Periodic operation applied to kinetic studies of CO2-methanation

Periodic operation was applied to the CO2 methanation reaction at 383 K on 2% Ru/TiO2. A continuous feed recycle reactor combined with a diffuse reflectance infrared cell and a mass spectrometer allowed to follow simultaneously the gas phase CO2 and CH4 as well as the adsorbed species (CO)a and (formate)a. Experiments consisting of periodic variations of CO2 in the hydrogen feed showed response curves with maxima/minima shifted in time in the sequence CO2, (formate)a --> (CO)a --> CH4. Similar delays measured for the (CO)a formation and hydrogenation indicate that both of these processes are limiting the overall reaction rate. A kinetic model was proposed and verified under periodic conditions. The main experimental trends, which are pronounced time lags between CO2, (CO)a and CH4, could be described satisfactorily

A break in the clouds: connecting community experiences in Mosser, Cumbria

This photo essay accompanies a short film, A Break in the Clouds, which explores everyday life in Mosser, a small former township on the north-west edge of the Lake District. Prompted by the historical diaries of two eighteenth-century Quaker farmers from the same area, connections were drawn between the experiences of the current farmers and those in the past. The text discusses those connections, the making of the film, and how our approach was designed to democratise the research process. The images, selected by the photographer, reflect on the key themes or ‘spaces’ that emerged during the research: home/work, land/family, landscape/weather

Arts on prescription for community‐dwelling older people with a range of health and wellness needs

Published evidence for the role of participatory art in supporting health and well‐being is growing. The Arts on Prescription model is one vehicle by which participatory art can be delivered. Much of the focus of Arts on Prescription has been on the provision of creative activities for people with mental health needs. This Arts on Prescription program, however, targeted community‐dwelling older people with a wide range of health and wellness needs. Older people were referred to the program by their healthcare practitioner. Professional artists led courses in visual arts, photography, dance and movement, drama, singing, or music. Classes were held weekly for 8–10 weeks, with six to eight participants per class, and culminated with a showing of work or a performance. Program evaluation involved pre‐ and postcourse questionnaires, and focus groups and individual interviews. Evaluation data on 127 participants aged 65 years and older were available for analysis. We found that Arts on Prescription had a positive impact on participants. Quantitative findings revealed a statistically significant improvement in the Warwick–Edinburgh Mental Well‐being Scale(WEMWBS) as well as a statistically significant increase in the level of self‐reported creativity and frequency of creative activities. Qualitative findings indicated that the program provided challenging artistic activities which created a sense of purpose and direction, enabled personal growth and achievement, and empowered participants, in a setting which fostered the development of meaningful relationships with others. This evaluation adds to the evidence base in support of Arts on Prescription by expanding the application of the model to older people with a diverse range of health and wellness needs

Skeletal muscle ATP turnover by 31P magnetic resonance spectroscopy during moderate and heavy bilateral knee-extension

During constant-power high-intensity exercise, the expected increase in oxygen uptake (V̇O2) is supplemented by a V̇O2 slow component (V̇O2 sc ), reflecting reduced work efficiency, predominantly within the locomotor muscles. The intracellular source of inefficiency is postulated to be an increase in the ATP cost of power production (an increase in P/W). To test this hypothesis, we measured intramuscular ATP turnover with (31)P magnetic resonance spectroscopy (MRS) and whole-body V̇O2 during moderate (MOD) and heavy (HVY) bilateral knee-extension exercise in healthy participants (n = 14). Unlocalized (31)P spectra were collected from the quadriceps throughout using a dual-tuned ((1)H and (31)P) surface coil with a simple pulse-and-acquire sequence. Total ATP turnover rate (ATPtot) was estimated at exercise cessation from direct measurements of the dynamics of phosphocreatine (PCr) and proton handling. Between 3 and 8 min during MOD, there was no discernable V̇O2 sc (mean ± SD, 0.06 ± 0.12 l min(-1)) or change in [PCr] (30 ± 8 vs. 32 ± 7 mm) or ATPtot (24 ± 14 vs. 17 ± 14 mm min(-1); each P = n.s.). During HVY, the V̇O2 sc was 0.37 ± 0.16 l min(-1) (22 ± 8%), [PCr] decreased (19 ± 7 vs. 18 ± 7 mm, or 12 ± 15%; P < 0.05) and ATPtot increased (38 ± 16 vs. 44 ± 14 mm min(-1), or 26 ± 30%; P < 0.05) between 3 and 8 min. However, the increase in ATPtot (ΔATPtot) was not correlated with the V̇O2 sc during HVY (r(2) = 0.06; P = n.s.). This lack of relationship between ΔATPtot and V̇O2 sc , together with a steepening of the [PCr]-V̇O2 relationship in HVY, suggests that reduced work efficiency during heavy exercise arises from both contractile (P/W) and mitochondrial sources (the O2 cost of ATP resynthesis; P/O)

KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.

Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that specifically inhibit the KRAS isoform by binding to an allosteric site encompassing the region around KRAS-specific residue histidine 95 at the helix α3/loop 7/helix α4 interface. We show that these DARPins specifically inhibit KRAS/effector interactions and the dependent downstream signalling pathways in cancer cells. Binding by the DARPins at that region influences KRAS/effector interactions in different ways, including KRAS nucleotide exchange and inhibiting KRAS dimerization at the plasma membrane. These results highlight the importance of targeting the α3/loop 7/α4 interface, a previously untargeted site in RAS, for specifically inhibiting KRAS function

No effect of glutamine supplementation and hyperoxia on oxidative metabolism and performance during high-intensity exercise.

addresses: Health and Biology, Liverpool Hope University, Liverpool, UK. [email protected]: Comparative Study; Journal ArticleThis is an Author's Accepted Manuscript of an article published in Journal of Sports Sciences, 2008, Vol. 26, Issue 10, pp. 1081 – 1090 © 2008 copyright Taylor & Francis, available online at: http://www.tandfonline.com/doi/abs/10.1080/02640410801930200Glutamine enhances the exercise-induced expansion of the tricarboxylic acid intermediate pool. The aim of the present study was to determine whether oral glutamine, alone or in combination with hyperoxia, influenced oxidative metabolism and cycle time-trial performance. Eight participants consumed either placebo or 0.125 g kg body mass(-1) of glutamine in 5 ml kg body mass(-1) placebo 1 h before exercise in normoxic (control and glutamine respectively) or hyperoxic (FiO(2) = 50%; hyperoxia and hyperoxia + glutamine respectively) conditions. Participants then cycled for 6 min at 70% maximal oxygen uptake (VO(2max)) immediately before completing a brief high-intensity time-trial (approximately 4 min) during which a pre-determined volume of work was completed as fast as possible. The increment in pulmonary oxygen uptake during the performance test (DeltaVO(2max), P = 0.02) and exercise performance (control: 243 s, s(x) = 7; glutamine: 242 s, s(x) = 3; hyperoxia: 231 s, s(x) = 3; hyperoxia + glutamine: 228 s, s(x) = 5; P < 0.01) were significantly improved in hyperoxic conditions. There was some evidence that glutamine ingestion increased DeltaVO(2max) in normoxia, but not hyperoxia (interaction drink/FiO(2), P = 0.04), but there was no main effect or impact on performance. Overall, the data show no effect of glutamine ingestion either alone or in combination with hyperoxia, and thus no limiting effect of the tricarboxylic acid intermediate pool size, on oxidative metabolism and performance during maximal exercise

Beetroot juice supplementation speeds O2 uptake kinetics and improves exercise tolerance during severe-intensity exercise initiated from an elevated metabolic rate

Recent research has suggested that dietary nitrate (NO3-) supplementation might alter the physiological responses to exercise via specific effects on type II muscle. Severe-intensity exercise initiated from an elevated metabolic rate would be expected to enhance the proportional activation of higher-order (type II) muscle fibers. The purpose of this study was therefore to test the hypothesis that, compared to placebo (PL), NO3--rich beetroot juice (BR) supplementation would speed the phase II o2 kinetics (τp) and enhance exercise tolerance during severe-intensity exercise initiated from a baseline of moderate-intensity exercise. Nine healthy, physically-active subjects were assigned in a randomized, double-blind, crossover design to receive BR (140 mL/day, containing ~8 mmol of NO3-) and PL (140 mL/day, containing ~0.003 mmol of NO3-) for 6 days. On days 4, 5 and 6 of the supplementation periods, subjects completed a double-step exercise protocol that included transitions from unloaded-to-moderate intensity exercise (U→M) followed immediately by moderate-to-severe-intensity exercise (M→S). Compared to PL, BR elevated resting plasma nitrite concentration (PL: 65 ± 32 vs. BR: 348 ± 170 nM, P0.05). During M→S exercise, the faster o2 kinetics coincided with faster NIRS-derived muscle [deoxyhemoglobin] kinetics (τ; PL: 20 ± 9 vs. BR: 10 ± 3 s, P<0.05) and a 22% greater time-to-task failure (PL: 521 ± 158 vs. BR: 635 ± 258 s, P<0.05). Dietary supplementation with NO3--rich BR juice speeds o2 kinetics and enhances exercise tolerance during severe-intensity exercise when initiated from an elevated metabolic rate

Vaginally Administered PEGylated LIF Antagonist Blocked Embryo Implantation and Eliminated Non-Target Effects on Bone in Mice

Female-controlled contraception/HIV prevention is critical to address health issues associated with gender inequality. Therefore, a contraceptive which can be administered in tandem with a microbicide to inhibit sexually transmitted infections, is desirable. Uterine leukemia inhibitory factor (LIF) is obligatory for blastocyst implantation in mice and associated with infertility in women. We aimed to determine whether a PEGylated LIF inhibitor (PEGLA) was an effective contraceptive following vaginal delivery and to identify non-uterine targets of PEGLA in mice