PARP inhibitors and the treatment of breast cancer: beyond BRCA1/2?

Poly(ADP-ribose) polymerase (PARP) inhibitors have been explored as therapeutic agents for the treatment of hereditary breast and ovarian cancers harboring mutations in BRCA1 or BRCA2. In a new study, Inbar-Rozensal and colleagues show that phenanthridine-derived PARP inhibitors promote cell cycle arrest and cell death in breast cancer cells lacking BRCA1 and BRCA2 mutations and prevent the growth of tumors from xenografts of these cells in immunocompromised mice. These results suggest a potential broader utility of PARP-1 inhibitors in the treatment of breast cancer, although further mechanistic studies are needed

A solid state light-matter interface at the single photon level

Coherent and reversible mapping of quantum information between light and matter is an important experimental challenge in quantum information science. In particular, it is a decisive milestone for the implementation of quantum networks and quantum repeaters. So far, quantum interfaces between light and atoms have been demonstrated with atomic gases, and with single trapped atoms in cavities. Here we demonstrate the coherent and reversible mapping of a light field with less than one photon per pulse onto an ensemble of 10 millions atoms naturally trapped in a solid. This is achieved by coherently absorbing the light field in a suitably prepared solid state atomic medium. The state of the light is mapped onto collective atomic excitations on an optical transition and stored for a pre-programmed time up of to 1 mu s before being released in a well defined spatio-temporal mode as a result of a collective interference. The coherence of the process is verified by performing an interference experiment with two stored weak pulses with a variable phase relation. Visibilities of more than 95% are obtained, which demonstrates the high coherence of the mapping process at the single photon level. In addition, we show experimentally that our interface allows one to store and retrieve light fields in multiple temporal modes. Our results represent the first observation of collective enhancement at the single photon level in a solid and open the way to multimode solid state quantum memories as a promising alternative to atomic gases.Comment: 5 pages, 5 figures, version submitted on June 27 200

Dissipative and Non-dissipative Single-Qubit Channels: Dynamics and Geometry

Single-qubit channels are studied under two broad classes: amplitude damping channels and generalized depolarizing channels. A canonical derivation of the Kraus representation of the former, via the Choi isomorphism is presented for the general case of a system's interaction with a squeezed thermal bath. This isomorphism is also used to characterize the difference in the geometry and rank of these channel classes. Under the isomorphism, the degree of decoherence is quantified according to the mixedness or separability of the Choi matrix. Whereas the latter channels form a 3-simplex, the former channels do not form a convex set as seen from an ab initio perspective. Further, where the rank of generalized depolarizing channels can be any positive integer upto 4, that of amplitude damping ones is either 2 or 4. Various channel performance parameters are used to bring out the different influences of temperature and squeezing in dissipative channels. In particular, a noise range is identified where the distinguishability of states improves inspite of increasing decoherence due to environmental squeezing.Comment: 12 pages, 4 figure

The sudden change phenomenon of quantum discord

Even if the parameters determining a system's state are varied smoothly, the behavior of quantum correlations alike to quantum discord, and of its classical counterparts, can be very peculiar, with the appearance of non-analyticities in its rate of change. Here we review this sudden change phenomenon (SCP) discussing some important points related to it: Its uncovering, interpretations, and experimental verifications, its use in the context of the emergence of the pointer basis in a quantum measurement process, its appearance and universality under Markovian and non-Markovian dynamics, its theoretical and experimental investigation in some other physical scenarios, and the related phenomenon of double sudden change of trace distance discord. Several open questions are identified, and we envisage that in answering them we will gain significant further insight about the relation between the SCP and the symmetry-geometric aspects of the quantum state space.Comment: Lectures on General Quantum Correlations and their Applications, F. F. Fanchini, D. O. Soares Pinto, and G. Adesso (Eds.), Springer (2017), pp 309-33

Linear Optics Simulation of Non-Markovian Quantum Dynamics

The simulation of quantum processes is a key goal for the grand programme aiming at grounding quantum technologies as the way to explore complex phenomena that are inaccessible through standard, classical calculators. Some interesting steps have been performed in this direction and this scenario has recently been extended to open quantum evolutions, marking the possibility to investigate important features of the way a quantum system interacts with its environment. Here we demonstrate experimentally the (non-)Markovianity of a process where system and environment are coupled through a simulated transverse Ising model. By engineering the evolution in a fully controlled photonic quantum simulator, we assess and demonstrate the role that system-environment correlations have in the emergence of memory effects.Comment: 4+2 pages, 4 figures, RevTeX

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4×10-48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3×10-43 cm2 (7.1×10-42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

Simulations of events for the LUX-ZEPLIN (LZ) dark matter experiment

The LUX-ZEPLIN dark matter search aims to achieve a sensitivity to the WIMP-nucleon spin-independent cross-section down to (1–2)×10−12 pb at a WIMP mass of 40 GeV/c2. This paper describes the simulations framework that, along with radioactivity measurements, was used to support this projection, and also to provide mock data for validating reconstruction and analysis software. Of particular note are the event generators, which allow us to model the background radiation, and the detector response physics used in the production of raw signals, which can be converted into digitized waveforms similar to data from the operational detector. Inclusion of the detector response allows us to process simulated data using the same analysis routines as developed to process the experimental data

Projected sensitivity of the LUX-ZEPLIN experiment to the 0νββ decay of Xe 136

The LUX-ZEPLIN (LZ) experiment will enable a neutrinoless double β decay search in parallel to the main science goal of discovering dark matter particle interactions. We report the expected LZ sensitivity to Xe136 neutrinoless double β decay, taking advantage of the significant (>600 kg) Xe136 mass contained within the active volume of LZ without isotopic enrichment. After 1000 live-days, the median exclusion sensitivity to the half-life of Xe136 is projected to be 1.06×1026 years (90% confidence level), similar to existing constraints. We also report the expected sensitivity of a possible subsequent dedicated exposure using 90% enrichment with Xe136 at 1.06×1027 years

Serum levels of Cartilage Oligomeric Matrix Protein (COMP) increase temporarily after physical exercise in patients with knee osteoarthritis

BACKGROUND: COMP (Cartilage oligomeric matrix protein) is a matrix protein, which is currently studied as a potential serum marker for cartilage processes in osteoarthritis (OA). The influence of physical exercise on serum COMP is not fully elucidated. The objective of the present study was to monitor serum levels of COMP during a randomised controlled trial of physical exercise vs. standardised rest in individuals with symptomatic and radiographic knee OA. METHODS: Blood samples were collected from 58 individuals at predefined time points before and after exercise or rest, one training group and one control group. The physical exercise consisted of a one-hour supervised session twice a week and daily home exercises. In a second supplementary study 7 individuals were subjected to the same exercise program and sampling of blood was performed at fixed intervals before, immediately after, 30 and 60 minutes after the exercise session and then with 60 minutes interval for another five hours after exercise to monitor the short-term changes of serum COMP. COMP was quantified with a sandwich-ELISA (AnaMar Medical, Lund, Sweden). RESULTS: Before exercise or rest no significant differences in COMP levels were seen between the groups. After 60 minutes exercise serum COMP levels increased (p < 0.001). After 60 minutes of rest the serum levels decreased (p = 0.003). Median serum COMP values in samples obtained prior to exercise or rest at baseline and after 24 weeks did not change between start and end of the study. In the second study serum COMP was increased immediately after exercise (p = 0.018) and had decreased to baseline levels after 30 minutes. CONCLUSION: Serum COMP levels increased during exercise in individuals with knee OA, whereas levels decreased during rest. The increased serum COMP levels were normalized 30 minutes after exercise session, therefore we suggest that samples of blood for analysis of serum COMP should be drawn after at least 30 minutes rest in a seated position. No increase was seen after a six-week exercise program indicating that any effect of individualized supervised exercise on cartilage turnover is transient

Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation

Background: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. Results: iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders