Two- and three-dimensional simulations of core-collapse supernovae with CHIMERA

Ascertaining the core-collapse supernova mechanism is a complex, and yet unsolved, problem dependent on the interaction of general relativity, hydrodynamics, neutrino transport, neutrino-matter interactions, and nuclear equations of state and reaction kinetics. Ab initio modeling of core-collapse supernovae and their nucleosynthetic outcomes requires care in the coupling and approximations of the physical components. We have built our multi-physics CHIMERA code for supernova modeling in 1-, 2-, and 3-D, using ray-by-ray neutrino transport, approximate general relativity, and detailed neutrino and nuclear physics. We discuss some early results from our current series of exploding 2D simulations and our work to perform computationally tractable simulations in 3D using the "Yin-Yang" grid.Comment: Proceedings of the 12th Symposium on Nuclei in the Cosmos. 5-12 August 2012. Cairns, Australia. Published online at http://pos.sissa.it/archive/conferences/146/208/NIC%20XII_208.pdf Corrected typ

Risk Based Maintenance Of Turbomachinery.

Tutorialpg. 177-188The authors help maintenance staff compete effectively for scarce corporate resources. Their presentation defines important concepts, including expected cost of failure ("risk"), avoided consequential cost, and value of maintenance/timing decisions. They link these concepts to maintenance expenditure. They describe evolving methods for applying them to turbomachinery, and they illustrate their use in optimizing maintenance strategy for the corporation

Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia

Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30–100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann’s area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-β) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated

The Role of Interleukins after Spinal Cord Injury

In skin wound healing the injured tissue goes through a normal progression, inflammation subsides and remodeling occurs. However after spinal cord injury inflammation persists and there is less progression into a regenerative/rebuilding phase. This inflammatory process after spinal cord injury is orchestrated by many cell types and numerous cytokines. Although there are several positive effects of inflammation after spinal cord injury, such as the removal of debris, the substantial upregulation of immune cells has been shown to contribute to neural degeneration. Several chemokines and cytokines including many interleukins are involved in guiding these immune cells to the lesion. While there are many inflammatory cytokines acting on these immune cells after SCI, there are also several anti-inflammatory interleukins that have shown beneficial effects in reducing inflammation. After SCI in a rat model, interleukin-10 and interleukin-19 have been shown to downregulate the synthesis of pro-inflammatory species including interleukin-1β and tumor necrosis factor-α, which resulted in a significant improvement in rat hind limb function. Also, interleukin-4 and interleukin-13 are related anti-inflammatory cytokines that regulate many aspects of inflammation and have also been shown to induce alternative macrophage activation. The differing and complex roles interleukins play, highlight their importance on the inflammation that persists after spinal cord injury. Here we review both the positive effects and negative effects that interleukins have during the multifaceted inflammation process following spinal cord injury

Comparison of TCP and TCP/HA Hybrid Scaffolds for Osteoconductive Activity

Two types of porous ceramic scaffolds were prepared, consisting of β-tricalcium phosphate (TCP) or the mixed powder of TCP and hydroxyapatite (HA) at a 2:1 mass ratio. A variety of methods have been used to fabricate bone scaffolds, while the sintering approach was adopted in this work. An extremely high temperature was used on sintering that proposed to consolidate the ceramic particles. As revealed by SEM, a well opened pore structure was developed within the scaffolds. The θ-values were measured to be of 73.3° and 6.5° for the composite scaffold and TCP sample, respectively. According to XRD patterns, the existence of grains coalescence and partial bonding between HA and TCP powders was demonstrated. Scaffold mechanical property in the term of flexural strength was also determined. The result showed decreasing of the strength by HA supplement, suggesting the more brittle characteristic of HA in comparison with TCP. By soaking the composite scaffold in PBS for a period of 2 weeks, transformation from particles to flank-like crystalline was clearly observed. Such change was found to be favorable for cell attachment, migration, and growth. By implanting cell-seeded scaffolds into nude mice, an abundant osseous extracellular matrix was identified for the composite implants. In contrast, the matrix was minimally detected in TCP implanted samples. Thus, the composite scaffold was found superior for hard tissue regeneration

Osteoinductive recombinant silk fusion proteins for bone regeneration

Protein polymers provide a unique opportunity for tunable designs of material systems due to the genetic basis of sequence control. To address the challenge of biomineralization interfaces with protein based materials, we genetically engineered spider silks to design organic-inorganic hybrid systems. The spider silk inspired domain (SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQGT)15 served as an organic scaffold to control material stability and to allow multiple modes of processing, whereas the hydroxyapatite binding domain VTKHLNQISQSY (VTK), provided control over osteogenesis. The VTK domain was fused either to the N-, C- or both terminals of the spider silk domain to understand the effect of position on material properties and mineralization. The addition of the VTK domain to silk did not affect the physical properties of the silk recombinant constructs, but it had a critical role in the induction of biomineralization. When the VTK domain was placed on both the C- and N-termini the formation of crystalline hydroxyapatite was significantly increased. In addition, all of the recombinant proteins in film format supported the growth and proliferation of human mesenchymal stem cells (hMSCs). Importantly, the presence of the VTK domain enhanced osteoinductive properties 2 up to 3-fold compared to the control (silk alone without VTK). Therefore, silk-VTK fusion proteins have been shown suitable for mineralization and functionalization for specific biomedical applications

Two-Photon Microscopy for Non-Invasive, Quantitative Monitoring of Stem Cell Differentiation

BACKGROUND: The engineering of functional tissues is a complex multi-stage process, the success of which depends on the careful control of culture conditions and ultimately tissue maturation. To enable the efficient optimization of tissue development protocols, techniques suitable for monitoring the effects of added stimuli and induced tissue changes are needed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present the quantitative use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a noninvasive means to monitor the differentiation of human mesenchymal stem cells (hMSCs) using entirely endogenous sources of contrast. We demonstrate that the individual fluorescence contribution from the intrinsic cellular fluorophores NAD(P)H, flavoproteins and lipofuscin can be extracted from TPEF images and monitored dynamically from the same cell population over time. Using the redox ratio, calculated from the contributions of NAD(P)H and flavoproteins, we identify distinct patterns in the evolution of the metabolic activity of hMSCs maintained in either propagation, osteogenic or adipogenic differentiation media. The differentiation of these cells is mirrored by changes in cell morphology apparent in high resolution TPEF images and by the detection of collagen production via SHG imaging. Finally, we find dramatic increases in lipofuscin levels in hMSCs maintained at 20% oxygen vs. those in 5% oxygen, establishing the use of this chromophore as a potential biomarker for oxidative stress. CONCLUSIONS/SIGNIFICANCE: In this study we demonstrate that it is possible to monitor the metabolic activity, morphology, ECM production and oxidative stress of hMSCs in a non-invasive manner. This is accomplished using generally available multiphoton microscopy equipment and simple data analysis techniques, such that the method can widely adopted by laboratories with a diversity of comparable equipment. This method therefore represents a powerful tool, which enables researchers to monitor engineered tissues and optimize culture conditions in a near real time manner

Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin.

The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not

Comparative characterization of mesenchymal stem cells from eGFP transgenic and non-transgenic mice

Abstract Background Adipose derived- and bone marrow-derived murine mesenchymal stem cells (mMSCs) may be used to study stem cell properties in an in vivo setting for the purposes of evaluating therapeutic strategies that may have clinical applications in the future. If these cells are to be used for transplantation, the question arises of how to track the administered cells. One solution to this problem is to transplant cells with an easily identifiable genetic marker such as enhanced green fluorescent protein (eGFP). This protein is fluorescent and therefore does not require a chemical substrate for identification and can be visualized in living cells. This study seeks to characterize and compare adipose derived- and bone marrow-derived stem cells from C57Bl/6 mice and eGFP transgenic C57Bl/6 mice. Results The expression of eGFP does not appear to affect the ability to differentiate along adipogenic or osteogenic lineages; however it appears that the tissue of origin can influence differentiation capabilities. The presence of eGFP had no effect on cell surface marker expression, and mMSCs derived from both bone marrow and adipose tissue had similar surface marker profiles. There were no significant differences between transgenic and non-transgenic mMSCs. Conclusion Murine adipose derived and bone marrow derived mesenchymal stem cells from non-transgenic and eGFP transgenic C57Bl/6 mice have very similar characterization profiles. The availability of mesenchymal stem cells stably expressing a genetic reporter has important applications for the advancement of stem cell research.</p