Determining the influence and effects of manufacturing variables on sulfur dioxide cells

A survey of the Li/SO2 manufacturing community was conducted to determine where variability exists in processing. The upper and lower limits of these processing variables might, by themselves or by interacting with other variables, influence safety, performance, and reliability. A number of important variables were identified and a comprehensive design experiment is being proposed to make the proper determinations

The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER

Human cytomegalovirus uses an E3 ubiquitin ligase to divert MHC I molecules into the ER-associated degradation pathway for destruction

Numerical simulation of explosive volcanic eruptions from the conduit flow to global atmospheric scales

Volcanic eruptions are unsteady multiphase phenomena, which encompass many inter-related processes across the whole range of scales from molecular and microscopic to macroscopic, synoptic and global. We provide an overview of recent advances in numerical modelling of volcanic effects, from conduit and eruption column processes to those on the Earth s climate. Conduit flow models examine ascent dynamics and multiphase processes like fragmentation, chemical reactions and mass transfer below the Earth surface. Other models simulate atmospheric dispersal of the erupted gas-particle mixture, focusing on rapid processes occurring in the jet, the lower convective regions, and pyroclastic density currents. The ascending eruption column and intrusive gravity current generated by it, as well as sedimentation and ash dispersal from those flows in the immediate environment of the volcano are examined with modular and generic models. These apply simplifications to the equations describing the system depending on the specific focus of scrutiny. The atmospheric dispersion of volcanic clouds is simulated by ash tracking models. These are inadequate for the first hours of spreading in many cases but focus on long-range prediction of ash location to prevent hazardous aircraft - ash encounters. The climate impact is investigated with global models. All processes and effects of explosive eruptions cannot be simulated by a single model, due to the complexity and hugely contrasting spatial and temporal scales involved. There is now the opportunity to establish a closer integration between different models and to develop the first comprehensive description of explosive eruptions and of their effects on the ground, in the atmosphere, and on the global climate

Mutations of the β- and γ-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas

β-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator in the Wnt signalling pathway. Although recent investigations have been focused on the role of the adenomatous polyposis coli (APC)/ β-catenin/Tcf pathway in human tumorigenesis, there have been very few reports on mutations of the β-catenin gene in a variety of tumour types. Using PCR and single-strand conformational polymorphism analysis, we examined 93 lung, 9 breast, 6 kidney, 19 cervical and 7 ovarian carcinoma cell lines for mutations in exon 3 of the β-catenin gene. In addition, we tested these same samples for mutations in the NH2-terminal regulatory region of the γ-catenin gene. Mutational analysis for the entire coding region of β-catenin cDNA was also undertaken in 20 lung, 9 breast, 5 kidney and 6 cervical carcinoma cell lines. Deletion of most β-catenin coding exons was confirmed in line NCI-H28 (lung mesothelioma) and a silent mutation at codon 214 in exon 5 was found in HeLa (cervical adenocarcinoma). A missense mutation at codon 19 and a silent mutation at codon 28 in the NH2-terminal regulatory region of the γ-catenin gene were found in H1726 (squamous cell lung carcinoma) and H1048 (small cell lung carcinoma), respectively. Neither deletions nor mutations of these genes were detected in the other cell lines examined. These results suggest that β- and γ-catenins are infrequent mutational targets during development of human lung, breast, kidney, cervical and ovarian carcinomas. © 2001 Cancer Research Campaign http://www.bjcancer.co

Pharmaceutical Cost-Sharing Systems and Savings for Health Care Systems from Parallel Trade

This paper analyzes the consequences of parallel trade on health care systems in a two-country model with a vertical distributor relationship. In particular, two cost-sharing systems - coinsurance and indemnity insurance - are compared with respect to changes in copayments and public health expenditure. Under both cost-sharing systems, parallel trade generates a price-decreasing competition effect in the destination country and a price-increasing double marginalization effect in the source country. In the destination country, copayments for patients decrease to a larger extent under indemnity insurance, whereas reductions of public health expenditure occur only under coinsurance. In the source country, copayments increase less under coinsurance, whereas health expenditure is reduced more under indemnity insurance. This illustrates that a harmonization of health care systems would not make sense

Parasite Evolution and Life History Theory

Beth F. Kochin is with Emory University, James J. Bull is with UT Austin, Rustom Antia is with Emory University.As a group, parasites are extraordinarily diverse. Even closely related parasites may behave very differently, infecting different host species, causing different pathologies, or infecting different tissues. For example, Escherichia coli bacteria, a typically harmless inhabitant of the human gut, can, in different forms, cause diarrhea, intestinal bleeding, urinary tract infections, kidney bleeding, meningitis, and other diseases. Underlying this diversity is evolution.This work is supported by the National Institutes of Health and the Fannie and John Hertz Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Cellular and Molecular Biolog

Can Charisma Be Taught? Tests of Two Interventions

We tested whether we could teach individuals to behave more charismatically, andwhether changes in charisma affected leader outcomes. In Study 1, a mixed-design fieldexperiment, we randomly assigned 34 middle-level managers to a control or anexperimental group. Three months later, we reassessed the managers using theircoworker ratings (Time 1 raters = 343; Time 2 raters = 321). In Study 2, a within-subjectslaboratory experiment, we videotaped 41 MBA participants giving a speech. We thentaught them how to behave more charismatically, and they redelivered the speech6 weeks later. Independent assessors (n = 135) rated the speeches. Results from thestudies indicated that the training had significant effects on ratings of leader charisma(mean D = .62) and that charisma had significant effects on ratings of leaderprototypicality and emergence...............................................................................................................................

Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs

Inhibition of a single transduction pathway is often inefficient due to activation of alternative signalling. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation, survival and angiogenic pathways and has been implicated in the resistance to EGFR inhibitors. Thus, mTOR blockade is pursued to interfere at multiple levels with tumour growth. We used everolimus (RAD001) to inhibit mTOR, alone or in combination with anti-EGFR drugs gefitinib or cetuximab, on human cancer cell lines sensitive and resistant to EGFR inhibitors, both in vitro and in vivo. We demonstrated that everolimus is active against EGFR-resistant cancer cell lines and partially restores the ability of EGFR inhibitors to inhibit growth and survival. Everolimus reduces the expression of EGFR-related signalling effectors and VEGF production, inhibiting proliferation and capillary tube formation of endothelial cells, both alone and in combination with gefitinib. Finally, combination of everolimus and gefitinib inhibits growth of GEO and GEO-GR (gefitinib resistant) colon cancer xenografts, activation of signalling proteins and VEGF secretion. Targeting mTOR pathway with everolimus overcomes resistance to EGFR inhibitors and produces a cooperative effect with EGFR inhibitors, providing a valid therapeutic strategy to be tested in a clinical setting

Filarial Parasites Develop Faster and Reproduce Earlier in Response to Host Immune Effectors That Determine Filarial Life Expectancy

During larval development, filarial nematodes adjust their lifelong reproductive strategy to the presence of anti-parasitic immune cells that determine host resistance and experimental vaccine efficacy

The community-based prevention of diabetes (ComPoD) study: A randomised, waiting list controlled trial of a voluntary sector-led diabetes prevention programme

© 2019 The Author(s). Objective: This two-site randomised trial compared the effectiveness of a voluntary sector-led, community-based diabetes prevention programme to a waiting-list control group at 6 months, and included an observational follow-up of the intervention arm to 12 months. Methods: Adults aged 18-75 years at increased risk of developing type 2 diabetes due to elevated blood glucose and being overweight were recruited from primary care practices at two UK sites, with data collected in participants' homes or community venues. Participants were randomised using an online central allocation service. The intervention, comprising the prototype "Living Well, Taking Control" (LWTC) programme, involved four weekly two-hour group sessions held in local community venues to promote changes in diet and physical activity, plus planned follow-up contacts at two, three, six, nine and 12 months alongside 5 hours of additional activities/classes. Waiting list controls received usual care for 6 months before accessing the programme. The primary outcome was weight loss at 6 months. Secondary outcomes included glycated haemoglobin (HbA1c), blood pressure, physical activity, diet, health status and well-being. Only researchers conducting analyses were blinded. Results: The target sample of 314 participants (157 each arm) was largely representative of local populations, including 44% men, 26% from ethnic minorities and 33% living in deprived areas. Primary outcome data were available for 285 (91%) participants (141 intervention, 144 control). Between baseline and 6 months, intervention participants on average lost more weight than controls (- 1.7 kg, 95% CI - 2.59 to - 0.85). Higher attendance was associated with greater weight loss (- 3.0 kg, 95% CI - 4.5 to - 1.5). The prototype LWTC programme more than doubled the proportion of participants losing > 5% of their body weight (21% intervention vs. 8% control, OR 2.83, 95% CI 1.36 to 5.90) and improved self-reported dietary behaviour and health status. There were no impacts on HbA1c, blood pressure, physical activity and well-being at 6 months and, amongst intervention participants, few further changes from six to 12-months (e.g. average weight re-gain 0.36 kg, 95% CI - 0.20 to 0.91). There were no serious adverse events but four exercise-related injuries were reported in the intervention arm. Conclusions: This voluntary sector-led diabetes prevention programme reached a broad spectrum of the population and had modest effects on weight-related outcomes, but limited impacts on other diabetes risk factors. Trial registration: Trial registration number: ISRCTN70221670, 5 September 2014 Funder (National Institute for Health Research School for Public Health Research) project reference number: SPHR-EXE-PES-COM