Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

Loop Quantum Gravity

The problem of finding the quantum theory of the gravitational field, and thus understanding what is quantum spacetime, is still open. One of the most active of the current approaches is loop quantum gravity. Loop quantum gravity is a mathematically well-defined, non-perturbative and background independent quantization of general relativity, with its conventional matter couplings. The research in loop quantum gravity forms today a vast area, ranging from mathematical foundations to physical applications. Among the most significative results obtained are: (i) The computation of the physical spectra of geometrical quantities such as area and volume; which yields quantitative predictions on Planck-scale physics. (ii) A derivation of the Bekenstein-Hawking black hole entropy formula. (iii) An intriguing physical picture of the microstructure of quantum physical space, characterized by a polymer-like Planck scale discreteness. This discreteness emerges naturally from the quantum theory and provides a mathematically well-defined realization of Wheeler's intuition of a spacetime ``foam''. Long standing open problems within the approach (lack of a scalar product, overcompleteness of the loop basis, implementation of reality conditions) have been fully solved. The weak part of the approach is the treatment of the dynamics: at present there exist several proposals, which are intensely debated. Here, I provide a general overview of ideas, techniques, results and open problems of this candidate theory of quantum gravity, and a guide to the relevant literature.Comment: Review paper written for the electronic journal `Living Reviews'. 34 page

A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4+ T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4+ T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells

Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity

There is recent evidence that galectin-3 participates in immunity to infections, mostly by tuning cytokine production. We studied the balance of Th1/Th2 responses to P. brasiliensis experimental infection in the absence of galectin-3. The intermediate resistance to the fungal infection presented by C57BL/6 mice, associated with the development of a mixed type of immunity, was replaced with susceptibility to infection and a Th2-polarized immune response, in galectin-3-deficient (gal3−/−) mice. Such a response was associated with defective inflammatory and delayed type hypersensitivity (DTH) reactions, high IL-4 and GATA-3 expression and low nitric oxide production in the organs of infected animals. Gal3−/− macrophages exhibited higher TLR2 transcript levels and IL-10 production compared to wild-type macrophages after stimulation with P. brasiliensis antigens. We hypothesize that, during an in vivo P. brasiliensis infection, galectin-3 exerts its tuning role on immunity by interfering with the generation of regulatory macrophages, thus hindering the consequent Th2-polarized type of response

IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence

IL-10 is an anti-inflammatory cytokine that regulates the extent of host immunity to infection by exerting suppressive effects on different cell types. Herpes viruses induce IL-10 to modulate the virus-host balance towards their own benefit, resulting in prolonged virus persistence. To define the cellular and molecular players involved in IL-10 modulation of herpes virus-specific immunity, we studied mouse cytomegalovirus (MCMV) infection. Here we demonstrate that IL-10 specifically curtails the MCMV-specific CD4 T cell response by suppressing the bidirectional crosstalk between NK cells and myeloid dendritic cells (DCs). In absence of IL-10, NK cells licensed DCs to effectively prime MCMV-specific CD4 T cells and we defined the pro-inflammatory cytokines IL-12, IFN-γ and TNF-α as well as NK cell activating receptors NKG2D and NCR-1 to regulate this bidirectional NK/DC interplay. Consequently, markedly enhanced priming of MCMV-specific CD4 T cells in Il10-/-mice led to faster control of lytic viral replication, bu

Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice

Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection

Discerning natural and anthropogenic organic matter inputs to salt marsh sediments of Ria Formosa lagoon (South Portugal)

Sedimentary organic matter (OM) origin and molecular composition provide useful information to understand carbon cycling in coastal wetlands. Core sediments from threors' Contributionse transects along Ria Formosa lagoon intertidal zone were analysed using analytical pyrolysis (Py-GC/MS) to determine composition, distribution and origin of sedimentary OM. The distribution of alkyl compounds (alkanes, alkanoic acids and alkan-2-ones), polycyclic aromatic hydrocarbons (PAHs), lignin-derived methoxyphenols, linear alkylbenzenes (LABs), steranes and hopanes indicated OM inputs to the intertidal environment from natural-autochthonous and allochthonous-as well as anthropogenic. Several n-alkane geochemical indices used to assess the distribution of main OM sources (terrestrial and marine) in the sediments indicate that algal and aquatic macrophyte derived OM inputs dominated over terrigenous plant sources. The lignin-derived methoxyphenol assemblage, dominated by vinylguaiacol and vinylsyringol derivatives in all sediments, points to large OM contribution from higher plants. The spatial distributions of PAHs (polyaromatic hydrocarbons) showed that most pollution sources were mixed sources including both pyrogenic and petrogenic. Low carbon preference indexes (CPI > 1) for n-alkanes, the presence of UCM (unresolved complex mixture) and the distribution of hopanes (C-29-C-36) and steranes (C-27-C-29) suggested localized petroleum-derived hydrocarbon inputs to the core sediments. Series of LABs were found in most sediment samples also pointing to domestic sewage anthropogenic contributions to the sediment OM.EU Erasmus Mundus Joint Doctorate fellowship (FUECA, University of Cadiz, Spain)EUEuropean Commission [FP7-ENV-2011, 282845, FP7-534 ENV-2012, 308392]MINECO project INTERCARBON [CGL2016-78937-R]info:eu-repo/semantics/publishedVersio

Cadence (steps/min) and intensity during ambulation in 6-20 year olds: The CADENCE-kids study

Background: Steps/day is widely utilized to estimate the total volume of ambulatory activity, but it does not directly reflect intensity, a central tenet of public health guidelines. Cadence (steps/min) represents an overlooked opportunity to describe the intensity of ambulatory activity. We sought to establish thresholds linking directly observed cadence with objectively measured intensity in 6-20 year olds.Methods: One hundred twenty participants completed multiple 5-min bouts on a treadmill, from 13.4 m/min (0.80 km/h) to 134.0 m/min (8.04 km/h). The protocol was terminated when participants naturally transitioned to running, or if they chose to not continue. Steps were visually counted and intensity was objectively measured using a portable metabolic system. Youth metabolic equivalents (METy) were calculated for 6-17 year olds, with moderate intensity defined as >/=4 and /=6 METy. Traditional METs were calculated for 18-20 year olds, with moderate intensity defined as >/=3 and /=6 METs. Optimal cadence thresholds for moderate and vigorous intensity were identified using segmented random coefficients models and receiver operating characteristic (ROC) curves.Result: Participants were on average (+/- SD) aged 13.1 +/- 4.3 years, weighed 55.8 +/- 22.3 kg, and had a BMI z-score of 0.58 +/- 1.21. Moderate intensity thresholds (from regression and ROC analyses) ranged from 128.4 steps/min among 6-8 year olds to 87.3 steps/min among 18-20 year olds. Comparable values for vigorous intensity ranged from 157.7 steps/min among 6-8 year olds to 119.3 steps/min among 18-20 year olds. Considering both regression and ROC approaches, heuristic cadence thresholds (i.e., evidence-based, practical, rounded) ranged from 125 to 90 steps/min for moderate intensity, and 155 to 125 steps/min for vigorous intensity, with higher cadences for younger age groups. Sensitivities and specificities for these heuristic thresholds ranged from 77.8 to 99.0%, indicating fair to excellent classification accuracy.Conclusions: These heuristic cadence thresholds may be used to prescribe physical activity intensity in public health recommendations. In the research and clinical context, these heuristic cadence thresholds have apparent value for accelerometer-based analytical approaches to determine the intensity of ambulatory activity.Peer reviewedCommunity Health Sciences, Counseling and Counseling Psycholog

Estimación de la concentración media diaria de material particulado fino en la región del Complejo Industrial y Portuario de Pecém, Ceará, Brasil

A exposição ao material particulado fino (MP2,5) está associada a inúmeros desfechos à saúde. Desta forma, monitoramento da concentração ambiental do MP2,5 é importante, especialmente em áreas amplamente industrializadas, pois abrigam potenciais emissores do MP2,5 e de substâncias com potencial de aumentar a toxicidade de partículas já suspensas. O objetivo desta pesquisa é estimar a concentração diária do MP2,5 em três áreas de influência do Complexo Industrial e Portuário do Pecém (CIPP), Ceará, Brasil. Foi aplicado um modelo de regressão não linear para a estimativa do MP2,5, por meio de dados de profundidade óptica monitorados por satélite. As estimativas foram realizadas em três áreas de influência (Ai) do CIPP (São Gonçalo do Amarante – Ai I, Paracuru e Paraipaba – Ai II e Caucaia – Ai III, no período de 2006 a 2017. As médias anuais das concentrações estimadas foram inferiores ao estabelecido pela legislação nacional em todas as Ai (8µg m-3). Em todas as Ai, os meses referentes ao período de seca (setembro a fevereiro) apresentaram as maiores concentrações e uma predominância de ventos leste para oeste. Os meses que compreendem o período de chuva (março a agosto) apresentaram as menores concentrações e ventos menos definidos. As condições meteorológicas podem exercer um papel importante nos processos de remoção, dispersão ou manutenção das concentrações do material particulado na região. Mesmo com baixas concentrações estimadas, é importante avaliar a constituição das partículas finas dessa região, bem como sua possível associação a efeitos adversos à saúde da população local.Exposure to fine particulate matter (PM2.5) is associated with numerous negative health outcomes. Thus, monitoring the environmental concentration of PM2.5 is important, especially in heavily industrialized areas, since they harbor potential emitters of PM2.5 and substances with the potential to increase the toxicity of already suspended particles. This study aims to estimate daily concentrations of PM2.5 in three areas under the influence of the Industrial and Port Complex of Pecém (CIPP), Ceará State, Brazil. A nonlinear regression model was applied to estimate PM2.5, using satellitemonitored optical depth data. Estimates were performed in three areas of influence (Ai) of the CIPP (São Gonçalo do Amarante – AiI, Paracuru and Paraipaba – AiII, and Caucaia – AiIII), from 2006 to 2017. Estimated mean annual concentrations were lower than established by Brazil’s national legislation in all three Ai (8µg m-³). In all the Ai, the months of the dry season (September to February) showed the highest concentrations and a predominance of east winds, while the months of the rainy season (March to August) showed the lowest concentrations and less defined winds Weather conditions can play an important role in the removal, dispersal, or maintenance of concentrations of particulate matter in the region. Even at low estimated concentrations, it is important to assess the composition of fine participles in this region and their possible association with adverse health outcomes in the local population.La exposición al material particulado fino (MP2,5) está asociada a innumerables problemas de salud. Por ello, la supervisión de la concentración ambiental del MP2,5 es importante, especialmente en áreas ampliamente industrializadas, puesto que albergan potenciales emisores de MP2,5 y de sustancias con potencial de aumentar la toxicidad de partículas ya suspendidas. El objetivo de esta investigación es estimar la concentración diaria del MP2,5 en tres áreas de influencia del Complejo Industrial y Portuario de Pecém (CIPP), Ceará, Brasil. Se aplicó un modelo de regresión no lineal para la estimación del MP2,5, mediante datos de profundidad óptica supervisados por satélite. Las estimaciones fueron realizadas en tres áreas de influencia (Ai) del CIPP (São Gonçalo do Amarante – Ai I, Paracuru y Paraipaba – Ai II y Caucaia – Ai III en el período de 2006 a 2017. Las medias anuales de las concentraciones estimadas fueron inferiores a lo establecido por la legislación nacional en todas las Ai (8µg m-³). En todas las Ai, los meses referentes al período de sequía (de setiembre a febrero) presentaron las mayores concentraciones y una predominancia de vientos este a oeste, los meses que comprenden el período de lluvia (marzo a agosto) presentaron las menores concentraciones y vientos menos definidos. Las condiciones meteorológicas pueden ejercer un papel importante en los procesos de eliminación, dispersión o mantenimiento de las concentraciones del material particulado en la región. Incluso con bajas concentraciones estimadas es importante que se evalúe la constitución de las partículas finas de esta región, así como su posible asociación con efectos adversos para la salud de la población local