Effects of Methyl Cycle Substrate Availability on Epigenetic Stability of Human Embryonic Stem Cells

A link has been hypothesised to occur between suboptimal maternal nutrition and impaired foetal development leading to a predisposition to a range of adult pathologies. As a clear connection between dietary intake of methyl group donors and epigenetic defects has been demonstrated both *in vivo* and *in vitro*, this project had the purpose of generating a disruption into the methyl/folate cycle to investigate DNA methylation alterations during human preimplantation embryo development, using human embryonic stem cells (hESCs) as an in vitro model. In particular, HUES-7 stem cells were employed and cultured using either standard or methyl deficient media to test this hypothesis. After the treatments, that included an inhibitor of a key enzyme of the cycle, Differentially Methylated Regions (DMRs) of six imprinted genes were analysed and assessed for their methylation status at Cytosine-phospho-Guanosine (CpG) sites. As a consistent decrease of methylation was observed for the gene *H19* in treated cultures, its allelic expression was then investigated and an initial process of Loss Of Imprinting (LOI) was found. Additionally, global DNA MethylTransferase (DNMT) activity was examined and a statistically significant decrease in treated samples was detected. Finally, hESCs were differentiated into Embryoid Bodies(hEBs), which were compared and stained for pluripotency and germ-layer specific markers. Consistently different expression of *OCT-4* and *NANOG* was noticed for treated-culture derived hEBs

Near-BPS baby Skyrmions with Gaussian tails

We consider the baby Skyrme model in a physically motivated limit of reaching the restricted or BPS baby Skyrme model, which is a model that enjoys area-preserving diffeomorphism invariance. The perturbation consists of the kinetic Dirichlet term with a small coefficient $\epsilon$ as well as the standard pion mass term, with coefficient $\epsilon m_1^2$. The pions remain lighter than the soliton for any $\epsilon$ and therefore the model is physically acceptable, even in the $\epsilon \to 0$ limit. The version of the BPS baby Skyrme model we use has BPS solutions with Gaussian tails. We perform full numerical computations in the $\epsilon\to 0$ limit and even reach the strict $\epsilon=0$ case, finding new nontrivial BPS solutions, for which we do not yet know the analytic form.Comment: LaTeX: 53 pages, 23 figure

First-order correction to counter the effect of eccentricity on the hole-drilling integral method with strain-gage rosettes:

The offset between the hole and the centre of the strain-gage rosette is unavoidable, although usually small, in the hole-drilling technique for residual stress evaluation. In this article, we revi..

Effetti sulla ripartizione dei carichi dovute alla configurazione dei satelliti in rotismi planetari

La conoscenza della ripartizione dei carichi sulle dentature è di cruciale importanza per la progettazione di rotismi planetari, in quanto permette di evitare che la trasmissione operi in condizioni non conformi alle specifiche, in cui possano avvenire rotture catastrofiche. La ripartizione del carico dipende sia dai parametri funzionali del rotismo (quali gioco dei cuscinetti, backlash, rigidezze dei componenti) sia dal numero di satelliti impiegati. Il presente lavoro mira ad investigare come il numero di satelliti possa influenzare la ripartizione dei carichi applicati a una trasmissione tipicamente impiegata in campo eolico e come questi effetti vengano amplificati oppure attenuati dalla variazione di parametri funzionali (quali il gioco dei cuscinetti, le rigidezze dei supporti e dell’ingranamento, ed il backlash) e dagli errori di montaggio. Lo studio è stato condotto impiegando un modello a parametri concentrati interamente parametrico che permette di identificare condizioni di malfunzionamento quali perdita di contatto e/o incuneamento oltre al carico agente su ciascun ingranamento in funzione dell’insieme dei suddetti parametri. Mappe di ripartizione del carico vengono proposte per rotismi aventi da tre a cinque satelliti.The knowledge of the distribution of loads on the teeth is of crucial importance for the design of planetary gearboxes, since it allows to avoid that the transmission operates in conditions that do not comply with the specifications, in which a catastrophic failure can take place. The load distribution depends both on the functional parameters of the gearing (such as bearing play, backlash, stiffness component) and on the number of planets. This paper aims to investigate how the number of planets will affect the distribution of loads applied to a transmission typically used in wind farms and how these effects are amplified or attenuated by the variation of operating parameters (such as bearing clearance, supports and tooth stiffness, and backlash) and the assembly errors. The study was conducted employing a lumped parameter model parametric spaces that allows to identify fault conditions such as loss of contact and/or wedging in addition to the load acting on each meshing on the basis of all of those parameters. Maps load distribution are proposed for gears having from three to five planets

Luces en una crisis global

El segundo semestre de 2008 fue especialmente difícil, en donde destacaron diversos puntos que se recogen en este número de Análisis Plural, como: los secuestros y el “ya basta”; los efectos de la crisis en México; el narcotráfico, terrorismo y corrupción; la “inacabada” reforma energética; el “avionazo” de Mouriño; la crisis en el Partido de la Revolución Democrática; el estallido bursátil estadounidense, de resonancia mundial, y los problemas energéticos agudizados por la globalización

Myocardial perfusion in chronic diabetic mice by the up-regulation of pLKB1 and AMPK signaling

Previous studies related impaired myocardial microcirculation in diabetes to oxidative stress and endothelial dysfunction. Thus, this study was aimed to determine the effect of up-regulating pAMPK-pAKT signaling on coronary microvascular reactivity in the isolated heart of diabetic mice. We measured coronary resistance in wild-type and streptozotocin (STZ)-treated mice, during perfusion pressure changes. Glucose, insulin, and adiponectin levels in plasma and superoxide formation, NOx levels and heme oxygenase (HO) activity in myocardial tissue were determined. In addition, the expression of HO-1, 3-nitrotyrosine, pLKB1, pAMPK, pAKT, and peNOS proteins in control and diabetic hearts were measured. Coronary response to changes in perfusion pressure diverged from control in a time-dependent manner following STZ administration. The responses observed at 28 weeks of diabetes (the maximum time examined) were mimicked by L-NAME administration to control animals and were associated with a decrease in serum adiponectin and myocardial pLKB1, pAMPK, pAKT, and pGSK-3 expression. Cobalt protoporphyrin treatment to induce HO-1 expression reversed the microvascular reactivity seen in diabetes towards that of controls. Up-regulation of HO-1 was associated with an increase in adiponectin, pLKB1, pAKT, pAMPK, pGSK-3, and peNOS levels and a decrease in myocardial superoxide and 3-nitrotyrosine levels. In the present study we describe the time course of microvascular functional changes during the development of diabetes and the existence of a unique relationship between the levels of serum adiponectin, pLKB1, pAKT, and pAMPK activation in diabetic hearts. The restoration of microvascular function suggests a new therapeutic approach to even advanced cardiac microvascular derangement in diabetes

Estimation of the susceptibility of a road network to shallow landslides with the integration of the sediment connectivity

Abstract. Landslides cause severe damage to the road network of the hit zone, in terms of both direct (partial or complete destruction of a road or blockages) and indirect (traffic restriction or the cut-off of a certain area) costs. Thus, the identification of the parts of the road network that are more susceptible to landslides is fundamental to reduce the risk to the population potentially exposed and the financial expense caused by the damage. For these reasons, this paper aimed to develop and test a data-driven model for the identification of road sectors that are susceptible to being hit by shallow landslides triggered in slopes upstream from the infrastructure. This model was based on the Generalized Additive Method, where the function relating predictors and response variable is an empirically fitted smooth function that allows fitting the data in the more likely functional form, considering also non-linear relations. This work also analyzed the importance, on the estimation of the susceptibility, of considering or not the sediment connectivity, which influences the path and the travel distance of the materials mobilized by a slope failure until hitting a potential barrier such as a road. The study was carried out in a catchment of northeastern Oltrepò Pavese (northern Italy), where several shallow landslides affected roads in the last 8 years. The most significant explanatory variables were selected by a random partition of the available dataset in two parts (training and test subsets), 100 times according to a bootstrap procedure. These variables (selected 80 times by the bootstrap procedure) were used to build the final susceptibility model, the accuracy of which was estimated through a 100-fold repetition of the holdout method for regression, based on the training and test sets created through the 100 bootstrap model selection. The presented methodology allows the identification, in a robust and reliable way, of the most susceptible road sectors that could be hit by sediments delivered by landslides. The best predictive capability was obtained using a model in which the index of connectivity was also calculated according to a linear relationship, was considered. Most susceptible road traits resulted to be located below steep slopes with a limited height (lower than 50 m), where sediment connectivity is high. Different land use scenarios were considered in order to estimate possible changes in road susceptibility. Land use classes of the study area were characterized by similar connectivity features. As a consequence, variations on the susceptibility of the road network according to different scenarios of distribution of land cover were limited. The results of this research demonstrate the ability of the developed methodology in the assessment of susceptible roads. This could give the managers of infrastructure information about the criticality of the different road traits, thereby allowing attention and economic budgets to be shifted towards the most critical assets, where structural and non-structural mitigation measures could be implemented

Rapporto tecnico sulle attività di campionamento della “Campagna Oceanografica CISAS_2” Crotone 07-12 dicembre 2017

Le attività di campionamento ed acquisizione dati svolte durante la campagna CISAS_2 si inseriscono in seno al progetto “Centro internazionale di studi avanzati su ambiente ed impatti su ecosistema e salute umana (CISAS)” del CNR. L’obiettivo principale del progetto CISAS è la comprensione dei processi e dei meccanismi di trasferimento di alcuni contaminanti convenzionali (metalli pesanti, POPs, radionuclidi, ecc.) e di alcuni contaminanti emergenti (PDBE, composti farmaceutici di nuova generazione, ecc.) dall’ambiente inteso come l’insieme di atmosfera-suoli-acque sotterranee-matrici marine (acque e sedimento) all’ecosistema e all’uomo. Le aree di indagine del progetto sono i Siti di Interesse Nazionale (SIN) di Priolo, Milazzo-Pace del Mela e Crotone che, per specificità e modalità di impatto antropogenico sull’ambiente, l’ecosistema e la salute umana, coprono un ampio spettro di tipologie di interesse. La campagna oceanografica CISAS_ 2 è stata dedicata alla caratterizzazione ambientale del SIN di Crotone, nonché all’identificazione delle sorgenti dei contaminanti la cui distribuzione si ritiene di interesse (per i valori di concentrazione riscontrati nelle diverse matrici ambientali e per livello di tossicità associata agli effetti degli stessi sulla salute dell’ecosistema e dell’uomo) e i pathways di deposizione nelle aree di interesse

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies.publishedVersio

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies