Inhibition of poly(ADP-ribosyl)ation in cancer: Old and new paradigms revisited

Abstract Inhibitors of poly(ADP-ribose) polymerases actualized the biological concept of synthetic lethality in the clinical practice, yielding a paradigmatic example of translational medicine. The profound sensitivity of tumors with germline BRCA mutations to PARP1/2 blockade owes to inherent defects of the BRCA-dependent homologous recombination machinery, which are unleashed by interruption of PARP DNA repair activity and lead to DNA damage overload and cell death. Conversely, aspirant BRCA-like tumors harboring somatic DNA repair dysfunctions (a vast entity of genetic and epigenetic defects known as "BRCAness") not always align with the familial counterpart and appear not to be equally sensitive to PARP inhibition. The acquisition of secondary resistance in initially responsive patients and the lack of standardized biomarkers to identify "BRCAness" pose serious threats to the clinical advance of PARP inhibitors; a feeling is also emerging that a BRCA-centered perspective might have missed the influence of additional, not negligible and DNA repair-independent PARP contributions onto therapy outcome. While regulatory approval for PARP1/2 inhibitors is still pending, novel therapeutic opportunities are sprouting from different branches of the PARP family, although they remain immature for clinical extrapolation. This review is an endeavor to provide a comprehensive appraisal of the multifaceted biology of PARPs and their evolving impact on cancer therapeutics

Stochastic resonance in Gaussian quantum channels

We determine conditions for the presence of stochastic resonance in a lossy bosonic channel with a nonlinear, threshold decoding. The stochastic resonance effect occurs if and only if the detection threshold is outside of a "forbidden interval". We show that it takes place in different settings: when transmitting classical messages through a lossy bosonic channel, when transmitting over an entanglement-assisted lossy bosonic channel, and when discriminating channels with different loss parameters. Moreover, we consider a setting in which stochastic resonance occurs in the transmission of a qubit over a lossy bosonic channel with a particular encoding and decoding. In all cases, we assume the addition of Gaussian noise to the signal and show that it does not matter who, between sender and receiver, introduces such a noise. Remarkably, different results are obtained when considering a setting for private communication. In this case the symmetry between sender and receiver is broken and the "forbidden interval" may vanish, leading to the occurrence of stochastic resonance effects for any value of the detection threshold.Comment: 17 pages, 6 figures. Manuscript improved in many ways. New results on private communication adde

A comparison of bioclimatic potential in two global regions during the late twentieth century and early twenty-first century

This work will evaluate the growing season conditions using indexes that combine growing season temperature and precipitation such as the hydrothermal coefficient (HTC) and the bioclimatic potential (BCP). Also, the interannual variability of these indexes in both regions was examined. In the Belgorod region, the increase in temperature combined with little change in precipitation produced mixed results in interpreting these indexe

Robustness against parametric noise of non ideal holonomic gates

Holonomic gates for quantum computation are commonly considered to be robust against certain kinds of parametric noise, the very motivation of this robustness being the geometric character of the transformation achieved in the adiabatic limit. On the other hand, the effects of decoherence are expected to become more and more relevant when the adiabatic limit is approached. Starting from the system described by Florio et al. [Phys. Rev. A 73, 022327 (2006)], here we discuss the behavior of non ideal holonomic gates at finite operational time, i.e., far before the adiabatic limit is reached. We have considered several models of parametric noise and studied the robustness of finite time gates. The obtained results suggest that the finite time gates present some effects of cancellation of the perturbations introduced by the noise which mimic the geometrical cancellation effect of standard holonomic gates. Nevertheless, a careful analysis of the results leads to the conclusion that these effects are related to a dynamical instead of geometrical feature.Comment: 8 pages, 8 figures, several changes made, accepted for publication on Phys. Rev.

Quantum state transfer in a q-deformed chain

We investigate the quantum state transfer in a chain of particles satisfying q-deformed oscillators algebra. This general algebraic setting includes the spin chain and the bosonic chain as limiting cases. We study conditions for perfect state transfer depending on the number of sites and excitations on the chain. They are formulated by means of irreducible representations of a quantum algebra realized through Jordan-Schwinger maps. Playing with deformation parameters, we can study the effects of nonlinear perturbations or interpolate between the spin and bosonic chain.Comment: 13 pages, 4 figure

Review of Evidence For Environmental Causes of Uveal Coloboma

Uveal coloboma is a condition defined by missing ocular tissues and is a significant cause of childhood blindness. It occurs from a failure of the optic fissure to close during embryonic development and may lead to missing parts of the iris, ciliary body, retina, choroid, and optic nerve. Because there is no treatment for coloboma, efforts have focused on prevention. While several genetic causes of coloboma have been identified, little definitive research exists regarding the environmental causes of this condition. We review the current literature on environmental factors associated with coloboma in an effort to guide future research and preventative counseling related to this condition