Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding.

Cellular inhibitor of apoptosis (cIAP) proteins, cIAP1 and cIAP2, are important regulators of tumor necrosis factor (TNF) superfamily (SF) signaling and are amplified in a number of tumor types. They are targeted by IAP antagonist compounds that are undergoing clinical trials. IAP antagonist compounds trigger cIAP autoubiquitylation and degradation. The TNFSF member TWEAK induces lysosomal degradation of TRAF2 and cIAPs, leading to elevated NIK levels and activation of non-canonical NF-kappaB. To investigate the role of the ubiquitin ligase RING domain of cIAP1 in these pathways, we used cIAP-deleted cells reconstituted with cIAP1 point mutants designed to interfere with the ability of the RING to dimerize or to interact with E2 enzymes. We show that RING dimerization and E2 binding are required for IAP antagonists to induce cIAP1 degradation and protect cells from TNF-induced cell death. The RING functions of cIAP1 are required for full TNF-induced activation of NF-kappaB, however, delayed activation of NF-kappaB still occurs in cIAP1 and -2 double knock-out cells. The RING functions of cIAP1 are also required to prevent constitutive activation of non-canonical NF-kappaB by targeting NIK for proteasomal degradation. However, in cIAP double knock-out cells TWEAK was still able to increase NIK levels demonstrating that NIK can be regulated by cIAP-independent pathways. Finally we show that, unlike IAP antagonists, TWEAK was able to induce degradation of cIAP1 RING mutants. These results emphasize the critical importance of the RING of cIAP1 in many signaling scenarios, but also demonstrate that in some pathways RING functions are not required.

Empirical testing of genuine savings as an indicator of weak sustainability: a three-country analysis of long run trends

Genuine Savings has emerged as a widely-used indicator of sustainable development. In this paper, we use long-term data stretching back to 1870 to undertake empirical tests of the relationship between Genuine Savings (GS) and future well-being for three countries: Britain, the USA and Germany. Our tests are based on an underlying theoretical relationship between GS and changes in the present value of future consumption. Based on both single country and panel results, we find evidence supporting the existence of a cointegrating (long run equilibrium) relationship between GS and future well-being, and fail to reject the basic theoretical result on the relationship between these two macroeconomic variables. This provides some support for the GS measure of weak sustainability. We also show the effects of modelling shocks, such as World War Two and the Great Depression.

Choice, Deferral and Consistency

In this paper we study decision making in situations where the individual’s preferences are not assumed to be complete. First, we identify conditions that are necessary and sufficient for choice behavior in general domains to be consistent with maximization of a possibly incomplete preference relation. In this model of maximally dominant choice, the agent defers/avoids choosing at those and only those menus where a most preferred option does not exist. This allows for simple explanations of conflict-induced deferral and choice overload. It also suggests a criterion for distinguishing between indifference and incomparability based on observable data. A simple extension of this model also incorporates decision costs and provides a theoretical framework that is compatible with the experimental design that we propose to elicit possibly incomplete preferences in the lab. The design builds on the introduction of monetary costs that induce choice of a most preferred feasible option if one exists and deferral otherwise. Based on this design we found evidence suggesting that a quarter of the subjects in our study had incomplete preferences, and that these made significantly more consistent choices than a group of subjects who were forced to choose. The latter effect, however, is mitigated once data on indifferences are accounted for.

Weak-type estimates for Haar shift operators: Sharp power on the A(p) characteristic

"Vegeu el resum a l'inici del document del fitxer adjunt."

The Visual Dysphagia Questionnaire: Piloting a New Tool for Assessing Food Consistency-Dependent Dysphagia in Eosinophilic Esophagitis

Background and Aims: The international EEsAI study group is currently developing the first activity index specific for Eosinophilic Esophagitis (EoE). None of the existing dysphagia questionnaires takes into account the consistency of the ingested food that considerably impacts the symptom presentation. Goal: To develop an EoE-specific questionnaire assessing dysphagia associated with different food consistencies. Methods: Based on patient chart reviews, an expert panel (EEsAI study group) identified internationally standardized food prototypes typically associated with EoE-related dysphagia. Food consistencies were correlated with EoE-related dysphagia, also considering potential food avoidance. This Visual Dysphagia Questionnaire (VDQ) was then tested, as a pilot, in 10 EoE patients. Results: The following 9 food consistency prototypes were identified: water, soft foods (pudding, jelly), grits, toast bread, French fries, dry rice, ground meat, raw fibrous foods (eg. apple, carrot), solid meat. Dysphagia was ranked on a 5-point Likert scale (0=no difficulties, 5=very severe difficulties, food will not pass). Severity of dysphagia in the 10 EoE patients was related to the eosinophil load and presence of esophageal strictures. Conclusions: The VDQ will be the first EoE-specific tool for assessing dysphagia related to internationally defined food consistencies. It performed well in a pilot study and will now be further evaluated in a cohort study including 100 adult and 100 pediatric EoE patients.

Local and global consistency properties for student placement

In the context of resource allocation on the basis of priorities, Ergin (2002) identifies a necessary and sufficient condition on the priority structure such that the student-optimal stable mechanism satisfies a consistency principle. Ergin (2002) formulates consistency as a local property based on a fixed population of agents and fixed resources -- we refer to this condition as local consistency and to his condition on the priority structure as local acyclicity. We identify a related but stronger necessary and sufficient condition (unit acyclicity) on the priority structure such that the student-optimal stable mechanism satisfies a more standard global consistency property. Next, we provide necessary and sufficient conditions for the student-optimal stable mechanism to satisfy converse consistency principles. We identify a necessary and sufficient condition (local shift-freeness) on the priority structure such that the student-optimal stable mechanism satisfies local converse consistency. Interestingly, local acyclicity implies local shift-freeness and hence the student-optimal stable mechanism more frequently satisfies local converse consistency than local consistency. Finally, in order for the student-optimal stable mechanism to be globally conversely consistent, one again has to impose unit acyclicity on the priority structure. Hence, unit acyclicity is a necessary and sufficient condition on the priority structure for the student-optimal stable mechanism to satisfy global consistency or global converse consistency.

Consistency and optimality

Assume that the problem Qo is not solvable in polynomial time. For theories T containing a sufficiently rich part of true arithmetic we characterize T U {ConT} as the minimal extension of T proving for some algorithm that it decides Qo as fast as any algorithm B with the property that T proves that B decides Qo. Here, ConT claims the consistency of T. Moreover, we characterize problems with an optimal algorithm in terms of arithmetical theories.

Pre-Election Positions and Voting Behaviour in Parliament: Consistency among Swiss MPs

This article examines the determinants of positional incongruence between pre-election statements and post-election behaviour in the Swiss parliament between 2003 and 2009. The question is examined at the individual MP level, which is appropriate for dispersion-of-powers systems like Switzerland. While the overall rate of political congruence reaches about 85%, a multilevel logit analysis detects the underlying factors which push or curb a candidate's propensity to change his or her mind once elected. The results show that positional changes are more likely when (1) MPs are freshmen, (2) individual voting behaviour is invisible to the public, (3) the electoral district magnitude is not small, (4) the vote is not about a party's core issue, (5) the MP belongs to a party which is located in the political centre, and (6) if the pre-election statement dissents from the majority position of the legislative party group. Of these factors, the last one is paramount.

Effects of MRI scan acceleration on brain volume measurement consistency.

PURPOSE: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency. MATERIALS AND METHODS: In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images. For quantitative analysis, differences in composite width (CW, a measure of image similarity) and boundary shift integral (BSI, a measure of whole-brain atrophy) were calculated. RESULTS: Intra- and intersession comparisons of CW and BSI measures from scans with equal acceleration demonstrated excellent scan-rescan accuracy, even at the highest acceleration applied. Pairs-of-scans acquired with different accelerations exhibited poor scan-rescan consistency only when differences in the acceleration factor were maximized. A change in the coil hardware between compared scans was found to bias the BSI measure. CONCLUSION: The most important findings are that the accelerated acquisitions appear to be compatible with the assessment of high-quality quantitative information and that for highest scan-rescan accuracy in serial scans the acquisition protocol should be kept as consistent as possible over time. J. Magn. Reson. Imaging 2012;36:1234-1240. ©2012 Wiley Periodicals, Inc.

The robustness of the weak selection approximation for the evolution of altruism against strong selection.

The weak selection approximation of population genetics has made possible the analysis of social evolution under a considerable variety of biological scenarios. Despite its extensive usage, the accuracy of weak selection in predicting the emergence of altruism under limited dispersal when selection intensity increases remains unclear. Here, we derive the condition for the spread of an altruistic mutant in the infinite island model of dispersal under a Moran reproductive process and arbitrary strength of selection. The simplicity of the model allows us to compare weak and strong selection regimes analytically. Our results demonstrate that the weak selection approximation is robust to moderate increases in selection intensity and therefore provides a good approximation to understand the invasion of altruism in spatially structured population. In particular, we find that the weak selection approximation is excellent even if selection is very strong, when either migration is much stronger than selection or when patches are large. Importantly, we emphasize that the weak selection approximation provides the ideal condition for the invasion of altruism, and increasing selection intensity will impede the emergence of altruism. We discuss that this should also hold for more complicated life cycles and for culturally transmitted altruism. Using the weak selection approximation is therefore unlikely to miss out on any demographic scenario that lead to the evolution of altruism under limited dispersal.

Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM) was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK), which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6% and 98.4% of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100% seroprotection (>0.15 µg/mL) with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT) was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7%, 100% and 99.9%, respectively, for DTP/Hib-BM, three lots altogether and 99.2%, 100% and 100% for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries.

BACKGROUND: Obesity is increasing worldwide because developing countries are adopting Western high-fat foods and sedentary lifestyles. In parallel, in many of them, hypertension is rising more rapidly, particularly with age, than in Western countries. OBJECTIVE: To assess the relationship between adiposity and blood pressure (BP) in a developing country with high average BP (The Seychelles, Indian Ocean, population mainly of African origin) in comparison to a developed country with low average BP (Switzerland, population mainly of Caucasian origin). DESIGN: Cross-sectional health examination surveys based on population random samples. SETTING: The main Seychelles island (Mahé) and two Swiss regions (Vaud-Fribourg and Ticino). SUBJECTS: Three thousand one hundred and sixteen adults (age range 35-64) untreated for hypertension. MEASUREMENTS: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), systolic and diastolic blood pressure (SBP and DBP, mean of two measures). METHODS: Scatterplot smoothing techniques and gender-specific linear regression models. RESULTS: On average, SBP and DBP were found to increase linearly over the whole variation range of BMI, WHR and WC. A modest, but statistically significant linear association was found between each indicator of adiposity and BP levels in separate regression models controlling for age. The regression coefficients were not significantly different between the Seychelles and the two Swiss regions, but were generally higher in women than in men. For the latter, a gain of 1.7 kg/m(2) in BMI, of 4.5 cm in WC or of 3.4% in WHR corresponded to an elevation of 1 mmHg in SBP. For women, corresponding figures were 1.25 kg/m(2), 2.5 cm and 1.8% respectively. Regression coefficients for age reflected a higher effect of this variable on both SBP and DBP in the Seychelles than in Switzerland. CONCLUSION: These findings suggest a stable linear relation of adiposity with BP, independent of age and body fat distribution, across developed and developing countries. The more rapid increase of BP with age observed in the latter countries are likely to reflect higher genetic susceptibility and/or higher cumulative exposure to another risk factor than adiposity.

Laser-ultraviolet-A induced ultra weak photon emission in human skin cells: A biophotonic comparison between keratinocytes and fibroblasts.

Photons participate in many atomic and molecular interactions and processes. Recent biophysical research has discovered an ultraweak radiation in biological tissues. It is now recognized that plants, animal and human cells emit this very weak biophotonic emission which can be readily measured with a sensitive photomultiplier system. UVA laser induced biophotonic emission of cultured cells was used in this report with the intention to detect biophysical changes between young and adult fibroblasts as well as between fibroblasts and keratinocytes. With suspension densities ranging from 1-8 x 106 cells/ml, it was evident that an increase of the UVA-laser-light induced photon emission intensity could be observed in young as well as adult fibroblastic cells. By the use of this method to determine ultraweak light emission, photons in cell suspensions in low volumes (100 microl) could be detected, in contrast to previous procedures using quantities up to 10 ml. Moreover, the analysis has been further refined by turning off the photomultiplier system electronically during irradiation leading to the first measurements of induced light emission in the cells after less than 10 micros instead of more than 100 milliseconds. These significant changes lead to an improvement factor up to 106 in comparison to classical detection procedures. In addition, different skin cells as fibroblasts and keratinocytes stemming from the same donor were measured using this new highly sensitive method in order to find new biophysical insight of light pathways. This is important in view to develop new strategies in biophotonics especially for use in alternative therapies.

Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in severe obesity is mediated by inflammation but not hypoxia.

CONTEXT Adipose tissue hypoxia and endoplasmic reticulum (ER) stress may link the presence of chronic inflammation and macrophage infiltration in severely obese subjects. We previously reported the up-regulation of TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in adipose tissue of severely obese type 2 diabetic subjects. OBJECTIVES The objective of the study was to examine TWEAK and Fn14 adipose tissue expression in obesity, severe obesity, and type 2 diabetes in relation to hypoxia and ER stress. DESIGN In the obesity study, 19 lean, 28 overweight, and 15 obese nondiabetic subjects were studied. In the severe obesity study, 23 severely obese and 35 control subjects were studied. In the type 2 diabetes study, 11 type 2 diabetic and 36 control subjects were studied. The expression levels of the following genes were analyzed in paired samples of sc and visceral adipose tissue: Fn14, TWEAK, VISFATIN, HYOU1, FIAF, HIF-1a, VEGF, GLUT-1, GRP78, and XBP-1. The effect of hypoxia, inflammation, and ER stress on the expression of TWEAK and Fn14 was examined in human adipocyte and macrophage cell lines. RESULTS Up-regulation of TWEAK/Fn14 and hypoxia and ER stress surrogate gene expression was observed in sc and visceral adipose tissue only in our severely obese cohort. Hypoxia modulates TWEAK or Fn14 expression in neither adipocytes nor macrophages. On the contrary, inflammation up-regulated TWEAK in macrophages and Fn14 expression in adipocytes. Moreover, TWEAK had a proinflammatory effect in adipocytes mediated by the nuclear factor-kappaB and ERK but not JNK signaling pathways. CONCLUSIONS Our data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity.