Homologous recombination deficiency and ovarian cancer

The discovery that PARP inhibitors block an essential pathway of DNA repair in cells harbouring a BRCA mutation has opened up a new therapeutic avenue for high-grade ovarian cancers. BRCA1 and BRCA2 proteins are essential for high-fidelity repair of double-strand breaks of DNA through the homologous recombination repair (HRR) pathway. Deficiency in HRR (HRD) is a target for PARP inhibitors. The first PARP inhibitor, olaparib, has now been licensed for BRCA-mutated ovarian cancers. While mutated BRCA genes are individually most commonly associated with HRD other essential HRR proteins may be mutated or functionally deficient potentially widening the therapeutic opportunities for PARP inhibitors. HRD is the first phenotypically defined predictive marker for therapy with PARP inhibitors in ovarian cancer. Several different PARP inhibitors are being trialled in ovarian cancer and this class of drugs has been shown to be a new selective therapy for high-grade ovarian cancer. Around 20% of high-grade serous ovarian cancers harbour germline or somatic BRCA mutations and testing for BRCA mutations should be incorporated into routine clinical practice. The expanded use of PARP inhibitors in HRD deficient (non-BRCA mutant) tumours using a signature of HRD in clinical practice requires validation

Infrared Hall conductivity of Na0.7_{0.7}CoO2_2

We report infrared Hall conductivity $\sigma_{xy}(\omega)$ of Na$_{0.7}$CoO$_2$ thin films determined from Faraday rotation angle $\theta_{F}$ measurements. $\sigma_{xy}(\omega)$ exhibits two types of hole conduction, Drude and incoherent carriers. The coherent Drude carrier shows a large renormalized mass and Fermi liquid-like behavior of Hall scattering rate, $\gamma_{H} \sim aT^{2}$. The spectral weight is suppressed and disappears at T = 120K. The incoherent carrier response is centered at mid-IR frequency and shifts to lower energy with increasing T. Infrared Hall constant is positive and almost independent of temperature in sharp contrast with the dc-Hall constant.Comment: 5 Pages, 5 Figures. Author list corrected in metadata only, paper is unchange

Effect of excited states and applied magnetic fields on the measured hole mobility in an organic semiconductor

Copyright 2010 by the American Physical Society. Article is available at

Spin phonon coupling in frustrated magnet CdCr2_2O4_4

The infrared phonon spectrum of the spinel CdCr2O4 is measured as a function temperature from 6 K to 300K. The triply degenerate Cr phonons soften in the paramagnetic phase as temperature is lowered below 100 K and then split into a singlet and doublet in the low T antiferromagnetic phase which is tetragonally distorted to relieve the geometric frustration in the pyrochlore lattice of Cr$^{3+}$ ions. The phonon splitting is inconsistent with the simple increase (decrease) in the force constants due to deceasing (increasing) bond lengths in the tetragonal phase. Rather they correspond to changes in the force constants due to the magnetic order in the antiferromagnetic state. The phonon splitting in this system is opposite of that observed earlier in ZnCr2O4 as predicted by theory. The magnitude of the splitting gives a measure of the spin phonon coupling strength which is smaller than in the case of ZnCr2O4.Comment: 4.2 pages, 4 figures, 1 reference added, submmite

A Spinal Opsin Controls Early Neural Activity and Drives a Behavioral Light Response

SummaryNonvisual detection of light by the vertebrate hypothalamus, pineal, and retina is known to govern seasonal and circadian behaviors [1]. However, the expression of opsins in multiple other brain structures [2–4] suggests a more expansive repertoire for light regulation of physiology, behavior, and development. Translucent zebrafish embryos express extraretinal opsins early on [5, 6], at a time when spontaneous activity in the developing CNS plays a role in neuronal maturation and circuit formation [7]. Though the presence of extraretinal opsins is well documented, the function of direct photoreception by the CNS remains largely unknown. Here, we show that early activity in the zebrafish spinal central pattern generator (CPG) and the earliest locomotory behavior are dramatically inhibited by physiological levels of environmental light. We find that the photosensitivity of this circuit is conferred by vertebrate ancient long opsin A (VALopA), which we show to be a Gαi-coupled receptor that is expressed in the neurons of the spinal network. Sustained photoactivation of VALopA not only suppresses spontaneous activity but also alters the maturation of time-locked correlated network patterns. These results uncover a novel role for nonvisual opsins and a mechanism for environmental regulation of spontaneous motor behavior and neural activity in a circuit previously thought to be governed only by intrinsic developmental programs