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

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

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

Development status of the LAUE project

We present the status of LAUE, a project supported by the Italian Space Agency (ASI), and devoted to develop Laue lenses with long focal length (up to 100 meters), for hard X--/soft gamma--ray astronomy (80-600 keV). Thanks to their focusing capability, the design goal is to improve the sensitivity of the current instrumention in the above energy band by 2 orders of magnitude, down to a few times $10^{-8}$ photons/(cm$^2$ s keV).Comment: 9 pages, 9 figures, presented at the Space Telescopes and Instrumentation Symposium in Amsterdam, 2012: Ultraviolet to Gamma Ray Conference. Published in the Proceedings of the SPIE, Volume 8443, id. 84430B-84430B-9 (2012

The LAUE project: latest developments

We present the status of the LAUE project devoted to develop a technology for building long focal length Laue lenses for hard X-/soft gamma-ray astronomy (80-600 keV). The Laue lens will be composed of bent crystals of Gallium Arsenide (GaAs, 220) and Germanium (Ge, 111), and, for the first time, the focusing property of bent crystals will be exploited for this field of applications. At the present the goal of the project is the building of a 20 m focal length Laue lens petal capable of focusing X-ray in the energy range 90-300 keV

Scientific prospects in soft gamma-ray astronomy enabled by the LAUE project

This paper summarizes the development of a successful project, LAUE, supported by the Italian Space Agency (ASI) and devoted to the development of long focal length (up to 100 m) Laue lenses for hard X--/soft gamma--ray astronomy (80-600 keV). The apparatus is ready and the assembling of a prototype lens petal is ongoing. The great achievement of this project is the use of bent crystals. From measurements obtained on single crystals and from simulations, we have estimated the expected Point Spread Function and thus the sensitivity of a lens made of petals. The expected sensitivity is a few $\times10^{-8}$ photons cm$^{-2}$ s$^{-1}$ keV$^{-1}$. We discuss a number of open astrophysical questions that can settled with such an instrument aboard a free-flying satellite.Comment: 17 pages, 18 figures, published in Proceedings of the SPIE, Volume 8861, id. 886106 17 pp. (2013

The role of autophagy in resistance to targeted therapies

Autophagy is a self-degradative cellular process, involved in stress response such as starvation, hypoxia, and oxidative stress. This mechanism balances macro-molecule recycling to regulate cell homeostasis. In cancer, autophagy play a role in the development and progression, while several studies describe it as one of the key processes in drug resistance. In the last years, in addition to standard anti-cancer treatments such as chemotherapies and irradiation, targeted therapy became one of the most adopted strategies in clinical practices, mainly due to high specificity and reduced side effects. However, similar to standard treatments, drug resistance is the main challenge in most patients. Here, we summarize recent studies that investigated the role of autophagy in drug resistance after targeted therapy in different types of cancers. We highlight positive results and limitations of pre-clinical and clinical studies in which autophagy inhibitors are used in combination with targeted therapies. Refereed/Peer-reviewe

A new inhibitor of glucose-6-phospate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo

Pentose Phosphate Pathway (PPP) is a major glucose metabolism pathway which has a fundamental role in cancer growth and metastasis. Even though PPP blockade has been pointed out as a very promising strategy against cancer, effective anti-PPP agents are not still available in the clinical setting. Here, we demonstrate that the natural molecule polydatin inhibits glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP. Polydatin blocks G6PD causing accumulation of reactive oxygen species and strong increase of endoplasmic reticulum stress. These effects are followed by cell cycle block in S phase, an about 50% of apoptosis, and 60% inhibition of invasion in vitro. Accordingly, in an orthotopic metastatic model of tongue cancer, 100 mg/kg polydatin induced an about 30% tumor size reduction with an about 80% inhibition of lymph node metastases and 50% reduction of lymph node size (p< 0.005). Polydatin is not toxic in animals up to a dose of 200 mg/kg and a phase II clinical trial shows that a is also well tolerated in humans (40 mg twice a day for 90 days). Thus, polydatin may be used as a reliable tool to limit human cancer growth and metastatic spread

Retinoic acid synergizes with the unfolded protein response and oxidative stress to induce cell death in FLT3-ITD+ AML.

Acute myeloid leukemia (AML) is often characterized by the expression of fusion or mutant proteins that cause impaired differentiation and enhanced proliferation and survival. The presence of mutant proteins prone to misfolding can render the cells sensitive to endoplasmic reticulum (ER) stress and oxidative stress that could otherwise be overcome. Here, we show that the triple combination of the differentiating agent retinoic acid (RA), the ER stress-inducing drug tunicamycin (Tm), and arsenic trioxide (ATO), able to generate oxidative stress, leads to the death of AML cell lines expressing fusion proteins involving the gene MLL and the internal tandem duplication (ITD) in the FLT3 tyrosine kinase receptor. Importantly, the combination of RA, Tm, and ATO decreased the colony-forming capacity of primary leukemic blasts bearing the FLT-ITD mutation without affecting healthy hematopoietic progenitor cells. We demonstrate in cell lines that combination of these drugs generates ER and oxidative stresses and impairs maturation and causes accumulation of FLT3 protein in the ER. Our data provide a proof of concept that low amounts of drugs that generate ER and oxidative stresses combined with RA could be an effective targeted therapy to hit AML cells characterized by MLL fusion proteins and FLT3-ITD mutation