Atomistic simulations of a thermotropic biaxial liquid crystal

We have performed molecular dynamics simulations of a 2,5-bis-(p-hydroxyphenyl)-1,3,4-oxadiazole mesogen ODBP-Ph-C7 at a fully atomistic level for a range of temperatures within the region that has experimentally been assigned to a biaxial nematic phase. Analysis of the data shows that the simulated nematic phase is biaxial but that the degree of biaxiality is small. The simulations show also the formation of ferroelectric domains in the nematic where the molecular short axis is aligned with the oxadiazole dipoles parallel to each other. Removal of electrostatic interactions leads to destabilization of ferroelectric domains and destabilization of the biaxiality. An additional simulation shows the slow growth of a mesophase directly from the isotropic fluid over a period of approximately 50 ns. This is the first time this has been achieved within the framework of an all-atom model

Moderate exercise increases affinity of large very low density lipoproteins for hydrolysis by lipoprotein lipase

Context: Postprandial triglyceride (TG) concentration is independently associated with cardiovascular disease risk. Exercise reduces postprandial TG concentrations but the mechanisms responsible are unclear. Objective: To determine the effects of exercise on affinity of chylomicrons, large very low density lipoproteins (VLDL1) and smaller VLDL (VLDL2) for lipoprotein lipase (LPL) mediated TG hydrolysis. Design: Within-participant cross-over study. Setting: A University metabolic investigation unit. Participants: Ten overweight/obese men. Interventions: Participants undertook two oral fat tolerance tests, separated by 7–14 days, in which they had blood taken fasting and for 4 hours after a high-fat mixed meal. On the afternoon before one test, they performed a 90-minute treadmill walk at 50% maximal oxygen uptake (EX); no exercise was performed before the control test (CON). Main outcome measures: Circulating TG-rich lipoprotein concentrations; affinity of chylomicrons, VLDL1, VLDL2 for LPL-mediated TG hydrolysis. Results: Exercise significantly reduced fasting VLDL1-TG concentration (CON: 0.49(0.33–0.72) mmol.l−1, EX: 0.36(0.22–0.59) mmol.l−1, [geometric means (95% confidence interval)]; p=0.04). Time-averaged postprandial chylomicron-TG (CON: 0.55±0.10 mmol.l−1, EX: 0.39±0.08 mmol.l−1, [mean±SEM], p=0.03) and VLDL1-TG (CON: 0.85±0.13 mmol.l−1, EX: 0.66±0.10 mmol.l−1, p=0.01) concentrations were both lower in EX than CON. Affinity of VLDL1 for LPL-mediated TG hydrolysis increased by 2.2(1.3–3.7) fold (geometric mean (95% confidence interval)) (p=0.02) in the fasted state and 2.6(1.8–2.6) fold (p=0.001) postprandially. Affinity of chylomicrons and VLDL2 was not significantly different between trials. Conclusions: Exercise increases affinity of VLDL1 for LPL-mediated TG hydrolysis both fasting and postprandially. This mechanism is likely to contribute to exercise's TG-lowering effect

Effects of breaking up sedentary time with "chair squats" on postprandial metabolism

Prolonged sitting induces adverse metabolic changes. We aimed to determine whether breaking up prolonged sedentary time with short periods of repeated sit-to-stand transitions (“chair squats”) every 20 minutes influences postprandial metabolic responses. Fourteen participants (11 men, 3 women), age 37 ± 16 years, BMI 30.5 ± 3.8 kg.m−2 (mean ± SD) each participated in two experimental trials in random order, in which they arrived fasted, then consumed a test breakfast (8 kcal.kg−1 body weight, 37% energy from fat, 49% carbohydrates, 14% protein) and, 3.5 hours later, an identical test lunch. Expired air and blood samples were taken fasted and for 6.5 hours postprandially. In one trial (SIT) participants sat continuously throughout the observation period; in the “Chair squat” trial (SIT/STAND), participants performed “chair squats” (10 × standing and sitting over 30 seconds, every 20 minutes). Compared to SIT, energy expenditure was 409.7 ± 41.6 kJ (16.6 ± 1.7%) higher in SIT/STAND (p < 0.0001). Postprandial insulin concentrations over the post-breakfast period were 10.9 ± 8.4% lower in SIT/STAND than SIT (p = 0.047), but did not differ between trials in the post-lunch period. Glucose and triglyceride concentrations did not differ significantly between trials. These data demonstrate that a simple, unobtrusive intervention to break up sedentary time can induce some favourable metabolic changes

Cost-effectiveness of eplerenone in patients with systolic heart failure and mild symptoms

Aim In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), aldosterone blockade with eplerenone decreased mortality and hospitalisation in patients with mild symptoms (New York Heart Association class II) and chronic systolic heart failure (HF). The present study evaluated the cost-effectiveness of eplerenone in the treatment of these patients in the UK and Spain.<p></p> Methods and results Results from the EMPHASIS-HF trial were used to develop a discrete-event simulation model estimating lifetime direct costs and effects (life years and quality-adjusted life years (QALYs) gained) of the addition of eplerenone to standard care among patients with chronic systolic HF and mild symptoms. Eplerenone plus standard care compared with standard care alone increased lifetime direct costs per patient by £4284 for the UK and €7358 for Spain, with additional quality-adjusted life expectancy of 1.22 QALYs for the UK and 1.33 QALYs for Spain. Mean lifetime costs were £3520 per QALY in the UK and €5532 per QALY in Spain. Probabilistic sensitivity analysis suggested a 100% likelihood of eplerenone being regarded as cost-effective at a willingness-to-pay threshold of £20 000 per QALY (UK) or €30 000 per QALY (Spain).<p></p> Conclusions By currently accepted standards of value for money, the addition of eplerenone to optimal medical therapy for patients with chronic systolic HF and mild symptoms is likely to be cost-effective.<p></p&gt

The use of Wonnolas in controlling gastrointestinal nematode infections in sheep under traditional grazing management in Indonesia

Blocks containing 3% phenothiazine in solidified molasses (Wonnolas, Animeal Australia Ltd .) were tested to control gastrointestinal nematode infections and the effect on mineral status in sheep in villages in Cirebon, Indonesia. Two hundred and thirteen Javanese Thin Tail sheep which were grazed during the day and housed at night were divided into two groups on the basis of location . One group was allowed in an access to Wonnolas blocks when penned for 24 weeks while the other group remained untreated. The bodyweight was recorded and faecal samples were collected for egg counts and larval culture every four weeks. Sera and saliva samples were collected from 20 adult sheep in each group at weeks 0, 12 and 24 for mineral analysis by AAS and colorimetry. The results indicated that the mean egg counts of the treated group decreased from 576 epg to 123 epg and the percentage of sheep producing viable larvae decreased from 50% to 24%. In contrast egg counts of the control group increased from 768 epg to 4,840 epg and the percentage of sheep producing viable larvae increased from 65% to 84% over the same period . In the treated group the number of Haenronchus larvae declined significantly (36% to 6 %) and at the end of the trial Tiichostrongylus larvae predominanted in larval cultures (80%) . Mineral analysis revealed deficiencies in sodium and copper, low levels of zinc and normal levels of potassium, calcium, magnesium and phosphorus . Wormolas had a significant effect on sodium and zinc status but not on copper although sufficient levels of this element were available. Comparison of bodyweight gains showed a significantly (P0.05) higher rate of increase in the treated animals

Constraining the Kahler Moduli in the Heterotic Standard Model

Phenomenological implications of the volume of the Calabi-Yau threefolds on the hidden and observable M-theory boundaries, together with slope stability of their corresponding vector bundles, constrain the set of Kaehler moduli which give rise to realistic compactifications of the strongly coupled heterotic string. When vector bundles are constructed using extensions, we provide simple rules to determine lower and upper bounds to the region of the Kaehler moduli space where such compactifications can exist. We show how small these regions can be, working out in full detail the case of the recently proposed Heterotic Standard Model. More explicitely, we exhibit Kaehler classes in these regions for which the visible vector bundle is stable. On the other hand, there is no polarization for which the hidden bundle is stable.Comment: 28 pages, harvmac. Exposition improved, references and one figure added, minor correction

Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system

Juvenile root traits show limited correlation with grain yield, yield components and grain mineral composition traits in Indian wheat under hostile soils

Correlations between juvenile wheat root traits, and grain yield and yield component traits under optimal field conditions have previously been reported in some conditions. The aim of this study was to test the hypothesis that juvenile wheat root traits correlate with yield, yield components and grain mineral composition traits under a range of soil environments in India. A diverse panel of 36 Indian wheat genotypes were grown for ten days in ‘pouch and wick’ high-throughput phenotyping (HTP) system (20 replicates). Correlations between juvenile root architecture traits, including primary and lateral root length, and grain yield, yield components and grain mineral composition traits were determined, using field data from previously published experiments at six sites in India. Only a limited number of juvenile root traits correlated with grain yield (GYD), yield components, and grain mineral composition traits. A narrow root angle, potentially representing a ‘steep’ phenotype, was associated with increased GYD and harvest index (HI) averaged across sites and years. Length related root traits were not correlated with GYD or HI at most sites, however, the total length of lateral roots and lateral root number correlated with GYD at a sodic site of pH 9.5. The total length of lateral roots (TLLR) correlated with grain zinc (Zn) concentration at one site. A wider root angle, representing a shallow root system, correlated with grain iron (Fe) concentration at most sites. The total length of all roots (TLAR) and total length of primary roots (TLPR) correlated with grain S concentration at most sites. Narrow root angle in juvenile plants could be a useful proxy trait for screening germplasm for improved grain yield. Lateral root and shallow root traits could potentially be used to improve grain mineral concentrations. The use of juvenile root traits should be explored further in wheat breeding for diverse environments

Simulation of bulk phases formed by polyphilic liquid crystal dendrimers

A coarse-grained simulation model for a third generation liquid crystalline dendrimer (LCDr) is presented. It allows, for the rst time, for a successful molecular simulation study of a relation between the shape of a polyphilic macromolecular mesogen and the symmetry of a macroscopic phase. The model dendrimer consists of a soft central sphere and 32 grafted chains each terminated by a mesogen group. The mesogenic pair interactions are modelled by the recently proposed soft core spherocylinder model of Lintuvuori and Wilson [J. Chem. Phys, 128, 044906, (2008)]. Coarse-grained (CG) molecular dynamics (MD) simulations are performed on a melt of 100 molecules in the anisotropic-isobaric ensemble. The model LCDr shows conformational bistability, with both rod-like and disc-like conformations stable at lower temperatures. Each conformation can be induced by an external aligning eld of appropriate symmetry that acts on the mesogens (uniaxial for rod-like and planar for disc-like), leading to formation of a monodomain smectic A (SmA) or a columnar (Col) phase, respectively. Both phases are stable for approximately the same temperature range and both exhibit a sharp transition to an isotropic cubic-like phase upon heating. We observe a very strong coupling between the conformation of the LCDr and the symmetry of a bulk phase, as suggested previously by theory. The study reveals rich potential in terms of the application of this form of CG modelling to the study of molecular self-assembly of liquid crystalline macromolecules.Розроблено огрублену модель рідкокристалічного дендримера (РКД) 3-ї генерації, завдяки чому вперше в літературі вивчено взаємозв'язок між формою рідкокристалічної макромолекули та симетрією макроскопічної фази за допомогою молекулярної динаміки. Модель складається з м'якої центральної сфери, до якої приєднано 32 ланцюжки, кожен із яких закінчується мезогенною групою. Останні взаємодіють за допомогою недавно запропонованого анізотропного потенціалу з м'якою серцевиною Лінтувуорі та Вілсона [J. Chem. Phys, 128, 044906, (2008)]. За допомогою методу огрубленої молекулярної динаміки змодельовано розплав 100 молекул РКД в анізотропно-ізобаричному ансамблі. Запропонована модель РКД продемонструвала конформаційну бістабільність, за якої як паличкоподібна, так і дископодібна конформації виявляються стабільними за низьких температур. Кожна з цих 2-х конформацій може ініціюватись зовнішнім полем із відповідною симетрією, в результаті в розплаві спонтанно формуються або монодоменна смектична фаза (із паличкоподібних конформацій, ініційованих одновісним полем), або стовпцева фаза (із дископодібних конформацій, ініційованих планарним полем). Обидві фази є стабільними приблизно в тому ж температурному інтервалі та у процесі нагрівання переходять в ізотропну кубічну фазу через яскраво виражений фазовий перехід. Спостережено сильний зв'язок між конформацією РКД і симетрією об'ємної фази, на що вказано раніше в теоретичних роботах. Дослідження виявляє великий потенціал в застосуванні огрубленого моделювання до опису просторової самоорганізації рідкокристалічних макромолекул