The role of the cytoskeleton in capacitaftive calcium entry in myenteric glia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73680/1/j.1365-2982.2003.00406.x.pd

Materials flow control in hybrid make-to-stock/make-to-order manufacturing

Today’s company competiveness is favoured by product customisation and fast delivery. A strategy to meet this challenge is to manufacture standard items to stock for product customisation. This configures a hybrid environment of make-to-stock and make-to-order. To explore the advantages of this requires good understanding of production control. Thus, we study production under hybrid MTS-MTO, organising the system in two stages. The 1 st manufactures items to inventory, which are then customised in the 2 nd . We analyse how the percentage of tardy orders is affected by the inventory of items required to achieve a given fill rate. The impact of two mechanisms for releasing orders to both stages is also analysed. Results of a simulation study indicate that most of the reduction on the percentage of tardy orders is achieved by a moderate increase in the stock level of semi-finished products. Moreover the percentage of tardy orders decreases if suitable controlled release of orders is exerted.This study had the financial support of FCT-Fundação para a Ciência e Tecnologia of Portugal under the project PEst2015-2020: UID/CEC/ 00319/2013.info:eu-repo/semantics/publishedVersio

Recall termination in free recall

Although much is known about the dynamics of memory search in the free recall task, relatively little is known about the factors related to recall termination. Reanalyzing individual trial data from 14 prior studies (1,079 participants in 28,015 trials) and defining termination as occurring when a final response is followed by a long nonresponse interval, we observed that termination probability increased throughout the recall period and that retrieval was more likely to terminate following an error than following a correct response. Among errors, termination probability was higher following prior-list intrusions and repetitions than following extralist intrusions. To verify that this pattern of results can be seen in a single study, we report a new experiment in which 80 participants contributed recall data from a total of 9,122 trials. This experiment replicated the pattern observed in the aggregate analysis of the prior studies

Pharmacological Undertreatment of Coronary Risk Factors in Patients with Psoriasis: Observational Study of the Danish Nationwide Registries

BACKGROUND: Patients with psoriasis have increased prevalence of coronary risk factors and limited recent results have suggested that these risk factors are undertreated in patients with psoriasis. This may contribute to the increased risk of cardiovascular diseases observed in patients with psoriasis. OBJECTIVE: To examine the pharmacological treatment of coronary risk factors in patients with severe psoriasis treated with biologic agents in a real-world setting. METHODS AND FINDINGS: Medical history of patients with severe psoriasis treated with biologic agents in the time period 2007-09 was retrieved from a Danish nationwide registry (DERMBIO). Individual-level linkage of nationwide administrative registries of hospitalizations, concomitant medications, and socioeconomic status was performed to gain insights into the use of pharmacological treatment. A total of 693 patients (mean age 46.1 ± 12.7 years, 65.7% male) with severe psoriasis treated with biologic agents were identified. Hypertension, hypercholesterolemia, and diabetes mellitus were identified in 16.6%, 9.2%, and 6.7% of cases, respectively. Patients with severe psoriasis were significantly less likely to receive cardiovascular pharmacotherapy compared to age, sex, and coronary risk factor matched controls. In psoriatic patients with hypertension 27.7% received no antihypertensive pharmacotherapy. Patients with dyslipidemia received cholesterol-lowering medications in 55.8% of cases and patients with diabetes mellitus received angiotensin converting enzyme inhibitors/angiotensin II receptor blockers and cholesterol-lowering medications in 42.1% and 23.7% of cases, respectively. Similar results were found for the subset of patients with >1 coronary risk factor and for high risk patients with established atherosclerotic disease. CONCLUSION: This nationwide study of patients with severe psoriasis demonstrated substantial undertreatment of coronary risk factors. Increased focus on identifying cardiovascular risk factors and initiation of preventive cardiovascular pharmacotherapy in patients with psoriasis is warranted

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the α-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2α have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2α were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2α (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2α. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2α (correlation coefficient 0.77, P=0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients

Nutrient Administration and Resistance Training

Skeletal muscle tissue is tightly regulated throughout our bodies by balancing its synthesis and breakdown. Many factors are known to exist that cause profound changes on the overall status of skeletal muscle, some of which include exercise, nutrition, hormonal influences and disease. Muscle hypertrophy results when protein synthesis is greater than protein breakdown. Resistance training is a popular form of exercise that has been shown to increase muscular strength and muscular hypertrophy. In general, resistance training causes a stimulation of protein synthesis as well as an increase in protein breakdown, resulting in a negative balance of protein. Providing nutrients, specifically amino acids, helps to stimulate protein synthesis and improve the overall net balance of protein. Strategies to increase the concentration and availability of amino acids after resistance exercise are of great interest and have been shown to effectively increase overall protein synthesis. [1-3] After exercise, providing carbohydrate has been shown to mildly stimulate protein synthesis while addition of free amino acids prior to and after exercise, specifically essential amino acids, causes a rapid pronounced increase in protein synthesis as well as protein balance.[1,3] Evidence exists for a dose-response relationship of infused amino acids while no specific regimen exists for optimal dosing upon ingestion. Ingestion of whole or intact protein sources (e.g., protein powders, meal-replacements) has been shown to cause similar improvements in protein balance after resistance exercise when compared to free amino acid supplements. Future research should seek to determine optimal dosing of ingested intact amino acids in addition to identifying the cellular mechanistic machinery (e.g. transcriptional and translational mechanisms) for causing the increase in protein synthesis

A Phylogenomic Supertree of Birds

It has long been appreciated that analyses of genomic data (e.g., whole genome sequencing or sequence capture) have the potential to reveal the tree of life, but it remains challenging to move from sequence data to a clear understanding of evolutionary history, in part due to the computational challenges of phylogenetic estimation using genome-scale data. Supertree methods solve that challenge because they facilitate a divide-and-conquer approach for large-scale phylogeny inference by integrating smaller subtrees in a computationally efficient manner. Here, we combined information from sequence capture and whole-genome phylogenies using supertree methods. However, the available phylogenomic trees had limited overlap so we used taxon-rich (but not phylogenomic) megaphylogenies to weave them together. This allowed us to construct a phylogenomic supertree, with support values, that included 707 bird species (~7% of avian species diversity). We estimated branch lengths using mitochondrial sequence data and we used these branch lengths to estimate divergence times. Our time-calibrated supertree supports radiation of all three major avian clades (Palaeognathae, Galloanseres, and Neoaves) near the Cretaceous-Paleogene (K-Pg) boundary. The approach we used will permit the continued addition of taxa to this supertree as new phylogenomic data are published, and it could be applied to other taxa as well.This research was funded by the US National Science Foundation, grant numbers DEB-1655683, DEB-1655624, DEB-1655559, DEB-1655736

Transcriptomic comparison of the retina in two mouse models of diabetes

Mouse models of type I diabetes offer the potential to combine genetic approaches with other pharmacological or physiological manipulations to investigate the pathophysiology and treatment of diabetic retinopathy. Type I diabetes is induced in mice through chemical toxins or can arise spontaneously from genetic mutations. Both models are associated with retinal vascular and neuronal changes. Retinal transcriptomic responses in C57BL/6J mice treated with streptozotocin and Ins2Akita/+ were compared after 3 months of hyperglycemia. Specific gene expression changes suggest a neurovascular inflammatory response in diabetic retinopathy. Genes common to the two models may represent the response of the retina to hyperglycemia, while changes unique to each model may represent time-dependent disease progression differences in the various models. Further investigation of the commonalities and differences between mouse models of type I diabetes may define cause and effect events in early diabetic retinopathy disease progression

Randomized comparison of the effects of the vitamin D(3 )adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients

BACKGROUND: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose. METHODS: We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003. RESULTS: In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 ± 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group, and 112 ± 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 ± 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001). CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D(3 )in patients who needed additional vitamin D