A Critical Role for Dna2 at Unwound Telomeres

Abstract Dna2 is a nuclease and helicase that functions redundantly with other proteins in Okazaki fragment processing, double-strand break resection, and checkpoint kinase activation. Dna2 is an essential enzyme, required for yeast and mammalian cell viability. Here, we report that numerous mutations affecting the DNA damage checkpoint suppress dna2∆ lethality in Saccharomyces cerevisiae. dna2∆ cells are also suppressed by deletion of helicases PIF1 and MPH1, and by deletion of POL32, a subunit of DNA polymerase δ. All dna2∆ cells are temperature sensitive, have telomere length defects, and low levels of telomeric 3′ single-stranded DNA (ssDNA). Interestingly, Rfa1, a subunit of the major ssDNA binding protein RPA, and the telomere-specific ssDNA binding protein Cdc13, often colocalize in dna2∆ cells. This suggests that telomeric defects often occur in dna2∆ cells. There are several plausible explanations for why the most critical function of Dna2 is at telomeres. Telomeres modulate the DNA damage response at chromosome ends, inhibiting resection, ligation, and cell-cycle arrest. We suggest that Dna2 nuclease activity contributes to modulating the DNA damage response at telomeres by removing telomeric C-rich ssDNA and thus preventing checkpoint activation.</jats:p

A Fiscal Union for the Euro: Some Lessons from History

The recent financial crisis 2007-2009 was the longest and the deepest recession since the Great Depression of 1930. The crisis that originated in subprime mortgage markets was spread and amplified through globalised financial markets and resulted in severe debt crises in several European countries in 2010 and 2011. Events revealed that the European Union had insufficient means to halt the spiral of European debt crisis. In particular, no pan-European fiscal mechanism to face a global crisis is available at present. The aim of this study is to identify the characteristics of a robust common fiscal policy framework that could have alleviated the consequences of the recent crisis. This is done by using the political and fiscal history of five federal states; Argentina, Brazil, Canada, Germany and the United States.

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Dust Devil Tracks

Dust devils that leave dark- or light-toned tracks are common on Mars and they can also be found on the Earth’s surface. Dust devil tracks (hereinafter DDTs) are ephemeral surface features with mostly sub-annual lifetimes. Regarding their size, DDT widths can range between ∼1 m and ∼1 km, depending on the diameter of dust devil that created the track, and DDT lengths range from a few tens of meters to several kilometers, limited by the duration and horizontal ground speed of dust devils. DDTs can be classified into three main types based on their morphology and albedo in contrast to their surroundings; all are found on both planets: (a) dark continuous DDTs, (b) dark cycloidal DDTs, and (c) bright DDTs. Dark continuous DDTs are the most common type on Mars. They are characterized by their relatively homogenous and continuous low albedo surface tracks. Based on terrestrial and martian in situ studies, these DDTs most likely form when surficial dust layers are removed to expose larger-grained substrate material (coarse sands of ≥500 μm in diameter). The exposure of larger-grained materials changes the photometric properties of the surface; hence leading to lower albedo tracks because grain size is photometrically inversely proportional to the surface reflectance. However, although not observed so far, compositional differences (i.e., color differences) might also lead to albedo contrasts when dust is removed to expose substrate materials with mineralogical differences. For dark continuous DDTs, albedo drop measurements are around 2.5 % in the wavelength range of 550–850 nm on Mars and around 0.5 % in the wavelength range from 300–1100 nm on Earth. The removal of an equivalent layer thickness around 1 μm is sufficient for the formation of visible dark continuous DDTs on Mars and Earth. The next type of DDTs, dark cycloidal DDTs, are characterized by their low albedo pattern of overlapping scallops. Terrestrial in situ studies imply that they are formed when sand-sized material that is eroded from the outer vortex area of a dust devil is redeposited in annular patterns in the central vortex region. This type of DDT can also be found in on Mars in orbital image data, and although in situ studies are lacking, terrestrial analog studies, laboratory work, and numerical modeling suggest they have the same formation mechanism as those on Earth. Finally, bright DDTs are characterized by their continuous track pattern and high albedo compared to their undisturbed surroundings. They are found on both planets, but to date they have only been analyzed in situ on Earth. Here, the destruction of aggregates of dust, silt and sand by dust devils leads to smooth surfaces in contrast to the undisturbed rough surfaces surrounding the track. The resulting change in photometric properties occurs because the smoother surfaces have a higher reflectance compared to the surrounding rough surface, leading to bright DDTs. On Mars, the destruction of surficial dust-aggregates may also lead to bright DDTs. However, higher reflective surfaces may be produced by other formation mechanisms, such as dust compaction by passing dust devils, as this may also cause changes in photometric properties. On Mars, DDTs in general are found at all elevations and on a global scale, except on the permanent polar caps. DDT maximum areal densities occur during spring and summer in both hemispheres produced by an increase in dust devil activity caused by maximum insolation. Regionally, dust devil densities vary spatially likely controlled by changes in dust cover thicknesses and substrate materials. This variability makes it difficult to infer dust devil activity from DDT frequencies. Furthermore, only a fraction of dust devils leave tracks. However, DDTs can be used as proxies for dust devil lifetimes and wind directions and speeds, and they can also be used to predict lander or rover solar panel clearing events. Overall, the high DDT frequency in many areas on Mars leads to drastic albedo changes that affect large-scale weather patterns

Effective team working in health care

In this chapter we show that team working is vital for high quality health care but that team working is often poor. We draw on research to show that effective team working is associated with fewer errors that harm staff and patients; fewer staff injuries; better staff well-being; higher levels of patient satisfaction; better quality of care; and lower patient mortality. “Pseudo team working” leads to the opposite outcomes. We describe how effective team based working can be developed and identify the importance of team objectives and leadership. The chapter describes the specific challenges for team working in health care, including the complexity of the context and the historical legacy of separate professional development and status hierarchies. We explore how these challenges can be overcome, arguing that ensuring effective team working in health care is critical to ensuring the delivery of high quality, continually improving and compassionate health care.</p

Possible remnants of a frozen mud lake in southern Elysium, Mars

In this work we estimate the minimum persistence time of subsurface ice in water rich sediment layers remaining after sublimation of a martian lake. We simulate sublimation of ice from layers of different granulations and thicknesses. Presented results assume insolation and atmospheric conditions characteristic for the present day southern Elysium, where data from Mars Express have identified surface features possibly indicating the very recent presence of a frozen body of water [Murray et al., 2005. Nature 434, 352–356]. The age of these features is estimated to be several million years. On this time scale, we find that most of the water ice must have sublimated away, however remnant ice at a few percent level cannot be excluded. This amount of water ice is sufficient for chemical cementation of the observed features and explains their relatively pristine appearance, without significant signs of erosion

Registration of MRI and iUS data to compensate brain shift using a symmetric block-matching based approach

This paper describes the application of an established block-matching based registration approach to the CuRIOUS 2018 MICCAI registration challenge. Different variations of this method are compared to demonstrate possible results of a fully automatic and general approach. The results can be used as a reference, for example when evaluating the performance of methods that are specifically developed for ultrasound to MRI registration.</p

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Poly(styrene-co-butadiene) Random Copolymer Thin Films and Nanostructures on a Mica Surface: Morphology and Contact Angles of Nanodroplets

The self-assembly of poly(styrene-co-butadiene) random copolymers on mica surfaces was studied by varying solution concentrations and polymer molecular weights. Toluene solutions of the poly(styrene-co-butadiene) samples were spin coated onto a mica surface and the resulting polymer morphology was investigated by atomic force microscopy. At higher concentrations, thin films formed with varying thicknesses; some dewetting was observed which depended on molecular weight. Total dewetting did not occur despite the polymer’s low glass transition temperature. Instead, partial dewetting was observed suggesting the polymer was in a metastable equilibrium state. At lower concentrations, spherical cap shaped nanodroplets formed with varying sizes from single polymer chains to aggregates containing millions of chains. As molecular weight was increased, fewer aggregates were observed on the surface, albeit with larger sizes resulting from increased solution viscosities and more chain entanglements at higher molecular weights. The contact angles of the nanodroplets were shown to be size dependent. A minimum contact angle occurs for droplets with radii of 100 nm – 250 nm at each molecular weight. Droplets smaller than 100 nm showed a sharp increase in contact angle; attributed to an increase in elastic modulus of the droplets, in addition, to a positive line tension value. Droplets larger than 250 nm also showed an increased contact angle due to surface heterogeneities which cannot be avoided for larger droplets. This increase in contact angle plateaus as the droplet size reaches the macroscopic scale