Miracle-dz/UniFAR-FTUs huggingface dataset:
The 26-kD transmembrane form of tumor necrosis factor alpha on activated CD4+ T cell clones provides a costimulatory signal for human B cell activation

Interleukin 4 (IL-4) induces immunoglobulin (Ig)E and IgG4 synthesis in human B cells. In addition to IL-4, costimulatory signals provided by activated CD4+ T cells are required for productive IgG4 and IgE synthesis. Here we report that the 26-kD transmembrane form of tumor necrosis factor alpha (mTNF-alpha), which is rapidly expressed on CD4+ T cell clones after activation, contributes to the costimulatory signals resulting in IL-4-dependent Ig synthesis by B cells, including IgG4 and IgE production. mTNF-alpha expression was induced on T cell clones within 2 h after activation with concanavalin A. Peak expression was observed at 24 h, followed by a gradual decrease, but appreciable levels of mTNF-alpha were still detectable 72 h after activation. The presence of the 26-kD membrane form of TNF-alpha on activated T cell clones was confirmed by immunoprecipitation. Monoclonal antibodies (mAbs) recognizing mTNF-alpha, or the p55 TNF receptor, inhibited IgM, IgG, IgG4, and IgE synthesis induced by IL-4 and activated CD4+ T cell clones in cultures of highly purified surface IgD+ B cells. The anti- TNF-alpha mAbs also blocked Ig production in cultures in which the activated CD4+ T cell clones were replaced by their plasma membranes. Furthermore, pretreatment of the plasma membranes with anti-TNF-alpha mAbs strongly reduced their capacity to stimulate B cells to produce Ig in the presence of IL-4, indicating that the anti-TNF-alpha mAbs blocked the effects of mTNF-alpha. Anti-TNF-alpha mAbs did not affect IgM, IgG, IgG4, or IgE synthesis induced by anti-CD40 mAbs and IL-4 in the absence of CD4+ T cells, supporting the notion that the anti-TNF- alpha mAbs indeed interfered with the costimulatory, contact-mediated signal provided by T cells, or their membranes. Collectively these results indicate that mTNF-alpha, which is rapidly induced after activation of CD4+ T cells, participates in productive T-B cell interactions resulting in IL-4-induced Ig production. This is a novel property of the T cell membrane form of TNF-alpha.
Engineering Earnings in Britain, 1914-68

SUMMARY The paper presents weekly earnings data for the British engineering industry over 1914-68 and comparable unemployment statistics. Additional information is provided to allow calculation of standard hourly and weekly earnings. The series cover the two key bargaining groups in the engineering industry, fitters and labourers, and 28 separate labour market areas across the whole geographical space of Great Britain. The main purpose of the paper is to provide an important additional source of earnings data which can be used for a variety of purposes, but a number of analyses of a particular subject, the regional earnings structure, is also undertaken.
Under the Surface

The present study yields an in-depth examination of the interpersonal and affective world of high-security and detention prisoners with possible (Psychopathy Checklist: Screening Version [PCL:SV] ≥ 13) and strong (PCL:SV ≥ 18) indications of psychopathy. A group of male inmates (n = 16) was compared with noncriminal and non–personality disordered controls (n = 35) on measures of self and other (Young Schema Questionnaire–Short Form [YSQ-SF], Inventory of Interpersonal Problems–Circumplex Scales [IIP-C]), and the experience and regulation of affect (Positive and Negative Affect Schedule [PANAS], Emotion Control Questionnaire 2 [ECQ2]). Results confirm the established grandiose, dominant, and callous characteristics of the psychopath (PCL:SV, Structured Clinical Interview for DSM-IV Axis II Disorders [SCID-II], DSM-IV and ICD-10 Personality Questionnaire [DIP-Q], IIP-C), while demonstrating personal distress and important nuances and variations in psychopathic offenders’ interpersonal and affective functioning (YSQ-SF, PANAS, ECQ2, SCID-II, DIP-Q). These preliminary findings support, expand, and challenge the ordinary portrayal of the psychopath and, if replicated in larger samples, point to a need for an expansion or reformulation of the concept, measurement, and treatment of psychopathy.
Generation of a conditionally null allele of the laminin α1 gene

Laminins are heterotrimeric glycoproteins of the basement membranes. Laminin 1 (α1, β1, γ1) is the major laminin expressed during early mouse embryogenesis. To gain access to the physiological function of laminin α1 chain, we developed a conditionally null allele of its encoding gene (Lama1) using the cre/loxP system. Floxed‐allele‐carrying mice (Lama1flox/flox) display no overt phenotype. Lama1flox/flox mice were crossed with transgenic deleter mice (CMV‐Cre) to generate Lama1‐deficient mice (Lama1Δ/Δ). Lama1Δ/Δ embryos die during the early postimplantation period after embryonic day 6.5. They lack Reichert's membrane, an extraembryonic basement membrane in which laminin α1 is normally highly expressed. In parallel, Lama1Δ/Δ embryos display 1) parietal and visceral endoderm differentiation defects with altered expression of cytokeratin 19 and GATA4, respectively, and 2) an induction of apoptosis. This new mouse model is of particular interest as it will allow time‐ and tissue‐specific inactivation of the Lama1 gene in various organs. genesis 43:59–70, 2005. © 2005 Wiley‐Liss, Inc.
Modulation Scheme for Three-Phase Differential-Mode Ćuk Inverter

Three-phase differential-mode inverters are single-stage inverters, which have the potential to reduce the number of devices and cost with higher power density. Among such inverter topologies, differential-mode three-phase Ćuk inverter (DTCI) has some advantage over other topologies, including modularity, lower number of switches, bidirectional power flow capability, and galvanic isolation. DTCI is a promising configuration for renewable-/alternative-energy applications with isolated and nonisolated structures. The continuous modulation scheme (CMS), which was introduced originally for the DTCI, activates all of three modules of the inverter. CMS increases the circulating power in modules and hence increases inverter power loss. This paper describes a discontinuous modulation scheme (DMS) for the DTCI which deactivates one module at a time resulting in a discontinuous operation of the inverter modules. The experimental open- and closed-loop results of DMS- and CMS-based DTCI are provided and compared. DMS reduces the circulating power, device voltage ratings, and mitigates the DTCI losses. The DTCI exhibits a nonlinear voltage gain with both DMS and CMS. It has been demonstrated that by feed-forwarding the input voltage and incorporating a static linearization method, the harmonic distortion of the output voltage is considerably reduced.
Revised prevalence estimates of mental disorders in the United States: using a clinical significance criterion to reconcile 2 surveys' estimates.

BACKGROUND Current US mental disorder prevalence estimates have limited usefulness for service planning and are often discrepant. Data on clinical significance from the National Institute of Mental Health Epidemiologic Catchment Area Program (ECA) and the National Comorbidity Survey (NCS) were used to produce revised estimates, for more accurate projections of treatment need and further explication of rate discrepancies. METHODS To ascertain the prevalence of clinically significant mental disorders in each survey, responses to questions on life interference from, telling a professional about, or using medication for symptoms were applied to cases meeting symptom criteria in the ECA (n = 20,861) and NCS (n = 8098). A revised national prevalence estimate was made by selecting the lower estimate of the 2 surveys for each diagnostic category, accounting for comorbidity, and combining categories. RESULTS Using data on clinical significance lowered the past-year prevalence rates of "any disorder" among 18- to 54-year-olds by 17% in the ECA and 32% in the NCS. For adults older than 18 years, the revised estimate for any disorder was 18.5%. Using the clinical significance criterion reduced disparities between estimates in the 2 surveys. Validity of the criterion was supported by associations with disabilities and suicidal behavior. CONCLUSIONS Establishing the clinical significance of disorders in the community is crucial for estimating treatment need. More work should be done in defining and operationalizing clinical significance, and characterizing the utility of clinically significant symptoms in determining treatment need even when some criteria of the disorder are not met. Discrepancies in ECA and NCS results are largely due to methodologic differences.
Effects of CP-532,623 and Torcetrapib, Cholesteryl Ester Transfer Protein Inhibitors, on Arterial Blood Pressure

ILLUMINATE, the phase 3 morbidity and mortality trial of the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, plus atorvastatin terminated in 2006. The underlying morbidity and mortality cause remains undetermined. In addition to lipoprotein changes, off-target increases in blood pressure (BP), sodium, bicarbonate, and aldosterone and potassium decreases were described. We report nonclinical and clinical studies using torcetrapib and a closely related CETP inhibitor, CP-532,623, to further characterize this pharmacology. Pressor effects of torcetrapib and CP-532,623 were observed in monkeys and human subjects. CETP inhibition and high-density lipoprotein cholesterol elevation were demonstrated. In humans, high- versus low-dose CP-532,623 produced significantly greater pressor effects despite similar maximal CETP inhibition. Inhibition of CETP was seen 48 hours post dose, whereas BP elevation dissipated by 24 hours, temporally dissociating CETP inhibition from BP changes. These data, and structural similarities between the compounds, support the conclusion that the BP effects are related to chemotype. We also observed an acute aldosterone increase without changes in renin in monkeys. Continuous BP measurements showed persistent elevations, whereas aldosterone changes were transient, suggesting that increases in BP were not directly the result of renin-angiotensin-aldosterone system activation and may, in part, be due to direct effects on blood vessels or other nongenomic effects.
Smart Aging Platform for Evaluating Cognitive Functions in Aging: A Comparison with the MoCA in a Normal Population

Background: Smart Aging is a Serious games (SGs) platform in a 3D virtual environment in which users perform a set of screening tests that address various cognitive skills. The tests are structured as 5 tasks of activities of daily life in a familiar environment. The main goal of the present study is to compare a cognitive evaluation made with Smart Aging with those of a classic standardized screening test, the Montreal Cognitive Assessment (MoCA). Methods: One thousand one-hundred thirty-one healthy adults aged between 50 and 80 (M = 64.3 ± 8.3) were enrolled in the study. They received a cognitive evaluation with the MoCA and the Smart Aging platform. Participants were grouped according to their MoCA global and specific cognitive domain (i.e., memory, executive functions, working memory, visual spatial elaboration, language, and orientation) scores and we explored differences among these groups in the Smart Aging indices. Results: One thousand eighty-six older adults (M = 64.0 ± 8.0) successfully completed the study and were stratified according to their MoCA score: Group 1 with MoCA < 27 (n = 360); Group 2 with 27 ≥ MoCA < 29 (n = 453); and Group 3 with MoCA ≥ 29 (n = 273). MoCA groups significantly differed in most of the Smart Aging indices considered, in particular as concerns accuracy (ps < 0.001) and time (ps < 0.001) for completing most of the platform tasks. Group 1 was outperformed by the other two Groups and was slower than them in these tasks, which were those supposed to assess memory and executive functions. In addition, significant differences across groups also emerged when considering the single cognitive domains of the MoCA and the corresponding performances in each Smart Aging task. In particular, this platform seems to be a good proxy for assessing memory, executive functions, working memory, and visual spatial processes. Conclusion: These findings demonstrate the validity of Smart Aging for assessing cognitive functions in normal aging. Future studies will validate this platform also in the clinical aging populations.
Keap1 modulates the redox cycle and hepatocyte cell cycle in regenerating liver

Keap1 negatively controls the activity of transcription factor Nrf2. This Keap1/Nrf2 pathway plays a critical role in combating oxidative stress. We aimed at determining whether and how Keap1 modulates the cell cycle of replicating hepatocytes during liver regeneration. Two-thirds partial hepatectomy (PH) was performed on wild-type mice and Keap1+/− (Keap1 knockdown) mice. We found that, following PH, Keap1 knockdown resulted in a delay in S-phase entry, disruption of S-phase progression, and loss of mitotic rhythm of replicating hepatocytes. These events are associated with dysregulation of c-Met, EGFR, Akt1, p70S6K, Cyclin A2, and Cyclin B1 in regenerating livers. Astonishingly, normal regenerating livers exhibited the redox fluctuation coupled with hepatocyte cell cycle progression, while keeping Nrf2 quiescent. Keap1 knockdown caused severe disruption in both the redox cycle and the cell cycle of replicating hepatocytes. Thus, we demonstrate that Keap1 is a potent regulator of hepatic redox cycle and hepatocyte cell cycle during liver regeneration.
Suction vs water seal after pulmonary resection: a randomized prospective study.

STUDY OBJECTIVE To evaluate whether suction or water seal is superior in the management of chest tubes after pulmonary resection. DESIGN A prospective, randomized, controlled trial. After an initial, brief period of suction, patients were randomized to water seal or - 20 cm H(2)O suction. SETTING University hospital. PATIENTS Sixty-eight patients who underwent wedge resection, segmentectomy, or lobectomy were included in the study. Those patients who underwent reoperative surgery or lung volume reduction surgery were excluded. RESULTS There were 34 patients in each group. The two groups were evenly matched for age, sex, operation performed, severity of lung disease, and nutritional status. Fifteen patients in each group (44%) had an air leak at the completion of surgery. The duration of the air leak was shorter in the water seal group than in the suction group (mean +/- SEM, 1.50 +/- 0.32 days vs 3.27 +/- 0.80 days, respectively; p = 0.05). The mean times to removal of chest tubes were 3.33 +/- 0.35 days in the water seal group and 5.47 +/- 0.98 days in the suction group (p = 0.06). The length of stapled parenchyma was measured for each patient and averaged 24.9 cm for the water seal group and 18.5 cm for the suction group (p = 0.18). When corrected for the length of staple lines, the duration of air leaks and days with chest tube were dramatically lower in the water seal group (p = 0.02 and p = 0.02, respectively). CONCLUSION Placing chest tubes on water seal after a brief period of suction after pulmonary resection shortens the duration of the air leak and likely decreases the time that the chest tubes remain in place. Adoption of this practice may result in lower morbidity and lower hospital costs.
Multiple paternity and kin recognition mechanisms in a guppy population

Help directed toward kin (nepotism) is an important example of social behaviour. Such helping behaviour requires a mechanism to distinguish kin from nonkin. The prevailing kin recognition hypothesis is that when familiarity is a reliable cue of relatedness, other mechanisms of recognition will not evolve. However, when familiarity is an unreliable cue of relatedness, kin recognition by phenotype matching is instead predicted to evolve. Here we use genetic markers to show that guppies (Poecilia reticulata) from a population in a tributary of the Paria River in Trinidad are characterized by a high degree of multiple mating with 95% of broods having more than one sire and some dams having offspring sired by six males. These levels of multiple mating are the highest reported among live‐bearing fishes. The mean relatedness of brood‐mates was 0.36 (as compared to 0.5 for full‐siblings). Therefore, familiarity does not seem to be a reliable mechanism to assess full‐sibling relatedness. Using two‐choice behavioural trials, we found that juveniles from this population use both phenotype matching and familiarity to distinguish kin from nonkin. However, we did not find strong evidence that the guppies use these mechanisms to form shoals of related individuals as adults, which is similar to results from other guppy populations in Trinidad. The use of both familiarity and phenotype matching is discussed in the context of the Paria River guppy population's mating system and ecology. Overall, these data provide support for the kin recognition hypothesis and increase our understanding of the evolution of kin recognition systems.
Validation of an asthma questionnaire for use in healthcare workers

Background: Previous studies have described increased occurrence of asthma among healthcare workers, but to our knowledge there are no validated survey questionnaires with which to study this occupational group. Aims: To develop, validate, and refine a new survey instrument on asthma for use in epidemiological studies of healthcare workers. Methods: An initial draft questionnaire, designed by a multidisciplinary team, used previously validated questions where possible; the occupational exposure section was developed by updating health services specific chemical lists through hospital walk-through surveys and review of material safety data sheets. A cross-sectional validation study was conducted in 118 non-smoking subjects, who also underwent bronchial challenge testing, an interview with an industrial hygienist, and measurement of specific IgE antibodies to common aeroallergens. Results: The final version consisted of 43 main questions in four sections. Time to completion of the questionnaire ranged from 13 to 25 minutes. Test–retest reliability of asthma and allergy items ranged from 75% to 94%, and internal consistency for these items was excellent (Cronbach’s α ⩾ 0.86). Against methacholine challenge, an eight item combination of asthma related symptoms had a sensitivity of 71% and specificity of 70%; against a physician diagnosis of asthma, this same combination showed a sensitivity of 79% and specificity of 98%. Agreement between self-reported exposures and industrial hygienist review was similar to previous studies and only moderate, indicating the need to incorporate more reliable methods of exposure assessment. Against the aerollergen panel, the best combinations of sensitivity and specificity were obtained for a history of allergies to dust, dust mite, and animals. Conclusions: Initial evaluation of this new questionnaire indicates good validity and reliability, and further field testing and cross-validation in a larger healthcare worker population is in progress. The need for development of more reliable occupational exposure assessment methods that go beyond self-report is underscored.
Prenatal exposure to endocrine disruptors: a developmental etiology for polycystic ovary syndrome

iv TABLE OF CONTENTS . vi LIST OF TABLES . viii LIST OF FIGURES . ix LIST OF ABBREVIATIONS . x INTRODUCTION . 1 Background . 2 Luteinizing Hormone Hypersecretion . 2 Hyperinsulinemia . 3 Hyperandrogenism . 3 Ovarian Dysfunction . 7 Clinical Presentation . 7 Biological Onset of Polycystic Ovary Syndrome and Fetal Programming . 8 Association of Environmental Factors with PCOS . 15 Endocrine Disruptors . 16 Specific Aims . 21
Localization of alg, opr, phn, pho, 4.5S RNA, 6S RNA, tox, trp, and xcp genes, rrn operons, and the chromosomal origin on the physical genome map of Pseudomonas aeruginosa PAO

The genes encoding the rrn operons, the 4.5S and 6S RNAs, elements of protein secretion, and outer membrane proteins F and I, and regulatory as well as structural genes for exotoxin A, alkaline phosphatase, and alginate and tryptophan biosynthesis, were assigned on the SpeI/DpnI macrorestriction map of the Pseudomonas aeruginosa PAO chromosome. The zero point of the map was relocated to the chromosomal origin of replication.
Bacterial colonization and biofilm development on minimally processed vegetables

Bacterial biofilms have been observed and reported on food and food‐processing surfaces and can contribute to increased risks for product quality and food safety. The colonization of fruit and vegetables by pectynolitic bacteria like Pseudonomas fluorescens attributable to conditions such as soft rot, can also manifest as biofilms. A developed biofilm structure can provide a protective environment for pathogens such as Listeria monocytogenes reducing the effectiveness of sanitisers and other inhibitory agents. Understanding the colonization of bacteria on leaf surfaces is essential to the development of a better understanding of the leaf ecology of vegetable products. Studies of microbial colonization of leaf surfaces have been conducted using SEM and more recently using confocal microsocpy techniques. In the current study, a Leica TCS NT laser scanning confocal microscope was used to investigate biofilm formation using vital fluorescence staining on intact vegetable leaves. Reflection contrast and fluorescence three‐dimensional imaging successfully delineated bacterial and biofilm morphology without disturbing the bacterial or leaf surface structure. The results demonstrate the presence and development of biofilm on the surface of lettuce. The biofilms appeared to originate on the cuticle in distinct micro‐environments such as in the natural depression of the stomata, or in the intercellular junction. Bacteria also adhered to and developed biofilm colonies within an hour of contact and with clean stainless steel surfaces. Our study investigates the progression of biofilm formation from leaf colonization, and will assist in characterising the critical mechanisms of plant/host interaction and facilitate the development of improved preservation, sanitising and packaging strategies for minimally processed vegetable products.
Is there a preferable DES in diabetic patients? A critical appraisal of the evidence

Drug‐eluting stent (DES) therapy reduces restenosis in patients with diabetes when compared with bare metal stent implantation. There are significant differences between commercially available DES platforms both in terms of design characteristics and clinical outcomes. Randomized active‐comparator inter‐DES trials powered for clinical endpoints are unlikely to be performed in patients with diabetes, however, direct comparison randomized trials utilizing surrogate endpoints support a superior anti‐restenotic efficacy with sirolimus‐ versus paclitaxel‐eluting stents. Thrombotic stent occlusion may be higher in patients with diabetes compared with nondiabetic patients, though there is no clear signal of a safety differential between the two platforms. Insufficient data on comparative performance in diabetics exist in relation to the approved zotarolimus‐eluting and everolimus‐eluting stent platforms. If all other factors are equal, then there seems to be no reason why the diabetic patient should not receive treatment with the sirolimus‐eluting stent, which appears to have superior antirestenotic efficacy in this patient group. © 2008 Wiley‐Liss, Inc.