gebhart/patrepeval huggingface dataset:
Genetic and environmental determinants of serum lipids and lipoproteins in French Canadian families. (1989)

The contribution of genetic and environmental factors in serum triglycerides (TG), total cholesterol (CHOL), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and HDL-C/CHOL ratio were studied in 1630 subjects from 375 families of French descent by using a path analysis procedure. Familial correlations were computed in several pairs of biological relatives and relatives by adoption after adjustment for age and gender effects and after further adjustment for physical fitness, level of habitual physical activity, total body fat and fat distribution, diet, smoking, and alcohol consumption. The model of path analysis allowed the separation of transmissible variance (t2) into genetic (h2) and cultural (b2) components of inheritance. Under the most parsimonious solution and after adjustment for age, gender, and concomitants, the transmissible variance was entirely accounted for by genetic factors (t2 = h2), with h2 estimates of 0.52, 0.55, 0.60, and 0.63 for TG, CHOL, LDL-C, HDL-C, and HDL-C/CHOL, respectively. These estimates were similar to those obtained after adjustment for age and gender effects only. The contribution of nontransmissible environmental factors ranged from 0.48 for TG to 0.37 for HDL-C/CHOL ratio. These results suggest that both genetic and environmental factors contribute to the variation in blood lipids and lipoproteins in this population and that nongenetic influences are not associated with cultural factors transmitted across generations.
Cystatin C as a Predictor of Mortality and Cardiovascular Events in a Population with Chronic Kidney Disease (2014)

Background. We examine whether cystatin C, a surrogate marker of renal function, could identify patients with chronic kidney disease (CKD) with an increased risk of renal disease progression, death, or cardiovascular events. Methods. Data were obtained for 180 patients, with a diagnosis of chronic renal failure based on serum creatinine estimated glomerular filtration rate (eGFRcreat) <90 mL/min/1.73 m(2). This population was grouped in tertiles according to cystatin C and creatinine values at baseline. Cardiovascular events and overall mortality were estimated for each tertile. Predictors of overall mortality and for the development of renal disease progression were analyzed. Results. The median age was 75 years (interquartile range 69-82) and the median eGFRcreat 38 mL/min m(2) (interquartile range 33-49). Overall mortality was lower on the first and on the second tertiles of cystatin C than on the third one (HR = 0.060; 95% CI: 0.008-0.447 and HR = 0.094; 95% CI: 0.022-0.406, resp.). Deaths related to the creatinine tertiles followed the same pattern, but differences were not as large. Cardiovascular mortality was lower on the second than on the third cystatin C tertile (HR = 0.198; 95% CI: 0.040-0.987), but it did not show differences on the first and the second creatinine tertiles compared with the third one (HR = 0.126; 95% CI: 0.013-1.265 and HR = 0.403; 95% CI: 0.093-1.740). The only independent predictors of mortality during followup were baseline cystatin C (OR = 0.100; 95% CI: 0.021-0.463) and baseline uric acid (OR = 1.377; 95% CI: 1.070-1.773). Conclusion. Cystatin C may be an alternative to creatinine for detecting a high risk of death and cardiovascular events in a population with CKD.
Soluble Donor DNA Concentrations in Recipient Serum Correlate with Pancreas-Kidney Rejection (2006)

Q-PCR for donor-specific genetic polymorphisms merits further investigation as a noninvasive approach to monitor pancreas-kidney as well as other types of allograft rejection.
Probiotic Lactobacillus reuteri biofilms produce antimicrobial and anti-inflammatory factors (2009)

L. reuteri biofilms secreted factors that confer specific health benefits such as immunomodulation and pathogen inhibition. Future probiotic selection strategies should consider a strain's ability to perform beneficial functions as a biofilm.
RAPID COMMUNICATION: Human Ovarian Cancers Express Somatostatin Receptors (2000)

Characteristics of receptors for somatostatin (SST) analog RC-160 on 17 surgical specimens of human epithelial ovarian cancer and two human ovarian cancer lines were determined by ligand competition assays. The expression of mRNA for four SST receptor subtypes (sst1, sst2A, sst3 and sst5) was investigated by RT-PCR. Thirteen of 17 specimens (76%) exhibited high affinity binding sites for RC-160 with Kd = 6.55 nmol/L and a Bmax = 575.4 fmol/mg membrane protein. Specific receptors for RC-160 were also found in xenografts of OV-1063 and UCI-107 human ovarian cancer lines. The mRNA for sst1 was detected in 65% of the ovarian cancer specimens, while the incidence of sst2A, sst3 and sst5 was 65%, 41% and 24%, respectively. Both ovarian cancer cell lines also expressed mRNA for these four subtypes. The presence of these SST receptor subtypes in human ovarian cancers allows the use of SST analogs and their radionuclide and cytotoxic derivatives for the diagnosis and treatment of this malignancy.
Discovery of Marinopyrrole A (Maritoclax) as a Selective Mcl-1 Antagonist that Overcomes ABT-737 Resistance by Binding to and Targeting Mcl-1 for Proteasomal Degradation (2012)

The anti-apoptotic Bcl-2 family of proteins, including Bcl-2, Bcl-X(L) and Mcl-1, are well-validated drug targets for cancer treatment. Several small molecules have been designed to interfere with Bcl-2 and its fellow pro-survival family members. While ABT-737 and its orally active analog ABT-263 are the most potent and specific inhibitors to date that bind Bcl-2 and Bcl-X(L) with high affinity but have a much lower affinity for Mcl-1, they are not very effective as single agents in certain cancer types because of elevated levels of Mcl-1. Accordingly, compounds that specifically target Mcl-1 may overcome this resistance. In this study, we identified and characterized the natural product marinopyrrole A as a novel Mcl-1-specific inhibitor and named it maritoclax. We found that maritoclax binds to Mcl-1, but not Bcl-X(L), and is able to disrupt the interaction between Bim and Mcl-1. Moreover, maritoclax induces Mcl-1 degradation via the proteasome system, which is associated with the pro-apoptotic activity of maritoclax. Importantly, maritoclax selectively kills Mcl-1-dependent, but not Bcl-2- or Bcl-X(L)-dependent, leukemia cells and markedly enhances the efficacy of ABT-737 against hematologic malignancies, including K562, Raji, and multidrug-resistant HL60/VCR, by ∼60- to 2000-fold at 1-2 μM. Taken together, these results suggest that maritoclax represents a new class of Mcl-1 inhibitors, which antagonizes Mcl-1 and overcomes ABT-737 resistance by targeting Mcl-1 for degradation.
The Role of Ectonucleotidases CD39 and CD73 and Adenosine Signaling in Solid Organ Transplantation (2014)

Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation. Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73. Accumulating evidence suggest that purinergic signaling is involved in the inflammatory response that accompanies acute rejection and chronic allograft dysfunction. Modification of the purinergic pathway has been shown to alter graft survival in a number of solid organ transplant models and the response to ischemia-reperfusion injury (IRI). Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function. Although T cells have traditionally been considered the orchestrators of acute allograft rejection, a role for B cells in chronic allograft loss is being increasingly appreciated. This review focuses on the role of the ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation including the effects on IRI and T and B cell biology.
Association Between Right Ventricular Function and Perfusion Abnormalities in Hemodynamically Stable Patients With Acute Pulmonary Embolism (1998)

The extent of right ventricular dysfunction in hemodynamically stable, previously normal patients with acute pulmonary embolism does not reflect the extent of the perfusion abnormalities. Further, right ventricular enlargement and systolic dysfunction are present and persistent despite treatment with heparin and warfarin therapy or vena caval interruption.
Fuse1 alcohols induce hyphal-like extensions and pseudohyphal formationin yeasts (1996)

At a concentration of 0.5% (v/v), isoamyl alcohol induced the formation of hyphal-like extensions in haploid and diploid strains of Saccharomyces cerevisiae in liquid complex medium. These extensions, which develop via bud initiation and elongation, undergo DNA replication and nuclear division and appear similar in many respects to an aberrant form of the cell division cycle. However, in 0.25% (v/v) isoamyl alcohol, S. cerevisiae formed pseudohyphae. Other 'fusel' alcohols (which are the products of amino acid catabolism) also induced hyphal-like extensions in this yeast, with n-amyl alcohol being as equally effective as isoamyl alcohol. Isoamyl alcohol induced the formation of pseudohyphae in two species of Candida and both hyphal-like extensions and pseudohyphae in Brettanomyces anomalus, suggesting a close relationship or a common basis to the development of the two morphologies.
The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis (2003)

Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary demyelination in multiple sclerosis. Although the disease-inducing role of MOG has been established, its precise function in the CNS remains obscure. To gain new insights into the physiological and immunopathological role of MOG, we determined the 1.8-A crystal structure of the MOG extracellular domain (MOGED). MOGED adopts a classical Ig (Ig variable domain) fold that was observed to form an antiparallel head-to-tail dimer. A dimeric form of native MOG was observed, and MOGED was also shown to dimerize in solution, consistent with the view of MOG acting as a homophilic adhesion receptor. The MOG35-55 peptide, a major encephalitogenic determinant recognized by both T cells and demyelinating autoantibodies, is partly occluded within the dimer interface. The structure of this key autoantigen suggests a relationship between the dimeric form of MOG within the myelin sheath and a breakdown of immunological tolerance to MOG that is observed in multiple sclerosis.
The Distribution, Purification, and Pharmacological Action of an Amphibian Neuromedin U (1989)

The distribution, primary structure, and relative biological activity of neuromedin U has been determined from the frog Rana temporaria. Following sequential column chromatography of a gastrointestinal extract, the peptide was sufficiently pure to enable characterization by micro-sequence analysis. The entire sequence was found to be an icosapentapeptide which displays marked sequence similarity to both porcine and rat neuromedin U. The sequence of the biologically active, COOH-terminal region is almost completely conserved across all species. Synthetic, COOH-terminally amidated amphibian neuromedin U, like the porcine and rat peptides, stimulates rat uterine contraction in vitro thereby fulfilling the criterion upon which the nomenclature of this peptide family is based. In addition, the peptide demonstrates parallel pressor effects when infused systemically into rats. The high degree of amino acid sequence conservation is indicative of strong evolutionary pressure acting to retain the presence of this possibly physiologically important peptide across the vertebrate subphylum.
A strategy of exon shuffling for making large peptide repertoires displayed on filamentous bacteriophage. (1996)

It has been suggested that recombination and shuffling between exons has been a key feature in the evolution of proteins. We propose that this strategy could also be used for the artificial evolution of proteins in bacteria. As a first step, we illustrate the use of a self-splicing group I intron with inserted lox-Cre recombination site to assemble a very large combinatorial repertoire (> 10(11) members) of peptides from two different exons. Each exon comprised a repertoire of 10 random amino acids residues; after splicing, the repertoires were joined together through a central five-residue spacer to give a combinatorial repertoire of 25-residue peptides. The repertoire was displayed on filamentous bacteriophage by fusion to the pIII phage coat protein and selected by binding to several proteins, including beta-glucuronidase. One of the peptides selected against beta-glucuronidase was chemically synthesized and shown to inhibit the enzymatic activity (inhibition constant: 17 nM); by further exon shuffling, an improved inhibitor was isolated (inhibition constant: 7 nM). Not only does this approach provide the means for making very large peptide repertoires, but we anticipate that by introducing constraints in the sequences of the peptides and of the linker, it may be possible to evolve small folded peptides and proteins.
Inducible high‐level mRNA amplification system by viral replicase in transgenic plants (2001)

We have constructed a new system for inducible high-level expression of mRNA for foreign genes in transgenic plants by introducing a glucocorticoid-inducible transcription system into the previously developed "mRNA amplification system" where target mRNA can be amplified as a subgenomic RNA by the replicase of a plant tripartite RNA virus, Brome mosaic virus (BMV). In the new amplification system, the amplification of mRNA is tightly regulated by the expression of a subunit of the BMV replicase. Transgenic Nicotiana benthamiana plants (designated GVG1 x 2FR) were produced that contained cDNA of BMV RNA1 coding a subunit of replicase under the control of a tightly regulated, glucocorticoid-inducible promoter. In addition GVG1 x 2FR plants contain cDNAs of BMV RNA2 coding another subunit of the replicase, and a replicable engineered BMV RNA3 derivative (FCP2IFN) carrying the human gamma interferon (IFN) gene under the control of the Cauliflower mosaic virus 35S promoter. When transgenic plants were treated with dexamethasone (DEX), a strong synthetic glucocorticoid, induction of replication and amplification of the 35S-driven FCP2IFN and synthesis of subgenomic mRNA for IFN were observed. Accumulation levels of amplified FCP2IFN were over 300 times higher than those of the 35S-driven FCP2IFN in the GVG1 x 2FR plant without the treatment and those of the mRNA for IFN were 30-230 times higher than in the previous, non-inducible mRNA amplification system. Without DEX treatment, no subgenomic mRNA for IFN was detected in the GVG1 x 2FR plant. The advantages and potential uses of this system are also discussed.
Treatable Forms of Retinitis Pigmentosa Associated with Systemic Neurological Disorders (2001)

In this chapter; we have described the role of nutritional supplements or selective dietary restriction (or both) on the maintenance and function of the retina and nervous system in some diseases. Oral vitamin A therapy has proven to be effective in the treatment of the common forms of retinitis pigmentosa. Bassen-Kornzweig disease can be treated with vitamin A and vitamin E and, in some cases, with vitamin K. Vitamin E therapy for Friedreich-like ataxia associated with retinitis pigmentosa has been shown to be effective in the short term. Classic Refsum's disease responds to a low phytol-low phytanic acid diet. Undoubtedly, future research will bring more insight into the biochemical pathways responsible for other diseases and, it is hoped, aid in developing treatments for additional retinal degenerations associated with systemic neurological disease.
A comparison of sleep profiles in patients with dementia with Lewy bodies and Alzheimer's disease (2000)

Both groups have extensive sleep problems. The DLB and AD groups have different sleep profiles that are of diagnostic importance and may suggest different treatment strategies. The results are consistent with those found from polysomnographic assessment and suggest that the questionnaires used are sensitive to detect differences previously documented with polysomnography.
T-buffer: fast visualization of relativistic effects in space-time (1990)

We have developed an innovative ray-tracing simulation algorithm to describe R elativistic E ffects in S pace T ime ("REST"). Our algorithm, called REST-frame , models light rays that have assumed infinite speed in conventional ray-tracing to have a finite speed in spacetime, and uses the non-Newtonian Lorentz Transformation to relate measurements of a single event in different inertial coordinate systems (inertial frames) . Our earlier work [5][6][7] explored the power of REST-frame as an experimentation tool to study the rich visual properties in natural world modeled by Special Relativity. Non-intuitive images of the anisotropic deformation ("warping") of space, the intensity concentration/spreading of light sources in spacetime, and the relativistic Doppler shift were visualized from our simulations.
An M protein with a single C repeat prevents phagocytosis of Streptococcus pyogenes: use of a temperature‐sensitive shuttle vector to deliver homologous sequences to the chromosome of S. pyogenes (1993)

The major virulence factor of the important human pathogen Streptococcus pyogenes is the M protein, which prevents phagocytosis of the bacterium. In different strains of streptococci, there are over 80 serologically different M proteins and there are additional M-like proteins, some of which bind immunoglobulins. Although the sequence of the M molecules differs among different S. pyogenes strains, all M proteins, and some of the immunoglobulin-binding molecules, have at least two copies of the C repeat region. We describe construction of a deletion mutation in S. pyogenes, which has only one C repeat copy, and show that the mutant strain is still resistant to phagocytosis. The mutation was constructed in vitro and used to replace the resident emm allele in an S. pyogenes strain. To facilitate homologous recombination into the streptococcal chromosome, we adapted a shuttle vector which is temperature sensitive for replication in Gram-positive bacteria but not in Gram-negative hosts. This new method for delivery of a homologous DNA fragment to the S. pyogenes chromosome is efficient and reproducible and should be of general use.
Novel C5a regulators in inflammatory disease (2005)

Complement is part of the innate immune system, acting to protect the host from microorganisms such as bacteria, and other foreign and abnormal cells. Although primarily protective, complement activation can also cause damage to the host. In a number of inflammatory diseases, including rheumatoid arthritis and dermatitis, there is excessive and inappropriate complement activation. Many of the toxic effects seen in these conditions are attributable to the excessive production of the anaphylatoxin C5a, which may contribute to both the initiation and progression of the disease. Therefore, the regulation of C5a production and modulation of its function are good pharmacological targets in these disorders. As yet, there are no effective agents for the therapeutic regulation of C5a in routine clinical practice. This review describes the role of C5a in inflammatory disease, animal models used to study C5a-related effects, and current strategies aimed at regulating C5a. There is also a discussion of the strengths and weaknesses of these approaches, and an outline of the likely progress of this class of drugs in the future.
Lifestyle Migration als Potenzial für ländlich-periphere Gebiete Europas? Die Bewertung wirtschaftlicher und sozialer Auswirkungen aus der Perspektive von Zuwanderern und lokalen Akteuren in Frankreich, Österreich und Spanien (2017)

In einigen ländlich-peripheren Gebieten Europas können in den letzten Jahrzehnten Zuwanderungen von sogenannten Lifestyle Migranten beobachtet werden. Am Beispiel von Regionen in Frankreich, Österreich und Spanien werden ökonomische und soziale Auswirkungen dieses Zuzugs diskutiert. Durch den Erwerb von (Ferien-)Immobilien "auf dem Land" agieren Briten in Westfrankreich, Deutsche in Südostspanien und Senioren in Ostösterreich als ökonomische Impulsgeber für die lokale Wirtschaft. Soziales Engagement beweisen die Zuwanderer durch nachbarschaftliche und wohltätige Unterstützungsleistungen. Ein aktives Einbringen in die Gesellschaft am neuen Wohnort wird in den meisten Fällen angestrebt. Auch wenn es sich bei vielen Zugezogenen um temporäre oder kurzfristige Zuwanderer handelt, so kann im Beitrag gezeigt werden, dass es sich um eine gewinnbringende Form der Einwanderung handelt. Ländliche Regionen können von der Zuwanderung von Lifestyle Migranten profitieren und die positive Bewertung der Lebensqualität vor Ort kann entscheidend zu einem Imagewandel ländlicher Räume Europas beitragen.
Comparison of Pancreas Juice Proteins from Cancer Versus Pancreatitis Using Quantitative Proteomic Analysis (2006)

Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer.
Reversible addition–fragmentation chain transfer graft copolymerization of styrene and m‐isopropenyl‐α,α′‐dimethylbenzyl isocyanate from polypropylene lanterns: Solid phases for scavenging applications (2005)

Abstract The γ‐initiated reversible addition–fragmentation chain transfer mediated free‐radical graft copolymerization of styrene and m ‐isopropenyl‐α,α′‐dimethylbenzyl isocyanate (TMI) from a polypropylene (PP) solid phase was performed with cumyl phenyldithioacetate (CPDA) as the chain‐transfer agent. The initial CPDA concentration was 8 × 10 −3 mol L −1 . Polymerizations were performed with a dose rate of 0.18 kGy h −1 at the ambient temperature. Initial comonomer mixtures with 15, 30, and 50 mol % TMI were used. Depending on the amount of TMI in the initial comonomer mixture, the plot of the grafting ratio versus the time showed two grafting regimes (for 15 and 50 mol % TMI) or one (for 30 mol % TMI). Scavenger lanterns with 15 and 50 mol % TMI featured two isocyanate loading regimes, the second with higher loading capacities. The scavenger lanterns with 30 mol % TMI showed a linear loading capacity over the full grafting ratio. A maximum loading capacity of 110 μmol per scavenger lantern was achieved with 50 mol % TMI at a grafting ratio of approximately 60 wt %. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 857–864, 2006