Deformation-Driven Diffusion and Plastic Flow in Two-Dimensional Amorphous Granular Pillars

We report a combined experimental and simulation study of deformation-induced diffusion in compacted two-dimensional amorphous granular pillars, in which thermal fluctuations play negligible role. The pillars, consisting of bidisperse cylindrical acetal plastic particles standing upright on a substrate, are deformed uniaxially and quasistatically by a rigid bar moving at a constant speed. The plastic flow and particle rearrangements in the pillars are characterized by computing the best-fit affine transformation strain and non-affine displacement associated with each particle between two stages of deformation. The non-affine displacement exhibits exponential crossover from ballistic to diffusive behavior with respect to the cumulative deviatoric strain, indicating that in athermal granular packings, the cumulative deviatoric strain plays the role of time in thermal systems and drives effective particle diffusion. We further study the size-dependent deformation of the granular pillars by simulation, and find that different-sized pillars follow self-similar shape evolution during deformation. In addition, the yield stress of the pillars increases linearly with pillar size. Formation of transient shear lines in the pillars during deformation becomes more evident as pillar size increases. The width of these elementary shear bands is about twice the diameter of a particle, and does not vary with pillar size.Comment: 14 pages, 11 figure

Job Satisfaction Among Methadone Maintenance Treatment Clinic Service Providers in Jiangsu, China: A Cross-sectional Survey.

ObjectiveService providers' job satisfaction is critical to the stability of the work force and thereby the effectiveness of methadone maintenance treatment (MMT) programs. This study aimed to explore MMT clinic service providers' job satisfaction and associated factors in Jiangsu, China.MethodsThis secondary study used baseline data of a randomized interventional trial implemented in Jiangsu, China. A survey was conducted among 76 MMT service providers using the computer-assisted self-interview (CASI) method. Job satisfaction responses were assessed via a 30-item scale, with a higher score indicating a higher level of job satisfaction. Perceived institutional support and perceived stigma due to working with drug users were measured using a 9-item scale. Correlation and multiple linear regression analyses were performed to identify factors associated with job satisfaction.ResultsCorrelation analyses found a significant association between job satisfaction and having professional experience in the prevention and control of HIV, other sexually transmitted infections, or other infectious diseases (P = 0.046). Multiple regression analyses revealed that working at MMT clinics affiliated with Center for Disease Control and Prevention sites was associated with a lower level of job satisfaction (P = 0.014), and perception of greater institutional support (P = 0.001) was associated with a higher level of job satisfaction.ConclusionJob satisfaction among MMT clinic service providers was moderate in our study. Our findings suggest that institutional support for providers should be improved, and that acquisition of additional expertise should be encouraged

The involvement of survival signaling pathways in rubella-virus induced apoptosis

Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3β were detected from 24–96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production

A re-examination of the BEST Trial using composite outcomes, including emergency department visits

Objectives: The influence of choice of endpoint on trial size, duration, and interpretation of results was examined in patients with heart failure who were enrolled in BEST (Beta-blocker Evaluation of Survival Trial). Background: The choice of endpoints in heart failure trials has evolved over the past 3 decades. Methods: In the BEST trial, we used Cox regression analysis to examine the effect of bucindolol on the current standard composite of cardiovascular death or heart failure hospitalization (CVD/HFH) compared with the original primary mortality endpoint and the expanded composite that included emergency department (ED) visits. We also undertook an analysis of recurrent events primarily using the Lin, Wei, Ying, and Yang model. Results: Overall, 448 (33%) patients on placebo and 411 (30%) patients on bucindolol died (hazard ratio [HR]: 0.90; 95% confidence interval [CI]: 0.78 to 1.02; p = 0.11). A total of 730 (54%) patients experienced CVD/HFH on placebo and 624 (46%) on bucindolol (HR: 0.80; 95% CI: 0.72 to 0.89; p < 0.001). Adding ED visits increased these numbers to 768 (57%) and 668 (49%), respectively (HR: 0.81; 95% CI: 0.73 to 0.90; p < 0.001). A total of 568 (42%) patients on placebo experienced HFH compared with 476 (35%) patients on bucindolol (HR: 0.78; 95% CI: 0.69 to 0.89; p < 0.001), with a total of 1,333 and 1,124 admissions, respectively. With the same statistical assumptions, using the composite endpoint instead of all-cause mortality would have reduced the trial size by 40% and follow-up duration by 69%. The rate ratio for recurrent events (CVD/HFH) was 0.83 (95% CI: 0.73 to 0.94; p = 0.003). Conclusions: Choice of endpoint has major implications for trial size and duration, as well as interpretation of results. The value of broader composite endpoints and inclusion of recurrent events needs further investigation. (Beta Blocker Evaluation in Survival Trial [BEST]; NCT00000560

A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice

Epigenetic changes can be induced by adverse environmental exposures, such as nutritional imbalance, but little is known about the nature or extent of these changes. Here we have explored the epigenomic effects of a sustained nutritional change, excess dietary methyl donors, by assessing genomic CpG methylation patterns in isogenic mice exposed for one or six generations. We find stochastic variation in methylation levels at many loci; exposure to methyl donors increases the magnitude of this variation and the number of variable loci. Several gene ontology categories are significantly overrepresented in genes proximal to these methylation-variable loci, suggesting that certain pathways are susceptible to environmental influence on their epigenetic states. Long-term exposure to the diet (six generations) results in a larger number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable. This finding presents the possibility that epigenetic variation within populations can be induced by environmental change, providing a vehicle for disease predisposition and possibly a substrate for natural selection.This work was supported by the Australian Research Council (DP0771859) and the National Health and Medical Research Council (#459412, #635510)

Impact of Irrigation Strategies on Tomato Root Distribution and Rhizosphere Processes in an Organic System.

Root exploitation of soil heterogeneity and microbially mediated rhizosphere nutrient transformations play critical roles in plant resource uptake. However, how these processes change under water-saving irrigation technologies remains unclear, especially for organic systems where crops rely on soil ecological processes for plant nutrition and productivity. We conducted a field experiment and examined how water-saving subsurface drip irrigation (SDI) and concentrated organic fertilizer application altered root traits and rhizosphere processes compared to traditional furrow irrigation (FI) in an organic tomato system. We measured root distribution and morphology, the activities of C-, N-, and P-cycling enzymes in the rhizosphere, the abundance of rhizosphere microbial N-cycling genes, and root mycorrhizal colonization rate under two irrigation strategies. Tomato plants produced shorter and finer root systems with higher densities of roots around the drip line, lower activities of soil C-degrading enzymes, and shifts in the abundance of microbial N-cycling genes and mycorrhizal colonization rates in the rhizosphere of SDI plants compared to FI. SDI led to 66.4% higher irrigation water productivity than FI, but it also led to excessive vegetative growth and 28.3% lower tomato yield than FI. Our results suggest that roots and root-microbe interactions have a high potential for coordinated adaptation to water and nutrient spatial patterns to facilitate resource uptake under SDI. However, mismatches between plant needs and resource availability remain, highlighting the importance of assessing temporal dynamics of root-soil-microbe interactions to maximize their resource-mining potential for innovative irrigation systems

On using Cholesky-based factorizations and regularization for solving rank-deficient sparse linear least-squares problems

By examining the performance of modern parallel sparse direct solvers and exploiting our knowledge of the algorithms behind them, we perform numerical experiments to study how they can be used to efficiently solve rank-deficient sparse linear least-squares problems arising from practical applications. The Cholesky factorization of the normal equations breaks down when the least-squares problem is rank-deficient, while applying a symmetric indefinite solver to the augmented system can give an unacceptable level of fill in the factors. To try to resolve these difficulties, we consider a regularization procedure that modifies the diagonal of the unregularized matrix. This leads to matrices that are easier to factorize. We consider both the regularized normal equations and the regularized augmented system. We employ the computed factors of the regularized systems as preconditioners with an iterative solver to obtain the solution of the original (unregularized) problem. Furthermore, we look at using limited-memory incomplete Cholesky-based factorizations and how these can offer the potential to solve very large problems

The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits

Pro-tobacco marketing and anti-tobacco campaigns aimed at vulnerable populations: A review of the literature.

INTRODUCTION:We reviewed research literature on pro-tobacco marketing and anti-tobacco campaigns targeting eight vulnerable populations to determine key findings and research gaps. Results can inform tobacco policy and control efforts and the design of public education campaigns for these groups. METHODS:Five journal databases in medicine, communication, and science, were used to identify 8875 peer-reviewed, original articles in English, published in the period 2004-2018. There were 144 articles that met inclusion criteria on pro-tobacco marketing or anti-tobacco campaigns aimed at eight US groups: women of reproductive age, racial/ethnic minority groups (African American, Hispanic/Latino, Asian/Pacific Islander and American Indian/Alaska Native), Lesbian/Gay/Bisexual/Transgender (LGBT) populations, groups with low socioeconomic status, rural/inner city residents, military/veterans, and people with mental health or medical co-morbidities. We summarized the number of articles for each population, type of tobacco, and pro-tobacco or anti-tobacco focus. Narrative summaries were organized by population and by pro-tobacco or anti-tobacco focus, with key strategies and gaps by group. RESULTS:There were more studies on pro-tobacco marketing rather than anti-tobacco campaigns, and on cigarettes rather than other tobacco products. Major gaps included studies on Asian Americans, American Indian/Alaska Natives, pregnant women, LGBT populations, and those with mental health or medical co-morbidities. Gaps related to tobacco products were found for hookah, snus, and pipe/roll-your-own tobacco in the pro-tobacco studies, and for all products except cigarettes in anti-tobacco studies. Common tobacco industry methods used were tailoring of product and package design and messages that were used to reach and appeal to different sociodemographic groups. Studies varied by research design making it difficult to compare results. CONCLUSIONS:We found major research gaps for specific groups and tobacco products. Public education campaigns need a stronger foundation in empirical studies focused on these populations. Research and practice would benefit from studies that permit comparisons across studies

Immediate Antiretroviral Therapy Decreases Mortality Among Patients With High CD4 Counts in China: A Nationwide, Retrospective Cohort Study.

BackgroundClinical trials have demonstrated that immediate initiation of antiretroviral therapy (ART) reduces AIDS-related morbidity and mortality. We tested the hypothesis that initiating ART ≤30 days after human immunodeficiency virus (HIV) diagnosis would be associated with reduced mortality among people living with HIV (PLWH) with CD4 counts >500 cells/μL.MethodsPLWH enrolled in the Chinese National HIV Information System between January 2012 and June 2014 with CD4 counts >500 cells/μL were followed for 12 months. Cox proportional hazards model was used to determine hazard ratios (HRs) for PLWH who initiated ART after HIV diagnosis. ART initiation was treated as a time-dependent variable.ResultsWe enrolled 34581 PLWH with CD4 >500 cells/μL; 1838 (5.3%) initiated ART ≤30 days after diagnosis (immediate ART group), and 19 deaths were observed with a mortality rate of 1.04 per 100 person-years (PY). Fifty-eight deaths were documented among the 5640 PLWH in the delayed ART group with a mortality rate of 2.25 per 100 PY. There were 713 deaths among the 27103 PLWH in the no ART group with a mortality rate of 2.39 per 100 PY. After controlling for potential confounding factors, ART initiation at ≤30 days (adjusted HR, 0.37 [95% confidence interval, .23-.58]) was a statistically significant protective factor.ConclusionsWe found that immediate ART is associated with a 63% reduction in overall mortality among PLWH with CD4 counts >500 cells/μL in China, supporting the recommendation to initiate ART immediately following HIV diagnosis