Does the meteorological origin of heat waves influence their impact on health? A 6-year morbidity and mortality study in Madrid (Spain)

In Spain, two synoptic-scale conditions influence heat wave formation. The first involves advection of warm and dry air masses carrying dust of Saharan origin. Objective: to determine whether the impact of heat waves on health outcomes in Madrid (Spain) during 2013–2018 varied by synoptic-scale condition.The authors wish to thank the funding provided by the ENPY 304/20, and ENPY 436/21 projects of the National Health Institute Carlos III (ISCIII)

Short hydrogen bonds enhance nonaromatic protein-related fluorescence.

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications

Short hydrogen bonds enhance nonaromatic protein-related fluorescence.

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

Development, implementation and use of simulation techniques based on the Theory of Time Dependent Density Functionals (TD-DFT) applied to photochemical processes

Las Dinámicas moleculares de estados excitados son de central importancia para el entendimiento de procesos biológicos, tales como la fotosíntesis, y en aplicaciones tecnológicas, como el desarrollo de celdas fotovoltaicas de gran eficiencia. Sin embargo, es aún pobremente entendida, debido a las complejidades intrínsecas relacionadas a su estudio tanto experimental como teórico. Desde el trabajo de Paul Dirac en 1927, sobre la teoría cuántica (QM) de absorción y emisión de radiación (quién fue premiado con el premio Nobel de Física en 1933), una gran variedad de metodologías computacionales han sido desarrolladas para el estudio de estados excitados. Sin embargo, todas ellas comparten la carga de un costo computacional excesivo, el cual ha dificultado el estudio de la mayoría de los sistemas de interés en química. Esta situación empeora cuando el problema en cuestión requiere la inclusión de efectos del ambiente, tales como el de moléculas en solución o asociadas a proteínas. Por lo tanto, uno siempre se ve obligado a caminar sobre un borde afilado, equilibrando un costo computacional asequible con suficiente detalle para obtener resultados significativos con cierto grado de poder explicativo. No resulta sorprendente entonces, que el desarrollo de nuevas metodologías de estados excitados es ahora, a casi 100 años del trabajo de Dirac, un campo muy activo. En este trabajo de tesis se desarrollaron, implementaron y se aplicaron una variedad de metodologías basadas en la Teoría del Funcional de la Densidad Dependientes del Tiempo (TDDFT) para la descripción de procesos fotoquímicos y fotofísicos en sistemas complejos, las cuales se caracterizan por tener una muy buena relación entre el costo computacional y la calidad del resultado. Este esfuerzo fue dividido en dos partes. Por un lado, el formalismo independiente del tiempo basado en la Teoría de Respuesta Lineal (LR-TDDFT), el cual permite estudiar aspectos estáticos de los estados excitados, tales como la energía y densidad electrónica de los autoestados y por otra parte, un formalismo dependiente del tiempo llamado Trajectory Surface Hopping (TSH), el cual permite el estudio de aspectos dinámicos de los fenómenos de los estados excitados. Todo esto en el contexto de simulaciones híbridas de multi-escala cuántico/clásicas (QM/MM) para ser capaces de incluir efectos del ambiente. Este trabajo fue implementado en el projecto de código libre LIO, desarrollado por nuestro grupo, y caracterizado por una estrategia de paralelización usando CPUs y Tarjetas Gráficas (GPUs) de manera de reducir el tiempo requerido para los cálculos, permitiendo el tratamiento de problemas de otra manera impracticables. Estas metodologías fueron aplicadas al estudio de diferentes sistemas y procesos. Dentro de los fenómenos estáticos, mencionados anteriormente, estudiamos el espectro de absorción de diferentes conformaciones de Biliverdinas. Por otro lado, por medio del formalismo dependiente del tiempo, pudimos estudiar aspectos dinámicos de los estados excitados, como ser el cálculo del rendimiento cuántico de fluorescencia del grupo indol en diferentes solventes. Adicionalmente, empleando una combinación de TSH y técnicas de Unsupervised Machine Learning propusimos los mecanismos moleculares y electrónicos por el cual sistemas desprovistos de grupos arómaticos (o dobles enlaces conjugados) presentan fluorescencia, fenómeno recientemente descubierto denominado como fluorescencia de compuestos no aromáticos.Molecular excited-state dynamics are of central importance for the understanding of biological processes, such as photosynthesis, and in technological applications, such as the development of high efficiency photovoltaic cells. However, excited state dynamics are still poorly understood, due to the intrinsic complexities related to their study in both the experimental and theoretical approaches. Since Paul Dirac's 1927 seminal work in the quantum theory (QM) of the absorption and emission of radiation (which awarded him a Physics Nobel Prize in 1933), a great variety of computational methodologies have been developed for the study of excited states. However all of them share the burden of an exceedingly prohibitive computational cost which has hindered the study of most interest systems in chemistry. This situation worsens when the problem at hand requires the inclusion of environmental effects, as it is the case for molecules in solution or associated with proteins. Therefore one is always forced to walk along a sharp edge, balancing an affordable computational cost with sufficient detail to obtain meaningful results with some degree of explanatory power. It comes as no surprise then, that the development of new excited state methodologies is, now more than ever, a very active field. In this thesis we developed, implemented and applied a variety of methodologies based on Time Dependent Density Functional Theory (TDDFT), to the description of photochemical and photophysical processes in complex systems, that has an excellent balance between computational cost and quality of results. We divided this endeavour in two fronts. On one hand, a time-independent formalism based on Linear Response Theory (LR-TDDFT), which allows the study of static aspects of excited states, such as energy eigenstates and electron densities, and on the other hand, a time-dependent formalism called Trajectory Surface Hopping (TSH), which allows the study of dynamical aspects of excited state phenomena. All of this in the context of multi-scale hybrid quantum/- classical simulations (QM/MM) in order to be able to include environmental effects. The entirety of this work was implemented in the open source project LIO, developed in our group, and characterized by a parallelization strategy using CPUs and Graphic Processing Units (GPUs) in order to reduce the time required for the calculations, allowing the treatment of otherwise impractical problems. These methodologies were applied to the study of different photochemical systems and processes. Within the static phenomena, mentioned above, we study the absorption spectrum of different conformations of Biliverdins. On the other hand, through the time-dependent formalism, we were able to study dynamic aspects of the excited states. such as the calculation of the fluorescence quantum yield of the indole group in different solvents. Additionally, using a combination of TSH and Unsupervised Machine Learning techniques, we proposed the molecular and electronic mechanisms by which systems de void of aromatic groups (or conjugated double bonds) fluoresce, a recently discovered phenomenon known as non-aromatic fluorescence.Fil: Díaz Mirón, Gonzalo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Fluorescence Quantum Yields in Complex Environments from QM-MM TDDFT Simulations: The Case of Indole in Different Solvents

Fluorescence is commonly exploited to probe microscopic properties. An important example is tryptophan in protein environments, where variations in fluorescence quantum yield, and in absorption and emission maxima, are used as indicators of changes in the environment. Modeling the fluorescence quantum yield requires the determination of both radiative and non-radiative decay constants, both on the potential energy surface of the excited fluorophore. Furthermore, the inclusion of complex environments implies their accurate representation as well as extensive configurational sampling. In this work, we present and test various methodologies based on TD-DFT and QM-MM molecular dynamics that take all these requirements into account to provide a quantitative prediction of the effect of the environment on the fluorescence quantum yield of indole, the tryptophan fluorophore. This investigation paves the way for applications to the realistic spectroscopic characterization of the local protein environment of tryptophan from computer simulations.Fil: Díaz Mirón, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentin

QM–MM Ehrenfest dynamics from first principles: photodissociation of diazirine in aqueous solution

This article describes an implementation of Ehrenfest molecular dynamics based on TDDFT and Gaussian basis sets, optimized for hybrid QM–MM simulations in GPU. The present method makes use of the equations of motion proposed by Chen et al. (J Chem Phys 135:044126, 2011), which, at variance with previous formulations of the Ehrenfest dynamics, takes into account the movement of the localized basis functions, thus improving accuracy and energy conservation. This methodology is used to explore the evolution and the stability of excited state dynamics for two different constructions of the initial excited state, consisting in the linear response TDDFT S1 solution, and in the ground state density matrix where the HOMO–LUMO occupancies have been switched, which is a widespread approach to model photoexcitation in electron dynamics simulations. It is found that the second kind of starting state leads to a larger numerical noise and to a poorer stability of the dynamics, aside from “awakening” inner electronic modes that become manifest in the frequency spectrum, and which are absent if the dynamics departs from the linear response TDDFT density matrix. Then, the method is applied to investigate the photodissociation of the diazirine molecule, CH2N2, both in vacuum and in aqueous solution. Diazirine decomposes into carbene and molecular nitrogen upon irradiation with UV light, and for this reason it has been widely adopted to photolabel biomolecules through the insertion of carbenes in the macromolecular surface. Our simulations suggest that the quantum yield of the dissociative reaction experiences a decrease in solution with respect to the gas phase, that can be understood in terms of the vibrational relaxation facilitated by the solvent molecules. Besides, the present results indicate that the isomerization and dissociation mechanism occur fully on the S1 excited state.Fil: Ramírez, Francisco Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Díaz Mirón, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Scherlis Perel, Damian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

The “Carbonyl-Lock” Mechanism Underlying Non-Aromatic Fluorescence in Biological Matter

Challenging the basis of our chemical intuition, recent experimental evidence reveals the presence of a new type of intrinsic fluorescence in biomolecules that exists even in the absence of aromatic or electronically conjugated chemical compounds. The origin of this phenomenon has remained elusive so far. In the present study, we identify a mechanism underlying this new type of fluorescence in different biological aggregates. By employing non-adiabatic ab initio molecular dynamics simulations combined with an unsupervised learning approach, we characterize the typical ultrafast non-radiative relaxation pathways active in non-fluorescent peptides. We show that the key vibrational mode for the non-radiative decay towards the ground state is the carbonyl elongation. Non-aromatic fluorescence appears to emerge from blocking this mode with strong local interactions such as hydrogen bonds. This "carbonyl-lock" mechanism for trapping the excited state leads to the fluorescence yield increase observed experimentally, and paves the way for design principles to realize novel non-invasive biocompatible probes with applications in bioimaging, sensing, and biophotonics

The carbonyl-lock mechanism underlying non-aromatic fluorescence in biological matter

Acknowledgements: G.D.M. and J.A.S. gratefully acknowledges CONICET doctoral fellowship. G.D.M. also acknowledges to CINECA supercomputing (project NAFAA - HP10B4ZBB2). UNM acknowledges CINECA supercomputing center (projects V-COINS - HP10C35IQ1 and V-CoIns - HP10BY0AET), and Elettra-TeraFERMI project 20224056. AH and G.D.M would like to acknowledge the European Commission for funding on the ERC Grant HyBOP 101043272. DAE, MCGL, JAS and UNM would like to acknowledge founding from PICT 2020 01828 UNM, MCGL, DAE, Agencia I-+d+i. IR gratefully acknowledges the use of HPC resources of the “Pôle Scientifique de Modélisation Numérique- (PSMN) of the ENS-Lyon, France. J.V’s work has partially received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska Curie grant agreement No. 101025385. We also acknowledge Prof. Sir John Walker, Prof. David Palmer, Dr. Johannes Schmidt, Dr. Zeinab Ebrahimpour, Dr. Pablo Videla, Prof. Victor S. Batista and Dr. Marcello Coreno for useful discussions.AbstractChallenging the basis of our chemical intuition, recent experimental evidence reveals the presence of a new type of intrinsic fluorescence in biomolecules that exists even in the absence of aromatic or electronically conjugated chemical compounds. The origin of this phenomenon has remained elusive so far. In the present study, we identify a mechanism underlying this new type of fluorescence in different biological aggregates. By employing non-adiabatic ab initio molecular dynamics simulations combined with a data-driven approach, we characterize the typical ultrafast non-radiative relaxation pathways active in non-fluorescent peptides. We show that the key vibrational mode for the non-radiative decay towards the ground state is the carbonyl elongation. Non-aromatic fluorescence appears to emerge from blocking this mode with strong local interactions such as hydrogen bonds. While we cannot rule out the existence of alternative non-aromatic fluorescence mechanisms in other systems, we demonstrate that this carbonyl-lock mechanism for trapping the excited state leads to the fluorescence yield increase observed experimentally, and set the stage for design principles to realize novel non-invasive biocompatible probes with applications in bioimaging, sensing, and biophotonics.</jats:p

La sala de relajación : un espacio para aprender a relajarse y controlar la conducta

Los alumnos de este centro son personas con Trastorno del Espectro Autista TEA y tienen dificultades, en determinadas situaciones, para relajarse y regular su conducta, así dificultan su desarrollo personal y su inclusión social. Por ello, el objetivo de este proyecto es crear un entorno con unos objetivos, contenidos, materiales y metodología que permita la adquisición de estas habilidades. Este objetivo no se limita sólo al centro sino que pretende desplazar esta conducta a los entornos significativos de las vidas de los alumnos, fomentando la inclusión y la independencia. Las actividades están relacionadas previamente con la formación en técnicas de relajación y respiración e integración sensorial y estimulación basal. Se pretende que el alumno localice espacialmente la sala de relajación; reconocer su esquema corporal; percibir sensaciones relajantes táctiles, vibratorias, auditivas o visuales; aprender a tolerar sensaciones y estímulos auditivos estresantes; percibir y controlar la capacidad respiratoria; reconocer y expresar estados emocionales propios y asociar percepciones corporales a estados emocionales propios. La metodología se basa en la propuesta de la AAMR (Asociación Americana de Retraso Mental) y se centra en desarrollar y mejorar competencias en las diez áreas de habilidades adaptativas que son desarrollo humano, educación-enseñanza, vida en el hogar, vida en la comunidad, empleo, salud-seguridad, conducta social, protección-defensa y comunicación. Estas áreas se desarrollan en tres ámbitos conceptuales, sociales y prácticos a través de aplicar los siguientes principios: funcionalidad, espontaneidad, generalización, individualización, aprendizaje significativo, motivación, estructuración, flexibilidad, integración y validez social. La evaluación se lleva a cabo con la creación de un fichero donde quedan recogidas las experiencias, materiales y actividades recopiladas a lo largo del curso y a través de reuniones periódicas se valoran los resultados. Los anexos muestran fotografías con algunos de los ejercicios desarrollados..Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Mejora de la Calidad de la EnseñanzaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES