gebhart/patrepeval huggingface dataset:
CD40 stimulation accelerates deletion of tumor-specific CD8+T cells in the absence of tumor-antigen vaccination (2001)

Previous work has established a role for CD40-mediated signals in eliciting helper-dependent CD8(+) T cell responses. Here we investigated the effects of in vivo CD40 stimulation on the survival and function of tumor-specific CD8(+) T cells in a mouse melanoma model system. We found that agonistic anti-CD40 antibody treatment alone of tumor-bearing mice accelerated the deletion of tumor-antigen-specific T cells. However, long-term survival and function of tumor-antigen-specific T cells could be achieved when viral immunization with tumor antigen and anti-CD40 treatment were combined. This rescue of CD8(+) T cells could not be easily replicated by inflammatory or antigen-specific stimuli alone, demonstrating the specificity of signals that regulate the deletion or survival of tumor-specific T cells. These results demonstrate that opposing effects can be elicited by CD40 stimulation in vivo and suggest the need for caution in using this treatment for cancer patients.
Optimal Design Features of Camelized Human Single-domain Antibody Libraries (2001)

We have constructed a human V(H) library based on a camelized V(H) sequence. The library was constructed with complete randomization of 19 of the 23 CDR3 residues and was panned against two monoclonal antibody targets to generate V(H) sequences for determination of the antigen contact residue positions. Furthermore, the feasibility and desirability of introducing a disulfide bridge between CDR1 and CDR3 was investigated. Sequences derived from the library showed a bias toward the use of C-terminal CDR3 residues as antigen contact residues. Mass spectrometric analyses indicated that CDR1-CDR3 disulfide formation was universal. However, surface plasmon resonance and NMR data showed that the CDR3 constraint imposed by the disulfide bridge was not always desirable. Very high yields of soluble protein products and lack of protein aggregation, as demonstrated by the quality of the (1)H-(15)N HSQC spectra, indicated that the V(H) sequence for library construction was a good choice. These results should be useful in the design of V(H) libraries with optimal features.
Comparative analysis of the regulation of the interferoninducible protein kinase PKR by Epstein - Barr virus RNAs EBER-1 and EBER-2 and adenovirus VA, RNA (1993)

The interferon-inducible protein kinase PKR interacts with a number of small viral RNA species, including adenovirus VAI RNA and the Epstein-Barr virus-encoded RNA EBER-1. These RNAs bind to PKR and protect protein synthesis from inhibition by double-stranded RNA in the reticulocyte lysate system. Using a peptide phosphorylation assay we show here that EBER-1, like VAI, directly inhibits the activation of purified PKR. A second Epstein-Barr virus RNA, EBER-2, also regulates PKR. EBER-1, EBER-2 and VAI RNA exhibit mutually competitive binding to the native or recombinant enzyme, as assessed by U.V. crosslinking experiments and filter binding assays. The affinities of all three RNAs for PKR in vitro are similar (Kd = ca. 0.3 nM). Since this protein kinase has been proposed to exert a tumour suppressor function in vivo, the ability of EBER-1 to inhibit its activation suggests a role for this small RNA in cell transformation by Epstein-Barr virus.
Soluble Flt-1 Gene Transfer Ameliorates Neointima Formation After Wire Injury in flt-1 Tyrosine Kinase–Deficient Mice (2009)

These results suggest that endogenous VEGF accelerates neointima formation through flk-1 by regulating MCP-1 expression in VSMCs and macrophage-mediated inflammation in injured vascular wall in murine model of wire injury.
Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease (2014)

Our results argue against the controversial TH1/TH2 or TH17/Treg paradigms. In contrast, they suggest that a subpopulation of TH17 cells sharing a TH1 signature may be specifically involved in intestinal inflammation in CD and UC. These findings provide a better understanding of IBD pathogenesis and may help explain the efficacy of anti-IL-12p40/IL-23 and failure of anti-IL-17A therapies despite the enrichment of TH17 cells.
Filter response of single-mode fibre recirculating delay lines (1982)

Single-mode fibre recirculating delay lines have been made on a single continuous loop of fibre with the use of fibre directional couplers. These devices have been demonstrated as bandpass filters and as notch filters at centre frequencies from 0.5 MHz to 1.3 GHz with a notch depth of over 45 dB.
CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. (1996)

p16 is involved in a cell cycle regulatory cascade that includes cyclin-dependent kinase 4 (cdk4), cyclin D1, and pRb (retinoblastoma). Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or in GBM cell lines. Because perturbation of any component in this pathway may have similar oncogenic effects, we studied the relationship between abnormalities of CDKN2/p16 and RB, the two commonly involved tumor suppressor genes, in 55 astrocytic gliomas (42 GBMs, 8 anaplastic astrocytomas, and 5 astrocytomas). By using comparative multiplex PCR, homozygous deletions of the CDKN2/p16 gene were detected in 24 GBMs (57%) and in 2 anaplastic astrocytomas. Two additional GBMs and one anaplastic astrocytoma had allelic loss of chromosome 9p, as assessed by microsatellite polymorphisms flanking the CDKN2/p16 region. Single-strand conformation polymorphism and DNA sequencing analysis of all three coding exons of CDKN2/p16 revealed a frameshift mutation (four-bp deletion) in one of the three GBMs that had lost the remaining 9p allele. Allelic loss of chromosome 13q at the RB gene, RB gene mutations, or loss of pRb expression was noted in 14 GBMs (33%) and 2 anaplastic astrocytomas. Thirty-six of 42 GBMs (86%) had alterations of either CDKN2/p16 (n = 22), RB (n = 10), or both (n = 4); these two genetic changes, however, were relatively exclusive (P = 0.003). Furthermore, of the six GBMs without either CDKN2/p16 or RB gene abnormalities, one case had CDK4 gene amplification. These data indicate that the vast majority of GBMs probably have inactivation of the p16-cdk4/cyclin D1-pRb pathway. The findings also provide corroborative evidence that CDKN2/p16 and RB are the critical glioma tumor suppressor genes on chromosomes 9p and 13q, respectively.
Fibrinogen Binding Sites P336 and Y338 of Clumping Factor A Are Crucial for Staphylococcus aureus Virulence (2008)

We have earlier shown that clumping factor A (ClfA), a fibrinogen binding surface protein of Staphylococcus aureus, is an important virulence factor in septic arthritis. When two amino acids in the ClfA molecule, P(336) and Y(338), were changed to serine and alanine, respectively, the fibrinogen binding property was lost. ClfAP(336)Y(338) mutants have been constructed in two virulent S. aureus strains Newman and LS-1. The aim of this study was to analyze if these two amino acids which are vital for the fibrinogen binding of ClfA are of importance for the ability of S. aureus to generate disease. Septic arthritis or sepsis were induced in mice by intravenous inoculation of bacteria. The clfAP(336)Y(338) mutant induced significantly less arthritis than the wild type strain, both with respect to severity and frequency. The mutant infected mice developed also a much milder systemic inflammation, measured as lower mortality, weight loss, bacterial growth in kidneys and lower IL-6 levels. The data were verified with a second mutant where clfAP(336) and Y(338) were changed to alanine and serine respectively. When sepsis was induced by a larger bacterial inoculum, the clfAP(336)Y(338) mutants induced significantly less septic death. Importantly, immunization with the recombinant A domain of ClfAP(336)SY(338)A mutant but not with recombinant ClfA, protected against septic death. Our data strongly suggest that the fibrinogen binding activity of ClfA is crucial for the ability of S. aureus to provoke disease manifestations, and that the vaccine potential of recombinant ClfA is improved by removing its ability to bind fibrinogen.
Brief electrical stimulation after facial nerve transection and neurorrhaphy: A randomized prospective animal study (2016)

This is the first study to use an implantable stimulator for serial BES following neurorrhaphy in a validated animal model. Results suggest performing BES after facial nerve transection and neurorrhaphy at the main trunk of the facial nerve is associated with accelerated whisker movement in a rat model compared with a control group.
Construction of an infectious molecular clone of the autonomous parvovirus minute virus of mice (1983)

The linear single-stranded DNA genome of minute virus of mice, an autonomous parvovirus, was cloned in duplex form into the bacterial plasmid pBR322. The recombinant clones of minute virus of mice were infectious when transfected into monolayers of human 324K cells and produced virus plaques with an efficiency of about 6% that obtained with duplex replicative-form DNA purified from cells infected with minute virus of mice. Southern blot analysis of transfected cells indicated that the cloned minute virus of mice genome requires both termini to be intact for excision and replication as a linear duplex molecule.
Differential involvement of group II and group III mGluRs as autoreceptors at lateral and medial perforant path synapses (1996)

1. Previous reports have shown that group III metabotropic glutamate receptors (mGluRs) serve as autoreceptors at the lateral perforant path, but to date there has been no rigorous determination of the roles of other mGluRs as autoreceptors at this synapse. Furthermore, it is not known which of the mGluR subtypes serve as autoreceptors at the medial perforant path synapse. With the use of whole cell patch-clamp and field excitatory postsynaptic potential (fEPSP) recording techniques, we examined the groups of mGluRs that act as autoreceptors at lateral and medial perforant path synapses in adult rat hippocampal slices. 2. Consistent with previous reports, the group III mGluR agonist (D,L)-2-amino-4-phosphonobutyric acid reduced fEPSPs and excitatory postsynaptic currents (EPSCs) in the dentate gyrus. However, the group-II-selective agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) also reduced fEPSPs and EPSCs, suggesting that multiple mGluR subtypes may serve as autoreceptors at perforant path synapses. 3. Selective activation of either medial or lateral perforant pathways revealed that micromolar concentrations of (L)-2-amino-4-phosphonobutyric acid (L-AP4) reduce fEPSPs in lateral but not medial perforant path, suggesting group III involvement at the lateral perforant pathway. Conversely, DCG-IV and 2R, 4R-4-aminopyrrolidine-2,4-dicarboxylate, another group-II-selective mGluR agonist, potently reduced fEPSPs at the medial but not lateral perforant path, suggesting that a group II mGluR may act as an autoreceptor at the medial perforant path-dentate gyrus synapse. 4. Antagonist studies with group-selective antagonists such as (2S,3S,4S)-2-methyl-2-(carboxycyclpropyl)glycine (MCCG; group II) and alpha-methyl-L-AP4 (MAP4; group III) suggest differential involvement of each group at these synapses. The effect of L-AP4 at the lateral perforant path synapse was blocked by MAP-4, but not MCCG. In contrast, the effect of DCG-IV was blocked by application of MCCG, but not MAP4. 5. Previous studies suggest that the effect of L-AP4 at the lateral perforant path synapse is mediated by a presynaptic mechanism. In the present studies, we found that concentrations of DCG-IV that reduce transmission at the medial perforant path synapse reduce paired-pulse depression and do not reduce kainate-evoked currents recorded from dentate granule cells. This is consistent with the hypothesis that DCG-IV also acts by a presynaptic mechanism.
Early transcription factor subunits are encoded by vaccinia virus late genes. (1990)

The vaccinia virus early transcription factor (VETF) was shown to be a virus-encoded heterodimer. The gene for the 82-kDa subunit was identified as open reading frame (ORF) A8L, based on the N-terminal sequence of factor purified by using DNA-affinity magnetic beads. The 70-kDa subunit of VETF was refractory to N-terminal analysis, and so N-terminal sequences were obtained for three internal tryptic peptides. All three peptides matched sequences within ORF D6R. ORFs A8L and D6R are located within the central region of the vaccinia virus genome and are separated by about 13,600 base pairs. Proteins corresponding to the 3' ends of ORFs A8L and D6R were overexpressed in Escherichia coli and used to prepare antisera that bound to the larger and smaller subunits, respectively, of affinity-purified VETF. Immunoblot analysis of proteins from infected cells indicated that both subunits are expressed exclusively in the late phase of infection, just prior to their packaging in virus particles. The two subunits of VETF have no significant local or overall amino acid sequence homology to one another, to other entries in biological sequence data bases including bacterial sigma factors, or to recently determined sequences of some eukaryotic transcription factors. The 70-kDa subunit, however, has motifs in common with a super-family of established and putative DNA and RNA helicases.
Recent Patents on the Pichia Pastoris Expression System: Expanding the Toolbox for Recombinant Protein Production (2009)

Pichia pastoris is a widely used host system for heterologous protein expression both for basic research and industrial production purposes. Recent developments expanding the P. pastoris protein expression toolbox reflect the increasing interest in the application of yeast expression systems for protein-based pharmaceutical products, as an alternative to Escherichia coli and mammalian cell factories. The commonly used expression system for P. pastoris and the recent patents relevant to the P. pastoris genetic toolbox for recombinant protein production are reviewed.
Developing a More Focal Magnetic Stimulator. Part I (1991)

Some general properties of currents induced by magnetic stimulators in volume conductors of any shape are first reviewed. Then, the property of focality (concentration at some internal point) of the current induced in a spherical model of the head is discussed, due to coils of various orientations and configurations. It is shown that one important property for focality is the complete absence of the radial component of current, regardless of the coil used. The theoretically computed current distributions in the sphere produced by three different coils are illustrated. These are (1) a circular coil parallel to the head (very nonfocal). (2) a circular coil erect on the head (more focal), and (3) a figure-eight coil parallel to the head (most focal). A computational search for yet more focal coil configurations shows that the figure-eight focality can only be altered somewhat, but basically not improved. A plot of focality of the figure-eight coil versus the diameter of its coils shows an improvement in focality with decreasing diameter down to one cm. At this diameter, the induced current at a level 2 cm below the coil is concentrated in a band 1.5 cm wide (half-maximum points). Finally, it is noted that as the diameter of the figure-eight coil is decreased, the current in the coil necessary for stimulation increases rapidly, with increasing engineering problems.
Single- and dual-axis lateral photodetectors of rectangular shape (1975)

A 2-dimensional diffusion model of rectagular single-and dual-axis, lateral photodiodes is analyzed and the different underlying lateral effects are discussed for the small-signal (unbiased) and fully reverse-biased modes, with either infinite terminating impedances at midlateral point contacts or zero loading impedances at extended lateral contacts. For the single-axis detector with two opposite extended contacts, previous results of the 1-dimensional model appear to remain valid, and the output current difference to sum ratio in the fully reverse-biased mode is a linear function of the position of a narrow incident light beam. For the dual-axis detector with extended contacts at all four sides--except for small gaps at the vertices--an approximately linear relation has been found between the light spot position along an axis and the log ratio of the corresponding output currents. The transient responses of these configurations are discussed, and the utility of operation in the small-signal mode is illustrated with some typical parameter values.
Peroxidase as a developmental marker in plant tissue culture (1991)

Peroxidase was studied as a developmental marker in pumpkin (Cucurbita pepo L.) callus lines and horse-radish (Armoracia lapathifolia Gilib) transformants. Embryogenic callus lines DE grown on MS medium with 2.4-D and NA-3 grown on medium with NAA and adenine sulfate showed about a 20 times higher enzyme activity than the habituated non-embryogenic line Z5b/T grown on medium without hormones. A rise in peroxidase activity indicated that somatic embryogenesis was triggered in a few habituated tissue cultures. Separated globular embryoids had a manifold lower enzyme activity than the callus from which they originated. SDS-electrophoresis showed distinct polypeptide patterns between the horse-radish leaves and crown galls, but the tumor characteristic protein bands failed to be identified. In horse-radish crown galls and short bushy plants regenerated from hairy roots an enhanced peroxidase activity was registered. Due to its high peroxidase level and abundant biomass production horse-radish transformants should facilitate enzyme production.
Laser power requirement for cutting thick-section steel and effects of processing parameters on mild steel cut quality (2011)

The high-power fibre laser presents a possibility for the application of solid-state lasers in thick-section metal cutting, a field which has been dominated by high-power CO 2 lasers. The current paper presents the lumped-parameter formulation of the laser power requirement as a function of cutting speed for oxygen-assisted laser cutting of mild steel and nitrogen-assisted laser cutting of stainless steel. The calculated laser power requirement is compared with the incident laser power used in the cutting of 15 mm mild steel with oxygen assist gas and 10 mm stainless steel with nitrogen assist gas using a multi-mode 5 kW fibre laser and a 4 kW CO 2 laser. The incident laser power required for cutting at a given cutting speed is found to be lower for fibre laser cutting than for the CO 2 laser cutting, indicating a higher absorption of the fibre laser beam. The effects of process parameters on the cut kerf quality in mild steel laser cutting with oxygen assist gas using the high-power fibre laser are presented. The critical process parameters affecting the quality of the cutting process and the resulting cut kerf are the cutting speed, oxygen pressure, and nozzle diameter.
Regulatory effects of Spirulina complex polysaccharides on growth of murine RSV‐M glioma cells through Toll‐like receptor 4 (2012)

This study is the first to report that Spirulina complex polysaccharides (CPS) suppress glioma growth by down-regulating angiogenesis via a Toll-like receptor 4 signal. Murine RSV-M glioma cells were implanted s.c. into C3H/HeN mice and TLR4 mutant C3H/HeJ mice. Treatment with either Spirulina CPS or Escherichia coli (E. coli) lipopolysaccharides (LPS) strongly suppressed RSV-M glioma cell growth in C3H/HeN, but not C3H/HeJ, mice. Glioma cells stimulated production of interleukin (IL)-17 in both C3H/HeN and C3H/HeJ tumor-bearing mice. Treatment with E. coli LPS induced much greater IL-17 production in tumor-bearing C3H/HeN mice than in tumor-bearing C3H/HeJ mice. In C3H/HeN mice, treatment with Spirulina CPS suppressed growth of re-transplanted glioma; however, treatment with E. coli LPS did not, suggesting that Spirulina CPS enhance the immune response. Administration of anti-cluster of differentiation (CD)8, anti-CD4, anti-CD8 antibodies, and anti-asialo GM1 antibodies enhanced tumor growth, suggesting that T cells and natural killer cells or macrophages are involved in suppression of tumor growth by Spirulina CPS. Although anti-interferon-γ antibodies had no effect on glioma cell growth, anti-IL-17 antibodies administered four days after tumor transplantation suppressed growth similarly to treatment with Spirulina CPS. Less angiogenesis was observed in gliomas from Spirulina CPS-treated mice than in those from saline- or E. coli LPS-treated mice. These findings suggest that, in C3H/HeN mice, Spirulina CPS antagonize glioma cell growth by down-regulating angiogenesis, and that this down-regulation is mediated in part by regulating IL-17 production.
Genetic regulation of the glyoxylate shunt in Escherichia coli K-12 (1982)

The expression of the glyoxylate shunt enzymes is required for growth of Escherichia coli on acetate or fatty acids as a sole carbon source. The genes for the two unique enzymes of the glyoxylate shunt, aceA and aceB, are located at 90 min on the E. coli K-12 genetic map. Polar mutations in the aceB gene eliminate aceA gene function, suggesting that these genes constitute an operon and the direction of transcription is from aceB to aceA. Mu d (Ap lac) fusions with the aceA gene have been constructed to study the regulation of the ace operon. Expression of the ace operon is under the transcriptional control of two genes: the iclR gene, which maps near the ace operon, and the fadR gene, which maps at 25 min, and is also involved in the regulation of the fatty acid degradation (fad) regulon. Merodiploid studies demonstrated that both the iclR and fadR genes regulate the glyoxylate shunt in a trans-dominant manner.
Mechanism of Action of Thalassospiramides, A New Class of Calpain Inhibitors (2015)

Thalassospiramides comprise a large family of lipopeptide natural products produced by Thalassospira and Tistrella marine bacteria. Here we provide further evidence of their nanomolar inhibitory activity against the human calpain 1 protease. Analysis of structure-activity relationship data supported our hypothesis that the rigid 12-membered ring containing an α,β-unsaturated carbonyl moiety is the pharmacologically active functional group, in contrast to classic electrophilic "warheads" in known calpain inhibitors. Using a combination of chemical modifications, mass spectrometric techniques, site-directed mutagenesis, and molecular modeling, we show the covalent binding of thalassospiramide's α,β-unsaturated carbonyl moiety to the thiol group of calpain's catalytic Cys115 residue by a Michael 1,4-addition reaction. As nanomolar calpain inhibitors with promising selectivity and low toxicity from natural sources are rare, we consider thalassospiramides as promising drug leads.
Antinociceptive activity of the bradykinin B1 and B2 receptor antagonists, des-Arg9, [Leu8]-BK and HOE 140, in two models of persistent hyperalgesia in the rat (1993)

There has been recent evidence linking bradykinin (BK) receptors with inflammation. This study has investigated the involvement of BK receptors in two models of persistent inflammatory hyperalgesia in rats. In a Freund's adjuvant-induced hyperalgesia model and an ultraviolet (UV)-induced hyperalgesia model in rats the specific B2 antagonist, D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-BK (HOE 140), was either ineffective or weakly active in reversing hyperalgesia. The specific B1 antagonist, des-Arg9, [Leu8]-BK, was effective in reversing or preventing the development of hyperalgesia in both Freund's adjuvant-induced hyperalgesia and UV-induced hyperalgesia. The B1 agonist, des-Arg9-BK, produced a small exacerbation of hyperalgesia in both models. Data suggest that in persistent inflammatory conditions in the rat bradykinin B1 receptors are involved in the accompanying hyperalgesia.