2,450 research outputs found
Aplicación del modelo Black-Litterman para la construcción de un portafolio de renta fija global, mediante la estructuración de un benchmark propio y estrategia de cobertura vÃa forwards
El acceso a diferentes activos de inversión, la búsqueda de alternativas de diversificación y la cuantificación y cobertura de los riesgos asociados a los portafolios, son factores de alta relevancia a la hora de construir y administrar portafolios de inversión con alcance internacional. De ahÃ, que el objetivo del presente trabajo se centra en la aplicación del modelo Black-Litterman para la construcción de un portafolio de renta fija global, compuesto por activos ETFs high yield e investment grade, asà como por bonos soberanos de paÃses desarrollados. Asimismo, con el fin de aumentar la cobertura, la capacidad de diversificación y minimizar el riesgo, se presenta un benchmark construido con base en diferentes Ãndices de renta fija global y activos de la misma categorÃa. Finalmente, se propondrá la utilización de una estrategia de cobertura vÃa forwards con el fin de mitigar el riesgo inherente a la devaluación de la divisa.The access to different investment assets, the search for diversification, and the application of measures as for quantification and hedging risk are relevant factors for building and managing international investment portfolios. Therefore, the objective of the present paper aims to the application of Black-Litterman portfolio model on building a global fixed income portfolio, which is made up of high yield and investment grade ETFs, as well as developed countries government bonds. Furthermore, in order to increase hedging, diversification ratio, and to minimize risk, a benchmark, which is made up of both global fixed income indices and assets from the same category will be built. Finally, a hedging strategy will be proposed through forwards in order to minimize the inherent risk due to currency depreciation
Hipotiroidismo y esteatosis hepática
La infiltración grasa es una condición en la que se produce depósito de lÃpidos en el citoplasma de los hepatocitos y se presenta en una serie de patologÃas entre las que podemos mencionar el hipotiroidismo. Entre los objetivos del presente estudio está el establecer la presencia de daño hepático en pacientes con disfunción tiroidea, incluir dentro del rastreo inicial de todo paciente hipotiroideo el estudio de enzimas hepáticas e instaurar la ecosonografÃa abdominal como auxiliar diagnóstico en pacientes con alto Ãndice de sospecha de esteatosis hepática.Las estadÃsticas a nivel mundial promedian entre un 25 y 30% de frecuencia de infiltración grasa hepática en el hipotiroidismo. En nuestros resultados lo más relevante fue ver que el 31.25% de nuestro universo padecÃa de este problema, lo cual concuerda con las cifras arrojadas en otros estudios médicos realizados.Podemos concluir además que debe ser parte del protocolo de seguimiento en todo paciente hipotiroideo, el estudio de la función hepática, con el afán de evitar o controlar la progresión de la esteatosis hepática si llegara a estar presente
Fisiopatologia de la cascada isquemica y su influencia en la isquemia cerebral
Ischemic stroke is triggered by a series of biochemical processes resulting from disruption of blood flow. It involves a complex mixture of different biomolecular events that originate and develop through the ischemic cascade, generating excitotoxicity, which together trigger irreversible cell injury. The study and knowledge of the different pathophysiological processes that occur in this cascade allows the understanding of the synthesis of this pathology in order to develop tools that allow the clinician to design neuroprotection and early detection strategies to prevent its consequences.El accidente cerebrovascular isquémico es desencadenado por una serie de procesos bioquÃmicos producto de la interrupción del flujo sanguÃneo cerebral. Involucra una mezcla compleja de diferentes acontecimientos biomoleculares que se originan y desarrollan a través de la cascada isquémica, generando excitotoxicidad, que en conjunto desencadenan la lesión celular irreversible. El estudio y comprensión de los diferentes procesos fisiopatológicos que ocurren en esta cascada permite conocer la sÃntesis de esta patologÃa para poder desarrollar herramientas que le faciliten al clÃnico el diseño de estrategias de neuroprotección y detección anticipada para prevenir las consecuencias de la misma.  
Three geographically separate domestications of Asian rice
Domesticated rice (Oryza sativa L.) accompanied the dawn of Asian civilization(1) and has become one of world's staple crops. From archaeological and genetic evidence various contradictory scenarios for the origin of different varieties of cultivated rice have been proposed, the most recent based on a single domestication(2,3). By examining the footprints of selection in the genomes of different cultivated rice types, we show that there were three independent domestications in different parts of Asia. We identify wild populations in southern China and the Yangtze valley as the source of the japonica gene pool, and populations in Indochina and the Brahmaputra valley as the source of the indica gene pool. We reveal a hitherto unrecognized origin for the aus variety in central India or Bangladesh. We also conclude that aromatic rice is a result of a hybridization between japonica and aus, and that the tropical and temperate versions of japonica are later adaptations of one crop. Our conclusions are in accord with archaeological evidence that suggests widespread origins of rice cultivation(1,4). We therefore anticipate that our results will stimulate a more productive collaboration between genetic and archaeological studies of rice domestication, and guide utilization of genetic resources in breeding programmes aimed at crop improvement.European Research Council [339941]info:eu-repo/semantics/publishedVersio
Safinamida como tratamiento complementario al levodopa para la enfermedad del Parkinson en fase media o avanzada
Safinamide is a novel drug with both dopaminergic and non-dopaminergic effects. Its mechanism works as a selective reversible inhibitor of monoamine oxidase-B approved as a complementary treatment to levodopa in patients with mid-to-late Parkinson's disease and motor fluctuations. Safinamide does not cause new dyskinesia or worsen the existing one but is able to reduce this symptom in these patients.La safinamida es un medicamento novedoso tanto con dopaminérgico como efectos no dopaminérgicos. Su mecanismo funciona como un inhibidor selectivo reversible de la monoaminooxidasa-B aprobado como tratamiento complementario a la levodopa en pacientes con enfermedad de Parkinson de etapa media a tardÃa y fluctuaciones motoras. La safinamida no causa discinesia nueva ni empeora la existente sino es capaz de reducir este sÃntoma en estos pacientes
Role of the reversible electrochemical deprotonation of phosphate species in anaerobic biocorrosion of steels
Sulphate reducing bacteria are known to play a major role in anaerobic microbiological influenced
corrosion of steels, but mechanisms behind their influence are still source of debates as certain
phenomena remain unexplained. Some experiments have shown that hydrogen consumption by SRB
or hydrogenase increased the corrosion rate of mild steel. This was observed only in the presence of
phosphate species. Here the cathodic behaviour of phosphate species on steel was studied to elucidate
the role of phosphate in anaerobic corrosion of steel. Results showed: a linear correlation
between reduction waves in linear voltammetry and phosphate concentration at a constant pH value;
that phosphate ions induced considerable anaerobic corrosion of mild steel, which was sensitive to
hydrogen concentration in the solution; and that the corrosion potential of stainless steel in presence
of phosphate was shifted to more negative values as molecular hydrogen was added to the atmosphere
in the reaction vessel. Phosphate species, and possibly other weak acids present in biofilms,
are suggested to play an important role in the anaerobic corrosion of steels via a reversible mechanism
of electrochemical deprotonation that may be accelerated by hydrogen removal
Nonlinear Localization in Metamaterials
Metamaterials, i.e., artificially structured ("synthetic") media comprising
weakly coupled discrete elements, exhibit extraordinary properties and they
hold a great promise for novel applications including super-resolution imaging,
cloaking, hyperlensing, and optical transformation. Nonlinearity adds a new
degree of freedom for metamaterial design that allows for tuneability and
multistability, properties that may offer altogether new functionalities and
electromagnetic characteristics. The combination of discreteness and
nonlinearity may lead to intrinsic localization of the type of discrete
breather in metallic, SQUID-based, and symmetric metamaterials. We
review recent results demonstrating the generic appearance of breather
excitations in these systems resulting from power-balance between intrinsic
losses and input power, either by proper initialization or by purely dynamical
procedures. Breather properties peculiar to each particular system are
identified and discussed. Recent progress in the fabrication of low-loss,
active and superconducting metamaterials, makes the experimental observation of
breathers in principle possible with the proposed dynamical procedures.Comment: 19 pages, 14 figures, Invited (Review) Chapte
HER2 testing in breast cancer: Opportunities and challenges
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results
A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.
Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases
Role of microbial biofilms in the maintenance of oral health and in the development of dental caries and periodontal diseases. Consensus report of group 1 of the Joint EFP/ORCA workshop on the boundaries between caries and periodontal disease.
BACKGROUND AND AIMS: The scope of this working group was to review (1) ecological interactions at the dental biofilm in health and disease, (2) the role of microbial communities in the pathogenesis of periodontitis and caries, and (3) the innate host response in caries and periodontal diseases. RESULTS AND CONCLUSIONS: A health-associated biofilm includes genera such as Neisseria, Streptococcus, Actinomyces, Veillonella and Granulicatella. Microorganisms associated with both caries and periodontal diseases are metabolically highly specialized and organized as multispecies microbial biofilms. Progression of these diseases involves multiple microbial interactions driven by different stressors. In caries, the exposure of dental biofilms to dietary sugars and their fermentation to organic acids results in increasing proportions of acidogenic and aciduric species. In gingivitis, plaque accumulation at the gingival margin leads to inflammation and increasing proportions of proteolytic and often obligately anaerobic species. The natural mucosal barriers and saliva are the main innate defence mechanisms against soft tissue bacterial invasion. Similarly, enamel and dentin are important hard tissue barriers to the caries process. Given that the present state of knowledge suggests that the aetiologies of caries and periodontal diseases are mutually independent, the elements of innate immunity that appear to contribute to resistance to both are somewhat coincidental
- …