A targeted gene panel that covers coding, non-coding and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington\u27s disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic variation was found in 54 patients; 27 patients demonstrated clinical profiles that matched the variants; and 16 patients whose original diagnosis were refined. A high concordance of variant calling were observed when comparing the results from TGP and whole-exome sequencing of four patients. Our in-house STR detection algorithm has reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combined comprehensive TGPs-bioinformatics pipeline can improve the clinical diagnosis of NDs

Kinetic equations for thermal degradation of polymers

Kinetic equations are analyzed for thermal degradation of polymers. The governing relations are based on the fragmentation-annihilation concept. Explicit solutions to these equations are derived in two particular cases of interest. For arbitrary values of adjustable parameters, the evolution of the number-average and mass-average molecular weights of polymers is analyzed numerically. Good agreement is demonstrated between the results of numerical simulation and experimental data. It is revealed that the model can correctly predict observations in thermo-gravimetric tests when its parameters are determined by matching experimental data for the decrease in molecular weight with exposure time

Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites

<p>Abstract</p> <p>Background</p> <p>Explaining parasite virulence (harm to the host) represents a major challenge for evolutionary and biomedical scientists alike. Most theoretical models of virulence evolution assume that virulence arises as a direct consequence of host exploitation, the process whereby parasites convert host resources into transmission opportunities. However, infection-induced disease can be immune-mediated (immunopathology). Little is known about how immunopathology affects parasite fitness, or how it will affect the evolution of parasite virulence. Here we studied the effects of immunopathology on infection-induced host mortality rate and lifetime transmission potential – key components of parasite fitness – using the rodent malaria model, <it>Plasmodium chabaudi chabaudi</it>.</p> <p>Results</p> <p>Neutralizing interleukin [IL]-10, an important regulator of inflammation, allowed us to experimentally increase the proportion of virulence due to immunopathology for eight parasite clones. <it>In vivo </it>blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in a shorter time to death that was independent of parasite density and was particularly marked for normally avirulent clones. This suggests that IL-10 induction may provide a pathway to avirulence for <it>P. c. chabaudi</it>. Despite the increased investment in transmission-stage parasites observed for some clones in response to IL-10R blockade, experimental enhancement of immunopathology incurred a uniform fitness cost to all parasite clones by reducing lifetime transmission potential.</p> <p>Conclusion</p> <p>This is the first experimental study to demonstrate that infection-induced immunopathology and parasite genetic variability may together have the potential to shape virulence evolution. In accord with recent theory, the data show that some forms of immunopathology may select for parasites that make hosts less sick.</p

Application of Fiber Optic Instrumentation

Fiber optic sensing technology has emerged in recent years offering tremendous advantages over conventional aircraft instrumentation systems. The advantages of fiber optic sensors over their conventional counterparts are well established; they are lighter, smaller, and can provide enormous numbers of measurements at a fraction of the total sensor weight. After a brief overview of conventional and fiber-optic sensing technology, this paper presents an overview of the research that has been conducted at NASA Dryden Flight Research Center in recent years to advance this promising new technology. Research and development areas include system and algorithm development, sensor characterization and attachment, and real-time experimentally-derived parameter monitoring for ground- and flight-based applications. The vision of fiber optic smart structure technology is presented and its potential benefits to aerospace vehicles throughout the lifecycle, from preliminary design to final retirement, are presented

Rigorous Theory of Optical Trapping by an Optical Vortex Beam

We propose a rigorous theory for the optical trapping by optical vortices, which is emerging as an important tool to trap mesoscopic particles. The common perception is that the trapping is solely due to the gradient force, and may be characterized by three real force constants. However, we show that the optical vortex trap can exhibit complex force constants, implying that the trapping must be stabilized by ambient damping. At different damping levels, particle shows remarkably different dynamics, such as stable trapping, periodic and aperiodic orbital motions

Quasi-static characterisation and impact testing of auxetic foam for sports safety applications

This study compared low strain rate material properties and impact force attenuation of auxetic foam and the conventional open-cell polyurethane counterpart. This furthers our knowledge with regards to how best to apply these highly conformable and breathable auxetic foams to protective sports equipment. Cubes of auxetic foam measuring 150 x 150 x 150 mm were fabricated using a thermo-mechanical conversion process. Quasi-static compression confirmed the converted foam to be auxetic, prior to being sliced into 20 mm thick cuboid samples for further testing. Density, Poisson’s ratio and the stress-strain curve were all found to be dependent on the position of each cuboid from within the cube. Impact tests with a hemispherical drop hammer were performed for energies up to 6 J, on foams covered with a polypropylene sheet between 1 and 2 mm thick. Auxetic samples reduced peak force by ~10 times in comparison to the conventional foam. This work has shown further potential for auxetic foam to be applied to protective equipment, while identifying that improved fabrication methods are required

‘How I feel About My School’: The construction and validation of a measure of wellbeing at school for primary school children

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.There is a growing focus on child wellbeing and happiness in schools, but we lack self-report measures for very young children. Three samples (N = 2345) were combined to assess the psychometric properties of the How I Feel About My School (HIFAMS) questionnaire, which was designed for children aged 4-8 years. Test re-test reliability was moderate (intraclass correlation coefficient = 0.62). HIFAMS assessed a single concept and had moderate internal consistency (Cronbach’s alpha values from 0.62 to 0.67). There were low correlations between scores on the child-reported HIFAMS and parent- and teacher reports. Children at risk of exclusion had significantly lower HIFAMS scores than the community sample (mean difference = 2.4; 95% CI: 1.6 to 3.2; p < 0.001). Schools contributed only 4.5% of the variability in HIFAMS score; the remaining 95.5% reflecting pupil differences within schools. Girls’ scores were 0.37 units (95% CI: 0.16 to 0.57; p < 0.001) higher than boys, while year group and deprivation did not predict HIFAMS score. HIFAMS is a promising measure that demonstrates moderate reliability and discriminates between groups even among very young children

RS1, Higher Derivatives and Stability

We demonstrate the classical stability of the weak/Planck hierarchy within the Randall-Sundrum scenario, incorporating the Goldberger-Wise mechanism and higher-derivative interactions in a systematic perturbative expansion. Such higher-derivative interactions are expected if the RS model is the low-energy description of some more fundamental theory. Generically, higher derivatives lead to ill-defined singularities in the vicinity of effective field theory branes. These are carefully treated by the methods of classical renormalization.Comment: 30 page

Radiative falloff of a scalar field in a weakly curved spacetime without symmetries

We consider a massless scalar field propagating in a weakly curved spacetime whose metric is a solution to the linearized Einstein field equations. The spacetime is assumed to be stationary and asymptotically flat, but no other symmetries are imposed -- the spacetime can rotate and deviate strongly from spherical symmetry. We prove that the late-time behavior of the scalar field is identical to what it would be in a spherically-symmetric spacetime: it decays in time according to an inverse power-law, with a power determined by the angular profile of the initial wave packet (Price falloff theorem). The field's late-time dynamics is insensitive to the nonspherical aspects of the metric, and it is governed entirely by the spacetime's total gravitational mass; other multipole moments, and in particular the spacetime's total angular momentum, do not enter in the description of the field's late-time behavior. This extended formulation of Price's falloff theorem appears to be at odds with previous studies of radiative decay in the spacetime of a Kerr black hole. We show, however, that the contradiction is only apparent, and that it is largely an artifact of the Boyer-Lindquist coordinates adopted in these studies.Comment: 17 pages, RevTeX