Diffusion of Point Defects in Two-Dimensional Colloidal Crystals

We report the first study of the dynamics of point defects, mono and di-vacancies, in a confined 2-D colloidal crystal in real space and time using digital video microscopy. The defects are introduced by manipulating individual particles with optical tweezers. The diffusion rates are measured to be $D_{mono}/a^{2}\cong3.27\pm0.03$Hz for mono-vacancies and $D_{di}/a^{2}\cong3.71\pm0.03$Hz for di-vacancies. The elementary diffusion processes are identified and it is found that the diffusion of di-vacancies is enhanced by a \textit{dislocation dissociation-recombination} mechanism. Furthermore, the defects do not follow a simple random walk but their hopping exhibits memory effects, due to the reduced symmetry (compared to the triangular lattice) of their stable configurations, and the slow relaxation rates of the lattice modes.Comment: 6 pages (REVTEX), 5 figures (PS

Synergy of stereo cloud top height and ORAC optimal estimation cloud retrieval: evaluation and application to AATSR

In this paper we evaluate the retrievals of cloud top height when stereo derived heights are combined with the radiometric cloud top heights retrieved from the ORAC (Optimal Retrieval of Aerosol and Cloud) algorithm. This is performed in a mathematically rigorous way using the ORAC optimal estimation retrieval framework, which includes the facility to use independent a priori information. Key to the use of a priori information is a characterisation of their associated uncertainty. This paper demonstrates the improvements that are possible using this approach and also considers their impact on the microphysical cloud parameters retrieved. The AATSR instrument has two views and three thermal channels so is well placed to demonstrate the synergy of the two techniques. The stereo retrieval is able to improve the accuracy of the retrieved cloud top height when compared to collocated Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), particularly in the presence of boundary layer inversions and high clouds. The impact on the microphysical properties of the cloud such as optical depth and effective radius was evaluated and found to be very small with the biggest differences occurring over bright land surfaces and for high clouds. Overall the cost of the retrievals increased indicating a poorer radiative fit of radiances to the cloud model, which currently uses a single layer cloud model. Best results and improved fit to the radiances may be obtained in the future if a multi-layer model is used

Social Disinhibition: Piloting a New Clinical Measure in Individuals with Traumatic Brain Injury

Social disinhibition difficulties are common following traumatic brain injury (TBI). However, clinically sensitive tools to objectively assess the difficulties are lacking. This study aimed to pilot a new clinical measure of social disinhibition, the social disinhibition task (SDT). Whether social disinhibition is dependent on the type of social information judgements required and whether disinhibited responses can be adjusted with additional guidance were also examined. Participants were 31 adults (25 Male) with moderate-to-severe TBI and 22 adult (17 Male) healthy control participants. Participants viewed scenes of complex social situations and were asked to describe a character in them (Part A), describe a character while inhibiting inappropriate or negative responses (Part B), and describe a character while not only inhibiting negative responses, but also providing positive responses (Part C). One-half of the items contained a faux pas requiring participants to make inferences about a character's mental state. TBI and control participants responded similarly to Part A, although control participants responded less positively than TBI participants in the faux pas items. TBI participants were significantly impaired on Part B indicating they experienced difficulties in inhibiting automatic responding. TBI participants were however able to adjust their responding in Part C so that they respond similarly to the control participants. Between group differences were not detected in reaction time. Overall, the SDT appears to be suitable to detect social inhibition difficulties in clinical settings and provides a new direction for remediation of the difficulties in individuals with TBI

Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdon: multicentre cohort study

Objectives: To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options. Design: Multicentre cohort study. Setting: Six large HIV treatment centres in southeast England. Participants: All individuals seen for care between 1 January 1996 and 31 December 2002. Main outcome measures: Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden. Results: Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of “viral load failure” with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3. Conclusions: The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients

Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine.

RATIONALE: Spatial working memory is dependent on the appropriate functioning of the prefrontal cortex (PFC). PFC activity can be modulated by noradrenaline (NA) released by afferent projections from the locus coeruleus. The coreuleo-cortical NA system could therefore be a target for cognitive enhancers of spatial working memory. Of the three classes of NA receptor potentially involved, the α2 and α1 classes seem most significant, though agents targeting these receptors have yielded mixed results. This may be partially due to the use of behavioural assays that do not translate effectively from the laboratory to the clinical setting. Use of a paradigm with improved translational potential may be essential to resolve these discrepancies. OBJECTIVES: The objective of this study was to assess the effects of PFC-infused α2 and α1 adrenergic receptor agonists on spatial working memory performance in the touchscreen continuous trial-unique non-matching to location (cTUNL) task in rats. METHODS: Young male rats were trained in the cTUNL paradigm. Cannulation of the mPFC allowed direct administration of GABA agonists for task validation, and phenylephrine and guanfacine to determine the effects of adrenergic agonists on task performance. RESULTS: Infusion of muscimol and baclofen resulted in a delay-dependent impairment. Administration of the α2 agonist guanfacine had no effect, whilst infusion of the α1 agonist phenylephrine significantly improved working memory performance. CONCLUSIONS: Spatial working memory as measured in the rat cTUNL task is dependent on the mPFC. Enhancement of noradrenergic signalling enhanced performance in this paradigm, suggesting a significant role for the α1 receptor in this facilitation.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA inkind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). CJH was funded by Wellcome Trust grant 089703/Z/09/Z.This is the final version of the article. It first appeared from Springer via http://link.springer.com/article/10.1007/s00213-015-4038-

Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. METHODS: Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. RESULTS: We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI,.1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided

Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions

During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render ~500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus

Characterising the phenotypic diversity of Papilio dardanus wing patterns using an extensive museum collection

The history of 20th Century evolutionary biology can be followed through the study of mimetic butterflies. From the initial findings of discontinuous polymorphism through the debates regarding the evolution of mimicry and the step-size of evolutionary change, to the studies on supergene evolution and molecular characterisation of butterfly genomes, mimetic butterflies have been at the heart of evolutionary thought for over 100 years. During this time, few species have received as much attention and in-depth study as Papilio dardanus. To assist all aspects of mimicry research, we present a complete data-derived overview of the extent of polymorphism within this species. Using historical samples permanently held by the NHM London, we document the extent of phenotypic variation and characterise the diversity present in each of the subspecies and how it varies across Africa. We also demonstrate an association between “imperfect” mimetic forms and the transitional race formed in the area where Eastern and Western African populations meet around Lake Victoria. We present a novel portal for access to this collection, www.mimeticbutterflies.org, allowing remote access to this unique repository. It is hoped that this online resource can act as a nucleus for the sharing and dissemination of other collections databases and imagery connected with mimetic butterflies

Permeability of fault rocks in siliciclastic reservoirs: Recent advances

It is common practice to create geologically realistic production simulation models of fault compartmentalized reservoirs. Data on fault rock properties are required, to calculate transmissibility multipliers that are incorporated into these models, to take into account the impact of fault rocks on fluid flow. Industry has generated large databases of fault rock permeability, which are commonly used for this purpose. Much of the permeability data were collected using two inappropriate laboratory practices with measurements being made at low confining pressure with distilled water as the permeant. New fault rock permeability measurements have been made at high confining pressures using formation compatible brines as the permeant. Fault permeability decreases by an average of five fold as net confining pressure is increased from that used in previous measurements (i.e. ∼70 psi) to that approaching in situ conditions (i.e. 5000 psi). On the other hand, permeability increases by around the same amount if reservoir brine is used as the permeant instead of distilled water. So overall, these two inappropriate laboratory practices used in previous studies cancel each other out meaning that legacy fault rock property data may still have value for modelling cross-fault flow in petroleum reservoirs. A poor correlation exists between clay content and fault rock permeability, which is easily explained by the application of a simple clay-sand mixing model. This emphasises the need to gather fault permeability data directly from the reservoir of interest. The cost of such studies could be significantly reduced by screening core samples using a CT scanner so that only samples that are likely to impact fluid flow are analyzed in detail. The stress dependence of fault permeability identified in this study is likely to be primarily caused by damage generated during or following coring. So it is probably not necessary to take into account the impact of stress on fault permeability in simulation models unless the faults of interest are likely to reach failure and reactivate