Proton translocation in proteins

The active transport of protons across the low dielectric barrier imposed by biological membranes is accomplished by a plethora of proteins that span the ca. 40 Å of the phospholipid bilayer. The free energy derived from the proton electrochemical potential established by the translocation of these protons can subsequently be used to drive vital chemical reactions of the cell, such as ATP synthesis and cell locomotion. Membrane-bound proton translocating proteins have now been found for a variety of organisms and tissues (1). The driving force for proton pumping in these proteins is supplied by numerous mechanisms, including light absorption (e.g. bacteriorhodopsin) (2a,b), ligand binding (e.g. ATPase) (3), and electrochemistry (e.g. electron transfer through cytochrome c oxidase) (4). Thus nature has devised a variety of methods for supplying the energy required for proton pumping by these proteins. Such diversity notwithstanding, the proteins most likely share some common elements of structure and mechanism that allow them to function as proton pumps. A number of theoretical mechanisms have been put forth for both general proton translocation (5-7) and for energy coupling in specific proton pumps. However, despite almost three decades of intensive research, the details of the mechanism(s) and structural requirements for proton pumping remain largely unresolved. To some extent this is the result of the paucity of structural information available for integral membrane proteins. This situation may soon improve as a result of advances in protein methodologies that have allowed several integral membrane proteins to be successfully crystalized (8), and the increased use of genetic engineering to obtain recombinant proton translocating proteins that will offer an opportunity to assess the importance of specific amino acids for the proton translocation process (9)

Space time neural networks for tether operations in space

A space shuttle flight scheduled for 1992 will attempt to prove the feasibility of operating tethered payloads in earth orbit. due to the interaction between the Earth's magnetic field and current pulsing through the tether, the tethered system may exhibit a circular transverse oscillation referred to as the 'skiprope' phenomenon. Effective damping of skiprope motion depends on rapid and accurate detection of skiprope magnitude and phase. Because of non-linear dynamic coupling, the satellite attitude behavior has characteristic oscillations during the skiprope motion. Since the satellite attitude motion has many other perturbations, the relationship between the skiprope parameters and attitude time history is very involved and non-linear. We propose a Space-Time Neural Network implementation for filtering satellite rate gyro data to rapidly detect and predict skiprope magnitude and phase. Training and testing of the skiprope detection system will be performed using a validated Orbital Operations Simulator and Space-Time Neural Network software developed in the Software Technology Branch at NASA's Lyndon B. Johnson Space Center

Learning characteristics of a space-time neural network as a tether skiprope observer

The Software Technology Laboratory at the Johnson Space Center is testing a Space Time Neural Network (STNN) for observing tether oscillations present during retrieval of a tethered satellite. Proper identification of tether oscillations, known as 'skiprope' motion, is vital to safe retrieval of the tethered satellite. Our studies indicate that STNN has certain learning characteristics that must be understood properly to utilize this type of neural network for the tethered satellite problem. We present our findings on the learning characteristics including a learning rate versus momentum performance table

The Application of FAST-NMR for the Identification of Novel Drug Discovery Targets

The continued success of genome sequencing projects has resulted in a wealth of information, but 40-50% of identified genes correspond to hypothetical proteins or proteins of unknown function. The Functional Annotation Screening Technology by NMR (FAST-NMR) screen was developed to assign a biological function for these unannotated proteins with a structure solved by the Protein Structure Initiative. FAST-NMR is based on the premise that a biological function can be described by a similarity in binding sites and ligand interactions with proteins of known function. The resulting co-structure and functional assignment may provide a starting point for a drug discovery effort

Bright Spots: Physical activity investments that work : Active for health Rotherham; Be active to stay healthy

Programme card: Active for Health Rotherham, Be active to stay healthy Country/locality/coverage Rotherham, South Yorkshire, United Kingdom which has an estimated population over 262,000. Target population People living in Rotherham with one or more of the following seven long term conditions; Cardiac, heart failure, stroke, COPD, cancer, lower back pain and a recent fall and/or fracture. What modes/types/domains of physical activity does the program promote? Functional physical activity delivered in community venues aimed at improving rehabilitation and recovery. Which of the 7 best investments the program addresses? Community wide programs and Healthcare What sectors does it involve? The project involves health professionals and exercise specialists by developing a pathway that bridges the gap between National Health Service (NHS) rehabilitation and community physical activity opportunities. Estimated program reach The programme reaches over 1000 patients a year, improving their health and wellbeing. At the time of this publication, 695 patients had registered for the programme and consented to participate in the evaluation. What is special about this program? The programme aims to revolutionise the role that physical activity plays in rehabilitation and recovery, by providing safe, effective and quality assured services in local communities resulting in notable improvements in health and wellbeing. Key programme details Programme website www.rotherhamgetactive.co.uk/activeforhealth #activeforhealth www.facebook.com/activeforhealth

Searching for Signatures of Cosmic Superstrings in the CMB

Because cosmic superstrings generically form junctions and gauge theoretic strings typically do not, junctions may provide a signature to distinguish between cosmic superstrings and gauge theoretic cosmic strings. In cosmic microwave background anisotropy maps, cosmic strings lead to distinctive line discontinuities. String junctions lead to junctions in these line discontinuities. In turn, edge detection algorithms such as the Canny algorithm can be used to search for signatures of strings in anisotropy maps. We apply the Canny algorithm to simulated maps which contain the effects of cosmic strings with and without string junctions. The Canny algorithm produces edge maps. To distinguish between edge maps from string simulations with and without junctions, we examine the density distribution of edges and pixels crossed by edges. We find that in string simulations without Gaussian noise (such as produced by the dominant inflationary fluctuations) our analysis of the output data from the Canny algorithm can clearly distinguish between simulations with and without string junctions. In the presence of Gaussian noise at the level expected from the current bounds on the contribution of cosmic strings to the total power spectrum of density fluctuations, the distinction between models with and without junctions is more difficult. However, by carefully analyzing the data the models can still be differentiated.Comment: 15 page

Octreotide in the Control of Post-Sclerotherapy Bleeding from Oesophageal Varices, Ulcers and Oesophagitis

Bleeding from oesophageal varices, oesophageal ulcers or oesophagitis is occasionally massive and difficult to control. Octreotide, a synthetic analogue of somatostin lowers portal pressure and collateral blood flow including that through varices, increases lower oesophageal sphincter pressure, and inhibits the gastric secretion of acid as well as pepsin. Our current experience suggests it is effective in controlling acute variceal haemorrhage. Therefore we have examined the efficacy of octreotide in the control of postsclerotherapy bleeding from oesophageal varices, oesophageal ulcers and oesophagitis. During the study period 77 patients experienced a significant gastrointestinal bleed (blood pressure < 100 mm Hg, pulse > 100 beats per min or the need to transfuse 2 or more units of blood to restore the haemoglobin level) following injection sclerotherapy of oesophageal varices. The source of bleeding was varices in 42 patients, oesophageal ulcers in 31 and oesophagitis in 4. All patients received a continuous intravenous infusion of octreotide (50 μg/h) for between 40–140h. If bleeding was not controlled in the first 12h after commencing octreotide hourly bolus doses (50 μg) for 24h were superimposed on the continuous infusion. Haemorrhage was successfully controlled by an infusion of octreotide in 38 of the 42 patients with bleeding from varices, in 30 of 31 patients with oesophageal ulceration, and all patients with oesophagitis. In the 1 patient with persistent bleeding from oesophageal ulceration and in 2 of the 4 with continued haemorrhage from varices, haemostasis was achieved by hourly boluses of 50 μg octreotide for 24h in addition to the continuous infusion. No major complications were associated with octreotide administration. The results of this study clearly indicate that octreotide is a safe and effective treatment for the control of severe haemorrhage after technically successful injection sclerotherapy

Intragastric balloon as an adjunct to lifestyle programme in severely obese adolescents: Impact on biomedical outcomes, and skeletal health"

Intragastric Balloons are a temporary, reversible, and safer option compared to bariatric surgery to promote significant weight loss leading to improved metabolic outcomes. However due to subsequent weight regain, alternative procedures are now preferred in adults. In adolescents, more amenable to lifestyle change, balloons may be an alternative to less reversible procedures. Our aim was to assess the tolerability and efficacy of the intragastric balloon in severely obese adolescents and the impact of associated weight loss on biomedical outcomes (glucose metabolism, blood pressure, lipid profiles) and bone density. A 2-year cohort study of 12 adolescents (BMI >3.5 s.d., Tanner stage >4) following 6 months intragastric balloon placement was carried out. Subjects underwent anthropometry, oral glucose tolerance test, and DEXA scans at 0, 6 and 24 months. Results showed clinically relevant improvements in blood pressure, insulin: glucose metabolism, liver function and sleep apnoea at 6 months. Changes were not sustained at 2 years though some parameters (Diastolic BP, HBA1c, insulin AUC) demonstrated longer-term improvement despite weight regain. Despite weight loss, bone mass accrual showed age appropriate increases. In conclusion, the intra-gastric balloon was safe, well tolerated and effective in supporting short-term weight loss and clinically relevant improvement in obesity related complications, which resolved in some individuals. Benefits were not sustained in the majority at 2 years.International Journal of Obesity accepted article preview online, 05 September 2017. doi:10.1038/ijo.2017.215

The Effect of Salsalate Therapy on Endothelial Function in a Broad Range of Subjects

Background: Inflammation is fundamental to the development of atherosclerosis. We examined the effect of anti‐inflammatory doses of salicylate on endothelium‐dependent vasodilation, a biomarker of cardiovascular risk, in a broad range of subjects. Methods and Results: We performed a randomized, double‐blind, placebo‐controlled crossover trial evaluating the effects of 4 weeks of high‐dose salsalate (disalicylate) therapy on endothelium‐dependent flow‐mediated and endothelium‐independent vasodilation. Fifty‐eight subjects, including 17 with metabolic syndrome, 13 with atherosclerosis, and 28 healthy controls, were studied. Among all subjects, endothelium‐dependent flow‐mediated vasodilation decreased after salsalate compared with placebo therapy (P=0.01), whereas nitroglycerin‐mediated, endothelium‐independent vasodilation was unchanged (P=0.97). Endothelium‐dependent flow‐mediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels (n=31, P0.2). Conclusions: Salsalate therapy, particularly when therapeutic salicylate levels are achieved, impairs endothelium‐dependent vasodilation in a broad range of subjects. These data raise concern about the possible deleterious effects of anti‐inflammatory doses of salsalate on cardiovascular risk. Clinical Trial Registration URL: www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827