Colloidal processing of Al2O3-doped zirconia ceramics with CaO–P2O5–SiO2 glass as additive

Well dispersed concentrated aqueous suspensions of Al2O3-doped Y-TZP (AY-TZP), AY-TZP with 5.4 vol% of CaO-P2O5-SiO2 (CaPSi) glass (AY-TZP5) and 10.5 vol% CaPSi glass (AY-TZP10), with ammonium polyacrylate (NH4PA) dispersant were prepared to produce slip cast compacts. The rheological properties of 35 and 40 vol% slips were studied. The densification, microstructure as well as hardness and fracture toughness were investigated as a function of CaPSi glass content at 1300-1500 oC. The optimum NH4PA concentration of 35 vol% AY-TZP5 and AY-TZP10 slips at pH ~9 was found to be about 43 and 67 % greater than that of AY-TZP slips, this behaviour was related to the greater amounts of Ca2+ ions leached out from the CaPSi glass surface. The viscosity of stabilized 40 vol% slips with NH4PA attained a minimum value at 5.4 vol% CaPSi glass addition, and resulted in a more dense packing of cast samples. AY-TZP5 can be sintered at a lower temperature (1300 oC) compared to that of AY-TZP. AY-TZP5 exhibited a fine microstructure of tetragonal ZrO2 (grain sizes below 0.3 m), and ZrSiO4 - Ca2P2O7 particles homogeneously distributed within the zirconia matrix. Its presented similar fracture toughness and a slightly lower hardness compared to those of AY-TZP.Fil: Soubelet, Clara Gabriela. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; ArgentinaFil: Albano, Maria Patricia. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; Argentin

Impact of a COPD Discharge Care Bundle on Readmissions following Admission with Acute Exacerbation: Interrupted Time Series Analysis.

We evaluated the impact of a COPD discharge care bundle on readmission rates following hospitalisation with an acute exacerbation.Interrupted time series analysis, comparing readmission rates for COPD exacerbations at nine trusts that introduced the bundle, to two comparison groups; (1) other NHS trusts in London and (2) all other NHS trusts in England. Care bundles were implemented at different times for different NHS trusts, ranging from October 2009 to April 2011.Nine NHS acute trusts in the London, England.Patients aged 45 years and older admitted to an NHS acute hospital in England for acute exacerbation of COPD. Data come from Hospital Episode Statistics, April 2002 to March 2012.Annual trend readmission rates (and in total bed days) within 7, 28 and 90 days, before and after implementation.In hospitals introducing the bundle readmission rates were rising before implementation and falling afterwards (e.g. readmissions within 28 days +2.13% per annum (pa) pre and -5.32% pa post (p for difference in trends = 0.012)). Following implementation, readmission rates within 7 and 28 day were falling faster than among other trusts in London, although this was not statistically significant (e.g. readmissions within 28 days -4.6% pa vs. -3.2% pa, p = 0.44). Comparisons with a national control group were similar.The COPD discharge care bundle appeared to be associated with a reduction in readmission rate among hospitals using it. The significance of this is unclear because of changes to background trends in London and nationally

Caloric and galvanic vestibular stimulation for the treatment of Parkinson’s disease: rationale and prospects

Introduction: Deeply embedded within the inner ear, the sensory organs of the vestibular system are exquisitely sensitive to the orientation and movement of the head. This information constrains aspects of autonomic reflex control as well as higher-level processes involved in cognition and affect. The anatomical pathways that underline these functional interactions project to many cortical and sub-cortical brain areas, and the question arises as to whether they can be therapeutically harnessed. Areas covered: The body of work reviewed here indicates that the controlled application of galvanic or thermal current to the vestibular end-organs can modulate activity throughout the ascending vestibular network and, under appropriate conditions, reduce motor and non-motor symptoms associated with Parkinson’s disease, a disease of growing prevalence and continued unmet clinical need. Expert opinion: The appeal of vestibular stimulation in Parkinson’s disease is underpinned by its noninvasive nature, favorable safety profile, and capacity for home-based administration. Clinical adoption now rests on the demonstration of cost-effectiveness and on the commercial availability of suitable devices, many of which are only permitted for research use or lack functionality. Dose optimization and mechanisms-of-action studies are also needed, along with a broader awareness amongst physicians of its therapeutic potential

Chaos and Elliptical Galaxies

Recent results on chaos in triaxial galaxy models are reviewed. Central mass concentrations like those observed in early-type galaxies -- either stellar cusps, or massive black holes -- render most of the box orbits in a triaxial potential stochastic. Typical Liapunov times are 3-5 crossing times, and ensembles of stochastic orbits undergo mixing on time scales that are roughly an order of magnitude longer. The replacement of the regular orbits by stochastic orbits reduces the freedom to construct self-consistent equilibria, and strong triaxiality can be ruled out for galaxies with sufficiently high central mass concentrations.Comment: uuencoded gziped PostScript, 12 pages including figure

Preferential killing of multidrug-resistant KB cells by inhibitors of glucosylceramide synthase

This study has compared the preferential killing of three multidrug-resistant (MDR) KB cell lines, KB-C1, KB-A1 and KB-V1 by two inhibitors of glucosylceramide synthase, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and 1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (PPPP), to the killing produced by these compounds in the drug-sensitive cell line, KB-3-1. Both of the inhibitors caused much greater induction of apoptosis in each of the three MDR cell lines than in the drug-sensitive cell line, as judged by morphological assay and confirmed by poly-(ADP-ribose)-polymerase cleavage. The highest level of apoptosis was produced following 24-h exposure to 5 μM PPPP. This treatment produced 75.8 (± 7.1)%, 73.6 (± 9.8)% and 75.3 (± 6.4)% apoptotic cells in the three MDR cell lines respectively, compared to 19.0 (± 9.8)% in the drug-sensitive cell line. A reduction in glucosylceramide level following inhibitor treatment occurred in KB-3-1 cells as well as in the MDR cell lines, suggesting that the increased apoptotic response in the MDR cells reflected a different downstream response to changes in the levels of this lipid in these cells compared to that in the drug-sensitive cells. These results suggest that the manipulation of glucosylceramide levels may be a fruitful way of causing the preferential killing of MDR cells in vitro and possibly in vivo. © 1999 Cancer Research Campaig

Genetic and transcriptomic analysis of transcription factor genes in the model halophilic Archaeon: coordinate action of TbpD and TfbA

<p>Abstract</p> <p>Background</p> <p>Archaea are prokaryotic organisms with simplified versions of eukaryotic transcription systems. Genes coding for the general transcription factors TBP and TFB are present in multiple copies in several Archaea, including <it>Halobacterium </it>sp. NRC-1. Multiple TBP and TFBs have been proposed to participate in transcription of genes via recognition and recruitment of RNA polymerase to different classes of promoters.</p> <p>Results</p> <p>We attempted to knock out all six TBP and seven TFB genes in <it>Halobacterium </it>sp. NRC-1 using the <it>ura</it>3-based gene deletion system. Knockouts were obtained for six out of thirteen genes, <it>tbp</it>CDF and <it>tfb</it>ACG, indicating that they are not essential for cell viability under standard conditions. Screening of a population of 1,000 candidate mutants showed that genes which did not yield mutants contained less that 0.1% knockouts, strongly suggesting that they are essential. The transcriptomes of two mutants, Δ<it>tbp</it>D and Δ<it>tfb</it>A, were compared to the parental strain and showed coordinate down regulation of many genes. Over 500 out of 2,677 total genes were regulated in the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutants with 363 regulated in both, indicating that over 10% of genes in both strains require the action of both TbpD and TfbA for normal transcription. Culturing studies on the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains showed them to grow more slowly than the wild-type at an elevated temperature, 49°C, and they showed reduced viability at 56°C, suggesting TbpD and TfbA are involved in the heat shock response. Alignment of TBP and TFB protein sequences suggested the expansion of the TBP gene family, especially in <it>Halobacterium </it>sp. NRC-1, and TFB gene family in representatives of five different genera of haloarchaea in which genome sequences are available.</p> <p>Conclusion</p> <p>Six of thirteen TBP and TFB genes of <it>Halobacterium </it>sp. NRC-1 are non-essential under standard growth conditions. TbpD and TfbA coordinate the expression of over 10% of the genes in the NRC-1 genome. The Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains are temperature sensitive, possibly as a result of down regulation of heat shock genes. Sequence alignments suggest the existence of several families of TBP and TFB transcription factors in <it>Halobacterium </it>which may function in transcription of different classes of genes.</p

Differences in smoking associated DNA methylation patterns in South Asians and Europeans

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Background DNA methylation is strongly associated with smoking status at multiple sites across the genome. Studies have largely been restricted to European origin individuals yet the greatest increase in smoking is occurring in low income countries, such as the Indian subcontinent. We determined whether there are differences between South Asians and Europeans in smoking related loci, and if a smoking score, combining all smoking related DNA methylation scores, could differentiate smokers from non-smokers. Results Illumina HM450k BeadChip arrays were performed on 192 samples from the Southall And Brent REvisited (SABRE) cohort. Differential methylation in smokers was identified in 29 individual CpG sites at 18 unique loci. Interaction between smoking status and ethnic group was identified at the AHRR locus. Ethnic differences in DNA methylation were identified in non-smokers at two further loci, 6p21.33 and GNG12. With the exception of GFI1 and MYO1G these differences were largely unaffected by adjustment for cell composition. A smoking score based on methylation profile was constructed. Current smokers were identified with 100% sensitivity and 97% specificity in Europeans and with 80% sensitivity and 95% specificity in South Asians. Conclusions Differences in ethnic groups were identified in both single CpG sites and combined smoking score. The smoking score is a valuable tool for identification of true current smoking behaviour. Explanations for ethnic differences in DNA methylation in association with smoking may provide valuable clues to disease pathways.Wellcome Trust Enhancement grantMedical Research CouncilDiabetes UKthe British Heart Foundatio

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

Reduced Diversity and High Sponge Abundance on a Sedimented Indo-Pacific Reef System: Implications for Future Changes in Environmental Quality

Although coral reef health across the globe is declining as a result of anthropogenic impacts, relatively little is known of how environmental variability influences reef organisms other than corals and fish. Sponges are an important component of coral reef fauna that perform many important functional roles and changes in their abundance and diversity as a result of environmental change has the potential to affect overall reef ecosystem functioning. In this study, we examined patterns of sponge biodiversity and abundance across a range of environments to assess the potential key drivers of differences in benthic community structure. We found that sponge assemblages were significantly different across the study sites, but were dominated by one species Lamellodysidea herbacea (42% of all sponges patches recorded) and that the differential rate of sediment deposition was the most important variable driving differences in abundance patterns. Lamellodysidea herbacea abundance was positively associated with sedimentation rates, while total sponge abundance excluding Lamellodysidea herbacea was negatively associated with rates of sedimentation. Overall variation in sponge assemblage composition was correlated with a number of variables although each variable explained only a small amount of the overall variation. Although sponge abundance remained similar across environments, diversity was negatively affected by sedimentation, with the most sedimented sites being dominated by a single sponge species. Our study shows how some sponge species are able to tolerate high levels of sediment and that any transition of coral reefs to more sedimented states may result in a shift to a low diversity sponge dominated system, which is likely to have subsequent effects on ecosystem functioning. © 2014 Powell et al

Non-thermal emission processes in massive binaries

In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres