Miracle-dz/UniFAR-FTUs huggingface dataset:
Genes predisposing to autoimmunity augment constitutive major histocompatibility complex class II‐associated presentation of the self‐antigen IgG2abin vivo

The self‐antigen IgG2ab is poorly presented to a γ2ab 435–451‐reactive I‐Ad‐restricted T‐cell hybridoma unless available in high concentrations or targeted to Fcγ‐ or complement receptors. Environmental factors, probably the extent of microbial challenge, profoundly influence the constitutive γ2ab/I‐Ad presentation in IgCHb, H‐2d mice. Here we report also a strong genetic impact. Constitutive presentation was highly efficient in spleen and thymus of (NZB × BXSB)F1 mice, which inherit a predisposition to develop lupus. Presentation correlated with disease progression and the serum levels of IgG2ab and IgG2ab complement factor 3 complexes. The finding that constitutive presentation was by far most efficient in males indicated that it was augmented by the Y chromosome‐linked autoimmune acceleration Yaa gene. In line with previous data for healthy mice, constitutive γ2ab/I‐Ad presentation was most pronounced in the adherent spleen cell fraction and improved by further enrichment for dendritic cells. Notably, however, whereas in normal mice the γ2ab determinant was undetectable on B cells lacking surface IgG2ab, such B cells contributed considerably to constitutive presentation in (NZB × BXSB)F1 hybrids. Presumably this resulted from complement receptor‐mediated internalization of IgG2ab‐containing immune complexes formed in lupus. These data add to the evidence that B cells with self‐reactive receptors, known to exist in the mature repertoire, may present non‐cognate foreign antigen to anti‐foreign helper T lymphocytes and thus differentiate into autoantibody‐secreting cells, and might likewise account for the polyclonal B‐cell activation characteristic of several autoimmune syndromes.
High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide predict mortality in stable coronary artery disease: results from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study

Abstract Background: The simultaneous assessment of high-sensitivity cardiac troponin T (hscTnT) and NT-proBNP for predicting death in stable coronary artery disease (CAD) has yet not been examined. We investigated the additional contribution of hscTnT to the risk of mortality prediction of NT-proBNP in patients with stable CAD. Methods: We studied 1469 patients with stable CAD enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). hscTnT and NT-proBNP were measured in baseline samples using immunoassays (Roche Diagnostics, Germany). Results: Thirty-five percent (n=525) of the patients died during a median follow-up of 7 and a half years. In total 59.0% of the non-survivors and 25.2% of the survivors exhibited concentrations of hscTnT≥14 ng/L. Logistic regression analysis identified hscTnT and NT-proBNP as independent risk markers for short-term (1-year follow-up) and long-term (9-years follow-up) mortality. ROC curve analysis determined optimal univariate cut-offs at 14 ng/L and 443 µg/L for hscTnT (AUC 0.725, p<0.0001) and NT-proBNP (AUC 0.742, p<0.0001), respectively. Kaplan-Meier survival analysis based on optimized cut-offs for the simultaneous determination of both biomarkers confirmed the usefulness of additive hscTnT especially in prediction of short-term mortality. The prognostic benefit of the combined assessment of hscTnT and NT-proBNP could be confirmed by a significantly increased reclassification index (NRI) of 24.2%. Conclusions: The majority of non-survivors exhibited increased hscTnT concentrations above 14 ng/L. The simultaneous determination of NT-proBNP and hscTnT was superior for risk stratification compared to determining either marker alone. Especially the prediction of the clinically important 1-year mortality was significantly improved by addition of hscTnT to NT-proBNP.
DsbA is required for stability of the type IV pilin of enteropathogenic Escherichia coli

The periplasmic Escherichia coli enzyme DsbA catalyses the efficient formation of disulphide linkages in numerous extracytoplasmic proteins. Enteropathogenic E. coli, a major cause of infantile diarrhoea worldwide, expresses a type IV fimbria known as the bundle‐forming pilus that promotes adherence to tissue‐culture cells. In this study, we report that transposon insertions in the dsbA locus abolish adherence and dramatically reduce the level of bundlin, the major structural subunit of the pilus encoded by the bfpA locus. Adherence and bundlin levels are restored by complementation with the cloned dsbA gene. DsbA has no effect on bfpA transcription as measured with bfpA–lacZ fusions. Replacement of either cysteine codon 129 or 179 of bfpA with a serine codon results in reduced levels of bundlin, similar to the effect of the dsbA mutation. As is the case with dsbA mutants, this decreased level of bundlin is not due to decreased transcription. The half‐life of bundlin as detected by pulse‐chase experiments is dramatically reduced in a dsbA mutant in comparison to the wild type. The effect of DsbA on bundlin oxidation is independent of signal‐peptide processing. Thus, we demonstrate that the DsbA enzyme is critical for the biogenesis of a type IV fimbria because of the essential role of a disulphide bond in the stability of the major structural subunit. These data illuminate the early steps in the biogenesis of type IV fimbriae by demonstrating that newly synthesized prepilin is a transmembrane protein accessible to periplasmic and cytoplasmic processing enzymes.
Variable-Octave Complex Smoothing for Loudspeaker-Room Response Equalization

In this paper we present a technique for processing room responses using a variable-octave complex-domain (viz., time-domain) smoother so as to design low-order FIR equalization filters. Traditional techniques for room response processing, for equalization and other applications such as auralization, have focused on a constant-octave (e.g., 1/3 octave) using only magnitude domain smoothing of these room responses. However, recent research by Olive [7] has shown that room responses need to be processed with a high frequency resolution (e.g., 1/20th octave), especially in the low-frequency region, to characterize discrete room modes which are distinctly audible. Using such a high-resolution at higher frequencies of the room response results in relatively long model (or equivalently filter lengths) due to the undesirable over-fitting of the model in the high-frequency region. Moreover, auditory filters have wider bandwidth (viz., lower frequency resolution) in the high-frequency part of the human hearing. Hence, the present paper proposes a variable-octave complex-domain smoothing where a lower octave smoothing is performed in the high-frequency part of the room response. Thus this paper incorporates, simultaneously, the high low-frequency resolution requirement as well as the requirement of relatively lower-resolution fitting of the room response in the high-frequency part through a perceptually motivated approach. As will be shown, using this approach, there is a significant reduction in the filter order for loudspeaker-room equalization. A proposal for (i) an overall perceptually relevant smoothing scheme and, (ii)selection of the transition frequency between high- resolution smoothing (in the low-frequency region) and low- resolution smoothing in the high-frequency region will be presented.
Development and Testing of the Feasibility and Acceptability of a Tailored Dietary Intervention in Patients With Heart Failure

Purpose:The aim of this study was to describe how to develop a theory-based tailored dietary intervention (TADI) and test its feasibility and acceptability in patients with heart failure (HF). Methods:The development team consisted of experts in HF, nutrition, and clinical trials. Four patients with HF and 3 additional experts reviewed intervention materials and provided feedback. The 5-session TADI was developed from this feedback and tested in 5 patients with HF (60% women; mean age, 55 years). Participation and intervention completion rates were collected for feasibility test. In addition, data on dietary adherence and the factors affecting dietary adherence were collected at baseline and after the intervention for feasibility test. Data on patient acceptability were collected at the end of sessions. Results:Sixty percent of patients we approached expressed interest in this study. Five patients completed all of the sessions and follow-up data collection. Mean dietary sodium consumption decreased from 2.38 to 1.30 g/d. Among the factors affecting dietary adherence, skills showed the greatest increase. Patient acceptability scores for sessions 1, 2, 3, and 4 were 98%, 97%, 100%, and 100% of 100%, respectively. Conclusion:The TADI is ready for testing in larger sample studies to manage sodium intake.
Cost-effective priorities for global mammal conservation

Global biodiversity priority setting underpins the strategic allocation of conservation funds. In identifying the first comprehensive set of global priority areas for mammals, Ceballos et al. [Ceballos G, Ehrlich PR, Soberón J, Salazar I, Fay JP (2005) Science 309:603–607] found much potential for conflict between conservation and agricultural human activity. This is not surprising because, like other global priority-setting approaches, they set priorities without socioeconomic objectives. Here we present a priority-setting framework that seeks to minimize the conflicts and opportunity costs of meeting conservation goals. We use it to derive a new set of priority areas for investment in mammal conservation based on (i) agricultural opportunity cost and biodiversity importance, (ii) current levels of international funding, and (iii) degree of threat. Our approach achieves the same biodiversity outcomes as Ceballos et al.'s while reducing the opportunity costs and conflicts with agricultural human activity by up to 50%. We uncover shortfalls in the allocation of conservation funds in many threatened priority areas, highlighting a global conservation challenge.
Analysis of Multiple Exposures: An Empirical Comparison of Results From Conventional and Semi-Bayes Modeling Strategies

Background: Analysts of epidemiologic data often contend with the problem of estimating the independent effects of many correlated exposures. General approaches include assessing each exposure separately, adjusting for some subset of other exposures, or assessing all exposures simultaneously in a single model such as semi-Bayes modeling. The optimal strategy remains uncertain, and it is unclear to what extent different reasonable approaches influence findings. We provide an empirical comparison of results from several modeling strategies. Methods: In an occupational case-control study of lung cancer with 184 exposure substances, we implemented 6 modeling strategies to estimate odds ratios for each exposure-cancer association. These included one-exposure-at-a-time models with various confounder selection criteria (such as a priori selection or a change-in-the-estimate criterion) and semi-Bayes models, one version of which integrated information on previous evidence and chemical properties. Results: While distributions of odds ratios were broadly similar across the 6 analytic strategies, there were some differences in point estimates and in substances manifesting statistically significant odds ratios, particularly between strategies with few or no occupational covariates and those with many. Semi-Bayes models produced fewer statistically significant odds ratios than other methods. A simple semi-Bayes model that shrank all the 184 estimates to a common mean yielded nearly identical results to one that integrated considerable prior information. Conclusion: Different modeling strategies can lead to different results. Considering the conceptual and pragmatic difficulties of identifying confounders, these results suggest that it would be unwise to place uncritical reliance on any single strategy.
Brain stem projections of sensory and motor components of the vagus complex in the cat: I. The cervical vagus and nodose ganglion

The motor and sensory connections of the cervical vagus nerve and of its inferior ganglion (nodose ganglion) have been traced in the medulla oblongata of 32 adult cats with the neuroanatomical methods of horseradish peroxidase (HRP) histochemistry and amino acid autoradiography (ARG). In 14 of these subjects, an aqueous solution of HRP was applied unilaterally to the central end of the severed cervical vagus nerve. In 13 other cases, HRP was injected directly into the nodose ganglion. Three of these 13 subjects had undergone infranodose vagotomy 6 weeks prior to the HRP injection. A mixture of tritiated amino acid was injected into the nodose ganglion in five additional cats. The retrograde transport of HRP yielded reaction product in nerve fibers and perikarya of parasympathetic and somatic motoneurons in the medulla oblongata. Furthermore, a tetramethyl benzidine (TMB) method for visualizing HRP enabled the demonstration of anterograde and transganglionic transport, so that central sensory connections of the nodose ganglion and of the vagus nerve could also be traced. The central distribution of silver grain following injections of tritiated amino acids in the nodose ganglion corresponded closely with the distribution of sensory projections demonstrated with HRP, thus confirming the validity of HRP histochemistry as a method for tracing these projections. The histochemical and autoradiographic experiments showed that the vagus nerve enters the medulla from its lateral aspect in multiple fascicles and that it contains three major components—axons of preganglionic parasympathetic neurones, axons of skeletal motoneurons, and central processes of the sensory neurons in the nodose ganglion. Retrogradely labeled neurons were seen in the dorsal motor nucleus of X(dmnX), the nucleus ambiguus (nA), the nucleus retroambigualis (nRA), the nucleus dorsomedialis (ndm) and the spinal nucleus of the accessory nerve (nspA). The axons arising from motoneurons in the nA did not traverse the medulla directly laterally; rather, all of these axons were initially directed dorsomedially toward the dmnX, where they formed a hairpin loop and then accompanied the axons of dmnX neurons to their points of exit. Afferent fibers in the vagus nerve reached most of the subnuclei of the nTS bilaterally, with the more intense labeling being found on the ipsilateral side. Labeling of sensory vagal projections was also found in the area postrema of both sides and around neurons of the dmnX. These direct sensory projections terminating within the dmnX may provide an anatomical substrate for vagally mediated monosynpatic reflexes. Following deefferentiation by infranodose vagotomy 6 weeks prior to HRP injections into the nodose ganglion, a number of neurons in the dmnX were still intensely labeled with the HRP reaction product. The axons of these HRP‐labeled perikarya may constitute the bulbar component of the accessory nerve.
Contraceptive counseling among pediatric primary care providers in Western Pennsylvania: A survey-based study

Objectives: Data suggest that adolescents in the United States receive inadequate contraceptive counseling. This study sought to determine factors affecting pediatricians’ discussion of contraception with adolescent patients, with a specific focus on long-acting reversible contraception—implantable contraception and intrauterine devices. Methods: A cross-sectional survey was sent via email to a convenience sample of pediatric residents and pediatric primary care providers in Western Pennsylvania. Self-reported contraceptive counseling and prescribing practices in response to clinical vignettes were assessed. Results: Of potential participants (287), 88 (31%) responded. Younger providers and providers who had received contraceptive training were significantly more likely to discuss long-acting reversible contraception methods. Discussion of contraceptive methods also varied by both the age and the sexual history of the patient. Conclusion: Variation in contraceptive counseling potentially results in missed opportunities to counsel about and provide the most effective contraceptive methods. More uniform, universal provider training might alleviate some of these inconsistencies.
THE MYROSINASE-GLUCOSINOLATE SYSTEM, ITS ORGANISATION AND BIOCHEMISTRY

The myrosinase-glucosinolate system is involved in a range of biological activities affecting herbivorous insects, plants and fungi. The system characteristic of the order Capparales includes sulphur-containing substrates, the degradative enzymes myrosinases, and cofactors. The enzyme-catalyzed hydrolysis of glucosinolates initially involves cleavage of the thioglucoside linkage, yielding D-glucose and an unstable thiohydroximate-O-sulphonate that spontaneously rearranges, resulting in the production of sulphate and one of a wide range of possible reaction products. The products are generally a thiocyanate, isothiocyanate or nitrile, depending on factors such as substrate, pH or availability of ferrous ions. Glucosinolates in crucifers exemplify components that are often present in food and feed plants and are a major problem in the utilization of products from the plants. Toxic degradation products restrict the use of cultivated plants, e.g. those belonging to the Brassicaceae. The myrosinase-glucosinolate system may, however, have several functions in the plant. The glucosinolate degradation products are involved in defence against insects and phytopathogens. and potentially in sulphur and nitrogen metabolism and growth regulation. The compartmentalization of the components of the myrosinase-glucosinolate system and the cell-specific expression of the myrosinase represents a unique plant defence system. In this review, we summarize earlier results and discuss the organisation and biochemistry of the myrosinase-glucosinolate system.
Pharmacokinetics of radiotracers in human plasma during positron emission tomography

Many radiopharmaceuticals for positron emission tomography (PET) are substantially metabolized in peripheral organs. Pharmacological treatments intended to alter cerebral metabolism might also alter radiotracer metabolism, consequently altering the cerebral uptake. First‐order rate constants for the metabolism of PET tracers can be calculated by a linear graphical method from the precursor and metabolite concentrations measured in plasma extracts fractionated by HPLC. We tested the effects of specific pharmacological challenges on the plasma kinetics of six tracers used for PET studies of neurotransmission. The rate of O‐methylation of circulating [18F]fluorodopa, a tracer of dopa decarboxylase activity in brain, was unaffected by pretreatment with amantadine, an antagonist of glutamate receptors. [11C]Deprenyl, a tracer of monoamine oxidase activity, was rapidly metabolized to [11C]methamphetamine and polar metabolites in healthy volunteers. The net rate constant of this metabolism was three times higher in a group of subjects under treatment for epilepsy, consistent with induction of hepatic microsomal enzymes by antiepileptic drugs. [11C]Sch 23390, a ligand for dopamine D1 receptors, was rapidly metabolized to polar metabolites. The net rate constant of metabolism was unaffected by pretreatment with lorazepam. [11C]‐(S)‐Nicotine, a ligand for nicotinic receptors, was rapidly metabolized to [11C]‐(S)‐cotenine, which is less polar than the parent compound. Pretreatment with mazindol, a dopamine uptake inhibitor, was without effect on peripheral metabolism of [11C]‐(S)‐nicotine. [11C]WIN 35,428, a tropane derivative which labels dopamine uptake sites, was metabolized to a nonpolar metabolite, but so slowly that the rate constant of this process could not be calculated. [11C]Raclopride, a ligand for dopamine D2 receptors, was first metabolized to a nonpolar metabolite, which then yielded two hydrophilic metabolites. The initial metabolic step was substantially blocked by pretreatment with amphetamine, possibly indicative of competitive inhibition of microsomal oxidation. Together, these results indicate that the linear graphic method is useful for estimating the kinetics of the plasma metabolism of many widely used PET tracers. Drug–drug interactions were revealed in subjects treated with specific pharmacological agents prior to tracer administration. Synapse 34:124–134, 1999. © 1999 Wiley‐Liss, Inc.
Elastic, piezoelectric, and dielectric properties of 0.955Pb(Zn/sub 1/3/Nb/sub 2/3/)O/sub 3/-0.45PbTiO/sub 3/ single crystal with designed multidomains

The elastic, piezoelectric, and dielectric properties of a 0.955Pb(Zn/sub 1/3/Nb/sub 2/3/)O/sub 3/-0.045PbTiO/sub 3/ (PZN-4.5%PT) multi-domain single crystal, poled along [001] of the original cubic direction, have been determined experimentally using combined resonance and ultrasonic methods. At room temperature, the PZN-4.5%PT single crystal has rhombohedral symmetry. After being poled along [001], four degenerate states still remain. Statistically, such a domain-engineered crystal may be treated as having an average tetragonal symmetry, and its material constants were determined based on 4 mm symmetry. It was confirmed that the electromechanical coupling coefficient k/sub 33/ for the domain-engineered samples is >90%, and the piezoelectric constant d/sub 33/ is >2000 pC/N. A soft shear mode with a velocity of 700 m/s was found in the [110] direction. From the measured experimental data, the orientational dependence of phase velocities and electromechanical coupling coefficients was calculated. The results showed that the transverse and longitudinal coupling coefficients, k/sub 31/ and k/sub 33/, reach their maximum along [110] and [001], respectively.