Ultrasonic characterization of structural ceramics

Ultrasonic velocity and attenuation measurements were used to characterize density and microstructure in monolithic silicon nitride and silicon carbide. Research samples of these structural ceramics exhibited a wide range of density and microstructural variations. It was shown that bulk density variations correlate with and can be estimated by velocity measurements. Variations in microstructural features such as grain size or shape and pore morphology had a minor effect on velocity. However, these features had a pronounced effect on ultrasonic attenuation. The ultrasonic results are supplemented by low-energy radiography and scanning laser acoustic microscopy

Reliability of void detection in structural ceramics using scanning laser acoustic microscopy

The reliability of scanning laser acoustic microscopy (SLAM) for detecting surface voids in structural ceramic test specimens was statistically evaluated. Specimens of sintered silicon nitride and sintered silicon carbide, seeded with surface voids, were examined by SLAM at an ultrasonic frequency of 100 MHz in the as fired condition and after surface polishing. It was observed that polishing substantially increased void detectability. Voids as small as 100 micrometers in diameter were detected in polished specimens with 0.90 probability at a 0.95 confidence level. In addition, inspection times were reduced up to a factor of 10 after polishing. The applicability of the SLAM technique for detection of naturally occurring flaws of similar dimensions to the seeded voids is discussed. A FORTRAN program listing is given for calculating and plotting flaw detection statistics

Latin as a Formal Language

An attempt at a Montague-style reconstruction of the semantics of Buridan's logic on a regimented fragment of Latin

Factors that affect reliability of nondestructive detection of flaws in structural ceramics

The factors that affect reliability of nondestructive detection of flaws in structural ceramics by microfocus radiography and scanning laser acoustic microscopy (SLAM) were investigated. Reliability of void detection in silicon nitride and silicon carbide by microfocus X-rays was affected by photon energy level, material chemistry in the immediate vicinity of the void, and the presence of loose powder aggregates inside the void cavity. The sensitivity of SLAM to voids was affected by material microstructure, the level of porosity, and the condition of the specimen surfaces. Statistical results are presented in the form of probability of detection as a function of void diameter for green compacts and sintered materials

Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior

Pathological modifications in the highly conserved and ubiquitously expressed heterogeneous ribonucleoprotein TDP-43 were recently associated to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a late-onset disorder that affects predominantly motoneurons [Neumann, M. et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133, Sreedharan, J. et al. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672, Kabashi, E. et al. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574]. However, the function of TDP-43 in vivo is unknown and a possible direct role in neurodegeneration remains speculative. Here, we report that flies lacking Drosophila TDP-43 appeared externally normal but presented deficient locomotive behaviors, reduced life span and anatomical defects at the neuromuscular junctions. These phenotypes were rescued by expression of the human protein in a restricted group of neurons including motoneurons. Our results demonstrate the role of this protein in vivo and suggest an alternative explanation to ALS pathogenesis that may be more due to the lack of TDP 43 function than to the toxicity of the aggregates. © 2009 Federation of European Biochemical Societies

An age-related reduction of brain TBPH/TDP-43 levels precedes the onset of locomotion defects in a Drosophila ALS model

n/

TDP-43 promotes the formation of neuromuscular synapses through the regulation of Disc-large expression in Drosophila skeletal muscles

Background: The ribonuclear protein TDP-43 has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS), with genetic mutations being linked to the neurological symptoms of the disease. Though alterations in the intracellular distribution of TDP-43 have been observed in skeletal muscles of patients suffering from ALS, it is not clear whether such modifications play an active role in the disease or merely represent an expression of muscle homeostatic mechanisms. Also, the molecular and metabolic pathways regulated by TDP-43 in the skeletal muscle remain largely unknown. Here, we analyze the function of TBPH, the Drosophila melanogaster ortholog of TDP-43, in skeletal muscles. Results: We modulated the activity of TDP-43 in Drosophila muscles by means of RNA interference and observed that it is required to promote the formation and growth of neuromuscular synapses. TDP-43 regulated the expression levels of Disc-large (Dlg), and restoring Dlg expression either in skeletal muscles or in motoneurons was sufficient to suppress the locomotive and synaptic defects of TDP-43-null flies. These results were validated by the observation of a decrease in Dlg levels in human neuroblastoma cells and iPSC-differentiated motoneurons derived from ALS patients, suggesting similar mechanisms may potentially be involved in the pathophysiology of the disease. Conclusions: Our results help to unveil the physiological role of TDP-43 in skeletal muscles as well as the mechanisms responsible for the autonomous and non-autonomous behavior of this protein concerning the organization of neuromuscular synapses

Evolutionarily conserved heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins functionally interact with human and drosophila tar DNA-binding protein 43 (TDP-43)

Background: TDP-43 and hnRNPA1/A2 factors are implicated in neurodegeneration. Results: The human and fruit fly TDP-43 and hnRNPA1/A2 orthologs show physical, genetic, and functional interplays. Conclusion: The functional cooperation between TBPH/Hrp38 and TDP-43/hnRNP A/B is conserved throughout evolution. Significance: TBPH/Hrp38 interplay can be critical for neurodegeneration, and Drosophila is a model suitable to study the impact of this interaction. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc