DAMPs and PDT-mediated photo-oxidative stress: exploring the unknown

Damage-associated molecular patterns (DAMPs) or cell death associated molecular patterns (CDAMPs) are a subset of endogenous intracellular molecules that are normally hidden within living cells but become either passively released by primary and secondary necrotic cells or actively exposed and secreted by the dying cells. Once released, DAMPs are sensed by the innate immune system and act as activators of antigen-presenting cells (APCs) to stimulate innate and adaptive immunity. Cancer cells dying in response to a subset of conventional anticancer modalities exhibit a particular composition of DAMPs at their cell surface, which has been recently shown to be vital for the stimulation of the host immune system and the control of residual disease. Photodynamic therapy (PDT) for cancer has long been shown to be capable of killing malignant cells and concomitantly stimulate the host immune system, properties that are likely linked to its ability of inducing exposure/release of certain DAMPs. PDT, by evoking oxidative stress at specific subcellular sites through the light activation of organelle-associated photosensitizers, may be unique in incorporating tumour cells destruction and antitumor immune response in one therapeutic paradigm. Here we review the current knowledge about mechanisms and signalling cascades leading to the exposure of DAMPs at the cell surface or promoting their release, the cell death mechanism associated to these processes and its immunological consequences. We also discuss how certain PDT paradigms may yield therapies that optimally stimulate the immune system and lead to the discovery of new DAMPs

Fast optimal transition between two equilibrium states

We demonstrate a technique based on invariants of motion for a time-dependent Hamiltonian, allowing a fast transition to a final state identical in theory to that obtained through a perfectly adiabatic transformation. This method is experimentally applied to the fast decompression of an ultracold cloud of Rubidium 87 atoms held in a harmonic magnetic trap, in the presence of gravity. We are able to decompress the trap by a factor of 15 within 35 ms with a strong suppression of the sloshing and breathing modes induced by the large vertical displacement and curvature reduction of the trap. When compared to a standard linear decompression, we achieve a gain of a factor of 37 on the transition time.Comment: 5 pages, 4 figures, an error in Eq. (2) has been correcte

Imagina que eres... Indagación sobre el uso de la lengua común en contexto matemático en la escuela media

Este artículo presenta los resultados de una investigación, realizada en la escuela media, sobre el uso de la lengua natural en contexto matemático, y sobre la producción de modelos externos en torno a las concepciones profundas de algunos conceptos elementales que poseen los alumnos. Con una técnica que invita a los alumnos a asumir un papel diferente del que usualmente juegan en la clase de matemáticas, se intentaba empujarlos a escribir acerca de asuntos matemáticos elementales en un lenguaje coloquial, sin los aparatos formales que con frecuencia exhiben. No obstante haber acogido bien el juego del cambio de papel que les propusimos y haber respondido a las situaciones problemáticas usando lengua natural, la mayoría de los alumnos presentó la tendencia a completar su respuesta inicial con una respuesta formal, a menudo vacía, que tenía poco que ver con la tarea. En casos en que los alumnos no usaron aparatos formales para responder se identificaron modelos que resultan interesantes en el plano de verificación de los aprendizajes

Slow breathing and hypoxic challenge: cardiorespiratory consequences and their central neural substrates

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge

Development and Initial Validation of a Questionnaire to Measure Health-Related Quality of Life of Adults with Common Variable Immune Deficiency: The CVID_QoL Questionnaire.

BACKGROUND: Generic health status quality of life (QoL) instruments have been used in patients with common variable immune deficiency (CVID). However, by their nature, these tools may over- or underestimate the impact of diseases on an individual's QoL. OBJECTIVE: The objective of this study was to develop and validate a questionnaire to measure specific-health-related QoL for adults with CVID (CVID_QoL). METHODS: The 32-item content of the CVID_QoL questionnaire was developed using focus groups and individual patient interviews. Validation studies included 118 adults with CVID who completed Short Form-36, Saint George Respiratory Questionnaire, General Health Questionnaire-12, and EuroQol-5D questionnaire in a single session. Principal component and factor analysis solutions identified 3 scores to be similar in number and content for each solution. Validation of 3 factor scores was performed by construct validity. Reproducibility, reliability, convergent validity, and discriminant validity were evaluated. Matrices consisting of correlations between the 32 items in the CVID_QOL were calculated. RESULTS: Factor analysis identified 3 dimensions: emotional functioning (EF), relational functioning (RF), and gastrointestinal and skin symptoms (GSS). The instrument had good internal consistency (Cronbach's alpha, min. 0.74 for GSS, max. 0.84 for RF, n = 118) and high reproducibility (intraclass correlation coefficient, min. 0.79 for RF, max 0.90 for EF, n = 27). EF and RF scores showed good convergent validity correlating with conceptually similar dimensions of other study scales. Acute and relapsing infections had a significant impact on EF and RF. CONCLUSIONS: This study provides evidence of the reliability and construct validity of the CVID_QoL to identify QoL issues in patients with CVID that may not be addressed by generic instruments

P2X7 Receptors in Neurological and Cardiovascular Disorders

P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X7, have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in a channel pore permeable to molecules as large as 900 daltons. The P2X7 receptor was originally described in cells of hematopoietic origin, and mediates the influx of Ca2+ and Na+ and Ca2+ and Na+ ions as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. Apoptotic cell death occurs in a number of vascular diseases, including atherosclerosis, restenosis, and hypertension, and may be linked to the release of ATP from endothelial cells, P2X7 receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2X7 receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems

Sparsity of the Field Signal-Based Method for Improving Spatial Resolution in Antenna Sensor Array Processing

The goal of array processing is to gather information from propagating radio-wave signals, as their Direction Of Arrival (DOA). The estimation of the DOA can be carried out by extracting the information of interest from the steering vector relevant to the adopted antenna sensor array. Such task can be accomplished in a number of different ways. However, in source estimation problems, it is essential to make use of a processing algorithm which feature not only good accuracy under ideal working conditions, but also robustness against non-idealities such as noise, limitations in the amount of collectible data, correlation between the sources, and modeling errors. In this work particular attention is devoted to spectrum estimation approaches based on sparsity. Conventional algorithms based on Beamforming fail wherein the radio sources are not within Rayleigh resolution range which is a function of the number of sensors and the dimension of the array. DOA estimation techniques such as MUSIC (MUltiple Signal Classifications) allow having a larger spatial resolution compared to Beamforming-based procedures, but if the sources are very close and the Signal to Noise Ratio (SNR) level is low, the resolution turns to be low as well. A better resolution can be obtained by exploiting sparsity: if the number of sources is small, the power spectrum of the signal with respect to the location is sparse. In this way, sparsity can enhance the accuracy of the estimation. In this paper, an estimation procedure based on the sparsity of the radio signals and useful to improve the conventional MUSIC method is presented and analyzed. The sparsity level is set in order to focus the signal energy only along the actual direction of arrival. The obtained numerical results have shown an improvement of the spatial resolution as well as a reduced error in DOA estimation with respect to conventional techniques