PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Precision Measurement of The Most Distant Spectroscopically Confirmed Supernova Ia with the Hubble Space Telescope

We report the discovery of a redshift 1.71 supernova in the GOODS North field. The Hubble Space Telescope (HST) ACS spectrum has almost negligible contamination from the host or neighboring galaxies. Although the rest frame sampled range is too blue to include any Si ii line, a principal component analysis allows us to confirm it as a Type Ia supernova with 92% confidence. A recent serendipitous archival HST WFC3 grism spectrum contributed a key element of the confirmation by giving a host-galaxy redshift of 1.713 +/- 0.007. In addition to being the most distant SN Ia with spectroscopic confirmation, this is the most distant Ia with a precision color measurement. We present the ACS WFC and NICMOS 2 photometry and ACS and WFC3 spectroscopy. Our derived supernova distance is in agreement with the prediction of LambdaCDM.Comment: 13 pages, 6 figures, published in ApJ with updated analysi

Evaluation of a brief anti-stigma campaign in Cambridge: do short-term campaigns work?

<p>Abstract</p> <p>Background</p> <p>In view of the high costs of mass-media campaigns, it is important to understand whether it is possible for a media campaign to have significant population effects over a short period of time. This paper explores this question specifically in reference to stigma and discrimination against people with mental health problems using the <it>Time to Change </it>Cambridge anti-stigma campaign as an example.</p> <p>Methods</p> <p>410 face-to-face interviews were performed pre, during and post campaign activity to assess campaign awareness and mental health-related knowledge, attitudes and behaviours.</p> <p>Results</p> <p>Although campaign awareness was not sustained following campaign activity, significant and sustained shifts occurred for mental health-related knowledge items. Specifically, there was a 24% (p < 0.001) increase in persons agreeing with the statement: <it>If a friend had a mental health problem, I know what advice to give them to get professional help</it>, following the campaign. Additionally, for the statement: <it>Medication can be an effective treatment for people with mental health problems</it>, there was a 10% rise (p = 0.05) in the proportion of interviewees responding 'agree' or 'strongly agree' following the campaign. These changes, however, were not evident for attitudinal or behaviour related questions.</p> <p>Conclusions</p> <p>Although these results only reflect the impact of one small scale campaign, these preliminary findings suggest several considerations for mass-media campaign development and evaluation strategies such as: (1) Aiming to influence outcomes pertaining to knowledge in the short term; (2) Planning realistic and targeted outcomes over the short, medium and long term during sustained campaigns; and (3) Monitoring indirect campaign effects such as social discourse or other social networking/contact in the evaluation.</p

The angular-momentum flux in the solar wind observed during Solar Orbiter's first orbit

Aims: We present the first measurements of the angular-momentum flux in the solar wind recorded by the Solar Orbiter spacecraft. Our aim is to validate these measurements to support future studies of the Sun’s angular-momentum loss. Methods: We combined 60-min averages of the proton bulk moments and the magnetic field measured by the Solar Wind Analyser (SWA) and the magnetometer (MAG) onboard Solar Orbiter. We calculated the angular-momentum flux per solid-angle element using data from the first orbit of the mission’s cruise phase in 2020. We separated the contributions from protons and from magnetic stresses to the total angular-momentum flux. Results: The angular-momentum flux varies significantly over time. The particle contribution typically dominates over the magneticfield contribution during our measurement interval. The total angular-momentum flux shows the largest variation and is typically anticorrelated with the radial solar-wind speed. We identify a compression region, potentially associated with a co-rotating interaction region or a coronal mass ejection, which leads to a significant localised increase in the angular-momentum flux, albeit without a significant increase in the angular momentum per unit mass. We repeated our analysis using the density estimate from the Radio and Plasma Waves (RPW) instrument. Using this independent method, we find a decrease in the peaks of positive angular-momentum flux, but otherwise, our results remain consistent. Conclusions: Our results largely agree with previous measurements of the solar wind’s angular-momentum flux in terms of amplitude, variability, and dependence on radial solar-wind bulk speed. Our analysis highlights the potential for more detailed future studies of the solar wind’s angular momentum and its other large-scale properties with data from Solar Orbiter. We emphasise the need for studying the radial evolution and latitudinal dependence of the angular-momentum flux in combination with data from Parker Solar Probe and other assets at heliocentric distances of 1 au and beyond

Metal-macrofauna interactions determine microbial community structure and function in copper contaminated sediments

Peer reviewedPublisher PD

One-dimensional Particle Processes with Acceleration/Braking Asymmetry

The slow-to-start mechanism is known to play an important role in the particular shape of the Fundamental diagram of traffic and to be associated to hysteresis effects of traffic flow.We study this question in the context of exclusion and queueing processes,by including an asymmetry between deceleration and acceleration in the formulation of these processes. For exclusions processes, this corresponds to a multi-class process with transition asymmetry between different speed levels, while for queueing processes we consider non-reversible stochastic dependency of the service rate w.r.t the number of clients. The relationship between these 2 families of models is analyzed on the ring geometry, along with their steady state properties. Spatial condensation phenomena and metastability is observed, depending on the level of the aforementioned asymmetry. In addition we provide a large deviation formulation of the fundamental diagram (FD) which includes the level of fluctuations, in the canonical ensemble when the stationary state is expressed as a product form of such generalized queues.Comment: 28 pages, 8 figure

Best practices for the diagnosis and evaluation of infants with robin sequence:a clinical consensus report

Importance: Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis, and upper airway obstruction. Currently, no consensus exists regarding the diagnosis and evaluation of children with RS. An international, multidisciplinary consensus group was formed to begin to overcome this limitation. Objective: To report a consensus-derived set of best practices for the diagnosis and evaluation of infants with RS as a starting point for defining standards and management. Evidence Review: Based on a literature review and expert opinion, a clinical consensus report was generated. Findings: Because RS can occur as an isolated condition or as part of a syndrome or multiple-anomaly disorder, the diagnostic process for each newborn may differ. Micrognathia is hypothesized as the initiating event, but the diagnosis of micrognathia is subjective. Glossoptosis and upper airway compromise complete the primary characteristics of RS. It can be difficult to judge the severity of tongue base airway obstruction, and the possibility of multilevel obstruction exists. The initial assessment of the clinical features and severity of respiratory distress is important and has practical implications. Signs of upper airway obstruction can be intermittent and are more likely to be present when the infant is asleep. Therefore, sleep studies are recommended. Feeding problems are common and may be exacerbated by the presence of a cleft palate. The clinical features and their severity can vary widely and ultimately dictate the required investigations and treatments. Conclusions and Relevance: Agreed-on recommendations for the initial evaluation of RS and clinical descriptors are provided in this consensus report. Researchers and clinicians will ideally use uniform definitions and comparable assessments. Prospective studies and the standard application of validated assessments are needed to build an evidence base guiding standards of care for infants and children with RS

Using seabird and whale distribution models to estimate spatial consumption of krill to inform fishery management

Ecosystem dynamics at the northwest Antarctic Peninsula are driven by interactions between physical and biological processes. For example, baleen whale populations are recovering from commercial harvesting against the backdrop of rapid climate change, including reduced sea ice extent and changing ecosystem composition. Concurrently, the commercial harvesting of Antarctic krill is increasing, with the potential to increase the likelihood for competition with and between krill predators and the fishery. However, understanding the ecology, abundance, and spatial distribution of krill predators is often limited, outdated, or at spatial scales that do not match those desired for effective fisheries management. We update current knowledge of predator dependence on krill by integrating telemetry-based data, at-sea observational surveys, estimates of predator abundance, and physiological data to estimate the spatial distribution of krill consumption during the austral summer by three species of Pygoscelis penguin, 11 species of flying seabirds, one species of pinniped, and two species of baleen whale. Our models show that the majority of important areas for krill predator foraging are close to penguin breeding colonies in nearshore areas where humpback whales also regularly feed, and along the shelf-break, though we caution that not all known krill predators are included in these analyses. We show that krill consumption is highly variable across the region, and often concentrated at fine spatial scales, emphasizing the need for the management of the local krill fishery at relevant temporal and spatial scales. We also note that krill consumption by recovering populations of krill predators provides further evidence in support of the krill surplus hypothesis, and highlight that despite less than comprehensive data, cetaceans are likely to consume a significant proportion of the krill consumed by natural predators but are not currently considered directly in the management of the krill fishery. If management of the krill fishery is to be precautionary and operate in a way that minimizes the risks to krill predator populations, it will be necessary in future analyses, to include up-to-date and precise abundance and consumption estimates for pack-ice seals, finfish, squid, and other baleen whale species not currently considered