Ab-initio molecular dynamics simulation of hydrogen diffusion in α\alpha-iron

First-principles atomistic molecular dynamics simulation in the micro-canonical and canonical ensembles has been used to study the diffusion of interstitial hydrogen in $\alpha$-iron. Hydrogen to Iron ratios between $\theta=1/16 and 1/2 have been considered by locating interstitial hydrogen atoms at random positions in a$2 \times 2 \times 2$ supercell. We find that the average optimum absorption site and the barrier for diffusion depend on the concentration of interestitials. Iron Debye temperature decreases monotonically for increasing concentration of interstitial hydrogen, proving that iron-iron interatomic potential is significantly weakened in the presence of a large number of diffusing hydrogen atoms

Desafios E Possibilidades Para A Profissionalização Da Pesquisa Científica Em Direito

The main objective of this paper is to present some considerations about scientific research in Law as a professional career. This paper departs from a historical rescue on the institutionalization of Bachelor of Law in Brazil, as well as postgraduate studies in this area, to reflect on the contradictions present in the field about the meanings of research in Law. Without forgetting the instrumental character of Law by maintaining and creating elites in Brazil, we present in the text strategies for permanence and maintenance in academic research as an option for professional practice in Law. In the final considerations, we register some questions for future reflections.Este artigo tem como objetivo central apresentar algumas considerações sobre a pesquisa científica na área do Direito enquanto carreira profissional. O artigo parte de um resgate histórico sobre a institucionalização do bacharelismo em Direito no país, bem como da pós-graduação nesta área, para refletir acerca das contradições presentes no campo sobre os sentidos da pesquisa em Direito. Sem se esquecer do caráter instrumental de manutenção e criação de elites do Brasil, apresentamos no texto estratégias de permanência e manutenção na pesquisa acadêmica enquanto opção de atuação profissional no Direito. Nas considerações finais, registramos algumas questões para futuras reflexões

Retinal OCT speckle as a biomarker for glaucoma diagnosis and staging

This paper presents a novel image analysis strategy that increases the potential of macular Optical Coherence Tomography (OCT) by using speckle features as biomarkers in different stages of glaucoma. A large pool of features (480) were computed for a subset of macular OCT volumes of the Leuven eye study cohort. The dataset contained 258 subjects that were divided into four groups based on their glaucoma severity: Healthy (56), Mild (94), Moderate (48), and Severe (60). The OCT speckle features were categorized as statistical properties, statistical distributions, contrast, spatial gray-level dependence matrices, and frequency domain features. The averaged thicknesses of ten retinal layers were also collected. Kruskal-Wallis H test and multivariable regression models were used to infer the most significant features related to glaucoma severity classification and to the correlation with visual field mean deviation. Four features were selected as being the most relevant: the ganglion cell layer (GCL) and the inner plexiform layer (IPL) thicknesses, and two OCT speckle features, the data skewness computed on the retinal nerve fiber layer (RNFL) and the scale parameter (a) of the generalized gamma distribution fitted to the GCL data. Based on a significance level of 0.05, the regression models revealed that RNFL skewness exhibited the highest significance among the features considered for glaucoma severity staging (p-values of 8.6×10-6 for the logistic model and 2.8×10-7 for the linear model). Furthermore, it demonstrated a strong negative correlation with the visual field mean deviation (ρ=-0.64). The post hoc analysis revealed that, when distinguishing healthy controls from glaucoma subjects, GCL thickness is the most relevant feature (p-value of 8.7×10-5). Conversely, when comparing the Mild versus Moderate stages of glaucoma, RNFL skewness emerged as the only feature exhibiting statistical significance (p-value = 0.001). This work shows that macular OCT speckle contains information that is currently not used in clinical practice, and not only complements structural measurements (thickness) but also has a potential for glaucoma staging

The Structure and Dynamics of the Upper Chromosphere and Lower Transition Region as Revealed by the Subarcsecond VAULT Observations

The Very high Angular resolution ULtraviolet Telescope (VAULT) is a sounding rocket payload built to study the crucial interface between the solar chromosphere and the corona by observing the strongest line in the solar spectrum, the Ly-a line at 1216 {\AA}. In two flights, VAULT succeeded in obtaining the first ever sub-arcsecond (0.5") images of this region with high sensitivity and cadence. Detailed analyses of those observations have contributed significantly to new ideas about the nature of the transition region. Here, we present a broad overview of the Ly-a atmosphere as revealed by the VAULT observations, and bring together past results and new analyses from the second VAULT flight to create a synthesis of our current knowledge of the high-resolution Ly-a Sun. We hope that this work will serve as a good reference for the design of upcoming Ly-a telescopes and observing plans.Comment: 28 pages, 11 figure

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Plants used traditionally to treat malaria in Brazil: the archives of Flora Medicinal

The archives of Flora Medicinal, an ancient pharmaceutical laboratory that supported ethnomedical research in Brazil for more than 30 years, were searched for plants with antimalarial use. Forty plant species indicated to treat malaria were described by Dr. J. Monteiro da Silva (Flora Medicinal leader) and his co-workers. Eight species, Bathysa cuspidata, Cosmos sulphureus, Cecropia hololeuca, Erisma calcaratum, Gomphrena arborescens, Musa paradisiaca, Ocotea odorifera, and Pradosia lactescens, are related as antimalarial for the first time in ethnobotanical studies. Some species, including Mikania glomerata, Melampodium divaricatum, Galipea multiflora, Aspidosperma polyneuron, and Coutarea hexandra, were reported to have activity in malaria patients under clinical observation. In the information obtained, also, there were many details about the appropriate indication of each plant. For example, some plants are indicated to increase others' potency. There are also plants that are traditionally employed for specific symptoms or conditions that often accompany malaria, such as weakness, renal failure or cerebral malaria. Many plants that have been considered to lack activity against malaria due to absence of in vitro activity against Plasmodium can have other mechanisms of action. Thus researchers should observe ethnomedical information before deciding which kind of screening should be used in the search of antimalarial drugs

HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

BACKGROUND: Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. METHODS: Sixty patients received preoperative docetaxel (75 mg/m(2)) in combination with epirubicin (50 mg/m(2)) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. RESULTS: Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. CONCLUSION: Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination

Development and implementation of a prescription opioid registry across diverse health systems

Objective: Develop and implement a prescription opioid registry in 10 diverse health systems across the US and describe trends in prescribed opioids between 2012 and 2018. Materials and Methods: Using electronic health record and claims data, we identified patients who had an outpatient fill for any prescription opioid, and/or an opioid use disorder diagnosis, between January 1, 2012 and December 31, 2018. The registry contains distributed files of prescription opioids, benzodiazepines and other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. Rates of outpatient opioid fills over the study period, standardized to health system demographic distributions, are described by age, gender, and race/ethnicity among members without cancer. Results: The registry includes 6 249 710 patients and over 40 million outpatient opioid fills. For the combined registry population, opioid fills declined from a high of 0.718 per member-year in 2013 to 0.478 in 2018, and morphine milligram equivalents (MMEs) per fill declined from 985 MMEs per fill in 2012 to 758 MMEs in 2018. MMEs per member declined from 692 MMEs per member in 2012 to 362 MMEs per member in 2018. Conclusion: This study established a population-based opioid registry across 10 diverse health systems that can be used to address questions related to opioid use. Initial analyses showed large reductions in overall opioid use per member among the combined health systems. The registry will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use