gebhart/patrepeval huggingface dataset:
Effect of vaccination with a pentavalent leptospiral vaccine containing Leptospira interrogans serovar hardjo type hardjo-bovis on type hardjo-bovis infection of cattle (1989)

Effectiveness of 2 pentavalent leptospiral vaccines containing Leptospira interrogans serovar hardjo was evaluated for protection of steers from infection with serovar hardjo type hardjo-bovis. The hardjo component of 1 vaccine was prepared from serovar hardjo type hardjoprajitno. The hardjo component of the other vaccine was prepared from serovar hardjo type hardjo-bovis. Two steers were vaccinated once and 4 steers were vaccinated twice with the pentavalent vaccine containing type hardjoprajitno. Four steers were vaccinated once and 4 steers were vaccinated twice with the pentavalent vaccine containing type hardjo-bovis. Four steers were maintained as non-vaccinated controls. Steers given vaccine containing type hardjo-bovis developed higher mean serum microscopic agglutination titers against serovar hardjo than steers given vaccine containing hardjoprajitno. Six months after the first vaccination, all steers were challenge-exposed on 3 occasions by conjunctival instillation of 10(7) serovar hardjo type hardjo-bovis organisms, and on 1 occasion by conjunctival instillation of urine from a steer shedding hardjo-bovis. All control and all vaccinated steers became infected and shed serovar hardjo type hardjo-bovis in the urine. Lesions were detected in kidneys of 3 of 4 nonvaccinated control steers, 5 of 6 steers given hardjoprajitno vaccine, and 6 of 8 steers given hardjo-bovis vaccine. Leptospires were detected in kidneys of 4 of 4 control steers and 13 of 14 vaccinated steers.
Bowel function during pain therapy with oxycodone/naloxone prolonged-release tablets in patients with advanced cancer (2011)

Patients with OXN treatment throughout the whole study phase showed a clinically relevant improvement in pain intensity and bowel function as well as increased satisfaction. Well-known disadvantages of laxative treatment might be spared or even circumvented under OXN treatment, if appropriate.
Selective Potassium Ion Recognition by Benzo-15-crown-5 Fluoroionophore/γ-Cyclodextrin Complex Sensors in Water (2000)

Three fluoroionophores Cn (n = 1, 3, 5), in which the crown ether unit and pyrenyl moiety are connected by a -(CH2)n- spacer, have been used to construct supramolecular Cn/gamma-cyclodextrin (gamma-CyD) complexes for alkali metal ion sensing in water. The Cn (n = 3, 5) are found to selectively form 2:1 complexes with K+ in the presence of gamma-CyD and exhibit the pyrene dimer emission in water. Equilibrium analysis of the C3/gamma-CyD complex reveals that the observed dimer emission arises from a 2:1:1 complex of C3 with K+ and gamma-CyD. In the absence of K+, the fluorescence lifetimes for the dimer species ((C3)2CyD and (C3)2(CyD)2) and the monomer species (C3CyD and C3(CyD)2) are 13-18 and 130-180 ns, respectively. Upon addition of 0.10 M KCI, a rising component corresponding to pyrene excimer formation is observed at the dimer emission region. For the C3/gamma-CyD complex, the apparent association constant for K+ of (3.8 +/- 1.3) x 10(9) M(-2) is only slightly affected by the presence of Na+. Although the C5/gamma-CyD complex shows high sensitivity for K+, the selectivity for K+ over Na+ is lower than that of the C3/gamma-CyD complex. In contrast, fluoroionophore C1 with the shortest methylene spacer exhibits no response for alkali metal cations in the presence of gamma-CyD. These results demonstrate that the response function of supramolecular Cn/gamma-CyD complexes is strongly affected by the methylene spacer length of Cn. The highest K+ selectivity is obtained for the C3/gamma-CyD complexes in water.
Inhibition of KRAS -Driven Tumorigenicity by Interruption of an Autocrine Cytokine Circuit (2014)

Although the roles of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling in KRAS-driven tumorigenesis are well established, KRAS activates additional pathways required for tumor maintenance, the inhibition of which are likely to be necessary for effective KRAS-directed therapy. Here, we show that the IκB kinase (IKK)-related kinases Tank-binding kinase-1 (TBK1) and IKKε promote KRAS-driven tumorigenesis by regulating autocrine CCL5 and interleukin (IL)-6 and identify CYT387 as a potent JAK/TBK1/IKKε inhibitor. CYT387 treatment ablates RAS-associated cytokine signaling and impairs Kras-driven murine lung cancer growth. Combined CYT387 treatment and MAPK pathway inhibition induces regression of aggressive murine lung adenocarcinomas driven by Kras mutation and p53 loss. These observations reveal that TBK1/IKKε promote tumor survival by activating CCL5 and IL-6 and identify concurrent inhibition of TBK1/IKKε, Janus-activated kinase (JAK), and MEK signaling as an effective approach to inhibit the actions of oncogenic KRAS.
DNA Vaccines Encoding Interleukin-8 and RANTES Enhance Antigen-Specific Th1-Type CD4+T-Cell-Mediated Protective Immunity against Herpes Simplex Virus Type 2 In Vivo (2000)

Chemokines are inflammatory molecules that act primarily as chemoattractants and as activators of leukocytes. Their role in antigen-specific immune responses is of importance, but their role in disease protection is unknown. Recently it has been suggested that chemokines modulate immunity along more classical Th1 and Th2 phenotypes. However, no data currently exist in an infectious challenge model system. We analyzed the modulatory effects of selected chemokines (interleukin-8 [IL-8], gamma interferon-inducible protein 10 [IP-10], RANTES, monocyte chemotactic protein 1 [MCP-1], and macrophage inflammatory protein 1 alpha [MIP-1 alpha]) on immune phenotype and protection against lethal challenge with herpes simplex virus type 2 (HSV-2). We observed that coinjection with IL-8 and RANTES plasmid DNAs dramatically enhanced antigen-specific Th1 type cellular immune responses and protection from lethal HSV-2 challenge. This enhanced protection appears to be mediated by CD4(+) T cells, as determined by in vitro and in vivo T-cell subset deletion. Thus, IL-8 and RANTES cDNAs used as DNA vaccine adjuvants drive antigen-specific Th1 type CD4(+) T-cell responses, which result in reduced HSV-2-derived morbidity, as well as reduced mortality. However, coinjection with DNAs expressing MCP-1, IP-10, and MIP-1 alpha increased mortality in the challenged mice. Chemokine DNA coinjection also modulated its own production as well as the production of cytokines. These studies demonstrate that chemokines can dominate and drive immune responses with defined phenotypes, playing an important role in the generation of protective antigen-specific immunity.
Clinical Activity and Immune Modulation in Cancer Patients Treated With CP-870,893, a Novel CD40 Agonist Monoclonal Antibody (2007)

The CD40 agonist mAb CP-870,893 was well tolerated and biologically active, and was associated with antitumor activity. Further studies of repeated doses of CP-870,893 alone and in combination with other antineoplastic agents are warranted.
Adenocarcinoma-reactive human monoclonal antibody MS2B6 defines an antigen in simple glandular epithelium (1992)

A human monoclonal antibody (MAb), MS2B6, produced from splenocytes isolated from a patient with advanced papillary serous cystadenocarcinoma of the ovary, defines a unique human tumor-associated antigen. This antigen, EA2B6 (epithelial antigen 2B6), is expressed in a tissue-restricted manner on cultured and fresh human adenocarcinomas and some normal glandular epithelial tissues. EA2B6 is a 38-48 kD protein antigen that co-fractionates with the nuclear matrix-intermediate filament scaffold of simple glandular epithelial tissues. EA2B6 is a molecule with restricted solubility, and in vitro antigen-antibody binding is dependent on the antigen being presented on a solid support. To determine if EA2B6 is a cytokeratin, competition studies were undertaken with several cytokeratin-specific murine monoclonal antibodies. None of these antibodies inhibited the binding of human MAb MS2B6 to partially purified EA2B6. Less than 1% of HT29 colon adenocarcinoma cells and fresh ovarian adenocarcinoma ascites cells express EA2B6 on their surface. The majority of EA2B6 is intracellular. Because of the restricted tissue distribution of this antigen and stability of the antibody, we believe MS2B6 is a good candidate for MAb-mediated diagnosis and therapy of human adenocarcinomas.
A pulse sequence for directly measuring the anharmonicities of coupled vibrations: Two-quantum two-dimensional infrared spectroscopy (2004)

We have experimentally demonstrated a pulse sequence for the acquisition of heterodyned two-dimensional infrared (2D IR) spectra that correlates the overtone and combination bands to the fundamental frequencies. The spectra are generated by Fourier transforming the time domain signal that is allowed to evolve during one- and two-quantum coherence times. In this manner, the overtone and combination bands appear along the two-quantum axis, resulting in a direct determination of the diagonal and off-diagonal anharmonicities. To demonstrate this pulse sequence, we have collected two-quantum 2D IR spectra of a ruthenium dicarbonyl complex, extracted the diagonal and off-diagonal anharmonicities, and simulated the spectra using an exciton model. Several polarization conditions are presented that suppress the diagonal or cross peaks and we have used them to improve the accuracy of the measurement.
A High Through-put Platform for Recombinant Antibodies to Folded Proteins (2015)

Antibodies are key reagents in biology and medicine, but commercial sources are rarely recombinant and thus do not provide a permanent and renewable resource. Here, we describe an industrialized platform to generate antigens and validated recombinant antibodies for 346 transcription factors (TFs) and 211 epigenetic antigens. We describe an optimized automated phage display and antigen expression pipeline that in aggregate produced about 3000 sequenced Fragment antigen-binding domain that had high affinity (typically EC50<20 nm), high stability (Tm∼80 °C), good expression in E. coli (∼5 mg/L), and ability to bind antigen in complex cell lysates. We evaluated a subset of Fabs generated to homologous SCAN domains for binding specificities. These Fragment antigen-binding domains were monospecific to their target SCAN antigen except in rare cases where they cross-reacted with a few highly related antigens. Remarkably, immunofluorescence experiments in six cell lines for 270 of the TF antigens, each having multiple antibodies, show that ∼70% stain predominantly in the cytosol and ∼20% stain in the nucleus which reinforces the dominant role that translocation plays in TF biology. These cloned antibody reagents are being made available to the academic community through our web site recombinant-antibodies.org to allow a more system-wide analysis of TF and chromatin biology. We believe these platforms, infrastructure, and automated approaches will facilitate the next generation of renewable antibody reagents to the human proteome in the coming decade.
Growth of semipolar {20–21} GaN and {20–2–1} GaN for GaN substrate (2015)

In this article, we present a semipolar {20–21} GaN layer and {20–2–1} GaN layer for large GaN substrates. The {20–21} GaN layer was fabricated on {22–43} patterned sapphire substrates (PSSs) by metal‐organic vapor‐phase epitaxy (MOVPE) and hydride vapor‐phase epitaxy (HVPE). We found that the surface roughening and crack generation during the HVPE growth were suppressed by the formation of SiO 2 ‐striped masks parallel to the c ‐axis on the MOVPE‐grown {20–21} GaN template. Furthermore, we demonstrated millimeter‐thick crystal growth on a {20–21} GaN layer and a {20–2–1} GaN layer on a GaN substrate using HVPE. The dark‐spot density in the {20–2–1} GaN layer was approximately 9.6 × 10 6 cm −2 for 960 min growth. The dark‐spot density in the {20–2–1} GaN layer decreased more rapidly than that in the {20–21} GaN layer as growth thickness increased.
Complementary DNA encoding the human T-cell FK506-binding protein, a peptidylprolyl cis-trans isomerase distinct from cyclophilin. (1990)

The recently discovered macrolide FK506 has been demonstrated to have potent immunosuppressive activity at concentrations 100-fold lower than cyclosporin A, a cyclic undecapeptide that is used to prevent rejection after transplantation of bone marrow and organs, such as kidney, heart, and liver. After the recent discovery that the cyclosporin A-binding protein cyclophilin is identical to peptidylprolyl cis-trans isomerase, a cellular binding protein for FK506 was found to be distinct from cyclophilin but to have the same enzymatic activity. In this study, we isolated a cDNA coding for FK506-binding protein (FKBP) from human peripheral blood T cells by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence, Glu-Asp-Gly-Lys-Lys-Phe-Asp, reported for bovine FKBP. The DNA isolated contained an open reading frame encoding 108 amino acid residues. The first 40 residues of the deduced amino acid sequence were identical to those of the reported amino-terminal sequence of bovine FKBP, indicating that the DNA sequence isolated represents the gene coding for FKBP. Computer-assisted analysis of the deduced amino acid sequence indicates that FKBP exhibits no internal homology and does not have significant sequence similarity to any other amino acid sequences of known proteins, including cyclophilin. This result suggests that two catalytically similar proteins, cyclophilin and FKBP, evolved independently. In Northern blot analysis, mRNA species of approximately 1.8 kilobases that hybridized with human FKBP cDNA were detected in poly(A)+ RNAs from brain, lung, liver, and placental cells and leukocytes. Induction of Jurkat leukemic T cells with phorbol 12-myristate 13-acetate and ionomycin did not affect the level of FKBP mRNA. Southern blot analysis of human genomic DNA digested with different restriction enzymes suggests the existence of only a few copies of the DNA sequence encoding FKBP. This is in contrast to the result that as many as 20 copies of the cyclophilin gene and possible pseudogenes may be present in the mammalian genome.
Ten questions worth asking about mobile computing. (1993)

"Mobile," or perhaps "nomadic," are the watchwords for the style of information management fast coming to the healthcare sector. No, mobile technology in healthcare is not to be confused with cellular-phones. Mobile computing goes where the user goes ... to the patient.
Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation (1991)

The existence of an immunologic antileukemia reaction associated with allogeneic bone marrow transplantation (BMT) is well established. However, a similar graft-versus-tumor effect against lymphomas has not been demonstrated. We analyzed the results of BMT in 118 consecutive patients with relapsed Hodgkin's disease or aggressive non-Hodgkin's lymphoma. The 38 patients less than 50 years of age with HLA-matched donors had allogenic marrow transplants, and the other 80 patients received purged autologous grafts. The median age was 26 years in both the allogeneic and the autologous graft recipients. The patient's response to conventional salvage therapy before transplant was the only factor that influenced the event-free survival after BMT (P less than .001). Both the patient's response to salvage therapy before BMT (P less than .001) and the type of graft (P = .02) significantly influenced the probability of relapse after BMT. The actuarial probability of relapse in patients who responded to conventional salvage therapy before BMT was only 18% after allogenic BMT compared with 46% after autologous BMT. However, the actuarial probability of event-free survival at 4 years was the same, 47% versus 41%, for patients with responsive lymphomas who received allogeneic and autologous transplants, respectively (P = .8). The beneficial antitumor effect of allogeneic BMT was offset by its higher transplant-related mortality (P = .01), largely resulting from graft-versus-host disease. Allogeneic BMT appears to induce a clinically significant graft-versus- lymphoma effect. The magnitude of this effect is similar to that reported against leukemias.
Studies on the Drug Release Properties of Polysaccharide Multilayers Encapsulated Ibuprofen Microparticles (2001)

Ibuprofen microcrystals sized between 5 and 40 μm have been encapsulated with polyelectrolyte multilayers (PEM) for the purpose of controlled release. The encapsulation was accomplished by a novel coating technology based on layer-by-layer assembly of oppositely charged polyelectrolytes. The biocompatible polyelectrolytes including chitosan, dextran sulfate, carboxymethyl cellulose, and sodium alginate were used as coating materials to fabricate PEM capsules with varying shell thicknesses from 20 to 60 nm. UV spectroscopy was employed to monitor the drug release processes in both pH 1.4 and pH 7.4 solutions. It was found that the release of ibuprofen from these microcapsules is dependent on several parameters such as the crystal size, the PEM capsule thickness, and the solubility of the core material in the bulk solutions. Our results reveal that the polysaccharide capsules can substantially prolong the release time of the encapsulated drug crystals.
Clinically Important Adverse Effects and Drug Interactions with H 2 ‐Receptor Antagonists: An Update (1987)

The H2-receptor antagonists cimetidine, ranitidine, and famotidine are well tolerated, with a low frequency and similar spectrum of adverse effects. The occasional problematic effects that have been associated with these agents include central nervous system symptoms (mental confusion, headache, and depression), rare cases of thrombocytopenia, and cardiovascular events related to the rate of intravenous infusion. Severe renal and hepatic impairment appear to be associated with a higher occurrence of central nervous system effects. Because the H2-receptor antagonists elevate gastric pH, bind to and inhibit the hepatic cytochrome P-450 enzyme system, and undergo renal tubular secretion, competition with other drugs sharing these pathways has resulted in a number of drug interactions, most of which are not clinically significant. The interaction that occurs with theophylline and warfarin when the cytochrome P-450 enzyme system is inhibited by cimetidine and ranitidine requires monitoring. Recent data suggest that administering cimetidine 800 mg at bedtime has less effect on the serum concentrations of warfarin and theophylline than other dosing regimens. Evidence to date indicates that famotidine does not bind to cytochrome P-450 to a significant extent, and interactions with drugs metabolized by this system have not been reported; however, clinical experience with this agent is very limited.
CCN3 (NOV) Interacts with Connexin43 in C6 Glioma Cells (2004)

Many tumor cells exhibit aberrant gap junctional intercellular communication, which can be restored by transfection with connexin genes. We have previously discovered that overexpression of connexin43 (Cx43) in C6 glioma cells not only reduces proliferation but also leads to production of soluble growth-inhibitory factors. We identified that several members of the CCN (Cyr61/connective tissue growth factor/nephroblastoma-overexpressed) family are up-regulated following Cx43 expression, including CCN3 (NOV). We now report evidence for an association between CCN3 and Cx43. Western blot analysis demonstrated that the 48-kDa full-length CCN3 protein was present in the lysate and conditioned medium of growth-suppressed C6-Cx43 cells, as well as primary astrocytes, but not in C6 parental and human glioma cells. Immunocytochemical examination of CCN3 revealed diffuse localization in parental C6 cells, whereas transfection of C6 cells with Cx43 (C6-Cx43) or with a modified Cx43 tagged to green fluorescent protein on its C terminus (Cx43-GFP) resulted in punctate staining, suggesting that CCN3 co-localizes with Cx43 in plaques at the plasma membrane. In cells expressing a C-terminal truncation of Cx43 (Cx43Delta244-382), this co-localization was lost. Glutathione S-transferase pull-down assay and co-immunoprecipitation demonstrated that CCN3 was able to physically interact with Cx43. In contrast, CCN3 was not found to associate with Cx43Delta244-382. Similar experiments revealed that CCN3 did not co-localize or associate with other connexins, including Cx40 or Cx32. Taken together, these data support an interaction of CCN3 with the C terminus of Cx43, which could play an important role in mediating growth control induced by specific gap junction proteins.
Strong magnetic coupling between an electronic spin qubit and a mechanical resonator (2009)

We describe a technique that enables a strong coherent coupling between a single electronic spin qubit associated with a nitrogen-vacancy impurity in diamond and the quantized motion of a magnetized nanomechanical resonator tip. This coupling is achieved via careful preparation of dressed spin states which are highly sensitive to the motion of the resonator but insensitive to perturbations from the nuclear-spin bath. In combination with optical pumping techniques, the coherent exchange between spin and motional excitations enables ground-state cooling and controlled generation of arbitrary quantum superpositions of resonator states. Optical spin readout techniques provide a general measurement toolbox for the resonator with quantum limited precision.
Position-dependent effects on stability in tricyclo-DNA modified oligonucleotide duplexes (2010)

A series of oligodeoxyribonucleotides and oligoribonucleotides containing single and multiple tricyclo(tc)-nucleosides in various arrangements were prepared and the thermal and thermodynamic transition profiles of duplexes with complementary DNA and RNA evaluated. Tc-residues aligned in a non-continuous fashion in an RNA strand significantly decrease affinity to complementary RNA and DNA, mostly as a consequence of a loss of pairing enthalpy ΔH. Arranging the tc-residues in a continuous fashion rescues T(m) and leads to higher DNA and RNA affinity. Substitution of oligodeoxyribonucleotides in the same way causes much less differences in T(m) when paired to complementary DNA and leads to substantial increases in T(m) when paired to complementary RNA. CD-spectroscopic investigations in combination with molecular dynamics simulations of duplexes with single modifications show that tc-residues in the RNA backbone distinctly influence the conformation of the neighboring nucleotides forcing them into higher energy conformations, while tc-residues in the DNA backbone seem to have negligible influence on the nearest neighbor conformations. These results rationalize the observed affinity differences and are of relevance for the design of tc-DNA containing oligonucleotides for applications in antisense or RNAi therapy.
Cancer stem cells in bladder cancer: a revisited and evolving concept (2010)

Functionally distinct CSCs exist in human bladder cancer and can be prospectively isolated. Continuing research will be important to identify their cell of origin, programs balancing self-renewal and differentiation and to identify additional therapeutic options to target bladder CSCs.