Rapid rotation of micron and submicron dielectric particles measured using optical tweezers

We demonstrate the use of a laser trap (‘optical tweezers’) and back-focal-plane position detector to measure rapid rotation in aqueous solution of single particles with sizes in the vicinity of 1 μm. Two types of rotation were measured: electrorotation of polystyrene microspheres and rotation of the flagellar motor of the bacterium Vibrio alginolyticus. In both cases, speeds in excess of 1000 Hz (rev s−1) were measured. Polystyrene beads of diameter about 1 μm labelled with smaller beads were held at the centre of a microelectrode array by the optical tweezers. Electrorotation of the labelled beads was induced by applying a rotating electric field to the solution using microelectrodes. Electrorotation spectra were obtained by varying the frequency of the applied field and analysed to obtain the surface conductance of the beads. Single cells of V. alginolyticus were trapped and rotation of the polar sodium-driven flagellar motor was measured. Cells rotated more rapidly in media containing higher concentrations of Na+, and photodamage caused by the trap was considerably less when the suspending medium did not contain oxygen. The technique allows single-speed measurements to be made in less than a second and separate particles can be measured at a rate of several per minute

Assembly and architecture of the EBV B cell entry triggering complex.

Epstein-Barr Virus (EBV) is an enveloped double-stranded DNA virus of the gammaherpesvirinae sub-family that predominantly infects humans through epithelial cells and B cells. Three EBV glycoproteins, gH, gL and gp42, form a complex that targets EBV infection of B cells. Human leukocyte antigen (HLA) class II molecules expressed on B cells serve as the receptor for gp42, triggering membrane fusion and virus entry. The mechanistic role of gHgL in herpesvirus entry has been largely unresolved, but it is thought to regulate the activation of the virally-encoded gB protein, which acts as the primary fusogen. Here we study the assembly and function of the reconstituted B cell entry complex comprised of gHgL, gp42 and HLA class II. The structure from negative-stain electron microscopy provides a detailed snapshot of an intermediate state in EBV entry and highlights the potential for the triggering complex to bring the two membrane bilayers into proximity. Furthermore, gHgL interacts with a previously identified, functionally important hydrophobic pocket on gp42, defining the overall architecture of the complex and playing a critical role in membrane fusion activation. We propose a macroscopic model of the initiating events in EBV B cell fusion centered on the formation of the triggering complex in the context of both viral and host membranes. This model suggests how the triggering complex may bridge the two membrane bilayers, orienting critical regions of the N- and C- terminal ends of gHgL to promote the activation of gB and efficient membrane fusion

THE ACTION OF TERRAMYCIN ON THE GROWTH OF STRAINS OF INFLUENZA, HERPES SIMPLEX, AND RABIES VIRUSES IN CHICK EMBRYOS AND MICE

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72961/1/j.1749-6632.1950.tb42175.x.pd

Lack of Evidence from Studies of Soluble Protein Fragments that Knops Blood Group Polymorphisms in Complement Receptor-Type 1 Are Driven by Malaria

Complement receptor-type 1 (CR1, CD35) is the immune-adherence receptor, a complement regulator, and an erythroid receptor for Plasmodium falciparum during merozoite invasion and subsequent rosette formation involving parasitized and non-infected erythrocytes. The non-uniform geographical distribution of Knops blood group CR1 alleles Sl1/2 and McCa/b may result from selective pressures exerted by differential exposure to infectious hazards. Here, four variant short recombinant versions of CR1 were produced and analyzed, focusing on complement control protein modules (CCPs) 15–25 of its ectodomain. These eleven modules encompass a region (CCPs 15–17) key to rosetting, opsonin recognition and complement regulation, as well as the Knops blood group polymorphisms in CCPs 24–25. All four CR1 15–25 variants were monomeric and had similar axial ratios. Modules 21 and 22, despite their double-length inter-modular linker, did not lie side-by-side so as to stabilize a bent-back architecture that would facilitate cooperation between key functional modules and Knops blood group antigens. Indeed, the four CR1 15–25 variants had virtually indistinguishable affinities for immobilized complement fragments C3b (KD = 0.8–1.1 µM) and C4b (KD = 5.0–5.3 µM). They were all equally good co-factors for factor I-catalysed cleavage of C3b and C4b, and they bound equally within a narrow affinity range, to immobilized C1q. No differences between the variants were observed in assays for inhibition of erythrocyte invasion by P. falciparum or for rosette disruption. Neither differences in complement-regulatory functionality, nor interactions with P. falciparum proteins tested here, appear to have driven the non-uniform geographic distribution of these alleles

Measuring errors and violations on the road: A bifactor modeling approach to the Driver Behavior Questionnaire

The Driver Behavior Questionnaire (DBQ) is a self-report measure of driving behavior that has been widely used over more than 20 years. Despite this wealth of evidence a number of questions remain, including understanding the correlation between its violations and errors sub-components, identifying how these components are related to crash involvement, and testing whether a DBQ based on a reduced number of items can be effective. We address these issues using a bifactor modeling approach to data drawn from the UK Cohort II longitudinal study of novice drivers. This dataset provides observations on 12,012 drivers with DBQ data collected at .5, 1, 2 and 3 years after passing their test. A bifactor model, including a general factor onto which all items loaded, and specific factors for ordinary violations, aggressive violations, slips and errors fitted the data better than correlated factors and second-order factor structures. A model based on only 12 items replicated this structure and produced factor scores that were highly correlated with the full model. The ordinary violations and general factor were significant independent predictors of crash involvement at 6 months after starting independent driving. The discussion considers the role of the general and specific factors in crash involvemen

The Seismic Noise Environment of Antarctica

This characterization of the seismic noise environment of Antarctica, documentation of instrument performance, and comparisons of installation conditions (e.g., ice vaults vs. rock sites) is intended to facilitate optimization of future seismological deployments in such environments. We analyze data from a range of recent experiments to provide a broad geographical characterization of Antarctica’s seismic noise environment, which can now include more substantial observations from regions that are free from anthropogenic noise contamination

Novice drivers’ individual trajectories of driver behavior over the first three years of driving

Identifying the changes in driving behavior that underlie the decrease in crash risk over the first few months of driving is key to efforts to reduce injury and fatality risk in novice drivers. This study represented a secondary data analysis of 1148 drivers who participated in the UK Cohort II study. The Driver Behavior Questionnaire was completed at 6 months and 1, 2 and 3 years after licensure. Linear latent growth models indicated significant increases across development in all four dimensions of aberrant driving behavior under scrutiny: aggressive violations, ordinary violations, errors and slips. Unconditional and conditional latent growth class analyses showed that the observed heterogeneity in individual trajectories was explained by the presence of multiple homogeneous groups of drivers, each exhibiting specific trajectories of aberrant driver behavior. Initial levels of aberrant driver behavior were important in identifying sub-groups of drivers. All classes showed positive slopes; there was no evidence of a group of drivers whose aberrant behavior decreased over time that might explain the decrease in crash involvement observed over this period. Male gender and younger age predicted membership of trajectories with higher levels of aberrant behavior. These findings highlight the importance of early intervention for improving road safety. We discuss the implications of our findings for understanding the behavioral underpinnings of the decrease in crash involvement observed in the early months of driving

GABA-ergic Dynamics in Human Frontotemporal Networks Confirmed by Pharmaco-Magnetoencephalography.

To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked 'mismatch negativity' response and transiently induced oscillations. Here, we probe GABAergic influences in the networks using double-blind placebo-controlled randomized-crossover administration of the GABA reuptake inhibitor, tiagabine (oral, 10 mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both drug sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. We found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco- magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.SIGNIFICANCE STATEMENT Understanding human brain function and developing new treatments require good models of brain function. We tested a detailed generative model of cortical microcircuits that accurately reproduced human magnetoencephalography, to quantify network dynamics and connectivity in frontotemporal cortex. This approach identified the effect of a test drug (GABA-reuptake inhibitor, tiagabine) on neuronal function (GABA-ergic dynamics), opening the way for psychopharmacological studies in health and disease with the mechanistic precision afforded by generative models of the brain