gebhart/patrepeval huggingface dataset:
Total and high density lipoprotein cholesterol in the serum and risk of mortality: evidence of a threshold effect. (1985)

The association of serum total and high density lipoprotein cholesterol values with 15 year mortality was examined in a cohort of 10 059 Israeli male civil servants and municipal employees aged 40 and above. In 618 of 1664 deaths in the cohort (37%) coronary heart disease was documented as the cause of death. Risk of mortality was analysed by quintiles. Neither total mortality nor coronary heart disease mortality rose with serum cholesterol concentrations up to 5.6 mmol/1 (216 mg/100 ml), representing 60% of the sample. Rates rose appreciably only in the highest quintile (cholesterol concentration greater than 6.2 mmol/1; greater than 241 mg/100 ml). High density lipoprotein cholesterol was similarly, although inversely, associated with total mortality when expressed as a percentage of total cholesterol. The inverse association of high density lipoprotein cholesterol with coronary heart disease mortality was, in contrast, continuous. These data support the hypothesis that over most of the range of cholesterol values coronary mortality risk and total mortality risk are nearly independent of total cholesterol and most probably independent of low density lipoprotein cholesterol values. In multivariate analysis a low concentration of high density lipoprotein cholesterol appeared to be more predictive of mortality than a high concentration of total cholesterol. The latter was very weakly related to mortality from all causes after multivariate adjustment. It is concluded that the findings of this and other major epidemiological studies support the notion of a "threshold effect." Success in reducing mortality through the pharmacological reduction of serum cholesterol in hypercholesterolaemic patients does not warrant a similar approach in people with average or slightly above average values. These findings appear to provide support for a "high risk strategy" in reducing the risk of coronary heart disease.
Portable spherical array probe for volumetric real-time optoacoustic imaging at centimeter-scale depths (2013)

We report on a novel hand-held imaging probe for real-time optoacoustic visualization of deep tissues in three dimensions. The system incorporates an annular two-dimensional array of ultrasonic sensors densely distributed on a spherical surface. Simultaneous recording and processing of time-resolved data from all the channels enables acquisition of entire volumetric data sets for each illumination laser pulse. The proposed solution utilizes a transparent membrane in order to allow efficient coupling of optoacoustically generated waves to the ultrasonic detectors while avoiding direct contact of the imaged object with the coupling medium. The hand-held approach further allows convenient handling of both pre-clinical experiments as well as clinical measurements in human subjects. Here we demonstrate an imaging speed of 10 volumetric frames per second with spatial resolution down to 200 micrometers in the imaged region while also achieving imaging depth of more than 1.5 cm in living tissues without signal averaging.
Allergen‐specific immunotherapy provides immediate, long‐term and preventive clinical effects in children and adults: the effects of immunotherapy can be categorised by level of benefit ‐the centenary of allergen specific subcutaneous immunotherapy (2012)

Allergen Specific Immunotherapy (SIT) for respiratory allergic diseases is able to significantly improve symptoms as well as reduce the need for symptomatic medication, but SIT also has the capacity for long-term clinical effects and plays a protective role against the development of further allergies and symptoms. The treatment acts on basic immunological mechanisms, and has the potential to change the pathological allergic immune response. In this paper we discuss some of the most important achievements in the documentation of the benefits of immunotherapy, over the last 2 decades, which have marked a period of extensive research on the clinical effects and immunological background of the mechanisms involved. The outcome of immunotherapy is described as different levels of benefit from early reduction in symptoms over progressive clinical effects during treatment to long-term effects after discontinuation of the treatment and prevention of asthma. The efficacy of SIT increases the longer it is continued and immunological changes lead to potential long-term benefits. SIT alone and not the symptomatic treatment nor other avoidance measures has so far been documented as the therapy with long-term or preventive potential. The allergic condition is driven by a subset of T-helper lymphocytes (Th2), which are characterised by the production of cytokines like IL-4, and IL-5. Immunological changes following SIT lead to potential curative effects. One mechanism whereby immunotherapy suppresses the allergic response is through increased production of IgG4 antibodies. Induction of specific IgG4 is able to influence the allergic response in different ways and is related to immunological effector mechanisms, also responsible for the reduced late phase hyperreactivity and ongoing allergic inflammation. SIT is the only treatment which interferes with the basic pathophysiological mechanisms of the allergic disease, thereby creating the potential for changes in the long-term prognosis of respiratory allergy. SIT should not only be recognised as first-line therapeutic treatment for allergic rhinoconjunctivitis but also as secondary preventive treatment for respiratory allergic diseases.
Inhibition of insulin receptor phosphorylation by peptides derived from major histocompatibility complex class I antigens. (1989)

Peptides from the alpha 1 region (residues 61-85) of the D and K molecules of the major histocompatibility complex class I antigens inhibit insulin-induced tyrosine kinase activity of the purified human insulin receptors (IRs) as measured both by autophosphorylation and IR-mediated substrate [poly(Glu,Tyr)] phosphorylation. Half-maximal effect of the Dk-(61-85) peptide on IR autophosphorylation is obtained at 1.2 microM, and almost complete inhibition of IR kinase activity is obtained at 10 microM peptide. The corresponding K kappa-(61-85) peptide has a significantly weaker effect on autophosphorylation. No such effects are observed with nine peptides of similar length, but unrelated to major histocompatibility complex class I antigens. Neither of the major histocompatibility complex class I-derived peptides has any effect on the constitutively active kinase of a genetically engineered cytoplasmic IR domain. Further, insulin binding to IR is unaltered in the presence of the major histocompatibility complex class I-derived peptides. The inhibitory activity of the peptides on insulin-induced IR phosphorylation facilitated the observation that IRs require insulin to become substrate for an independent tyrosine kinase. In the presence of an inhibitory peptide, the constitutively active cytoplasmic IR kinase domain only phosphorylates the intact IR in the presence of insulin. We conclude that the tyrosine kinase activity of IRs may be altered by peptide interaction at an allosteric site and, moreover, IRs require insulin to assume a conformation permitting phosphorylation by an independent kinase.
High-Affinity Binding of the Neonatal Fc Receptor to Its IgG Ligand Requires Receptor Immobilization (1997)

The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the acquisition of passive immunity by the fetus or newborn. In adult mammals, FcRn also binds IgG and returns it to the bloodstream, thus protecting IgG from a default degradative pathway. Biosensor assays have been used to characterize the interaction of a soluble form of FcRn with IgG. We use the statistical method of cross-validation to show that there are two classes of noninteracting binding sites, and these are sufficient to account for previously observed nonlinear Scatchard plots of FcRn/IgG binding data. We demonstrate that immobilization of FcRn on the biosensor surface reproduces the high-affinity IgG binding observed for membrane-bound FcRn, whereas immobilization of IgG results in lower affinity binding similar to that of the FcRn/IgG interaction in solution. The dependence of FcRn/IgG binding affinity on the coupled molecule provides further evidence in support of the previously hypothesized model that an FcRn dimer forms the high-affinity IgG binding site.
The Psa Fimbriae of Yersinia pestis Interact with Phosphatidylcholine on Alveolar Epithelial Cells and Pulmonary Surfactant (2006)

The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae with adhesive properties of potential importance for the pathogenesis of plague, including pneumonic plague. The Psa fimbriae mediate bacterial binding to human alveolar epithelial cells. The Psa fimbriae bound mostly to one component present in the total lipid extract from type II alveolar epithelial cells of the cell line A549 separated by thin-layer chromatography (TLC). The Psa receptor was identified as phosphatidylcholine (PC) by TLC using alkali treatment, molybdenum blue staining, and Psa overlays. The Psa fimbriae bound to PC in a dose-dependent manner, and binding was inhibited by phosphorylcholine (ChoP) and choline. Binding inhibition was dose dependent, although only high concentrations of ChoP completely blocked Psa binding to PC. In contrast, less than 1 muM of a ChoP-polylysine polymer inhibited specifically the adhesion of Psa-fimbriated Escherichia coli to PC, and type I (WI-26 VA4) and type II alveolar epithelial cells. These results indicated that the homopolymeric Psa fimbriae are multimeric adhesins. Psa also bound to pulmonary surfactant, which covers the alveolar surface as a product of type II alveolar epithelial cells and includes PC as the major component. The observed dose-dependent interaction of Psa with pulmonary surfactant was blocked by ChoP. Interestingly, surfactant did not inhibit Psa-mediated bacterial binding to alveolar cells, suggesting that both surfactant and cell membrane PC retain Psa-fimbriated bacteria on the alveolar surface. Altogether, the results indicate that Psa uses the ChoP moiety of PC as a receptor to mediate bacterial binding to pulmonary surfactant and alveolar epithelial cells.
Isomerization of 11-cis- Retinoids to All-trans-retinoids in Vitro and in Vivo (2001)

The regeneration of 11-cis-retinal, the universal chromophore of the vertebrate retina, is a complex process involving photoreceptors and adjacent retinal pigment epithelial cells (RPE). 11-cis-Retinal is coupled to opsins in both rod and cone photoreceptor cells and is photoisomerized to all-trans-retinal by light. Here, we show that RPE microsomes can catalyze the reverse isomerization of 11-cis-retinol to all-trans-retinol (and 13-cis-retinol), and membrane exposure to UV light further enhances the rate of this reaction. This conversion is inhibited when 11-cis-retinol is in a complex with cellular retinaldehyde-binding protein (CRALBP), providing a clear demonstration of the protective effect of retinoid-binding proteins in retinoid processes in the eye, a function that has been long suspected but never proven. The reverse isomerization is nonenzymatic and specific to alcohol forms of retinoids, and it displays stereospecific preference for 11-cis-retinol and 13-cis-retinol but is much less efficient for 9-cis-retinol. The mechanism of reverse isomerization was investigated using stable isotope-labeled retinoids and radioactive tracers to show that this reaction occurs with the retention of configuration of the C-15 carbon of retinol through a mechanism that does not eliminate the hydroxyl group, in contrast to the enzymatic all-trans-retinol to 11-cis-retinol reaction. The activation energy for the conversion of 11-cis-retinol to all-trans-retinol is 19.5 kcal/mol, and 20.1 kcal/mol for isomerization of 13-cis-retinol to all-trans-retinol. We also demonstrate that the reverse isomerization occurs in vivo using exogenous 11-cis-retinol injected into the intravitreal space of wild type and Rpe65-/- mice, which have defective forward isomerization. This study demonstrates an uncharacterized activity of RPE microsomes that could be important in the normal flow of retinoids in the eye in vivo during dark adaptation.
Study Of Laser Beam Modulation Influence On Structure Of Materials Produced By Additive Manufacturing (2016)

In the article, the study of laser beam modulation influence on the structure of materials produced by one of the methods of additive manufacturing as selective laser melting (SLM) is provided. For the purpose of creating a smoother temperature gradient and the optimal conditions of the heat and mass transfer in the melting pool, an experimental stand for SLM-processing with the system of laser beam power density distribution modulation was created. The laser beam modulation gives promising results for higher parameters’ combinations such as power more than 150W and scanning velocity more than 50 mm/sec. The single track’s formation was produced by different power density distribution as Gaussian, Flat-top and Inverse Gaussian (Donut). All the received single tracks were studied with the use of optical and SEM microscopy. The results produce important data about reducing the width of powder consolidation zone, more even structure and higher productivity.
Polyurethane and Related Foams (2006)

Polyurethane and Related Foams: Chemistry and Technology is an in-depth examination of the current preparation, processing, and applications of polyurethanes (PURs) and other polymer foams. Drawing attention to novel raw materials, alternative blowing agents, and new processing methods, the book accentuates recent innovations that meet incre
Barriers to the Use of Health Status Measures in Clinical Investigation, Patient Care, and Policy Research (1989)

Despite growing interest and sophistication in health status assessment, these measures are not widely used in settings where they would be appropriate. The reasons include conceptual, methodologic, practical, and attitudinal barriers, some of which are common to a variety of applications (e.g., clinical research, patient care, or policy research). These barriers include skepticism about the validity and importance of self-rated health; preferences for physiologic outcomes or death rates; unfamiliarity with questionnaire scores; a paucity of direct instrument comparisons to aid in selection; and the costs of pilot testing, data collection, and data manipulation. In clinical trials, the uncertain responsiveness of questionnaire instruments to small but clinically important changes may be of particular concern. For patient care, additional barriers are posed by the need for rapidly processing data, the need for providing highly understandable results to clinicians, and clinicians' uncertainty about how to use the information. In policy research, there is often insufficient time for responding (with health status measurement) to decision makers' needs, and many have reservations about concepts such as quality-adjusted life years that arise from health status measurement. To facilitate a better intuitive grasp of health status scores, more comparisons with traditional clinical scales and physiologic measures are needed. More effort should be given to demonstrating (and improving) the responsiveness of scales to clinically important changes and to developing very brief questionnaires. Better education of health professionals about these measurement techniques is needed, as well as better methods of presenting results. Finally, a "laboratory" to provide measurement services to investigators and clinicians may make use of these scales more attractive.
Allosteric Modulation of Family 3 GPCRs (2005)

Abstract This article reviews recent advances towards an understanding of the transmembrane structure, its activation and binding sites of family 3 G‐Protein‐Coupled Receptors (3‐GPCRs). First, the prediction of their 3D structure via homology models based on the crystal structure of bovine rhodopsin will be discussed. Then, different kinetic mechanisms of ligand‐binding inside the heptahelical domain are presented before an overview of most common structural motifs of 3‐GPCR allosteric modulators will be given. Here, special focus lies in the characterization of their binding pocket within the transmembrane domain as well as their interaction with crucial amino acids. The overview of available mutation data inside the ligand‐binding domains as well as the influence of exchanged amino acids on the activity of different receptors leads to the question whether allosteric ligands of family 3 GPCRs bind to the same binding pocket and if there exists a common binding site of family 1 GPCRs and family 3 GPCRs.
Theophylline metabolism in acute asthma with MxA‐indicated viral infection (2006)

Viral infection appeared to affect theophylline metabolism. Flow cytometric assay of lymphoid MxA protein expression in whole blood is an easy and useful method of evaluating viral infection in acute asthma exacerbation.
Transparent thin-film transistors with zinc indium oxide channel layer (2005)

High mobility, n-type transparent thin-film transistors (TTFTs) with a zinc indium oxide (ZIO) channel layer are reported. Such devices are highly transparent with ∼85% optical transmission in the visible portion of the electromagnetic spectrum. ZIO TTFTs annealed at 600 °C operate in depletion-mode with threshold voltages −20 to −10V and turn-on voltages ∼3V less than the threshold voltage. These devices have excellent drain current saturation, peak incremental channel mobilities of 45–55cm2V−1s−1, drain current on-to-off ratios of ∼106, and inverse subthreshold slopes of ∼0.8V∕decade. In contrast, ZIO TTFTs annealed at 300 °C typically operate in enhancement-mode with threshold voltages of 0–10V and turn-on voltages 1–2V less than the threshold voltage. These 300 °C devices exhibit excellent drain–current saturation, peak incremental channel mobilities of 10–30cm2V−1s−1, drain current on-to-off ratios of ∼106, and inverse subthreshold slopes of ∼0.3V∕decade. ZIO TTFTs with the channel layer deposited near room temperature are also demonstrated. X-ray diffraction analysis indicates the channel layers of ZIO TTFTs to be amorphous for annealing temperatures up to 500 °C and polycrystalline at 600 °C. Low temperature processed ZIO is an example of a class of high performance TTFT channel materials involving amorphous oxides composed of heavy-metal cations with (n−1)d10ns0(n⩾4) electronic configurations.
Translating dosages from animal models to human clinical trials—revisiting body surface area scaling (2015)

Body surface area (BSA) scaling has been used for prescribing individualized dosages of various drugs and has also been recommended by the U.S. Food and Drug Administration as one method for using data from animal model species to establish safe starting dosages for first-in-human clinical trials. Although BSA conversion equations have been used in certain clinical applications for decades, recent recommendations to use BSA to derive interspecies equivalents for therapeutic dosages of drug and natural products are inappropriate. A thorough review of the literature reveals that BSA conversions are based on antiquated science and have little justification in current translational medicine compared to more advanced allometric and physiologically based pharmacokinetic modeling. Misunderstood and misinterpreted use of BSA conversions may have disastrous consequences, including underdosing leading to abandonment of potentially efficacious investigational drugs, and unexpected deadly adverse events. We aim to demonstrate that recent recommendations for BSA are not appropriate for animal-to-human dosage conversions and use pharmacokinetic data from resveratrol studies to demonstrate how confusion between the "human equivalent dose" and "pharmacologically active dose" can lead to inappropriate dose recommendations. To optimize drug development, future recommendations for interspecies scaling must be scientifically justified using physiologic, pharmacokinetic, and toxicology data rather than simple BSA conversion.
Fetal Heart Rate Patterns in Infants in Whom Necrotizing Enterocolitis Develops (1980)

Perinatal changes in fetal heart rate (FHR) were monitored in infants in whom necrotizing enterocolitis (NEC) developed. Eleven of 16 monitoring strips indicated severe FHR changes consistent with perinatal hypoxia, two indicated mild changes, two indicated tachycardia alone, and only one was normal. Severe variable FHR decelerations indicating umbilical cord compression occurred in four cases, persistent late FHR decelerations occurred in two cases, persistent late and severe variable FHR decelerations occurred in two cases, prolonged bradycardia occurred in two cases, and bradycardia with persistent late FHR decelerations occurred in one case. These findings confirm that NEC does occur in infants with perinatal hypoxia and indicate that intestinal ischemia may occur before delivery and after delivery from hypoxia and acidosis from lung disease, exchange transfusion, or sepsis. Perinatal monitoring may become an important determinant in identifying the infant in whom NEC will develop.
Discovering New Enzymes and Metabolic Pathways:  Conversion of Succinate to Propionate by Escherichia coli (2000)

The Escherichia coli genome encodes seven paralogues of the crotonase (enoyl CoA hydratase) superfamily. Four of these have unknown or uncertain functions; their existence was unknown prior to the completion of the E. coli genome sequencing project. The gene encoding one of these, YgfG, is located in a four-gene operon that encodes homologues of methylmalonyl CoA mutases (Sbm) and acyl CoA transferases (YgfH) as well as a putative protein kinase (YgfD/ArgK). We have determined that YgfG is methylmalonyl CoA decarboxylase, YgfH is propionyl CoA:succinate CoA transferase, and Sbm is methylmalonyl CoA mutase. These reactions are sufficient to form a metabolic cycle by which E. coli can catalyze the decarboxylation of succinate to propionate, although the metabolic context of this cycle is unknown. The identification of YgfG as methylmalonyl CoA decarboxylase expands the range of reactions catalyzed by members of the crotonase superfamily.
Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. (1992)

Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis patient populations carry the major CF mutation (delta F508). Since different Jewish ethnic groups tended to live as closed isolates until recent times, high frequencies of specific mutations are expected among the remainder cystic fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence the severity of the disease. It is therefore expected that different mutations will be associated with either severe or mild phenotype. Direct genomic sequencing of exons included in the two nucleotide-binding folds of the putative CFTR protein was performed on 119 Israeli cystic fibrosis patients from 97 families. One sequence alteration which is expected to create a termination at residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57 (60%) are of Ashkenazi origin. Together with the delta F508 (23% in this group), G542X, N1303K, and 1717-1G----A mutations, the identification of 92% of cystic fibrosis chromosomes of Ashkenazi origin becomes possible. Patients homozygous for the W1282X mutation (n = 16) and patients heterozygous for the delta F508 and W1282X mutations (n = 22) had similarly severe disease, reflected by pancreatic insufficiency, high incidence of meconium ileus (37% and 27%, respectively), early age at diagnosis, poor nutritional status, and variable pulmonary function. In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in the Ashkenazi Jewish patient population in Israel. This nonsense mutation is associated with presentation of severe disease.