In Xenopus oocytes, progesterone stimulates the cytoplasmic polyadenylation and resulting translational activation of c-mos mRNA, which is necessary for the induction of oocyte maturation. Although details of the biochemistry of polyadenylation are beginning to emerge, the mechanism by which 3' poly(A) addition stimulates translation initiation is enigmatic. A previous report showed that polyadenylation induced cap-specific 2'-O-methylation, and suggested that this 5' end modification was important for translational activation. Here, we demonstrate that injected c-mos RNA undergoes polyadenylation and cap ribose methylation. Inhibition of this methylation by S-isobutylthioadenosine (SIBA), a methyltransferase inhibitor, has little effect on progesterone-induced c-mos mRNA polyadenylation or general protein synthesis, but prevents the synthesis of Mos protein as well as oocyte maturation. Maturation can be rescued, however, by the injection of factors that act downstream of Mos, such as cyclin A and B mRNAs. Most importantly, we show that the translational efficiency of injected mRNAs containing cap-specific 2'-O-methylation (cap I) is significantly enhanced compared to RNAs that do not contain the methylated ribose (cap 0). These results suggest that cap ribose methylation of c-mos mRNA is important for translational recruitment and for the progression of oocytes through meiosis.
Expression of Secreted Platelet-Derived Growth Factor-B by Recombinant Nonreplicating and Noncytopathic Vaccinia Virus (1996)

These results provide important preliminary evidence for the ability to treat nonhealing wounds with nonreplicating and noncytopathic recombinant vaccinia viruses encoding cytokine growth factors.
Identification and Prediction of Promiscuous Aggregating Inhibitors among Known Drugs (2003)

Some small molecules, often hits from screening, form aggregates in solution that inhibit many enzymes. In contrast, drugs are thought to act specifically. To investigate this assumption, 50 unrelated drugs were tested for promiscuous inhibition via aggregation. Each drug was tested against three unrelated model enzymes: beta-lactamase, chymotrypsin, and malate dehydrogenase, none of which are considered targets of these drugs. To be judged promiscuous, the drugs had to inhibit all three enzymes, do so in a time-dependent manner, be sensitive to detergent and to enzyme concentration, and form particles detectable by light scattering. Of the 50 drugs tested, 43 were nonpromiscuous by these criteria. Surprisingly, four of the drugs showed promiscuous, aggregation-based inhibition at concentrations below 100 microM: clotrimazole, benzyl benzoate, nicardipine, and delavirdine. Three other drugs also behaved as aggregation-based inhibitors, but only at high concentrations (about 400 microM). To investigate possible structure-activity relationships among promiscuous drugs, five analogues of the antifungal clotrimazole were studied. Three of these, miconazole, econazole, and sulconazole, were promiscuous but the other two, fluconazole and ketoconazole, were not. Using recursive partitioning, these experimental results were used to develop a model for predicting aggregate-based promiscuity. This model correctly classified 94% of 111 compounds-47 aggregators and 64 nonaggregators-that have been studied for this effect. To evaluate the model, it was used to predict the behavior of 75 drugs not previously investigated for aggregation. Several preliminary points emerge. Most drugs are not promiscuous, even at high concentrations. Nevertheless, at high enough concentrations (20-400 microM), some drugs can aggregate and act promiscuously, suggesting that aggregation may be common among small molecules at micromolar concentrations, at least in biochemical buffers.