Proton NMR studies of the electronic structure of ZrH/sub x/

The proton spin lattice relaxation times and Knight shifts were measured in f.c.c. (delta-phase) and f.c.t. (epsilon-phase) ZrH/sub x/ for 1.5 or = to x or = to 2.0. Both parameters indicate that N(E/sub F/) is very dependent upon hydrogen content with a maximum occurring at ZrH1 83. This behavior is ascribed to modifications in N(E/sub F/) through a fcc/fct distortion in ZrH/sub x/ associated with a Jahn-Teller effect

Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes

Asset liability modelling and pension schemes: the application of robust optimization to USS

This paper uses a novel numerical optimization technique - robust optimization - that is well suited to solving the asset-liability management (ALM) problem for pension schemes. It requires the estimation of fewer stochastic parameters, reduces estimation risk and adopts a prudent approach to asset allocation. This study is the first to apply it to a real-world pension scheme, and the first ALM model of a pension scheme to maximise the Sharpe ratio. We disaggregate pension liabilities into three components - active members, deferred members and pensioners, and transform the optimal asset allocation into the scheme’s projected contribution rate. The robust optimization model is extended to include liabilities and used to derive optimal investment policies for the Universities Superannuation Scheme (USS), benchmarked against the Sharpe and Tint, Bayes-Stein, and Black-Litterman models as well as the actual USS investment decisions. Over a 144 month out-of-sample period robust optimization is superior to the four benchmarks across 20 performance criteria, and has a remarkably stable asset allocation – essentially fix-mix. These conclusions are supported by six robustness checks

A Dynamic Programming Approach to Adaptive Fractionation

We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a "favorable" anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5 - 85%) depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting), and (iii) we allow large daily fraction size deviations.Comment: 17 pages, 4 figures, 1 tabl

Squamous Cell Carcinoma Metastatic to the Heart Mimicking ST-Elevation Myocardial Infarction

INTRODUCTION Heart disease remains the leading cause of mortality in the United States, accounting for about one quarter of all deaths in 20131. Acute ischemic heart disease is a major subpopulation of this group, and typically presents with characteristic electrocardiographic (EKG) changes. The most concerning of these findings are ST-elevations, as ST Elevation Myocardial Infarction (STEMI) typically indicates the need for emergent reperfusion therapy because 30-day mortality of untreated STEMI is approximately 10-15% versus 5% in treated cases2. As a result, clinicians are taught to recognize the symptoms and signs of myocardial ischemia and STEMI in order to achieve timely reperfusion either via thrombolytic therapy within 30 minutes or percutaneous coronary intervention within 90 minutes. However, ST-elevations may result from etiologies other than acute ischemia, and can be secondary to other acutely life-threatening pathologies or relatively benign, subacute causes. For example, ventricular aneurysms resulting from prior myocardial infarction and pericarditis can result in ST-elevation on EKG. Intracranial hemorrhage or stress (takotsubo) cardiomyopathy can also present with ST-elevations, theorized to be the result of increased catecholamines. Left ventricular hypertrophy, a sequela of poorly controlled hypertension, can also lead to J point elevations mimicking STEMI3,4. Here we review a case of unusual ST-elevation in a patient with oropharyngeal squamous cell carcinoma metastatic to the heart

Alignment between PIN1 Polarity and Microtubule Orientation in the Shoot Apical Meristem Reveals a Tight Coupling between Morphogenesis and Auxin Transport

Morphogenesis during multicellular development is regulated by intercellular signaling molecules as well as by the mechanical properties of individual cells. In particular, normal patterns of organogenesis in plants require coordination between growth direction and growth magnitude. How this is achieved remains unclear. Here we show that in Arabidopsis thaliana, auxin patterning and cellular growth are linked through a correlated pattern of auxin efflux carrier localization and cortical microtubule orientation. Our experiments reveal that both PIN1 localization and microtubule array orientation are likely to respond to a shared upstream regulator that appears to be biomechanical in nature. Lastly, through mathematical modeling we show that such a biophysical coupling could mediate the feedback loop between auxin and its transport that underlies plant phyllotaxis

Revitalization of the NASA Langley Research Center's Infrastructure

The NASA Langley Research Center (Langley) was founded in 1917 as the nation's first civilian aeronautical research facility and NASA's first field center. For nearly 100 years, Langley has made significant contributions to the Aeronautics, Space Exploration, and Earth Science missions through research, technology, and engineering core competencies in aerosciences, materials, structures, the characterization of earth and planetary atmospheres and, more recently, in technologies associated with entry, descent, and landing. An unfortunate but inevitable outcome of this rich history is an aging infrastructure where the longest serving building is close to 80 years old and the average building age is 44 years old. In the current environment, the continued operation and maintenance of this aging and often inefficient infrastructure presents a real challenge to Center leadership in the trade space of sustaining infrastructure versus not investing in future capabilities. To address this issue, the Center has developed a forward looking revitalization strategy that ties future core competencies and technical capabilities to the Center Master Facility Plan to maintain a viable Center well into the future. This paper documents Langley's revitalization strategy which integrates the Center's missions, the Langley 2050 vision, the Center Master Facility Plan, and the New Town repair-by-replacement program through the leadership of the Vibrant Transformation to Advance Langley (ViTAL) Team