Circadian Rhythms

Circadian rhythms are a ubiquitous adaptation of eukaryotic organisms to the most reliable and predictable of environmental changes, the daily cycles of light and temperature. Prominent daily rhythms in behavior, physiology, hormone levels and biochemistry (including gene expression) are not merely responses to these environmental cycles, however, but embody the organism's ability to keep and tell time. At the core of circadian systems is a mysterious mechanism, located in the brain (actually the Suprachiasmatic nucleus of the hypothalamus) of mammals, but present even in unicellular organisms, that functions as a clock. This clock drives circadian rhythms. It is independent of, but remains responsive to, environmental cycles (especially light). The interest in temporal regulation — its organization, mechanism and consequences — unites investigators in diverse disciplines studying otherwise disparate systems. This diversity is reflected in the brief reviews that summarize the presentations at a meeting on circadian rhythms held in New York City on October 31, 1992. The meeting was sponsored by the Fondation pour l'Étude du Systéme Nerveux (FESN) and followed a larger meeting held 18 months earlier in Geneva, whose proceedings have been published (M. Zatz (Ed.), Report of the Ninth FESN Study Group on ‘Circadian Rhythms’, Discussions in Neuroscience, Vol. VIII, Nos. 2 + 3, Elsevier, Amsterdam, 1992). Some speakers described progress made in the interim, while others addressed aspects of the field not previously covered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60639/1/circadian_rhythms.pd

Genome-Wide Analysis of Light- and Temperature-Entrained Circadian Transcripts in Caenorhabditis elegans

Transcriptional profiling experiments identify light- and temperature-entrained circadian transcripts in C. elegans

Third Report on Chicken Genes and Chromosomes 2015

Following on from the First Report on Chicken Genes and Chromosomes [Schmid et al., 2000] and the Second Report in 2005 [Schmid et al., 2005], we are pleased to publish this long-awaited Third Report on the latest developments in chicken genomics. The First Report highlighted the availability of genetic and physical maps, while the Second Report was published as the chicken genome sequence was released. This report comes at a time of huge technological advances (particularly in sequencing methodologies) which have allowed us to examine the chicken genome in detail not possible until now. This has also heralded an explosion in avian genomics, with the current availability of more than 48 bird genomes [Zhang G et al., 2014b; Eöry et al., 2015], with many more planned

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations.

The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1r mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1r mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r rodents. Csf1r mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Development Of 1 L Hr \u3csup\u3e-1\u3c/sup\u3e Scale Hydrogen Liquefier Using Gifford-Mcmahon (Gm) Cryocooler

Korea Institute of Science and Technology (KIST) and Florida Solar Energy Center (FSEC) have collaborated to develop a demonstration-scale hydrogen liquefier for future liquid hydrogen research in Korea. A 1 L hr-1 liquefaction rate, direct-cooling type hydrogen liquefier using a commercially available GM cryocooler has been designed, fabricated, and tested at KIST. The liquefier consists of a GM cryocooler, finned heat pipe, liquid nitrogen precooler, ortho-para hydrogen converter, and vacuum jacketed internal storage tank. The system successfully demonstrated more than 1 L hr-1 of hydrogen liquefaction rate from ambient temperature gas. A detailed design method, loss analysis, overview of component fabrication, and experimental results are discussed in this paper

Development Of A 1 L/H Scale Liquid Hydrogen System

A small-scale hydrogen liquefaction plant consists of cryocooler, cryostat, liquid nitrogen (LN2) precooling bath, two ortho-para (o-p) hydrogen converters, a heat pipe, multilayer insulations (MLI), sensors and auxiliary components. The liquefaction plant was designed as both a cryocooler-cooled liquefier and a long-term zero boil-off liquid storage reservoir. A Gifford-McMahon (GM) cryocooler was selected as a cold sink and purchased from Cryomech Inc. A vacuum-jacketed 200 L capacity cryostat was designed to provide highly efficient thermal protection to LH2 storage space. A heat pipe was uniquely designed and installed in the cryostat to enhance heat transfer between the cryocooler and hydrogen gas and liquid. A LN2-cooled precooling bath was designed to act as a precooler and an o-p hydrogen converter. MLT blankets with hydrogen getter under high vacuum in the cryostat minimize heat loss into LH2 storage. All the components were carefully assembled in dust, oil and solvent-free environment with extra caution of vacuum tightness followed by dry nitrogen and helium purge. After initial cool-down of the cryocooler under vacuum, 99.999% of 300 K hydrogen gas was introduced to the liquefaction plant. From a series of liquefaction tests with or without LN2 precooling, the hydrogen liquefaction plant successfully demonstrated 1.4 L/h of hydrogen liquefaction with LN2 precooling and two o-p hydrogen converters, and 0.7 L/h without LN2 precooling

Development Of A 1 L/Hr Scale Liquid Hydrogen System

Various industries including automotive, aerospace, semiconductor manufacturing, military surveillance, commercial communication, fuel cell, solar panel etc. are showing great interests in liquid hydrogen (LH2) as one of the most efficient hydrogen storage methods for their applications. However, there are only few large-scale LH2 plants available in foreign commercial market, which are not readily accessible by researchers and engineers in related fields. In order to acquire hydrogen liquefaction and storage technology and mature them to be applied to future research, a small-scale LH2 plant was developed. The hydrogen liquefaction plant consists of cryocooler, cryostat, liquid nitrogen (LN2) precooling bath, two ortho-para (o-p) hydrogen converters, heat pipe, multilayer insulations, sensors and auxiliary components. The liquefaction plant was designed as both a cryocooler-cooled liquefier and a long-term zero boil-off liquid storage reservoir to meet various demands from applications. A Gifford-McMahon (GM) cryocooler was selected as a cold sink and purchased from Cryomech Inc. A vacuum-jacketed 200 L capacity cryostat was designed to provide highly efficient thermal protection to LH2 storage space by intensive thermal and structural analysis. A heat pipe was uniquely designed and installed in the cryostat to enhance heat transfer between the cryocooler and hydrogen gas and liquid. A LN2-cooled precooling bath was designed in a way that it can act as a precooler and an o-p hydrogen converter at given temperature. A temperature sensor rake, a liquid level sensor and multiple pressure sensors provide thermophysical status of hydrogen in the cryostat to National Instrument data acquisition system in real time. Multilayer insulation blankets with hydrogen getter under high vacuum in the cryostat minimize heat loss into LH2 storage. All the components were carefully assembled in dust, oil and solvent-free environment with extra caution of vacuum tightness followed by dry nitrogen and helium purge. After initial cool-down of the cryocooler under vacuum, 99.999% of 300K hydrogen gas was introduced to the liquefaction plant. From a series of liquefaction tests with or without LN2 precooling, the hydrogen liquefaction plant successfully demonstrated 1.4 L/hr of hydrogen liquefaction with LN2 precooling and two o-p hydrogen converters, and 0.7 L/hr without LN2 precooling

Performance Test Of A 6 L Liquid Hydrogen Fuel Tank For Unmanned Aerial Vehicles

A 6 L liquid hydrogen fuel tank has been designed, fabricated and tested to optimize boil-off rate and minimize weight for a 200 W light weight fuel cell in an unmanned aerial vehicle (UAV). The 200 W fuel cell required a maximum flow rate of 2.3 SLPM or less liquid hydrogen boil-off from the fuel tank. After looking at several different insulation schemes, the system was optimized as two concentric lightweight aluminum cylinders with high vacuum and multi-layer insulation in between. MLI thickness and support structures were designed to minimize the tank weight. For support, filling and feed gas to a fuel-cell, the system was designed with two G-10 CR tubes which connected the inner vessel to the outer shell. A secondary G10-CR support structure was also added to ensure stability and durability during a flight. After fabrication the fuel tank was filled with liquid hydrogen. A series of boil-off tests were performed in various operating conditions to confirm thermal performance of the fuel tank for a 200 W fuel cell