66 research outputs found
Freezing of Spinodal Decompostion by Irreversible Chemical Growth Reaction
We present a description of the freezing of spinodal decomposition in
systems, which contain simultaneous irreversible chemical reactions, in the
hydrodynamic limit approximation. From own results we conclude, that the
chemical reaction leads to an onset of spinodal decomposition also in the case
of an initial system which is completely miscible and can lead to an extreme
retardation of the dynamics of the spinodal decomposition, with the probability
of a general freezing of this process, which can be experimetally observed in
simultaneous IPN formation.Comment: 10 page
Fluctuating Bond Aggregation: a Model for Chemical Gel Formation
The Diffusion-Limited Cluster-Cluster Aggregation (DLCA) model is modified by
including cluster deformations using the {\it bond fluctuation} algorithm. From
3 computer simulations, it is shown that, below a given threshold value
of the volumic fraction , the realization of all intra-aggregate
bonding possibilities prevents the formation of a gelling network. For ,
the sol-gel transition occurs at a time which, in contrast to DLCA,
doesnot diverge with the box size. Several results are reported including small
angle scattering curves and possible applications are discussed.Comment: RevTex, 9 pages + 3 postscript figures appended using "uufiles". To
appear in Phys. Rev. Let
Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction
Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes
Effect of aggregation on thermal conduction in colloidal nanofluids
Using effective medium theory we demonstrate that the thermal conductivity of nanofluids can be significantly enhanced by the aggregation of nanoparticles into clusters. The enhancement is based purely on conduction and does not require a novel mechanism. Predictions of the effective medium theory are in excellent agreement with detailed numerical calculations on model nanofluids involving fractal clusters and show the importance of cluster morphology on thermal conductivity enhancements
Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice
Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes
Rhodium catalysed asymmetric hydroformylation with diphosphite ligands based on sugar backbones
DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks
Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations
Mice Lacking beta2-Integrin Function Remain Glucose Tolerant in Spite of Insulin Resistance, Neutrophil Infiltration and Inflammation
Beta2-integrins are important in leukocyte trafficking and function, and are regulated through the binding of cytoplasmic proteins, such as kindlin-3, to their intracellular domain. Here, we investigate the involvement of beta2-integrins in the regulation of metabolic disease using mice where the kindlin-3 binding site in the beta2-integrin cytoplasmic tail has been mutated (TTT/AAA-beta2-integrin knock-in (KI) mice), leading to expressed but dysfunctional beta2-integrins and significant neutrophilia in vivo. Beta2-integrin KI mice fed on a high fat diet showed normal weight gain, and normal accumulation of macrophages and lymphocytes in white adipose tissue (WAT) and liver, but increased neutrophil numbers especially in WAT. In addition, beta2-integrin KI mice fed on a high fat diet showed significantly increased peripheral insulin resistance in response to high-fat feeding. However, this was associated with improved glucose disposal following glucose load. Interestingly, beta2-integrin KI neutrophils produced more elastase in vitro, in response to stimulation. Beta2-integrin KI mice displayed variability of tissue inflammatory status, with liver and WAT exhibiting little or no difference in inflammation compared to high fat fed controls, whereas skeletal muscle demonstrated a raised inflammatory profile in association with higher elastase levels and diminished signalling through the IRS1-PKB pathway. In conclusion, although expression of dysfunctional beta2-integrins increased neutrophil production and infiltration into tissue, skeletal muscle was the most affected tissue exhibiting evidence of higher neutrophil activity and insulin resistance. Thus, beta2-integrins modulate glucose homeostasis during high fat feeding predominantly through actions on skeletal muscle to affect metabolic phenotype in vivo.Peer reviewe
The Bace1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling
Objective -secretase/-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a key enzyme involved in Alzheimer's disease that has recently been implicated in insulin-independent glucose uptake in myotubes. However, it is presently unknown whether BACE1 and the product of its activity, soluble APPsAPPcontribute to lipid-induced inflammation and insulin resistance in skeletal muscle cells. Materials/Methods Studies were conducted in mouse C2C12 myotubes, skeletal muscle from Bace1-/-mice and mice treated with sAPP and adipose tissue and plasma from obese and type 2 diabetic patients. Results We show that BACE1 inhibition or knockdown attenuates palmitate-induced endoplasmic reticulum (ER) stress, inflammation, and insulin resistance and prevents the reduction in Peroxisome Proliferator- Activated Receptor Co-activator 1 (PGC-1) and fatty acid oxidation caused by palmitate in myotubes. The effects of palmitate on ER stress, inflammation, insulin resistance, PGC-1 down-regulation, and fatty acid oxidation were mimicked by soluble APP in vitro. BACE1 expression was increased in subcutaneous adipose tissue of obese and type 2 diabetic patients and this was accompanied by a decrease in PGC-1 mRNA levels and by an increase in sAPPplasma levels of obese type 2 diabetic patients compared to obese non-diabetic subjects. Acute sAPP administration to mice reduced PGC-1 levels and increased inflammation in skeletal muscle and decreased insulin sensitivity. Conclusions Collectively, these findings indicate that the BACE1 product sAPP is a key determinant in ER stress, inflammation and insulin resistance in skeletal muscle and gluconeogenesis in liver
Progress Toward the Study of Laboratory Scale, Astrophysically Relevant, Turbulent Plasmas
Recent results from an ongoing series of Rayleigh-Taylor instability experiments being conducted on the Omega Laser are described. The goal of these experiments is to study, in a controlled laboratory setting, the mixing that occurs at an unstable interface subjected to an acceleration history similar to the explosion phase of a core-collapse supernova. In a supernova, the Reynolds number characterizing this mixing is extremely large (Re > 10 10 ) and is more than sufficient to produce a turbulent flow at the interface. In the laboratory experiment, by contrast, the spatial scales are much smaller, but are still sufficiently large (Re > 10 5 ) to support a turbulent flow and therefore recreate the conditions relevant to the supernova problem. The data from these experiments will be used to validate astrophysical codes as well as to better understand the transition to turbulence in such high energy density systems. The experimental results to date using two-dimensional initial perturbations demonstrate a clear visual transition from a well-ordered perturbation structure consisting of only a few modes to one with considerable modal content. Analysis of these results, however, indicates that while a turbulent spectrum visually appears to be forming, the layer has not yet reached the asymptotic growth rate characteristic of a fully turbulent layer. Recent advances in both target fabrication and diagnostic techniques are discussed as well. These advances will allow for the study of well-controlled 3D perturbations, increasing our ability to recreate the conditions occurring in the supernova.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42030/1/10509_2005_Article_3906.pd
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