An adaptive POD approximation method for the control of advection-diffusion equations

We present an algorithm for the approximation of a finite horizon optimal control problem for advection-diffusion equations. The method is based on the coupling between an adaptive POD representation of the solution and a Dynamic Programming approximation scheme for the corresponding evolutive Hamilton-Jacobi equation. We discuss several features regarding the adaptivity of the method, the role of error estimate indicators to choose a time subdivision of the problem and the computation of the basis functions. Some test problems are presented to illustrate the method.Comment: 17 pages, 18 figure

Neutrinoless double beta decay in SO(10) inspired seesaw models

By requiring the lower limit for the lightest right-handed neutrino mass, obtained in the baryogenesis from leptogenesis scenario, and a Dirac neutrino mass matrix similar to the up-quark mass matrix we predict small values for the $\nu_e$ mass and for the matrix element $m_{ee}$ responsible of the neutrinoless double beta decay, $m_{\nu_e}$ around $5\cdot10^{-3}$ eV and $m_{ee}$ smaller than $10^{-3}$ eV, respectively. The allowed range for the mass of the heaviest right-handed neutrino is centered around the value of the scale of B - L breaking in the SO(10) gauge theory with Pati-Salam intermediate symmetry.Comment: 9 pages, RevTex4. Revised, title change

MTOR cross-talk in cancer and potential for combination therapy

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer. Single-agent mTOR targeting, mostly using rapalogs, has so far met limited clinical success; however, due to the extensive cross-talk between mTOR and other pathways, combined approaches are the most promising avenues to improve clinical efficacy of available therapeutics and overcome drug resistance. This review provides a brief and up-to-date narrative on the regulation of mTOR function, the relative contributions of mTORC1 and mTORC2 complexes to cancer development and progression, and prospects for mTOR inhibition as a therapeutic strategy

Near-infrared spectroscopy study of tourniquet-induced forearm ischaemia in patients with coronary artery disease

Near-Infrared Spectroscopy (NIR) can be employed to monitor local changes in haemodynamics and oxygenation of human tissues. A preliminary study has been performed in order to evaluate the NIRS transmittance response to induced forearm ischaemia in patients with coronary artery disease (CAD). The population consists in 40 patients with cardiovascular risk factors and angiographically documented CAD, compared to a group of 13 normal subjects. By inflating and subsequently deflating a cuff placed around the patient arm, an ischaemia has been induced and released, and the patients have been observed until recovery of the basal conditions. A custom LAIRS spectrometer (IRIS) has been used to collect the backscattered light intensities from the patient forearm throughout the ischaemic and the recovery phase. The time dependence of the near-infrared transmittance on the control group is consistent with the available literature. On the contrary, the magnitude and dynamics of the NIRS signal on the CAD patients show deviations from the documented normal behavior, which can be tentatively attributed to abnormal vessel stiffness. These preliminary results, while validating the performance of the IRIS spectrometer, are strongly conducive towards the applicability of the NIRS technique to ischaemia analysis and to endothelial dysfunction characterization in CAD patients with cardiovascular risk factors.Publisher PD

Leptogenesis and Low-energy Observables

We relate leptogenesis in a class of theories to low-energy experimental observables: quark and lepton masses and mixings. With reasonable assumptions motivated by grand unification, one can show that the CP-asymmetry parameter takes a universal form. Furthermore the dilution mass is related to the light neutrino masses. Overall, these models offer a natural explanation for a lepton asymmetry in the early universe.Comment: 10 pages, revised discussion on light neutrino masse

Seesaw mechanism, baryon asymmetry and neutrinoless double beta decay

A simplified but very instructive analysis of the seesaw mechanism is here performed. Assuming a nearly diagonal Dirac neutrino mass matrix, we study the forms of the Majorana mass matrix of right-handed neutrinos, which reproduce the effective mass matrix of left-handed neutrinos. As a further step, the important effect of a non diagonal Dirac neutrino mass matrix is explored. The corresponding implications for the baryogenesis via leptogenesis and for the neutrinoless double beta decay are reviewed. We propose two distinct models where the baryon asymmetry is enhanced.Comment: 21 pages, RevTex. Revise

Testing quark mass matrices with right-handed mixings

In the standard model, several forms of quark mass matrices which correspond to the choice of weak bases lead to the same left-handed mixings $V_L=V_{CKM}$, while the right-handed mixings $V_R$ are not observable quantities. Instead, in a left-right extension of the standard model, such forms are ansatze and give different right-handed mixings which are now observable quantities. We partially select the reliable forms of quark mass matrices by means of constraints on right-handed mixings in some left-right models, in particular on $V^R_{cb}$. Hermitian matrices are easily excluded.Comment: 12 pages RevTex, no figures. Minor corrections. Comment on SO(10) changed and one reference adde

<b><i>Topoisomerase 1</i></b> Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients. Methods: With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival). Results: No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1). Conclusion: Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens

Fermion masses and mixings in gauge theories

The recent evidence for neutrino oscillations stimulate us to discuss again the problem of fermion masses and mixings in gauge theories. In the standard model, several forms for quark mass matrices are equivalent. They become ansatze within most extensions of the standard model, where also relations between quark and lepton sectors may hold. In a seesaw framework, these relations can constrain the scale of heavy neutrino mass, which is often related to the scale of intermediate or unification gauge symmetry. As a consequence, two main scenarios arise. Hierarchies of masses and mixings may be explained by broken horizontal symmetries.Comment: 25 pages, RevTex, no figures. Few misprints corrected and two references adde