gebhart/patrepeval huggingface dataset:
Identification of the U‐937 membrane‐associated proteinase interacting with the V3 loop of HIV‐1 gp12O as cathepsin G (1994)

We have purified a serine proteinase from the membrane of U-937 cells that was inhibited in a tight-binding manner by recombinant gp120 and by peptides mimicking the V3 loop of gp120 [(1993) FEBS Lett. 317, 167-172]. This proteinase has now been characterized, both structurally and functionally. It has a dual trypsin- and chymotrypsin-like specificity, and N-terminal sequence analysis of the first 32 residues indicates complete identity with leukocyte cathepsin G. Cathepsin G-like material was located at the surface of U-937 cells using a monoclonal antibody directed against leukocyte cathepsin G, and polyclonal anti-cathepsin G antibodies precipitated the purified proteinase. However, the U-937 enzyme differs slightly from commercial leukocyte cathepsin G in its apparent M(r) because of different glycosylation. No other protein structurally related to cathepsin G was found upon screening a U-937 cDNA library using several oligonucleotide probes constructed from the membrane proteinase N-terminal amino acid sequence. The possible interaction of a cathepsin G-like proteinase at the surface of U-937 cells with the V3 loop of HIV-1 gp120 is discussed.
Radiation induced CNS toxicity – molecular and cellular mechanisms (2001)

Radiotherapy of tumours proximal to normal CNS structures is limited by the sensitivity of the normal tissue. Prior to the development of prophylactic strategies or treatment protocols a detailed understanding of the mechanisms of radiation induced CNS toxicity is mandatory. Histological analysis of irradiated CNS specimens defines possible target structures prior to a delineation of cellular and molecular mechanisms. Several lesions can be distinguished: Demyelination, proliferative and degenerative glial reactions, endothelial cell loss and capillary occlusion. All changes are likely to result from complex alterations within several functional CNS compartments. Thus, a single mechanism responsible cannot be separated. At least four factors contribute to the development of CNS toxicity: (1) damage to vessel structures; (2) deletion of oligodendrocyte-2 astrocyte progenitors (O-2A) and mature oligodendrocytes; (3) deletion of neural stem cell populations in the hippocampus, cerebellum and cortex; (4) generalized alterations of cytokine expression. Several underlying cellular and molecular mechanisms involved in radiation induced CNS toxicity have been identified. The article reviews the currently available data on the cellular and molecular basis of radiation induced CNS side effects.
Detective quantum efficiency of direct flat-panel x-ray imaging detectors for fluoroscopy (1998)

Our goal is to develop a large area, flat panel solid-state detector for fluoroscopy. The detector employs a layer of photoconductor to convert incident x-rays directly to a charge image, which is then read out in real-time using a two dimensional array of thin film transistors (TFTs), or 'active matrix.' In order to guide the design of an optimum fluoroscopic flat-panel detector, a cascaded linear systems model was developed, from which the spatial frequency dependent detective quantum efficiency [DQE(f)] can be obtained. Then DQE(f) was calculated as a function of different detector design parameters, e.g. pixel fill-factor, x-ray exposure, Swank factor, electronic noise, and the calculation was performed for three different x-ray photoconductors: amorphous selenium (a-Se), cadmium zinc telluride (CZT), and lead iodide (PbI<SUB>2</SUB>). A critical comparison was made of the advantages and disadvantages of each photoconductor. The results showed that the DQE(0) of all direct detectors has a linear dependence on the pixel fill- factor. For an a-Se layer with an electric field of 10 V/micrometer, DQE(f) is significantly degraded by the electronic noise of the detector, especially at very low x-ray exposure rates (e.g. 0.1 (mu) R/frame). With CZT and PbI<SUB>2</SUB>, the detector is more tolerant of electronic noise because of the larger number of charge generated for each absorbed x-ray. We have applied our cascaded linear systems model of the direct, flat-panel detector to fluoroscopy. The theoretical predictions of DQE(f) for different detector parameters, e.g. the type of x-ray photoconductor, fill-factor, and electronic noise, provide a guideline for an optimum detector design for fluoroscopy.
Oral bile acid treatment and the patient with zellweger syndrome (1992)

The cerebrohepatorenal syndrome of Zellweger is a congenital syndrome of multiple manifestations, including hepatomegaly and liver dysfunction. Treatment is generally of a supportive nature, aimed at improving nutrition and growth, controlling the central nervous system symptoms and limiting progression of liver disease. Because the liver disease in Zellweger syndrome may be attributed to an overproduction and accumulation of cholestanoic acids, exacerbated by diminished primary bile acid synthesis, we hypothesized that primary bile acid administration would be beneficial in improving liver function by a mechanism involving down-regulation in the synthesis of these atypical bile acids. We report here the clinical and biochemical responses to primary bile acid administration in a 2-mo-old boy who was seen with the typical signs of Zellweger syndrome. Liver disease was evident from hepatomegaly and elevated serum liver enzymes and bilirubin. The diagnosis was supported by markedly elevated serum very long chain fatty acids and the bile acids dihydroxycholestanoic acid and trihydroxycholestanoic acid. Confirmation of the lack of peroxisomes was established by electron microscopy. When the patient was 6 mo old, the primary bile acids cholic acid and chenodeoxycholic acid, (100 mg each/day) were administered orally. A significant improvement in biochemical indices of liver function occurred with a normalization of the serum bilirubin and liver enzymes and a histological improvement in the extent of inflammation and bile duct proliferation and disappearance of cannalicular plugs. Serum and urinary cholestanoic acids showed a significant decrease within a few days. A striking and sustained increase in growth was observed after therapy, and an improvement in neurological symptoms was noted. In conclusion, this study indicates that primary bile acid therapy improves liver function and growth in the patient with peroxisomal dysfunction and should be considered in the supportive therapies for this condition.
Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno-associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism (2016)

Adeno-associated virus (AAV) has become the vector of choice for viral gene transfer and has shown great promise in clinical trials. The need for development of an easy, less invasive injection route for ocular gene therapy is met by intravitreal delivery, but delivery of AAV by this route results in poor transduction outcomes. The inner limiting membrane (ILM) creates a barrier separating the vitreous and the retina. Binding of AAV to heparan sulfate proteoglycan (HSPG) at the ILM may allow the virus to traverse this barrier for better retinal transduction. We show that HSPG binding is correlated with greater accumulation and penetration of AAV in the retina. We demonstrated that this accumulation is conserved across mouse and human retinas and that the addition of HSPG binding to other AAV capsids can increase the number of vectors accumulating at the ILM without dictating tropism.
Direct Synthesis of Vinylidene Fluoride-Based Amphiphilic Diblock Copolymers by RAFT/MADIX Polymerization (2012)

We herein report the synthesis of original vinylidene fluoride (VDF)-based amphiphilic block copolymers by RAFT/MADIX polymerization. The controlled polymerization of VDF could be successfully mediated by a xanthate chain transfer agent as evidenced by size exclusion chromatography (SEC), <sup>19</sup>F NMR, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Copolymers of VDF and perfluoro(methyl vinyl ether) (PMVE) of varying controlled chain lengths were also obtained. Finally, the direct synthesis of main-chain fluorinated amphiphilic block copolymers was performed from hydrophilic poly(<i>N</i>,<i>N</i>-dimethylacrylamide) macro-RAFT agents. It is expected that this finding will open interesting perspectives for the development of new class of polymeric surfactants for the stabilization of emulsions based on water and supercritical carbon dioxide media.
Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. (1985)

Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the J5 mutant of Escherichia coli, which is deficient in O antigenic side chains. This deficiency exposes the core oligosaccharide, common to LPS of all Gram-negative bacteria. The mAbs cross-reacted strongly with endotoxins from a wide range of unrelated species of Gram-negative bacteria. The mAbs also gave strong protection against LPS in the dermal Shwartzman reaction and against lethal Gram-negative bacteremia in mice. These findings indicate that monoclonal IgM against LPS endotoxin can neutralize its toxicity in vivo and might be valuable for treatment of patients with Gram-negative bacteremia. Analysis of one of the hybridoma clones, A6(H4C5), showed that the IgM mAb is directed against the covalently bound lipid A, which represents the most conservative and least variable structural element of LPS.
Cloning and characterization of a Pseudomonas mendocina KR1 gene cluster encoding toluene-4-monooxygenase (1991)

Pseudomonas mendocina KR1 metabolizes toluene as a carbon source by a previously unknown pathway. The initial step of the pathway is hydroxylation of toluene to form p-cresol by a multicomponent toluene-4-monooxygenase (T4MO) system. The T4MO enzyme system has broad substrate specificity and provides a new opportunity for biodegradation of toxic compounds and bioconversions. Its known activities include conversion of a variety of phenyl compounds into the phenolic derivatives and the complete degradation of trichloroethylene. We have cloned and characterized a gene cluster from KR1 that determines the offO activity. To clone the T4MO genes, KR1 DNA libraries were constructed in Escherichia coli HB101 by using a broad-host-range vector and transferred to a KR1 mutant able to grow on p-cresol but not on toluene. An insert consisting of two SacI fragments of identical size (10.2 kb) was shown to complement the mutant for growth on toluene. One of the SacI fragments, when cloned into the E. coli vector pUC19, was found to direct the synthesis of indigo dye. The indigo-forming property was correlated with the presence of T4MO activity. The T4MO genes were mapped to a 3.6-kb region, and the direction of transcription was determined. DNA sequencing and N-terminal amino acid determination identified a five-gene cluster, tmoABCDE, within this region. Expression of this cluster carrying a single mutation in each gene demonstrated that each of the five genes is essential for T4MO activity. Other evidence presented indicated that none of the tmo genes was involved in the regulation of the tmo gene cluster, in the control of substrate transport for the T4MO system, or in major processing of the products of the tmo genes. It was tentatively concluded that the tmoABCDE genes encode structural polypeptides of the T4MO enzyme system. One of the tmo genes was tentatively identified as a ferredoxin gene.
Synthetic Studies on Methyl α-Trioxacarcinoside B (1983)

Abstract Trioxacarcinose B is a unique carbohydrate which has been discovered in antibiotic trioxacarcin A as a component. As a step of total synthesis of the antibiotic, methyl α-trioxacarcinoside B has been synthesized from methyl 2,3-anhydro-6-deoxy-α-l-allo-hexopyranoside by a 7 steps reaction in a yield of 4.3%. The product has been identified by comparison with the authentic sample which was prepared by methanolysis of the antibiotic.
Evolutionary Computation Meets Machine Learning: A Survey (2011)

Evolutionary computation (EC) is a kind of optimization methodology inspired by the mechanisms of biological evolution and behaviors of living organisms. In the literature, the terminology evolutionary algorithms is frequently treated the same as EC. This article focuses on making a survey of researches based on using ML techniques to enhance EC algorithms. In the framework of an ML-technique enhanced-EC algorithm (MLEC), the main idea is that the EC algorithm has stored ample data about the search space, problem features, and population information during the iterative search process, thus the ML technique is helpful in analyzing these data for enhancing the search performance. The paper presents a survey of five categories: ML for population initialization, ML for fitness evaluation and selection, ML for population reproduction and variation, ML for algorithm adaptation, and ML for local search.
Specific immunotherapy with suppressor function inhibition for metastatic renal cell carcinoma. (1986)

In this pilot clinical investigation we have investigated the concept of modulating suppressor T lymphocyte (Ts) function to augment delayed type hypersensitivity (DTH) and antitumor immunity in patients with metastatic renal cell carcinoma. Cyclophosphamide (CY) was used for modulating Ts function. We used three doses of CY per 100 mg/m2, 500 mg/m2, and 1000 mg/m2. Cyclophosphamide was administered i.v. 24 h prior to the first of 6 weekly immunizations with irradiated autologous tumor cells mixed with Corynebacterium parvum. Twenty of 26 patients were evaluable for response. Five of these 20 (25%) evaluable patients had responses, one complete response and four partial responses. Fifteen patients had post-treatment skin testing with autologous tumor cells. Four of these 15 (26%) patients developed DTH to autologous tumor cells. Of the four patients acquiring skin test positivity three also had clinical responses, whereas among the 11 skin-test negative patients, only one clinical response was observed. Six of six (100%) patients who had serial T lymphocyte subset studies done had increases in their mean T helper/inducer:T suppressor/cytotoxic ratios after CY administration and immunization. These observations in an exploratory study suggest that further investigations of Ts modulation, autologous tumor cell skin testing, and T lymphocyte subsets may be of value.
The structures of cytochalasins A and B (1967)

The structures of cytochalasins A and B, metabolites of Helminthosporium dematioideum showing novel effects on mammalian cells, have been determined. Cytochalasin B is identical with phomin. (–)-α-Methyladipic acid is shown to have the R-configuration contrary to a previous assignment; the absolute configurations of the Nupheus alkaloids therefore require revision.
Ocular Gene Therapy (1993)

THIS ISSUE of theArchivescommemorates the 40th anniversary of the publication of Watson and Crick's 1 classic paper on the structure of DNA. In 1953, gene therapy was mentioned only in the realm of science fiction. Now, a mere 40 years later, gene therapy has become a reality. 2 A number of clinical trials are already in progress, and the number of proposed trials is increasing almost daily. 2-5 Current trials involve diseases as diverse as severe combined immunodeficiency, cancer, and cystic fibrosis. Although to date none of these trials involves the eye, this situation is sure to change in the near future. (In one sense, ocular gene therapy is already a reality. The murine retinal degeneration [ rd ] and retinal degeneration slow [ rds ] mutations have been rescued using transgenic mouse technology. 6,7 However, transgenesis involves germ line transformation and is not directly applicable to human gene therapy.) Genetic disease
Phylogenetic Incongruence among Oncogenic Genital Alpha Human Papillomaviruses (2005)

The human papillomaviruses (HPVs) have long been thought to follow a monophyletic pattern of evolution with little if any evidence for recombination between genomes. On the basis of this model, both oncogenicity and tissue tropism appear to have evolved once. Still, no systematic statistical analyses have shown whether monophyly is the rule across all HPV open reading frames (ORFs). We conducted a taxonomic analysis of 59 mucosal/genital HPVs using whole-genome and sliding-window similarity measures; maximum-parsimony, neighbor-joining, and Bayesian phylogenetic analyses; and localized incongruence length difference (LILD) analyses. The algorithm for the LILD analyses localized incongruence by calculating the tree length differences between constrained and unconstrained nodes in a total-evidence tree across all HPV ORFs. The process allows statistical evaluation of every ORF/node pair in the total-evidence tree. The most significant incongruence was observed at the putative high-risk (i.e., cancer-associated) node, the common oncogenic ancestor for alpha HPV species 9 (e.g., HPV type 16 [HPV16]), 11, 7 (e.g., HPV18), 5, and 6. Although these groups share early-gene homology, including high degrees of similarity among E6 and E7, groups 9 and 11 diverge from groups 7, 5, and 6 with respect to L2 and L1. The HPV species groups primarily associated with cervical and anogenital cancers appear to follow two distinct evolutionary paths, one conferred by the early genes and another by the late genes. The incongruence in the genital HPV phylogeny could have occurred from an early recombination event, an ecological niche change, and/or asymmetric genome convergence driven by intense selection. These data indicate that the phylogeny of the oncogenic HPVs is complex and that their evolution may not be monophyletic across all genes.
Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering (1992)

Integrins are heterodimeric cell surface proteins that mediate both cell-cell and cell-extracellular matrix interactions. We and others recently identified cDNAs encoding a novel integrin beta subunit, beta 7, in lymphocytes. We have now detected beta 7 mRNA in mouse TK-1 T lymphoma cells, which are known to express the putative Peyer's patch homing receptor alpha 4 beta P. We used an anti-peptide antiserum and a novel mAb against the beta 7 subunit to show that TK-1 cells express beta 7 as the only subunit associated with alpha 4. We conclude that beta 7 and beta P are identical. We also show that activated peripheral blood T cells express alpha 4 beta 7. We studied the function of alpha 4 beta 7/alpha 4 beta P in TK-1 cells, which do not express very late antigen (VLA)-4 (alpha 4 beta 1). Cells adhered to intact fibronectin and to a fibronectin fragment containing the CS-1 region, but not to a fragment containing the RGD sequence. Adhesion to fibronectin was inhibited by antibodies to alpha 4, suggesting that alpha 4 beta 7 is a fibronectin receptor. We confirmed that alpha 4 beta 7 binds to the CS-1 region of fibronectin using affinity chromatography. TK-1 cell adhesion to the vascular cell adhesion molecule VCAM-1 was also inhibited by antibodies to alpha 4, implying that alpha 4 beta 7 also plays a role in the adherence of lymphocytes to endothelial cells. TK-1 cell binding to fibronectin and VCAM-1 is markedly increased by brief PMA stimulation. We also found that mAbs against alpha 4 and beta 7 induce homotypic clustering of TK-1 cells. Taken together these results suggest that alpha 4 beta 7/alpha 4 beta P recognizes some or all of the same widely distributed ligands recognized by VLA-4 (alpha 4 beta 1) and that the role of alpha 4 beta 7/alpha 4 beta P may not be restricted to lymphocyte homing.
Rapid production of recombinant human IgG With improved ADCC effector function in a transient expression system (2009)

Rapid production of recombinant human IgG with improved antibody dependent cell-mediated cytotoxicity (ADCC) effector function is presented. The technique employs transient expression of IgG in suspension growing HEK-293F cells in the presence of the glycosidase inhibitor kifunensine. The procedure takes approximately 7 days, provided that expression plasmids encoding the IgG of interest are available. Kifunensine inhibits the N-linked glycosylation pathway of HEK-293F cells in the endoplasmatic reticulum, resulting in IgG with oligomannose type glycans lacking core-fucose. IgG1 transiently produced in kifunensine- treated HEK-293F cells has improved affinity for the FcgammaRIIIA molecule as measured in an ELISA based assay, and almost eightfold enhanced ADCC using primary peripheral blood mononuclear effector cells.
The Diversity of Torque Teno Viruses: In Vitro Replication Leads to the Formation of Additional Replication-Competent Subviral Molecules (2011)

The family Anelloviridae comprises torque teno viruses (TTVs) diverse in genome structure and organization. The isolation of a large number of TTV genomes (TTV Heidelberg [TTV-HD]) of 26 TTV types is reported. Several isolates from the same type indicate sequence variation within open reading frame 1 (ORF1), resulting in considerably modified open reading frames. We demonstrate in vitro replication of 12 full-length genomes of TTV-HD in 293TT cells. Propagation of virus was achieved by several rounds of infections using supernatant and frozen whole cells of initially infected cells. Replication of virus was measured by PCR amplification and transcription analyses. Subgenomic molecules (μTTV), arising early during propagation and ranging in size from 401 to 913 bases, were cloned and characterized. Propagation of these μTTV in in vitro cultures was demonstrated in the absence of full-length genomes.
Cancer Immunotherapy: A Treatment for the Masses (2004)

Cancer immunotherapy attempts to harness the exquisite power and specificity of the immune system for the treatment of malignancy. Although cancer cells are less immunogenic than pathogens, the immune system is clearly capable of recognizing and eliminating tumor cells. However, tumors frequently interfere with the development and function of immune responses. Thus, the challenge for immunotherapy is to use advances in cellular and molecular immunology to develop strategies that effectively and safely augment antitumor responses.
Intensive Immunosuppression in Progressive Multiple Sclerosis (1983)

Fifty-eight patients with severe, progressive multiple sclerosis were prospectively randomized to one of three treatments: 20 received intravenous ACTH, 20 received high-dose intravenous cyclophosphamide plus ACTH, and 18 were placed on a regimen consisting of plasma exchange, low-dose oral cyclophosphamide, and ACTH. The three groups were similar in age, sex, duration and type of disease, and degree of disability. Before treatment and six months and one year after treatment, a disability-status score, ambulation index, and functional-status score were determined, and a quantitative neurologic examination was performed. In the ACTH group, the number of patients stabilized or improved was 8 of 20 at six months and 4 of 20 at one year; in the cyclophosphamide-ACTH group, 18 of 20 at six months and 16 of 20 at one year; and in the plasma exchange group, 11 of 18 at six months and 9 of 18 at one year. High-dose cyclophosphamide plus ACTH was most effective in halting progression of the disease at both 6 and 12 months (at 12 months, cyclophosphamide-ACTH vs. ACTH, P = 0.0004; cyclophosphamide-ACTH vs. plasma exchange, P = 0.087). Thus, progressive multiple sclerosis may be stabilized by short-term, intensive immunosuppression with cyclophosphamide plus ACTH.