Glycogen Synthase Kinase 3 Inhibitors in the Next Horizon for Alzheimer's Disease Treatment

Glycogen synthase kinase 3 (GSK-3), a proline/serine protein kinase ubiquitously expressed and involved in many cellular signaling pathways, plays a key role in the pathogenesis of Alzheimer's disease (AD) being probably the link between β-amyloid and tau pathology. A great effort has recently been done in the discovery and development of different new molecules, of synthetic and natural origin, able to inhibit this enzyme, and several kinetics mechanisms of binding have been described. The small molecule called tideglusib belonging to the thiadiazolidindione family is currently on phase IIb clinical trials for AD. The potential risks and benefits of this new kind of disease modifying drugs for the future therapy of AD are discussed in this paper

Variation of the ultraviolet extinction law across the Taurus-Auriga star forming complex. A GALEX based study

The Taurus-Auriga molecular complex (TMC) is the main laboratory for the study of low mass star formation. The density and properties of interstellar dust are expected to vary across the TMC. These variations trace important processes such as dust nucleation or the magnetic field coupling with the cloud. In this article, we show how the combination of near ultraviolet (NUV) and infrared (IR) photometry can be used to derive the strength of the 2175 \AA\ bump and thus any enhancement in the abundance of small dust grains and PAHs in the dust grains size distribution. This technique is applied to the envelope of the TMC, mapped by the GALEX All Sky Survey (AIS). UV and IR photometric data have been retrieved from the GALEX-AIS and the 2MASS catalogues. NUV and K-band star counts have been used to identify the areas in the cloud envelope where the 2175 \AA\ bump is weaker than in the diffuse ISM namely, the low column density extensions of L1495, L1498 and L1524 in Taurus, L1545, L1548, L1519, L1513 in Auriga and L1482-83 in the California region. This finding agrees with previous results on dust evolution derived from Spitzer data and suggests that dust grains begin to decouple from the environmental galactic magnetic field already in the envelope.Comment: Accepted in Monthly Notices of the Royal Astronomical Societ

Synthetic and structural studies of mixed sodium bis(trimethylsilyl)amide/sodium halide aggregates in the presence of η2-N,N-, η3-N,N,N/N,O,N-, and η4-N,N,N,N-donor ligands

When the important utility amide sodium bis(trimethylsilyl)amide is combined with hydrocarbon-soluble molecular forms of sodium halide salts, a complex structural chemistry is observed. Through utilization of several different multidentate donor molecules, it is possible to isolate a series of compounds that have structural motifs previously not observed in sodium chemistry

Agreement on Access and Benefit-sharing for Academic Research: A toolbox for drafting Mutually Agreed Terms for access to Genetic Resources and to Associated Traditional Knowledge and Benefit-sharing

This manual contains a set of model clauses that enables users and providers of genetic resources and associated traditional knowledge to set up a legal contract that is adapted to the individual academic research situation. If mutually negotiated and agreed upon by the involved partners this agreement can yield a “Mutually Agreed Terms” ABS contract

Adaptive function approximation based on the Discrete Cosine Transform (DCT)

This paper studies the cosine as basis function for the approximation of univariate and continuous functions without memory. This work studies a supervised learning to obtain the approximation coefficients, instead of using the Discrete Cosine Transform (DCT). Due to the finite dynamics and orthogonality of the cosine basis functions, simple gradient algorithms, such as the Normalized Least Mean Squares (NLMS), can benefit from it and present a controlled and predictable convergence time and error misadjustment. Due to its simplicity, the proposed technique ranks as the best in terms of learning quality versus complexity, and it is presented as an attractive technique to be used in more complex supervised learning systems. Simulations illustrate the performance of the approach. This paper celebrates the 50th anniversary of the publication of the DCT by Nasir Ahmed in 1973.Comment: Accepted paper in 26th International Conference on Circuits, Systems, Communications and Computers (CSCC

Disparities and Microbiome Affecting Liver Disease Progression

Non-alcoholic fatty liver disease (NAFLD) is a metabolic illness that encompasses a wide range of pathological states, from simple steatosis to steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma. NAFLD is the most prevalent liver disease in the world, accounting for 25% of all liver diseases cases. A high-fat diet, smoking, and alcohol consumption have all been proven to disrupt the balance of beneficial and possibly pathogenic bacterial species, resulting in intestinal dysbiosis. The prevalence of liver cancer (LC) among Latinos in South Texas remains greater than elsewhere in the United States, necessitating further research on population-specific risk factors and aggressive mortality. Incidence rates among Hispanics are three to four times greater than among non-Hispanic whites. There are no precise molecular markers or imaging modalities that have the sensitivity or specificity to identify NAFLD patients at an early stage of illness or at a high risk of developing NASH/Cirrhosis or HCC and consider them candidates for early surgical intervention. Therefore, there is a need for the creation of non-invasive, selective molecular markers for detecting precursor lesions with dysplasia that advance to HCC. The makeup of the human gut microbiota, which is made up of hundreds of microbial species, can change with chronic illnesses that underpin health inequities that disproportionately afflict ethnic minorities. In this study, we explored the incidence and mortality rates of liver cancer in different ethnicities, Hispanics, African Americans, and non-Hispanic whites (NHW). Hispanics have the highest microbial richness and evenness in both study groups, followed by Non-Hispanic whites and Asian Pacific Islanders. Obesity, diabetes, and lifestyle changes, among other factors, have contributed to an increase in the number of instances of NAFLD in Hispanics. An increase in the number of Enterobacteriaceae, Veillonellaceae, and Streptococcaceae, as well as a reduction in the abundance of Lachnospiracea is witnessed in cirrhosis patients. There are different microbial fingerprints and interspecies interactions in several liver disorders that are susceptible to develop in HCC across ethnicities. Future studies are warranted to investigate the role of microbiota in conversion of NAFLD patients, role of microbiota in mediating HC

Influence of nominal composition variation on phase evolution and creep life of Type 316H austenitic stainless steel components

AbstractThe present work aims to understand the influence of variation in chemical composition in the long term evolution of secondary phases. Three samples with nominal composition of Type 316H but different specific composition have been exposed to 505°C during 150, 145 and 300 kh. The percentage of ferrite and M23C6 carbide have been measured using EBSD and compared with Thermo-Calc predictions. In addition, thin foils were prepared and characterized to identify secondary phases in the samples. The discussion is focused on the influence of the secondary phases on creep deformation and failure

Hacer es pensar: el aprendizaje a través del inventariado y el dibujo del patrimonio arquitectónico

Las materias de la Composición Arquitectónica (Historia, Teoría, Crítica y Patrimonio de Arquitectura), por sus fuertes dosis humanísticas, parece que se nutran, fundamentalmente, de textos escritos y reflexiones teóricas. Sin embargo, todas estas fuentes hermenéuticas se refieren, en primera y última instancia, a la realidad, a los hechos que fueron o son: ciudades y arquitecturas. Así pues, los contenidos docentes que abordan las teorías de intervención en el patrimonio arquitectónico se sustentan sobre la base de la existencia de inventarios y de textos teóricos. ¿Cómo podemos ampliar las bases de este conocimiento y verificar el aprendizaje de los principios que rigen los criterios de actuación sobre el patrimonio? En atención a esta reflexión y a la máxima de que “Hacer es Pensar”, se propone redirigir la asignatura de Composición Arquitectónica 6 (Grado de Arquitectura) hacia las labores de investigación mediante los trabajos de campo de inventariado de arquitecturas, su documentación gráfica y cartográfica (levantamientos) y la aplicación al mismo de propuestas de intervención individuales y de conjunto. Aprender supondrá investigar ampliando los inventarios con trabajos de campo y tomando estos documentos gráficos como punto de partida de los proyectos de intervención en el patrimonio urbano y arquitectónico