Agents that stimulate human pancreatic beta cell proliferation are needed to improve diabetes mellitus treatment. Recently, a small molecule, WS6, was observed to stimulate human beta cell ...proliferation. However, little is known about its other effects on human islets. To better understand the role of WS6 as a possible beta cell regenerative therapy, we carried out in-depth phenotypic analysis of WS6-treated human islets, exploring its effects on non-beta cell proliferation, beta cell differentiation, and islet cell viability. WS6 not only stimulated beta cell proliferation in cultured human islets (in agreement with previous reports), but also human alpha cell proliferation, indicating that WS6 is not a beta cell-specific mitogen. WS6 did not change the proportion of insulin-positive beta cells or the expression of beta cell-specific transcription factors, suggesting that WS6 does not alter beta cell differentiation, and WS6 had no effect on human islet cell apoptosis or viability. In conclusion, WS6 stimulates proliferation of both human beta and alpha cells while maintaining cellular viability and the beta cell differentiated phenotype. These findings expand the literature on WS6 and support the suggestion that WS6 may help increase human islet mass needed for successful treatment of diabetes.
Annual forest loss in the Brazilian Amazon had in 2012 declined to less than 5,000 sqkm, from over 27,000 in 2004. Mounting empirical evidence suggests that changes in Brazilian law enforcement ...strategy and the related governance system may account for a large share of the overall success in curbing deforestation rates. At the same time, Brazil is experimenting with alternative approaches to compensate farmers for conservation actions through economic incentives, such as payments for environmental services, at various administrative levels. We develop a spatially explicit simulation model for deforestation decisions in response to policy incentives and disincentives. The model builds on elements of optimal enforcement theory and introduces the notion of imperfect payment contract enforcement in the context of avoided deforestation. We implement the simulations using official deforestation statistics and data collected from field-based forest law enforcement operations in the Amazon region. We show that a large-scale integration of payments with the existing regulatory enforcement strategy involves a tradeoff between the cost-effectiveness of forest conservation and landholder incomes. Introducing payments as a complementary policy measure increases policy implementation cost, reduces income losses for those hit hardest by law enforcement, and can provide additional income to some land users. The magnitude of the tradeoff varies in space, depending on deforestation patterns, conservation opportunity and enforcement costs. Enforcement effectiveness becomes a key determinant of efficiency in the overall policy mix.
The topic of end-of-life (EOL) care planning has received a surge of attention in recent years. Programs designed to ensure that care preferences are appropriately implemented in actual care when a ...person is facing a serious advancing illness have been a high priority, with a particular focus on improving how preferences are communicated across care settings. However, both implementation and educational challenges have emerged. The purpose of this symposium is to explore the process of determining patient EOL care preferences in a variety of care settings, as well as to evaluate the role of educational resources that can be drawn upon to support this process. The first three studies all focus on issues around the implementation of the MOLST (Medical Orders for Life-Sustaining Treatment) in Massachusetts. Chen and colleagues focus on MOLST completion in the hospital setting, Boerner and colleagues examine how nursing home staff experience the MOLST process, and DeSanto-Madeya and colleagues highlight the voice of key stakeholders in identifying implementation challenges and training and education needs. The final presentation by Gazarian focuses more generally on the capacity of educational resources and decision aids in supporting both patients and health care providers as they engage in thoughtful EOL discussions. The discussion will reflect on the shared experiences and develop a dialogue about ways to overcome the identified implementation and educational challenges.
Social relationships in very late life are an important public health issue, given the extensive and prolonged care needs of very old adults and the profound physical and emotional consequences for ...the involved caregivers, typically children who have also reached old age. Very old parents and their “old” children are a growing group in industrialized countries worldwide. However, virtually nothing is known about the nature and implications of this relationship constellation. The proposed symposium offers insights from four countries to address this gap in the literature. Jopp and colleagues present findings on support exchanges in Swiss older parent-child dyads, using a novel methodological approach of observing real-time supportive behaviors in the context of an interaction task. Boerner and colleagues report findings from standardized support assessments and qualitative interviews, highlighting the notable presence of downstream support (parent to child) among very old parent-old child dyads in Greater Boston, USA. Ribeiro and colleagues draw on qualitative interviews with children caring for a centenarian parent in Portugal, to portray how these children view their caregiving role and the contribution centenarians make to the family system. Han and Kim present findings on Korean very old parent-child dyads. Qualitative interviews yield evidence of both continuity and change in parent-child relationship dynamics, with increase in mutual understanding representing an element of positive change and assigning caregiving roles among children representing sources of strain. Findings will be discussed with a comparative eye for similarities and differences in observations across national cultures as well as methodological approaches used.
Objective: This study was conducted to estimate genetic parameters for milk yield traits using daily milk yield records from parlour data generated in an intensively managed commercial dairy farm ...with Jersey and Jersey-Friesian cows in Sri Lanka. Methods: Genetic parameters were estimated for first and second lactation predicted and realized 305-day milk yield using univariate animal models. Genetic parameters were also estimated for total milk yield for each 30-day intervals of the first lactation using univariate animal models and for daily milk yield using random regression models fitting second-order Legendre polynomials and assuming heterogeneous residual variances. Breeding values for predicted 305-day milk yield were estimated using an animal model. Results: For the first lactation, the heritability of predicted 305-day milk yield in Jersey cows (0.08±0.03) was higher than that of Jersey-Friesian cows (0.02±0.01). The second lactation heritability estimates were similar to that of first lactation. The repeatability of the daily milk records was 0.28±0.01 and the heritability ranged from 0.002±0.05 to 0.19±0.02 depending on day of milk. Pearson product-moment correlations between the bull estimated breeding values (EBVs) in Australia and bull EBVs in Sri Lanka for 305-day milk yield were 0.39 in Jersey cows and -0.35 in Jersey-Friesian cows. Conclusion: The heritabilities estimated for milk yield in Jersey and Jersey-Friesian cows in Sri Lanka were low, and were associated with low additive genetic variances for the traits. Sire differences in Australia were not expressed in the tropical low-country of Sri Lanka. Therefore, genetic progress achieved by importing genetic material from Australia can be expected to be slow. This emphasizes the need for a within-country evaluation of bulls to produce locally adapted dairy cows.
Rye (Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of ...genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye's incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye-wheat introgressions.
The plasma and neutral transport in the plasma edge of a nuclear fusion reactor is usually simulated using coupled finite volume (FV)/Monte Carlo (MC) codes. However, under conditions of future ...reactors like ITER and DEMO, convergence issues become apparent. This paper examines the convergence behaviour and the numerical error contributions with a simplified FV/MC model for three coupling techniques: Correlated Sampling, Random Noise and Robbins Monro. Also, practical procedures to estimate the errors in complex codes are proposed. Moreover, first results with more complex models show that an order of magnitude speedup can be achieved without any loss in accuracy by making use of averaging in the Random Noise coupling technique.
Adaptation of bacteria to changes in their environment is often accomplished by changes of the transcriptome. While we learned a lot on the impact of transcriptional regulation in bacterial ...adaptation over the last decades, much less is known on the role of ribonucleases. This study demonstrates an important function of the endoribonuclease RNase E in the adaptation to different growth conditions. It was shown previously that RNase E activity does not influence the doubling time of the facultative phototroph Rhodobacter sphaeroides during chemotrophic growth, however, it has a strong impact on phototrophic growth. To better understand the impact of RNase E on phototrophic growth, we now quantified gene expression by RNA-seq and mapped 5' ends during chemotrophic growth under high oxygen or low oxygen levels and during phototrophic growth in the wild type and a mutant expressing a thermosensitive RNase E. Based on the RNase E-dependent expression pattern, the RNAs could be grouped into different classes. A strong effect of RNase E on levels of RNAs for photosynthesis genes was observed, in agreement with poor growth under photosynthetic conditions. RNase E cleavage sites and 5' ends enriched in the rne
ts
mutant were differently distributed among the gene classes. Furthermore, RNase E affects the level of RNAs for important transcription factors thus indirectly affecting the expression of their regulons. As a consequence, RNase E has an important role in the adaptation of R. sphaeroides to different growth conditions.
Salinity is one of the most important abiotic stresses causing a significant reduction of crop plants yield. To gain a better understanding of salinity tolerance mechanisms in barley (Hordeum ...vulgare), we investigated the changes in root proteome of salt-sensitive (DH14) and tolerant (DH187) lines in response to salt-stress. The seeds of both barley lines were germinating in water or in 100mM NaCl for 6 days. The root proteins were separated by two-dimensional gel electrophoresis. To identify proteins regulated in response to salt stress, MALDI-TOF/TOF mass spectrometry was applied. It was demonstrated that the sensitive and tolerant barley lines respond differently to salt stress. Some of the identified proteins are well-documented as markers of salinity resistance, but several proteins have not been detected in response to salt stress earlier, although they are known to be associated with other abiotic stresses. The most significant differences concerned the proteins that are involved in signal transduction (annexin, translationally-controlled tumor protein homolog, lipoxygenases), detoxification (osmotin, vacuolar ATP-ase), protein folding processes (protein disulfide isomerase) and cell wall metabolism (UDP-glucuronic acid decarboxylase, β-d-glucan exohydrolase, UDP-glucose pyrophosphorylase). The results suggest that the enhanced salinity tolerance of DH187 line results mainly from an increased activity of signal transduction mechanisms eventually leading to the accumulation of stress protective proteins and cell wall structure changes.
A computational method is given for solving the forward modelling problem for transient electromagnetic exploration. Its key features are the discretization of the quasi-static Maxwell's equations in ...space using the first-kind family of curl-conforming Nédélec elements combined with time integration using rational Krylov methods. We show how rational Krylov methods can also be used to solve the same problem in the frequency domain followed by a synthesis of the transient solution using the fast Hankel transform, and we argue that the pure time-domain solution is more efficient. We also propose a new surrogate optimization approach for selecting the pole parameters of the rational Krylov method which leads to convergence within an a priori determined number of iterations independent of mesh size and conductivity structure. These poles are repeated in a cyclic fashion, which, in combination with direct solvers for the discrete problem, results in significantly faster solution times than previously proposed schemes.
PDF
