gebhart/patrepeval huggingface dataset:
Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis (2015)

The prognostic value of FoxP3(+) regulatory T cells (Tregs) in cancer remains controversial. We did a meta-analysis to assess the prognostic effect of FoxP3(+) Treg across different types of cancer and to investigate factors associated with variations in this effect. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched to identify eligible studies. In total, we analyzed 76 articles encompassing 17 types of cancer, and including 15,512 cancer cases. The overall pooled analysis including all types of cancer suggested FoxP3(+)Tregs had a significant negative effect on overall survival (OS) (OR 1.46, P < 0.001), but the prognostic effect varied greatly according to tumor site. High FoxP3(+) Tregs infiltration was significantly associated with shorter OS in the majority of solid tumors studied, including cervical, renal, melanomas, and breast cancers, et al; whereas, FoxP3(+) Tregs were associated with improved survival in colorectal, head and neck, and oesophageal cancers. The stratified analysis suggested the molecular subtype and tumor stage significantly influenced the prognostic value of FoxP3(+) Tregs in certain types of cancer. In conclusion, our meta-analysis suggests that the prognostic role of FoxP3(+) Tregs was highly influenced by tumor site, and was also correlated with the molecular subtype and tumor stage.
Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats. (1988)

Parathyroid hormone-like adenylate cyclase-stimulating proteins (hACSPs) have been implicated as one of the calcemic, bone-resorbing agents in patients with humoral hypercalcemia of malignancy. We report the synthesis of an amino-terminal hACSP fragment, Tyr36 hACSP (1-36) amide. The synthetic hACSP is a potent agonist of renal membrane adenylate cyclase (Km, 1.7 X 10(-10)) and of bone cell adenylate cyclase (Km 1 X 10(-9)M). It is a potent bone-resorbing agent in vitro, stimulating 45Ca release from fetal rat long bones at a concentration of 10(-9) M. When infused via osmotic minipumps into rats, it is also a potent calcemic factor in vivo, inducing a rise in serum calcium from (mean +/- SD) 10.6 +/- 0.6 to 19.7 +/- 3.2 mg/dl when infused at 1.4 micrograms/h and from 9.9 +/- 0.7 to 11.4 +/- 1.2 mg/dl when infused at 0.14 micrograms/h. These findings indicate that biologically active hACSP fragments can be synthesized. One such synthetic peptide possesses the in vitro and in vivo bioactivities demonstrated in native, tumor-derived hACSPs. It is also a potent calcemic, bone-resorbing agent.
Image/video deblurring using a hybrid camera (2008)

We propose a novel approach to reduce spatially varying motion blur using a hybrid camera system that simultaneously captures high-resolution video at a low-frame rate together with low-resolution video at a high-frame rate. Our work is inspired by Ben-Ezra and Nayar who introduced the hybrid camera idea for correcting global motion blur for a single still image. We broaden the scope of the problem to address spatially varying blur as well as video imagery. We also reformulate the correction process to use more information available in the hybrid camera system, as well as iteratively refine spatially varying motion extracted from the low-resolution high-speed camera. We demonstrate that our approach achieves superior results over existing work and can be extended to deblurring of moving objects.
Superconducting phase sequence inRxC60fullerides (R=Smand Yb) (2006)

The true superconducting phase in rare-earth ${\mathrm{C}}_{60}$ fullerides ${R}_{x}{\mathrm{C}}_{60}$ ($R=\mathrm{Yb}$ and Sm) is not ${R}_{2.75}{\mathrm{C}}_{60}$ previously reported. Moreover, no superconductivity is observed in $\mathrm{Sm}\text{\ensuremath{-}}{\mathrm{C}}_{60}$ fullerides. The phase sequence between $\mathrm{Yb}\text{\ensuremath{-}}{\mathrm{C}}_{60}$ fullerides and $\mathrm{Sm}\text{\ensuremath{-}}{\mathrm{C}}_{60}$ ones as a function of the intercalant concentration of $x$ is shown to be greatly different, although Yb and Sm are the same family of rare-earth elements with the divalent valence state. This can explain the loss of superconductivity in ${\mathrm{Sm}}_{x}{\mathrm{C}}_{60}$ and suggests the true superconducting phase. The whole picture of rare-earth ${\mathrm{C}}_{60}$ fullerides is described.
Comparison and evolution of human immunoglobulin VH segments located in the 3' 0.8-megabase region. Evidence for unidirectional transfer of segmental gene sequences. (1994)

Nucleotide sequences of 64 VH segments within the 3' 0.8-megabase region of the human immunoglobulin germ line VH locus were compared with trace evolution of human VH segments. Based on alignment of the deduced amino acid sequences of 37 functional germ line VH segments, a phylogenetic tree was generated using the neighbor-joining method. The phylogenetic tree clearly supports the previous classification of human VH segments into six families, which correlate roughly with mouse VH families with varying conservation. The human VH-III family is most homologous to mouse VH segments, suggesting that members of the VH-III family may be conserved by some functional constraint. The 5'-flanking region of each family has a family-specific structure. The sequenced 64 VH segments include 31 pseudogenes, of which 24 were highly conserved. Unidirectional transfer of segmental sequences was identified within the VH-III and VH-IV families, providing clear examples of germ line gene conversion. Such gene conversion may contribute to conserve structures of pseudo-VH segments. Comparison of the VH-IV family members indicates that recent repeated duplications and frequent gene conversions are responsible for strong conservation of this family, although functional selection is not completely excluded.
Protein grafting of an HIV-1-inhibiting epitope (2003)

Protein grafting, the transfer of a binding epitope of one ligand onto the surface of another protein, is a potentially powerful technique for presenting peptides in preformed and active three-dimensional conformations. Its utility, however, has been limited by low biological activity of the designed ligands and low tolerance of the protein scaffolds to surface substitutions. Here, we graft the complete binding epitope (19 nonconsecutive amino acids with a solvent-accessible surface area of >2,000 A2) of an HIV-1 C-peptide, which is derived from the C-terminal region of HIV-1 gp41 and potently inhibits HIV-1 entry into cells, onto the surface of a GCN4 leucine zipper. The designed peptide, named C34coil, displays a potent antiviral activity approaching that of the native ligand. Moreover, whereas the linear C-peptide is unstructured and sensitive to degradation by proteases, C34coil is well structured, conformationally stable, and exhibits increased resistance to proteolytic degradation compared with the linear peptide. In addition to being a structured antiviral inhibitor, C34coil may also serve as the basis for the development of an alternative class of immunogens. This study demonstrates that "one-shot" protein grafting, without subsequent rounds of optimization, can be used to create ligands with structural conformations and improved biomedical properties.
Effective information retrieval using genetic algorithms based matching functions adaptation (2005)

Knowledge intensive organizations have vast array of information contained in large document repositories. With the advent of E-commerce and corporate intranets/extranets, these repositories are expected to grow at a fast pace. This explosive growth has led to huge, fragmented, and unstructured document collections. Although it has become easier to collect and store information in document collections, it has become increasingly difficult to retrieve relevant information from these large document collections. This paper addresses the issue of improving retrieval performance (in terms of precision and recall) for retrieval from document collections. There are three important paradigms of research in the area of information retrieval (1R): Probabilistic IR, Knowledge-based IR, and, Artificial Intelligence based techniques like neural networks and symbolic learning. Very few researcher have tried to use evolutionary algorithms like genetic algorithms (GAs). Previous attempts at using GAs have concentrated on modifying document representations or modifying query representations. This work looks at the possibility of applying GAs to adapt various matching functions. It is hoped that such an adaptation of the matching functions in lead to a better retrieval performance than that obtained by using a single matching function. An overall matching function is treated as an weighted combination of scores produced by individual matching functions. This overall score is asked to rank and retrieve documents. Weights associated with individual functions are searched using Genetic Algorithms. The idea is tested on a real document collection called the Cranfield collection. The results look very encouraging.
ChemInform Abstract: Preparation of the Trianions of Acetylacetone and Acetoacetanilide and Their Reactions with Selected Electrophilic Reagents for the Synthesis of New Heterocyclic Compounds and Related Materials. (1990)

Abstract The trianion salt (IV), prepared by reaction of acetylacetone (I) with NaH (II) and excess LDA (III), reacts with benzophenone (V) to give the dihydroxy diketone (VI).
The Role of Type Specific and Cross Reacting Structural Antigens in the Neutralization of Herpes Simplex Virus Types 1 and 2 (1973)

SUMMARY The structural antigen Band II was present in cells infected with either type 1 or type 2 herpes simplex virus. Antiserum to Band II neutralized the infectivity of both virus types. General antisera to either type exhibited type specific neutralizing activity after absorption with heterologous antigen. Absorption of the antisera with Band II antigen from cells infected with either type 1 or type 2 virus also abolished the type common but not the type specific neutralizing activity. Fractions obtained by preparative polyacrylamide gel electrophoresis have been examined in serum blocking tests. The results suggest that particles of herpes simplex virus possess at least two type specific antigens and one type common antigen (Band II); interaction of any of these with the corresponding antibody causes loss of virus infectivity.
Liver as a target for oligonucleotide therapeutics (2013)

Oligonucleotide-based therapeutics are an emerging class of drugs that hold the promise for silencing "un-druggable" targets,thus creating unique opportunities for innovative medicines. As opposed to gene therapy, oligonucleotides are considered to be more akin to small molecule therapeutics because they are small,completely synthetic in origin, do not integrate into the host genome,and have a defined duration of therapeutic activity after which effects recover to baseline. They offer a high degree of specificity at the genetic level, thereby reducing off-target effects.At the same time, they provide a strategy for targeting any gene in the genome, including transcripts that produce mutated proteins.Oligonucleotide-based therapeutics include short interfering RNA (siRNA), that degrade target mRNA through RISC mediated RNAi; anti-miRs, that target miRNAs; miRNA mimics, that regulate target mRNA; antisense oligonucleotides, that may be working through RNAseH mediated mRNA decay; mRNA upregulation,by targeting long non-coding RNAs; and oligonucleotides induced alternative splicing [1]. All these approaches require some minimal degree of homology at the nucleic acid sequence level for them to be functional. The different mechanisms of action and their relevant activity are outlined in Fig. 1. Besides homology,RNA secondary structure has also been exploited in the case of ribozymes and aptamers, which act by binding to nucleic acids or proteins, respectively. While there have been many reports of gene knockdown and gene modulation in cell lines and mice with all these methods, very few have advanced to clinical stages.The main obstacle to date has been the safe and effective intracellular delivery of these compounds in higher species, including humans. Indeed, their action requires direct interaction with DNA/RNA within the target cell so even when one solves the issues of tissue and cellular access, intracellular/intranuclear location represents yet another barrier to overcome. To date,hepatic delivery of oligonucleotides has been the area with greatest progress, and thus we have focused on liver-targeted therapeutics that have shown promise at the preclinical and/or clinical level.The liver is the largest internal organ in the body, playing a central role in metabolism, detoxification, synthesis, and secretion of major plasma proteins (carrier proteins, coagulation factors,complement components, hormones, and apolipoproteins),and iron homeostasis. It is therefore not surprising that a large number of disease targets reside in the liver where they are susceptible to modulation by oligonucleotide therapies.
Bhc-diol as a Photolabile Protecting Group for Aldehydes and Ketones (2003)

[reaction: see text] 6-Bromo-4-(1,2-dihydroxyethyl)-7-hydroxycoumarin (Bhc-diol) can be used under simulated physiological conditions as a photoremovable protecting group for aldehydes and ketones. The single- and two-photon-induced release of benzaldehyde, piperonal, acetophenone, and cyclohexanone is demonstrated.
Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia (2016)

Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.
Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1–dependent mechanism that is up-regulated by interleukin-13 (2010)

Myeloid-derived suppressor cells (MDSCs) are a well-defined population of cells that accumulate in the tissue of tumor-bearing animals and are known to inhibit immune responses. Within 4 days, bone marrow cells cultured in granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor resulted in the generation of CD11b(+)Ly6G(lo)Ly6C(+) MDSCs, the majority of which are interleukin-4Rα (IL-4Rα(+)) and F4/80(+). Such MDSCs potently inhibited in vitro allogeneic T-cell responses. Suppression was dependent on L-arginine depletion by arginase-1 activity. Exogenous IL-13 produced an MDSC subset (MDSC-IL-13) that was more potently suppressive and resulted in arginase-1 up-regulation. Suppression was reversed with an arginase inhibitor or on the addition of excess L-arginine to the culture. Although both MDSCs and MDSC-IL-13 inhibited graft-versus-host disease (GVHD) lethality, MDSC-IL-13 were more effective. MDSC-IL-13 migrated to sites of allopriming. GVHD inhibition was associated with limited donor T-cell proliferation, activation, and proinflammatory cytokine production. GVHD inhibition was reduced when arginase-1-deficient MDSC-IL-13 were used. MDSC-IL-13 did not reduce the graft-versus-leukemia effect of donor T cells. In vivo administration of a pegylated form of human arginase-1 (PEG-arg1) resulted in L-arginine depletion and significant GVHD reduction. MDSC-IL-13 and pegylated form of human arginase-1 represent novel strategies to prevent GVHD that can be clinically translated.
High-speed two-dimensional laser scanner based on Bragg gratings stored in photothermorefractive glass (2003)

A high-speed free-space wavelength-multiplexed optical scanner with high-speed wavelength selection coupled with narrowband volume Bragg gratings stored in photothermorefractive (PTR) glass is reported. The proposed scanner with no moving parts has a modular design with a wide angular scan range, accurate beam pointing, low scanner insertion loss, and two-dimensional beam scan capabilities. We present a complete analysis and design procedure for storing multiple tilted Bragg-grating structures in a single PTR glass volume (for normal incidence) in an optimal fashion. Because the scanner design is modular, many PTR glass volumes (each having multiple tilted Bragg-grating structures) can be stacked together, providing an efficient throughput with operations in both the visible and the infrared (IR) regions. A proof-of-concept experimental study is conducted with four Bragg gratings in independent PTR glass plates, and both visible and IR region scanner operations are demonstrated.
Construction and Preclinical Evaluation of an Anti-CD19 Chimeric Antigen Receptor (2009)

T cells can be engineered to express the genes of chimeric antigen receptors (CARs) that recognize tumor-associated antigens. We constructed and compared 2 CARs that contained a single chain variable region moiety that recognized CD19. One CAR contained the signaling moiety of the 4-1BB molecule and the other did not. We selected the CAR that did not contain the 4-1BB moiety for further preclinical development. We demonstrated that gammaretroviruses encoding this receptor could transduce human T cells. Anti-CD19-CAR-transduced CD8+ and CD4+ T cells produced interferon-gamma and interleukin-2 specifically in response to CD19+ target cells. The transduced T cells specifically killed primary chronic lymphocytic leukemia (CLL) cells. We transduced T cells from CLL patients that had been previously treated with chemotherapy. We induced these T cells to proliferate sufficiently to provide enough cells for clinical adoptive T cell transfer with a protocol consisting of an initial stimulation with an anti-CD3 monoclonal antibody (OKT3) before transduction followed by a second OKT3 stimulation 7 days after transduction. This protocol was successfully adapted for use in CLL patients with high peripheral blood leukemia cell counts by depleting CD19+ cells before the initial OKT3 stimulation. In preparation for a clinical trial that will enroll patients with advanced B cell malignancies, we generated a producer cell clone that produces retroviruses encoding the anti-CD19 CAR, and we produced sufficient retroviral supernatant for the proposed clinical trial under good manufacturing practice conditions.
The recognition of a viral antigenic moiety by class I MHC-restricted cytolytic T lymphocytes is limited by the availability of the endogenously processed antigen. (1990)

The transmembrane hydrophobic domain of the type A influenza A/JAPAN/305/57 (H2N2) hemagglutinin (HA) contains an immunodominant site encompassing amino acids 523-545 (J523-545) recognized by class I MHC-restricted cytolytic T lymphocytes (CTL). Class I CTL of two fine specificity subsets map to this transmembrane (TM) site. One of these CTL subpopulations is subtype specific. These T lymphocytes recognize the site generated during infection of target cells with A/JAPAN/305/57 virus (H2N2) but not target cells expressing the comparable TM site of the influenza A/PR/8/34 virus (H1N1) hemagglutinin (P527-549) after infection with this virus. The other CTL subpopulation is cross-reactive and recognizes the TM site of the A/JAPAN/305/57 HA and the A/PR/8/34 HA with similar efficiency. Analyses of the critical amino acids in the TM site necessary for CTL recognition with the use of synthetic peptides unexpectedly revealed reactivity for the A/PR/8 HA TM site by subtype-specific CTL. This reactivity was only observed with truncated peptides corresponding to a limited portion of the A/PR/8 HA TM site but also required peptide concentrations greater than 10(-7) M. These results suggested either that the endogenously processed A/PR/8 HA TM site generated during infection was larger than the site defined by the truncated cross-reactive peptides or that the concentration of endogenously processed TM site produced during infection was limiting. To distinguish between these possibilities, we expressed in target cells synthetic minigenes encoding only the portion of the A/PR/8 HA transmembrane sites defined by the synthetic peptides. Unlike the peptides, the "preprocessed" endogenous minigene products were not recognized by subtype-specific CTL. These data suggest that the level of available endogenously processed Ag rather than selectivity in the site of fragmentation of newly synthesized Ag may play a critical role in determining whether the complex of the antigenic moiety and class I MHC is efficiently presented to and recognized by class I CTL.
Effects of a Neutrophil Elastase Inhibitor (ONO-5046) on Acute Pulmonary Injury Induced by Tumor Necrosis Factor Alpha (TNF α ) and Activated Neutrophils in Isolated Perfused Rabbit Lungs (1998)

The aim of this study was to examine the effect of ONO-5046, a neutrophil elastase (NE) inhibitor, on a model of acute lung injury induced by tumor necrosis factor alpha (TNFalpha) and phorbol myristate acetate (PMA)-activated neutrophils in isolated perfused rabbit lungs. 120 min after TNFalpha (4,000 JRU/ml) was injected into the pulmonary artery (PA), 5 x 10(7) PMA-stimulated neutrophils were infused into the PA together with 1251-rabbit serum albumin (RSA). In the ONO-5046-treated group (ONO), ONO-5046 (20 mg/kg/h) was continuously infused during the experimental period from 30 min prior to neutrophil administration. Saline, the ONO-5046 vehicle, was infused instead of ONO-5046 in the positive control group (ALD) and nonactivated neutrophils were infused without TNFalpha in the negative control group (Cont). PA pressure was monitored over a 240 min period, and bronchoalveolar lavage (BAL) was performed at the end of the experiment. Lung tissues were examined immunohistochemically for the expression of thrombomodulin (TM). The levels of TM in the perfusate were also measured by ELISA and the radioactivities in the BAL fluid, lung tissue and perfusate were determined to calculate the permeability index (PI) as an indicator of alveolar septal or vascular endothelial damage. The rabbit lungs infused with ONO-5046 showed slower and less increases in PA pressure compared with ALD group. The PI was significantly higher in ALD group (PI[BAL] = 0.028 +/- 0.014, PI[LUNG] = 0.04 +/- 0.003) than Cont (PI[BAL] = 0.002 +/- 0.001, PI[LUNG] = 0.015 +/- 0.003) and ONO group (PI[BAL] = 0.004 +/- 0.003, PI[LUNG] = 0.028 +/- 0.003 (p < 0.05). ALD group had higher TM levels in the perfusate and showed decreased expression of TM on the vascular endothelium compared to Cont and ONO group, suggesting that there was shedding of TM on endothelium and ONO-5046 attenuated a shedding of TM. In conclusion, ONO-5046 attenuated acute lung injury by inhibiting the alveolar epithelial and vascular endothelial injury triggered by activated neutrophils. NE appears to play an important role in the neutrophil-induced increase of pulmonary epithelial and microvascular permeability observed in acute lung injury.
Attachment of reporter groups to specific, selected cytidine residues in RNA using a bisulfitecatalyzed transamination reaction (1984)

Bisulfite catalyzes transamination of cytidine at the N4 position; the suitability of this reaction for attaching reporter groups to selected cytidine residues in RNA molecules has been investigated. Poly(C) is nearly quantitatively converted to the poly (N4 aminoethyl-C) derivative after 3 hrs at 42 degrees C with ethylene diamine (pK1 = 7.6) and bisulfite. This derivative reacts quantitatively with N-hydroxysuccinimide esters; the linkage of a fluorescent dye, nitrobenzofurazan, to cytidine by this reaction is demonstrated. To direct the bisulfite reaction to selected cytidines within a large RNA molecule, the RNA is hybridized to complementary DNA containing a deletion. Only the cytidines in the single strand RNA loop (corresponding to the DNA deletion) are reactive. Two cytidines in the middle of a 340 base RNA fragment from 16S ribosomal RNA have been modified by this technique.