Emergent Universe with Exotic Matter

A general framework for an emergent universe scenario has been given which makes use of an equation of state. The general features of the model have also been studied and possible primordial composition of the universe have been suggested.Comment: 11 pages, no fi

A powerful bursting radio source towards the Galactic Centre

Transient astronomical sources are typically powered by compact objects and usually signify highly explosive or dynamic events. While radio astronomy has an impressive record of obtaining high time resolution observations, usually it is achieved in quite narrow fields-of-view. Consequently, the dynamic radio sky is poorly sampled, in contrast to the situation in the X- and gamma-ray bands in which wide-field instruments routinely detect transient sources. Here we report a new transient source, GCRT J1745-3009, detected in 2002 during a moderately wide-field radio transient monitoring program of the Galactic center (GC) region at 0.33 GHz. The characteristics of its bursts are unlike those known for any other class of radio transient. If located in or near the GC, its brightness temperature (~10^16 K) and the implied energy density within GCRT J1745-3009 vastly exceeds that observed in most other classes of radio astronomical sources, and is consistent with coherent emission processes rarely observed. We conclude that GCRT J1745-3009 is the first member of a new class of radio transient sources, the first of possibly many new classes to be identified through current and upcoming radio surveys.Comment: 16 pages including 3 figures. Appears in Nature, 3 March 200

Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The repeat resides in an encoded region of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein. We evaluated temporal cerebellar expression profiles by RNA sequencing of ATXN2Q127 mice versus wild-type (WT) littermates. ATXN2Q127 mice are characterized by a progressive motor phenotype onset, and have progressive cerebellar molecular and neurophysiological (Purkinje cell firing frequency) phenotypes. Our analysis revealed previously uncharacterized early and progressive abnormal patterning of cerebellar gene expression. Weighted Gene Coexpression Network Analysis revealed four gene modules that were significantly correlated with disease status, composed primarily of genes associated with GTPase signaling, calcium signaling and cell death. Of these genes, few overlapped with differentially expressed cerebellar genes that we identified in Atxn2−/− knockout mice versus WT littermates, suggesting that loss-of-function is not a significant component of disease pathology. We conclude that SCA2 is a disease characterized by gain of function for ATXN2

An economic analysis of email-based telemedicine: A cost minimisation study of two service models

<p>Abstract</p> <p>Background</p> <p>Email-based telemedicine has been reported to be an efficient method of delivering online health services to patients at a distance and is often described as a low-cost form of telemedicine. The service may be low-cost if the healthcare organisation utilise their existing email infrastructure to provide their telemedicine service. Many healthcare organisations use commercial-off-the-shelf (COTS) email applications. COTS email applications are designed for peer-to-peer communication; hence, in situations where multiple clinicians need to be involved, COTS applications may be deficient in delivering telemedicine. Larger services often rely on different staff disciplines to run their service and telemedicine tools for supervisors, clinicians and administrative staff are not available in COTS applications. Hence, some organisations may choose to develop a purpose-written email application to support telemedicine. We have conducted a cost-minimisation analysis of two different service models for establishing and operating an email service. The first service model used a COTS email application and the second used a purpose-written telemedicine application.</p> <p>Methods</p> <p>The actual costs used in the analysis were from two organisations that originally ran their counselling service with a COTS email application and later implemented a purpose-written application. The purpose-written application automated a number of the tasks associated with running an email-based service. We calculated a threshold at which the higher initial costs for software development were offset by efficiency gains from automation. We also performed a sensitivity analysis to determine the effect of individual costs on the threshold.</p> <p>Results</p> <p>The cost of providing an email service at 1000 consultations per annum was $19,930 using a COTS email application and$31,925 using a purpose-written application. At 10,000 consultations per annum the cost of providing the service using COTS email software was $293,341 compared to$272,749 for the purpose-written application. The threshold was calculated at a workload of 5216 consultations per annum. When more than 5216 email consultations per annum are undertaken, the purpose-written application was cheaper than the COTS service model. The sensitivity analysis showed the threshold was most sensitive to changes in administrative staff salaries.</p> <p>Conclusion</p> <p>In the context of telemedicine, we have compared two different service models for email-based communication – purpose-written and COTS applications. Under the circumstances described in the paper, when workload exceeded 5216 email consultations per annum, there were savings made when a purpose-written email application was used. This analysis provides a useful economic model for organisations contemplating the use of an email-based telemedicine system.</p

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2

There are no disease-modifying treatments for adult human neurodegenerative diseases. Here we test RNA-targeted therapies1 in two mouse models of spinocerebellar ataxia type 2 (SCA2), an autosomal dominant polyglutamine disease2. Both models recreate the progressive adult-onset dysfunction and degeneration of a neuronal network that are seen in patients, including decreased firing frequency of cerebellar Purkinje cells and a decline in motor function3,4. We developed a potential therapy directed at the ATXN2 gene by screening 152 antisense oligonucleotides (ASOs). The most promising oligonucleotide, ASO7, downregulated ATXN2 mRNA and protein, which resulted in delayed onset of the SCA2 phenotype. After delivery by intracerebroventricular injection to ATXN2-Q127 mice, ASO7 localized to Purkinje cells, reduced cerebellar ATXN2 expression below 75% for more than 10 weeks without microglial activation, and reduced the levels of cerebellar ATXN2. Treatment of symptomatic mice with ASO7 improved motor function compared to saline-treated mice. ASO7 had a similar effect in the BAC-Q72 SCA2 mouse model, and in both mouse models it normalized protein levels of several SCA2-related proteins expressed in Purkinje cells, including Rgs8, Pcp2, Pcp4, Homer3, Cep76 and Fam107b. Notably, the firing frequency of Purkinje cells returned to normal even when treatment was initiated more than 12 weeks after the onset of the motor phenotype in BAC-Q72 mice. These findings support ASOs as a promising approach for treating some human neurodegenerative diseases

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

The Effects of Mechanical Stress on the Growth, Differentiation, and Paracrine Factor Production of Cardiac Stem Cells

Stem cell therapies have been clinically employed to repair the injured heart, and cardiac stem cells are thought to be one of the most potent stem cell candidates. The beating heart is characterized by dynamic mechanical stresses, which may have a significant impact on stem cell therapy. The purpose of this study is to investigate how mechanical stress affects the growth and differentiation of cardiac stem cells and their release of paracrine factors. In this study, human cardiac stem cells were seeded in a silicon chamber and mechanical stress was then induced by cyclic stretch stimulation (60 cycles/min with 120% elongation). Cells grown in non-stretched silicon chambers were used as controls. Our result revealed that mechanical stretching significantly reduced the total number of surviving cells, decreased Ki-67-positive cells, and increased TUNEL-positive cells in the stretched group 24 hrs after stretching, as compared to the control group. Interestingly, mechanical stretching significantly increased the release of the inflammatory cytokines IL-6 and IL-1β as well as the angiogenic growth factors VEGF and bFGF from the cells in 12 hrs. Furthermore, mechanical stretching significantly reduced the percentage of c-kit-positive stem cells, but increased the expressions of cardiac troponin-I and smooth muscle actin in cells 3 days after stretching. Using a traditional stretching model, we demonstrated that mechanical stress suppressed the growth and proliferation of cardiac stem cells, enhanced their release of inflammatory cytokines and angiogenic factors, and improved their myogenic differentiation. The development of this in vitro approach may help elucidate the complex mechanisms of stem cell therapy for heart failure

The costs and potential savings of a novel telepaediatric service in Queensland

BACKGROUND: There are few cost-minimisation studies in telemedicine. We have compared the actual costs of providing a telepaediatric service to the potential costs if patients had travelled to see the specialist in person. METHODS: In November 2000, we established a novel telepaediatric service for selected regional hospitals in Queensland. Instead of transferring patients to Brisbane, the majority of referrals to specialists in Brisbane were dealt with via videoconference. Since the service began, 1499 consultations have been conducted for a broad range of paediatric sub-specialities including burns, cardiology, child development, dermatology, diabetes, endocrinology, gastroenterology, nephrology, neurology, oncology, orthopaedics, paediatric surgery and psychiatry. RESULTS: During a five year period, the total cost of providing 1499 consultations through the telepaediatric service was A$955,996. The estimated potential cost of providing an outpatient service to the same number of patients at the Royal Children's Hospital in Brisbane was A$1,553,264; thus, telepaediatric services resulted in a net saving of approximately A$600,000 to the health service provider. CONCLUSION: Telepaediatrics was a cheaper method for the delivery of outpatient services when the workload exceeded 774 consultations. A sensitivity analysis showed that the threshold point was most sensitive to changes related to patient travel costs, coordinator salaries and videoconference equipment costs. The study showed substantial savings for the health department, mainly due to reduced costs associated with patient travel

Direct entropy determination and application to artificial spin ice

From thermodynamic origins, the concept of entropy has expanded to a range of statistical measures of uncertainty, which may still be thermodynamically significant. However, laboratory measurements of entropy continue to rely on direct measurements of heat. New technologies that can map out myriads of microscopic degrees of freedom suggest direct determination of configurational entropy by counting in systems where it is thermodynamically inaccessible, such as granular and colloidal materials, proteins and lithographically fabricated nanometre-scale arrays. Here, we demonstrate a conditional-probability technique to calculate entropy densities of translation-invariant states on lattices using limited configuration data on small clusters, and apply it to arrays of interacting nanometre-scale magnetic islands (artificial spin ice). Models for statistically disordered systems can be assessed by applying the method to relative entropy densities. For artificial spin ice, this analysis shows that nearest-neighbour correlations drive longer-range ones.Comment: 10 page

Quantum-inspired interferometry with chirped laser pulses

We introduce and implement an interferometric technique based on chirped femtosecond laser pulses and nonlinear optics. The interference manifests as a high-visibility (> 85%) phase-insensitive dip in the intensity of an optical beam when the two interferometer arms are equal to within the coherence length of the light. This signature is unique in classical interferometry, but is a direct analogue to Hong-Ou-Mandel quantum interference. Our technique exhibits all the metrological advantages of the quantum interferometer, but with signals at least 10^7 times greater. In particular we demonstrate enhanced resolution, robustness against loss, and automatic dispersion cancellation. Our interferometer offers significant advantages over previous technologies, both quantum and classical, in precision time delay measurements and biomedical imaging.Comment: 6 pages, 4 figure