Novel recurrent chromosome anomalies in Shwachman Diamond syndrome

Clonal chromosome anomalies are frequently acquired in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS), and two are the most frequent: an isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q). Patients with SDS have a risk of developing myelodysplasia (MDS) and/or acute myeloid leukaemia (AML), and the presence of chromosome changes was studied in relation with this risk. Starting in 1999 we have monitored the cytogenetic picture of a cohort of 92 Italian patients with SDS by all suitable cytogenetic and molecular methods. Clonal anomalies in BM were present in 41/92 patients. The i(7)(q10) was observed in 16 patients, and the del(20)(q) in 15, both these changes in four, but in independent clones. So, the most frequent clonal anomalies were found in 35 patients. Other, different, clonal anomalies were found in the BM of 13 patients, in eight cases in the absence of i(7)(q10) or del(20)(q), in five cases in association with one of these changes. In these less common clonal anomalies, the distribution of the chromosomes involved was markedly disparate, and some of them were novel and recurrent: - structural rearrangements of chromosome 7, mainly unbalanced (deletions, inversions or translocations), were present in five of our 13 patients, three of whom developed MDS/AML. - a further complex rearrangement of the more common del(20)(q), leading to duplicated and deleted portions, was identical in two patients, with almost identical a-CGH profiles, neither developed MDS/AML. - an unbalanced translocation t(3;6), with partial trisomy of the long arm of chromosome 3 and partial monosomy of the long arm of chromosome 6, was not identical but very similar in two patients, one of whom developed MDS/AML

Application of a Switching Control Strategy to Extract Energy from Turbulence by a Fixed-wing UAV

The objective of this paper is to design a control law to allow a small fixed-wing Unmanned Aerial Vehicle to extract energy from atmospheric turbulence. From literature data the properties of atmospheric gusts at low altitude are discussed and a single point measurement is proved to be representative of the wind field. The longitudinal flight dynamics of the aircraft is analyzed and the phugoid mode is found to be the main driver of the energy extraction process. A switching controller that places the poles of the phugoid mode depending on the instantaneous variation of energy of the aircraft is designed. Statistical simulations show an increase of energy of the aircraft when this strategy is applied

Long-lived nonthermal electron distribution in aluminum excited by femtosecond extreme ultraviolet radiation

We report a time-resolved study of the relaxation dynamics of Al films excited by ultrashort intense free-electron laser (FEL) extreme ultraviolet pulses. The system response was measured through a pump-probe detection scheme, in which an intense FEL pulse tuned around the Al L2,3 edge (72.5 eV) acted as the pump, while a time-delayed ultrafast pulse probed the near-infrared (NIR) reflectivity of the Al film. Remarkably, following the intense FEL excitation, the reflectivity of the film exhibited no detectable variation for hundreds of femtoseconds. Following this latency time, sizable reflectivity changes were observed. Exploiting recent theoretical calculations of the EUV-excited electron dynamics [N. Medvedev et al., Phys. Rev. Lett. 107, 165003 (2011)], the delayed NIR-reflectivity evolution is interpreted invoking the formation of very-long-living nonthermal hot electron distributions in Al after exposure to EUV pulses. Our data represent the first evidence in the time domain of such an intriguing behavior

Integrating social preferences in spatial analysis: The case of the Mendocinian piedmont natural areas

En esta investigación se estima el cambio en el bienestar social por un cambio de paisaje de los espacios naturales del piedemonte mendocino. Para ello, se utiliza el método de valoración contingente para inferir el valor social de un cambio de paisaje por la acción antrópica sobre tres cuencas hidrográficas ubicadas al oeste del Gran Mendoza. Los resultados del estudio muestran que un cambio de paisaje, simulado mediante una disminución de la cobertura vegetal, disminuye el bienestar de los ciudadanos del Gran Mendoza. En particular, el cambio de paisaje equivale en pérdida de bienestar individual, en promedio, a un gasto anual de 78 pesos en moneda de 2013, a partir de ahora y durante 10 años. Por consiguiente, la continuidad de un proceso de planificación territorial que no impida el deterioro del paisaje de los espacios naturales del piedemonte implica una pérdida de bienestar social. En este sentido, la valoración económica genera un nuevo espacio de participación ciudadana, al integrar las preferencias sociales al diseño de la gestión, y construir sobre esa base, en diálogo con el juicio experto, una gestión territorial eficiente y sustentable desde un punto de vista social.In this study is estimated the change in social welfare for a landscape change of the Mendocinian piedmont natural areas. It is used the contingent valuation method to elicit the social value for a landscape change of anthropogenic-pressures on three basins placed at the west of Gran Mendoza. The results show that a landscape change, simulated through plant cover reduction, reduces the social welfare of Gran Mendoza's citizens. In particular, this landscape change represents for each citizen a welfare lost equivalent, on average, to an annual expense of pesos 78 (in 2013 currency) in the coming 10 years. Consequently, a territorial programme omitting the landscape decline of the natural areas of the Mendocinian piedmont worsens social welfare. So, the economic valuation creates room for citizens' participation by integrating social preferences into programmes design, and allows with a team of experts to build an efficient and sustainable territorial planning, from a social perspective.Fil: Farreras González, Verónica Inés. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Salvador, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas; ArgentinaFil: Vaccarino Pasquali, Emilce Liliana Belén. Universidad Nacional de Cuyo. International Center For Earth Sciences; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

Targeting protein kinase C by Enzastaurin restrains proliferation and secretion in human pancreatic endocrine tumors

Dysregulation of the protein kinase C (PKC) signaling pathway has been implicated in tumor progression. In this study, we investigate the effects of a PKC inhibitor, Enzastaurin, in human pancreatic neuroendocrine neoplasms (PNN) primary cultures and in the human pancreatic endocrine cancer cell line, BON1. To this aim six human PNN dispersed in primary cultures and BON1 cells were treated without or with 1–10 μM Enzastaurin and/or 100 nM IGF1 in the presence or absence of serum. Cell viability and apoptosis were evaluated after 48–72 h; Chromogranin A (CgA) and/or insulin secretion was assessed after 6 h of incubation. PKC expression was investigated by immunofluorescence and western blot. We found that Enzastaurin significantly reduced human PNN primary culture cell viability, as well as CgA and insulin secretion. Moreover, in the BON1 cell line Enzastaurin inhibited cell proliferation at 5 and 10 μM by inducing caspase-mediated apoptosis, and reduced phosphorylation of glycogen synthetase kinase 3β (GSK3β) and of Akt, both downstream targets of PKC pathway and pharmacodynamic markers for Enzastaurin. In addition, Enzastaurin blocked the stimulatory effect of IGF1 on cell proliferation, and reduced CgA expression and secretion in BON1 cells. Two different PKC isoforms are expressed at different levels and have partially different subcellular localization in BON1 cells. In conclusion, Enzastaurin reduces cell proliferation by inducing apoptosis, with a mechanism likely involving GSK3β signaling, and inhibits secretory activity in PNNin vitromodels, suggesting that Enzastaurin might represent a possible medical treatment of human PNN

Further constraining galaxy evolution models through the Size Function of SDSS Early-type galaxies

We discuss how the effective radius Phi(Re) function (ERF) recently worked out by Bernardi et al. (2009) represents a new testbed to improve the current understanding of Semi-analytic Models of Galaxy formation. In particular, we here show that a detailed hierarchical model of structure formation can broadly reproduce the correct peak in the size distribution of local early-type galaxies, although it significantly overpredicts the number of very compact and very large galaxies. This in turn is reflected in the predicted size-mass relation, much flatter than the observed one, due to too large (~3 kpc) low-mass galaxies (<10^11 \msun), and to a non-negligible fraction of compact ( 10^11 \msun). We also find that the latter discrepancy is smaller than previously claimed, and limited to only ultracompact (Re < 0.5 kpc) galaxies when considering elliptical-dominated samples. We explore several causes behind these effects. We conclude that the former problem might be linked to the initial conditions, given that large and low-mass galaxies are present at all epochs in the model. The survival of compact and massive galaxies might instead be linked to their very old ages and peculiar merger histories. Overall, knowledge of the galactic stellar mass {\em and} size distributions allows a better understanding of where and how to improve models.Comment: 15 pages, 10 Figures. Accepted by MNRA

The use of antimicrobials in Italian heavy pig fattening farms

Data on antimicrobial use (AMU) in heavy pig production (>150 kg) are limited. The aim of this study was to investigate the AMU in this production. Data from 2015 were collected for 143 fattening farms. The AMU was estimated through a treatment index per 100 days (TI100) using the defined daily dose animal for Italy (DDDAit). When possible, a comparison with the European Medicines Agency's defined daily doses for animals (DDDvet) was performed. The median TI100 was 10.7 (range, 0.2-49.5). Group treatments represented 94.6% of overall consumption. The AMU calculated using DDDAit and DDDvet were strongly correlated (rho = 0.976; p < 0.001). The AMU was negatively correlated with injectables use (rho = -0.46, p < 0.001) and positively correlated with oral products (rho = 0.21, p = 0.014), premixes (rho = 0.26, p = 0.002), and mortality (rho = 0.18; p = 0.027). Farm size was negatively correlated with AMU (rho = -0.29, p < 0.001). Smaller farms were more frequently above the median TI100 (odds ratio = 2.3, 95% confidence interval = 1.2-4.7), suggesting that they may have lower biosecurity and management standards. The results of this study should provide useful insights for the development of an Italian monitoring system

The distinct stellar-to-halo mass relations of satellite and central galaxies: insights from the IllustrisTNG simulations

We study the stellar-to-halo mass relation (SHMR) for central and satellite galaxies with total dynamical masses above 10^10.5 Msun using the suite of cosmological magneto-hydrodynamical simulations IllustrisTNG. In particular, we quantify environmental effects on satellite populations from TNG50, TNG100, and TNG300 located within the virial radius of group- and cluster-like hosts with total masses of 10^12-15.2 Msun. At fixed stellar mass, the satellite SHMR exhibits a distinct shift towards lower dynamical mass compared to the SHMR of centrals. Conversely, at fixed dynamical mass, satellite galaxies appear to have larger stellar-to-total mass fractions than centrals by up to a factor of a few. The systematic deviation from the central SHMR is larger for satellites in more massive hosts, at smaller cluster-centric distances, with earlier infall times, and that inhabit higher local density environments; moreover, it is in place already at early times (z < 2). Systematic environmental effects might contribute to the perceived galaxy-to-galaxy variation in the measured SHMR when galaxies cannot be separated into satellites and centrals. The SHMR of satellites exhibits a larger scatter than centrals, over the whole range of dynamical mass (by up to 0.8 dex). The shift of the satellite SHMR results mostly from tidal stripping of their dark matter, which affects satellites in an outside-in fashion: the departure of the satellite SHMR from the centrals' relation diminishes for measurements of dynamical mass in progressively smaller apertures. Finally, we provide a family of fitting functions for the SHMR predicted by IllustrisTNG.Comment: Published in MNRAS. Key figures: 1 &

Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (ORhom = 2.08, 95% CI 1.05-4.11, p = 0.035). This SNP is in linkage disequilibrium with another polymorphic variant associated with increased risk of several cancer types. In silico analysis suggested that the SNP could alter the sequence recognized by the Neuron-Restrictive Silencer Factor (NRSF), whose deregulation has been associated with the development of several tumors. The mechanistic link between the allele and the disease has not been completely clarified yet but the epidemiologic evidences that link the DNA region to increased cancer risk are convincing. In conclusion, our results suggest rs2518719 as a pleiotropic CDKN2A variant associated with the risk of developing PNETs