Model-based spacecraft and mission design for the evaluation of technology

In order to meet the future vision of robotic missions, engineers will face intricate mission concepts, new operational approaches, and technologies that have yet to be developed. The concept of smaller, model driven projects helps this transition by including life-cycle cost as part of the decision making process. For example, since planetary exploration missions have cost ceilings and short development periods, heritage flight hardware is utilized. However, conceptual designs that rely solely on heritage technology will result in estimates that may not be truly representative of the actual mission being designed and built. The Laboratory for Spacecraft and Mission Design (LSMD) at the California Institute of Technology is developing integrated concurrent models for mass and cost estimations. The purpose of this project is to quantify the infusion of specific technologies where the data would be useful in guiding technology developments leading up to a mission. This paper introduces the design-to-cost model to determine the implications of various technologies on the spacecraft system in a collaborative engineering environment. In addition, comparisons of the benefits of new or advanced technologies for future deep space missions are examined

Testing departure from additivity in Tukey's model using shrinkage: application to a longitudinal setting

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109558/1/sim6281-sup-0001-WebBased.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109558/2/sim6281.pd

Importance of Reward and Prefrontal Circuitry in Hunger and Satiety: Prader-Willi Syndrome vs. Simple Obesity

Background: The majority of research on obesity has focused primarily on clinical features (eating behavior, adiposity measures), or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions which are associated with appetite-regulatory hormones are also involved in the development and maintenance of obesity. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic obesity. Simple (non-PWS) obesity (OB) represents an obesity control state. Objective: This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (i.e., hypothalamus, amygdala) and prefrontal regions associated with cognitive control [i.e., dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC)] after eating. Design and Participants: Fourteen individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls (HWC) viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC, and DLPFC. Results: Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in hypothalamus and hippocampus, in response to food (vs. non-food) images pre-meal. Post-meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared to OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion: In PWS compared with obesity per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple obesity

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

The Impact of Patient Navigation on the Delivery of Diagnostic Breast Cancer Care in the National Patient Navigation Research Program: A Prospective Meta-Analysis.

Patient navigation is emerging as a standard in breast cancer care delivery, yet multi-site data on the impact of navigation at reducing delays along the continuum of care are lacking. The purpose of this study was to determine the effect of navigation on reaching diagnostic resolution at specific time points after an abnormal breast cancer screening test among a national sample. A prospective meta-analysis estimated the adjusted odds of achieving timely diagnostic resolution at 60, 180, and 365 days. Exploratory analyses were conducted on the pooled sample to identify which groups had the most benefit from navigation. Clinics from six medical centers serving vulnerable populations participated in the Patient Navigation Research Program. Women with an abnormal breast cancer screening test between 2007 and 2009 were included and received the patient navigation intervention or usual care. Patient navigators worked with patients and their care providers to address patient-specific barriers to care to prevent delays in diagnosis. A total of 4675 participants included predominantly racial/ethnic minorities (74 %) with public insurance (40 %) or no insurance (31 %). At 60 days and 180 days, there was no statistically significant effect of navigation on achieving timely diagnostic care, but a benefit of navigation was seen at 365 days (aOR 2.12, CI 1.36-3.29). We found an equal benefit of navigation across all groups, regardless of race/ethnicity, language, insurance status, and type of screening abnormality. Patient navigation resulted in more timely diagnostic resolution at 365 days among a diverse group of minority, low-income women with breast cancer screening abnormalities. Trial registrations clinicaltrials.gov Identifiers: NCT00613275, NCT00496678, NCT00375024, NCT01569672

Lepton flavour violation in the MSSM

We derive new constraints on the quantities delta_{XY}^{ij}, X,Y=L,R, which parametrise the flavour-off-diagonal terms of the charged slepton mass matrix in the MSSM. Considering mass and anomalous magnetic moment of the electron we obtain the bound |delta^{13}_{LL} delta^{13}_{RR}|<0.1 for tan beta=50, which involves the poorly constrained element delta^{13}_{RR}. We improve the predictions for the decays tau -> mu gamma, tau -> e gamma and mu -> e gamma by including two-loop corrections which are enhanced if tan beta is large. The finite renormalisation of the PMNS matrix from soft SUSY-breaking terms is derived and applied to the charged-Higgs-lepton vertex. We find that the experimental bound on BR(tau -> e gamma) severely limits the size of the MSSM loop correction to the PMNS element U_{e3}, which is important for the proper interpretation of a future U_{e3} measurement. Subsequently we confront our new values for delta^{ij}_{LL} with a GUT analysis. Further, we include the effects of dimension-5 Yukawa terms, which are needed to fix the Yukawa unification of the first two generations. If universal supersymmetry breaking occurs above the GUT scale, we find the flavour structure of the dimension-5 Yukawa couplings tightly constrained by mu -> e gamma.Comment: 37 pages, 15 figures; typo in Equation (35) and (49) correcte

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Flavor Physics in an SO(10) Grand Unified Model

In supersymmetric grand-unified models, the lepton mixing matrix can possibly affect flavor-changing transitions in the quark sector. We present a detailed analysis of a model proposed by Chang, Masiero and Murayama, in which the near-maximal atmospheric neutrino mixing angle governs large new b -> s transitions. Relating the supersymmetric low-energy parameters to seven new parameters of this SO(10) GUT model, we perform a correlated study of several flavor-changing neutral current (FCNC) processes. We find the current bound on B(tau -> mu gamma) more constraining than B(B -> X_s gamma). The LEP limit on the lightest Higgs boson mass implies an important lower bound on tan beta, which in turn limits the size of the new FCNC transitions. Remarkably, the combined analysis does not rule out large effects in B_s-B_s-bar mixing and we can easily accomodate the large CP phase in the B_s-B_s-bar system which has recently been inferred from a global analysis of CDF and DO data. The model predicts a particle spectrum which is different from the popular Constrained Minimal Supersymmetric Standard Model (CMSSM). B(tau -> mu gamma) enforces heavy masses, typically above 1 TeV, for the sfermions of the degenerate first two generations. However, the ratio of the third-generation and first-generation sfermion masses is smaller than in the CMSSM and a (dominantly right-handed) stop with mass below 500 GeV is possible.Comment: 44 pages, 5 figures. Footnote and references added, minor changes, Fig. 2 corrected; journal versio

Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90

Act1 is an essential adaptor molecule in IL-17-mediated signaling and is recruited to the IL-17 receptor upon IL-17 stimulation. Here, we report that Act1 is a client protein of the molecular chaperone, Hsp90. The Act1 variant (D10N) linked to psoriasis susceptibility is defective in its interaction with Hsp90, resulting in a global loss of Act1 function. Act1-/- mice modeled the mechanistic link between Act1 loss of function and psoriasis susceptibility. Although Act1 is necessary for IL-17-mediated inflammation, Act1-/- mice exhibited a hyper TH17 response and developed spontaneous IL-22-dependent skin inflammation. In the absence of IL-17-signaling, IL-22 is the main contributor to skin inflammation, providing a molecular mechanism for the association of Act1 (D10N) with psoriasis susceptibility

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed