Reconfigurable Systems: A Potential Solution to the von Neumann Bottleneck

The difficulty of overcoming the disparity between processor speeds and data access speeds, a condition known as the von Neumann bottleneck, has been a source of consternation for computer hardware developers for many years. Although a number of temporary solutions have been proposed and implemented in modern machines, these solutions have only managed to treat the major symptoms, rather than solve the root problem. As the number of transistors on a chip roughly doubles every two years, the von Neumann bottleneck has continued to tighten in spite of these solutions, prompting some computer hardware professionals to advocate a paradigm shift away from the von Neumann architecture into something entirely new. Many have begun advocating the relatively new technology of reconfigurable systems, popularly known as morphware. The difficulty with adopting a new architectural paradigm, however, is that developers on both sides of the software-hardware spectrum must start from scratch, creating entirely new operating systems, hardware peripherals, application software, and user interfaces, all of which must seem familiar to the end user, yet still take advantage of the improvements morphware has to offer. With this in mind, this thesis builds off of the fundamental theory and current implementations of morphware to describe the processes and products necessary to develop and deliver morphware to the average user as a viable alternative to current technology

The challenges of detecting subtle population structure and its importance for the conservation of emperor penguins

Understanding the boundaries of breeding populations is of great importance for conservation efforts and estimates of extinction risk for threatened species. However, determining these boundaries can be difficult when population structure is subtle. Emperor penguins are highly reliant on sea ice, and some populations may be in jeopardy as climate change alters sea-ice extent and quality. An understanding of emperor penguin population structure is therefore urgently needed. Two previous studies have differed in their conclusions, particularly whether the Ross Sea, a major stronghold for the species, is isolated or not. We assessed emperor penguin population structure using 4,596 genome-wide single nucleotide polymorphisms (SNPs), characterized in 110 individuals (10–16 per colony) from eight colonies around Antarctica. In contrast to a previous conclusion that emperor penguins are panmictic around the entire continent, we find that emperor penguins comprise at least four metapopulations, and that the Ross Sea is clearly a distinct metapopulation. Using larger sample sizes and a thorough assessment of the limitations of different analytical methods, we have shown that population structure within emperor penguins does exist and argue that its recognition is vital for the effective conservation of the species. We discuss the many difficulties that molecular ecologists and managers face in the detection and interpretation of subtle population structure using large SNP data sets, and argue that subtle structure should be taken into account when determining management strategies for threatened species, until accurate estimates of demographic connectivity among populations can be made.</p

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity. Hyperpolarized magnetic resonance imaging (MRI) can assess real-time metabolic fluxes in vivo. Here we show that cardiac functional decline in a clinically relevant rat-model of DOX-HF is preceded by a change in oxidative mitochondrial carbohydrate metabolism, measured by hyperpolarized MRI. The decreased metabolic fluxes were predominantly due to mitochondrial loss and additional mitochondrial dysfunction, and not, as widely assumed hitherto, to oxidative stress. Since hyperpolarized MRI has been successfully translated into clinical trials this opens up the potential to test cancer patients receiving DOX for early signs of cardiotoxicity

The Reproducibility of 31-Phosphorus MRS Measures of Muscle Energetics at 3 Tesla in Trained Men

Magnetic resonance spectroscopy (MRS) provides an exceptional opportunity for the study of in vivo metabolism. MRS is widely used to measure phosphorus metabolites in trained muscle, although there are no published data regarding its reproducibility in this specialized cohort. Thus, the aim of this study was to assess the reproducibility of (31)P-MRS in trained skeletal muscle

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Beliefs and practices of patients with advanced cancer: implications for communication

The aim of this study was to investigate the beliefs that patients with advanced cancer held about the curability of their cancer, their use of alternatives to conventional medical treatment, and their need to have control over decisions about treatment. Of 149 patients who fulfilled the criteria for participation and completed a self-administered questionnaire, 45 patients (31%) believed their cancer was incurable, 61 (42%) were uncertain and 39 (27%) believed their cancer was curable. The index of need for control over treatment decisions was low in 53 patients (35.6%) and high in only 17 patients (11.4%). Committed users of alternatives to conventional medical treatments were more likely to believe that their cancer was curable (

Fundamental movement skills are more than run, throw and catch: The role of stability skills.

Introduction In motor development literature fundamental movement skills are divided into three constructs: locomotive, object control and stability skills. Most fundamental movement skills research has focused on children's competency in locomotor and object control skills. The first aim of this study was to validate a test battery to assess the construct of stability skills, in children aged 6 to 10 (M age = 8.2, SD = 1.2). Secondly we assessed how the stability skills construct fitted into a model of fundamental movement skill. Method The Delphi method was used to select the stability skill battery. Confirmatory factor analysis (CFA) was used to assess if the skills loaded onto the same construct and a new model of FMS was developed using structural equation modelling. Results Three postural control tasks were selected (the log roll, rock and back support) because they had good face and content validity. These skills also demonstrated good predictive validity with gymnasts scoring significantly better than children without gymnastic training and children from a high SES school performing better than those from a mid and low SES schools and the mid SES children scored better than the low SES children (all p < .05). Inter rater reliability tests were excellent for all three skills (ICC = 0.81, 0.87, 0.87) as was test retest reliability (ICC 0.87-0.95). CFA provided good construct validity, and structural equation modelling revealed stability skills to be an independent factor in an overall FMS model which included locomotor (r = .88), object control (r = .76) and stability skills (r = .81). Discussion This study provides a rationale for the inclusion of stability skills in FMS assessment. The stability skills could be used alongside other FMS assessment tools to provide a holistic assessment of children's fundamental movement skills. Copyright

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Novel AlkB Dioxygenases—Alternative Models for In Silico and In Vivo Studies

Background: ALKBH proteins, the homologs of Escherichia coli AlkB dioxygenase, constitute a direct, single-protein repair system, protecting cellular DNA and RNA against the cytotoxic and mutagenic activity of alkylating agents, chemicals significantly contributing to tumor formation and used in cancer therapy. In silico analysis and in vivo studies have shown the existence of AlkB homologs in almost all organisms. Nine AlkB homologs (ALKBH1–8 and FTO) have been identified in humans. High ALKBH levels have been found to encourage tumor development, questioning the use of alkylating agents in chemotherapy. The aim of this work was to assign biological significance to multiple AlkB homologs by characterizing their activity in the repair of nucleic acids in prokaryotes and their subcellular localization in eukaryotes. Methodology and Findings: Bioinformatic analysis of protein sequence databases identified 1943 AlkB sequences with eight new AlkB subfamilies. Since Cyanobacteria and Arabidopsis thaliana contain multiple AlkB homologs, they were selected as model organisms for in vivo research. Using E. coli alkB2 mutant and plasmids expressing cyanobacterial AlkBs, we studied the repair of methyl methanesulfonate (MMS) and chloroacetaldehyde (CAA) induced lesions in ssDNA, ssRNA, and genomic DNA. On the basis of GFP fusions, we investigated the subcellular localization of ALKBHs in A. thaliana and established its mostly nucleo-cytoplasmic distribution. Some of the ALKBH proteins were found to change their localization upon MMS treatment. Conclusions: Our in vivo studies showed highly specific activity of cyanobacterial AlkB proteins towards lesions and nucleic acid type. Subcellular localization and translocation of ALKBHs in A. thaliana indicates a possible role for these proteins in the repair of alkyl lesions. We hypothesize that the multiplicity of ALKBHs is due to their involvement in the metabolism of nucleo-protein complexes; we find their repair by ALKBH proteins to be economical and effective alternative to degradation and de novo synthesis

A Pipeline Strategy for Grain Crop Domestication

In the interest of diversifying the global food system, improving human nutrition, and making agriculture more sustainable, there have been many proposals to domesticate wild plants or complete the domestication of semidomesticated orphan crops. However, very few new crops have recently been fully domesticated. Many wild plants have traits limiting their production or consumption that could be costly and slow to change. Others may have fortuitous preadaptations that make them easier to develop or feasible as high-value, albeit low-yielding, crops. To increase success in contemporary domestication of new crops, we propose a pipeline approach, with attrition expected as species advance through the pipeline. We list criteria for ranking domestication candidates to help enrich the starting pool with more preadapted, promising species. We also discuss strategies for prioritizing initial research efforts once the candidates have been selected: developing higher value products and services from the crop, increasing yield potential, and focusing on overcoming undesirable traits. Finally, we present new-crop case studies that demonstrate that wild species’ limitations and potential (in agronomic culture, shattering, seed size, harvest, cleaning, hybridization, etc.) are often only revealed during the early phases of domestication. When nearly insurmountable barriers were reached in some species, they have been (at least temporarily) eliminated from the pipeline. Conversely, a few species have moved quickly through the pipeline as hurdles, such as low seed weight or low seed number per head, were rapidly overcome, leading to increased confidence, farmer collaboration, and program expansion.Fil: DeHaan, Lee R.. The Land Institute; Estados UnidosFil: Van Tassel, David L.. The Land Institute; Estados UnidosFil: Anderson, James A.. University of Minnesota; Estados UnidosFil: Asselin, Sean R.. University of Manitoba; CanadáFil: Barnes, Richard. University of Minnesota; Estados UnidosFil: Baute, Gregory J.. University of British Columbia; CanadáFil: Cattani, Douglas J.. University of Manitoba; CanadáFil: Culman, Steve W.. Ohio State University; Estados UnidosFil: Dorn, Kevin M.. University of Minnesota; Estados UnidosFil: Hulke, Brent S.. United States Department of Agriculture. Agriculture Research Service; Estados UnidosFil: Kantar, Michael. University of British Columbia; CanadáFil: Larson, Steve. Forage and Range Research Laboratory; Estados UnidosFil: David Marks, M.. University of Minnesota; Estados UnidosFil: Miller, Allison J.. Saint Louis University; Estados UnidosFil: Poland, Jesse. Kansas State University; Estados UnidosFil: Ravetta, Damián Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Paleontológico Egidio Feruglio; ArgentinaFil: Rude, Emily. University of Wisconsin; Estados UnidosFil: Ryan, Matthew R.. Cornell University; Estados UnidosFil: Wyse, Don. University of Minnesota; Estados UnidosFil: Zhang, Xiaofei. University of Minnesota; Estados Unido