Study of Advanced Propulsion Systems for Small Transport Aircraft Technology (STAT) Program

Definitions of takeoff gross weight, performance, and direct operating cost for both a 30 and 50 passenger airplane were established. The results indicate that a potential direct operating cost benefit, resulting from advanced technologies, of approximately 20 percent would be achieved for the 1990 engines. Of the numerous design features that were evaluated, only maintenance-related items contributed to a significant decrease in direct operating cost. Recommendations are made to continue research and technology programs for advanced component and engine development

A systematic review of the role of parents in the development of anxious cognitions in children

Anxious cognitions and parental behavior are important in the development of child anxiety. The current review aims to appraise the literature on the relationship between parental factors and chid anxious cognitions. Online database searches of PsycInfo, Scopus, ProQuest Dissertations and Web of Science were systematically searched using key terms related to 'parent', 'child', 'anxiety' and 'cognitions'. Included studies (N = 13) were quality assessed and study findings were appraised in line with cognitive behavioral frameworks of the parental pathways to the development of anxious cognitions in children. Reviewed studies confirmed that parental factors have a role in the development of their children's anxious cognitions by modelling fearful responses, reducing their child's autonomy, and indirectly via their own expectations about their child. Limitations of the literature are considered, including issues of measurement. Future research should consider multi-modal assessment of parental factors and examine parental behavior and child anxious cognitions in the context of real-life threatening events

A meta-analysis of parental multidimensional perfectionism and child psychological outcomes

Multidimensional perfectionism is a vulnerability factor for poor individual psychological well-being. Less is known about how parental perfectionism is associated with risk for poor child psychological outcomes. The aim of the current meta-analysis was to summarise the nature and magnitude of the association between dimensions of parental perfectionism (perfectionistic concerns; PC or perfectionistic strivings; PS) and child psychological outcomes. Fourteen studies (N = 2,721) met inclusion criteria. The random effects meta-analysis revealed a small, significant, and positive average association between parental PC and child distress when unadjusted, ravg = .153, CI [.08, .22], and when accounting for the contributions of parental PS, ravg = .164, CI [.08, .25]. Moderation analysis of the unadjusted effects found that they varied as a function of the perfectionism scale used, but were robust to differences in parent and child gender. For parental PS, there was a non-significant negative average association with child distress, ravg = -.049, CI [-.13, .04], which was significant after accounting for the contributions of parental PC, ravg = -.084, CI [-.15, -.02]. The current findings suggest that the differential links of perfectionism dimensions with psychological well-being extend to the parent-child relationship, and that parental PC creates vulnerability for child distress

What is psychosis? A meta-synthesis of inductive qualitative studies exploring the experience of psychosis

Qualitative studies have played an important role in elucidating the lived experience of psychosis and there has recently been an increase in the number of such studies. There is now an urgent need to draw together the findings of these studies. This paper performed a meta-synthesis of inductive qualitative peer-reviewed research into psychosis. Ninety-eight articles were identified for systematic appraisal. Four themes, ‘Losing’, ‘Identifying a need for, and seeking, help’, ‘Rebuilding and reforging’, and ‘Better than new: gifts from psychosis’, were identified. The important implications these themes for clinicians and future research are examined upon. These findings also highlight that the experience of psychosis is much more than simply just hallucinations and/or delusions

Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition

Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme–PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores

MicroRNA-31 is required for astrocyte specification

Previously, we determined microRNA-31 (miR-31) is a noncoding tumor suppressive gene frequently deleted in glioblastoma (GBM); miR-31 suppresses tumor growth, in part, by limiting the activity of NF-κB. Herein, we expand our previous studies by characterizing the role of miR-31 during neural precursor cell (NPC) to astrocyte differentiation. We demonstrate that miR-31 expression and activity is suppressed in NPCs by stem cell factors such as Lin28, c-Myc, SOX2 and Oct4. However, during astrocytogenesis, miR-31 is induced by STAT3 and SMAD1/5/8, which mediate astrocyte differentiation. We determined miR-31 is required for terminal astrocyte differentiation, and that the loss of miR-31 impairs this process and/or prevents astrocyte maturation. We demonstrate that miR-31 promotes astrocyte development, in part, by reducing the levels of Lin28, a stem cell factor implicated in NPC renewal. These data suggest that miR-31 deletions may disrupt astrocyte development and/or homeostasis

Monocyte apoptosis in patients with active lupus

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37808/1/1780390827_ftp.pd

Physicochemical characteristics of soluble oligomeric A β and their pathologic role in Alzheimer's disease

Extracellular fibrillar amyloid deposits are prominent and universal Alzheimer's disease (AD) features, but senile plaque abundance does not always correlate directly with the degree of dementia exhibited by AD patients. The mechanism(s) and dynamics of Abeta fibril genesis and deposition remain obscure. Enhanced Abeta synthesis rates coupled with decreased degradative enzyme production and accumulating physical modifications that dampen proteolysis may all enhance amyloid deposit formation. Amyloid accumulation may indirectly exert the greatest pathologic effect on the brain vasculature by destroying smooth muscle cells and creating a cascade of negative impacts on cerebral blood flow. The most visible manifestation of amyloid dis-equilibrium could actually be a defense mechanism employed to avoid serious vascular wall degradation while the major toxic effects to the gray and white matter neurons are mediated by soluble oligomeric Abeta peptides with high beta-sheet content. The recognition that dynamic soluble oligomeric Abeta pools exist in AD and are correlated to disease severity led to neurotoxicity and physical conformation studies. It is now recognized that the most basic soluble Abeta peptides are stable dimers with hydrophobic regions sequestered from the aqueous environment and are capable of higher order aggregations. Time course experiments employing a modified ELISA method able to detect Abeta oligomers revealed dynamic intermolecular interactions and additional experiments physically confirmed the presence of stable amyloid multimers. Amyloid peptides that are rich in beta-sheet structure are capable of creating toxic membrane ion channels and a capacity to self-assemble as annular structures was confirmed in vitro using atomic force microscopy. Biochemical studies have established that soluble Abeta peptides perturb metabolic processes, provoke release of deleterious reactive compounds, reduce blood flow, induce mitochondrial apoptotic toxicity and inhibit angiogenesis. While there is no question that gross amyloid deposition does contribute to AD pathology, the destructive potential now associated with soluble Abeta suggests that treatment strategies that target these molecules may be efficacious in preventing some of the devastating effects of AD.Fil: Watson, Desiree. Pfizer Global Research and Development; Estados UnidosFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Kokjohn, Tyler A.. Midwestern University; Estados UnidosFil: Kuo, Yu Min. National Cheng Kung University; República de ChinaFil: Lyubchenko, Yuri. University of Nebrasca; Estados UnidosFil: Pinsky, David. University of Michigan; Estados UnidosFil: Connolly, E. Sander. Columbia University; Estados UnidosFil: Esh, Chera. Sun Health Research Institute; Estados UnidosFil: Luehrs, Dean C.. Sun Health Research Institute; Estados UnidosFil: Stine, W. Blaine. Midwestern University; Estados UnidosFil: Rowse, Linda M.. Midwestern University; Estados UnidosFil: Emmerling, Mark R.. Midwestern University; Estados UnidosFil: Roher, Alex E.. Sun Health Research Institute; Estados Unido

Cornish identities and migration: a multi-scalar approach

The definitive version is available at www.blackwell-synergy.com. 24 month embargo by the publisher. Article will be released July 2009.In this article we argue that theories of transnationalism have value in exploring the historical context of migration and that historical contexts help to shape such theoretical conceptualizations. Historians of migration have now begun to engage more directly with the literature of transnationalism, focusing on the networks that linked settler and home communities. Here we add to this by examining a nineteenth-century migrant community from a British region through the lens of transnationalism, applying the concept to the case of the Cornish, whose economic specialization produced culturally distinct Cornish communities on the mining frontiers of North America, Australia and South Africa. In doing so, we bring together the issues of scale and time. We review the multiple levels of the Cornish transnational space of the late nineteenth century, which exhibited aspects of both core transnationalism and translocalism. This waned, but in the later twentieth century, a renewed interest in a transnational Cornish identity re-emerged, articulating with changing identity claims in Cornwall itself. To capture better the experience of the Cornish over these two very different phases of transnationalism we identify another subset of transnationalism - that of transregionalism.Leverhulme Trus

Master planned estates : parish or panacea?

Master planned estates in Australia emerge from two major directions: one aims to address the inadequacies of 1970s suburbanisation and the other comes from governments and developers seeking to realise alternatives. The very idea of master planning has a longer history, one that arguably dates back to 19th-century Utopian Socialism and Baron Haussmann\u27s redesign of Paris, which involved a large-scale, comprehensive alternative vision realised by a sanctioned authority. Master planning thereby partakes of both utopianism and authoritarianism. These associations have infused the discussion and construction of Australian master planned estates rendering them both pariah and panacea. But research and my own experience suggests that they are far more panaceas than pariahs