Exercise interventions for adults and children with cerebral palsy (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: - The primary aim of this systematic review is to evaluate the effect of exercise interventions on activity, participation, and health-related quality of life (HRQoL) in adults and children with CP. - The secondary aim is to evaluate the effect of exercise interventions on body functions and body structures.Jennifer M Ryan is receiving funding from Action Medical Research and the Chartered Society of Physiotherapy Charitable Trust to evaluate the feasibility, acceptability, and efficacy of resistance training in adolescents with cerebral palsy

Binding interface change and cryptic variation in the evolution of protein-protein interactions

Background:Physical interactions between proteins are essential for almost all biological functions and systems. To understand the evolution of function it is therefore important to understand the evolution of molecular interactions. Of key importance is the evolution of binding specificity, the set of interactions made by a protein, since change in specificity can lead to “rewiring” of interaction networks. Unfortunately, the interfaces through which proteins interact are complex, typically containing many amino-acid residues that collectively must contribute to binding specificity as well as binding affinity, structural integrity of the interface and solubility in the unbound state. Results: In order to study the relationship between interface composition and binding specificity, we make use of paralogous pairs of yeast proteins. Immediately after duplication these paralogues will have identical sequences and protein products that make an identical set of interactions. As the sequences diverge, we can correlate amino-acid change in the interface with any change in the specificity of binding. We show that change in interface regions correlates only weakly with change in specificity, and many variants in interfaces are functionally equivalent. We show that many of the residue replacements within interfaces are silent with respect to their contribution to binding specificity. Conclusions: We conclude that such functionally-equivalent change has the potential to contribute to evolutionary plasticity in interfaces by creating cryptic variation, which in turn may provide the raw material for functional innovation and coevolution.BBSRCWellcome Trust Institutional Strategic Support Awar

Multifluorescence High‐Resolution Episcopic Microscopy for 3D Imaging of Adult Murine Organs

3D microscopy of large biological samples (>0.5 cm^{3})is transforming biological research. Many existing techniques require trade-offs between image resolution, sample size, and method complexity. A simple robust instrument with the potential to conduct large-volume 3D imaging currently exists in the form of the optical high-resolution episcopic microscopy (HREM). However, the development of the instrument to date is limited to single-fluorescent wavelength imaging with nonspecific eosin staining. Herein, developments to realize the potential of the HREM to become multifluorescent high-resolution episcopic microscopy (MF-HREM) are presented. MF-HREM is a serial-sectioning and block-facing wide-field fluorescence imaging technique, which does not require tissue clearing or optical sectioning. Multiple developments are detailed in sample preparation and image postprocessing to enable multiple specific stains in large samples and show how these enable segmentation and quantification of the data. The application of MF-HREM is demonstrated in a variety of biological contexts: 3D imaging of whole tumor vascular networks and tumor cell invasion in xenograft tumors up to 7.5 mm^{3} at resolutions of 2.75 μm, quantification of glomeruli volume in the adult mouse kidney, and quantification of vascular networks and white-matter track orientation in adult mouse brain

Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible

The First Detection of Co in a Damped Lyman Alpha System

The study of elemental abundances in Damped Lyman Alpha systems (DLAs) at high redshift represents one of our best opportunities to probe galaxy formation and chemical evolution at early times. By coupling measurements made in high z DLAs with our knowledge of abundances determined locally and with nucleosynthetic models, we can start to piece together the star formation histories of these galaxies. Here, we discuss the clues to galactic chemical evolution that may be gleaned from studying the abundance of Co in DLAs. We present high resolution echelle spectra of two QSOs, Q2206-199 and Q1223+17, both already known to exhibit intervening damped systems. These observations have resulted in the first ever detection of Co at high redshift, associated with the z= 1.92 DLA in the sightline towards Q2206-199. We find that the abundance of Co is approximately 1/4 solar and that there is a clear overabundance relative to iron, [Co/Fe] = +0.31 +/- 0.05. From the abundance of Zn, we determine that this is a relatively metal-rich DLA, with a metallicity approximately 1/3 solar. Therefore, this first detection of Co is similar to the marked overabundance relative to Fe seen in Galactic bulge and thick disk stars.Comment: Accepted for publication in MNRAS, 10 page

First-generation black-hole-forming supernovae and the metal abundance pattern of a very iron-poor star

It has been proposed theoretically that the first generation of stars in the Universe (population III) would be as massive as 100 solar masses (100Mo), because of inefficient cooling of the precursor gas clouds. Recently, the most iron-deficient (but still carbon-rich) low-mass star -- HE0107-5240 -- was discovered. If this is a population III that gained its metals (elements heavier than helium) after its formation, it would challenge the theoretical picture of the formation of the first stars. Here we report that the patterns of elemental abundance in HE0107-5240 (and other extremely metal-poor stars) are in good accord with the nucleosynthesis that occurs in stars with masses of 20-130Mo when they become supernovae if, during the explosions, the ejecta undergo substantial mixing and fall-back to form massive black holes. Such supernovae have been observed. The abundance patterns are not, however, consistent with enrichment by supernovae from stars in the range 130-300 Mo. We accordingly infer that the first-generation supernovae came mostly from explosions of ~ 20-130Mo stars; some of these produced iron-poor but carbon- and oxygen-rich ejecta. Low-mass second-generation stars, like HE0107-5240, could form because the carbon and oxygen provided pathways for gas to cool.Comment: To appear in NATURE 422 (2003), 871-873 (issue 24 April 2003); Title and the first paragraph have been changed and other minor corrections have been mad

Hypernova Nucleosynthesis and Galactic Chemical Evolution

We study nucleosynthesis in 'hypernovae', i.e., supernovae with very large explosion energies ( \gsim 10^{52} ergs) for both spherical and aspherical explosions. The hypernova yields compared to those of ordinary core-collapse supernovae show the following characteristics: 1) Complete Si-burning takes place in more extended region, so that the mass ratio between the complete and incomplete Si burning regions is generally larger in hypernovae than normal supernovae. As a result, higher energy explosions tend to produce larger [(Zn, Co)/Fe], small [(Mn, Cr)/Fe], and larger [Fe/O], which could explain the trend observed in very metal-poor stars. 2) Si-burning takes place in lower density regions, so that the effects of $\alpha$-rich freezeout is enhanced. Thus $^{44}$Ca, $^{48}$Ti, and $^{64}$Zn are produced more abundantly than in normal supernovae. The large [(Ti, Zn)/Fe] ratios observed in very metal poor stars strongly suggest a significant contribution of hypernovae. 3) Oxygen burning also takes place in more extended regions for the larger explosion energy. Then a larger amount of Si, S, Ar, and Ca ("Si") are synthesized, which makes the "Si"/O ratio larger. The abundance pattern of the starburst galaxy M82 may be attributed to hypernova explosions. Asphericity in the explosions strengthens the nucleosynthesis properties of hypernovae except for "Si"/O. We thus suggest that hypernovae make important contribution to the early Galactic (and cosmic) chemical evolution.Comment: To be published in "The Influence of Binaries on Stellar Population Studies", ed. D. Vanbeveren (Kluwer), 200

Smart Contracts for Global Sourcing Arrangements

While global sourcing arrangements are highly complex and usually represent large value to the partners, little is known of the use of e-contracts or smart contracts and contract management systems to enhance the contract management process. In this paper we assess the potential of emerging technologies for global sourcing. We review current sourcing contract issues and evaluate three technologies that have been applied to enhance contracting processes. These are (1) semantic standardisation, (2) cognitive technologies and (3) smart contracts and blockchain. We discuss that each of these seem to have their merit for contract management and potentially can contribute to contract management in more complex and dynamic sourcing arrangements. The combination and configuration in which these three technologies will provide value to sourcing should be on the agenda for future research in sourcing contract management.</p

The primordial Helium-4 abundance determination: systematic effects

By extrapolating to O/H = N/H = 0 the empirical correlations Y-O/H and Y-N/H defined by a relatively large sample of ~ 45 Blue Compact Dwarfs (BCDs), we have obtained a primordial 4Helium mass fraction Yp= 0.2443+/-0.0015 with dY/dZ = 2.4+/-1.0. This result is in excellent agreement with the average Yp= 0.2452+/-0.0015 determined in the two most metal-deficient BCDs known, I Zw 18 (Zsun/50) and SBS 0335-052 (Zsun/41), where the correction for He production is smallest. The quoted error (1sigma) of < 1% is statistical and does not include systematic effects. We examine various systematic effects including collisional excitation of Hydrogen lines, ionization structure and temperature fluctuation effects, and underlying stellar HeI absorption, and conclude that combining all systematic effects, our Yp may be underestimated by ~ 2-4%. Taken at face value, our Yp implies a baryon-to-photon number ratio eta = 4.7x10^-10 and a baryon mass fraction Omega_b h^2_{100} = 0.017+/-0.005 (2sigma), consistent with the values obtained from deuterium and Cosmic Microwave Background measurements. Correcting Yp upward by 2-4% would make the agreement even better.Comment: 12 pages, 5 PS figures, to appear in "Matter in the Universe", ed P. Jetzer, K. Pretzl and R. von Steiger, Kluwer, Dordrecht (2002

Exploring the Universe with Metal-Poor Stars

The early chemical evolution of the Galaxy and the Universe is vital to our understanding of a host of astrophysical phenomena. Since the most metal-poor Galactic stars (with metallicities down to [Fe/H]\sim-5.5) are relics from the high-redshift Universe, they probe the chemical and dynamical conditions of the Milky Way and the origin and evolution of the elements through nucleosynthesis. They also provide constraints on the nature of the first stars, their associated supernovae and initial mass function, and early star and galaxy formation. The Milky Way's dwarf satellites contain a large fraction (~30%) of the known most metal-poor stars that have chemical abundances that closely resemble those of equivalent halo stars. This suggests that chemical evolution may be universal, at least at early times, and that it is driven by massive, energetic SNe. Some of these surviving, ultra-faint systems may show the signature of just one such PopIII star; they may even be surviving first galaxies. Early analogs of the surviving dwarfs may thus have played an important role in the assembly of the old Galactic halo whose formation can now be studied with stellar chemistry. Following the cosmic evolution of small halos in simulations of structure formation enables tracing the cosmological origin of the most metal-poor stars in the halo and dwarf galaxies. Together with future observations and additional modeling, many of these issues, including the reionization history of the Milky Way, may be constrained this way. The chapter concludes with an outlook about upcoming observational challenges and ways forward is to use metal-poor stars to constrain theoretical studies.Comment: 34 pages, 11 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin