Results of the simulations of the petal/lens as part of the LAUE project

In the context of the LAUE project for focusing hard X-/gamma rays, a petal of the complete lens is being assembled at the LARIX facility in the Department of Physics and Earth Science of the University of Ferrara. The lens petal structure is composed of bent Germanium and Gallium Arsenide crystals in transmission geometry. We present the expectations derived from a mathematical model of the lens petal. The extension of the model for the complete LAUE project in the 90 -- 600 keV energy range will be discussed as well. A quantitative analysis of the results of these simulations is also presented.Comment: 12 pages, 26 figures, SPIE optics + Photonics conference 2013, Vol: 886

Expected performances of a Laue lens made with bent crystals

In the context of the LAUE project devoted to build a Laue lens prototype for focusing celestial hard X-/soft gamma-rays, a Laue lens made of bent crystal tiles, with 20 m focal length, is simulated. The focusing energy passband is assumed to be 90--600 keV. The distortion of the image produced by the lens on the focal plane, due to effects of crystal tile misalignment and radial distortion of the crystal curvature, is investigated. The corresponding effective area of the lens, its point spread function and sensitivity are calculated and compared with those exhibited by a nominal Laue lens with no misalignment and/or distortion. Such analysis is crucial to estimate the optical properties of a real lens, in which the investigated shortcomings could be present.Comment: 20 pages, 14 figure

Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

Sex differences in cardiovascular disease (CVD) are often recognized from experimental and clinical studies examining the prevalence, manifestations, and response to therapies. Compared to age-matched men, women tend to have reduced CV risk and a better prognosis in the premenopausal period. However, with menopause, this risk increases exponentially, surpassing that of men. Although several mechanisms have been provided, including sex hormones, an emerging role in these sex differences has been suggested for β-adrenergic receptor (β-AR) signaling. Importantly, β-ARs are the most important G protein-coupled receptors (GPCRs), expressed in almost all the cell types of the CV system, and involved in physiological and pathophysiological processes. Consistent with their role, for decades, βARs have been considered the first targets for rational drug design to fight CVDs. Of note, β-ARs are seemingly associated with different CV outcomes in females compared with males. In addition, even if there is a critical inverse correlation between β-AR responsiveness and aging, it has been reported that gender is crucially involved in this age-related effect. This review will discuss how β-ARs impact the CV risk and response to anti-CVD therapies, also concerning sex and age. Further, we will explore how estrogens impact β-AR signaling in women

Hard x-ray broad band Laue lenses (80 - 600 keV): building methods and performances

We present the status of the laue project devoted to develop a technology for building a 20 meter long focal length Laue lens for hard x-/soft gamma-ray astronomy (80 - 600 keV). The Laue lens is composed of bent crystals of Gallium Arsenide (GaAs, 220) and Germanium (Ge, 111), and, for the first time, the focusing property of bent crystals has been exploited for this field of applications. We show the preliminary results concerning the adhesive employed to fix the crystal tiles over the lens support, the positioning accuracy obtained and possible further improvements. The Laue lens petal that will be completed in a few months has a pass band of 80 - 300 keV and is a fraction of an entire Laue lens capable of focusing X-rays up to 600 keV, possibly extendable down to 20 - 30 keV with suitable low absorption crystal materials and focal length. The final goal is to develop a focusing optics that can improve the sensitivity over current telescopes in this energy band by 2 orders of magnitude

The LAUE project for broadband gamma-ray focusing lenses

We present the LAUE project devoted to develop an advanced technology for building a high focal length Laue lens for soft gamma--ray astronomy (80-600 keV). The final goal is to develop a focusing optics that can improve the current sensitivity in the above energy band by 2 orders of magnitude.Comment: 7 pages, 6 figures, presented at the SPIE conference on "Optics for EUV, X-ray, and Gamma-ray Astronomy". To be published in the Proceedings of SPIE, vol.8147, 201

Identification and molecular characterization of a novel mutation in MSH2 gene in a lynch syndrome family

Background and aim of the work: The Lynch Syndrome (LS) is associated with germline mutations in one of the MisMatch Repair (MMR) genes, including MLH1, MSH2, MSH6, PMS2, MLH3 and MSH3. The molecular characterization of mutations in these MMR genes facilitates the pre-symptomatic diagnosis of subjects at risk to develop a colon cancer or a cancer LS-related. Methods: DHPLC and direct sequencing were performed for the mutation detection analysis. Results: In this study, we identified a novel frame shift mutation, the named is c.170delT in MSH2 gene that determined a premature stop codon and consequently, the formation of a truncated protein (p. Val56Glyfs*7). This is a novel mutation, as it has not been reported before in the international scientific literature. This mutation was found in two subjects (father and son) belonging to a LS family. However, they showed a different phenotype disease. Conclusion: In this study, we identified and characterized a novel MSH2 mutation; moreover, this study reaffirmed the importance of genetic testing in Lynch syndrome

Involvement of large rearrangements in MSH6 and PMS2 genes in southern Italian patients with Lynch syndrome

Background and aim of the work: The Lynch Syndrome (LS) is associated with germline mutations in one of the MisMatch Repair (MMR) genes. Most of germline mutations are point variants, followed by large rearrangements that account to 15-55% of all pathogenic mutations. Many study reporting the frequency of large rearrangements in the MLH1 and MSH2 genes were performed, while, little is known about the contribution of large rearrangements in other MMR genes, as PMS2 and MSH6. Therefore, in this study we investigated the involvment of large rearrangements in MSH6 and PMS2 genes in a well-characterized series of 20 LS southern Italian patients. Methods: These large rearrangements are not usually detected by methods of mutation analysis, such as denaturing high-performance liquid chromatography (DHPLC) and direct DNA sequencing, but they are detectable by a known technique as the Multiplex Ligation-Probe Dependent Amplification (MLPA) assay. Results: No large rearrangements were identified in MSH6 gene; instead, a large rearrangement was identified in PMS2 gene. A large duplication including the exons 3 and 4 of the PMS2 gene was identified in a patient who developed a rectum carcinoma at 45 years of age, an endometrial carcinoma and a vaginal cancer at the 65 years of age. Conclusion: We can affirm that the detection of large rearrangements in the MSH6 and PMS2 genes should be included in the routine testing for Lynch syndrome, especially considering the simplicity of the MLPA assay

Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of patients do not respond to current treatments, including biologics. Small-molecule therapies offer an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5 years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed. Since JAKs are essential for cell signaling in immune cells, in particular controlling the response to many cytokines, their inhibitors quickly became a promising class of oral therapeutics that proved effective in the treatment of RA. Tofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit an overall acceptable safety profile similar to that of biologic agents, with infections being the most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still limited. Long-term follow-up and further research are needed to evaluate the general safety profile and the global risk of malignancy of these small molecules, although no clear association with malignancy has been reported to date. Here, we will review the main characteristics of JAK inhibitors, including details on their molecular targets and on the clinical evidences obtained so far in the treatment of RA

Coulomb-gas formulation of SU(2) branes and chiral blocks

We construct boundary states in $SU(2)_k$ WZNW models using the bosonized Wakimoto free-field representation and study their properties. We introduce a Fock space representation of Ishibashi states which are coherent states of bosons with zero-mode momenta (boundary Coulomb-gas charges) summed over certain lattices according to Fock space resolution of $SU(2)_k$. The Virasoro invariance of the coherent states leads to families of boundary states including the B-type D-branes found by Maldacena, Moore and Seiberg, as well as the A-type corresponding to trivial current gluing conditions. We then use the Coulomb-gas technique to compute exact correlation functions of WZNW primary fields on the disk topology with A- and B-type Cardy states on the boundary. We check that the obtained chiral blocks for A-branes are solutions of the Knizhnik-Zamolodchikov equations.Comment: 14 pages, 3 figures, revtex4. Essentially the published versio