Coercion-resistant Proxy Voting

In general, most elections follow the principle of equality, or as it came to be known, the principle of “one man – one vote”. However, this principle might pose difficulties for voters, who are not well informed regarding the particular matter that is voted on. In order to address this issue, a new form of voting has been proposed, namely proxy voting. In proxy voting, each voter has the possibility to delegate her voting right to another voter, so called proxy, that she considers a trusted expert on the matter. In this paper we propose an end-to-end verifiable Internet voting scheme, which to the best of our knowledge is the first scheme to address voter coercion in the proxy voting setting

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study

Background Previous studies on childhood cancer and nuclear power plants (NPPs) produced conflicting results. We used a cohort approach to examine whether residence near NPPs was associated with leukaemia or any childhood cancer in Switzerland

Mathematical Formulation Requirements and Specifications for the Process Models

The Advanced Simulation Capability for Environmental Management (ASCEM) is intended to be a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The ASCEM program is aimed at addressing critical EM program needs to better understand and quantify flow and contaminant transport behavior in complex geological systems. It will also address the long-term performance of engineered components including cementitious materials in nuclear waste disposal facilities, in order to reduce uncertainties and risks associated with DOE EM's environmental cleanup and closure activities. Building upon national capabilities developed from decades of Research and Development in subsurface geosciences, computational and computer science, modeling and applied mathematics, and environmental remediation, the ASCEM initiative will develop an integrated, open-source, high-performance computer modeling system for multiphase, multicomponent, multiscale subsurface flow and contaminant transport. This integrated modeling system will incorporate capabilities for predicting releases from various waste forms, identifying exposure pathways and performing dose calculations, and conducting systematic uncertainty quantification. The ASCEM approach will be demonstrated on selected sites, and then applied to support the next generation of performance assessments of nuclear waste disposal and facility decommissioning across the EM complex. The Multi-Process High Performance Computing (HPC) Simulator is one of three thrust areas in ASCEM. The other two are the Platform and Integrated Toolsets (dubbed the Platform) and Site Applications. The primary objective of the HPC Simulator is to provide a flexible and extensible computational engine to simulate the coupled processes and flow scenarios described by the conceptual models developed using the ASCEM Platform. The graded and iterative approach to assessments naturally generates a suite of conceptual models that span a range of process complexity, potentially coupling hydrological, biogeochemical, geomechanical, and thermal processes. The Platform will use ensembles of these simulations to quantify the associated uncertainty, sensitivity, and risk. The Process Models task within the HPC Simulator focuses on the mathematical descriptions of the relevant physical processes

The exported protein PbCP1 localises to cleft-like structures in the rodent malaria parasite Plasmodium berghei

Protein export into the host red blood cell is one of the key processes in the pathobiology of the malaria parasite Plasmodiumtrl falciparum, which extensively remodels the red blood cell to ensure its virulence and survival. In this study, we aimed to shed further light on the protein export mechanisms in the rodent malaria parasite P. berghei and provide further proof of the conserved nature of host cell remodeling in Plasmodium spp. Based on the presence of an export motif (R/KxLxE/Q/D) termed PEXEL (Plasmodium export element), we have generated transgenic P. berghei parasite lines expressing GFP chimera of putatively exported proteins and analysed one of the newly identified exported proteins in detail. This essential protein, termed PbCP1 (P. berghei Cleft-like Protein 1), harbours an atypical PEXEL motif (RxLxY) and is further characterised by two predicted transmembrane domains (2TMD) in the C-terminal end of the protein. We have functionally validated the unusual PEXEL motif in PbCP1 and analysed the role of the 2TMD region, which is required to recruit PbCP1 to discrete membranous structures in the red blood cell cytosol that have a convoluted, vesico-tubular morphology by electron microscopy. Importantly, this study reveals that rodent malaria species also induce modifications to their host red blood cell

Mediator of DNA Damage Checkpoint 1 (MDC1) Contributes to High NaCl-Induced Activation of the Osmoprotective Transcription Factor TonEBP/OREBP

Background: Hypertonicity, such as induced by high NaCl, increases the activity of the transcription factor TonEBP/OREBP whose target genes increase osmoprotective organic osmolytes and heat shock proteins. Methodology: We used mass spectrometry to analyze proteins that coimmunoprecipitate with TonEBP/OREBP in order to identify ones that might contribute to its high NaCl-induced activation. Principal Findings: We identified 20 unique peptides from Mediator of DNA Damage Checkpoint 1 (MDC1) with high probability. The identification was confirmed by Western analysis. We used small interfering RNA knockdown of MDC1 to characterize its osmotic function. Knocking down MDC1 reduces high NaCl-induced increases in TonEBP/OREBP transcriptional and transactivating activity, but has no significant effect on its nuclear localization. We confirm six previously known phosphorylation sites in MDC1, but do not find evidence that high NaCl increases phosphorylation of MDC1. It is suggestive that MDC1 acts as a DNA damage response protein since hypertonicity reversibly increases DNA breaks, and other DNA damage response proteins, like ATM, also associate with TonEBP/OREBP and contribute to its activation by hypertonicity. Conclusions/Significance: MDC1 associates with TonEBP/OREBP and contributes to high NaCl-induced increase of tha

Selective Condensation Drives Partitioning and Sequential Secretion of Cyst Wall Proteins in Differentiating Giardia lamblia

Controlled secretion of a protective extracellular matrix is required for transmission of the infective stage of a large number of protozoan and metazoan parasites. Differentiating trophozoites of the highly minimized protozoan parasite Giardia lamblia secrete the proteinaceous portion of the cyst wall material (CWM) consisting of three paralogous cyst wall proteins (CWP1–3) via organelles termed encystation-specific vesicles (ESVs). Phylogenetic and molecular data indicate that Diplomonads have lost a classical Golgi during reductive evolution. However, neogenesis of ESVs in encysting Giardia trophozoites transiently provides basic Golgi functions by accumulating presorted CWM exported from the ER for maturation. Based on this “minimal Golgi” hypothesis we predicted maturation of ESVs to a trans Golgi-like stage, which would manifest as a sorting event before regulated secretion of the CWM. Here we show that proteolytic processing of pro-CWP2 in maturing ESVs coincides with partitioning of CWM into two fractions, which are sorted and secreted sequentially with different kinetics. This novel sorting function leads to rapid assembly of a structurally defined outer cyst wall, followed by slow secretion of the remaining components. Using live cell microscopy we find direct evidence for condensed core formation in maturing ESVs. Core formation suggests that a mechanism controlled by phase transitions of the CWM from fluid to condensed and back likely drives CWM partitioning and makes sorting and sequential secretion possible. Blocking of CWP2 processing by a protease inhibitor leads to mis-sorting of a CWP2 reporter. Nevertheless, partitioning and sequential secretion of two portions of the CWM are unaffected in these cells. Although these cysts have a normal appearance they are not water resistant and therefore not infective. Our findings suggest that sequential assembly is a basic architectural principle of protective wall formation and requires minimal Golgi sorting functions

Geophysical monitoring and reactive transport modeling of ureolytically-driven calcium carbonate precipitation

Ureolytically-driven calcium carbonate precipitation is the basis for a promising in-situ remediation method for sequestration of divalent radionuclide and trace metal ions. It has also been proposed for use in geotechnical engineering for soil strengthening applications. Monitoring the occurrence, spatial distribution, and temporal evolution of calcium carbonate precipitation in the subsurface is critical for evaluating the performance of this technology and for developing the predictive models needed for engineering application. In this study, we conducted laboratory column experiments using natural sediment and groundwater to evaluate the utility of geophysical (complex resistivity and seismic) sensing methods, dynamic synchrotron x-ray computed tomography (micro-CT), and reactive transport modeling for tracking ureolytically-driven calcium carbonate precipitation processes under site relevant conditions. Reactive transport modeling with TOUGHREACT successfully simulated the changes of the major chemical components during urea hydrolysis. Even at the relatively low level of urea hydrolysis observed in the experiments, the simulations predicted an enhanced calcium carbonate precipitation rate that was 3-4 times greater than the baseline level. Reactive transport modeling results, geophysical monitoring data and micro-CT imaging correlated well with reaction processes validated by geochemical data. In particular, increases in ionic strength of the pore fluid during urea hydrolysis predicted by geochemical modeling were successfully captured by electrical conductivity measurements and confirmed by geochemical data. The low level of urea hydrolysis and calcium carbonate precipitation suggested by the model and geochemical data was corroborated by minor changes in seismic P-wave velocity measurements and micro-CT imaging; the latter provided direct evidence of sparsely distributed calcium carbonate precipitation. Ion exchange processes promoted through NH4+ production during urea hydrolysis were incorporated in the model and captured critical changes in the major metal species. The electrical phase increases were potentially due to ion exchange processes that modified charge structure at mineral/water interfaces. Our study revealed the potential of geophysical monitoring for geochemical changes during urea hydrolysis and the advantages of combining multiple approaches to understand complex biogeochemical processes in the subsurface