gebhart/patrepeval huggingface dataset:
Triglycerides and Cardiovascular Risk (2009)

In 1996 a meta-analysis was published showing that an increase in plasma triglyceride (TG) levels was associated with an increase in CHD risk, even after adjustment for high density lipoprotein cholesterol (HDL-C) levels. Very recently, two studies were published that further extent the early observation and showed the importance of nonfasting plasma triglyceride (TG) levels in the prediction of risk on coronary heart disease (CHD). In the current review we have summarized all available evidence obtained in clinical studies showing that treatment guidelines should reconsider to include nonfasting TG in their risk assessments as nonfasting TG levels may better predict CVD risk.
Characterization of the effects of asparaginase from escherichia coli and a glutaminase‐free asparaginase from vibrio succinogenes on specific cell‐mediated cytotoxicity (1981)

Abstract Asparaginases isolated from Escherichia coli and Erwinia carotovora are effective in the treatment of acute lymphoblastic leukemia in man. During treatment with either of these enzymes, patients frequently experience pronounced toxicity, including liver and pancreatic dysfunction and immunosuppression. The capabilities of these enzymes to hydrolyze L‐glutamine, an important amino acid in mammalian intermediary metabolism, have led investigators to suggest that the glutaminase activity may be responsible for the observed toxicities. Unlike other asparaginases, an enzyme isolated in our laboratory from Vibrio succinogenes , has been shown to be a potent antilymphoma agent and to be highly specific for L‐asparagine. Our previous work has established that the glutaminase‐free asparaginase from V. succinogenes does not suppress the in vivo humoral or cell‐mediated immune responses of mice to sheep red blood cells, whereas the E. coli enzyme abolishes these responses. In this study, we describe the mechanisms by which E. coli asparaginase suppresses specific antibody‐dependent cell‐mediated cytotoxicity. An analysis of the kinetics of appearance of the specific cell‐mediated cytotoxic response of spleen cells after immunization with sheep red blood cells revealed that it paralleled the IgG plaque‐forming cell response. In addition, 18‐h culture supernatants from immune spleen cells conferred upon non‐immune cells the ability to specifically lyse sheep red blood cells. Pretreatment of immune supernatants with protein A‐Sepharose 4B absorbed out the soluble arming factor. An analysis of E. coli asparaginase‐induced suppression of specific antibody‐dependent cell‐mediated cytotoxicity revealed that a decreased synthesis of specific IgG was responsible for the observed reduction in cytotoxic reactivity. When culture supernatants from spleen cells of immunized animals not treated with asparaginase were added to spleen cells from E. coli asparaginase‐treated mice, however, there was an increased cytotoxic response. This suggested that there was an increase in the number or ratio of effector cells for the specific antibody‐dependent cell‐mediated cytotoxic response in spleens of enzyme‐treated animals. Through the characterization of the immunosuppressive effects of two asparaginases—one having the catalytic capability to hydrolyze L‐glutamine and the other lacking this catalytic activity—we now have evidence that the immunosuppressive effects of E. coli asparaginase on specific antibody‐dependent cell‐mediated cytotoxicity cannot be the result of asparagine depletion alone. Our data demonstrate that the glutaminase‐free asparaginase from V. succinogenes is not immunosuppressive and suggest that an asparaginase with high substrate specificity for L‐asparagine may be a safer treatment for leukemia patients.
Analysis of cellular fatty acids by gas chromatography as a tool in the identification of medically important coryneform bacteria (1985)

The fatty acid methyl esters of nineteen unidentified pathogenic coryneform bacteria were analysed by gas-liquid chromatography and the resulting profiles were compared with those of type or reference strains of possibly related species, namely Caseobacter polymorphus, Corynebacterium bovis, C. diphtheriae, C. xerosis and Rhodococcus equi. All of the strains had distinct fatty acid profiles but most of them conformed to a general pattern, with high levels of octadecanoic acids and only trace amounts of 10-methyl octadecanoic acid (tuberculostearic acid). These profiles were very similar to those from C. diphtheriae and C. xerosis but could be differentiated from C. bovis, Cas. polymorphus, R. equi and two unidentified pathogenic strains which had significantly higher levels of tuberculostearic acid.
Novel Aliphatic Polyesters Based on Functional Cyclic (Di)Esters (2003)

Abstract Recent progress in the chemical synthesis of novel aliphatic polyesters via ring‐opening polymerization of functional cyclic (di)esters are reviewed in this article. Syntheses of these functional aliphatic polyesters are being classified into three groups according to the structure of the cyclic monomers: (i) cyclic diesters, (ii) morpholine‐2,5‐dione derivatives, and (iii) cyclic esters. Progress in the synthesis and polymerization of monomers in each category is reported with an emphasis on controlled synthesis. The recent achievements have enabled the synthesis of a variety of novel aliphatic polyesters, including hydrophilic, halogenated, and unsaturated polyesters. Structure of the most common R‐functionalized cyclic precursors of aliphatic polyesters. magnified image Structure of the most common R‐functionalized cyclic precursors of aliphatic polyesters.
Specific Occlusion of Murine and Human Tumor Vasculature by VCAM-1–Targeted Recombinant Fusion Proteins (2005)

Recombinant tissue factor-based fusion proteins directed against an intraluminal tumor endothelial cell marker induce tumor-selective intravascular coagulation, tumor tissue necrosis, and tumor growth delay.
Mechanism of iris prolapse: A qualitative analysis and implications for surgical technique (1995)

A theoretical explanation of the mechanism of iris prolapse is presented using simple flow mechanics and the Bernouille principle, which states that fluid pressure varies inversely to fluid velocity. Rapid aqueous escape into an anterior chamber perforation thus creates a relative vacuum anterior to the iris. Further analysis shows that the tendency of the iris to prolapse into an anterior chamber wound increases as an inverse function of the fourth power of the radial distance between the iris and the perforation. Anterior wound placement, clear of the iris plane, should help to prevent iris prolapse. Minimizing the irrigation velocity (and hence the fluid outflow velocity) should also help to prevent intraoperative prolapse.
Experimental optimisation of MQW electroabsorptionmodulatorswith up to 40 GHz bandwidths (1994)

Three MQW electroabsorption modulator structures made of 7, 13 and 20 wells are reported. The bandwidth is shown to increase linearly with intrinsic region thickness up to 40 GHz, with negligible penalty on the drive voltage which remains at less than 2 V. It is suggested that 100 GHz bandwidth should be reached with low drive voltage.
Dynamically reparameterized light fields (2000)

This research further develops the light field and lumigraph image-based rendering methods and extends their utility. We present alternate parameterizations that permit 1) interactive rendering of moderately sampled light fields of scenes with significant, unknown depth variation and 2) low-cost, passive autostereoscopic viewing. Using a dynamic reparameterization, these techniques can be used to interactively render photographic effects such as variable focus and depth-of-field within a light field. The dynamic parameterization is independent of scene geometry and does not require actual or approximate geometry of the scene. We explore the frequency domain and ray-space aspects of dynamic reparameterization, and present an interactive rendering technique that takes advantage of today's commodity rendering hardware.
Ruthenium-catalysed Z-selective cross metathesis of allylic-substituted olefins (2013)

The <i>Z</i>-selective cross metathesis of allylic-substituted olefins is explored with recently developed ruthenium-based metathesis catalysts. The reaction proceeds with excellent stereoselectivity for the <i>Z</i>-isomer (typically >95%) and yields of up to 88% for a variety of allylic substituents. This includes the first synthesis of <i>Z</i>-α,β-unsaturated acetals by cross metathesis and their elaboration to Z-α,β-unsaturated aldehydes. In addition, the reaction is tolerant of a variety of cross partners, varying in functionality and steric profile.
Immunophotodiagnosis of colon carcinomas in patients injected with fluoresceinated chimeric antibodies against carcinoembryonic antigen. (1992)

Based on previous experiments in nude mice, showing that fluoresceinated monoclonal antibodies against carcinoembryonic antigen localized specifically in human carcinoma xenografts and could be detected by laser-induced fluorescence, we performed a feasibility study to determine whether this immunophotodiagnosis method could be applied in the clinic. Six patients, with known primary colorectal carcinoma, received an i.v. injection of 4.5 or 9 mg of mouse-human chimeric anti-carcinoembryonic antigen monoclonal antibody coupled with 0.10-0.28 mg of fluorescein (molar ratio 1/10 to 1/14). The monoclonal antibody was also labeled with 0.2-0.4 mCi of 125I (1 Ci = 37 GBq). Photodetection of the tumor was done ex vivo on surgically resected tissues for the six patients and in vivo by fluorescence rectosigmoidoscopy for the sixth patient. Upon laser irradiation, clearly detectable heterogeneous green fluorescence from the dye-antibody conjugate was visually observed on all six tumors; almost no such fluorescence was detectable on normal mucosa. The yellowish tissue autofluorescence, which was emitted from both tumor and normal mucosa, could be subtracted by real-time image processing. Radioactivity measurements confirmed the specificity of tumor localization by the conjugate; tissue concentrations of up to 0.059% injected dose per g of tumor and 10 times less (0.006%) per g of normal mucosa were found. The overall results demonstrate the feasibility of tumor immunophotodiagnosis at the clinical level.
Hepatocyte-directed Gene Delivery by Receptor-mediated Endocytosis (1999)

The application of gene therapy to liver disease is contingent on the development of an effective gene delivery vehicle. Receptor-mediated endocytosis can be exploited as a means of selective and efficient targeting of gene therapy vectors to hepatocytes. DNA-binding conjugates have been directed to the liver by the attachment of asialoglycoproteins or other ligands for receptors expressed on hepatocytes. Recent studies suggest refinements in this approach through which high transduction rates in vitro may be reproduced in vivo. The intrinsic liver tropism of viral vectors and liposomes can be augmented by the addition of targeting features, as demonstrated in animal models. With further modification, such as the incorporation of hepatotropic elements of the hepatitis viruses or lipoproteins, the next generation of delivery systems may achieve efficient, persistent expression of therapeutic genes in a safe and cell type-specific manner.
CD4 T cell traffic control:in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles (1999)

We report here that CD40- but not lipopolysaccharide (LPS)-activated murine dendritic cells (DC) express OX40-ligand (OX40L) as has been reported in humans. To understand how OX40 ligation affects differentiation of CD4 T cells at the time of priming, we constitutively expressed OX40L on DC using the DC-specific promoter of CD11c. Transgenic mice showed greatly increased numbers of CD4 but not CD8 T cells in their B cell areas. This effect was to a great extent immunization dependent, as spleen and lymphoid tissue with no germinal center reactions from mice which had not been deliberately immunized did not show marked CD4 T cell accumulation. The increased numbers of CD4+ CD62low cells in transgenic mice suggest that it is activated CD4 T cells that accumulate within B cell follicles. These data are consistent with the notion that physiological engagement of OX40 (CD134) on activated CD4 T cells either initiates their migration into or causes them to be retained in B follicles. In contrast, LPS-treated CD did not up-regulate OX40L expression. This dichotomy provides a molecular explanation of how DC might integrate environmental and accessory signals to control cytokine differentiation and migration in CD4 effector cells.
Newer insulin analogues and inhaled insulin (2006)

Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin. Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera) is recently approved by FDA and appears promising.
Antibodies Against IL-12 Prevent Superantigen-Induced and Spontaneous Relapses of Experimental Autoimmune Encephalomyelitis (1998)

Abstract Immunization of (PL/J × SJL/J)F1 mice with myelin basic protein (MBP) induces relapsing experimental autoimmune encephalomyelitis (EAE). Relapses occur 7 to 10 days after recovery from the initial paralysis. Staphylococcal enterotoxins (SE) A or B, administered after recovery from the initial paralysis, induce immediate relapses. IL-12 is involved in the induction of EAE. Here, we show that SEA and SEB induce IL-12 in splenocytes from (PL/J × SJL/J)F1 mice in vitro and increase the level of IL-12 in the sera of mice treated with these superantigens. IL-12 administration mimics SE in inducing spontaneous relapses and in enhancing the severity and frequency of spontaneous relapses. IL-12 neutralization blocks SE-induced and subsequent relapses of EAE, and, when instituted after recovery from the initial attack, prevents spontaneous relapse. This is the first report of prevention of relapses of EAE with anti-IL-12 Ab, an approach which may prove useful in the prevention of exacerbations in multiple sclerosis.
Dynamics of the Ras/ERK MAPK Cascade as Monitored by Fluorescent Probes (2006)

To comprehend the Ras/ERK MAPK cascade, which comprises Ras, Raf, MEK, and ERK, several kinetic simulation models have been developed. However, a large number of parameters that are essential for the development of these models are still missing and need to be set arbitrarily. Here, we aimed at collecting these missing parameters using fluorescent probes. First, the levels of the signaling molecules were quantitated. Second, to monitor both the activation and nuclear translocation of ERK, we developed probes based on the principle of fluorescence resonance energy transfer. Third, the dissociation constants of Ras.Raf, Raf.MEK, and MEK.ERK complexes were estimated using a fluorescent tag that can be highlighted very rapidly. Finally, the same fluorescent tag was used to measure the nucleocytoplasmic shuttling rates of ERK and MEK. Using these parameters, we developed a kinetic simulation model consisting of the minimum essential members of the Ras/ERK MAPK cascade. This simple model reproduced essential features of the observed activation and nuclear translocation of ERK. In this model, the concentration of Raf significantly affected the levels of phospho-MEK and phospho-ERK upon stimulation. This prediction was confirmed experimentally by decreasing the level of Raf using the small interfering RNA technique. This observation verified the usefulness of the parameters collected in this study.
Inhibition of Human Cancer Cell Growth and Metastasis in Nude Mice by Oral Intake of Modified Citrus Pectin (2002)

MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effects on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.
Zinc Ejection as a New Rationale for the Use of Cystamine and Related Disulfide-Containing Antiviral Agents in the Treatment of AIDS (1997)

The highly conserved and mutationally intolerant retroviral zinc finger motif of the HIV-1 nucleocapsid protein (NC) is an attractive target for drug therapy due to its participation in multiple stages of the viral replication cycle. A literature search identified cystamine, thiamine disulfide, and disulfiram as compounds that have been shown to inhibit HIV-1 replication by poorly defined mechanisms and that have electrophilic functional groups that might react with the metal-coordinating sulfur atoms of the retroviral zinc fingers and cause zinc ejection. 1H NMR studies reveal that these compounds readily eject zinc from synthetic peptides with sequences corresponding to the HIV-1 NC zinc fingers, as well as from the intact HIV-1 NC protein. In contrast, the reduced forms of disulfiram and cystamine, diethyl dithiocarbamate and cysteamine, respectively, were found to be ineffective at zinc ejection, although cysteamine formed a transient complex with the zinc fingers. Studies with HIV-1-infected human T-cells and monocyte/macrophage cultures revealed that cystamine and cysteamine possess significant antiviral properties at nontoxic concentrations, which warrant their consideration as therapeutically useful anti-HIV agents.
Finding approximate matches in large lexicons (1995)

Abstract Approximate string matching is used for spelling correction and personal name matching. In this paper we show how to use string matching techniques in conjunction with lexicon indexes to find approximate matches in a large lexicon. We test several lexicon indexing techniques, including n ‐grams and permuted lexicons, and several string matching techniques, including string similarity measures and phonetic coding. We propose methods for combining these techniques, and show experimentally that these combinations yield good retrieval effectiveness while keeping index size and retrieval time low. Our experiments also suggest that, in contrast to previous claims, phonetic codings are markedly inferior to string distance measures, which are demonstrated to be suitable for both spelling correction and personal name matching.
Genetic basis of tooth development and dental defects (2000)

Tooth development is under strict genetic control, and during recent years an increasing number of genes have been identified that are involved in the regulation of tooth morphogenesis. One of the organs in which development is now beginning to be understood at the gene level, the tooth is an example of a typical vertebrate organ starting as an epithelial bud and undergoing complex morphogenesis, regulated by interactions between epithelial and mesenchymal tissue layers. It has become evident that developmental regulatory genes have been conserved to a high degree during evolution and that similar gene networks regulate the development of teeth as of other vertebrate organs. So far, all genes that have been linked with early tooth morphogenesis have developmental regulatory functions in other organs, too. The majority of these genes are associated with the signaling pathways transmitting interactions between cells and tissues. They include genes encoding the actual signals as well as their receptors, mediators of signaling in the cytoplasm and transcription factors regulating gene expression in the nucleus. Deletion of the function of many of these genes in transgenic mice results in arrested tooth development, but all these mutants also show defects in many other tissues. Mutations in several of these genes in humans have been identified as causes of dental defects, mainly hypodontia.
Stabilization of the active form(s) of human paraoxonase by human phosphate-binding protein (2007)

While there is a consensus that human PON1 (paraoxonase-1) has a protective role, its primary biological function remains unclear. A protective role against poisoning by organophosphates [OPs (organophosphorus compounds)] drove earlier works. Clinical interest has recently focused on a protective role of PON1 against vascular diseases. PON1 resides mainly on HDL (high-density lipoprotein) particles, and converging recent works show that both its activities and stability dramatically depend on this versatile and dynamic molecular environment. The discovery that HPBP (human phosphate-binding protein) has a firm tendency to associate with PON1 has steered new directions for characterizing PON1 functional state(s). Storage stability studies provided evidence that HPBP is involved in maintaining physiologically active PON1 conformation(s). Thermal stability studies showed that human PON1 is remarkably thermostable and that its association with HPBP strongly contributes to slowing down the denaturation rate. A hybrid PON1, displaying mutations that stabilized recombinant enzyme expressed in Escherichia coli, was shown to be more thermostable than natural human PON1. Predictably, its stability was unaffected by the presence of HPBP. Synergistic efforts on characterizing natural PON1 and rPON1 (recombinant PON1) provide information for the design of future stable mutants of PON1-based bioscavengers to be used as safe and effective countermeasures to challenge OPs. Maintaining a stable environment for such administrable human rPON1 should, at least, preserve the anti-atherogenic activity of the enzyme.