Free-living and laboratory gait characteristics in patients with multiple sclerosis.

BACKGROUND: Wearable sensors offer the potential to bring new knowledge to inform interventions in patients affected by multiple sclerosis (MS) by thoroughly quantifying gait characteristics and gait deficits from prolonged daily living measurements. The aim of this study was to characterise gait in both laboratory and daily life conditions for a group of patients with moderate to severe ambulatory impairment due to MS. To this purpose, algorithms to detect and characterise gait from wearable inertial sensors data were also validated. METHODS: Fourteen patients with MS were divided into two groups according to their disability level (EDSS 6.5-6.0 and EDSS 5.5-5.0, respectively). They performed both intermittent and continuous walking bouts (WBs) in a gait laboratory wearing waist and shank mounted inertial sensors. An algorithm (W-CWT) to estimate gait events and temporal parameters (mean and variability values) using data recorded from the waist mounted sensor (Dynaport, Mc Roberts) was tested against a reference algorithm (S-REF) based on the shank-worn sensors (OPAL, APDM). Subsequently, the accuracy of another algorithm (W-PAM) to detect and classify WBs was also tested. The validated algorithms were then used to quantify gait characteristics during short (sWB, 5-50 steps), intermediate (iWB, 51-100 steps) and long (lWB, >100 steps) daily living WBs and laboratory walking. Group means were compared using a two-way ANOVA. RESULTS: W-CWT compared to S-REF showed good gait event accuracy (0.05-0.10 s absolute error) and was not influenced by disability level. It slightly overestimated stride time in intermittent walking (0.012 s) and overestimated highly variability of temporal parameters in both intermittent (17.5%-58.2%) and continuous walking (11.2%-76.7%). The accuracy of W-PAM was speed-dependent and decreased with increasing disability. The ANOVA analysis showed that patients walked at a slower pace in daily living than in the laboratory. In daily living gait, all mean temporal parameters decreased as the WB duration increased. In the sWB, the patients with a lower disability score showed, on average, lower values of the temporal parameters. Variability decreased as the WB duration increased. CONCLUSIONS: This study validated a method to quantify walking in real life in people with MS and showed how gait characteristics estimated from short walking bouts during daily living may be the most informative to quantify level of disability and effects of interventions in patients moderately affected by MS. The study provides a robust approach for the quantification of recognised clinically relevant outcomes and an innovative perspective in the study of real life walking

Two-level system with a thermally fluctuating transfer matrix element: Application to the problem of DNA charge transfer

Charge transfer along the base-pair stack in DNA is modeled in terms of thermally-assisted tunneling between adjacent base pairs. Central to our approach is the notion that tunneling between fluctuating pairs is rate-limited by the requirement of their optimal alignment. We focus on this aspect of the process by modeling two adjacent base pairs in terms of a classical damped oscillator subject to thermal fluctuations as described by a Fokker-Planck equation. We find that the process is characterized by two time scales, a result that is in accord with experimental findings.Comment: original file is revtex4, 10 pages, three eps figure

Osmium isotope evidence for two pulses of increased continental weathering linked to Early Jurassic volcanism and climate change

Large igneous provinces (LIPs) are proposed to have caused a number of episodes of abrupt environmental change by increasing atmospheric CO2 levels, which were subsequently alleviated by drawdown of CO2 via enhanced continental weathering and burial of organic matter. Here the sedimentary records of two such episodes of environmental change, the Toarcian oceanic anoxic event (T-OAE) and preceding Pliensbachian–Toarcian (Pl-To) event (both possibly linked to the Karoo-Ferrar LIP), are investigated using a new suite of geochemical proxies that have not been previously compared. Stratigraphic variations in osmium isotope (187Os/188Os) records are compared with those of mercury (Hg) and carbon isotopes (d13C) in samples from the Mochras core, Llanbedr Farm, Cardigan Bay Basin, Wales. These sedimentary rocks are confirmed as recording an open-marine setting by analysis of molybdenum/uranium enrichment trends, indicating that the Os isotope record in these samples reflects the isotopic composition of the global ocean. The Os isotope data include the first results across the Pl-To boundary, when seawater 187Os/188Os increased from ~0.40 to ~0.53, in addition to new data that show elevated 187Os/188Os (from ~0.42 to ~0.68) during the T-OAE. Both increases in 187Os/188Os correlate with negative carbon isotope excursions and increased mercury concentrations, supporting an interplay between terrestrial volcanism, weathering, and climate that was instrumental in driving these distinct episodes of global environmental change. These observations also indicate that the environmental impact of the Karoo-Ferrar LIP was not limited solely to the T-OAE

Evaluating airborne and ground based gamma spectrometry methods for detecting particulate radioactivity in the environment: a case study of Irish Sea beaches

In several places, programmes are in place to locate and recover radioactive particles that have the potential to cause detrimental health effects in any member of the publicwho may encounter them. A model has been developed to evaluate the use of mobile gamma spectrometry systems within such programmes, with particular emphasis on large volume (16 l) NaI(Tl) detectors mounted in low flying helicopters. This model uses a validated Monte Carlo code with assessment of local geochemistry and natural and anthropogenic background radiation concentrations and distributions. The results of the model, applied to the example of particles recovered from beaches in the vicinity of Sellafield, clearly show the ability of rapid airborne surveys conducted at 75 m ground clearance and 120 kph speeds to demonstrate the absence of sources greater than 5 MBq 137Cs within large areas (10–20 km2 h−1), and identify areas requiring further ground based investigation. Lowering ground clearance for airborne surveys to 15 m whilst maintaining speeds covering 1–2 km2 h−1 can detect buried 137Cs sources of 0.5 MBq or greater activity. A survey design to detect 100 kBq 137Cs sources at 10 cm depth has also been defined, requiring surveys at b15 m ground clearance and b2 m s−1 ground speed. The response of airborne systems to the Sellafield particles recovered to date has also been simulated, and the proportion of the existing radiocaesium background in the vicinity of the nuclear site has been established. Finally the rates of area coverage and sensitivities of both airborne and ground based approaches are compared, demonstrating the ability of airborne systems to increase the rate of particle recovery in a cost effective manner. The potential for equipment and methodological developments to improve performance are discussed

Rate-equation calculations of the current flow through two-site molecular device and DNA-based junction

Here we present the calculations of incoherent current flowing through the two-site molecular device as well as the DNA-based junction within the rate-equation approach. Few interesting phenomena are discussed in detail. Structural asymmetry of two-site molecule results in rectification effect, which can be neutralized by asymmetric voltage drop at the molecule-metal contacts due to coupling asymmetry. The results received for poly(dG)-poly(dC) DNA molecule reveal the coupling- and temperature-independent saturation effect of the current at high voltages, where for short chains we establish the inverse square distance dependence. Besides, we document the shift of the conductance peak in the direction to higher voltages due to the temperature decrease.Comment: 12 pages, 6 figure

Reconciliation Revisited: Handling Multiple Optima when Reconciling with Duplication, Transfer, and Loss

Phylogenetic tree reconciliation is a powerful approach for inferring evolutionary events like gene duplication, horizontal gene transfer, and gene loss, which are fundamental to our understanding of molecular evolution. While duplication–loss (DL) reconciliation leads to a unique maximum-parsimony solution, duplication-transfer-loss (DTL) reconciliation yields a multitude of optimal solutions, making it difficult to infer the true evolutionary history of the gene family. This problem is further exacerbated by the fact that different event cost assignments yield different sets of optimal reconciliations. Here, we present an effective, efficient, and scalable method for dealing with these fundamental problems in DTL reconciliation. Our approach works by sampling the space of optimal reconciliations uniformly at random and aggregating the results. We show that even gene trees with only a few dozen genes often have millions of optimal reconciliations and present an algorithm to efficiently sample the space of optimal reconciliations uniformly at random in O(mn[superscript 2]) time per sample, where m and n denote the number of genes and species, respectively. We use these samples to understand how different optimal reconciliations vary in their node mappings and event assignments and to investigate the impact of varying event costs. We apply our method to a biological dataset of approximately 4700 gene trees from 100 taxa and observe that 93% of event assignments and 73% of mappings remain consistent across different multiple optima. Our analysis represents the first systematic investigation of the space of optimal DTL reconciliations and has many important implications for the study of gene family evolution.National Science Foundation (U.S.) (CAREER Award 0644282)National Institutes of Health (U.S.) (Grant RC2 HG005639)National Science Foundation (U.S.). Assembling the Tree of Life (Program) (Grant 0936234

Electrically tunable solid-state silicon nanopore ion filter

We show that a nanopore in a silicon membrane connected to a voltage source can be used as an electrically tunable ion filter. By applying a voltage between the heavily doped semiconductor and the electrolyte, it is possible to invert the ion population inside the nanopore and vary the conductance for both cations and anions in order to achieve selective conduction of ions even in the presence of significant surface charges in the membrane. Our model based on the solution of the Poisson equation and linear transport theory indicates that in narrow nanopores substantial gain can be achieved by controlling electrically the width of the charge double layer

Young and Intermediate-age Distance Indicators

Distance measurements beyond geometrical and semi-geometrical methods, rely mainly on standard candles. As the name suggests, these objects have known luminosities by virtue of their intrinsic proprieties and play a major role in our understanding of modern cosmology. The main caveats associated with standard candles are their absolute calibration, contamination of the sample from other sources and systematic uncertainties. The absolute calibration mainly depends on their chemical composition and age. To understand the impact of these effects on the distance scale, it is essential to develop methods based on different sample of standard candles. Here we review the fundamental properties of young and intermediate-age distance indicators such as Cepheids, Mira variables and Red Clump stars and the recent developments in their application as distance indicators.Comment: Review article, 63 pages (28 figures), Accepted for publication in Space Science Reviews (Chapter 3 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Tight-binding parameters for charge transfer along DNA

We systematically examine all the tight-binding parameters pertinent to charge transfer along DNA. The $\pi$ molecular structure of the four DNA bases (adenine, thymine, cytosine, and guanine) is investigated by using the linear combination of atomic orbitals method with a recently introduced parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are discussed and then used for calculating the corresponding wavefunctions of the two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO and LUMO energies of the bases are in good agreement with available experimental values. Our results are then used for estimating the complete set of charge transfer parameters between neighboring bases and also between successive base-pairs, considering all possible combinations between them, for both electrons and holes. The calculated microscopic quantities can be used in mesoscopic theoretical models of electron or hole transfer along the DNA double helix, as they provide the necessary parameters for a tight-binding phenomenological description based on the $\pi$ molecular overlap. We find that usually the hopping parameters for holes are higher in magnitude compared to the ones for electrons, which probably indicates that hole transport along DNA is more favorable than electron transport. Our findings are also compared with existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc