The convergence of radiation and immunogenic cell death signaling pathways.

Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill. As a result, traditional measurements of radiation-induced tumor cell death, in vitro, fail to represent the extent of clinically observed responses, including reductions in loco-regional failure rates and improvements in metastases free and overall survival. Hence, understanding the immunological responses to the type of radiation-induced cell death is critical. In this review, the mechanisms of radiation-induced tumor cell death are described, with particular focus on immunogenic cell death (ICD). Strategies combining radiotherapy with specific chemotherapies or immunotherapies capable of inducing a repertoire of cancer specific immunogens might potentiate tumor control not only by enhancing cell kill but also through the induction of a successful anti-tumor vaccination that improves patient survival

L’inibizione tireotropinica da metformina non si associa a segni cardiologici di ipertiroidismo subclinico

Recenti dati di letteratura hanno evidenziato come metformina determini una riduzione/soppressione dei livelli sierici di tireotro- pina (TSH), simulando un ipertiroidismo subclinico il cui signifi- cato clinico rimane a oggi ancora assai controverso. Sebbene l’ipertiroidismo subclinico sia nella maggioranza dei casi una condizione clinica asintomatica, è altrettanto noto come esso si associ a un aumentato rischio di aritmie (più frequentemente la fibrillazione atriale) e ad alterazioni morfo-funzionali cardiache determinando un aumento di morbilità e mortalità cardiovasco- lare. Scopo del presente studio è stato quello di valutare retrospetti- vamente le alterazioni di differenti indici elettrocardiografici in pazienti diabetici eutiroidei che, dopo aver intrapreso terapia con metformina, hanno sviluppato riduzione/soppressione dei valori di TSH comparando i dati con quelli ottenuti in pazienti con iper- tiroidismo subclinico secondario a patologie tiroidee o a terapia soppressiva con L-tiroxina. I parametri elettrocardiografici (frequenza cardiaca, durata del- l’onda P, indice di dispersione dell’onda P, QT max, QT min, indice di dispersione dell’intervallo QT) sono stati valutati in 23 pazienti diabetici in terapia con metformina prima e dopo 6 mesi dall’instaurarsi della soppressione del TSH e in 31 con- trolli con ipertiroidismo subclinico. Nessuna modifica significa- tiva è stata osservata tra i parametri elettrocardiografici rilevati prima e dopo la riduzione del TSH. Al contrario, significative dif- ferenze nella durata dell’onda P (102,9 ± 7,4 vs 92,1 ± 5,8 ms, p < 0,001), dell’indice di dispersione dell’onda P (13,1 ± 3,4 vs 7,1 ± 3,5 ms, p < 0,001), del QT max (399 ± 18 vs 388 ± 16 ms, p = 0,024), del QT min (341 ± 14 vs 350 ± 17 ms, p = 0,038) e di quello dell’intervallo QT (49,9 ± 9,6 vs 30,9 ± 9,2 ms, p < 0,001) sono state rilevate tra i controlli con iperti- roidismo subclinico e il gruppo di pazienti diabetici con valori ridotti/soppressi di TSH. I risultati del nostro studio evidenzierebbero come l’effetto di riduzione/soppressione del TSH osservato in alcuni pazienti dia- betici in terapia con metformina non si associ a marker periferi- ci cardiaci da eccesso di ormoni tiroidei. L’alterazione del profilo tiroideo metformina-indotto sembrerebbe non indicativo di iper- tiroidismo subclinico, suggerendo quindi che non sussiste la necessità di sottoporre a stretti controlli della funzione tiroidea i pazienti diabetici in terapia con metformin

On the Parity Problem in One-Dimensional Cellular Automata

We consider the parity problem in one-dimensional, binary, circular cellular automata: if the initial configuration contains an odd number of 1s, the lattice should converge to all 1s; otherwise, it should converge to all 0s. It is easy to see that the problem is ill-defined for even-sized lattices (which, by definition, would never be able to converge to 1). We then consider only odd lattices. We are interested in determining the minimal neighbourhood that allows the problem to be solvable for any initial configuration. On the one hand, we show that radius 2 is not sufficient, proving that there exists no radius 2 rule that can possibly solve the parity problem from arbitrary initial configurations. On the other hand, we design a radius 4 rule that converges correctly for any initial configuration and we formally prove its correctness. Whether or not there exists a radius 3 rule that solves the parity problem remains an open problem.Comment: In Proceedings AUTOMATA&JAC 2012, arXiv:1208.249

Atmospheric aerosols at the Pierre Auger Observatory and environmental implications

The Pierre Auger Observatory detects the highest energy cosmic rays. Calorimetric measurements of extensive air showers induced by cosmic rays are performed with a fluorescence detector. Thus, one of the main challenges is the atmospheric monitoring, especially for aerosols in suspension in the atmosphere. Several methods are described which have been developed to measure the aerosol optical depth profile and aerosol phase function, using lasers and other light sources as recorded by the fluorescence detector. The origin of atmospheric aerosols traveling through the Auger site is also presented, highlighting the effect of surrounding areas to atmospheric properties. In the aim to extend the Pierre Auger Observatory to an atmospheric research platform, a discussion about a collaborative project is presented.Comment: Regular Article, 16 pages, 12 figure

Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery.

Drug malabsorption is a potential concern after bariatric surgery. We present four case reports of hypothyroid patients who were well replaced with thyroxine tablets to euthyroid thyrotropin (TSH) levels prior to Roux-en-Y gastric bypass surgery. These patients developed elevated TSH levels after the surgery, the TSH responded reversibly to switching from treatment with oral tablets to a liquid formulation

How surface properties influence mineral dust emissions in the Sahelian region ? A modelling case study during AMMA

Tropical mesoscale convective systems (MCSs) are a prominent feature of the African meteorology. A continuous monitoring of the aeolian activity in an experimental site located in Niger shows that such events are responsible for the major part of the annual local wind erosion, i.e. for most of the Sahelian dust emissions [Rajot, 2001]. However, the net effect of these MCSs on mineral dust budget has to be estimated: on the one hand, these systems produce extremely high surface wind velocities leading to intense dust uptake, but on the other hand, rainfalls associated with these systems can efficiently remove the emitted dust from the atmosphere. High resolution modelling appears as a relevant approach to correctly reproduce the surface meteorology associated with such meteorological systems [Bouet et al., submitted]. The question now arising concerns the reliability of surface characteristics available for the Sahelian region, especially soil texture and surface roughness, which are critical parameters for dust emissions. Contrary to arid regions, which are now well documented, data is still missing to correctly characterize semi-arid regions like the Sahel. This is in particular due to the well pronounced annual cycles of precipitations and vegetation in these regions and to the impact of land-use on surface properties. This study focuses on a case study of dust emission associated with the passage of a MCS observed during one of the Special Observing Periods of the international African Monsoon Multidisciplinary Analysis (AMMA &#8211; SOPs 1-2) program. The simulations were made using the Regional Atmospheric Modeling System (RAMS, Cotton et al. [2003]) coupled online with the dust production model developed by Marticorena and Bergametti [1995] and recently improved by Laurent et al. [2008] for Africa. The sensitivity of dust emission associated with the passage of the MCS to surface features is investigated using different data sets of surface properties (Harmonized World Soil Database, HWSD) and land-use (GLOBCOVER). In-situ measurements of dust concentrations (both ground-based and airborne), and of dust emission flux are used to validate the simulations

Variability of aerosol vertical distribution in the Sahel

In this work, we have studied the seasonal and inter-annual variability of the aerosol vertical distribution over Sahelian Africa for the years 2006, 2007 and 2008, characterizing the different kind of aerosols present in the atmosphere in terms of their optical properties observed by ground-based and satellite instruments, and their sources searched for by using trajectory analysis. This study combines data acquired by three ground-based micro lidar systems located in Banizoumbou (Niger), Cinzana (Mali) and M'Bour (Senegal) in the framework of the African Monsoon Multidisciplinary Analysis (AMMA), by the AEROsol RObotic NETwork (AERONET) sun-photometers and by the space-based Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) onboard the CALIPSO satellite (Cloud-Aerosol Lidar and Infrared Pathfinder Observations). &lt;br&gt;&lt;br&gt; During winter, the lower levels air masses arriving in the Sahelian region come mainly from North, North-West and from the Atlantic area, while in the upper troposphere air flow generally originates from West Africa, crossing a region characterized by the presence of large biomass burning sources. The sites of Cinzana, Banizoumbou and M'Bour, along a transect of aerosol transport from East to West, are in fact under the influence of tropical biomass burning aerosol emission during the dry season, as revealed by the seasonal pattern of the aerosol optical properties, and by back-trajectory studies. &lt;br&gt;&lt;br&gt; Aerosol produced by biomass burning are observed mainly during the dry season and are confined in the upper layers of the atmosphere. This is particularly evident for 2006, which was characterized by a large presence of biomass burning aerosols in all the three sites. &lt;br&gt;&lt;br&gt; Biomass burning aerosol is also observed during spring when air masses originating from North and East Africa pass over sparse biomass burning sources, and during summer when biomass burning aerosol is transported from the southern part of the continent by the monsoon flow. &lt;br&gt;&lt;br&gt; During summer months, the entire Sahelian region is under the influence of Saharan dust aerosols: the air masses in low levels arrive from West Africa crossing the Sahara desert or from the Southern Hemisphere crossing the Guinea Gulf while in the upper layers air masses still originate from North, North-East. The maximum of the desert dust activity is observed in this period which is characterized by large AOD (above 0.2) and backscattering values. It also corresponds to a maximum in the extension of the aerosol vertical distribution (up to 6 km of altitude). In correspondence, a progressive cleaning up of the lowermost layers of the atmosphere is occurring, especially evident in the Banizoumbou and Cinzana sites. &lt;br&gt;&lt;br&gt; Summer is in fact characterized by extensive and fast convective phenomena. &lt;br&gt;&lt;br&gt; Lidar profiles show at times large dust events loading the atmosphere with aerosol from the ground up to 6 km of altitude. These events are characterized by large total attenuated backscattering values, and alternate with very clear profiles, sometimes separated by only a few hours, indicative of fast removal processes occurring, likely due to intense convective and rain activity. &lt;br&gt;&lt;br&gt; The inter-annual variability in the three year monitoring period is not very significant. An analysis of the aerosol transport pathways, aiming at detecting the main source regions, revealed that air originated from the Saharan desert is present all year long and it is observed in the lower levels of the atmosphere at the beginning and at the end of the year. In the central part of the year it extends upward and the lower levels are less affected by air masses from Saharan desert when the monsoon flow carries air from the Guinea Gulf and the Southern Hemisphere inland

Morbid Obesity in Women is Associated to a Lower Prevalence of Thyroid Nodules.

BACKGROUND: Few studies have recently showed functional and morphological changes of the thyroid gland in relation to obesity. To our knowledge, no data are available about the prevalence of thyroid nodules in female obese patients. The aim of this study was to investigate the prevalence of thyroid nodules in morbidly obese women. METHODS: One hundred eight consecutive female obese patients were selected from those referred to our medical and surgery outpatients providing that following criteria were satisfied: (1) affected by morbid obesity (body mass index (BMI) >40 kg/m(2)); (2) no previous diagnosis of thyroid disease; (3) biochemically proven euthyroid state at the time of recruitment. Ninety-seven control subjects, constituted by normo-weight and/or slightly overweight (BMI ≤ 30 kg/m(2)) women, should satisfy the above criteria 2 and 3. All the subjects were submitted to ultrasound investigation. RESULTS: The two groups of patients displayed no differences for age and fT4 levels. Obese patients clearly showed a lower prevalence of thyroid nodules [odds ratio 0.294, 95% confidence interval 0.206-0.382]. A single nodule was found in 23% of obese patients as compared to 65% of control subjects (p < 0.0001). No difference for age (year) was found between obese and non-obese subjects with nodules (40.5 ± 8.2 vs. 44.2 ± 8.9, respectively, p = 0.07). CONCLUSIONS: Our data clearly show a significantly lower prevalence of thyroid nodules in morbidly obese patients. Further studies are needed to confirm and to understand this first observation

Relating hygroscopicity and optical properties to chemical composition and structure of secondary organic aerosol particles generated from the ozonolysis of α-pinene

Secondary organic aerosol (SOA) were generated from the ozonolysis of α-pinene in the CESAM (French acronym for Experimental Multiphasic Atmospheric Simulation Chamber) simulation chamber. The SOA formation and aging were studied by following their optical, hygroscopic and chemical properties. The optical properties were investigated by determining the particle complex refractive index (CRI). The hygroscopicity was quantified by measuring the effect of relative humidity (RH) on the particle size (size growth factor, GF) and on the scattering coefficient (scattering growth factor, f(RH)). The oxygen to carbon atomic ratios (O : C) of the particle surface and bulk were used as a sensitive parameter to correlate the changes in hygroscopic and optical properties of the SOA composition during their formation and aging in CESAM. The real CRI at 525 nm wavelength decreased from 1.43–1.60 (±0.02) to 1.32–1.38 (±0.02) during the SOA formation. The decrease in the real CRI correlated to the O : C decrease from 0.68 (±0.20) to 0.55 (±0.16). In contrast, the GF remained roughly constant over the reaction time, with values of 1.02–1.07 (±0.02) at 90% (±4.2%) RH. Simultaneous measurements of O : C of the particle surface revealed that the SOA was not composed of a homogeneous mixture, but contained less oxidised species at the surface which may limit water absorption. In addition, an apparent change in both mobility diameter and scattering coefficient with increasing RH from 0 to 30% was observed for SOA after 14 h of reaction. We postulate that this change could be due to a change in the viscosity of the SOA from a predominantly glassy state to a predominantly liquid state