gebhart/patrepeval huggingface dataset:
Molecular Determinants of Oligomer Formation and Complement Fixation in Mannose-binding Proteins (1999)

Rat serum mannose-binding protein (MBP-A) functions as part of the innate immune system by targetting complement toward potentially pathogenic microorganisms. In order to examine the molecular basis for complement activation, rat MBP-A has been overproduced in Chinese hamster ovary cells. Recombinant protein is post-translationally modified in the same way as the native lectin. Hydrodynamic studies indicate that MBP-A consists predominantly of covalent oligomers containing one to four copies of a subunit that comprises a trimer of polypeptides. These oligomers are non-interconverting and do not assemble into higher order structures at concentrations in excess of those normally found in serum. Disulfide bonds formed between cysteine residues at the N-terminal end of the collagen-like domain link polypeptides to form covalent oligomers. Analysis of wild-type MBP-A and MBP-A containing the substitution Cys6 --> Ser suggests that polypeptides within each trimeric structural unit are mostly linked by disulfide bonds between cysteine residues at positions 13 and 18 arranged in an asymmetrical configuration. Disulfide bonds involving Cys6 connect polypeptides within separate trimers. Analysis of chimeras between MBP-A and rat liver MBP (MBP-C) indicates that residues within the N-terminal region of the collagenous domain and the cysteine-rich domain of MBP-A enable assembly of trimers into higher order oligomers. The activity of MBP-A in a hemolytic complement fixation assay using mannan-coated sheep erythrocytes was approximately 20-fold greater than the activity of MBP-C. Analysis of the MBP chimeras and isolated oligomers of MBP-A reveals that the larger oligomers are more efficient at complement activation. These data indicate that the overall complement fixing activity of MBP-A is a function of the individual molecular activities of oligomers and their relative abundance within the serum.
Accelerator-control-system interface for intelligent power supplies (2003)

A number of high-current high-precision magnet power supplies have been installed at the proton storage ring at the Los Alamos National Laboratory Accelerator Complex. The units power large dipole magnets in the ring. These bending magnets require a high-current supply that is precise and stable. The control and interface design for these power supplies represents a departure from all others on-site. The supplies have sophisticated microprocessor control on-board and communicate with the accelerator control system via RS-422 (serial communications). The units, built by Alpha Scientific Electronics, Hayward, CA use a high-level ASCII control protocol. The low-level front-end software used by the accelerator control system has been written to accommodate these new devices. They communicate with the control system through a terminal server port connected to the site-wide ethernet backbone. Details of the software implementation for the analog and digital control of the supplies through the accelerator control system are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Kinase Inhibitors Sunitinib (Sutent®) and Sorafenib (Nexavar®) Differentially Affect Reactivity of NK Cells Against Renal Cell Cancer. (2007)

Abstract Sunitinib (Sutent®) and Sorafenib (Nexavar®) are multikinase inhibitors licensed for the treatment of patients with advanced renal cell cancer (RCC) because of their direct and indirect anti-tumor and anti-angiogenic effects. Sunitinib and Sorafenib target, among others, vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR), the stem cell factor receptor (cKIT) and Fms-like tyrosine kinase-3 (Flt3). Beyond that, Sorafenib additionally inhibits c-RAF and B-RAF. NK cells play an important role in the immune surveillance of tumors. Their reactivity is governed by different surface receptors leading to activation of various kinases, phosphatases and transcription factors. Up to now, nothing is known regarding the influence of Sunitinib and Sorafenib on NK cells. Here we report that Sunitinib and Sorafenib differentially affect NK cell cytotoxicity. Analysis of peripheral blood mononuclear cells from 10 independent donors revealed that Sorafenib but not Sunitinib significantly (p&lt;0.05, Mann-Whitney U-test) reduced cell surface CD107a expression (about 50%) on NK cells as a surrogate marker for degranulation in response to tumor targets. In line, pharmacological levels of Sorafenib significantly (p&lt;0.05, Mann-Whitney U-test) diminished cytotoxicity of primary NK cells against the RCC cell lines A498, ACHN and CAKI-2 (from 46% to 14%, from 52% to 22% and from 63% to 42%, respectively) in chromium release assays. Again, no inhibition of cytotoxicity was observed in the presence of pharmacological concentrations of Sunitinib. Since activation of MAP kinases leading to ERK phosphorylation regulates the movement of lytic granula towards target cells, which is responsible for NK cell cytotoxicity we investigated the influence of Sunitinib and Sorafenib on ERK phosphorylation. While Sunitinib had no effect, Sorafenib, alike the specific c-RAF inhibitor ZM336372 or the specific MEK inhibitor PD98059, markedly reduced ERK phosphorylation as determined by Western Blot. Our results indicate that NK cell anti-tumor reactivity is impaired by Sorafenib but not by Sunitinib due to the additional inhibitory effect of Sorafenib on the ERK pathway, which has been demonstrated to dictate NK cell cytotoxicity. We therefore conclude that Sunitinib is exquisitely suitable for combination with immunotherapeutic approaches in RCC patients.
First-class runtime generation of high-performance types using exotypes (2014)

We introduce exotypes, user-defined types that combine the flexibility of meta-object protocols in dynamically-typed languages with the performance control of low-level languages. Like objects in dynamic languages, exotypes are defined programmatically at run-time, allowing behavior based on external data such as a database schema. To achieve high performance, we use staged programming to define the behavior of an exotype during a runtime compilation step and implement exotypes in Terra, a low-level staged programming language.
Immune-Based Therapy for Spinal Cord Repair: Autologous Macrophages and Beyond (2006)

Spinal cord injury is a devastating condition of the central nervous system (CNS), often resulting in severe loss of tissue, functional impairment, and only limited repair. Studies over the last few years have shown that response to the insult and spontaneous attempts at repair are multiphasic processes, with varying and sometimes conflicting requirements. This knowledge has led to novel strategies of therapeutic intervention. Our view is that a pivotal role in repair, maintenance, healing, and cell renewal in the CNS, as in other tissues, is played by the immune system. The mode and timing of intervention must be carefully selected, however, as the capacity of the CNS to tolerate local repair mechanisms is limited. Studies have shown that the spontaneously evoked early innate response to CNS injury is characterized by invasion of neutrophils and is unfavorable for cell survival. This is followed by a response of the resident innate immune cells (microglia), which however cannot supply all the needs of the damaged tissue; moreover, once evoked, and for as long as the damage persists, the microglial response remains beyond the capacity of the CNS to tolerate it. Immune-based clinical intervention is most effective in improving functional and morphological recovery when delayed for a certain period. Effective intervention might be in the form of (1) local injection of "alternatively activated" macrophages, (2) systemic injection of dendritic cells specific to CNS antigens, or (3) T-cell-based vaccination. The treatment of choice depends on the severity of the insult, the site of injury, the therapeutic window, and safety considerations.
Adult Schistosoma mansoni worms positively modulate soluble egg antigen-induced inflammatory hepatic granuloma formation in vivo. Stereological analysis and immunophenotyping of extracellular matrix proteins, adhesion molecules, and chemokines. (1997)

Synchronized liver granulomas were induced by injecting Sepharose beads to which SEA soluble egg antigen (SEA) or the concanavalin A binding fraction of SEA had been coupled into a mesenteric vein in naive, single-sex (35 days) and bisexually (28 days) Schistosoma mansoni-infected and Plasmodium berghei-immunized mice. Stereological analysis revealed that peak granuloma formation was already reached 8 days after injection in single-sex infected mice compared with 16 days in naive animals. No difference in granuloma formation between naive and P. berghei-immunized animals and between unisexually and bisexually S. mansoni-infected mice was observed. This suggests that the positive immunomodulatory effect on the granulomogenesis is worm specific and not likely to be due to arousal of the immune system by unrelated factors, nor is it influenced by the gender or degree of maturation of female worms. At all stages in time, the concanavalin A binding-fraction-induced granulomas reached only 65 to 70% of the volume of SEA-induced granulomas. Immunophenotyping of extracellular matrix proteins around deposited heads revealed that fibronectin was the dominant extracellular matrix protein and that also type I and IV collagen and laminin were deposited. Temporal analysis of the expression of the adhesion molecules ICAM-1, LFA-1, VLA-4, and VLA-6 was performed. Morphological evidence is presented for the role of adhesion molecules in the initiation and maintenance of hepatic granuloma formation. The chemokine monocyte chemoattractant protein-1 was expressed in the granuloma and in hepatic artery branches. From these data, it is concluded that adult S. mansoni worms positively modulate schistosomal hepatic granuloma formation in vivo. Adhesion molecules and chemokines play important roles in schistosomal granuloma formation.
New trends in capillary isotachophoresis (1993)

Modern ideas concerning electrical transport in electrolyte solutions and capillary isotachophoresis — one of the microanalytical methods based on the different mobilities of ions in electrolyte solutions — are briefly considered. The isotachophoretic methods are classified in terms of the positions of the solutions and the directions of motion of the boundaries. The application of the coulophoretic method to the analysis of solutions, the measurement of the amount of electricity passed through the system, and the measurement of the internal cross-section of the capillaries are described. A description is also given of the electromigration method for crystallisation in capillaries and the isitachophoretic method for the determination of the electrical transport of the solvent in electrolyte solutions. The bibliography includes 96 references.
Formation of Water-in-CO2 Microemulsions with Non-fluorous Surfactant Ls-54 and Solubilization of Biomacromolecules (2002)

A non-fluorous and non-siloxane nonionic surfactant Ls-54 can form water-in-CO2 microemulsions, which can solubilize lysozyme. The figure shows the UV absorption band of lysozyme (276 nm) solubilized in 0.02 M Ls-54 based water-in-CO2 microemulsions with W0=8.0 at 308.15 K and 22.00 MPa. The solubility of Ls-54 surfactant in supercritical CO2 was determined. It was found that the surfactant was highly soluble in SC CO2 and the water-in-CO2 microemulsions could be formed, despite it being a non-fluorous and non-siloxane nonionic surfactant. The main reasons for the high solubility and formation of the microemulsions may be that the surfactant has four CO2-philic groups (propylene oxide) and five hydrophilic groups (ethylene oxide) and its molecular weight are relatively low. The results of this work provide useful information for designing CO2-soluble non-fluorous and non-siloxane surfactants. The phase behavior of the CO2/Ls-54/H2O system, solvatochromic probe study, and the UV spectrum of lysozyme proved the existence of water domains in the SC CO2 microemulsions. The method of synchrotron radiation small-angle X-ray scattering was used to obtain the structural information on the Ls-54 based water-in-CO2 reverse micelles. By using the Guinier plot (ln I(q) versus q 2) on the data sets in a defined small q range (0.022–0.040 Å−1), the radii of the reverse micelles were obtained at different pressures and molar ratio of water to surfactant, W0, which were in the range of 20.4–25.2 Å.
Macular atrophy in patients with long‐term anti‐VEGF treatment for neovascular age‐related macular degeneration (2016)

A majority of patients show MA after long-term anti-VEGF treatment. Reticular pseudodrusen (RPD), IRC and PVD but not number of injections or treatment duration seem to be associated with the MA size.
RBP38, a Novel RNA-Binding Protein from Trypanosomatid Mitochondria, Modulates RNA Stability (2003)

We describe here the isolation and characterization of a novel RNA-binding protein, RBP38, from Leishmania tarentolae mitochondria. This protein does not contain any known RNA-binding motifs and is highly conserved among the trypanosomatids, but no homologues were found in other organisms. Recombinant LtRBP38 binds single and double-stranded (ds) RNA substrates with dissociation constants in the 100 nM range, as determined by fluorescence polarization analysis. Downregulation of expression of the homologous gene, TbRBP38, in procyclic Trypanosoma brucei by using conditional dsRNA interference resulted in 80% reduction of steady-state levels of RNAs transcribed from both maxicircle and minicircle DNA. In organello pulse-chase labeling experiments were used to determine the stability of RNAs in mitochondria that were depleted of TbRBP38. The half-life of metabolically labeled RNA decreased from approximately 160 to approximately 60 min after depletion. In contrast, there was no change in transcriptional activity. These observations suggest a role of RBP38 in stabilizing mitochondrial RNA.
Protein- and DNA-Based Active Immunotherapy Targeting Interleukin-13 Receptor Alpha2 (2008)

High-grade astrocytoma (HGA) is an invariably fatal malignancy with a mean survival of 14 months despite surgery, radiation, and chemotherapy. We have found that a restricted receptor for interleukin-13 (IL-13), IL-13 receptor alpha 2 (IL13Ralpha2), is abundantly overexpressed in the vast majority of HGAs but is not appreciably expressed in normal tissue, with the exception of the testes. Therefore, IL-13Ralpha2 is a very attractive target for anti-HGA immunotherapy. In order to test protein and genetic vaccines that target IL13Ralpha2, we developed a G26-IL13Ralpha2-expressing syngeneic immunocompetent murine glioma model. Using this glioma model, mice were immunized with recombinant extracellular IL13Ralpha2 protein (IL13Ralpha2ex) or a DNA expression vector containing the gene for IL13Ralpha2 and were subsequently challenged with IL13Ralpha2( + ) G26 tumors. Mice immunized with either recombinant or genetic IL13Ralpha2, but not mock-immunized controls, demonstrated complete protection against IL13Ralpha2( + ) glioma growth and mortality. Of interest, only the recombinant-protein-based vaccines generated detectable anti-IL13Ralpha2 antibodies. These studies demonstrate the in vivo efficiency of protein- and DNA-based immunotherapy strategies that target IL13Ralpha2 that may play a clinical role to eradicate the residual microscopic HGA cells that inevitably cause disease recurrence and mortality.
Polypeptides with nonsuppressible insulin-like and cell-growth promoting activities in human serum: isolation, chemical characterization, and some biological properties of forms I and II. (1976)

Serum contains a polypeptide with insulin-like activity not suppressible by insulin antibodies (NSILA). A large-scale isolation procedure for NSILA is described, starting from an acid ethanol extract of a Cohn fraction (precipitate B) obtained from human plasma. Two homogenous polypeptides with insulin-like and cell-growth promoting activities could be isolated by gel filtration, ion exchange chromatography, and preparative polyacrylamide gel electrophoresis. Both components are slightly basic polypeptides with a minimal molecular weight of 5800 +/- 400. Both are single-chain molecules with two intrachain disulfide bridges each and no free sulfhydryl groups. NSILA I and II differ, however, in their amino acid compositions. The N-terminal amino acid sequences are Gly-Pro-Glu- in NSILA I, and Ala-Tyr-Arg- and Tyr-Arg- in NSILA II. Both NSILA I and II enhance net gas exchange in adipose tissue with a specific activity 60 times lower than that of insulin. In the range of 1-50 ng/ml, both substances stimulate [3H]thymidine incorporation into DNA of chick embryo fibroblasts. The same effect can be obtained with insulin but only at concentrations 50-100 times higher than those of NSILA. These results suggest that NSILA I and II are two forms of an insulin-like hormone with predominating effects on cell and tissue growth parameters.
Asynchronous stochastic gradient descent for DNN training (2013)

It is well known that state-of-the-art speech recognition systems using deep neural network (DNN) can greatly improve the system performance compared with conventional GMM-HMM. However, what we have to pay correspondingly is the immense training cost due to the enormous parameters of DNN. Unfortunately, it is difficult to achieve parallelization of the minibatch-based back-propagation (BP) algorithm used in DNN training because of the frequent model updates. In this paper we describe an effective approach to achieve an approximation of BP - asynchronous stochastic gradient descent (ASGD), which is used to parallelize computing on multi-GPU. This approach manages multiple GPUs to work asynchronously to calculate gradients and update the global model parameters. Experimental results show that it achieves a 3.2 times speed-up on 4 GPUs than the single one, without any recognition performance loss.
Neuronal Signal Substances as Biomarkers of Migraine (2006)

Of the sensory nervous system associated signal substances it is only calcitonin generelated peptide (CGRP) that is reliably associated with the degree of pain in the acute attacks of primary headaches. The treatment with triptans alleviates both the pain and the associated CGRP release, putatively via a presynaptic effect on the sensory nerves. The studies of opoids and other sensory neuropeptides are inconsistent and require further analysis. Initial positive data on endothelin and its receptors have turned out negative. Nitric oxide mechanisms are still debated both in terms of initiation of attacks and for the treatment.
The Arabidopsis Abscisic Acid Response Locus ABI4 Encodes an APETALA2 Domain Protein (1998)

Arabidopsis abscisic acid (ABA)-insensitive abi4 mutants have pleiotropic defects in seed development, including decreased sensitivity to ABA inhibition of germination and altered seed-specific gene expression. This phenotype is consistent with a role for ABI4 in regulating seed responses to ABA and/or seed-specific signals. We isolated the ABI4 gene by positional cloning and confirmed its identity by complementation analysis. The predicted protein product shows homology to a plant-specific family of transcriptional regulators characterized by a conserved DNA binding domain, the APETALA 2 domain. The single mutant allele identified has a single base pair deletion, resulting in a frameshift that should disrupt the C-terminal half of the protein but leave the presumed DNA binding domain intact. Expression analyses showed that despite the seed-specific nature of the mutant phenotype, ABI4 expression is not seed specific.
Silencing Human NKG2D, DAP10, and DAP12 Reduces Cytotoxicity of Activated CD8+ T Cells and NK Cells (2005)

Human CD8+ T cells activated and expanded by TCR cross-linking and high-dose IL-2 acquire potent cytolytic ability against tumors and are a promising approach for immunotherapy of malignant diseases. We have recently reported that in vitro killing by these activated cells, which share phenotypic and functional characteristics with NK cells, is mediated principally by NKG2D. NKG2D is a surface receptor that is expressed by all NK cells and transmits an activating signal via the DAP10 adaptor molecule. Using stable RNA interference induced by lentiviral transduction, we show that NKG2D is required for cytolysis of tumor cells, including autologous tumor cells from patients with ovarian cancer. We also demonstrated that NKG2D is required for in vivo antitumor activity. Furthermore, both activated and expanded CD8+ T cells and NK cells use DAP10. In addition, direct killing was partially dependent on the DAP12 signaling pathway. This requirement by activated and expanded CD8+ T cells for DAP12, and hence stimulus from a putative DAP12-partnered activating surface receptor, persisted when assayed by anti-NKG2D Ab-mediated redirected cytolysis. These studies demonstrated the importance of NKG2D, DAP10, and DAP12 in human effector cell function.
Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantation. (1995)

Despite the use of conventional chemoprophylaxis regimens, patients receiving unrelated-donor BMT are at high risk of developing severe acute GVHD. We evaluated a prophylactic regimen combining CsA, MTX and anti-CD5-ricin A chain immunotoxin (H65-RTA) in 31 patients; pentoxifylline was also given to reduce the anticipated nephrotoxicity of CsA. In most cases, planned doses of CsA, MTX and H65-RTA were given (i.e. to 77%, 77% and 93% of patients, respectively). Although fluid retention requiring diuretic therapy was frequent, only 1 patient had a > 10% unexplained increase in body weight during the first 21 days post-BMT. Also, while significant increase of the baseline serum creatinine was noted in 7 patients, none required dialysis. One patient suffered a reversible allergic reaction to the immunotoxin; no other side effects attributable to this regimen were observed. All but 2 patients engrafted (1 died of fungemia on d + 19 and the other had persistent leukemia) and no late graft failures were observed. Seventeen patients developed acute GVHD grade > or = II (probability, 58% [95% CI 41-76%]); 7 had grade > or = III (probability, 24% [95% CI 12-43%]). In the 27 patients who achieved stable engraftment and have survived beyond d + 100, the 3-year probability of developing chronic GVHD was 66% (95% CI 48-84%). As of the last follow-up prior to 01 May 1994, 13 patients are alive in CR and one in relapse; 9 of these patients are off all immunosuppressives and well. Four other patients relapsed and died, and 13 died of other transplant-related causes.(ABSTRACT TRUNCATED AT 250 WORDS)