A
bstract
We study global 1- and (
d −
2)-form symmetries for gauge theories based on disconnected gauge groups which include charge conjugation. For pure gauge theories, the 1-form symmetries are ...shown to be non-invertible. In addition, being the gauge groups disconnected, the theories automatically have a ℤ
2
global (
d −
2)-form symmetry. We propose String Theory embeddings for gauge theories based on these groups. Remarkably, they all automatically come with twist vortices which break the (
d −
2)-form global symmetry. This is consistent with the conjectured absence of global symmetries in Quantum Gravity.
Evaluation of right ventricular (RV) function after tricuspid valve surgery is complex. The objective was to identify the most appropriate RV function parameters for this purpose. This prospective ...study included 70 patients undergoing cardiac and tricuspid valve (TV) surgery. RV size and function parameters were determined at 3 months and 1-year post-surgery. Categorical variables were analyzed with the McNemar test and numerical variables with the Student's t-test for related samples or, when non-normally distributed, the Wilcoxon test. Spearman's rho was used to determine correlations between variables at 3 months and 1 year. RV diameters were reduced at 3 months post-surgery and were then unchanged at 1 year. Tricuspid annular plane systolic excursion (TAPSE) and S' wave values were worse at 3 months and then improved at 1 year (t-score-2.35, p 0.023; t-score-2.68; p 0.010). There was no significant reduction in free wall longitudinal strain (LS) or shortening fraction (SF) at 3 months (t-score 1.421 and - 1.251; p 0.218 and 0.172), and they were only slightly below pre-surgical values at 1 year. No relationship was found between RV function parameters and mortality or major complications. During the first few months after TV surgery, LS may be a more appropriate parameter to evaluate global ventricular function in comparison to TAPSE. At 1 year, good correlations are observed between TAPSE, S' wave, and LS values.
The continuous technological advancement of nanomedicine has enabled the development of novel vehicles for the effective delivery of therapeutic substances. Synthetic drug delivery systems are ...nano-sized carriers made from various materials that can be designed to deliver therapeutic cargoes to cells or tissues. However, rapid clearance by the immune system and the poor targeting profile of synthetic drug delivery systems are examples of the pressing obstacles faced in nanomedicine, which have directed the field toward the development of alternative strategies. Extracellular vesicles (EVs) are nanoscale particles enclosed by a protein-rich lipid bilayer; they are released by cells and are considered to be important mediators of intercellular communication. Owing to their natural composition, EVs have been suggested to exhibit good biocompatibility and to possess homing properties to specific cell types. Combining EVs with synthetic nanoparticles by defined hybridization steps gives rise to a novel potential drug delivery tool, i.e., EV-based hybrid systems. These novel therapeutic vehicles exhibit potential advantageous features as compared to synthetic drug delivery systems such as enhanced cellular uptake and cargo delivery, immuno-evasive properties, capability of crossing biological barriers, and tissue targeting profile. Here, we provide an overview of the various strategies practiced to produce EV-based hybrid systems and elucidate those advantageous features obtained by synthetic drug delivery systems upon hybridization with EVs.
We explore the hypothesis that fluctuations in commodity prices are an important driver of business cycles in small emerging market economies (EMEs). First, we document that commodity prices exhibit ...strong comovement with other macro variables along the business cycle of these economies; and that a common factor accounts for most of the time series dynamics of these commodity prices. Guided by these stylized facts, we embed a commodity sector into a dynamic, stochastic, multi-country business cycle model of EMEs where exogenous fluctuations in commodity prices coexist with other driving forces. Commodity prices follow a common dynamic factor structure in the model. When estimated with EMEs data, the model gives to commodity shocks, mostly in the form of perturbations to their common factor, a paramount role when accounting for aggregate dynamics: more than a third of the variance of real output across the EMEs considered is associated to commodity price shocks. The model also performs well when accounting for other business cycle facts. A further amplification mechanism is a “spillover” effect from commodity prices to interest rates. Yet, sometimes, positive commodity price shocks have also cushioned other negative domestic shocks, particularly during the fast recovery from the world financial crisis.
There is a need to increase and maintain physical activity in patients with chronic obstructive pulmonary disease (COPD). We assessed 12-month efficacy and effectiveness of the Urban Training ...intervention on physical activity in COPD patients.This randomised controlled trial (NCT01897298) allocated 407 COPD patients from primary and hospital settings 1:1 to usual care (n=205) or Urban Training (n=202). Urban Training consisted of a baseline motivational interview, advice to walk on urban trails designed for COPD patients in outdoor public spaces and other optional components for feedback, motivation, information and support (pedometer, calendar, physical activity brochure, website, phone text messages, walking groups and a phone number). The primary outcome was 12-month change in steps·day
measured by accelerometer.Efficacy analysis (with per-protocol analysis set, n=233 classified as adherent to the assigned intervention) showed adjusted (95% CI) 12-month difference +957 (184-1731) steps·day
between Urban Training and usual care. Effectiveness analysis (with intention-to-treat analysis set, n=280 patients completing the study at 12 months including unwilling and self-reported non-adherent patients) showed no differences between groups. Leg muscle pain during walks was more frequently reported in Urban Training than usual care, without differences in any of the other adverse events.Urban Training, combining behavioural strategies with unsupervised outdoor walking, was efficacious in increasing physical activity after 12 months in COPD patients, with few safety concerns. However, it was ineffective in the full population including unwilling and self-reported non-adherent patients.
Summary
That functional traits should affect individual performance and, in turn, determine fitness and population growth, is a foundational assumption of trait‐based ecology. This assumption is, ...however, not supported by a strong empirical base.
Here, we measured simultaneously two individual performance metrics (survival and growth), seven traits and 10 environmental properties for each of 3981 individuals of 205 species in a 50‐ha stem‐mapped subtropical forest. We then modelled survival/growth as a function of traits, environments and trait × environment interactions, and quantified their relative importance at both the species and individual levels.
We found evidence of alternative functional designs and multiple performance peaks along environmental gradients, indicating the presence of complicated trait × environment interactions. However, such interactions were relatively unimportant in our site, which had relatively low environmental variations. Moreover, individual performance was not better predicted, and trait × environment interactions were not more likely detected, at the individual level than at the species level.
Although the trait × environment interactions might be safely ignored in relatively homogeneous environments, we encourage future studies to test the interactive effects of traits and environments on individual performances and lifelong fitness at larger spatial scales or along experimentally manipulated environmental gradients.
A growing body of literature is exploring firm export and R&D activities. However, most studies examine the first one, whilst considering the second as an explanatory variable or vice versa. This ...paper contributes to this literature by exploring the joint dynamics of exports and R&D using data from a representative sample of small and medium-sized enterprises in Spanish manufacturing over the 1990-2006 period. The results confirm the existence of a strong interdependence between export and R&D activities. Indeed, engaging in export (R&D) activities will increase a firm's chances of also engaging in R&D (export) activities. This, in turn, increases firms' chances of succeeding in export (R&D) activities. Additionally, once we control for firm heterogeneity, strong persistence still remains in each activity due to true state dependence. The results are robust in the use of alternative measures of internationalization (i.e. imports) and innovative activities (product and process innovation).
We introduce gauge theories based on a class of disconnected gauge groups, called principal extensions. Although in this work we focus on 4d theories with N=2 SUSY, such construction is independent ...of spacetime dimensions and supersymmetry. These groups implement in a consistent way the discrete gauging of charge conjugation, for arbitrary rank. Focusing on the principal extension of SU(N), we explain how many of the exact methods for theories with 8 supercharges can be put into practice in that context. We then explore the physical consequences of having a disconnected gauge group: we find that the Coulomb branch is generically non-freely generated, and the global symmetry of the Higgs branch is modified in a non-trivial way.
Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell ...fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization. The regulation of IRE1α signaling by Hsp47 is evolutionarily conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency sensitized cells and animals to experimental ER stress, revealing the significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47 adjusts IRE1α signaling by fine-tuning the threshold to engage an adaptive UPR.
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•Proteomic screening identified the ER chaperone Hsp47 as an adjustor of the UPR•Hsp47 is a selective regulator of the ER stress transducer IRE1α•Hsp47 displaces BiP from the IRE1 UPRosome to promote its oligomerization•The regulation of the UPR by Hsp47 is conserved in evolution
Sepulveda et al. use interactome screening and functional validation to identify a role for Hsp47 as a selective regulator of the unfolded protein response (UPR). Fine-tuning the UPR may be a useful strategy for treatment of diseases involving chronic endoplasmic reticulum stress.
1 Servei de Pneumologia (Institut del Tòrax), Hospital Clinic, Institut d'Investigacions Biomédiques August Pi i Sunyer, 2 Fundació Clinic de Recerca Biomèdica, and 3 Ciber Enfermedades ...Respiratorias, Universitat de Barcelona, Barcelona, Spain; and 4 Division of Physiology, University of California, San Diego, California
Submitted 28 January 2009
; accepted in final form 9 April 2009
Chronic obstructive pulmonary disease (COPD) is characterized by a decline in forced expiratory volume in 1 s (FEV 1 ) and, in many advanced patients, by arterial hypoxemia with or without hypercapnia. Spirometric and gas exchange abnormalities have not been found to relate closely, but this may reflect a narrow range of severity in patients studied. Therefore, we assessed the relationship between pulmonary gas exchange and airflow limitation in patients with COPD across the severity spectrum. Ventilation-perfusion ( A / ) mismatch was measured using the multiple inert gas elimination technique in 150 patients from previous studies. The distribution of patients according to the GOLD stage of COPD was: 15 with stage 1; 40 with stage 2; 32 with stage 3; and 63 with stage 4. In GOLD stage 1, AaP O 2 and A / mismatch were clearly abnormal; thereafter, hypoxemia, AaP O 2 , and A / imbalance increased, but the changes from GOLD stages 1–4 were modest. Postbronchodilator FEV 1 was related to Pa O 2 ( r = 0.62) and Pa CO 2 ( r = –0.59) and to overall A / heterogeneity ( r = –0.48) ( P < 0.001 each). Pulmonary gas exchange abnormalities in COPD are related to FEV 1 across the spectrum of severity. A / imbalance, predominantly perfusion heterogeneity, is disproportionately greater than airflow limitation in GOLD stage 1, suggesting that COPD initially involves the smallest airways, parenchyma, and pulmonary vessels with minimal spirometric disturbances. That progression of A / inequality with spirometric severity is modest may reflect pathogenic processes that reduce both local ventilation and blood flow in the same regions through airway and alveolar disease and capillary involvement.
airflow limitation; arterial blood gases; chronic respiratory failure; global initiative for COPD; pulmonary gas exchange
Address for reprint requests and other correspondence: R. Rodríguez-Roisin, Servei de Pneumologia, Hospital Clínic, Villarroel, 170. 08036 Barcelona, Spain (e-mail: rororo{at}clinic.ub.es )
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