Miracle-dz/UniFAR-FTUs huggingface dataset:
Differentiation-dependent functional and epigenetic landscapes for cytokine genes in virus-specific CD8+ T cells

Although the simultaneous engagement of multiple effector mechanisms is thought to characterize optimal CD8+ T-cell immunity and facilitate pathogen clearance, the differentiation pathways leading to the acquisition and maintenance of such polyfunctional activity are not well understood. Division-dependent profiles of effector molecule expression for virus-specific T cells are analyzed here by using a combination of carboxyfluorescein succinimidyl ester dilution and intracellular cytokine staining subsequent to T-cell receptor ligation. The experiments show that, although the majority of naive CD8+ T-cell precursors are preprogrammed to produce TNF-α soon after stimulation and a proportion make both TNF-α and IL-2, the progressive acquisition of IFN-γ expression depends on continued lymphocyte proliferation. Furthermore, the extensive division characteristic of differentiation to peak effector activity is associated with the progressive dominance of IFN-γ and the concomitant loss of polyfunctional cytokine production, although this is not apparent for long-term CD8+ T-cell memory. Such proliferation-dependent variation in cytokine production appears tied to the epigenetic signatures within the ifnG and tnfA proximal promoters. Specifically, those cytokine gene loci that are rapidly expressed following antigen stimulation at different stages of T-cell differentiation can be shown (by ChIP) to have permissive epigenetic and RNA polymerase II docking signatures. Thus, the dynamic changes in cytokine profiles for naive, effector, and memory T cells are underpinned by specific epigenetic landscapes that regulate responsiveness following T-cell receptor ligation.
Insights into the Phosphoregulation of β‐Secretase Sorting Signal by the VHS Domain of GGA1

BACE (β‐site amyloid precursor protein cleaving enzyme, β‐secretase) is a type‐I membrane protein which functions as an aspartic protease in the production of β‐amyloid peptide, a causative agent of Alzheimer's disease. Its cytoplasmic tail has a characteristic acidic‐cluster dileucine motif recognized by the VHS domain of adaptor proteins, GGAs (Golgi‐localizing, γ‐adaptin ear homology domain, ARF‐interacting). Here we show that BACE is colocalized with GGAs in the trans‐Golgi network and peripheral structures, and phosphorylation of a serine residue in the cytoplasmic tail enhances interaction with the VHS domain of GGA1 by about threefold. The X‐ray crystal structure of the complex between the GGA1‐VHS domain and the BACE C‐terminal peptide illustrates a similar recognition mechanism as mannose 6‐phosphate receptors except that a glutamine residue closes in to fill the gap created by the shorter BACE peptide. The serine and lysine of the BACE peptide point their side chains towards the solvent. However, phosphorylation of the serine affects the lysine side chain and the peptide backbone, resulting in one additional hydrogen bond and a stronger electrostatic interaction with the VHS domain, hence the reversible increase in affinity.
Overt subjects in English: evidence for the marking of person in an English-Italian bilingual child

Data from one English-Italian bilingual child (1;10–3;1) are presented in this study which challenge the hypothesis that the consistent realization of overt subjects in English is caused by the emergence of finite verbal morphology in the child's grammar. The argument is made for the emergence of subjects as an independent grammatical property of English, namely the marking of person deixis. Throughout the period of observation there is a significant proportion of overt subjects in the child's English utterances appearing both with finite and non-finite verb forms. Production of subjects stabilizes at 90% of obligatory contexts when no morphological correlates of finiteness have been acquired yet. While subjects are produced at significantly lower rates in Italian, we observe the consolidation of a number of inflected forms marking person agreement. The emergence of overt subjects in English on the one hand, and of subject–verb agreement in Italian on the other suggest that this bilingual child is grammaticalizing the all-important function of person deixis in language-specific ways: the same function is expressed by different forms in the child's two languages.
A New Methodology for Assessing Social Work Practice: The Adaptation of the Objective Structured Clinical Evaluation (SW-OSCE)

The Objective Structured Clinical Evaluation (OSCE) methodology was originally developed to assess medical students. OSCE is a carefully scripted, standardized, simulated interview, in which students’ interactional skills are observed and assessed. Here it is examined for its potential use in assessing social work practice skills. The development of the Social Work OSCE (SW-OSCE) and the Clinical Competence-based Behavioural Checklist (CCBC) are described. Findings from a pilot study assessing MSW students’ clinical skills with explicit observable criteria of the CCBC are presented. A quantitative and qualitative mixed-methods data analysis was applied. The CCBC had high internal reliability, for both the overall sample and for the different case scenarios, with Cronbach's alpha values ranging from 0.888 to 0.965. The validity of the instrument was also examined: qualitative content analysis of the taped interviews indicated that clinical skills and cultural empathy are not synonymous. The racial/ethnic match between the student and the ‘client’ did not predict better rapport or more cultural empathy. Examination grades are not necessarily consistent with actual performance in either clinical competence or cultural empathy or vice versa. Nevertheless, the results provide some support for the use of the SW-OSCE as a tool for assessing performance in social work practice. They also indicate its potential for evaluating the outcomes of educational programmes.
3.8 A 0.45-to-0.7V 1-to-6Gb/S 0.29-to-0.58pJ/b source-synchronous transceiver using automatic phase calibration in 65nm CMOS

Supply voltage (VDD) scaling offers a means to greatly reduce power in serial link transceivers. Ideally, power efficiency at a given data rate can be improved by reducing VDD while increasing the number of multiplexed circuits operating in parallel at lower clock frequencies [1]. Though increasing the amount of parallelism is desirable to scale VDD, in practice, it is limited by two main factors. First, increased sensitivity to device variations (threshold voltage/dimension mismatch) at lower VDD makes it extremely challenging to generate equally spaced multi-phase clocks needed in multiplexed transmitter and receiver. Phase calibration methods can correct phase-spacing errors [2,3], but their effectiveness at lower VDD is limited as the calibration circuits themselves become sensitive to device variations. Second, as oscillator output swing reduces with VDD, its phase noise degrades, making low-noise clock generation difficult to implement with low power dissipation. Phase noise can be suppressed by embedding the oscillator in a wide bandwidth analog phase-locked loop (APLL), but conventional charge-pump-based APLLs are difficult to design at low supply voltages (VDD <;0.5V). Digital PLLs (DPLLs) can operate at low VDD, but they suffer from conflicting noise bandwidth tradeoffs, which prevent increasing the bandwidth to suppress oscillator phase noise adequately. In this paper, we present a phase-calibration method that enables the operation of a source-synchronous transceiver down to VDD of 0.45V. The energy efficiency and data-rate of the prototype transceiver scale from 0.29 to 0.58pJ/b and 1.3Gb/s to 6Gb/s, respectively, as VDD is varied from 0.45 to 0.7V.
#3: Continuous Labor Support

In this position paper—one of six care practice papers published by Lamaze International and reprinted here with permission—the benefit of continuous labor support is discussed and presented as an evidence-based practice that helps promote, protect, and support normal birth. The paper is written for childbearing women and their families. Women with continuous support are less likely to have a cesarean, an instrument delivery, and regional anesthesia. They are also less likely to report dissatisfaction with or negatively rate their childbirth experience. The value of the doula for both the laboring woman and her labor partner is discussed. The accompanying commentary—written by a leading proponent of maternity care practices—supports evidence that promotes continuous labor support. Lamaze International encourages women to plan for a supportive birth environment that includes continuous support.
Predictors Associated with Terminal Renal Function in Deceased Organ Donors in the Intensive Care Unit

Background:Factors determining renal function at organ recovery in deceased kidney donors are not well established. Methods:The authors studied the prevalence and risk factors associated with elevated prerecovery creatinine and calculated glomerular filtration rate in 458 deceased organ donors identified through the California Donor Transplant Network between January 2005 and December 2006. Data collected retrospectively included demographics, medical history, laboratory values, mechanism of death, and medical treatment in the intensive care unit. Factors were analyzed by both univariate and multivariate analysis. Results:There were 260 men and 198 women in the study. The age was 43.2 ± 14.9 yr, and body mass index was 26.9 ± 6.0 (mean ± SD). In multivariate analysis, several factors were important determinants of both prerecovery creatinine and glomerular filtration rate. Admission creatinine or glomerular filtration rate were major determinants of respective prerecovery values (P < 0.0001). Higher body mass index was associated with worse renal function (P < 0.01). Higher average glucose values and greater variability in glucose (when included) were associated with worse prerecovery renal function (P < 0.01). Administration of desmopressin acetate was highly associated with preserved renal function (P < 0.001). Lower platelet count (P < 0.0001) and proteinuria (P = 0.005) were also associated with worse renal function. Conclusion:The data identify several important factors that predict renal function at kidney recovery in deceased donors. In particular, tighter control of blood glucose may improve renal function in potential organ donors, but prospective studies are needed to confirm these findings.
Music, philosophy, and modernity

Introduction 1. Form, feeling, metaphysics, and music 2. Music, language, and the origins of modernity 3. Rhythm and Romanticism 4. Hegelianism and music 5. Music and the subjects of Romantics 6. Music, freedom, and the critique of metaphysics 7. Pro and contra Wagner 8. Music, language and being: Wittgenstein and Heidegger 9. Adorno: musical philosophy or philosophical music? Conclusion.
Safety and tolerability of high-intensity focused ultrasonography for noninvasive body sculpting: 24-week data from a randomized, sham-controlled study.

BACKGROUND High-intensity focused ultrasonography (HIFU) is a nonsurgical, noninvasive method for body sculpting in nonobese patients. The technique ablates subcutaneous adipose tissue by causing molecular vibrations that increase tissue temperature and induce rapid cell necrosis. OBJECTIVES The authors evaluate the long-term safety of a HIFU device for sculpting the abdomen and flanks. METHODS Adults with subcutaneous abdominal fat ≥2.5 cm in thickness who met screening criteria were randomized to receive HIFU treatment of the anterior abdomen and flanks at 1 of 3 energy levels (3 passes per patient): 47 J/cm(2) (141 J/cm(2) total), 59 J/cm(2) (177 J/cm(2) total), or 0 J/cm(2) (no energy applied; sham control). Safety was assessed for 24 weeks and included laboratory testing, physical examinations, and documentation of adverse events. RESULTS Adverse events (AE) included mild to moderate discomfort, ecchymosis, and edema, all of which were transient. There were no reports of scarring or burns and no clinically meaningful changes in lipid panel findings, inflammatory markers, or renal or hepatic function. Physical examination results were unremarkable. CONCLUSIONS This HIFU device exhibited an AE profile similar to that of sham treatment. There were no significant changes from baseline in laboratory values, including lipid levels.
Determination of Cortisol in Human Plasma by Isotope Dilution-Mass Spectrometry. Definitive Methods in Clinical Chemistry, I

A definitive method is described for the determination of cortisol in human plasma. The method is based on the principle of isotope dilution-mass spectrometry. The analytical procedure comprises the following steps: (1) Addition of [4-14C]cortisol to the plasma sample; (2) extraction of the 14C-labelled and of the non-labelled cortisol by dichloromethane; (3) purification of the cortisol fraction by column chromatography on Sephadex LH-20; (4) formation of the trimethylsilyl ether of cortisol methoxime; (5) selected ion monitoring at m/z-values 605, 607, 636 and 638 during gas liquid chromatography. The accuracy of the method is based on the high specificity of mass spectrometry and on the exact control of recovery employing the principle of isotope dilution. The precision of the method was evaluated by calculation of the coefficient of variation from day to day; this varied from 0.7-2.3% in the range of 256-845 nmol/l. The lower limit of detection (ratio of signal to noise 3:1) is 200 pg cortisol per sample.
Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers.

RATIONALE Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. OBJECTIVES Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. METHODS Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. MEASUREMENTS AND MAIN RESULTS A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory. ” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively. CONCLUSIONS The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
Symmetries and reversing symmetries of toral automorphisms

Toral automorphisms, represented by unimodular integer matrices, are investigated with respect to their symmetries and reversing symmetries. We characterize the symmetry groups of {GL}(n,) matrices with a simple spectrum through their connection with unit groups in orders of algebraic number fields. For the question of reversibility, we derive necessary conditions in terms of the characteristic polynomial and the polynomial invariants. We also briefly discuss extensions to (reversing) symmetries within affine transformations, to {PGL}(n,) matrices, and to the more general setting of integer matrices beyond the unimodular ones.
Clinical effects of at-home bleaching along with desensitizing agent application.

PURPOSE To evaluate whether the use of a desensitizing agent before at-home vital bleaching decreased this sensitivity. METHODS After informed consent, 60 subjects, 18-31 years of age, participated in the study and were divided into desensitizer and placebo groups. Before bleaching treatment with 16% carbamide peroxide (CP), a placebo or desensitizer gel (DG; 5% potassium nitrate and 2% sodium fluoride) was applied in the tray and used by patients for 10 minutes. Color was evaluated at the baseline, second and fourth week following the initial delivery of bleaching trays. Color change was measured using the Vita Classic Shade Guide arranged by value. The subjects recorded their perception of tooth sensitivity on a 0-4 scale. The bleaching treatment at each week recall was evaluated by repeated measures ANOVA. The percentage of patients with tooth sensitivity was evaluated by Chi-square test. The tooth intensity ratio (% of days with tooth sensitivity) as well as the tooth sensitivity intensity between groups were analyzed using chi-square and the Mann-Whitney tests, respectively (alpha = 0.05). RESULTS The use of DG did not affect the bleaching efficacy of the CP (P > 0.05). The prevalence and intensity of tooth sensitivity was similar for both groups (P > 0.05). However, participants from the placebo group had sensitivity in 33.6% of the bleaching days, which was significantly higher than the DG experimental group (20.1%) (P < 0.05).
Yeast mutant defective in phosphatidylcholine synthesis

The Saccharomyces cerevisiae opi3-3 mutant was shown to be defective in the synthesis of phosphatidylcholine via methylation of phosphatidylethanolamine. The opi3-3 mutant was isolated on the basis of an inositol excretion phenotype and was not auxotrophic for choline. Inositol, but not choline, stimulated growth of the mutant. The opi3-3 mutation was recessive and was genetically linked to the ino4 locus. When grown in the absence of exogenous choline, the opi3-3 mutant had a phospholipid composition consisting of 2 to 3% phosphatidylcholine compared with 40 to 50% in wild-type strains. In addition, the mutant accumulated elevated amounts of two intermediates, phosphatidylmonomethylethanolamine and phosphatidyldimethylethanolamine. The incorporation of label from [methyl-14C]methionine into phosphatidylcholine was reduced 80 to 90% in the mutant compared with wild-type strains. However, label was recovered in the intermediates phosphatidylmonomethylethanolamine and phosphatidyldimethylethanolamine. The mutant is believed to be defective in the third and possibly the second methylation reaction in the formation of phosphatidylcholine from phosphatidylethanolamine. The first methylation reaction appeared to be occurring at normal or even elevated levels. Based upon incorporation of choline into phosphatidylcholine, it is concluded that the opi3-3 mutant has no defect in the synthesis of phosphatidylcholine from exogenous choline. Furthermore, phosphatidylcholine represents over 25% of the phospholipid composition of the mutant when it is grown in the presence of exogenous choline.
Detection of inducible clindamycin resistance among clinical isolates of staphylococcus aureus in a tertiary care hospital

The resistance to different antimicrobial agents am ong staphylococci is an increasing problem. Clindamycin (CL) is considered to be one of the alternative dru g in these infections. Inducible clindamycin resist ance cannot be detected by the routine conventional antimicrobi al susceptibility test. This study demonstrates a s imple, reliable method (double-disc diffusion test) for de tecting inducible resistance to clindamycin in eryt hromycinresistance (ER-R) isolates of S. aureus . Therefore, this study was undertaken to detect in ducible clindamycin resistance among isolates of Staphylococcus aureus. To detect the prevalence of inducible clindamycin resistance among clinical isolates of Staphylococcus aureus in our hospital by Disk approximation test (D-test ). A total 450 isolates of Staphylococci aureus from various clinical samples were used in this st udy. A total 135 (30%) isolates were resistant to Erythromycin. Out of these 84 isolates were MRSA and 51 were MSSA. Constitutive clindamycin resistance (cMLSB) was 03.55%, Inducible clindamycin resistance (iMLSB) was 11.11% and MS Phenotype was 15.33% in all isolates of Staphylococci aureus . Conclusion: - In conclusion the D‐test is an easy, simple, test to perform along wi th routine susceptibility testing therefore D-test should be used as a mandatory method in routine disc diffusio n testing to detect inducible clindamycin resistanc e.
STUDIES ON ERYTHRO‐KINETICS IN INFANCY X. Red Cell Volume of Newborn Infants in Relation to Gestational Age

Red cell volume measurements were performed with a 51Cr‐dilution method in 27 newborn infants with a gestational age of 222–295 days. The results were in agreement with and supplemented earlier findings. A positive correlation was found between red cell volume and gestational age. After 230 days (±10 days) of intrauterine life, the red cell volume varied between 45 and 100 ml. After a gestational period of 280 days (±10 days) the red cell volume was 120–190 ml. The main source of the large variation probably arises from errors in determining the gestational age, and variations in amount of placental transfusion.
Vaccination and allergic disease: a birth cohort study.

OBJECTIVES We examined the effect of vaccination for diphtheria; polio; pertussis and tetanus; or measles, mumps, and rubella on the incidence of physician-diagnosed asthma and eczema. METHODS We used a previously established birth cohort in the West Midlands General Practice research database. RESULTS We found an association between vaccination and the development of allergic disease; however, this association was present only among children with the fewest physician visits and can be explained by this factor. CONCLUSIONS Our data suggest that currently recommended routine vaccinations are not a risk factor for asthma or eczema.
Transgene Insertion on Mouse Chromosome 6 Impairs Function of the Uterine Cervix and Causes Failure of Parturition1

Abstract The molecular mechanisms controlling the initiation of parturition remain largely undefined. We report a new animal model in which parturition does not occur. A line of mice expressing a human apolipoprotein B (APOB) gene fail to deliver their young if the transgene is present in homozygous (Tg/Tg), but not in heterozygous (Tg/Wt), form. Cloning and mapping of the transgene insertion locus indicate that 10 copies of the 80-kilobase APOB genomic fragment inserted into mouse chromosome 6 result in a small, 390-base pair deletion of mouse genomic DNA. Nine other lines expressing the transgene have normal labor, suggesting that transgene insertion in this mutant line disrupted a mouse gene crucial for successful parturition. The pathophysiology of parturition failure in these animals was defined using physiological, endocrinological, and morphological techniques. Results indicate that luteolysis occurs in Tg/Tg mice but is delayed by 1 day. Delivery did not occur in mutant mice at term after spontaneous luteolysis or even after removal of progesterone action by ovariectomy or antiprogestin treatment. Biomechanical and functional studies of the uterus and cervix revealed that the primary cause of failed parturition in Tg/Tg mice was not inadequate uterine contractions of labor but, rather, a rigid, inelastic cervix at term that was abnormally rich in neutrophils and tissue monocytes. Characterization of the transgene insertional mutant, Tg/Tg, indicates that progesterone withdrawal is insufficient to complete parturition in the presence of inadequate cervical ripening at term.