Hybrid FEA/SEA Assessment for an Orthogrid Cylindrical Panel Section and Periodic Subsystem Modeling Evaluation

In the lower frequency range, where particular boundary conditions can make a significant difference to panel response characteristics Statistical Energy Analysis (SEA) has never been the analytical tool of choice. In addition to boundary condition effects, SEA is not well suited in frequency bands where no modes or less than a few modes exist. The advent of the Hybrid Module has enabled integration of Finite Element Analysis to expand and enhance the capability for response calculations within VA One into the lower frequency range. Exploration of several additional modeling approaches was completed for the cylindrical orthogrid panel test article that was examined in Reference 1. Comparison of the new analytical response predictions with the measured response data from ground test and the pure SEA results from the reference will be presented. One approach that is considered promising is the periodic subsystem capability. Initially, a detailed FEM of just one region of the test article is defined. After evaluating this small region using symmetric boundary conditions, the FEM may be expanded to determine the properties of the entire system using similar connected regions that map over the entire test article. Another approach is the direct use of a very detailed finite element model of the entire panel, explicitly modeling pocket and rib details of the structure. A third approach is to approximate localized structure geometry details with a smeared property generalization using a PCOMP (NASTRAN card used to define layered composite structures) to define skin layer and ribbed layer for the orthogrid panel. The authors expect to demonstrate that the integrated Hybrid/FEM approach increases confidence in response prediction in the lower frequency range (for example from 20-300 Hz for the test article under consideration). In addition the strength and weakness of each additional approach will be highlighted and compared to those reported with those reported in an earlier pape

Nano-Scale Strain-Induced Giant Pseudo-Magnetic Fields and Charging Effects in CVD-Grown Graphene on Copper

Scanning tunneling microscopic and spectroscopic (STM/STS) studies of graphene grown by chemical vapor deposition (CVD) on copper reveal that the monolayer carbon structures remaining on copper are strongly strained and rippled, with different regions exhibiting different lattice structures and local electronic density of states (LDOS). The large and non-uniform strain induces pseudo-magnetic field up to ∼ 50 Tesla, as manifested by the integer and fractional pseudo-magnetic field quantum Hall effects (IQHE and FQHE) in the LDOS of graphene. Additionally, ridges appear along the boundaries of different lattice structures, which exhibit excess charging effects. For graphene transferred from copper to SiO_2 substrates after the CVD growth, the average strain and the corresponding charging effects and pseudo-magnetic fields become much reduced. These findings suggest the feasibility of strain-engineering of graphene-based nano-electronics

Control of T lymphocyte morphology by the GTPase Rho

BACKGROUND: Rho family GTPase regulation of the actin cytoskeleton governs a variety of cell responses. In this report, we have analyzed the role of the GTPase Rho in maintenance of the T lymphocyte actin cytoskeleton. RESULTS: Inactivation of the GTPase Rho in the human T lymphocytic cell line HPB-ALL does not inhibit constitutively high adhesion to the integrin β1 substrate fibronectin. It did however result in the aberrant extension of finger-like dendritic processes on the substrates VCAM-1, Fn, and mAb specific to β1 integrins. Time-lapse video microscopy demonstrated that C3 induced extensions were primarily the result of an altered pseudopod elongation rather than retraction. Once the stellate pseudopodia extended, none retracted, and cells became completely immobile. Filipodial structures were absent and the dendritic-like processes in C3 treated cells were rich in filamentous actin. Immunolocalization of RhoA in untreated HPB-ALL cells spreading on fibronectin demonstrated a diffuse staining pattern within the pseudopodia. In C3 treated cells, clusters of RhoA were pronounced and localized within the altered extensions. CONCLUSIONS: GTPase Rho is actively involved in the regulation of T lymphocyte morphology and motility

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

Asthma outcomes: Exacerbations

The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining “exacerbation,” or about how to characterize an episode’s severity

Comparison of Direct Acoustic Impingement of Avionics Equipment to Vibration Base Shake Response

No abstract availabl