The J- and H-bands of dye aggregate spectra: Analysis of the coherent exciton scattering (CES) approximation

The validity of the CES approximation is investigated by comparison with direct diagonalisation of a model vibronic Hamiltonian of $N$ identical monomers interacting electronically. Even for quite short aggregates (N\gtrsim 6) the CES approximation is shown to give results in agreement with direct diagonalisation, for all coupling strengths, except that of intermediate positive coupling (the H-band region). However, previously excellent agreement of CES calculations and measured spectra in the H-band region was obtained [A. Eisfeld, J. S. Briggs, Chem. Phys. 324, 376]. This is shown to arise from use of the measured monomer spectrum which includes implicitly dissipative effects not present in the model calculation

A P53-Independent DNA Damage Response Suppresses Oncogenic Proliferation and Genome Instability

The Mre11-Rad50-Nbs1 complex is a DNA double-strand break sensor that mediates a tumor-suppressive DNA damage response (DDR) in cells undergoing oncogenic stress, yet the mechanisms underlying this effect are poorly understood. Using a genetically inducible primary mammary epithelial cell model, we demonstrate that Mre11 suppresses proliferation and DNA damage induced by diverse oncogenic drivers through a p53-independent mechanism. Breast tumorigenesis models engineered to express a hypomorphic Mre11 allele exhibit increased levels of oncogene-induced DNA damage, R-loop accumulation, and chromosomal instability with a characteristic copy number loss phenotype. Mre11 complex dysfunction is identified in a subset of human triple-negative breast cancers and is associated with increased sensitivity to DNA-damaging therapy and inhibitors of ataxia telangiectasia and Rad3 related (ATR) and poly (ADP-ribose) polymerase (PARP). Thus, deficiencies in the Mre11-dependent DDR drive proliferation and genome instability patterns in p53-deficient breast cancers and represent an opportunity for therapeutic exploitation

An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity

Alpha-1 adrenergic receptors (α1-ARs) play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, the authors administered dabuzalgron to mice treated with doxorubicin (DOX), a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to heart failure (HF). Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF

Mirror Energy Differences at Large Isospin Studied through Direct Two-Nucleon Knockout

The first spectroscopy of excited states in Ni52 (Tz=-2) and Co51 (Tz=-3/2) has been obtained using the highly selective two-neutron knockout reaction. Mirror energy differences between isobaric analogue states in these nuclei and their mirror partners are interpreted in terms of isospin nonconserving effects. A comparison between large-scale shell-model calculations and data provides the most compelling evidence to date that both electromagnetic and an additional isospin nonconserving interactions for J=2 couplings, of unknown origin, are required to obtain good agreement. � 2013 American Physical Society

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

Mirrored one-nucleon knockout reactions to the T-z = +/- 3/2 A=53 mirror nuclei

Background: The study of excited states in mirror nuclei allows us to extract information on charge-dependent (i.e., isospin-nonconserving) interactions in nuclei. Purpose: To extend previous studies of mirror nuclei in the f72 region, investigating charge symmetry breaking of the strong nuclear force. Methods: γ-ray spectroscopy has been performed for the mirror (Tz=±32) pair Ni53 and Mn53, produced via mirrored one-nucleon knockout reactions. Results: Several new transitions have been identified in Ni53 from which a new level scheme has been constructed. Cross sections for knockout have been analyzed and compared with reaction model calculations where evidence is found for knockout from high-spin isomeric states. Mirror energy differences between isobaric analog states have been computed, compared to large scale shell-model calculations, and interpreted in terms of isospin-nonconserving effects. In addition, lifetimes for the long-lived Jπ=52−1 analog states in both Mn53 and Ni53 have been extracted through lineshape analysis, giving half-lives of t12=120(14) ps and t12=198(12) ps, respectively. Conclusions: The inclusion of a set of isovector isospin-nonconserving matrix elements to the shell-model calculations gave the best agreement with the experimental data

The JCMT Legacy Survey of the Gould Belt: a first look at Orion B with HARP

‘The definitive version is available at www3.interscience.wiley.com '. Copyright Royal Astronomical Society.The Gould Belt Legacy Survey will survey nearby star-forming regions (within 500 pc), using Heterodyne Array Receiver Programme (HARP), Submillimetre Common-User Bolometer Array 2 and Polarimeter 2 on the James Clerk Maxwell Telescope. This paper describes the initial data obtained using HARP to observe 12CO, 13CO and C18O J= 3 → 2 towards two regions in Orion B, NGC 2024 and NGC 2071. We describe the physical characteristics of the two clouds, calculating temperatures and opacities utilizing all the three isotopologues. We find good agreement between temperatures calculated from CO and from dust emission in the dense, energetic regions. We determine the mass and energetics of the clouds, and of the high-velocity material seen in 12CO emission, and compare the relative energetics of the high- and low-velocity material in the two clouds. We present a clumpfind analysis of the 13CO condensations. The slope of the condensation mass functions, at the high-mass ends, is similar to the slope of the initial mass function.Peer reviewe