Gamma-Rays from Dark Matter Mini-Spikes in M31

The existence of a population of wandering Intermediate Mass Black Holes (IMBHs) is a generic prediction of scenarios that seek to explain the formation of Supermassive Black Holes in terms of growth from massive seeds. The growth of IMBHs may lead to the formation of DM overdensities called "mini-spikes", recently proposed as ideal targets for indirect DM searches. Current ground-based gamma-ray experiments, however, cannot search for these objects due to their limited field of view, and it might be challenging to discriminate mini-spikes in the Milky Way from the many astrophysical sources that GLAST is expected to observe. We show here that gamma-ray experiments can effectively search for IMBHs in the nearby Andromeda galaxy (also known as M31), where mini-spikes would appear as a distribution of point-sources, isotropically distributed in a \thickapprox 3^{\circ} circle around the galactic center. For a neutralino-like DM candidate with a mass m_{\chi}=150 GeV, up to 20 sources would be detected with GLAST (at 5\sigma, in 2 months). With Air Cherenkov Telescopes such as MAGIC and VERITAS, up to 10 sources might be detected, provided that the mass of neutralino is in the TeV range or above.Comment: 9 pages, 5 figure

Unsupervised Continual Learning From Synthetic Data Generated with Agent-Based Modeling and Simulation: A preliminary experimentation

Continual Learning enables to learn a variable number of tasks sequentially without forgetting knowledge obtained from the past. Catastrophic forgetting usually occurs in neural networks for their inability to learn different tasks in sequence since the performance on the previous tasks drops down in a significant way. One way to solve this problem is providing a subset of the previous examples to the model while learning a new task. In this paper we evaluate the continual learning performance of an unsupervised model for anomaly detection by generating synthetic data using an Agent-based modeling and simulation technique. We simulated the movement of different types of individuals in a building and evaluate their trajectories depending on their role. We collected training and test sets based on their trajectories. We included, in the test set, negative examples that contain wrong trajectories. We applied a replay-based continual learning to teach the model how to distinguish anomaly trajectories depending on the users’ roles. The results show that using ABMS synthetic data it is enough a small percentage of synthetic data replay to mitigate the Catastrophic Forgetting and to achieve a satisfactory accuracy on the final binary classification (anomalous / non-anomalous)

High-Performance Computing and ABMS for High-Resolution COVID-19 Spreading Simulation

This paper presents an approach for the modeling and the simulation of the spreading of COVID-19 based on agent-based modeling and simulation (ABMS). Our goal is not only to support large-scale simulations but also to increase the simulation resolution. Moreover, we do not assume an underlying network of contacts, and the person-to-person contacts responsible for the spreading are modeled as a function of the geographical distance among the individuals. In particular, we defined a commuting mechanism combining radiation-based and gravity-based models and we exploited the commuting properties at different resolution levels (municipalities and provinces). Finally, we exploited the high-performance computing (HPC) facilities to simulate millions of concurrent agents, each mapping the individual’s behavior. To do such simulations, we developed a spreading simulator and validated it through the simulation of the spreading in two of the most populated Italian regions: Lombardy and Emilia-Romagna. Our main achievement consists of the effective modeling of 10 million of concurrent agents, each one mapping an individual behavior with a high-resolution in terms of social contacts, mobility and contribution to the virus spreading. Moreover, we analyzed the forecasting ability of our framework to predict the number of infections being initialized with only a few days of real data. We validated our model with the statistical data coming from the serological analysis conducted in Lombardy, and our model makes a smaller error than other state of the art models with a final root mean squared error equal to 56,009 simulating the entire first pandemic wave in spring 2020. On the other hand, for the Emilia-Romagna region, we simulated the second pandemic wave during autumn 2020, and we reached a final RMSE equal to 10,730.11

A prospective evaluation on external jugular vein cut-down approach for TIVAD implantation

BACKGROUND: Totally implantable venous access devices can be implanted both by percutaneous approaches and by surgical approaches with cephalic vein or external jugular vein cut-down techniques that are related to low intraoperative complication rates. The authors report a prospective evaluation of 83 consecutive external jugular vein cut-down approaches for totally implantable venous access devices implantation. METHODS: Eighty three consecutive patients (28 M, 55 F, mean age 54.2) suffering from solid tumors (58) or hematologic diseases (25) were consecutively submitted to totally implantable venous access devices insertion through external jugular vein cut-down approach (75 on right side, 8 on left side). RESULTS: All devices were surgically implanted; no instances of intraoperative complications were detected. After a minimum follow-up of 150 days, only one case of wound hematoma and one case of device malfunction due to incorrect catheter angulation were noted. Postoperative patient satisfaction was evaluated by the use of specific questionnaire that demonstrated a good satisfaction and compliance (92.8 %) of patients with implanted devices. CONCLUSIONS: Despite the lack of controlled studies comparing external jugular vein cut-down approach vs other approaches, this approach should be considered as a tool for long-term central vein catheters positioning, both as an alternative and for primary approach

Steel based retrofitting interventions for existing masonry walls: a comparative numerical investigation

Masonry buildings constitute a significant portion of the architectural heritage all over the world, also in regions affected by a high seismic hazard. Since this constructional material is characterized by lack of tensile strength, as well as small deformation capacity, masonry structures could result hugely damaged if shaken by seismic forces. In order to avoid collapses and reduce structural damage, innovative retrofitting interventions are necessary to improve the seismic behavior of masonry structures. In this context, steel-based techniques could be considered among the most suitable solutions. In fact, by using such a high-performant material, additional strength and ductility may be conferred to existing masonry structures. Based on these premises, the present paper focuses on a numerical investigation of two different retrofitting techniques: the CAM© system and the application of steel grids on both faces of a masonry wall. In particular, on the base of an experimental test carried out within the research project In.CAM.M.I.N.O. on an unreinforced masonry wall tested in condition of constant vertical force and horizontal loads, a reference FE Model has been calibrated in Abaqus by using a macro-modelling approach with a damage-plasticity material model for the masonry. Then, based on the reference model, the efficiency of the two systems has been investigated and compared by means of numerical analyses, in order to evaluate the strength and ductility increases obtainable by the application of the two retrofitting techniques

SCD5 restored expression favors differentiation and epithelial-mesenchymal reversion in advanced melanoma

Our previous data supported a role for the Stearoyl-CoA desaturase (SCD5) in protection against malignancy, whereby it appears to functionally modify tumor stroma impairing tumor spread. SCD5 is significantly expressed in primary melanoma, but becomes barely detectable at tumor advanced stages. Looking for the regulatory mechanisms underlying SCD5 reduced expression during melanoma progression, we demonstrated a significantly lower stability of SCD5 protein as well as the direct targeting of SCD5 mRNA by the oncogenic miR-221 & 222 in metastatic cell lines. Moreover, our results indicated the existence of a negative feedback loop between SCD5 and miR-221 & 222, in good agreement with their opposite functions. Also, we showed how SCD5 re-expression and the direct supplementation of its main product oleic acid (OA) can drive advanced melanoma cell lines toward differentiation and reversion of the epithelial-mesenchymal (EMT)-like process, eventually inducing a less malignant phenotype. Indeed, SCD5 re-established the sensitivity to all-trans retinoic acid in A375M metastatic melanoma, associated with increased levels of Tyrosinase, melanin production and reduced proliferation. As evidenced by the correct modulation of some key transcription factors, SCD5 managed by favoring a partial mesenchymal-to-epithelial (MET) transition in in vitro studies. Interestingly, a more complete MET, including E-cadherin re-expression correctly localized at cell membranes, was obtained in in vivo xenograft models, thus indicating the requirement of direct contacts between tumor cells and the surrounding microenvironment as well as the presence of some essential factors for SCD5 complete function

Gut mesenchymal stromal cells in immunity

Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal). In Crohn’s disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC). The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFN) is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn’s disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer

HDAC inhibition is associated to valproic acid induction of early megakaryocytic markers

Valproic acid (VPA), a histone deacetylase inhibitor, causes differentiation in different cell lines and in a cell-specific manner; yet, its effect on megakaryocytic (MK) differentiation has not been studied. We evaluated whether VPA induces MK differentiation in a UT-7 cell line through histone acetylation in the GpIIIa gene region and activation of the ERK pathway. UT-7 cells, derived from megakaryoblastic leukemia, were treated with VPA at various concentrations, and the expression of differentiation markers as well as the gene expression profile was assessed. Flow cytometry, immunoblot analysis, and RT-PCR demonstrated that VPA induced the expression of the early MK markers GpIIIa (CD61) and GpIIb/IIIa (CD41) in a dose-dependent manner. The VPA-treated cells showed hyperacetylation of the histones H3 and H4; in particular, histone acetylation was found to have been associated with CD61 expression, in that the GpIIIa promoter showed H4 hyperacetylation, as demonstrated by the chromatin immunoprecipitation assay. Furthermore, activation of the ERK pathway was involved in VPA-mediated CD61/CD41 expression and in cell adhesion, as demonstrated by using the MEK/ERK inhibitor U0126. In conclusion, the capacity of VPA to commit UT-7 cells to MK differentiation is mediated by its inhibitory action on HDAC and the long-lived activation of ERK1/2