Analysis and Prediction of Protein-Protein Recognition

The aims of the work presented in this thesis were two-fold. Firstly, an existing protein-protein docking algorithm was re-implemented on a type of computer more available than that used originally, and its behaviour was analysed in detail. This analysis led to changes in the scoring function, a treatment of electrostatic complementarity, and side-chain truncation. The algorithm had problems with its representation of surface, but more generally it pointed to difficulties in dealing with conformational change on association. Thus such changes were the second problem studied. They were measured in thirty-nine pairs of structures of complexed and unbound proteins, averaged over interface and non-interface regions and for individual residues. The significance of the changes was evaluated by comparison with the differences seen in twelve pairs of independently solved structures of identical proteins. Just over half had some substantial overall movement. Movements involved main-chains as well as side-chains, and large changes in the interface were closely involved with complex formation, while those of exposed non-interface residues were caused by flexibility and disorder. Interface movements in enzymes were similar in extent to those of inhibitors. All eight of the complexes that had structures of both components in an unbound form available showed some significant interface movement. An algorithm that was tested on five of these complexes was seen to be successful even when some of the largest changes occurred. The situation may be different in systems other than the enzyme-inhibitors which dominate this study. Thus the general model of protein-protein recognition was found to be induced fit. However, because there is only limited conformational change in many systems, recognition can be treated as lock and key to a first approximation

Carbohydrate–protein ingestion during recovery from prolonged exercise in man

Evidence supports that the ingestion of carbohydrate solutions in the post-exercise period can facilitate the restoration of exercise capacity both through providing the fluid necessary for rehydration and through stimulating carbohydrate storage. The accrual of this evidence has now established many components of the optimal carbohydrate feeding strategy during recovery and further progress has been sought through investigating the potential influence of other macronutrients. Specifically, combined ingestion of protein and carbohydrate may promote a more rapid re-synthesis of endogenous glycogen stores than when either nutrient is ingested in isolation. This possibility has led to speculation that ingestion of a mixed carbohydrate-protein solution (CHO–PRO) might restore the capacity for physical exercise more completely during a short-term recovery than when a matched quantity of carbohydrate alone is ingested. However, evidence in support of this hypothesis is not yet available and the present series of studies will therefore attempt to directly examine the effects of CHO–PRO ingestion on recovery of exercise capacity. [Continues.

Recovery of endurance running capacity: effect of carbohydrate-protein mixtures

Including protein in a carbohydrate solution may accelerate both the rate of glycogen storage and the restoration of exercise capacity following prolonged activity. Two studies were undertaken with nine active men in study A and seven in study B. All participants performed 2 trials, each involving a 90 min run at 70% VO2max followed by a 4 h recovery. During recovery, either a 9.3% carbohydrate solution (CHO) or the same solution plus 1.5% protein (CHO-PRO) was ingested every 30 min in volumes providing either 1.2 g CHO · kg-1 · h-1 (study A) or 0.8 g CHO · kg-1 · h-1 (study B). Exercise capacity was then assessed by run time to exhaustion at 85% VO2max. Ingestion of CHO-PRO elicited greater insulinemic responses than CHO (P less than or equal to 0.05) but with no differences in run times to exhaustion. Within the context of this experimental design, CHO and CHO-PRO restored running capacity with equal effect

Carbohydrate availability as a regulator of energy balance with exercise:Carbohydrates and energy balance

We explore the novel hypothesis that carbohydrate availability is involved in the regulation of energy balance with exercise, via hormonal and neural signals. We propose that carbohydrate availability could play a direct mechanistic role and partially explain previously documented relations between a more active lifestyle and tighter control of energy balance.</p

Postexercise glucose–fructose coingestion augments cycling capacity during short-term and overnight recovery from exhaustive exercise, compared with isocaloric glucose:Fructose co-ingestion augments overnight recovery

During short-term recovery, postexercise glucose–fructose coingestion can accelerate total glycogen repletion and augment recovery of running capacity. It is unknown if this advantage translates to cycling, or to a longer (e.g., overnight) recovery. Using two experiments, the present research investigated if postexercise glucose–fructose coingestion augments exercise capacity following 4-hr (short experiment; n = 8) and 15-hr (overnight experiment; n = 8) recoveries from exhaustive exercise in trained cyclists, compared with isocaloric glucose alone. In each experiment, a glycogen depleting exercise protocol was followed by a 4-hr recovery, with ingestion of 1.5 or 1.2 g·kg −1·hr −1 carbohydrate in the short experiment (double blind) and the overnight experiment (single blind), respectively. Treatments were provided in a randomized order using a crossover design. Four or fifteen hours after the glycogen depletion protocol, participants cycled to exhaustion at 70% W max or 65% W max in the short experiment and the overnight experiment, respectively. In both experiments there was no difference in substrate oxidation or blood glucose and lactate concentrations between treatments during the exercise capacity test (trial effect, p &gt; .05). Nevertheless, cycling capacity was greater in glucose + fructose versus glucose only in the short experiment (28.0 ± 8.4 vs. 22.8 ± 7.3 min, d = 0.65, p = .039) and the overnight experiment (35.9 ± 10.7 vs. 30.6 ± 9.2 min, d = 0.53, p = .026). This is the first study to demonstrate that postexercise glucose–fructose coingestion enhances cycling capacity following short-term (4 hr) and overnight (15 hr) recovery durations. Therefore, if multistage endurance athletes are ingesting glucose for rapid postexercise recovery then fructose containing carbohydrates may be advisable. </p

Laryngeal lymphoma : the high and low grades of rare lymphoma involvement sites

The larynx is an extremely rare site of involvement by lymphomatous disease.We present two cases of isolated laryngeal high-grade and another low-grade lymphoma, together with a literature review of laryngeal lymphoma management.peer-reviewe

Circles, columns and screenings: mapping the institutional, discursive, physical and gendered spaces of film criticism in 1940s London

This article revisits the period considered within ‘The Quality Film Adventure: British Critics and the Cinema 1942-1948’, mapping the professional cultures, working contexts and industry relationships that underpinned the aesthetic judgements and collective directions which John Ellis has observed within the critics published writings. Drawing on the records of the Critics’ Circle, Dilys Powell’s papers and Kinematograph Weekly, it explores the evolution of increasingly organised professional cultures of film criticism and film publicity, arguing that the material conditions imposed by war caused tensions between them to escalate. In the context of two major challenges to critical integrity and practice – the evidence given by British producer R.J. Minney in front of the 1948 Royal Commission on the Press and an ongoing libel case between a BBC critic and MGM – the different spaces of hospitality and film promotion became highly contested sites. This article focuses on the ways in which these spaces were characterised, used, and policed. It finds that the value and purpose of press screenings were hotly disputed and observes the way the advancement of women within one sector (film criticism) but not the other (film publicity) created particular difficulties, as key female critics avoided the more compromised masculine spaces of publicity, making them harder for publicists to reach and fuelling trade resentment. More broadly, the article asserts the need to consider film critics as geographically and culturally located audiences, who experience films as ‘professional’ viewers within extended and embodied cultures of habitual professional practice and physical space

A Tool to Explore Discrete-Time Data: The Time Series Response Analyser:Time Series Response Analyser

The analysis of time series data is common in nutrition and metabolism research for quantifying the physiological responses to various stimuli. The reduction of many data from a time series into a summary statistic(s) can help quantify and communicate the overall response in a more straightforward way and in line with a specific hypothesis. Nevertheless, many summary statistics have been selected by various researchers, and some approaches are still complex. The time-intensive nature of such calculations can be a burden for especially large datasets and may, therefore, introduce computational errors, which are difficult to recognize and correct. In this short commentary, we introduce a newly-developed tool that automates many of the processes commonly used by researchers for discrete-time series analysis, with particular emphasis on how the tool may be implemented within nutrition and exercise science research

Design of optimal Earth pole-sitter transfers using low thrust propulsion

Recent studies have shown the feasibility of an Earth pole-sitter mission using low-thrust propulsion. This mission concept involves a spacecraft following the Earth's polar axis to have a continuous, hemispherical view of one of the Earth's poles. Such a view will enhance future Earth observation and telecommunications for high latitude and polar regions. To assess the accessibility of the pole-sitter orbit, this paper investigates optimum Earth pole-sitter transfers employing low-thrust propulsion. A launch from low Earth orbit (LEO) by a Soyuz Fregat upper stage is assumed after which a solar-electric-propulsion thruster transfers the spacecraft to the pole-sitter orbit. The objective is to minimise the mass in LEO for a given spacecraft mass to be inserted into the pole-sitter orbit. The results are compared with a ballistic transfer that exploits the manifolds winding off the pole-sitter orbit. It is shown that, with respect to the ballistic case, low-thrust propulsion can achieve significant mass savings in excess of 200 kg for a pole-sitter spacecraft of 1000 kg upon insertion. To finally obtain a full low-thrust transfer from LEO up to the pole-sitter orbit, the Fregat launch is replaced by a low-thrust, minimum time spiral through an orbital averaging technique, which provides further mass savings, but at the cost of an increased time of flight