A development cooperation Erasmus Mundus partnership for capacity building in earthquake mitigation science and higher education

Successful practices have shown that a community’s capacity to manage and reduce its seismic risk relies on capitalization on policies, on technology and research results. An important role is played by education, than contribute to strengthening technical curricula of future practitioners and researchers through university and higher education programs. EUNICE is a European Commission funded higher education partnership for international development cooperation with the objective to build capacity of individuals who will operate at institutions located in seismic prone Asian Countries. The project involves five European Universities, eight Asian universities and four associations and NGOs active in advanced research on seismic mitigation, disaster risk management and international development. The project consists of a comprehensive mobility scheme open to nationals from Afghanistan, Bangladesh, China, Nepal, Pakistan, Thailand, Bhutan, India, Indonesia, Malaysia, Maldives, North Korea, Philippines, and Sri Lanka who plan to enroll in school or conduct research at one of five European partner universities in Italy, Greece and Portugal. During the 2010-14 time span a total number of 104 mobilities are being involved in scientific activities at the undergraduate, masters, PhD, postdoctoral and academic-staff exchange levels. Researchers, future policymakers and practitioners build up their curricula over a range of disciplines in the fields of earthquake engineering, seismology, disaster risk management and urban planning

Pathway Analyses Implicate Glial Cells in Schizophrenia

Background: The quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge. Method Ten publically available gene sets (pathways) related to glia, mitochondria, and glutamate were tested for association to schizophrenia and bipolar disorder using MAGENTA as the primary analysis method. To determine the robustness of associations, secondary analyses were performed with: ALIGATOR, INRICH, and Set Screen. Data from the Psychiatric Genomics Consortium (PGC) were used for all analyses. There were 1,068,286 SNP-level p-values for schizophrenia (9,394 cases/12,462 controls), and 2,088,878 SNP-level p-values for bipolar disorder (7,481 cases/9,250 controls). Results: The Glia-Oligodendrocyte pathway was associated with schizophrenia, after correction for multiple tests, according to primary analysis (MAGENTA p = 0.0005, 75% requirement for individual gene significance) and also achieved nominal levels of significance with INRICH (p = 0.0057) and ALIGATOR (p = 0.022). For bipolar disorder, Set Screen yielded nominally and method-wide significant associations to all three glial pathways, with strongest association to the Glia-Astrocyte pathway (p = 0.002). Conclusions: Consistent with findings of white matter abnormalities in schizophrenia by other methods of study, the Glia-Oligodendrocyte pathway was associated with schizophrenia in our genomic study. These findings suggest that the abnormalities of myelination observed in schizophrenia are at least in part due to inherited factors, contrasted with the alternative of purely environmental causes (e.g. medication effects or lifestyle). While not the primary purpose of our study, our results also highlight the consequential nature of alternative choices regarding pathway analysis, in that results varied somewhat across methods, despite application to identical datasets and pathways

Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have been designed to achieve highly selective binding to DNA G-quadruplexes with much weaker binding to DNA duplexes. A systematic set of structurally analogous trimethine cyanines has been synthesized and evaluated for quadruplex targeting. The results reveal that elevated quadruplex binding and specificity are highly sensitive to the polymethine chain length, heterocyclic structure and intrinsic charge of the compound. Biophysical experiments show that the compounds display significant selectivity for quadruplex binding with a higher preference for parallel stranded quadruplexes, such as cMYC. NMR studies revealed the primary binding through an end-stacking mode and SPR studies showed the strongest compounds have primary KD values below 100 nM that are nearly 100-fold weaker for duplexes. The high selectivity of these newly designed trimethine cyanines for quadruplexes as well as their ability to discriminate between different quadruplexes are extremely promising features to develop them as novel probes for targeting quadruplexes in vivo

Advanced Technology Composite Fuselage - Materials and Processes

The goal of Boeing's Advanced Technology Composite Aircraft Structures (ATCAS) program was to develop the technology required for cost and weight efficient use of composite materials in transport fuselage structure. This contractor report describes results of material and process selection, development, and characterization activities. Carbon fiber reinforced epoxy was chosen for fuselage skins and stiffening elements and for passenger and cargo floor structures. The automated fiber placement (AFP) process was selected for fabrication of monolithic and sandwich skin panels. Circumferential frames and window frames were braided and resin transfer molded (RTM'd). Pultrusion was selected for fabrication of floor beams and constant section stiffening elements. Drape forming was chosen for stringers and other stiffening elements. Significant development efforts were expended on the AFP, braiding, and RTM processes. Sandwich core materials and core edge close-out design concepts were evaluated. Autoclave cure processes were developed for stiffened skin and sandwich structures. The stiffness, strength, notch sensitivity, and bearing/bypass properties of fiber-placed skin materials and braided/RTM'd circumferential frame materials were characterized. The strength and durability of cocured and cobonded joints were evaluated. Impact damage resistance of stiffened skin and sandwich structures typical of fuselage panels was investigated. Fluid penetration and migration mechanisms for sandwich panels were studied

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development

Book reviews

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46105/1/168_2005_Article_BF01287741.pd

Sprouty2 in the Dorsal Hippocampus Regulates Neurogenesis and Stress Responsiveness in Rats

Both the development and relief of stress-related psychiatric conditions such as major depression (MD) and post-traumatic stress disorder (PTSD) have been linked to neuroplastic changes in the brain. One such change involves the birth of new neurons (neurogenesis), which occurs throughout adulthood within discrete areas of the mammalian brain, including the dorsal hippocampus (HIP). Stress can trigger MD and PTSD in humans, and there is considerable evidence that it can decrease HIP neurogenesis in laboratory animals. In contrast, antidepressant treatments increase HIP neurogenesis, and their efficacy is eliminated by ablation of this process. These findings have led to the working hypothesis that HIP neurogenesis serves as a biomarker of neuroplasticity and stress resistance. Here we report that local alterations in the expression of Sprouty2 (SPRY2), an intracellular inhibitor of growth factor function, produces profound effects on both HIP neurogenesis and behaviors that reflect sensitivity to stressors. Viral vector-mediated disruption of endogenous Sprouty2 function (via a dominant negative construct) within the dorsal HIP of adult rats stimulates neurogenesis and produces signs of stress resilience including enhanced extinction of conditioned fear. Conversely, viral vector-mediated elevation of SPRY2 expression intensifies the behavioral consequences of stress. Studies of these manipulations in HIP primary cultures indicate that SPRY2 negatively regulates fibroblast growth factor-2 (FGF2), which has been previously shown to produce antidepressant- and anxiolytic-like effects via actions in the HIP. Our findings strengthen the relationship between HIP plasticity and stress responsiveness, and identify a specific intracellular pathway that could be targeted to study and treat stress-related disorders

A variational approach to a circular hyperelastic membrane problem

The variational principles of nonlinear elasticity are applied to a problem of axially symmetric deformation of a uniform circular hyperelastic membrane. The supported edge of the membrane is in a horizontal plane and its radius is equal to that of the undeformed plane reference configuration, so that an initially plane unstretched membrane is subjected to a dead load due to its weight.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41727/1/707_2005_Article_BF01177244.pd

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table