INVESTIGATING THE SEATED DOUBLE POLING CYCLE: IDENTIFYING BASELINE MEASURES FOR THE PREPARATION PHASE

The purpose of this study was to identify baseline measures (BM) for the preparation phase (PREP) within the linear stroking cycle for the sport of sledge hockey. The addition of this phase to seated double poling is unclear biomechanically; full arm extension to pick-plant. A validated solid-static prototype mimicking the average single-armed adult male with dynamic shoulder joint was used to determine BM in 3 dimensions and initial pick-impact forces (GRF). Results indicated that average peak GRF occurred prior to 5.0x10-3s post initial contact; Fy=179N, Fz=515N and Fx=573N. Evidence indicated PREP should initiate slightly below the horizon in order to produce the greatest non-contracting force for sledge propulsion. Isolated data provides insight to the biomechanics of the dynamic limb within PREP assisting with its importance to the complete cycle

Neuroimaging and biomarker evidence of neurodegeneration in asthma

Background: Epidemiological studies have shown that Alzheimer’s disease and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency. // Objective: To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (p-Tau181), neurodegeneration (NfL) and glial activation (GFAP). // Methods: dMRI data were obtained in 111 individuals with asthma, ranging in disease severity from mild to severe, and 135 healthy controls. Regression analyses were used to test the relationships between asthma severity and neuroimaging measures, as well as AD pathology, neurodegeneration and glial activation, indexed by plasma p-Tau181, NfL and GFAP respectively. Additional relationships were tested with cognitive function. // Results: Asthma participants had widespread and large magnitude differences in several dMRI metrics, which were indicative of neuroinflammation and neurodegeneration, and robustly associated with GFAP and to a lesser extent, with NfL. The AD biomarker p-Tau181 was only minimally associated with neuroimaging outcomes. Further, asthma severity was associated with deleterious changes in neuroimaging outcomes, which in turn, were associated with slower processing speed, a test of cognitive performance. // Conclusion: These data suggest that asthma, particularly when severe, is associated with characteristics of neuroinflammation and neurodegeneration and may be a potential risk factor for neural injury and cognitive dysfunction. The results suggest a need to determine how asthma may affect brain health and whether treatment directed toward characteristics of asthma associated with these risks can mitigate these effects

Multicomponent fractional quantum Hall effect in graphene

We report observation of the fractional quantum Hall effect (FQHE) in high mobility multi-terminal graphene devices, fabricated on a single crystal boron nitride substrate. We observe an unexpected hierarchy in the emergent FQHE states that may be explained by strongly interacting composite Fermions with full SU(4) symmetric underlying degrees of freedom. The FQHE gaps are measured from temperature dependent transport to be up 10 times larger than in any other semiconductor system. The remarkable strength and unusual hierarcy of the FQHE described here provides a unique opportunity to probe correlated behavior in the presence of expanded quantum degrees of freedom.Comment: 5 pages, 3 figure

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease

IMPORTANCE: The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE: To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING AND PARTICIPANTS: Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES: Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS: The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. CONCLUSIONS AND RELEVANCE: These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials

Wigner Crystallization in a Quasi-3D Electronic System

When a strong magnetic field is applied perpendicularly (along z) to a sheet confining electrons to two dimensions (x-y), highly correlated states emerge as a result of the interplay between electron-electron interactions, confinement and disorder. These so-called fractional quantum Hall (FQH) liquids form a series of states which ultimately give way to a periodic electron solid that crystallizes at high magnetic fields. This quantum phase of electrons has been identified previously as a disorder-pinned two-dimensional Wigner crystal with broken translational symmetry in the x-y plane. Here, we report our discovery of a new insulating quantum phase of electrons when a very high magnetic field, up to 45T, is applied in a geometry parallel (y-direction) to the two-dimensional electron sheet. Our data point towards this new quantum phase being an electron solid in a "quasi-3D" configuration induced by orbital coupling with the parallel field

Applications of Laboratory Technology in the Evaluation of the Risk of Rabies Transmissions by Biting Dogs and Cats

While rabies is not a common disease in domestic animal species of the United States, potential exposures to rabies in the form of bites are very common and increasing. A nationwide study conducted among general hospitals shows that 1 percent of emergency room visits are for animal bites, of which 80-90 percent are inflicted by the dog (Callaham 1980). This figure is conservative, as the study did not include pediatric hospitals, the bite of victims that progress only to a physician\u27s office, or those that receive no medical care at all. In Missouri alone, this study would infer about 1500 dog bites per year reaching only the general hospital. The number of dog and other animal bites across the country is unknown but may safely be assumed to be staggering in magnitude

Phenotypic Plasticity and Contemporary Evolution in Introduced Populations: Evidence from Translocated Populations of White Sands Pupfish (Cyrpinodon tularosa)

Contemporary evolution has been shown in a few studies to be an important component of colonization ability, but seldom have researchers considered whether phenotypic plasticity facilitates directional evolution from the invasion event. In the current study, we evaluated body shape divergence of the New Mexico State-threatened White Sands pupfish (Cyprinodon tularosa) that were introduced to brackish, lacustrine habitats at two different time in the recent past (approximately 30 years and 1 year previously) from the same source population (saline river environment). Pupfish body shape is correlated with environmental salinity: fish from saline habitats are characterized by slender body shapes, whereas fish from fresher, yet brackish springs are deep-bodied. In this study, lacustrine populations consisted of an approximately 30-year old population and several 1-year old populations, all introduced from the same source. The body shape divergence of the 30-year old population was significant and greater than any of the divergences of the 1-year old populations (which were for the most part not significant). Nonetheless, all body shape changes exhibited body deepening in less saline environments. We conclude that phenotypic plasticity potentially facilitates directional evolution of body deepening for introduced pupfish populations

High accuracy genotyping directly from genomic DNA using a rolling circle amplification based assay

BACKGROUND: Rolling circle amplification of ligated probes is a simple and sensitive means for genotyping directly from genomic DNA. SNPs and mutations are interrogated with open circle probes (OCP) that can be circularized by DNA ligase when the probe matches the genotype. An amplified detection signal is generated by exponential rolling circle amplification (ERCA) of the circularized probe. The low cost and scalability of ligation/ERCA genotyping makes it ideally suited for automated, high throughput methods. RESULTS: A retrospective study using human genomic DNA samples of known genotype was performed for four different clinically relevant mutations: Factor V Leiden, Factor II prothrombin, and two hemochromatosis mutations, C282Y and H63D. Greater than 99% accuracy was obtained genotyping genomic DNA samples from hundreds of different individuals. The combined process of ligation/ERCA was performed in a single tube and produced fluorescent signal directly from genomic DNA in less than an hour. In each assay, the probes for both normal and mutant alleles were combined in a single reaction. Multiple ERCA primers combined with a quenched-peptide nucleic acid (Q-PNA) fluorescent detection system greatly accellerated the appearance of signal. Probes designed with hairpin structures reduced misamplification. Genotyping accuracy was identical from either purified genomic DNA or genomic DNA generated using whole genome amplification (WGA). Fluorescent signal output was measured in real time and as an end point. CONCLUSIONS: Combining the optimal elements for ligation/ERCA genotyping has resulted in a highly accurate single tube assay for genotyping directly from genomic DNA samples. Accuracy exceeded 99 % for four probe sets targeting clinically relevant mutations. No genotypes were called incorrectly using either genomic DNA or whole genome amplified sample

SAMQA: error classification and validation of high-throughput sequenced read data

<p>Abstract</p> <p>Background</p> <p>The advances in high-throughput sequencing technologies and growth in data sizes has highlighted the need for scalable tools to perform quality assurance testing. These tests are necessary to ensure that data is of a minimum necessary standard for use in downstream analysis. In this paper we present the SAMQA tool to rapidly and robustly identify errors in population-scale sequence data.</p> <p>Results</p> <p>SAMQA has been used on samples from three separate sets of cancer genome data from The Cancer Genome Atlas (TCGA) project. Using technical standards provided by the SAM specification and biological standards defined by researchers, we have classified errors in these sequence data sets relative to individual reads within a sample. Due to an observed linearithmic speedup through the use of a high-performance computing (HPC) framework for the majority of tasks, poor quality data was identified prior to secondary analysis in significantly less time on the HPC framework than the same data run using alternative parallelization strategies on a single server.</p> <p>Conclusions</p> <p>The SAMQA toolset validates a minimum set of data quality standards across whole-genome and exome sequences. It is tuned to run on a high-performance computational framework, enabling QA across hundreds gigabytes of samples regardless of coverage or sample type.</p