Nematic Ordering of Rigid Rods in a Gravitational Field

The isotropic-to-nematic transition in an athermal solution of long rigid rods subject to a gravitational (or centrifugal) field is theoretically considered in the Onsager approximation. The new feature emerging in the presence of gravity is a concentration gradient which coupled with the nematic ordering. For rodlike molecules this effect becomes noticeable at centrifugal acceleration g ~ 10^3--10^4 m/s^2, while for biological rodlike objects, such as tobacco mosaic virus, TMV, the effect is important even for normal gravitational acceleration conditions. Rods are concentrated near the bottom of the vessel which sometimes leads to gravity induced nematic ordering. The concentration range corresponding to phase separation increases with increasing g. In the region of phase separation the local rod concentration, as well as the order parameter, follow a step function with height.Comment: Full article http://prola.aps.org/abstract/PRE/v60/i3/p2973_

Long-range potential fluctuations and 1/f noise in hydrogenated amorphous silicon

We present a microscopic theory of the low-frequency voltage noise (known as "1/f" noise) in micrometer-thick films of hydrogenated amorphous silicon. This theory traces the noise back to the long-range fluctuations of the Coulomb potential produced by deep defects, thereby predicting the absolute noise intensity as a function of the distribution of defect activation energies. The predictions of this theory are in very good agreement with our own experiments in terms of both the absolute intensity and the temperature dependence of the noise spectra.Comment: 8 pages, 3 figures, several new parts and one new figure are added, but no conceptual revision

Embodied Knowledge: Writing Researchers’ Bodies Into Qualitative Health Research

After more than a decade of postpositivist health care research and an increase in narrative writing practices, social scientific, qualitative health research remains largely disembodied. The erasure of researchers’ bodies from conventional accounts of research obscures the complexities of knowledge production and yields deceptively tidy accounts of research. Qualitative health research could benefit significantly from embodied writing that explores the discursive relationship between the body and the self and the semantic challenges of writing the body by incorporating bodily details and experiences into research accounts. Researchers can represent their bodies by incorporating autoethnographic narratives, drawing on all of their senses, interrogating the connections between their bodily signifiers and research processes, and experimenting with the semantics of self and body. The author illustrates opportunities for embodiment with excerpts from an ethnography of a geriatric oncology team and explores implications of embodied writing for the practice of qualitative health research

“I h 8 u”: Findings from a five-year study of text and e-mail bullying

Copyright @ 2010 British Educational Research Association. The final version of this article is available at the link below.This study charts reports of nasty or threatening text and e-mail messages received by students in academic years 7 and 8 (11-13 years of age) attending 13 secondary schools in the North of England between 2002-2006. Annual surveys were undertaken on behalf of the local education authority (LEA) to monitor bullying. Results indicated that, over five years, the number of pupils receiving one or more nasty or threatening text messages or e-mails increased significantly, particularly among girls. However, receipt of frequent nasty or threatening text and e-mail messages remained relatively stable. For boys, being a victim of direct-physical bullying was associated with receiving nasty or threatening text and e-mail messages; for girls it was being unpopular among peers. Boys received more hate-related messages and girls were primarily the victims of name-calling, Findings are discussed with respect to theoretical and policy developments, and recommendations for future research are offered

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals

The impact of XENON100 and the LHC on Supersymmetric Dark Matter

The effect of 2010 and 2011 LHC data are discussed in connection to the potential for the direct detection of supersymmetric dark matter. The impact of the recent XENON100 results are contrasted to these predictions.Comment: 14 pages, 23 figures, To be published in the Proceedings of the 7th DSU Conference, Beijing Chin

Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa : a modelling study

BACKGROUND: There is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high. METHODS: The HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year. FINDINGS: A transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost. INTERPRETATION: A future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to be effective and cost-effective in low-income settings in sub-Saharan Africa at any prevalence of pre-ART NNRTI resistance. The urgency of the transition will depend largely on the country-specific prevalence of NNRTI resistance. FUNDING: Bill & Melinda Gates Foundation, World Health Organization

ESC Working Group Cellular Biology of the Heart: Position Paper: Improving the pre-clinical assessment of novel cardioprotective therapies

Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischemia-reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed pre-clinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the pre-clinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes

Three non-autonomous signals collaborate for nuclear targeting of CrMYC2, a Catharanthus roseus bHLH transcription factor

<p>Abstract</p> <p>Background</p> <p>CrMYC2 is an early jasmonate-responsive bHLH transcription factor involved in the regulation of the expression of the genes of the terpenic indole alkaloid biosynthesis pathway in <it>Catharanthus roseus</it>. In this paper, we identified the amino acid domains necessary for the nuclear targeting of CrMYC2.</p> <p>Findings</p> <p>We examined the intracellular localization of whole CrMYC2 and of various deletion mutants, all fused with GFP, using a transient expression assay in onion epidermal cells. Sequence analysis of this protein revealed the presence of four putative basic nuclear localization signals (NLS). Assays showed that none of the predicted NLS is active alone. Further functional dissection of CrMYC2 showed that the nuclear targeting of this transcription factor involves the cooperation of three domains located in the C-terminal region of the protein. The first two domains are located at amino acid residues 454-510 and 510-562 and contain basic classical monopartite NLSs; these regions are referred to as NLS3 (KRPRKR) and NLS4 (EAERQRREK), respectively. The third domain, between residues 617 and 652, is rich in basic amino acids that are well conserved in other phylogenetically related bHLH transcription factors. Our data revealed that these three domains are inactive when isolated but act cooperatively to target CrMYC2 to the nucleus.</p> <p>Conclusions</p> <p>This study identified three amino acid domains that act in cooperation to target the CrMYC2 transcription factor to the nucleus. Further fine structure/function analysis of these amino acid domains will allow the identification of new NLS domains and will allow the investigation of the related molecular mechanisms involved in the nuclear targeting of the CrMYC2 bHLH transcription factor.</p