On mesh quality considerations for the discontinuous Galerkin method

It is widely accepted that the accuracy and efficiency of computational fluid dynamics (CFD) simulations is heavily influenced by the quality of the mesh upon which the solution is computed. Unfortunately, the computational tools available for assessing mesh quality remain rather limited. This report describes a methodology for rigorously investigating the interaction between a flow solver and a variety of mesh configurations for the purposes of deducing which mesh properties produce the best results from the solver. The techniques described herein permit a more detailed exploration of what constitutes a quality mesh in the context of a given solver and a desired flow regime. In the present work, these newly developed tools are used to investigate mesh quality as it pertains to a high-order accurate discontinuous Galerkin solver when it is used to compute inviscid and high-Reynolds number flows in domains possessing smoothly curving boundaries. For this purpose, two flow models have been generated and used to conduct parametric studies of mesh configurations involving curved elements. The results of these studies allow us to make some observations regarding mesh quality when the discontinuous Galerkin method is used to solve these types of problems. Briefly, we have found that for inviscid problems, the mesh elements used to resolve curved boundaries should be at least third order accurate. For viscous problems, the domain boundaries must be approximated by mesh elements that are of the same order as the polynomial approximation of the solution if the theoretical order of accuracy of the scheme is to be maintained. Increasing the accuracy of the boundary elements to at least one order higher than the solution approximation typically results in a noticeable improvement in the computed error norms. It is also noted that C1-continuity of the mesh is not required at element interfaces along the boundary

Resolving genetic engineering signatures in yeast on-site with the MinION and iSeq

Generating an assembly that captures all of the genome and plasmid modifications resulting from metabolic engineering is essential for quality control, connecting genotype to phenotype, establishing and protecting intellectual property, and generating “ground truth” for monitoring potential release events. Furthermore, high quality de novo assemblies can be used to accurately determine the presence and function of metabolic engineering signatures in an unknown sample. Here, we use two new inexpensive sequencers, the Oxford Nanopore MinION and the Illumina iSeq, to enable fast acquisition of sequence on-site. We also use new processing algorithms to enable fast transformation of sequence information into a high-quality genome assembly. The resulting pipeline can generate de novo microbial genome assemblies that capture complete chromosomal pathways and episomal plasmids. We further extend the pipeline to resequence six nonconventional yeasts of interest for metabolic engineering. To establish the most accurate workflow, we evaluated four nanopore de novo assemblers and three polishing algorithms at varying genome coverage depths for the lab strain S. cerevisiae CEN.PK113-7D. Our results show that (1) nanopore genome coverage depth must be at least 40X, (2) Flye and Canu are currently the best assemblers due to their combination of structure, completeness, and accuracy, and (3) Illumina data is essential for polishing. Our final pipeline (Figure 1A) generated a better S. cerevisiae CEN.PK113-7D assembly than the publicly available reference genome. Please click Additional Files below to see the full abstract

Automation of a Positron-emission Tomography (PET) Radiotracer Synthesis Protocol for Clinical Production.

The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological targets and processes. However, the increasing number of different tracers creates challenges for their production at radiopharmacies. While historically it has been practical to dedicate a custom-configured radiosynthesizer and hot cell for the repeated production of each individual tracer, it is becoming necessary to change this workflow. Recent commercial radiosynthesizers based on disposable cassettes/kits for each tracer simplify the production of multiple tracers with one set of equipment by eliminating the need for custom tracer-specific modifications. Furthermore, some of these radiosynthesizers enable the operator to develop and optimize their own synthesis protocols in addition to purchasing commercially-available kits. In this protocol, we describe the general procedure for how the manual synthesis of a new PET tracer can be automated on one of these radiosynthesizers and validated for the production of clinical-grade tracers. As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [18F]Clofarabine ([18F]CFA), a PET tracer to measure in vivo deoxycytidine kinase (dCK) enzyme activity. Translating a manual synthesis involves breaking down the synthetic protocol into basic radiochemistry processes that are then translated into intuitive chemistry "unit operations" supported by the synthesizer software. These operations can then rapidly be converted into an automated synthesis program by assembling them using the drag-and-drop interface. After basic testing, the synthesis and purification procedure may require optimization to achieve the desired yield and purity. Once the desired performance is achieved, a validation of the synthesis is carried out to determine its suitability for the production of the radiotracer for clinical use

Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Brain dopamine, particularly in the nucleus accumbens, has been implicated in activational aspects of motivation and effort-related processes. Accumbens dopamine depletions reduce the tendency of rats to work for food, and alter effort-related decision making, but leave aspects of food motivation such as appetite intact. Recent evidence indicates that the purine neuromodulator adenosine, largely through actions on adenosine A2A receptors, also participates in regulating effort-related processes. Adenosine A2A antagonists can reverse the effects of dopamine D2 antagonists on effort-related choice, and intra- accumbens injections of adenosine A2A agonists produce effects that are similar to those induced by accumbens dopamine depletion or antagonism. These studies have implications for the understanding and treatment of energy-related disorders such as anergia and fatigue in psychiatry and neurology

A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria

Fragmentation Functions for Lepton Pairs

We calculate the fragmentation function for a light quark to decay into a lepton pair to leading order in the QCD coupling constant. In the formal definition of the fragmentation function, a QED phase must be included in the eikonal factor to guarantee QED gauge invariance. We find that the longitudinal polarization fraction is a decreasing function of the factorization scale, in accord with the intuitive expectation that the virtual photon should behave more and more like a real photon as the transverse momomentum of the fragmenting quark increases.Comment: 13 pages, 4 figures, normalization corrected, text abbreviate

Presentation and Treatment Outcomes of Liberian Children Age 5 Years and Under Diagnosed With Severe Malaria

Malaria is endemic in Liberia with a prevalence rate of up to 60% in some regions, and it has been a major cause of death in children under 5 years of age. Prior to the recent Ebola epidemic, we undertook a prospective, hospital-based pilot study at the National Referral Hospital in Monrovia, to characterize the presentation, accuracy of diagnosis, and treatment outcomes of children presenting for treatment of malaria. From June 2013 to May 2014, we recruited children 5 years and under who presented to the JFK Medical Center with suspected malaria. We collected both clinical and laboratory data on admission and on discharge. We enrolled 477 patients with an average age of 1.6 years. Demographic factors associated with testing negative for malaria included regular bed net use and prior treatment for malaria. The most common presenting symptoms of severe malaria in this population were headache and seizures. Of 246 patients admitted and treated for severe malaria, 33% tested negative by rapid diagnostic test and blood smear for malaria. The case fatality rate was higher for the patients who tested negative for malaria (4.9%) versus those who tested positive (0.6%). Three children who tested negative for malaria showed evidence of undiagnosed Salmonella typhi infection. These results suggest that malaria may be overdiagnosed and that the diagnoses of other infectious diseases, which present in a similar fashion, may be neglected. These findings underscore the need to develop rapid diagnostic tests to screen for alternative causes of febrile illness

Exponentiation of the Drell-Yan cross section near partonic threshold in the DIS and MSbar schemes

It has been observed that in the DIS scheme the refactorization of the Drell-Yan cross section leading to exponentiation of threshold logarithms can also be used to organize a class of constant terms, most of which arise from the ratio of the timelike Sudakov form factor to its spacelike counterpart. We extend this exponentiation to include all constant terms, and demonstrate how a similar organization may be achieved in the MSbar scheme. We study the relevance of these exponentiations in a two-loop analysis.Comment: 20 pages, JHEP style, no figure