The CLIC Programme: Towards a Staged e+e- Linear Collider Exploring the Terascale : CLIC Conceptual Design Report

This report describes the exploration of fundamental questions in particle physics at the energy frontier with a future TeV-scale e+e- linear collider based on the Compact Linear Collider (CLIC) two-beam acceleration technology. A high-luminosity high-energy e+e- collider allows for the exploration of Standard Model physics, such as precise measurements of the Higgs, top and gauge sectors, as well as for a multitude of searches for New Physics, either through direct discovery or indirectly, via high-precision observables. Given the current state of knowledge, following the observation of a 125 GeV Higgs-like particle at the LHC, and pending further LHC results at 8 TeV and 14 TeV, a linear e+e- collider built and operated in centre-of-mass energy stages from a few-hundred GeV up to a few TeV will be an ideal physics exploration tool, complementing the LHC. In this document, an overview of the physics potential of CLIC is given. Two example scenarios are presented for a CLIC accelerator built in three main stages of 500 GeV, 1.4 (1.5) TeV, and 3 TeV, together with operating schemes that will make full use of the machine capacity to explore the physics. The accelerator design, construction, and performance are presented, as well as the layout and performance of the experiments. The proposed staging example is accompanied by cost estimates of the accelerator and detectors and by estimates of operating parameters, such as power consumption. The resulting physics potential and measurement precisions are illustrated through detector simulations under realistic beam conditions.Comment: 84 pages, published as CERN Yellow Report https://cdsweb.cern.ch/record/147522

Proton and cadmium adsorption by the archaeon Thermococcus zilligii: Generalising the contrast between thermophiles and mesophiles as sorbents

Adsorption by microorganisms can play a significant role in the fate and transport of metals in natural systems. Surface complexation models (SCMs) have been applied extensively to describe metal adsorption by mesophilic bacteria, and several recent studies have extended this framework to thermophilic bacteria. We conduct acid-base titrations and batch experiments to characterise proton and Cd adsorption onto the thermophilic archaeon Thermococcus zilligii. The experimental data and the derived SCMs indicate that the archaeon displays significantly lower overall sorption site density compared to previously studied thermophilic bacteria such Anoxybacillus flavithermus, Geobacillus stearothermophilus, G. thermocatenulatus, and Thermus thermophilus. The thermophilic bacteria and archaea display lower sorption site densities than the mesophilic microorganisms that have been studied to date, which points to a general pattern of total concentration of cell wall adsorption sites per unit biomass being inversely correlated to growth temperature

Severe dialyzer dysfunction undetectable by standard reprocessing validation tests

Severe dialyzer dysfunction undetectable by standard reprocessing validation tests. It is generally accepted that careful monitoring of total cell volume and ultrafiltration rates will ensure adequate function of reprocessed dialyzers. During routine urea kinetic measurements we noted that the percent of patients with clearances less than 200ml/min increased from 5% to 48% despite adherence to these validation tests. As these patients did not have evidence of recirculation in the vascular access, possible causes of dialyzer dysfunction were investigated. Injection of methylene blue into the dialysate port revealed non-uniform flow of dialysate in dialyzers from patients with markedly reduced clearances. In vitro studies of dialyzers subjected to sequential daily reprocessing, without patient exposure, demonstrated that in vitro clearances declined in one lot but not another. The initial clearances of 218 ± 4ml/min fell progressively to 112 ± 18 (P < 0.001) after 15 reuses. No effects of reprocessing were found in a different lot (230 ± 2 vs. 226 ± 4 ml/min). Soaking the dialyzers from the affected lot in either the disinfectant or dialysate solution caused a decline in the clearances which was less than that of serial reuse. Although the magnitude of the problem of dialyzer malfunction with reuse is unknown, careful attention to dialyzer function is warranted in patients treated with reprocessed dialyzers

Contribution of potential evaporation forecasts to 10-day streamflow forecast skill for the Rhine River

Medium-term hydrologic forecast uncertainty is strongly dependent on the forecast quality of meteorological variables. Of these variables, the influence of precipitation has been studied most widely, while temperature, radiative forcing and their derived product potential evapotranspiration (PET) have received little attention from the perspective of hydrological forecasting. This study aims to fill this gap by assessing the usability of potential evaporation forecasts for 10-day-ahead streamflow forecasting in the Rhine basin, Europe. In addition, the forecasts of the meteorological variables are compared with observations. Streamflow reforecasts were performed with the daily wflow_hbv model used in previous studies of the Rhine using the ECMWF 20-year meteorological reforecast dataset. Meteorological forecasts were compared with observed rainfall, temperature, global radiation and potential evaporation for 148 subbasins. Secondly, the effect of using PET climatology versus using observation-based estimates of PET was assessed for hydrological state and for streamflow forecast skill. We find that (1) there is considerable skill in the ECMWF reforecasts to predict PET for all seasons, and (2) using dynamical PET forcing based on observed temperature and satellite global radiation estimates results in lower evaporation and wetter initial states, but (3) the effect on forecasted 10-day streamflow is limited. Implications of this finding are that it is reasonable to use meteorological forecasts to forecast potential evaporation and use this is in medium-range streamflow forecasts. However, it can be concluded that an approach using PET climatology is also sufficient, most probably not only for the application shown here, but also for most models similar to the HBV concept and for moderate climate zones. As a by-product, this research resulted in gridded datasets for temperature, radiation and potential evaporation based on the Makkink equation for the Rhine basin. The datasets have a spatial resolution of 1.2×1.2&thinsp;km and an hourly time step for the period from July 1996 through 2015. This dataset complements an earlier precipitation dataset for the same area, period and resolution.</p

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.Peer reviewe

Distributed Evaluation of Local Sensitivity Analysis (DELSA), with application to hydrologic models

This is the published version. Copyright 2014 American Geophysical UnionThis paper presents a hybrid local-global sensitivity analysis method termed the Distributed Evaluation of Local Sensitivity Analysis (DELSA), which is used here to identify important and unimportant parameters and evaluate how model parameter importance changes as parameter values change. DELSA uses derivative-based “local” methods to obtain the distribution of parameter sensitivity across the parameter space, which promotes consideration of sensitivity analysis results in the context of simulated dynamics. This work presents DELSA, discusses how it relates to existing methods, and uses two hydrologic test cases to compare its performance with the popular global, variance-based Sobol' method. The first test case is a simple nonlinear reservoir model with two parameters. The second test case involves five alternative “bucket-style” hydrologic models with up to 14 parameters applied to a medium-sized catchment (200 km2) in the Belgian Ardennes. Results show that in both examples, Sobol' and DELSA identify similar important and unimportant parameters, with DELSA enabling more detailed insight at much lower computational cost. For example, in the real-world problem the time delay in runoff is the most important parameter in all models, but DELSA shows that for about 20% of parameter sets it is not important at all and alternative mechanisms and parameters dominate. Moreover, the time delay was identified as important in regions producing poor model fits, whereas other parameters were identified as more important in regions of the parameter space producing better model fits. The ability to understand how parameter importance varies through parameter space is critical to inform decisions about, for example, additional data collection and model development. The ability to perform such analyses with modest computational requirements provides exciting opportunities to evaluate complicated models as well as many alternative models

The benefits of spatial resolution increase in global simulations of the hydrological cycle evaluated for the Rhine and Mississippi basins

To study the global hydrological cycle and its response to a changing climate, we rely on global climate models (GCMs) and global hydrological models (GHMs). The spatial resolution of these models is restricted by computational resources and therefore limits the processes and level of detail that can be resolved. Increase in computer power therefore permits increase in resolution, but it is an open question where this resolution is invested best: in the GCM or GHM. In this study, we evaluated the benefits of increased resolution, without modifying the representation of physical processes in the models. By doing so, we can evaluate the benefits of resolution alone. We assess and compare the benefits of an increased resolution for a GCM and a GHM for two basins with long observational records: the Rhine and Mississippi basins. Increasing the resolution of a GCM (1.125 to 0.25∘) results in an improved precipitation budget over the Rhine basin, attributed to a more realistic large-scale circulation. These improvements with increased resolution are not found for the Mississippi basin, possibly because precipitation is strongly dependent on the representation of still unresolved convective processes. Increasing the resolution of the GCM improved the simulations of the monthly-averaged discharge for the Rhine, but did not improve the representation of extreme streamflow events. For the Mississippi basin, no substantial differences in precipitation and discharge were found with the higher-resolution GCM and GHM. Increasing the resolution of parameters describing vegetation and orography in the high-resolution GHM (from 0.5 to 0.05∘) shows no significant differences in discharge for both basins. A straightforward resolution increase in the GHM is thus most likely not the best method to improve discharge predictions, which emphasizes the need for better representation of processes and improved parameterizations that go hand in hand with resolution increase in a GHM.</p

Polysaccharide Biosynthesis: Glycosyltransferases and Their Complexes

Glycosyltransferases (GTs) are enzymes that catalyze reactions attaching an activated sugar to an acceptor substrate, which may be a polysaccharide, peptide, lipid, or small molecule. In the past decade, notable progress has been made in revealing and cloning genes encoding polysaccharide-synthesizing GTs. However, the vast majority of GTs remain structurally and functionally uncharacterized. The mechanism by which they are organized in the Golgi membrane, where they synthesize complex, highly branched polysaccharide structures with high efficiency and fidelity, is also mostly unknown. This review will focus on current knowledge about plant polysaccharide-synthesizing GTs, specifically focusing on protein-protein interactions and the formation of multiprotein complexes

Global re-analysis datasets to improve hydrological assessment and snow water equivalent estimation in a sub-Arctic watershed

Hydrological modelling in the Canadian sub-Arctic is hindered by sparse meteorological and snowpack data. The snow water equivalent (SWE) of the winter snowpack is a key predictor and driver of spring flow, but the use of SWE data in hydrological applications is limited due to high uncertainty. Global re-analysis datasets that provide gridded meteorological and SWE data may be well suited to improve hydrological assessment and snowpack simulation. To investigate representation of hydrological processes and SWE for application in hydropower operations, global re-analysis datasets covering 1979–2014 from the European Union FP7 eartH2Observe project are applied to global and local conceptual hydrological models. The recently developed Multi-Source Weighted-Ensemble Precipitation (MSWEP) and the WATCH Forcing Data applied to ERA-Interim data (WFDEI) are used to simulate snowpack accumulation, spring snowmelt volume and annual streamflow. The GlobSnow-2 SWE product funded by the European Space Agency with daily coverage from 1979 to 2014 is evaluated against in situ SWE measurement over the local watershed. Results demonstrate the successful application of global datasets for streamflow prediction, snowpack accumulation and snowmelt timing in a snowmelt-driven sub-Arctic watershed. The study was unable to demonstrate statistically significant correlations (p &lt; 0.05) among the measured snowpack, global hydrological model and GlobSnow-2 SWE compared to snowmelt runoff volume or peak discharge. The GlobSnow-2 product is found to under-predict late-season snowpacks over the study area and shows a premature decline of SWE prior to the true onset of the snowmelt. Of the datasets tested, the MSWEP precipitation results in annual SWE estimates that are better predictors of snowmelt volume and peak discharge than the WFDEI or GlobSnow-2. This study demonstrates the operational and scientific utility of the global re-analysis datasets in the sub-Arctic, although knowledge gaps remain in global satellite-based datasets for snowpack representation, for example the relationship between passive-microwave-measured SWE to snowmelt runoff volume.</p