High precision zinc stable isotope measurement of certified biological reference materials using the double spike technique and multiple collector-ICP-MS

Biological reference materials with well-characterized s table isotope compositions are lacking in the field of ‘isotope biochemistry’, which seeks to understand bodily processes that rely on essential metals by determining metal stable isotope ratios. Here, we present Zn stable isotope data for six biological reference materials with certified trace metal concentrations, fish muscle, bovine muscle, pig kidney, human hair, human blood serum and human urine. Replicate analyses of multiple aliquots of each material achieved reproducibilities (2sd) of 0.04-0.13 ‰ for δ66/64Zn 22 (which denotes the deviation of the 66 Zn/64Zn ratio of a sample from a pure Zn reference material in parts per 1000). This implies only very minor isotopic heterogeneities within the samples, rendering them suitable as quality control materials for Zn isotopeanalyses. This endorsement is reinforced by (i) the close agreement of our Zn isotope data for two of the samples (bovine 2 muscle and human blood serum) to previously published results for different batches of the same material and (ii) the similarity of the isotopic data for the samples (δ66/64Zn≈ –0.8 to 0.0 ‰) to previously published Zn isotope results for similar biological materials. Further tests revealed that the applied Zn separation procedure is sufficiently effective to enable accurate data acquisition even at low mass resolving power (M/ΔM ≈ 400), as measurements and analyses conducted at much higher mass resolution (M/ΔM ≈ 8500) delivered essentially identical results

Evaluation of a community dental service for homeless and 'hard to reach' people

Objective Since 2013, Revive Dental Care has been operating a community outreach dental service for homeless and 'hard-to-reach' patients. This research aimed to (a) explore the dental care experienced by people accessing the service, (b) examine barriers and facilitators to using a dental service, (c) examine the impact of the service and (d) identify good practice in providing dental services for homeless people. Methods Semi-structured interviews with 20 patients, nine members of the dental staff and four staff members from the community centres providing services for homeless people. Results Findings suggest that homeless patients have overall poor daily dental care and experience significant dental problems due to a range of lifestyle factors. Most participants had not seen a dentist for many years and previous experiences of seeing a dentist were often unpleasant. Barriers to care included fear, embarrassment, lack of money, living chaotic lifestyles, not prioritising dental care and difficulties finding an NHS dentist that would take on homeless people. Service provision for homeless and/or hard-to-reach patients needs to be proactive with dental staff going to community settings and making personal contact. Conclusion Crucially, providers must acknowledge that the patients are vulnerable. A successful service needs to be informal, adapt to patient needs and accommodates chaotic lives

Measuring our universe from galaxy redshift surveys

Galaxy redshift surveys have achieved significant progress over the last couple of decades. Those surveys tell us in the most straightforward way what our local universe looks like. While the galaxy distribution traces the bright side of the universe, detailed quantitative analyses of the data have even revealed the dark side of the universe dominated by non-baryonic dark matter as well as more mysterious dark energy (or Einstein's cosmological constant). We describe several methodologies of using galaxy redshift surveys as cosmological probes, and then summarize the recent results from the existing surveys. Finally we present our views on the future of redshift surveys in the era of Precision Cosmology.Comment: 82 pages, 31 figures, invited review article published in Living Reviews in Relativity, http://www.livingreviews.org/lrr-2004-

Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury

Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation of cell proliferation through modulation of the sonic hedgehog pathway, a key NSC regulatory pathway, could lead to functional improvement. We assessed sonic hedgehog (Shh) protein levels in the cerebrospinal fluid (CSF) of patients with TBI. Using the cortical contusion injury (CCI) model in rodents, we used pharmacological modulators of Shh signaling to assess cell proliferation within the injured cortex using the marker 5-Ethynyl-2’-deoxyuridine (EdU); 50mg/mL. The phenotype of proliferating cells was determined and quantified. Motor function was assessed using the rotarod test. In patients with TBI there is a reduction of Shh protein in CSF compared with control patients. In rodents, following a severe CCI, quiescent cells become activated. Pharmacologically modulating the Shh signaling pathway leads to changes in the number of newly proliferating injury-induced cells. Upregulation of Shh signaling with Smoothened agonist (SAG) results in an increase of newly proliferating cells expressing glial fibrillary acidic protein (GFAP), whereas the Shh signaling inhibitor cyclopamine leads to a reduction. Some cells expressed doublecortin (DCX) but did not mature into neurons. The SAG-induced increase in proliferation is associated with improved recovery of motor function. Localized restoration of Shh in the injured rodent brain, via increased Shh signaling, has the potential to sustain endogenous cell proliferation and the mitigation of TBI-induced motor deficits albeit without the neuronal differentiation

Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure

Drone-based large-scale particle image velocimetry applied to tidal stream energy resource assessment

Resource quantification is vital in developing a tidal stream energy site but challenging in high energy areas. Drone-based large-scale particle image velocimetry (LSPIV) may provide a novel, low cost, low risk approach that improves spatial coverage compared to ADCP methods. For the first time, this study quantifies performance of the technique for tidal stream resource assessment, using three sites. Videos of the sea surface were captured while concurrent validation data were obtained (ADCP and surface drifters). Currents were estimated from the videos using LSPIV software. Variation in accuracy was attributed to wind, site geometry and current velocity. Root mean square errors (RMSEs) against drifters were 0.44 m s−1 for high winds (31 km/h) compared to 0.22 m s−1 for low winds (10 km/h). Better correlation was found for the more constrained site (r2 increased by 4%); differences between flood and ebb indicate the importance of upstream bathymetry in generating trackable surface features. Accuracy is better for higher velocities. A power law current profile approximation enables translation of surface current to currents at depth with satisfactory performance (RMSE = 0.32 m s−1 under low winds). Overall, drone video derived surface velocities are suitably accurate for “first-order” tidal resource assessments under favourable environmental conditions

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Stain-Free Quantification of Chromosomes in Live Cells Using Regularized Tomographic Phase Microscopy

Refractive index imaging is a label-free technique that enables long-term monitoring of the internal structures and molecular composition in living cells with minimal perturbation. Existing tomographic methods for the refractive index imaging lack 3-D resolution and result in artifacts that prevent accurate refractive index quantification. To overcome these limitations without compromising the capability to observe a sample in its most native condition, we have developed a regularized tomographic phase microscope (RTPM) enabling accurate refractive index imaging of organelles inside intact cells. With the enhanced accuracy, we quantify the mass of chromosomes in intact living cells, and differentiate two human colon cancer lines, HT-29 and T84 cells, solely based on the non-aqueous (dry) mass of chromosomes. In addition, we demonstrate chromosomal imaging using a dual-wavelength RTPM, which shows its potential to determine the molecular composition of cellular organelles in live cells.National Institute of Biomedical Imaging and Bioengineering (U.S.) (9P41EB015871-26A1