Cosmology with baryons: modelling the cosmic matter distribution for Large-Scale Structure analyses.

La interacción entre las fuerzas gravitatorias e hidrodinámicas en la formación de la estructura del Universo es compleja y aún se desconoce en gran medida. Las fuerzas gravitatorias son dominantes a gran escala, donde las perturbaciones de la densidad son pequeñas y, por tanto, se pueden describir mediante una teoría lineal. Sin embargo, en las escalas pequeñas surgen no linealidades y, por lo tanto, la teoría analítica no es suficiente. El gas es perturbado tanto por las fuerzas hidrodinámicas como por la gravedad, y tienen lugar varios procesos astrofísicos. La formación de galaxias desencadena explosiones de supernovas y la inyección de energía de los agujeros negros supermasivos que se acrecientan, perturbando la distribución de la masa y remodelando el potencial gravitatorio, lo que provoca posteriormente una reacción inversa en la materia oscura.La falta de una modelización precisa de estos procesos bariónicos es una de las principales fuentes de incertidumbre en los actuales estudios de lentes gravitatorias débiles, y se espera que su impacto aumente drásticamente en las próximas campañas de observación previstas.En esta tesis, queremos desarrollar un marco para modelar de forma consistente la distribución espacial y la evolución temporal de la materia oscura, el gas y las galaxias, en la Estructura a Gran Escala del Universo. Utilizamos un enfoque basado en simulaciones, variando simultáneamente la cosmología y los procesos astrofísicos. El núcleo de nuestro marco está dado por grandes simulaciones de alta resolución, que garantizan una modelización robusta de las no linealidades a pequeñas escalas, y predicciones precisas a grandes escalas. En una fase de posprocesamiento, desplazamos las partículas en nuestras simulaciones para explorar diferentes escenarios cosmológicos y bariónicos, mediante la combinación de dos algoritmos de última generación: el modelo de escalado cosmológico y el de corrección bariónica. Implementamos versiones extendidas y optimizadas de ambos algoritmos, para alcanzar la precisión requerida por los estudios de próxima generación, y los probamos sistemáticamente por separado y en combinación. Por último, utilizamos técnicas modernas de aprendizaje automático, y en concreto redes neuronales artificiales, entrenadas para aprender las conexiones entre los parámetros cosmológicos y astrofísicos y las estadísticas relevantes del campo de materia cósmica, tal y como se miden en nuestras simulaciones. De este modo, nuestras predicciones pueden realizarse con un coste computacional insignificante, y la contribución lineal, no lineal y bariónica puede calcularse por separado. Nuestros emuladores de redes neuronales están disponibles públicamente y pueden incorporarse fácilmente a una análisis de lentes gravitatorias débiles. Utilizando nuestro marco de trabajo, la modelización de la densidad cosmica puede extenderse a escalas pequeñas sin precedentes, de forma muy precisa y con una aceleración consistente en el tiempo de cálculo. Esperamos que las técnicas desarrolladas y los resultados presentados aquí sean útiles para una amplia gama de aplicaciones en los análisis de estructuras a gran escala, y en particular en studios de lentes gravitatorias débiles y galaxias.<br /

Nano-based approved pharmaceuticals for cancer treatment : present and future challenges

Altres ajuts: RICORS RD21/0012/0001 (co-funded by the European Regional Development Fund, "A way to make Europe"); Fundación Mutua Madrileña (FMMA) through the project "Targeted therapy for selective elimination of metastatic stem cells CXCR4+ in endometrial cancer" (AP1666942017); Asociación Española contra el cancer (AECC) through the project "Development of an antitumor protein delivery system into ovarian cancer cells using the subcellular vault" (IDEAS18038BENI)Cancer is one of the main causes of death worldwide. To date, and despite the advances in conventional treatment options, therapy in cancer is still far from optimal due to the non-specific systemic biodistribution of antitumor agents. The inadequate drug concentrations at the tumor site led to an increased incidence of multiple drug resistance and the appearance of many severe unde-sirable side effects. Nanotechnology, through the development of nanoscale-based pharmaceuticals, has emerged to provide new and innovative drugs to overcome these limitations. In this review, we provide an overview of the approved nanomedicine for cancer treatment and the rationale behind their designs and applications. We also highlight the new approaches that are currently under investigation and the perspectives and challenges for nanopharmaceuticals, focusing on the tumor microenvironment and tumor disseminate cells as the most attractive and effective strategies for cancer treatments

La estimación de proporciones mediante técnicas Bayesianas

The estimation procedures based on Bayes' Theorem are still an unusual option in many of the environments of classic parametric inference. The aim of this paper is to show an effective scheme for the use of Bayesian estimation of unknown parameters. We have opted to focus on the estimation of parameters under the assumption of a binomial model, so that it can be followed by all those situations that meet the aforementioned probabilistic model. This approximation was studied in comparison with the classic parametric approximation, both in its point version and by means of interval estimation. On a study, by simulating samples of several sizes, we obtained empirical evidence regarding the advantage of the Bayesian procedure.ResumenLos procedimientos de estimación basados en el teorema de Bayes son inusuales en los diferentes ámbitos de aplicación de la inferencia paramétrica clásica. El objetivo de este trabajo es presentar un esquema para la estimación bayesiana de parámetros bajo los supuestos de un modelo binomial. El procedimiento Bayes se estudia en comparación con la aproximación paramétrica cl??sica, ambas opciones, en su versión puntual y mediante intervalos de estimación. Se presenta también un estudio de simulación con diferentes tamaños muestrales en el que se ponen de manifiesto las ventajas del procedimiento bayesiano.AbstractThe estimation procedures based on Bayes' Theorem are still an unusual option in many of the environments of classic parametric inference. The aim of this paper is to show an effective scheme for the use of Bayesian estimation of unknown parameters. We have opted to focus on the estimation of parameters under the assumption of a binomial model, so that it can be followed by all those situations that meet the aforementioned probabilistic model. This approximation was studied in comparison with the classic parametric approximation, both in its point version and by means of interval estimation. On a study, by simulating samples of several sizes, we obtained empirical evidence regarding the advantage of the Bayesian procedure

Impact of Neuroprotection on Incidence of Alzheimer's Disease

Converging evidence suggests that high levels of education and intellectual activity increase the cognitive reserve and reduce the risk of dementia. However, little is known about the impact that different neuroprotective strategies may have on the incidence of Alzheimer's disease. Using a simple mathematical regression model, it is shown here that age-specific counts of basic cognitive units (surrogate of neurons or synapses) in the normal population can be estimated from Alzheimer's incidence rates. Hence, the model can be used to test the effect of neuroprotection on Alzheimer's incidence. It was found that the number of basic cognitive units decreases with age, but levels off in older people. There were no gender differences after correcting for survival. The model shows that even modest neuroprotective effects on basic cognitive units can lead to dramatic reductions in the number of Alzheimer's cases. Most remarkably, a 5% increase in the cognitive reserve would prevent one third of Alzheimer's cases. These results suggest that public health policies aimed at increasing the cognitive reserve in the general population (e.g., implementing higher levels of education) are likely the most effective strategy for preventing Alzheimer's disease

A proteomic insight into the midgut proteome of Ornithodoros moubata females reveals novel information on blood digestion in argasid ticks

[Background]: The argasid tick Ornithodoros moubata is the main African vector of the human relapsing fever agent Borrelia duttoni and the African swine fever virus. Together with saliva, the tick midgut forms part of the host-tick-pathogen interface, and numerous midgut proteins play key functions in the blood digestion-related process and the infection and transmission of pathogens. This work explores the composition of the midgut proteome of unfed and fed O. moubata females with the aim to complete the biological information already obtained from the midgut transcriptome and provide a more robust and comprehensive perspective of this biological system.[Methods]: Midgut tissues taken from females before feeding and 48 h after feeding were subjected to LC/MS-MS analysis. After functional characterization and classification of the proteins identified, the differences in the proteome between unfed and fed females were analysed and discussed. Additionally, a detailed analysis of particular groups of proteins that are involved in the processes of nutrient digestion and responses to the oxidative stress was carried out.[Results]: 1491 non-redundant tick proteins were identified: 1132 of them in the midgut of unfed ticks, 1138 in the midgut of fed ticks, and up to 779 shared by both physiological conditions. Overall, the comparative analysis of the midgut proteomes of O. moubata females before and after feeding did not reveal great differences in the number or class of proteins expressed, enzymatic composition or functional classification.[Conclusions]: The hemoglobinolytic system in ixodids and argasids is very similar in spite of the fact that they display very different feeding and reproductive strategies. Although the main source of nutrients in ticks are proteins, lipids and carbohydrates also constitute significant nutritional sources and play an important part in the process of blood digestion. The genes and proteins involved in intracellular transport mechanisms, defensive responses, detoxifying responses and stress responses seem to be closely regulated, highlighting the complexity and importance of these processes in tick biology, which in turn assigns them a great interest as targets for therapeutic and immunological interventions.We acknowledge the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).This research was funded by project AGL2013–42745-P granted by the Spanish Ministry of Economy and Competitiveness.Peer reviewe

Caracterización de pacientes pediátricos usuarios de fototerapia en el Servicio de Dermatología, Hospital Clínico Universidad de Chile (2007-2015)

Background: Phototherapy is the use of specific wavelenghts of light that have shown effectiveness in the treatment of several cutaneous diseases. Current indications for phototherapy in Dermatology include multiple pathologies and it is considered to be cost- effective. Literature about its use in children is rare, there are no studies on phototherapy in Chilean children. PATIENTS AND METHODS: Observational, descriptive, retrospective study. Clinical records of pediatric patients treated with phototherapy at University of Chile Clinical Hospital between 2007 and 2015, were studied. For each patient, the following parameters were analyzed: age of starting treatment, sex, skin phenotype, diagnosis, prescribed phototherapy and weekly frecuency. RESULTS: 146 patients, 85 girls and 51 boys, average age 11.7 ± 4.0 years. Predominant skin phenotype, was Fitzpatrick type III. Vitiligo was identified as the most common indication for phototherapy (52,2 %), followed by psoriasis (22,6 %). By a large margin, the most used type of phototherapy was nb UVB (96.6 %). Most of the patients were treated twice per week (69.2 %). DISCUSSION: The obtained results in this group are similar to those results described in the international literature. Further studies are required for a better knowledge about efficacy and possible long-term effects of phototherapy on Chilean children

Silencing expression of the defensin, varisin, in male Dermacentor variabilis by RNA interference results in reduced Anaplasma marginale infections

Antimicrobial peptides, including defensins, are components of the innate immune system in ticks that have been shown to provide protection against both gram-negative and gram-positive bacteria. Varisin, one of the defensins identified in Dermacentor variabilis, was shown to be produced primarily in hemocytes but transcript levels were also expressed in midguts and other tick cells. In this research, we studied the role of varisin in the immunity of ticks to the gram-negative cattle pathogen, Anaplasma marginale. Expression of the varisin gene was silenced by RNA interference (RNAi) in which male ticks were injected with varisin dsRNA and then allowed to feed and acquire A. marginale infection on an experimentally-infected calf. Silencing expression of varisin in hemocytes, midguts and salivary glands was confirmed by real time RT-PCR. We expected that silencing of varisin would increase A. marginale infections in ticks, but the results demonstrated that bacterial numbers, as determined by an A. marginale msp4 quantitative PCR, were significantly reduced in the varisin-silenced ticks. Furthermore, colonies of A. marginale in ticks used for RNAi were morphologically abnormal from those seen in elution buffer injected control ticks. The colony shape was irregular and in some cases the A. marginale appeared to be free in the cytoplasm of midgut cells. Some ticks were found to be systemically infected with a microbe that may have been related to the silencing of varisin. This appears to be the first report of the silencing of expression of a defensin in ticks by RNAi that resulted in reduced A. marginale infections.This research was partially supported by the Oklahoma Agricultural Experiment Station (project 1669), the Walter R. Sitlington Endowed Chair for Food Animal Research (K. M. Kocan, Oklahoma State University), Pfizer Animal Health, Kalamazoo, MI, USA, the Junta de Comunidades de Castilla-La Mancha, Spain (project 06036-00 ICS-JCCM), and Ministry of Science and Education (MEC), Spain (project AGL2005-07401). Dr. Raúl Manzano-Roman was funded by Ministerio de Educación y Ciencia, Spain. V. Naranjo was founded by Consejería de Educación, JCCM, Spain. Support, in part, is gratefully acknowledged by a grant from the National Science Foundation, IBN 0212901 (Hynes & Sonenshine) and a grant from the National Research Fund for Tick-borne Diseases (Hynes & Sonenshine).Peer reviewe