Genetic determinants of cellular addiction to DNA polymerase theta

Polymerase theta (Pol θ, gene name Polq) is a widely conserved DNA polymerase that mediates a microhomology-mediated, error-prone, double strand break (DSB) repair pathway, referred to as Theta Mediated End Joining (TMEJ). Cells with homologous recombination deficiency are reliant on TMEJ for DSB repair. It is unknown whether deficiencies in other components of the DNA damage response (DDR) also result in Pol θ addiction. Here we use a CRISPR genetic screen to uncover 140 Polq synthetic lethal (PolqSL) genes, the majority of which were previously unknown. Functional analyses indicate that Pol θ/TMEJ addiction is associated with increased levels of replication-associated DSBs, regardless of the initial source of damage. We further demonstrate that approximately 30% of TCGA breast cancers have genetic alterations in PolqSL genes and exhibit genomic scars of Pol θ/TMEJ hyperactivity, thereby substantially expanding the subset of human cancers for which Pol θ inhibition represents a promising therapeutic strategy

Amorphization threshold in Si-implanted strained SiGe alloy layers

The authors have examined the damage produced by Si-ion implantation into strained Si{sub 1{minus}x}Ge{sub x} epilayers. Damage accumulation in the implanted layers was monitored in situ by time-resolved reflectivity and measured by ion channeling techniques to determine the amorphization threshold in strained Si{sub 1{minus}x}Ge{sub x} (x = 0.16 and 0.29) over the temperature range 30--110 C. The results are compared with previously reported measurements on unstrained Si{sub 1{minus}x}Ge{sub x}, and with the simple model used to describe those results. They report here data which lend support to this model and which indicate that pre-existing strain does not enhance damage accumulation in the alloy layer

Amorphization Threshold in Si-Implanted Strained Sige Alloy Layers

The authors have examined the damage produced by Si-ion implantation into strained Si{sub 1{minus}x}Ge{sub x} epilayers. Damage accumulation in the implanted layers was monitored in situ by time-resolved reflectivity and measured by ion channeling techniques to determine the amorphization threshold in strained Si{sub 1{minus}x}Ge{sub x} (x = 0.16 and 0.29) over the temperature range 30--110 C. The results are compared with previously reported measurements on unstrained Si{sub 1{minus}x}Ge{sub x}, and with the simple model used to describe those results. They report here data which lend support to this model and which indicate that pre-existing strain does not enhance damage accumulation in the alloy layer

Evolving collective structures in the transitional nuclei W-162 and W-164

Excited states in the neutron-deficient nuclides W8874162 and W9074164 were investigated by using the γ-ray spectrometer Jurogam. A change in structure is apparent from the first rotational alignments in W162 and W164, whose rotationally aligned bands are interpreted as ν(h9/2)2 and ν(i13/2)2 configurations, respectively. The level schemes have been extended using recoil (-decay) correlations with the observation of excited collective structures. Configuration assignments have been made on the basis of comparisons of the deduced aligned angular momentum, as a function of rotational frequency, with the predictions of the cranked shell model

Probing the limit of nuclear existence: Proton emission from 159Re

AbstractThe observation of the new nuclide 15975Re84 provides important insights into the evolution of single-particle structure and the mass surface in heavy nuclei beyond the proton drip line. This nuclide, 26 neutrons away from the nearest stable rhenium isotope, was synthesised in the reaction 106Cd(58Ni, p4n) and identified via its proton radioactivity using the ritu gas-filled separator and the great focal-plane spectrometer. Comparisons of the measured proton energy (Ep=1805±20 keV) and decay half-life (t1/2=21±4 μs) with values calculated using the WKB method indicate that the proton is emitted from an h11/2 state. The implications of these results for future experimental investigations into even more proton unbound nuclei using in-flight separation techniques are considered

The Mathematical Universe

I explore physics implications of the External Reality Hypothesis (ERH) that there exists an external physical reality completely independent of us humans. I argue that with a sufficiently broad definition of mathematics, it implies the Mathematical Universe Hypothesis (MUH) that our physical world is an abstract mathematical structure. I discuss various implications of the ERH and MUH, ranging from standard physics topics like symmetries, irreducible representations, units, free parameters, randomness and initial conditions to broader issues like consciousness, parallel universes and Godel incompleteness. I hypothesize that only computable and decidable (in Godel's sense) structures exist, which alleviates the cosmological measure problem and help explain why our physical laws appear so simple. I also comment on the intimate relation between mathematical structures, computations, simulations and physical systems.Comment: Replaced to match accepted Found. Phys. version, 31 pages, 5 figs; more details at http://space.mit.edu/home/tegmark/toe.htm

The geometry of r-adaptive meshes generated using optimal transport methods

The principles of mesh equidistribution and alignment play a fundamental role in the design of adaptive methods, and a metric tensor M and mesh metric are useful theoretical tools for understanding a methods level of mesh alignment, or anisotropy. We consider a mesh redistribution method based on the Monge-Ampere equation, which combines equidistribution of a given scalar density function with optimal transport. It does not involve explicit use of a metric tensor M, although such a tensor must exist for the method, and an interesting question to ask is whether or not the alignment produced by the metric gives an anisotropic mesh. For model problems with a linear feature and with a radially symmetric feature, we derive the exact form of the metric M, which involves expressions for its eigenvalues and eigenvectors. The eigenvectors are shown to be orthogonal and tangential to the feature, and the ratio of the eigenvalues (corresponding to the level of anisotropy) is shown to depend, both locally and globally, on the value of the density function and the amount of curvature. We thereby demonstrate how the optimal transport method produces an anisotropic mesh along a given feature while equidistributing a suitably chosen scalar density function. Numerical results are given to verify these results and to demonstrate how the analysis is useful for problems involving more complex features, including for a non-trivial time dependant nonlinear PDE which evolves narrow and curved reaction fronts

Observing Supermassive Black Holes across cosmic time: from phenomenology to physics

In the last decade, a combination of high sensitivity, high spatial resolution observations and of coordinated multi-wavelength surveys has revolutionized our view of extra-galactic black hole (BH) astrophysics. We now know that supermassive black holes reside in the nuclei of almost every galaxy, grow over cosmological times by accreting matter, interact and merge with each other, and in the process liberate enormous amounts of energy that influence dramatically the evolution of the surrounding gas and stars, providing a powerful self-regulatory mechanism for galaxy formation. The different energetic phenomena associated to growing black holes and Active Galactic Nuclei (AGN), their cosmological evolution and the observational techniques used to unveil them, are the subject of this chapter. In particular, I will focus my attention on the connection between the theory of high-energy astrophysical processes giving rise to the observed emission in AGN, the observable imprints they leave at different wavelengths, and the methods used to uncover them in a statistically robust way. I will show how such a combined effort of theorists and observers have led us to unveil most of the SMBH growth over a large fraction of the age of the Universe, but that nagging uncertainties remain, preventing us from fully understating the exact role of black holes in the complex process of galaxy and large-scale structure formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and Treves A. (Eds), 2015, Springer International Publishing AG, Cha

Forest Biodiversity Assessment in Peruvian Andean Montane Cloud Forest

Cloud forests are unusual and fragile habitats, being one of the least studied and least understood ecosystems. The tropical Andean dominion is considered one of the most significant places in the world as rega rds biological diversity, with a very high level of endemism. The biodiversity was analysed in an isolated remnant area of a tropical montane cloud forest known as the ?Bosque de Neblina de Cuyas?, in the North of the Peruvian Andean range. Composition, structure and dead wood were measured or estimated. The values obtained were compared with other cloud forests. The study revealed a high level of forest biodiversity, although the level of biodiversity differs from one area to another: in the inner areas, where human pressure is almost inexistent, the biodiversity values increase. The high species richness and the low dominance among species bear testimony to this montane cloud forest as a real enclave of biodiversity