Caracterización de las propiedades mecánicas de bacteriófagos mediante microscopía de fuerzas atómicas

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de la Materia Condensada. Fecha de lectura: 05-06-201

Artificial intelligence methodologies and their application to diabetes

In the past decade diabetes management has been transformed by the addition of continuous glucose monitoring and insulin pump data. More recently, a wide variety of functions and physiologic variables, such as heart rate, hours of sleep, number of steps walked and movement, have been available through wristbands or watches. New data, hydration, geolocation, and barometric pressure, among others, will be incorporated in the future. All these parameters, when analyzed, can be helpful for patients and doctors' decision support. Similar new scenarios have appeared in most medical fields, in such a way that in recent years, there has been an increased interest in the development and application of the methods of artificial intelligence (AI) to decision support and knowledge acquisition. Multidisciplinary research teams integrated by computer engineers and doctors are more and more frequent, mirroring the need of cooperation in this new topic. AI, as a science, can be defined as the ability to make computers do things that would require intelligence if done by humans. Increasingly, diabetes-related journals have been incorporating publications focused on AI tools applied to diabetes. In summary, diabetes management scenarios have suffered a deep transformation that forces diabetologists to incorporate skills from new areas. This recently needed knowledge includes AI tools, which have become part of the diabetes health care. The aim of this article is to explain in an easy and plane way the most used AI methodologies to promote the implication of health care providers?doctors and nurses?in this field

How Continuous Monitoring Changes the Interaction of Patients with a Mobile Telemedicine System

The use of continuous glucose monitor changes the way patients manage their diabetes, as observed in the increased number of daily insulin bolus, the increased number of daily BG measurements, and the differences in the distribution of BG measurements throughout the day. Continuous monitoring also increases the interaction of patients with the information system and modifies their patterns of use

Personalized rule-based closed-loop control algorithm for type 1 diabetes

Type 1 diabetes-mellitus implies a life-threatening absolute insulin deficiency. Artificial pancreas (CGM sensor, insulin pump and control algorithm) is promising to outperform current open-loop therapies

Electronic Report Generation Web Service evaluated within a Telemedicine System

This work presents a generic tool based on a client-server architecture that generates electronic reports helping the evaluation process of any information system. For the specific evaluation of telemedicine systems the defined reports cover four dimensions: auditory of the system; evolution of clinical protocols; results from the questionnaires for user acceptance and quality of life; and surveillance of clinical variables. The use of a Web Service approach allows multiplatform use of the developed electronic report service and the modularity followed in the implementation enables easy system evolution and scalability

Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural variations among human adenoviruses

Enteric adenoviruses, one of the main causes of viral gastroenteritis in the world, must withstand the harsh conditions found in the gut. This requirement suggests that capsid stability must be different from that of other adenoviruses. We report the 4-Å-resolution structure of a human enteric adenovirus, HAdV-F41, and compare it with that of other adenoviruses with respiratory (HAdV-C5) and ocular (HAdV-D26) tropisms. While the overall structures of hexon, penton base, and internal minor coat proteins IIIa and VIII are conserved, we observe partially ordered elements reinforcing the vertex region, which suggests their role in enhancing the physicochemical capsid stability of HAdV-F41. Unexpectedly, we find an organization of the external minor coat protein IX different from all previously characterized human and nonhuman mastadenoviruses. Knowledge of the structure of enteric adenoviruses provides a starting point for the design of vectors suitable for oral delivery or intestinal targetingThis work was supported by grants PID2019-104098GB-I00/AEI/10.13039/501100011033 and BFU2016-74868-P, cofunded by the Spanish State Research Agency and the European Regional Development Fund; BFU2013-41249-P and BIO2015-68990-REDT (the Spanish Adenovirus Network, AdenoNet) from the Spanish Ministry of Economy, Industry, and Competitiveness; and the Agencia Estatal CSIC (2019AEP045) to C.S.M. The CNB-CSIC is further supported by a Severo Ochoa Excellence grant (SEV 2017-0712). Work in M.B’s. lab was supported by grant 194562-08 from the Natural Sciences and Engineering Research Council of is a recipient of a Juan de la Cierva postdoctoral contract funded by the Spanish State Research Agency. M.P.-I. holds a predoctoral contract from La Caixa Foundation (ID 100010434), under agreement LCF/BQ/SO16/52270032. Access to CEITEC was supported by iNEXT, project number 653706, funded by the Horizon 2020 Programme of the European Union. The CEITEC Cryo-electron Microscopy and Tomography core facility is supported by MEYS CR (LM2018127

Cementing proteins provide extra mechanical stabilization to viral cages

The study of virus shell stability is key not only for gaining insights into viral biological cycles but also for using viral capsids in materials science. The strength of viral particles depends profoundly on their structural changes occurring during maturation, whose final step often requires the specific binding of ‘decoration’ proteins (such as gpD in bacteriophage lambda) to the viral shell. Here we characterize the mechanical stability of gpD-free and gpD-decorated bacteriophage lambda capsids. The incorporation of gpD into the lambda shell imparts a major mechanical reinforcement that resists punctual deformations. We further interrogate lambda particle stability with molecular fatigue experiments that resemble the sub-lethal Brownian collisions of virus shells with macromolecules in crowded environments. Decorated particles are especially robust against collisions of a few kBT (where kB is the Boltzmann’s constant and T is the temperature ~300 K), which approximate those anticipated from molecular insults in the environmentWe acknowledge the MINECO of Spain (PIB2010US-00233, FIS3011-29493, Consolider CSD2010-00024, CAMprojectNo.S3009/MAT-1467), and the US National Science Foundation (MCB-1158107) for their financial support of this researc

Determinación del estado metabólico de pacientes con diabetes gestacional mediante autómatas finitos

Los nuevos criterios de diagnóstico de la diabetes gestacional recomendados por la IADPSGC disminuyen los efectos adversos de la hiperglucemia tanto en la madre como en el recién nacido, pero su aplicación supondría un aumento de la prevalencia llegando a triplicar el número de casos actual. Para que los Servicios de Endocrinología y Nutrición puedan hacer frente a la carga que supondría este aumento de prevalencia es necesario emplear nuevos procesos asistenciales que incluyan el uso de las TICs. Este trabajo presenta una herramienta de análisis automático de datos de monitorización que determina el estado metabólico de las pacientes con diabetes gestacional a partir de sus datos de glucemia, dieta y cetonuria. Su diseño se basa en dos autómatas finitos, uno para el análisis de la glucemia y de la dieta y el otro para el análisis de la cetonuria. La salida de ambos autómatas se combina para determinar el estado metabólico de la paciente a lo largo del tiempo. La herramienta se ha evaluado con datos retrospectivos de 25 pacientes pertenecientes al Hospital Parc Taulí de Sabadell comparando los 1288 estados metabólicos resultantes con los 47 ajustes de terapia realizados por el equipo médico. Se observó que el 91,49% de los cambios de tratamiento coincidieron con estados metabólicos deficientes determinados por la herramienta de análisis. La herramienta ayuda a diferenciar pacientes complejas que requieren una evaluación exhaustiva y un ajuste de terapia de las que tienen buen control metabólico y no necesitan ser evaluadas por el personal médico

Using a causal smoothing to improve the performance of an on-line neural network glucose prediction algorithm

This work evaluates a spline-based smoothing method applied to the output of a glucose predictor. Methods:Our on-line prediction algorithm is based on a neural network model (NNM). We trained/validated the NNM with a prediction horizon of 30 minutes using 39/54 profiles of patients monitored with the Guardian® Real-Time continuous glucose monitoring system The NNM output is smoothed by fitting a causal cubic spline. The assessment parameters are the error (RMSE), mean delay (MD) and the high-frequency noise (HFCrms). The HFCrms is the root-mean-square values of the high-frequency components isolated with a zero-delay non-causal filter. HFCrms is 2.90±1.37 (mg/dl) for the original profiles

Acidification induces condensation of the adenovirus core

The adenovirus (AdV) icosahedral capsid encloses a nucleoprotein core formed by the dsDNA genome bound to numerous copies of virus-encoded, positively charged proteins. For an efficient delivery of its genome, AdV must undergo a cascade of dismantling events from the plasma membrane to the nuclear pore. Throughout this uncoating process, the virion moves across potentially disruptive environments whose influence in particle stability is poorly understood. In this work we analyze the effect of acidic conditions on AdV particles by exploring their mechanical properties, genome accessibility and capsid disruption. Our results show that under short term acidification the AdV virion becomes softer and its genome less accessible to an intercalating dye, even in the presence of capsid openings. The AFM tip penetrates deeper in virions at neutral pH, and mechanical properties of genome-less particles are not altered upon acidification. Altogether, these results indicate that the main effect of acidification is the compaction of the nucleoproteic core, revealing a previously unknown role for chemical cues in AdV uncoating. Statement of significance: Studying the behavior of virus particles under changing environmental conditions is key to understand cell entry and propagation. One such change is the acidification undergone in certain cell compartments, which is thought to play a role in the programmed uncoating of virus genomes. Mild acidification in the early endosome has been proposed as a trigger signal for human AdV uncoating. However, the actual effect of low pH in AdV stability and entry is not well defined. Understanding the consequences of acidification in AdV structure and stability is also relevant to define storage conditions for therapeutic vectors, or design AdV variants resistant to intestinal conditions for oral administration of vaccinesWe thank M. G. Mateu (CBMSO-CSIC-UAM) for careful reading and insightful comments on early drafts, M. Castellanos and L. A. Campos (CNB-CSIC) for advice with fluorescence measurements and analyses, and M.I. Laguna (CNB-CSIC) for expert technical help. This work was supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness (FIS2017- 89549- R; “Maria de Maeztu” Program for Units of Excellence in R&D MDM-2014-0377; and FIS2017-90701-REDT) and from the Human Frontiers Science Program (HFSPO RGP0012/2018) to P.J.P.; as well as grants PID2019-104098GB-I00/AEI/10.13039/501100011033 and BFU2016-74868-P, co-funded by the Spanish State Research Agency and the European Regional Development Fund, and 2019AEP045 from the Agencia Estatal CSIC to C.S.M. The CNB-CSIC is further supported by a Severo Ochoa Excellence grant (SEV 2017-0712). MM was funded by grant RTI2018-099985-B-I00, (MICINN/FEDER, UE) and the Ciber of Respiratory Diseases (CIBERES), an initiative from the Spanish Institute of Health Carlos III (ISCIII). M.H.-P. was a recipient of a Juan de la Cierva Incorporation postdoctoral contract funded by the Spanish State Research Agency. M.P.-I. held a predoctoral contract from La Caixa Foundation (ID 100010434, under agreement LCF/BQ/SO16/52270032). J. G. is a re cipient of a FPI predoctoral contract (BES-2017-079868) funded by the Spanish State Research Agenc