First-principles method for high-QQ photonic crystal cavity mode calculations

We present a first-principles method to compute radiation properties of ultra-high quality factor photonic crystal cavities. Our Frequency-domain Approach for Radiation (FAR) can compute the far-field radiation pattern and quality factor of cavity modes $\sim 100$ times more rapidly than conventional finite-difference time domain calculations. It also provides a simple rule for engineering the cavity's far-field radiation pattern

Improving the mechanical properties of single-walled carbon nanotube sheets by intercalation of polymeric adhesives

Organic polymers, such as poly(vinyl alcohol), poly(vinyl pyrrolidone), and poly(styrene), were intercalated into single-walled carbon nanotube sheets by soaking the sheets in polymer solutions. Even for short soak times, significant polymer intercalation into existing free volume was observed. Tensile tests on intercalated sheets showed that the Young\u27s modulus, strength, and toughness increased by factors of 3, 9, and 28, respectively, indicating that the intercalated polymer enhances load transmission between nanotubes

Anomalous field-dependent specific heat in charge-ordered Pr1−x_{1-x}Cax_xMnO3_3 and La0.5_{0.5}Ca0.5_{0.5}MnO3_3

We report low temperature specific heat measurements of Pr$_{1-x}$Ca$_{x}$MnO$_{3}$ ($0.3\leq x \leq 0.5$) and La$_{0.5}$Ca$_{0.5}$MnO$_{3}$ with and without applied magnetic field. An excess specific heat, $C^{\prime}(T)$, of non-magnetic origin associated with charge ordering is found for all the samples. A magnetic field sufficient to induce the transition from the charge-ordered state to the ferromagnetic metallic state does not completely remove the $C^{\prime}$ contribution. This suggests that the charge ordering is not completely destroyed by a "melting" magnetic field. In addition, the specific heat of the Pr$_{1-x}$Ca$_{x}$MnO$_{3}$ compounds exhibit a large contribution linear in temperature ($\gamma T$) originating from magnetic and charge disorder.Comment: submitted to PRL 5 pages, 3 figures include

Multilevel analysis of systolic blood pressure and ACE gene I/D polymorphism in 438 Swedish families – a public health perspective

BACKGROUND: Individuals belonging to the same family share a number of genetic as well as environmental circumstances that may condition a common SBP level. Among the genetic factors, the angiotensin converting enzyme (ACE) gene I/D polymorphism appears as a possible candidate as it might influence both SBP and the pharmacological effect of ACE inhibitors. We aimed to combine genetic epidemiology with public health ideas concerning life-course and multilevel epidemiology in order to understand the role of familial factors regarding individual SBP. METHODS: We applied multilevel regression analysis on 1926 individuals nested within 438 families from South Sweden. Modelling familial SBP variance as a function of age and use of ACE inhibitors we calculates a variance partition coefficient and the proportional change in familial SBP variance attributable to differences in ACE gene I/D polymorphism RESULTS: Our results suggest the existence of genetic or environmental circumstances that produce a considerable familial clustering of SBP, especially among individuals using ACE-inhibitors. However, ACE gene I/D polymorphism seems to play a minor role in this context. In addition, familial factors – genetic, environmental or their interaction – shape SBP among non-users of ACE inhibitors but their effect is expressed later in the life-course. CONCLUSION: Strategies directed to prevent hypertension should be launched in younger rather than in older ages and both prevention of hypertension and its treatment with ACE inhibitors should be focused on families rather than on individuals

Structural and doping effects in the half-metallic double perovskite A2A_2CrWO6_6

he structural, transport, magnetic and optical properties of the double perovskite $A_2$CrWO$_6$ with $A=\text{Sr, Ba, Ca}$ have been studied. By varying the alkaline earth ion on the $A$ site, the influence of steric effects on the Curie temperature $T_C$ and the saturation magnetization has been determined. A maximum $T_C=458$ K was found for Sr$_2$CrWO$_6$ having an almost undistorted perovskite structure with a tolerance factor $f\simeq 1$. For Ca$_2$CrWO$_6$ and Ba$_2$CrWO$_6$ structural changes result in a strong reduction of $T_C$. Our study strongly suggests that for the double perovskites in general an optimum $T_C$ is achieved only for $f \simeq 1$, that is, for an undistorted perovskite structure. Electron doping in Sr$_2$CrWO$_6$ by a partial substitution of Sr$^{2+}$ by La$^{3+}$ was found to reduce both $T_C$ and the saturation magnetization $M_s$. The reduction of $M_s$ could be attributed both to band structure effects and the Cr/W antisites induced by doping. Band structure calculations for Sr$_2$CrWO$_6$ predict an energy gap in the spin-up band, but a finite density of states for the spin-down band. The predictions of the band structure calculation are consistent with our optical measurements. Our experimental results support the presence of a kinetic energy driven mechanism in $A_2$CrWO$_6$, where ferromagnetism is stabilized by a hybridization of states of the nonmagnetic W-site positioned in between the high spin Cr-sites.Comment: 14 pages, 10 figure

The Ontario printed educational message (OPEM) trial to narrow the evidence-practice gap with respect to prescribing practices of general and family physicians: a cluster randomized controlled trial, targeting the care of individuals with diabetes and hypertension in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>There are gaps between what family practitioners do in clinical practice and the evidence-based ideal. The most commonly used strategy to narrow these gaps is the printed educational message (PEM); however, the attributes of successful printed educational messages and their overall effectiveness in changing physician practice are not clear. The current endeavor aims to determine whether such messages change prescribing quality in primary care practice, and whether these effects differ with the format of the message.</p> <p>Methods/design</p> <p>The design is a large, simple, factorial, unblinded cluster-randomized controlled trial. PEMs will be distributed with <b><it>informed</it></b>, a quarterly evidence-based synopsis of current clinical information produced by the Institute for Clinical Evaluative Sciences, Toronto, Canada, and will be sent to all eligible general and family practitioners in Ontario. There will be three replicates of the trial, with three different educational messages, each aimed at narrowing a specific evidence-practice gap as follows: 1) angiotensin-converting enzyme inhibitors, hypertension treatment, and cholesterol lowering agents for diabetes; 2) retinal screening for diabetes; and 3) diuretics for hypertension.</p> <p>For each of the three replicates there will be three intervention groups. The first group will receive <b><it>informed </it></b>with an attached postcard-sized, short, directive "outsert." The second intervention group will receive <b><it>informed </it></b>with a two-page explanatory "insert" on the same topic. The third intervention group will receive <b><it>informed</it></b>, with both the above-mentioned outsert and insert. The control group will receive <b><it>informed </it></b>only, without either an outsert or insert.</p> <p>Routinely collected physician billing, prescription, and hospital data found in Ontario's administrative databases will be used to monitor pre-defined prescribing changes relevant and specific to each replicate, following delivery of the educational messages. Multi-level modeling will be used to study patterns in physician-prescribing quality over four quarters, before and after each of the three interventions. Subgroup analyses will be performed to assess the association between the characteristics of the physician's place of practice and target behaviours.</p> <p>A further analysis of the immediate and delayed impacts of the PEMs will be performed using time-series analysis and interventional, auto-regressive, integrated moving average modeling.</p> <p>Trial registration number</p> <p>Current controlled trial ISRCTN72772651.</p

Investigating Bacterial Sources of Toxicity as an Environmental Contributor to Dopaminergic Neurodegeneration

Parkinson disease (PD) involves progressive neurodegeneration, including loss of dopamine (DA) neurons from the substantia nigra. Select genes associated with rare familial forms of PD function in cellular pathways, such as the ubiquitin-proteasome system (UPS), involved in protein degradation. The misfolding and accumulation of proteins, such as α-synuclein, into inclusions termed Lewy Bodies represents a clinical hallmark of PD. Given the predominance of sporadic PD among patient populations, environmental toxins may induce the disease, although their nature is largely unknown. Thus, an unmet challenge surrounds the discovery of causal or contributory neurotoxic factors that could account for the prevalence of sporadic PD. Bacteria within the order Actinomycetales are renowned for their robust production of secondary metabolites and might represent unidentified sources of environmental exposures. Among these, the aerobic genera, Streptomyces, produce natural proteasome inhibitors that block protein degradation and may potentially damage DA neurons. Here we demonstrate that a metabolite produced by a common soil bacterium, S. venezuelae, caused DA neurodegeneration in the nematode, Caenorhabditis elegans, which increased as animals aged. This metabolite, which disrupts UPS function, caused gradual degeneration of all neuronal classes examined, however DA neurons were particularly vulnerable to exposure. The presence of DA exacerbated toxicity because neurodegeneration was attenuated in mutant nematodes depleted for tyrosine hydroxylase (TH), the rate-limiting enzyme in DA production. Strikingly, this factor caused dose-dependent death of human SH-SY5Y neuroblastoma cells, a dopaminergic line. Efforts to purify the toxic activity revealed that it is a highly stable, lipophilic, and chemically unique small molecule. Evidence of a robust neurotoxic factor that selectively impacts neuronal survival in a progressive yet moderate manner is consistent with the etiology of age-associated neurodegenerative diseases. Collectively, these data suggest the potential for exposures to the metabolites of specific common soil bacteria to possibly represent a contributory environmental component to PD

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

Inhibition of protein ubiquitination by paraquat and 1-methyl-4-phenylpyridinium impairs ubiquitin-dependent protein degradation pathways

Intracytoplasmic inclusions of protein aggregates in dopaminergic cells (Lewy bodies) are the pathological hallmark of Parkinson’s disease (PD). Ubiquitin (Ub), alpha [α]-synuclein, p62/sequestosome 1 and oxidized proteins are major components of Lewy bodies. However, the mechanisms involved in the impairment of misfolded/oxidized protein degradation pathways in PD are still unclear. PD is linked to mitochondrial dysfunction and environmental pesticide exposure. In this work, we evaluated the effect of the pesticide paraquat (PQ) and the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) on Ub-dependent protein degradation pathways. No increase in the accumulation of Ub-bound proteins or aggregates was observed in dopaminergic cells (SK-N-SH) treated with PQ or MPP+, or in mice chronically exposed to PQ. PQ decreased Ub protein content, but not its mRNA transcription. Protein synthesis inhibition with cycloheximide depleted Ub levels and potentiated PQ–induced cell death. Inhibition of proteasomal activity by PQ was found to be a late event in cell death progression, and had no effect on either the toxicity of MPP+ or PQ, or the accumulation of oxidized sulfenylated, sulfonylated (DJ-1/PARK7 and peroxiredoxins) and carbonylated proteins induced by PQ. PQ- and MPP+-induced Ub protein depletion prompted the dimerization/inactivation of the Ub-binding protein p62 that regulates the clearance of ubiquitinated proteins by autophagic. We confirmed that PQ and MPP+ impaired autophagy flux, and that the blockage of autophagy by the overexpression of a dominant-negative form of the autophagy protein 5 (dnAtg5) stimulated their toxicity, but there was no additional effect upon inhibition of the proteasome. PQ induced an increase in the accumulation of α-synuclein in dopaminergic cells and membrane associated foci in yeast cells. Our results demonstrate that inhibition of protein ubiquitination by PQ and MPP+ is involved in the dysfunction of Ub-dependent protein degradation pathways