Radiological assessment for Space Station Freedom

Circumstances have made it necessary to reassess the risks to Space Station Freedom crewmembers that arise from exposure to the space radiation environment. An option is being considered to place it in an orbit similar to that of the Russian Mir space station. This means it would be in a 51.6 deg inclination orbit instead of the previously planned 28.5 deg inclination orbit. A broad range of altitudes is still being considered, although the baseline is a 407 km orbit. In addition, recent data from the Japanese A-bomb survivors has made it necessary for NASA to have the exposure limits reviewed. Preliminary findings of the National Council on Radiation Protection and Measurements indicate that the limits must be significantly reduced. Finally, the Space Station will be a laboratory where effects of long-term zero gravity on human physiology will be studied in detail. It is possible that a few crewmembers will be assigned to as many as three 1-year missions. Thus, their accumulated exposure will exceed 1,000 days. Results of this radiation risk assessment for Space Station Freedom crewmembers finds that females less than 35 years old will be confined to mission assignments where the altitude is less than about 400 km. Slight restrictions may also need to be made for male crewmembers less than 35 years old

Applications of Partial Supersymmetry

I examine quantum mechanical Hamiltonians with partial supersymmetry, and explore two main applications. First, I analyze a theory with a logarithmic spectrum, and show how to use partial supersymmetry to reveal the underlying structure of this theory. This method reveals an intriguing equivalence between two formulations of this theory, one of which is one-dimensional, and the other of which is infinite-dimensional. Second, I demonstrate the use of partial supersymmetry as a tool to obtain the asymptotic energy levels in non-relativistic quantum mechanics in an exceptionally easy way. In the end, I discuss possible extensions of this work, including the possible connections between partial supersymmetry and renormalization group arguments.Comment: 11 pages, harvmac, no figures; typo corrected in identifying info on title pag

The Uniqueness Theorem for Entanglement Measures

We explore and develop the mathematics of the theory of entanglement measures. After a careful review and analysis of definitions, of preliminary results, and of connections between conditions on entanglement measures, we prove a sharpened version of a uniqueness theorem which gives necessary and sufficient conditions for an entanglement measure to coincide with the reduced von Neumann entropy on pure states. We also prove several versions of a theorem on extreme entanglement measures in the case of mixed states. We analyse properties of the asymptotic regularization of entanglement measures proving, for example, convexity for the entanglement cost and for the regularized relative entropy of entanglement.Comment: 22 pages, LaTeX, version accepted by J. Math. Phy

Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies

BACKGROUND: Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery. METHODS: In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, ((99m)Tc-DTPA) and ((99m)Tc-MDP), and two lipophilic tracers, ((99m)Tc-ECD) and ((99m)Tc-MIBI), were used as drug models. RESULTS: Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for (99m)Tc-DTPA, (99m)Tc-ECD and (99m)Tc-MIBI. High correlation coefficients were found for (99m)Tc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies. CONCLUSION: Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics

Group Averaging of massless scalar fields in 1+1 de Sitter

Perturbative gravity in global de Sitter space is subject to so-called linearization stability constraints: If they are to couple consistently to the gravitational field, quantum states must be invariant under the de Sitter isometries. While standard Fock spaces contain no de Sitter-invariant states apart from (possibly) the vacuum, a full Hilbert space of de Sitter-invariant quantum states can be constructed via group averaging techiniques. We re-examine the simple toy model of de Sitter group averaging given by the free 1+1 scalar field, expanding on an earlier analysis by Higuchi. Our purpose is twofold: to include the scalar zero-mode, and to explicitly count the number of de Sitter-invariant states as a function of an appropriately defined energy.Comment: 14 pages, accepted to Classical and Quantum Gravit

On local indistinguishability of orthogonal pure states by using a bound on distillable entanglement

We show that the four states a|00>+b|11>, b^*|00>-a^*|11>, c|01>+d|10> and d^*|01>-c^*|10> cannot be discriminated with certainty if only local operations and classical communication (LOCC) are allowed and if only a single copy is provided, except in the case when they are simply |00>, |11>, |01> and |10> (in which case they are trivially distinguishable with LOCC). We go on to show that there exists a continuous range of values of a, b, c and d such that even three states among the above four are not locally distinguishable, if only a single copy is provided. The proof follows from the fact that logarithmic negativity is an upper bound of distillable entanglement.Comment: 6 pages latex, no figure

Testing for heterogeneity among the components of a binary composite outcome in a clinical trial

<p>Abstract</p> <p>Background</p> <p>Investigators designing clinical trials often use composite outcomes to overcome many statistical issues. Trialists want to maximize power to show a statistically significant treatment effect and avoid inflation of Type I error rate due to evaluation of multiple individual clinical outcomes. However, if the treatment effect is not similar among the components of this composite outcome, we are left not knowing how to interpret the treatment effect on the composite itself. Given significant heterogeneity among these components, a composite outcome may be judged as being invalid or un-interpretable for estimation of the treatment effect. This paper compares the power of different tests to detect heterogeneity of treatment effect across components of a composite binary outcome.</p> <p>Methods</p> <p>Simulations were done comparing four different models commonly used to analyze correlated binary data. These models included: logistic regression for ignoring correlation, logistic regression weighted by the intra cluster correlation coefficient, population average logistic regression using generalized estimating equations (GEE), and random effects logistic regression.</p> <p>Results</p> <p>We found that the population average model based on generalized estimating equations (GEE) had the greatest power across most scenarios. Adequate power to detect possible composite heterogeneity or variation between treatment effects of individual components of a composite outcome was seen when the power for detecting the main study treatment effect for the composite outcome was also reasonably high.</p> <p>Conclusions</p> <p>It is recommended that authors report tests of composite heterogeneity for composite outcomes and that this accompany the publication of the statistically significant results of the main effect on the composite along with individual components of composite outcomes.</p

Corncrake conservation genetics at a European scale: the impact of biogeographical and anthropological processes

Understanding patterns of genetic structure, gene flow and diversity across a species range is required if we are to determine the genetic status and viability of small peripheral populations. This is especially crucial in species distributed across a large range where spatial heterogeneity makes it difficult to predict the distribution of genetic diversity. Although biogeographical models provide expectations of how spatially structured genetic variation may be at the range scale, human disturbance may cause strong deviations from these theoretical predictions. In this study, we investigated genetic structure and demography at a pan-European scale, in the corncrake Crex crex, a grassland bird species strongly affected by agricultural changes. We assessed population structure and genetic diversity, as well as demographic trends and direction of gene flow, in and among 15 contemporary populations of this species. Analyses revealed low genetic structure across the entire range with high levels of genetic diversity in all sites. However, we found some evidence that the westernmost populations were, to a very limited extent, differentiated from the rest of the European population. Demographic trends showed that population numbers have decreased in western Europe and remained constant across eastern Europe. Results may also suggest asymmetric gene flow from eastern to western populations. In conclusion, we suggest that the most likely scenario is that contrasting demographic regimes between eastern and western populations, driven by heterogeneous human activity, has caused asymmetric gene flow that has buffered small peripheral populations against genetic diversity loss, but also erased any genetic structure that may have existed. Our study highlight the need of coordinated actions at the European scale to preserve source populations and ensure the maintenance of reproductive productivity in the most threatened sites, in order to avoid losing any adaptive potential and too strongly relying on sink source populations whose future is uncertain

Increased Expression of PS1 Is Sufficient to Elevate the Level and Activity of γ-Secretase In Vivo

Increase in the generation and deposition of amyloid-β (Aβ) plays a central role in the development of Alzheimer's Disease (AD). Elevation of the activity of γ-secretase, a key enzyme required for the generation for Aβ, can thus be a potential risk factor in AD. However, it is not known whether γ-secretase can be upregulated in vivo. While in vitro studies showed that expression of all four components of γ-secretase (Nicastrin, Presenilin, Pen-2 and Aph-1) are required for upregulation of γ-secretase, it remains to be established as to whether this is true in vivo. To investigate whether overexpressing a single component of the γ-secretase complex is sufficient to elevate its level and activity in the brain, we analyzed transgenic mice expressing either wild type or familial AD (fAD) associated mutant PS1. In contrast to cell culture studies, overexpression of either wild type or mutant PS1 is sufficient to increase levels of Nicastrin and Pen-2, and elevate the level of active γ-secretase complex, enzymatic activity of γ-secretase and the deposition of Aβ in brains of mice. Importantly, γ-secretase comprised of mutant PS1 is less active than that of wild type PS1-containing γ-secretase; however, γ-secretase comprised of mutant PS1 cleaves at the Aβ42 site of APP-CTFs more efficiently than at the Aβ40 site, resulting in greater accumulation of Aβ deposits in the brain. Our data suggest that whereas fAD-linked PS1 mutants cause early onset disease, upregulation of PS1/γ-secretase activity may be a risk factor for late onset sporadic AD