Measurement of the Permanent Electric Dipole Moment of the 129^{129}Xe Atom

We report on a new measurement of the CP-violating permanent Electric Dipole Moment (EDM) of the neutral $^{129}$Xe atom. Our experimental approach is based on the detection of the free precession of co-located nuclear spin-polarized $^3$He and $^{129}$Xe samples. The EDM measurement sensitivity benefits strongly from long spin coherence times of several hours achieved in diluted gases and homogeneous weak magnetic fields of about 400~nT. A finite EDM is indicated by a change in the precession frequency, as an electric field is periodically reversed with respect to the magnetic guiding field. Our result, $\left(-4.7\pm6.4\right)\cdot 10^{-28}$ ecm, is consistent with zero and is used to place a new upper limit on the $^{129}$Xe EDM: $|d_\text{Xe}|<1.5 \cdot 10^{-27}$ ecm (95% C.L.). We also discuss the implications of this result for various CP-violating observables as they relate to theories of physics beyond the standard model

Acid-Labile Traceless Click Linker for Protein Transduction

Intracellular delivery of active proteins presents an interesting approach in research and therapy. We created a protein transduction shuttle based on a new traceless click linker that combines the advantages of click reactions with implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic anhydride (AzMMMan) linker was found compatible with different click chemistries, demonstrated in bioreversible protein modification with dyes, polyethylene glycol, or a transduction carrier. Linkages were stable at physiological pH but reversible at the mild acidic pH of endosomes or lysosomes. We show that pH-reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane amino)amide carrier generates an effective shuttle for protein delivery. The cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences efficient cellular uptake and endosomal escape into the cytosol, followed by import into the nucleus. In contrast, irreversible linkage to the same shuttle hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the cytosol. Successful intracellular delivery of bioactive ß-galactosidase as a model enzyme was also demonstrated using the pH-controlled shuttle system

Clinicopathological Profile and Surgical Treatment of Abdominal Tuberculosis: A Single Centre Experience in Northwestern Tanzania.

Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival

Immunomodulation with self-crosslinked polyelectrolyte multilayer-based coatings

This study aims to design an optimal polyelectrolyte multilayer film of poly-L-lysine (PLL) and hyaluronic acid(HA) as an anti-inflammatory cytokine release system in order to decrease the implant failure due to any immune reactions. The chemical modification of the HA with aldehyde moieties allows self-cross-linking of the film and an improvement in the mechanical properties of the film. The cross-linking of the film and the release of immunomodulatory cytokine (IL-4) stimulate the differentiation of primary human monocytes seeded on the films into pro-healing macrophages phenotype. This induces the production of antiinflammatory cytokines (IL1-RA and CCL18) and the decrease of proinflammatory cytokines secreted (IL-12, TNF-α, and IL-1β). Moreover, we demonstrate that cross-linking PLL/HA film using HA-aldehyde is already effective by itself to limit inflammatory processes. Finally, this functionalized self-cross-linked PLL/HA-aldehyde films constitutes an innovative and efficient candidate for immunomodulation of any kind of implants of various architecture and properties

Fiber-Based Laser Transmitter at 1.57 Micrometers for Remote Sensing of Atmospheric Carbon Dioxide from Satellites

Over the past 20 years, NASA Goddard has successfully developed space-based lidar for remote sensing studies of the Earth and planets. The lidar in all missions to date have used diode pumped Nd:YAG laser transmitters. Recently we have been concentrating work on developing integrated path differential absorption (IPDA) lidar to measure greenhouse gases, with the goal of measurements from space. Due to the absorption spectrum of CO2 a fiber-based master oscillator power amplifier (MOPA) laser with a tunable seed source is an attractive laser choice. Fiber-based lasers offer a number of potential advantages for space, but since they are relatively new, challenges exist in developing them. In order to reduce risks for new missions using fiber-based lasers, we developed a 30- month plan to mature the technology of a candidate laser transmitter for space-based CO2 measurements to TRL-6. This work is also intended to reduce development time and costs and increase confidence in future mission success

Atribuciones causales y nivel educativo familiar en la comprensión del desempeño escolar en alumnos portugueses

Este artigo analisa o contributo específico do nível educativo familiar e das atribuições causais para o bom e fraco rendimento escolar dos alunos na explicação do seu desempenho nas disciplinas de Língua Portuguesa e de Matemática numa amostra de 2.082 alunos do ensino público de 11 escolas de Portugal, incluindo as Regiões Autónomas dos Açores e da Madeira. As atribuições causais foram avaliadas por meio do Questionário das Atribuições Causais para os Resultados Escolares (QARE). O nível educativo familiar foi estimado levando em conta o nível escolar do progenitor com maior habilitação escolar. As classificações obtidas pelos alunos nas disciplinas de língua portuguesa e matemática foram também examinadas. Os resultados apontam para correlações estatisticamente significativas, destacando as atribuições na capacidade para a explicação do rendimento escolar, situação que contrasta com a atribuição dos níveis de rendimento a variáveis externas ao aluno. A análise de regressão permite associar 34,5% da variância no rendimento conjunto em Língua Portuguesa e em Matemática no ensino básico, assim como 21,3% no ensino secundário, às dimensões atribucionais e ao nível educativo familiar. Implicações educacionais são derivadas a partir dos achados.This paper analyzes the contribution of both family educational level and causal attributions in explaining students´ academic performance in Mathematics and Portuguese Language in a sample of 2.082 public school students from mainland Portugal and the Azores and Madeira regions. Causal attributions were assessed by the Causal Attributions Questionnaire for School Results (QARE). The family educational level was estimated taking into account the educational level of the parent with higher academic degree. The academic grades obtained by students in mathematics and portuguese language were also considered. The results show statistically significant correlations between variables. Internal causal attributions such as capacity and study methods were predominant to explain school performance in the sample and stood out in contrast to external attributions explanations. Regression analyses revealed that 34.5% of the variance in the combined achievement on Portuguese Language and Mathematics in primary education and 21.3% in secondary education could be explained by both the attributional dimensions and family education level. Some educational implications are present taking these data.Este artículo analiza la contribución específica del nivel educativo familiar y de las atribuciones causales para el buen y el flaco rendimiento escolar de los alumnos en la explicación de su desempeño en las disciplinas de Lengua Portuguesa y Matemáticas en una muestra de 2.082 alumnos de enseñanza pública de 11 escuelas de Portugal, incluyendo las Regiones Autónomas de Açores y Madeira. Las atribuciones causales fueron evaluadas por medio del “Questionário das Atribuições Causais para os Resultados Escolares” (QARE). El nivel educativo familiar fue estimado teniendo en cuenta el nivel escolar del progenitor con mayor habilitación escolar. Las clasificaciones obtenidas por los alumnos en las disciplinas de lengua portuguesa y matemáticas fueron también examinadas. Los resultados señalaron correlaciones estadísticamente significativas, destacando las atribuciones en la capacidad para la explicación del rendimiento escolar, situación que contrasta con la atribución de los niveles de rendimiento a variables externas al alumno. El análisis de regresión permite asociar 34.5% de la variancia en el rendimiento conjunto de la Lengua Portuguesa y las Matemáticas en la enseñanza básica, así como 21.3% en la enseñanza secundaria, a las dimensiones de atribución y al nivel educativo familiar. Implicaciones educacionales son derivadas a partir de los hallazgos.Editora Universitária São Francisc

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Speech features for telemonitoring of Parkinson's disease symptoms.

The aim of this paper is tracking Parkinson's disease (PD) progression based on its symptoms on vocal system using Unified Parkinsons Disease Rating Scale (UPDRS). We utilize a standard speech signal feature set, which contains 6373 static features as functionals of low-level descriptor (LLD) contours, and select the most informative ones using the maximal relevance and minimal redundancy based on correlations (mRMRC) criteria. Then, we evaluate performance of Gaussian mixture regression (GMR) and support vector regression (SVR) on estimating the third subscale of UPDRS, i.e., UPDRS: motor subscale (UPDRS-III). Among the most informative features, a list of features are selected after redundancy reduction. The selected features depict that LLDs providing information about spectrum flatness, spectral distribution of energy, and hoarseness of voice are the most important ones for estimating UPDRS-III. Moreover, the most informative statistical functions are related to range, maximum, minimum and standard deviation of LLDs, which is an evidence of the muscle weakness due to the PD. Furthermore, GMR outperforms SVR on compact feature sets while the performance of SVR improves by increasing number of features