Probing yield stress fluids with a vibrational rheometer

Low volume fraction colloidal gels can possess small yield stresses that are able to trap particles or bubbles within the matrix indefinitely. At rest, the stress applied to the network by a probe particle is limited by the density difference between the probe and continuous phase materials. However, vibration of the sample is an acceleration that causes the inertial particles to impart a stress on the fluid; the stress that results from a vibration is also a function of the frequency and amplitude of the vibration. The microscale fluid properties around the probe particles can be elucidated by studying the effects of vibration on the sample. While applying a vertical mechanical vibration to the sample (1 to 5 mm amplitude, 10 to 100 Hz), we make use of high speed particle tracking to record particle trajectories and measure strain, yielding, flow, and recovery of various complex fluid networks. The measurements enable comparison of the suspension and yielding behaviour of complex fluids with similar rheology but greatly varying microstructures, allowing determination of the optimal approaches to stabilisation of various formulations. Dispersions of colloidal microgels, nanofibres, and wormlike micelles are used in different combinations to explore the robustness of disparate structures to repeated perturbations. Measurements are made of local strain, elasticity, yield stress, and sedimentation rate and compared to continuum predictions for yield stress fluids with more homogeneous microstructures. Please click Additional Files below to see the full abstract

Feedback inhibition of L1 and alu retrotransposition through altered double strand break repair kinetics

<p>Abstract</p> <p>Background</p> <p>Cells adapt to various chronic toxic exposures in a multitude of ways to minimize further damage and maximize their growth potential. Expression of L1 elements in the human genome can be greatly deleterious to cells, generating numerous double strand breaks (DSBs). Cells have been reported to respond to chronic DSBs by altering the repair of these breaks, including increasing the rate of homology independent DSB repair. Retrotransposition is strongly affected by proteins involved in DSB repair. Therefore, L1 expression has the potential to be a source of chronic DSBs and thus bring about the changes in cellular environment that could ultimately restrict its own retrotransposition.</p> <p>Results</p> <p>We demonstrate that constitutive L1 expression leads to quicker DSB repair and decreases in the retrotransposition potential of L1 and other retrotransposons dependent on L1 expression for their mobility. This cellular adaptation results in reduced sensitivity to L1 induced toxicity. These effects can be induced by constitutive expression of the functional L1 ORF2 alone, but not by the constitutive expression of an L1 open reading frame 2 with mutations to its endonuclease and reverse transcriptase domains. This adaptation correlates with the relative activity of the L1 introduced into the cells.</p> <p>Conclusions</p> <p>The increased number of DSBs resulting from constitutive expression of L1 results in a more rapid rate of repair. The cellular response to this L1 expression also results in attenuation of retrotransposition and reduced sensitivity of the cells to negative consequences of L1 ORF2 expression. The influence does not appear to be through RNA interference. We believe that the increased rate of DSB repair is the most likely cause of the attenuation of retrotransposition. These alterations act as a fail safe mechanism that allows cells to escape the toxicity associated with the unchecked L1 expression. This gives cells that overexpress L1, such as tumor cells, the ability to survive the high levels of expression. However, the increased rate of break repair may come at the cost of accuracy of repair of the lesion, resulting in increased genomic instability.</p

Preliminary evidence for human globus pallidus pars interna neurons signaling reward and sensory stimuli.

The globus pallidus pars interna (GPi) is a component of the basal ganglia, a network of subcortical nuclei that process motor, associative, and limbic information. While non-human primate studies have suggested a role for the GPi in non-motor functions, there have been no single-unit studies of non-motor electrophysiological behavior of human GPi neurons. We therefore sought to extend these findings by collecting single-unit recordings from awake patients during functional stereotactic neurosurgery targeting the GPi for deep brain stimulation. To assess cellular responses to non-motor information, patients performed a reward task where virtual money could be won, lost, or neither, depending on their performance while cellular activity was monitored. Changes in the firing rates of isolated GPi neurons after the presentation of reward-related stimuli were compared between different reward contingencies (win, loss, null). We observed neurons that modulated their firing rate significantly to the presentation of reward-related stimuli. We furthermore found neurons that responded to visual-stimuli more broadly. This is the first single-unit evidence of human GPi neurons carrying non-motor information. These results are broadly consistent with previous findings in the animal literature and suggest non-motor information may be represented in the single-unit activity of human GPi neurons.NAH is supported by a Unilever/Lipton Graduate Fellowship in Neuroscience and a University of Toronto Fellowship. WDH is supported by a CIHR operating grant (98006). VV is a Wellcome Trust (WT) intermediate Clinical Fellow (WT093705MA).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neuroscience.2016.04.02

Adaptive responses to cool climate promotes persistence of a non-native lizard

Successful establishment and range expansion of non-native species often require rapid accommodation of novel environments. Here, we use common-garden experiments to demonstrate parallel adaptive evolutionary response to a cool climate in populations of wall lizards (Podarcis muralis) introduced from southern Europe into England. Low soil temperatures in the introduced range delay hatching, which generates directional selection for a shorter incubation period. Non-native lizards from two separate lineages have responded to this selection by retaining their embryos for longer before oviposition-hence reducing the time needed to complete embryogenesis in the nest-and by an increased developmental rate at low temperatures. This divergence mirrors local adaptation across latitudes and altitudes within widely distributed species and suggests that evolutionary responses to climate can be very rapid. When extrapolated to soil temperatures encountered in nests within the introduced range, embryo retention and faster developmental rate result in one to several weeks earlier emergence compared with the ancestral state. We show that this difference translates into substantial survival benefits for offspring. This should promote short- and long-term persistence of non-native populations, and ultimately enable expansion into areas that would be unattainable with incubation duration representative of the native range

The ugrizYJHK luminosity distributions and densities from the combined MGC, SDSS and UKIDSS LAS datasets

We combine data from the MGC, SDSS and UKIDSS LAS surveys to produce ugrizYJHK luminosity functions and densities from within a common, low redshift volume (z<0.1, ~71,000 h_1^-3 Mpc^3 for L* systems) with 100 per cent spectroscopic completeness. In the optical the fitted Schechter functions are comparable in shape to those previously reported values but with higher normalisations (typically 0, 30, 20, 15, 5 per cent higher phi*-values in u, g, r, i, z respectively over those reported by the SDSS team). We attribute these to differences in the redshift ranges probed, incompleteness, and adopted normalisation methods. In the NIR we find significantly different Schechter function parameters (mainly in the M* values) to those previously reported and attribute this to the improvement in the quality of the imaging data over previous studies. This is the first homogeneous measurement of the extragalactic luminosity density which fully samples both the optical and near-IR regimes. Unlike previous compilations that have noted a discontinuity between the optical and near-IR regimes our homogeneous dataset shows a smooth cosmic spectral energy distribution (CSED). After correcting for dust attenuation we compare our CSED to the expected values based on recent constraints on the cosmic star-formation history and the initial mass function.Comment: 17 pages, 13 figures, Accepted in MNRAS: 2010 January 18; in original form 2009 August 1

Macroscopic effects of the spectral structure in turbulent flows

Two aspects of turbulent flows have been the subject of extensive, split research efforts: macroscopic properties, such as the frictional drag experienced by a flow past a wall, and the turbulent spectrum. The turbulent spectrum may be said to represent the fabric of a turbulent state; in practice it is a power law of exponent \alpha (the "spectral exponent") that gives the revolving velocity of a turbulent fluctuation (or "eddy") of size s as a function of s. The link, if any, between macroscopic properties and the turbulent spectrum remains missing. Might it be found by contrasting the frictional drag in flows with differing types of spectra? Here we perform unprecedented measurements of the frictional drag in soap-film flows, where the spectral exponent \alpha = 3 and compare the results with the frictional drag in pipe flows, where the spectral exponent \alpha = 5/3. For moderate values of the Reynolds number Re (a measure of the strength of the turbulence), we find that in soap-film flows the frictional drag scales as Re^{-1/2}, whereas in pipe flows the frictional drag scales as Re^{-1/4} . Each of these scalings may be predicted from the attendant value of \alpha by using a new theory, in which the frictional drag is explicitly linked to the turbulent spectrum. Our work indicates that in turbulence, as in continuous phase transitions, macroscopic properties are governed by the spectral structure of the fluctuations.Comment: 6 pages, 3 figure

Looking to the future: predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Background Chronic kidney disease (CKD) is common and important due to poor outcomes. An ability to stratify CKD care based on outcome risk should improve care for all. Our objective was to develop and validate 5-year outcome prediction tools in a large population-based CKD cohort. Model performance was compared with the recently reported ‘kidney failure risk equation’ (KFRE) models. Methods Those with CKD in the Grampian Laboratory Outcomes Mortality and Morbidity Study-I (3396) and -II (18 687) cohorts were used to develop and validate a renal replacement therapy (RRT) prediction tool. The discrimination, calibration and overall performance were assessed. The net reclassification index compared performance of the developed model and the 3- and 4-variable KFRE model to predict RRT in the validation cohort. Results The developed model (with measures of age, sex, excretory renal function and proteinuria) performed well with a C-statistic of 0.938 (0.918–0.957) and Hosmer–Lemeshow (HL) χ2 statistic 4.6. In the validation cohort (18 687), the developed model falsely identified fewer as high risk (414 versus 3278 individuals) compared with the KFRE 3-variable model (measures of age, sex and excretory renal function), but had more false negatives (58 versus 21 individuals). The KFRE 4-variable model could only be applied to 2274 individuals because of a lack of baseline urinary albumin creatinine ratio data, thus limiting its use in routine clinical practice. Conclusions CKD outcome prediction tools have been developed by ourselves and others. These tools could be used to stratify care, but identify both false positives and -negatives. Further refinement should optimize the balance between identifying those at increased risk with clinical utility for stratifying care

Is routine hospital episode data sufficient for identifying individuals with chronic kidney disease?

Internationally, investment in the availability of routine health care data for improving health, health surveillance and health care is increasing. We assessed the validity of hospital episode data for identifying individuals with chronic kidney disease compared to biochemistry data in a large population-based cohort, the Grampian Laboratory Outcomes, Morbidity and Mortality Study-II (n = 70,435). Grampian Laboratory Outcomes, Morbidity and Mortality Study-II links hospital episode data to biochemistry data for all adults in a health region with impaired kidney function and random samples of individuals with normal and unmeasured kidney function in 2003. We compared identification of individuals with chronic kidney disease by hospital episode data (based on International Classification of Diseases-10 codes) to the reference standard of biochemistry data (at least two estimated glomerular filtration rates 97%). Using routine health care data from multiple sources offers the best opportunity to identify individuals with chronic kidney disease

Definitions of progression in chronic kidney disease-predictors and relationship to renal replacement therapy in a population cohort with a 6 year follow-up

Background. Chronic kidney disease (CKD) is common, important and associated with increased healthcare needs due to CKD progression. Definitions of renal disease progression are multiple, and not always comparable. A measure of 'progression' directly comparable with renal replacement therapy (RRT) initiation would identify 'progressors' in research and for healthcare planning.Methods. The Grampian Laboratory Outcomes Morbidity and Mortality Study (GLOMMS-I) is a community cohort with CKD from 2003, followed up to June 2009 for (i) RRT initiation and (ii) 'progression': sustained reduction in estimated glomerular filtration rate (eGFR) by 15 mL/min/1.73 m(2) (equivalent to CKD stage change), or to <10 mL/min/1.73 m(2), whichever occurs first. Predictors were baseline demographics and comorbidity. The use of the Kidney Disease: Improving Global Outcomes-2012 progression definition was also explored.Results. Two thousand two hundred and eighty-nine and 1044 had Stage 3 and 4 CKD, 44% were males. Overall, RRT initiation and progression rates were 0.97 and 3.50 per 100 patient-years (py). Females had significantly lower progression and RRT initiation rates. The progression rate was not dependent on CKD stage [incidence rate ratio (IRR) for Stage 4 (versus Stage 3) 0.9 (95% CI 0.8-1.2)], whereas the RRT initiation rate was [IRR 5.6 (95% CI 3.8-8.2)]. Increased proteinuria was associated with both greater RRT initiation and progression rates.Conclusions. Progression and RRT initiation rate ratios allow comparison of predictors of these outcomes. Higher rates of both in males suggest that greater RRT initiation rate is biological rather than due to preferential treatment. Similar progression but very different RRT initiation rates in Stage 3 and 4 CKD suggests that CKD stage effect on RRT initiation is a function of endpoint proximity rather than faster renal function deterioration.Background. Chronic kidney disease (CKD) is common, important and associated with increased healthcare needs due to CKD progression. Definitions of renal disease progression are multiple, and not always comparable. A measure of 'progression' directly comparable with renal replacement therapy (RRT) initiation would identify 'progressors' in research and for healthcare planning.Methods. The Grampian Laboratory Outcomes Morbidity and Mortality Study (GLOMMS-I) is a community cohort with CKD from 2003, followed up to June 2009 for (i) RRT initiation and (ii) 'progression': sustained reduction in estimated glomerular filtration rate (eGFR) by 15 mL/min/1.73 m(2) (equivalent to CKD stage change), or to <10 mL/min/1.73 m(2), whichever occurs first. Predictors were baseline demographics and comorbidity. The use of the Kidney Disease: Improving Global Outcomes-2012 progression definition was also explored.Results. Two thousand two hundred and eighty-nine and 1044 had Stage 3 and 4 CKD, 44% were males. Overall, RRT initiation and progression rates were 0.97 and 3.50 per 100 patient-years (py). Females had significantly lower progression and RRT initiation rates. The progression rate was not dependent on CKD stage [incidence rate ratio (IRR) for Stage 4 (versus Stage 3) 0.9 (95% CI 0.8-1.2)], whereas the RRT initiation rate was [IRR 5.6 (95% CI 3.8-8.2)]. Increased proteinuria was associated with both greater RRT initiation and progression rates.Conclusions. Progression and RRT initiation rate ratios allow comparison of predictors of these outcomes. Higher rates of both in males suggest that greater RRT initiation rate is biological rather than due to preferential treatment. Similar progression but very different RRT initiation rates in Stage 3 and 4 CKD suggests that CKD stage effect on RRT initiation is a function of endpoint proximity rather than faster renal function deterioration