The Two Roads to "Intrinsic Charm" in B Decays

We describe two complementary ways to show the presence of higher order effects in the 1/m_Q expansion for inclusive B decays that have been dubbed "Intrinsic Charm". Apart from the lessons they can teach us about QCD's nonperturbative dynamics their consideration is relevant for precise extractions of |V_{cb}|: for they complement the estimate of the potential impact of 1/m_Q^4 contributions. We draw semiquantitative conclusions for the expected scale of Weak Annihilation in semileptonic B decays, both for its valence and non-valence components.Comment: 17 pages, 3 figure

The significance of planning and management of the subsurface to achieve sustainable cities

Introduction: The subsurface is the foundation upon which all cities rest. But the subsurface is not only a construction basis which provide physical space for infrastructure and the possibility to create a better surface living environment: the subsurface is a multifunctional natural resource. Apart from physical space, it provides water, energy, materials, habitats for ecosystems, support for surface life, and a repository for cultural heritage and geological archives. Currently, the subsurface is often utilised according to the “first-come-first-served” principle, which hinders possibilities to take strategic decisions on prioritisation and optimisation of competing subsurface uses, as well as fair inter- and intragenerational distribution of limited natural resources. A great disadvantage is the invisibility of the subsurface and consequently a lack of understanding of it as a multifunctional resource: the recently launched concept of geosystem services could help mitigate its underrating. Methods: In order to better acknowledge and lift forward the significance of the subsurface in achieving a sustainable future, the 17 SDGs are scrutinized in relation to the resources of subsurface, and specifically how better planning and management of the subsurface can contribute in achieving the goals. Results: Subsurface planning and management is relevant to at least seven (3, 6, 7, 9, 11, 12, 13) out of seventeen SDGs. Although the subsurface is not explicitly mentioned in the SDGs (except for aquifers), the subsurface can significantly contribute in achieving several of these goals. Conclusions: Sound planning and management of the subsurface can support the achievement of the mapped SDGs in various ways. The subsurface must be recognised as a precious and multifunctional resource which require careful planning and sensitive management in accordance with its potential and its value to society.Grant support: Swedish Research Council Formas (942-2016-50), Swedish Rock Engineering Research Foundation (BeFo 385), Swedish Institute Visby Programme (23887/2017)

Weather in stellar atmosphere: the dynamics of mercury clouds in alpha Andromedae

The formation of long-lasting structures at the surfaces of stars is commonly ascribed to the action of strong magnetic fields. This paradigm is supported by observations of evolving cool spots in the Sun and active late-type stars, and stationary chemical spots in the early-type magnetic stars. However, results of our seven-year monitoring of mercury spots in non-magnetic early-type star alpha Andromedae show that the picture of magnetically-driven structure formation is fundamentally incomplete. Using an indirect stellar surface mapping technique, we construct a series of 2-D images of starspots and discover a secular evolution of the mercury cloud cover in this star. This remarkable structure formation process, observed for the first time in any star, is plausibly attributed to a non-equilibrium, dynamical evolution of the heavy-element clouds created by atomic diffusion and may have the same underlying physics as the weather patterns on terrestrial and giant planets.Comment: 10 pages, 2 figures; to be published in Nature Physic

Arterial line pressure control enhanced extracorporeal blood flow prescription in hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>In hemodialysis, extracorporeal blood flow (Qb) recommendation is 300–500 mL/min. To achieve the best Qb, we based our prescription on dynamic arterial line pressure (DALP).</p> <p>Methods</p> <p>This prospective study included 72 patients with catheter Group 1 (G1), 1877 treatments and 35 arterio-venous (AV) fistulae Group 2 (G2), 1868 treatments. The dialysis staff was trained to prescribe Qb sufficient to obtain DALP between -200 to -250 mmHg. We measured ionic clearance (IK: mL/min), access recirculation, DALP (mmHg) and Qb (mL/min). Six prescription zones were identified: from an optimal A zone (Qb > 400, DALP -200 to -250) to zones with lower Qb E (Qb < 300, DALP -200 to -250) and F (Qb < 300, DALP > -199).</p> <p>Results</p> <p>Treatments distribution in A was 695 (37%) in G1 vs. 704 (37.7%) in G2 (<it>P </it>= 0.7). In B 150 (8%) in G1 vs. 458 (24.5%) in G2 (<it>P </it>< 0.0001). Recirculation in A was 10.0% (Inter quartile rank, IQR 6.5, 14.2) in G1 vs. 9.8% (IQR 7.5, 14.1) in G2 (<it>P </it>= 0.62). IK in A was 214 ± 34 (G1) vs. 213 ± 35 (G2) (<it>P </it>= 0.65). IK Anova between G2 zones was: A vs. C and D (<it>P </it>< 0.000001). Staff prescription adherence was 81.3% (G1) vs. 84.1% (G2) (<it>P </it>= 0.02).</p> <p>Conclusion</p> <p>In conclusion, an optimal Qb can de prescribed with DALP of -200 mmHg. Staff adherence to DLAP treatment prescription could be reached up to 81.3% in catheters and 84.1% in AV fistulae.</p

Function and Regulation of Vibrio campbellii Proteorhodopsin: Acquired Phototrophy in a Classical Organoheterotroph

Proteorhodopsins (PRs) are retinal-binding photoproteins that mediate light-driven proton translocation across prokaryotic cell membranes. Despite their abundance, wide distribution and contribution to the bioenergy budget of the marine photic zone, an understanding of PR function and physiological significance in situ has been hampered as the vast majority of PRs studied to date are from unculturable bacteria or culturable species that lack the tools for genetic manipulation. In this study, we describe the presence and function of a horizontally acquired PR and retinal biosynthesis gene cluster in the culturable and genetically tractable bioluminescent marine bacterium Vibrio campbellii. Pigmentation analysis, absorption spectroscopy and photoinduction assays using a heterologous over-expression system established the V. campbellii PR as a functional green light absorbing proton pump. In situ analyses comparing PR expression and function in wild type (WT) V. campbellii with an isogenic ΔpR deletion mutant revealed a marked absence of PR membrane localization, pigmentation and light-induced proton pumping in the ΔpR mutant. Comparative photoinduction assays demonstrated the distinct upregulation of pR expression in the presence of light and PR-mediated photophosphorylation in WT cells that resulted in the enhancement of cellular survival during respiratory stress. In addition, we demonstrate that the master regulator of adaptive stress response and stationary phase, RpoS1, positively regulates pR expression and PR holoprotein pigmentation. Taken together, the results demonstrate facultative phototrophy in a classical marine organoheterotrophic Vibrio species and provide a salient example of how this organism has exploited lateral gene transfer to further its adaptation to the photic zone

Utility of Survival Motor Neuron ELISA for Spinal Muscular Atrophy Clinical and Preclinical Analyses

Genetic defects leading to the reduction of the survival motor neuron protein (SMN) are a causal factor for Spinal Muscular Atrophy (SMA). While there are a number of therapies under evaluation as potential treatments for SMA, there is a critical lack of a biomarker method for assessing efficacy of therapeutic interventions, particularly those targeting upregulation of SMN protein levels. Towards this end we have engaged in developing an immunoassay capable of accurately measuring SMN protein levels in blood, specifically in peripheral blood mononuclear cells (PBMCs), as a tool for validating SMN protein as a biomarker in SMA.A sandwich enzyme-linked immunosorbent assay (ELISA) was developed and validated for measuring SMN protein in human PBMCs and other cell lysates. Protocols for detection and extraction of SMN from transgenic SMA mouse tissues were also developed.The assay sensitivity for human SMN is 50 pg/mL. Initial analysis reveals that PBMCs yield enough SMN to analyze from blood volumes of less than 1 mL, and SMA Type I patients' PBMCs show ∼90% reduction of SMN protein compared to normal adults. The ELISA can reliably quantify SMN protein in human and mouse PBMCs and muscle, as well as brain, and spinal cord from a mouse model of severe SMA.This SMN ELISA assay enables the reliable, quantitative and rapid measurement of SMN in healthy human and SMA patient PBMCs, muscle and fibroblasts. SMN was also detected in several tissues in a mouse model of SMA, as well as in wildtype mouse tissues. This SMN ELISA has general translational applicability to both preclinical and clinical research efforts

Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair

Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase theta (Pol theta), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol theta contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol theta. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol theta can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol theta and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance

Guiding principles for the development and application of solid-phase phosphorus adsorbents for freshwater ecosystems

While a diverse array of phosphorus (P)-adsorbent materials is currently available for application to freshwater aquatic systems, selection of the most appropriate P-adsorbents remains problematic. In particular, there has to be a close correspondence between attributes of the P-adsorbent, its field performance, and the management goals for treatment. These management goals may vary from a rapid reduction in dissolved P to address seasonal enrichments from internal loading, targeting external fluxes due to anthropogenic sources, or long term inactivation of internal P inventories contained within bottom sediments. It also remains a challenge to develop new methods and materials that are ecologically benign and cost-effective. We draw on evidence in the literature and the authors’ personal experiences in the field, to summarise the attributes of a range of P-adsorbent materials. We offer 'guiding principles' to support practical use of existing materials and outline key development needs for new materials

HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality

Background Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3–8.8 million people (1.1–1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission