Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae. VI: The Sixth Year (2013-2014)

Continuing the project described by Kato et al. (2009, PASJ, 61, S395, arXiv:0905.1757), we collected times of superhump maxima for 56 SU UMa-type dwarf novae mainly observed during the 2013-2014 season and characterized these objects. We detected negative superhumps in VW Hyi and indicated that the low number of normal outbursts in some supercycle can be interpreted as a result of the disk tilt. This finding, combined with the Kepler observation of V1504 Cyg and V344 Lyr, suggests that the disk tilt is responsible for modulating the outburst pattern in SU UMa-type dwarf novae. We also studied the deeply eclipsing WZ Sge-type dwarf nova MASTER OT J005740.99+443101.5 and found evidence of a sharp eclipse during the phase of early superhumps. The profile can be reproduced by a combination of the eclipse of the axisymmetric disk and the uneclipsed light source of early superhumps. This finding confirms the lack of evince of a greatly enhanced hot spot during the early stage of WZ Sge-type outburst. We detected growing (stage A) superhumps in MN Dra and give a suggestion that some of SU UMa-type dwarf novae situated near the critical condition of tidal instability may show long-lasting stage A superhumps. The large negative period derivatives reported in such systems can be understood a result of the combination of stage A and B superhumps. The WZ Sge-type dwarf novae AL Com and ASASSN-13ck showed a long-lasting (plateau-type) rebrightening. In the early phase of the rebrightening, both objects showed a precursor-like outburst, suggesting that the long-lasting rebrightening is triggered by a precursor outburst.Comment: 73 pages, 88 figures, accepted for publication in PAS

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Negative Cross Resistance Mediated by Co-treated bed nets: A Potential Means of Restoring Pyrethroid-susceptibility to Malaria Vectors.

Insecticide-treated nets and indoor residual spray programs for malaria control are entirely dependent on pyrethroid insecticides. The ubiquitous exposure of Anopheles mosquitoes to this chemistry has selected for resistance in a number of populations. This threatens the sustainability of our most effective interventions but no operationally practicable way of resolving the problem currently exists. One innovative solution involves the co-application of a powerful chemosterilant (pyriproxyfen or PPF) to bed nets that are usually treated only with pyrethroids. Resistant mosquitoes that are unaffected by the pyrethroid component of a PPF/pyrethroid co-treatment remain vulnerable to PPF. There is a differential impact of PPF on pyrethroid-resistant and susceptible mosquitoes that is modulated by the mosquito's behavioural response at co-treated surfaces. This imposes a specific fitness cost on pyrethroid-resistant phenotypes and can reverse selection. The concept is demonstrated using a mathematical model

Ediacaran metazoan reveals lophotrochozoan affinity and deepens root of Cambrian Explosion

Through exceptional preservation, we establish a phylogenetic connection between Ediacaran and Cambrian metazoans. We describe the first three-dimensional, pyritized soft tissue in Namacalathus from the Ediacaran Nama Group, Namibia, which follows the underlying form of a stalked, cup-shaped, calcitic skeleton, with six radially arranged lobes projecting into an apical opening and lateral lumens. A thick body wall and probable J-shaped gut are present within the cup, and the middle layer of the often-spinose skeleton and skeletal pores are selectively pyritized, supporting an organic-rich composition and tripartite construction with possible sensory punctae. These features suggest a total group lophotrochozoan affinity. These morphological data support molecular phylogenies and demonstrates that the origin of modern lophotrochozoan phyla, and their ability to biomineralize, had deep roots in the Ediacaran

An economic evaluation of Alexander Technique lessons or acupuncture sessions for patients with chronic neck pain : A randomized trial (ATLAS)

OBJECTIVES: To assess the cost-effectiveness of acupuncture and usual care, and Alexander Technique lessons and usual care, compared with usual GP care alone for chronic neck pain patients. METHODS: An economic evaluation was undertaken alongside the ATLAS trial, taking both NHS and wider societal viewpoints. Participants were offered up to twelve acupuncture sessions or twenty Alexander lessons (equivalent overall contact time). Costs were in pounds sterling. Effectiveness was measured using the generic EQ-5D to calculate quality adjusted life years (QALYs), as well as using a specific neck pain measure-the Northwick Park Neck Pain Questionnaire (NPQ). RESULTS: In the base case analysis, incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander groups, respectively, in comparison to usual GP care, indicating moderate health benefits for both interventions. Incremental costs were £451 for acupuncture and £667 for Alexander, mainly driven by intervention costs. Acupuncture was likely to be cost-effective (ICER = £18,767/QALY bootstrapped 95% CI £4,426 to £74,562) and was robust to most sensitivity analyses. Alexander lessons were not cost-effective at the lower NICE threshold of £20,000/QALY (£25,101/QALY bootstrapped 95% CI -£150,208 to £248,697) but may be at £30,000/QALY, however, there was considerable statistical uncertainty in all tested scenarios. CONCLUSIONS: In comparison with usual care, acupuncture is likely to be cost-effective for chronic neck pain, whereas, largely due to higher intervention costs, Alexander lessons are unlikely to be cost-effective. However, there were high levels of missing data and further research is needed to assess the long-term cost-effectiveness of these interventions

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Europa Environmental Testing of Thermal Hardware for the Mapping Imaging Spectrometer for Europa (MISE) Instrument

The Europa Clipper spacecraft, scheduled for launch in June 2022, hosts a suite of instruments including the Mapping Imaging Spectrometer for Europa (MISE). MISE is a high-optical through-put push-broom infrared imaging spectrometer that can collect measurements within Europa’s challenging radiation environment. It is externally mounted to the spacecraft and as a result is exposed to high radiation levels and cold temperatures. The instrument consists of a scan mirror assembly, an optical bench including a Dyson spectrometer and a telescope, and a structure that supports a cryocooler and a radiator. The cryocooler is used to actively cool the focal plane array and the spectrometer. The heat from the cryocooler is rejected through pyrolytic graphite sheet thermal straps to a honeycomb radiator. MISE will implement thermal hardware that will either not be used on other parts of the spacecraft or have a more extreme environment than the spacecraft. As a result, the MISE instrument performed numerous environmental tests on its thermal hardware. This paper discusses the results of the thermal cycling and radiation tests performed on the MISE thermal hardware including a Lockheed Martin Micro1-2 cryocooler, Pyrolytic graphite sheet thermal straps, Annealed pyrolytic graphite K-Core, Rosemount Platinum Resistance Thermometers, Tayco Kapton Thermofoil heaters, MIL-PRF-18546 Vishay resistors and components of an aluminum honeycomb radiator

Diel surface temperature range scales with lake size

Ecological and biogeochemical processes in lakes are strongly dependent upon water temperature. Long-term surface warming of many lakes is unequivocal, but little is known about the comparative magnitude of temperature variation at diel timescales, due to a lack of appropriately resolved data. Here we quantify the pattern and magnitude of diel temperature variability of surface waters using high-frequency data from 100 lakes. We show that the near-surface diel temperature range can be substantial in summer relative to long-term change and, for lakes smaller than 3 km2, increases sharply and predictably with decreasing lake area. Most small lakes included in this study experience average summer diel ranges in their near-surface temperatures of between 4 and 7°C. Large diel temperature fluctuations in the majority of lakes undoubtedly influence their structure, function and role in biogeochemical cycles, but the full implications remain largely unexplored