Application of residual feedback to lunar orbiter residual analysis Final report

Orbit determination of Lunar Orbiter using residual feedbac

Pharmacological And Genetic Reversal Of Age-Dependent Cognitive Deficits Attributable To Decreased Presenilin Function

Alzheimer\u27s disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced

From Victims of Trafficking to Freedom Fighters: Rethinking Migrant Domestic Workers in the Middle East

Throughout the Middle East migrant women are employed to work in people’s homes. While some experience good working relations with employers, others experience forms of abuse and labour coercion. This chapter evaluates critically different ways that system of unfree labour has been variously described and analysed as a form of ‘contract slavery’, ‘debt bondage’ and ‘trafficking’. It also shows how migrant women who describe themselves as ‘freelancers’ exit their original employer’s home both to escape that relation and in hopes of securing a better situation outside of the regular system of employment. Freelancing is more than simply a form of resistance. Rather, women who work as freelance migrant domestic workers challenge directly that state enforced control over their mobility and are on the vanguard of those migrants who are seeking through their own actions to effect social change

Social presence and dishonesty in retail

Self-service checkouts (SCOs) in retail can benefit consumers and retailers, providing control and autonomy to shoppers independent from staff, together with reduced queuing times. Recent research indicates that the absence of staff may provide the opportunity for consumers to behave dishonestly, consistent with a perceived lack of social presence. This study examined whether a social presence in the form of various instantiations of embodied, visual, humanlike SCO interface agents had an effect on opportunistic behaviour. Using a simulated SCO scenario, participants experienced various dilemmas in which they could financially benefit themselves undeservedly. We hypothesised that a humanlike social presence integrated within the checkout screen would receive more attention and result in fewer instances of dishonesty compared to a less humanlike agent. This was partially supported by the results. The findings contribute to the theoretical framework in social presence research. We concluded that companies adopting self-service technology may consider the implementation of social presence in technology applications to support ethical consumer behaviour, but that more research is required to explore the mixed findings in the current study.<br/

PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome:phenotype comparison in two related syndromes

Background Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. Methods Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. Results Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. Conclusions Results show significant between and within syndrome variability. DifferentNFIXvariants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit

Diasporic Encounters, Sacred Journeys: Ritual, Normativity and the Religious Imagination Among International Asian Migrant Women

This issue highlights recent ethnographic work that discloses migrant women’s creative engagements with the people and landscapes in the places they migrate to. We challenge a dominant view that construes women international migrants from Asia as docile bodies shaped and constrained by their transnational (re)productive labours. And we reject simplistic contemporary formulations of transnational migration that posit a singular, homogeneous ‘transnational social field’. Three key processes, relatively ignored and under theorised are interrogated: diaspora formation, ritual performance and changing normativities. A focus on diaspora encourages us to move beyond a political and economic analysis to consider cultural practices, continuities and discontinuities in migrants’ relationships with the people and places they travel to, as well as those left behind. A focus on ritual emphasises the significance of religious performance in the making of place and convivial sociality. A focus on normativity foregrounds the ways that people’s affective relationships are performatively reworked and transgressed within and across discrepant diasporic spaces

Using Multi-view Recognition and Meta-data Annotation to Guide a Robot's Attention

In the transition from industrial to service robotics, robots will have to deal with increasingly unpredictable and variable environments. We present a system that is able to recognize objects of a certain class in an image and to identify their parts for potential interactions. The method can recognize objects from arbitrary viewpoints and generalizes to instances that have never been observed during training, even if they are partially occluded and appear against cluttered backgrounds. Our approach builds on the implicit shape model of Leibe et al. We extend it to couple recognition to the provision of meta-dat

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons—Leu844, Cys845, Ala846, Leu847, and Gly848—located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844–848 exists and will be valuable in the management and genetic counseling of a significant number of individuals

Mediated Diasporas: Material Translations of the Philippines in a Globalized World

Recent work demonstrates the ways that new media and ICTs both in the Philippines and among Filipino diasporans have become central to contemporary processes of identity formation, altering and enabling the articulation of alternative selves and expanding spatially Filipino national identifications and definitions of ‘home’ (Pertierra 2002, 2006, 2010 Tyner and Kuhlke 2000, Ignacio 2005). While attending to media in the specific sense of particular social technologies of mass communication, we extend that work here drawing together new empirical studies both to demonstrate the various ways that a wide range of differently situated migrants make use of those media and by considering processes of mediation in a much broader sense (Mazzarella 2004), an approach that draws together both an analysis of the ‘materialities of migration’ (Basu and Coleman 2008) and ‘the technics of translation’ (Rafael 2005)