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Hard X-/soft Gamma-ray astronomy is a key field for the study of important astrophysical phenomena such as the electromagnetic counterparts of gravitational waves, gamma-ray bursts, black holes physics and many more. However, the spatial localization, imaging capabilities and sensitivity of the measurements are strongly limited for the energy range $>$70 keV due to the lack of focusing instruments operating in this energy band. A new generation of instruments suitable to focus hard X-/ soft Gamma-rays is necessary to shed light on the nature of astrophysical phenomena which are still unclear due to the limitations of current direct-viewing telescopes. Laue lenses can be the answer to those needs. A Laue lens is an optical device consisting of a large number of properly oriented crystals which are capable, through Laue diffraction, of concentrating the radiation into the common Laue lens focus. In contrast with the grazing incidence telescopes commonly used for softer X-rays, the transmission configuration of the Laue lenses allows us to obtain a significant sensitive area even at energies of hundreds of keV. At the University of Ferrara we are actively working on the modelization and construction of a broad-band Laue lens. In this work we will present the main concepts behind Laue lenses and the latest technological developments of the TRILL (Technological Readiness Increase for Laue Lenses) project, devoted to the advancement of the technological readiness of Laue lenses by developing the first prototype of a lens sector made of cylindrical bent crystals of Germanium., 13 pages, 9 figures, sixteenth Marcel Grossmann Meeting - Conference Proceedings

Gamma-ray astronomy is a branch whose potential has not yet been fully exploited. The observations of elemental and isotopic abundances in supernova (SN) explosions are key probes not only of the stellar structure and evolution but also for understanding the physics that makes Type-Ia SNe as standard candles for the study of the Universe expansion properties. In spite of its crucial role, nuclear astrophysics remains a poorly explored field mainly for the typical emission lines intensity which are vanishing small and requires very high sensitivities of the telescopes. Furthermore, in spite that the Galactic bulge-dominated intensity of positron annihilation line at 511 keV has been measured, its origin is still a mystery due to the poor angular resolution and insufficient sensitivity of the commonly employed instrumentation in the sub-MeV energy domain. To answer these scientific issues a jump in sensitivity and angular resolution with respect to the present instrumentation is required. Conceived within the EU project AHEAD, a new high energy mission, capable of tackling the previously mentioned topics, has been proposed. This concept of mission named ASTENA (Advanced Surveyor of Transient Events and Nuclear Astrophysics), includes two instruments: a Wide Field Monitor with Imaging and Spectroscopic (WFM-IS, 2 keV - 20 MeV) capabilities and a Narrow Field Telescope (NFT, 50 - 700 keV). Thanks to the combination of angular resolution, sensitivity and large FoV, ASTENA will be a breakthrough in the hard X and soft gamma--ray energy band, also enabling polarimetry in this energy band. In this talk the science goals of the mission are discussed, the payload configuration is described and expected performances in observing key targets are shown., Comment: 17 pages, 7 figures, sixteenth Marcel Grossmann Meeting - Conference Proceedings

This paper presents a new MRAS speed observer for high performance FOC induction motor drives which employs the flux error for estimating the rotor speed, but overcomes the pure integration problems by using a novel adaptive integration method based on neural adaptive filtering. A linear neuron (the ADALINE) is employed for the estimation of both the rotor speed and the rotor flux-linkage using a recursive TLS (Total Least Squares) algorithm (the TLS EXIN neuron) for on-line training. This neural model is also used as a predictor with no feedback loops between the output of the neural network and its input. The proposed scheme has been implemented in a test setup and compared with an MRAS OLS (Ordinary Least Squares) speed estimation with low-pass filter integration and with the well- known Schauder's scheme. The experimental results show the in the high and medium speed ranges with and without load, the three algorithms give practically the same results, while in low speed ranges (i.e. below 10 rad/s ) the TLS based algorithm outperforms the other two algorithms. Experiments have also been made to test the robustness of the algorithm to load perturbations and to test its performance at zero speed operation.

The plasminogen activator system is known to play a crucial role in the angiogenesis process by modulating the adhesive properties of endothelial cells to the extracellular matrix and cell-cell interaction. In the present study, we demonstrated that the urokinase-type plasminogen activator (u-PA) induced neovascular growth in the avascular rabbit cornea and dose-dependently promoted growth, chemotaxis, and matrix invasion of cultured endothelial cells. Interaction between u-PA and its receptor appears to be mandatory for the angiogenic effect of u-PA because monoclonal antibodies anti-u-PA and anti-u-PA receptor (u-PAR) blocked the proangiogenic effects of u-PA at the endothelial cell level. We then assessed the signaling pathway activated in endothelial cells by u-PA. u-PAR activation by u-PA produced de novo synthesis of diacylglycerol (DAG) from glucose by a cytochalasin B-inhibitable mechanism, indicating the involvement of a specific glucose transporter (GLUT). Endothelial cells expressed GLUT2, whose activation was tyrosine kinase-dependent and protein kinase C (PKC)-independent. The increase of glucose uptake led to DAG production, which resulted in PKC activation/translocation. Impairment of u-PAR availability by monoclonal antibodies and by antisense oligonucleotides (aODN) against u-PAR mRNA inhibited glucose uptake, DAG neosynthesis, and PKC activation, resulting in the blockade of endothelial cell proliferation, chemotaxis, and chemoinvasion. These data suggest that u-PAR activation consequent to the binding of u-PA can be regarded as an "angiogenic switch" and disclose the possibility that an anti-u-PAR aODN strategy may efficiently target endothelial cell function to control angiogenesis in vivo.

On the basis of both 125I-labelled urokinase-like plasminogen activator binding analysis and transmission electron microscopy of an urokinase-gold complex, we have shown the presence of specific receptors for human urokinase on the cell membrane of human synovial cells. By radio-ligand binding experiments we have shown the existence of similar receptors on the surface of human chondrocytes. In both cases the specific binding is attributable to interaction between the receptor and the A chain of the ligand, as previously shown in other cell model systems. Treatment of synoviocytes with 1,8-diacetoxy-anthraquinone-3-carboxylic acid (diacetylrhein) is able to reduce the number of surface urokinase receptors. At the same time the drug can reduce the fibrinolytic activity released into the culture medium of human synovial cells. Preliminary data indicate that chondrocytes from osteoarthritic patients have a larger number of urokinase receptors than chondrocytes of normal patients. Diacetylrhein can restore the receptor number to normal levels; the amount of urokinase in the synovial fluid of ostroarthritic patients is also reduced. We conclude that the use of this drug has the chance to significantly modify the natural history of osteoarthritis.

Cannabinoids have been shown to have a beneficial effect in both animal models of multiple sclerosis (MS) and human disease, although the mechanisms of action are unclear. We examined expression of the major cannabinoid receptors [(CBRs) cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2)] and a key enzyme involved in synthesis of the endocannabinoid anandamide [N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] in autopsy brain samples from patients with MS. CB1 was expressed in neurons, injured axons, oligodendrocytes, macrophages/microglia, some astrocytes, endothelial cells, smooth muscle cells and pericytes. CB2 and NAPE-PLD were localized to cerebral endothelial cells, pericytes, smooth muscle cells, astrocytes and macrophages/microglia. NAPE-PLD immunoreactivity was also seen in neurons. Endothelial CB2 expression was greatest in chronic inactive plaques, and in areas was seen in segments of endothelium where the endothelial expression of adhesion molecules (VCAM-1 and ICAM-1) was focally undetectable, and was often expressed in areas of blood-brain barrier damage. Vascular density was increased in chronic active plaques and normal-appearing white matter compared with controls. These data support findings from animal models which suggest a role for the endocannabinoid system in the MS, particularly in the regulation of endothelial leukocyte adhesion and the cellular response to injury.

Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds.

This article proposes an adaptive input-output Feedback Linearization Control ( FLC ) techniques for Synchronous Reluctance Motor ( SynRM ) drives, taking into consideration the iron losses. As a main original content, this work proposes a control law based on a new dynamic model of the SynRM including iron losses as well as the on-line estimation of the static inductances. The on-line estimation of the SynRM static inductances permits to inherently take into consideration the magnetic saturation phenomena occuring on both axes. As a major result, it permits a null stator current steady state tracking error even with a proportional derivative controller. The estimation law is obtained thanks to a Lyapunov-based analysis and thus the stability of the entire control system, including the estimation algorithm, is intrinsically guaranteed. The proposed adaptive FLC technique, has been tested experimentally on a suitably developed test set-up, and compared experimentally with its non-adaptive versions in both tuned and detuned working conditions. Moreover, a sensitivity analysis of the performance of the adaptive FLC to the variations of the stator resistance at low speed has been made. Finally, an analysis of the effects of the iron losses on the control performance and stability at high speed in the field weakening region at medium/high loads has been made.

This study proposes a state formulation of the space-vector dynamic model of the Synchronous Reluctance Motor (SynRM) considering both saturation and cross-saturation effects. The proposed model adopts the stator currents as state variables and has been theoretically developed in both the rotor and stator reference frames. The proposed magnetic model is based on a flux versus current approach and relies on the knowledge of 11 parameters. Starting from the definition of a suitable co-energy variation function, new flux versus current functions have been initially developed, based on the hyperbolic functions and, consequently, the static and dynamic inductance versus current functions have been deduced. The dynamic inductance functions have been derived so to fulfill the reciprocity conditions. This study presents also a technique for the estimation of the parameters of the proposed magnetic model, which is based on stand-still tests without the need to lock the rotor. The identification process has been performed based on the minimization of a suitably defined error function including the difference between the measured and estimated stator fluxes. The proposed parameter estimation technique has been tested in both numerical simulation and experimentally on a suitably developed test set-up, permitting the experimental validation of the proposed model.

Bidirectional DC/DC converters such as the Split-pi can be used to integrate an energy storage system (ESS) into a DC microgrid providing manifold benefits. However, this integration deserves careful design because the ESS converter must behave like a stiff voltage generator, a non-stiff voltage generator, or a current generator depending on the microgrid configuration. Part I of this work presented a comprehensive theoretical analysis of the Split-pi used as an ESS converter in all the possible DC microgrid scenarios. Five typical microgrid scenarios were identified. Each of them required a specific state-space model of the Split-pi and a suitable control scheme. The present paper completes the study validating the theoretical analysis based on simulations and experimental tests. The chosen case study encompassed a 48 V, 750 W storage system interfaced with a 180 V DC microgrid using a Split-pi converter. It can represent a reduced-power prototype of terrestrial and marine microgrids. A prototypal Split-pi converter was realized in the lab, and several experimental tests were performed to assess the performance in each scenario. The results obtained from the experimental tests were coherent with the simulations and validated the study.

Prostate cancer (PCa) is the most common cancer in men. Nowadays, it is diagnosed through the test of serum prostate-specific antigen (PSA) and rectal examination; however, there is still debate about the PSA-based diagnosis. Seminal fluid (SF), contains a high concentration of subcellular lipid-bound microparticles, traditionally termed "prostasomes", that are extracellular vesicles (EVs) released into the extracellular space by prostate gland's epithelial cells. These vesicles, first described in 1982 promote motility of sperm cells, regulation of sperm cell capacitation, acrosome reaction and immune suppression within the female reproductive tract. It was demonstrated that prostasomes could contain PCa specific molecular fingerprints that can represent the status of their parental cells. Until now the analysis of isolated prostasomes released by PCa cells has proved several advantages compared to the analysis of parental cells. Moreover, the molecular composition of prostasomes could reflect their capacity to influence PCa growth and metastasis. In this review, we discuss the role of prostasomes in PCa, focusing in the possibility of exosomes to represent a non-invasive test for PCa diagnosis and as a possible agent for enhance the sexual transmission diseases (STD) through immunomodulation.

This paper proposes a nonlinear controller based on feedback linearization for Synchronous Reluctance Motors (SynRM) drives that takes into consideration the self and cross-saturation effects. Such control technique permits the dynamics of both the speed and flux loops to be maintained constant independently from the load and the saturation of the iron core. The proposed technique has been tested experimentally on a suitably developed test set-up.

To evaluate the change over time of vision-related quality of life (QoL) and glaucoma symptoms in a population of newly-diagnosed primary open angle glaucoma (POAG) patients. Multicenter, prospective study. Consecutive newly-diagnosed POAG patients were enrolled and followed-up for one year. Follow-up visits were scheduled at 6 and 12 months from baseline. At each visit, vision-related QoL and glaucoma-related symptoms were assessed by the means of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the Glaucoma Symptom Scale (GSS), respectively. Trends over time for NEI-VFQ-25 and GSS scores were evaluated with longitudinal linear mixed models. One-hundred seventy-eight patients were included in the analysis. At baseline, early to moderate glaucoma stages were associated with higher scores for most GSS and NEI-VFQ-25 items, while lower best-corrected visual acuity was associated with lower scores for 4 of the 12 NEI-VFQ-25 items. During the follow-up, all the GSS scores, the NEI-VFQ-25 total score, and 7 of the 12 NEI-VFQ-25 scores significantly improved (p

Glycosylation consists in the covalent, enzyme mediated, attachment of sugar chains to proteins and lipids. A large proportion of membrane and secreted proteins are indeed glycoproteins, while glycolipids are fundamental component of cell membranes. The biosynthesis of sugar chains is mediated by glycosyltransferases, whose level of expression represents a major factor of regulation of the glycosylation process. In cancer, glycosylation undergoes profound changes, which often contribute to invasion and metastasis. Epithelial to mesenchymal transition (EMT) is a key step in metastasis formation and is intimately associated with glycosylation changes. Numerous carbohydrate structures undergo up- or down-regulation during EMT and often regulate the process. In this review, we will discuss the relationship with EMT of the N-glycans, of the different types of O-glycans, including the classical mucin-type, O-GlcNAc, O-linked fucose, O-linked mannose and of glycolipids. Finally, we will discuss the role in EMT of galectins, a major class of mammalian galactoside-binding lectins. While the expression of specific carbohydrate structures can be used as a marker of EMT and of the propensity to migrate, the manipulation of the glycosylation machinery offers new perspectives for cancer treatment through inhibition of EMT.

This paper proposes an input-output feedback linearization techniques for linear induction motors, taking into consideration the dynamic end-effects. As a main original content, this work proposes a new control law based on the on-line estimation of the induced-part time constant. The estimation law is obtained thanks to a Lyapunov based analysis and thus the stability of the entire control system, including the estimation algorithm, is intrinsically guaranteed. Moreover, with such an approach even the on-lihe variation of the induced-part time constant with the speed is retrieved, thus improving the behavior of previously developed approaches where such a variation vs. speed is considered a priori known. The proposed control technique, integrating the on-line induced-part time constant estimation, is tested by means of simulations and experiments carried out on a suitably developed test set-up. (C) 2016 Elsevier Ltd. All rights reserved.

Background: The Sda antigen and its biosynthetic enzyme B4GALNT2 are highly expressed in healthy colon but undergo a variable down-regulation in colon cancer. The biosynthesis of the malignancy-associated sialyl Lewis x (sLex) antigen in normal and cancerous colon is mediated by fucosyltransferase 6 (FUT6) and is mutually exclusive from that of Sda. It is thought that the reduced malignancy associated with high B4GALNT2 was due to sLex inhibition. Methods: We transfected the cell lines SW480 and SW620, derived respectively from a primary tumor and a metastasis of the same patient, with the cDNAs of FUT6 or B4GALNT2, generating cell variants expressing either the sLex or the Sda antigens. Transfectants were analyzed for growth in poor adherence, wound healing, stemness and gene expression profile. Results: B4GALNT2/Sda expression down-regulated all malignancy-associated phenotypes in SW620 but only those associated with stemness in SW480. FUT6/sLex enhanced some malignancy-associated phenotypes in SW620, but had little effect in SW480. The impact on the transcriptome was stronger for FUT6 than for B4GALNT2 and only partially overlapping between SW480 and SW620. Conclusions: B4GALNT2/Sda inhibits the stemness-associated malignant phenotype, independently of sLex inhibition. The impact of glycosyltransferases on the phenotype and the transcriptome is highly cell-line specific.

This paper proposes a space-vector dynamic model of the Synchronous Reluctance Motor (SynRM) including both self-saturation and cross-saturation effects and selecting as state variables the stator currents. The proposed dynamic model is based on an original function between the stator flux and stator current components, and relies on 8 coefficients (fewer than other models in the scientific literature), presenting an interesting physical interpretation. Starting from this approach, both the static and dynamic inductances expressions of the model have been analytically developed, so that the reciprocity conditions for the cross saturation is satisfied. This paper presents also a technique for the estimation of the parameters of the inductances expressions, which is based on stand-still tests without the need of locking the rotor. This technique is based on the minimization of a suitably defined error function which includes the difference between the measured and estimated currents The proposed parameter estimation technique has been tested in both numerical simulation and experimentally on a suitably developed test set-up.

Purpose: The purpose of this article was to evaluate the potential association between sociodemographic factors with clinical characteristics, vision-related quality of life (QoL), and glaucoma-related symptoms scores in a large cohort of primary open-angle glaucoma patients. Materials and Methods: Multicenter, cross-sectional study involving academic and nonacademic centers. Previously diagnosed primary open-angle glaucoma patients aged >18 years were enrolled. At baseline, information on demographic characteristics, social, medical and ocular history, clinical presentation and treatments was collected. Vision-related QoL was evaluated by means of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), while glaucoma-related symptoms were evaluated using the Glaucoma Symptom Scale (GSS) questionnaire. The associations between sociodemographic factors with clinical characteristics (mean deviation, pattern standard deviation, best-corrected visual acuity), NEI-VFQ-25, and GSS scores were evaluated by means of univariate and multivariate general linear models. Results: A total of 3227 patients were enrolled. Older age and male sex were significantly associated with lower mean deviation (P

This paper proposes a sensorless technique for an induction machine Flywheel Energy Storage System (FESS) based on a non-linear observer integrated with a total least-squares speed estimator taking into consideration the IM (Induction Machine) saturation effects. The nonlinear observer is based on an original formulation of the dynamic model of the IM including the magnetic saturation, rearranged in a space-state form, after assuming as state variables the stator current and the rotor magnetizing current space-vectors in the stator reference frame. The choice of the observer gain has been made by the use of Lyapunov's method. The speed signal needed by the non-linear observer for the flux estimation is provided by the Total Least Square (TLS) based speed estimator, which itself takes into consideration the magnetic saturation for the speed estimation. The proposed nonlinear observer has been tested in numerical simulation and verified experimentally on a suitably developed test set-up, demonstrating its applicability as far as FESS is concerned.

Here we show the increase of invasion of three breast cancer cell lines (8701-BC, MDA-MB-231 and SKBR3) upon long-term co-incubation with culture medium of normal microvascular endothelial cells (MVEC) and normal breast epithelial cells (HB2). The enhancement of invasion relied on the interaction of microvascular endothelial cell and normal breast epithelial cell CXCL12 (SDF1) chemokine, whose expression by breast cancer cells was very low, with the cognate CXCR4 receptor of malignant cells, which resulted in over-expression of the urokinase-type plasminogen activator receptor (uPAR) on their surfaces. uPAR over-expression, showed by RT-PCR and Western blotting, was paralleled by increased urokinase-type plasminogen activator (uPA) partitioning on the cell surface with respect to the fluid phase, as demonstrated by zymography. Long-term interaction of SDF1 with CXCR4 stimulated sustained activation of JNK phosphorylation. Blocking antibodies to CXCR4 were able to block the endothelial/epithelial cell-dependent enhancement of invasion, as well as to inhibit SDF1-CXCR4-dependent JNK phosphorylation and uPAR over-expression of malignant cells. We suggest that acquisition of the angiogenic phenotype by breast cancer cells triggers an amplification loop, in which endothelial cells and normal breast epithelial cells of the tumour cooperate to provide facilitated routes to cell invasion and metastasis and to enhance the aggressive phenotype of cancer cells. Copyright (c) 2008 Pathological Society of Great Britain and Ireland

This paper proposes a non-linear observer for In- duction Machine (IM) drives which takes into consideration the saturation effects. The non-linear observer is based on an original formulation of the dynamic model of the IM taking into consideration the magnetic saturation of the iron core. A Lyapunov based convergence analysis is proposed in order to suitably compute the observer gain guaranteeing the stability of the observer. The proposed non-linear observer has been tested in numerical simulation and experimentally on a suitably developed test set-up. Its behaviour has been compared to that obtained with a classic Full-Order Luenberger Observer (FOLO) in variable flux working conditions, in terms of accuracy of the amplitude and phase of both the rotor flux linkage and the stator currents space vectors. Results have shown the capability of the proposed non-linear observer to correctly estimate the rotor flux linkage amplitude and phase under flux varying conditions including strong variation of the saturation of the iron path with accuracy in the flux estimation much higher than that obtained with the classic FOLO.