2,095 research outputs found

    Controlled lasing from active optomechanical resonators

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    Planar microcavities with distributed Bragg reflectors (DBRs) host, besides confined optical modes, also mechanical resonances due to stop bands in the phonon dispersion relation of the DBRs. These resonances have frequencies in the sub-terahertz (10E10-10E11 Hz) range with quality factors exceeding 1000. The interaction of photons and phonons in such optomechanical systems can be drastically enhanced, opening a new route toward manipulation of light. Here we implemented active semiconducting layers into the microcavity to obtain a vertical-cavity surface-emitting laser (VCSEL). Thereby three resonant excitations -photons, phonons, and electrons- can interact strongly with each other providing control of the VCSEL laser emission: a picosecond strain pulse injected into the VCSEL excites long-living mechanical resonances therein. As a result, modulation of the lasing intensity at frequencies up to 40 GHz is observed. From these findings prospective applications such as THz laser control and stimulated phonon emission may emerge

    Novas opções para o tratamento preventivo da migrânea: revisão com considerações fisiopatológicas

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    BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world.INTRODUÇÃO: O tratamento farmacológico da migrânea pode ser dividido em agudo e preventivo. Crises de migrânea severas, de longa duração e incapacitante requerem profilaxia. Múltiplas linhas de pesquisa ao longo dos últimos 15 anos sedimentaram o conceito de que a migrânea é gerada a partir de um cérebro hiperexcitável. Variadas causas para essa hiperexcitabilidade têm sido sugeridas e incluem baixo nível de magnésio cerebral, anormalidades mitocondriais, disfunções relacionadas ao óxido nítrico e a existência de distúrbios nos canais de cálcio do tipo P/Q. O melhor conhecimento sobre a fisiopatologia da migrânea nos permite discutir novas opções terapêuticas. OBJETIVOS: O objetivo do presente estudo é apresentar revisão baseada em evidências de novos agentes e outros que, embora disponíveis há mais tempo, não são freqüentemente utilizados, com considerações fisiopatológicas. MÉTODOS/RESULTADOS: Serão revistos anticonvulsivantes com vários mecanismos de ação, como gabapentina, lamotrigina, topiramato, tiagabina, levetiracetam e zonisamida. Serão revistos também produtos naturais, como riboflavina e magnésio, toxina botulínica do tipo A, um antagonista CGRP específico e uma nova opção para o tratamento da asma, o montelukast. CONCLUSÕES: Objetivamos apresentar artigo de atualização em opções novas ou não freqüentemente utilizadas no tratamento preventivo da migrânea, drogas que podem reduzir o fardo e os custos de uma doença que deve ser considerada um problema de saúde pública em todo o mundo

    Measuring kinetic coefficients by molecular dynamics simulation of zone melting

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    Molecular dynamics simulations are performed to measure the kinetic coefficient at the solid-liquid interface in pure gold. Results are obtained for the (111), (100) and (110) orientations. Both Au(100) and Au(110) are in reasonable agreement with the law proposed for collision-limited growth. For Au(111), stacking fault domains form, as first reported by Burke, Broughton and Gilmer [J. Chem. Phys. {\bf 89}, 1030 (1988)]. The consequence on the kinetics of this interface is dramatic: the measured kinetic coefficient is three times smaller than that predicted by collision-limited growth. Finally, crystallization and melting are found to be always asymmetrical but here again the effect is much more pronounced for the (111) orientation.Comment: 8 pages, 9 figures (for fig. 8 : [email protected]). Accepted for publication in Phys. Rev.

    Time course of salivary protein responses to cranberry-derived polyphenol exposure as a function of PROP taster status

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    Astringency is a complex oral sensation, commonly experienced when dietary polyphenols interact with salivary proteins. Most astringent stimuli alter protein levels, which then require time to be replenished. Although it is standard practice in astringency research to provide breaks in between stimuli, there is limited consensus over the amount of time needed to restore the oral environment to baseline levels. Here we examined salivary protein levels after exposure to 20 mL of a model stimulus (cranberry polyphenol extract, 0.75 g/L CPE) or unsweetened cranberry juice (CJ), over a 10 min period. Whole saliva from healthy subjects (n = 60) was collected at baseline and after 5 and 10 min following either stimulus. Five families of proteins: basic proline-rich proteins (bPRPs); acidic proline-rich proteins (aPRPs); histatins; statherin; and S-type cystatins, were analyzed in whole saliva via HPLC-low resolution-ESI-IT-MS, using the area of the extracted ion current (XIC) peaks. Amylase was quantified via immunoblotting. In comparison to baseline (resting), both stimuli led to a rise in levels of aPRPs (p < 0.000) at 5 min which remained elevated at 10 min after stimulation. Additionally, an interaction of PROP taster status and time was observed, wherein super-tasters had higher levels of amylase in comparison to non-tasters after stimulation with CJ at both timepoints (p = 0.014–0.000). Further, male super-tasters had higher levels of bPRPs at 5 min after stimulation with both CJ and CPE (p = 0.015–0.007) in comparison to baseline. These data provide novel findings of interindividual differences in the salivary proteome that may influence the development of astringency and that help inform the design of sensory experiments of astringency

    Progestogen-only contraceptive use among breastfeeding women: a systematic review.

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    Background: Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes. Objectives: We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs. Search strategy: We searched the PubMed database for all articles published from database inception through December 2014. Selection criteria: We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, injectables, implants or hormonal intrauterine devices (IUDs). The main outcomes were breastfeeding performance (as measured by initiation, continuation, frequency and exclusivity of breastfeeding) and infant health (as measured by growth, development or adverse health effects). Results: Forty-nine articles reporting on 47 different studies were identified that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Studies ranged from poor to fair methodological quality and generally failed to show negative effects of the use of POCs on breastfeeding outcomes or on infant growth or development. One randomized controlled trial (RCT) raises concerns that immediate insertion of the levonorgestrel IUD postpartum may be associated with poorer breastfeeding performance when compared with delayed insertion, although two other RCTs evaluating early etonogestrel implants compared with delayed initiation of implants or depot medroxyprogesterone acetate failed to find such an association. Conclusion: The preponderance of evidence fails to demonstrate adverse breastfeeding outcomes or negative health outcomes in infants such as restricted growth, health problems or impaired development. Evidence newly added to this review was largely consistent with previous evidence

    Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation.

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    Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We combined RNA-sequencing, flow cytometry and TCR-sequencing to dissect the impact of immunotherapy and of immunotherapy combined with ablation on local and systemic immune components. Results: With administration of a toll-like receptor agonist agonist (CpG) alone or CpG combined with same-site ablation, we found dramatic differences between the local and distant tumor environments, where the directly treated tumors were skewed to high expression of F4/80, Cd11b and Tnf and the distant tumors to enhanced Cd11c, Cd3 and Ifng. When ablation was added to immunotherapy, 100% (n=20/20) of directly treated tumors and 90% (n=18/20) of distant tumors were responsive. Comparing the combined ablation-immunotherapy treatment to immunotherapy alone, we find three major mechanistic differences. First, while ablation alone enhanced intratumoral antigen cross-presentation (up to ~8% of CD45+ cells), systemic cross-presentation of tumor antigen remained low. Combining same-site ablation with CpG amplified cross-presentation in the draining lymph node (~16% of CD45+ cells) compared to the ablation-only (~0.1% of CD45+ cells) and immunotherapy-only cohorts (~10% of CD45+ cells). Macrophages and DCs process and present this antigen to CD8+ T-cells, increasing the number of unique T-cell receptor rearrangements in distant tumors. Second, type I interferon (IFN) release from tumor cells increased with the ablation-immunotherapy treatment as compared with ablation or immunotherapy alone. Type I IFN release is synergistic with toll-like receptor activation in enhancing cytokine and chemokine expression. Expression of genes associated with T-cell activation and stimulation (Eomes, Prf1 and Icos) was 27, 56 and 89-fold higher with ablation-immunotherapy treatment as compared to the no-treatment controls (and 12, 32 and 60-fold higher for immunotherapy-only treatment as compared to the no-treatment controls). Third, we found that the ablation-immunotherapy treatment polarized macrophages and dendritic cells towards a CD169 subset systemically, where CD169+ macrophages are an IFN-enhanced subpopulation associated with dead-cell antigen presentation. Conclusion: While the local and distant responses are distinct, CpG combined with ablative focal therapy drives a highly effective systemic immune response
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