1,819 research outputs found
Sharpey‐Schafer, Langley and Sherrington: ‘swordsmen’ of physiology. A historical look to the future
Health Beliefs, Behavior, Spiritual Growth, and Salvation in a Global Population of Seventh‑day Adventists
Background The Seventh-day Adventist Church is a growing global denomination with strict substance use abstinence and recommended dietary requirements that together are called the “Health Message.” Abstinence from alcohol and tobacco is a requirement of membership and a plant-based diet is strongly advised. Purpose While a wide variety of research has reported the Adventist health advantage, very little research has been conducted on Adventist members’ attitudes toward and adherence to the Health Message. This research examines members\u27 views, from a global survey, about the health message, personal adherence, and belief that adherence ensures salvation. Methods The survey was conducted in 2017/2018 with a total N of 63,756. The questionnaire was translated into about 60 languages and then back-translated into English for improved accuracy. Results Over 80% of the respondents reported that they agreed the Adventist health message was wholistic, core to Adventist beliefs, supported by science, and increased the probability of a longer life. There were very few differences by global regions. About 80% also agreed that they should abstain from tobacco and alcohol and follow a healthy diet. However, about 45% believed that they could pick and choose which parts to follow with only a little over one-third reporting that they followed the Health Message a great deal. Strict adherence appeared to be in abstinence from alcohol (91%) and tobacco (97%). Only about 19% reported being vegetarian or vegan. Over 47%, mostly in the Southern Hemisphere, reported the belief that if they kept the Health Message completely, they would be assured of salvation, though this is at odds with formal doctrine. Conclusions and Implications The data suggest that church leadership has been successful in obtaining global acceptance of the Health Message, convincing members of its scientific basis, and to abstain from tobacco and alcohol use. However, the data also show almost half of members believe that they can pick and choose elements to follow. In addition, these data have major implications for church leadership in disentangling the implications and expectations of the Health Message from the Church’s fundamental belief that salvation is only through faith in Christ
Bifurcation and fine structure phenomena in critical collapse of a self-gravitating -field
Building on previous work on the critical behavior in gravitational collapse
of the self-gravitating SU(2) -field and using high precision numerical
methods we uncover a fine structure hidden in a narrow window of parameter
space. We argue that this numerical finding has a natural explanation within a
dynamical system framework of critical collapse
Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug
Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-powder electrostatic process. The AC-SES demonstrated enhanced drug stability under simulated use conditions and consistent drug delivery balanced with coating erosion in a porcine coronary implant model. The initial drug burst was eliminated and drug release was sustained after implantation. The coating was absorbed within 90 days.
Following implantation into porcine coronary arteries the AC-SES coating is distributed in the surrounding intimal tissue over the course of several weeks. Computational modeling of drug delivery characteristics demonstrates how distributed coating optimizes the load of drug immediately around each stent strut and extends drug delivery between stent struts. The result was a highly efficient arterial uptake of drug with superior performance to a clinical bare metal stent (BMS). Neointimal thickness (0.17 ± 0.07 mm vs. 0.28 ± 0.11 mm) and area percent stenosis (22 ± 9% vs. 35 ± 12%) were significantly reduced (p < 0.05) by the AC-SES compared to the BMS 30 days after stent implantation in an overlap configuration in porcine coronary arteries. Inflammation was significantly reduced in the AC-SES compared to the BMS at both 30 and 90 days after implantation.
Biocompatible, rapidly absorbable stent coatings enable the matching of drug release with coating erosion and provide for the controlled migration of coating material into tissue to reduce vicissitudes in drug tissue levels, optimizing efficacy and reducing potential toxicity.Micell Technologies, Inc.National Institutes of Health (U.S.) (R01 GM49039
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Reproductive Ecology of the Azooxanthellate Coral Tubastraea coccinea in the Equatorial Eastern Pacific: Part V. Dendrophylliidae
The reproductive ecology of Tubastraea coccinea Lesson, an azooxanthellate tropical scleractinian coral, was studied over various periods from 1985 to 2006 at four principal eastern Pacific locations in Costa Rica, Panamá, and the Galápagos Islands (Ecuador). This small (polyp diameter 0.8–1.0 cm), relatively cryptic species produced ova and planulae year round, including colonies with as few as 2–10 polyps. Of 424 colonies examined histologically, 13.7% contained both ova and sperm. Mature ova varied in diameter from ~300 to 800 µm and the time from spawning and fertilization of oocytes to release of brooded planulae was about 6 weeks. Planulae were 0.5–1.5 mm long and they settled and metamorphosed on a variety of substrates after 1–3 days. Spermaries, though more difficult to distinguish in histological sections, were present throughout the year. Spent spermaries were never observed in sections, but several colonies in Panamá and the Galápagos Islands released sperm from night one to night five after full moon, indicating the potential for cross-fertilization among colonies. Planula release was observed at Uva Island (Panamá) in March, May, June, and July, and in general planula presence was higher at warm ocean temperatures at all sites, whether or not the sites were inXuenced by seasonal upwelling. Annual fecundity estimates for T. coccinea are comparable with other high fecundity brooding species, including the zooxanthellate Porites panamensis, with which it co-occurs in Panamá. Tubastraea coccinea is widely distributed in the tropical Indo-Pacific and has colonized substrates in the western Atlantic. In addition to the reproductive characteristics described in the present study, other features of the biology of T. coccinea, such as an ability to withstand conditions that produce bleaching and mortality in zooxanthellate species, may account for its widespread, low-latitude distribution in multiple oceans
An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer
KRAS mutated tumours represent a large fraction of human cancers, but the vast majority remains refractory to current clinical therapies. Thus, a deeper understanding of the molecular mechanisms triggered by KRAS oncogene may yield alternative therapeutic strategies. Here we report the identification of a common transcriptional signature across mutant KRAS cancers of distinct tissue origin that includes the transcription factor FOSL1. High FOSL1 expression identifies mutant KRAS lung and pancreatic cancer patients with the worst survival outcome. Furthermore, FOSL1 genetic inhibition is detrimental to both KRAS-driven tumour types. Mechanistically, FOSL1 links the KRAS oncogene to components of the mitotic machinery, a pathway previously postulated to function orthogonally to oncogenic KRAS. FOSL1 targets include AURKA, whose inhibition impairs viability of mutant KRAS cells. Lastly, combination of AURKA and MEK inhibitors induces a deleterious effect on mutant KRAS cells. Our findings unveil KRAS downstream effectors that provide opportunities to treat KRAS-driven cancers
Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2-MALT1 in MALT lymphoma.
MALT1 is the only known paracaspase and is a critical mediator of B- and T-cell receptor signalling. The function of the MALT1 gene is subverted by oncogenic chimeric fusions arising from the recurrent t(11;18)(q21;q21) aberration, which is the most frequent translocation in mucosa-associated lymphoid tissue (MALT) lymphoma. API2-MALT1-positive MALT lymphomas manifest antibiotic resistance and aggressive clinical behaviour with poor clinical outcome. However, the mechanisms underlying API2-MALT1-induced MALT lymphomagenesis are not fully understood. Here we show that API2-MALT1 induces paracaspase-mediated cleavage of the tumour suppressor protein LIMA1. LIMA1 binding by API2-MALT1 is API2 dependent and proteolytic cleavage is dependent on MALT1 paracaspase activity. Intriguingly, API2-MALT1-mediated proteolysis generates a LIM domain-only (LMO)-containing fragment with oncogenic properties in vitro and in vivo. Importantly, primary MALT lymphomas harbouring the API2-MALT1 fusion uniquely demonstrate LIMA1 cleavage fragments. Our studies reveal a novel paracaspase-mediated oncogenic gain-of-function mechanism in the pathogenesis of MALT lymphoma.This work was
supported in part by NIH grants R01 DE119249 and R01 CA136905 (K.S.J.E-J.), R01
CA140806 (M.S.L.) and the Department of Pathology at the University of Michigan.This is the accepted manuscript. The final version is available from Nature at http://www.nature.com/ncomms/2015/150108/ncomms6908/full/ncomms6908.html
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