Quantitative image mean squared displacement (iMSD) analysis of the dynamics of profilin 1 at the membrane of live cells.

Image mean square displacement analysis (iMSD) is a method allowing the mapping of diffusion dynamics of molecules in living cells. However, it can also be used to obtain quantitative information on the diffusion processes of fluorescently labelled molecules and how their diffusion dynamics change when the cell environment is modified. In this paper, we describe the use of iMSD to obtain quantitative data of the diffusion dynamics of a small cytoskeletal protein, profilin 1 (pfn1), at the membrane of live cells and how its diffusion is perturbed when the cells are treated with Cytochalasin D and/or the interactions of pfn1 are modified when its actin and polyphosphoinositide binding sites are mutated (pfn1-R88A). Using total internal reflection fluorescence microscopy images, we obtained data on isotropic and confined diffusion coefficients, the proportion of cell areas where isotropic diffusion is the major diffusion mode compared to the confined diffusion mode, the size of the confinement zones and the size of the domains of dynamic partitioning of pfn1. Using these quantitative data, we could demonstrate a decreased isotropic diffusion coefficient for the cells treated with Cytochalasin D and for the pfn1-R88A mutant. We could also see changes in the modes of diffusion between the different conditions and changes in the size of the zones of pfn1 confinements for the pfn1 treated with Cytochalasin D. All of this information was acquired in only a few minutes of imaging per cell and without the need to record thousands of single molecule trajectories

Relationship Between Quantitative MRI Biomarkers and Patient-Reported Outcome Measures After Cartilage Repair Surgery: A Systematic Review.

Background:Treatment of articular cartilage injuries remains a clinical challenge, and the optimal tools to monitor and predict clinical outcomes are unclear. Quantitative magnetic resonance imaging (qMRI) allows for a noninvasive biochemical evaluation of cartilage and may offer advantages in monitoring outcomes after cartilage repair surgery. Hypothesis:qMRI sequences will correlate with early pain and functional measures. Study Design:Systematic review; Level of evidence, 3. Methods:A PubMed search was performed with the following search terms: knee AND (cartilage repair OR cartilage restoration OR cartilage surgery) AND (delayed gadolinium-enhanced MRI OR t1-rho OR T2 mapping OR dgemric OR sodium imaging OR quantitative imaging). Studies were included if correlation data were included on quantitative imaging results and patient outcome scores. Results:Fourteen articles were included in the analysis. Eight studies showed a significant relationship between quantitative cartilage imaging and patient outcome scores, while 6 showed no relationship. T2 mapping was examined in 11 studies, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in 4 studies, sodium imaging in 2 studies, glycosaminoglycan chemical exchange saturation transfer (gagCEST) in 1 study, and diffusion-weighted imaging in 1 study. Five studies on T2 mapping showed a correlation between T2 relaxation times and clinical outcome scores. Two dGEMRIC studies found a correlation between T1 relaxation times and clinical outcome scores. Conclusion:Multiple studies on T2 mapping, dGEMRIC, and diffusion-weighted imaging showed significant correlations with patient-reported outcome measures after cartilage repair surgery, although other studies showed no significant relationship. qMRI sequences may offer a noninvasive method to monitor cartilage repair tissue in a clinically meaningful way, but further refinements in imaging protocols and clinical interpretation are necessary to improve utility

Symmetries of Abelian Orbifolds

Using the Polya Enumeration Theorem, we count with particular attention to C^3/Gamma up to C^6/Gamma, abelian orbifolds in various dimensions which are invariant under cycles of the permutation group S_D. This produces a collection of multiplicative sequences, one for each cycle in the Cycle Index of the permutation group. A multiplicative sequence is controlled by its values on prime numbers and their pure powers. Therefore, we pay particular attention to orbifolds of the form C^D/Gamma where the order of Gamma is p^alpha. We propose a generalization of these sequences for any D and any p.Comment: 75 pages, 13 figures, 30 table

Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation

Heavy metal compounds have toxic and medicinal potential through capacity to form strong specific bonds with macromolecules, and the interaction of platinum drugs at the major groove nitrogen atom of guanine bases primarily underlies their therapeutic activity. By crystallographic analysis of transition metal-and in particular platinum compound-DNA site selectivity in the nucleosome core, we establish that steric accessibility, which is controlled by specific structural parameters of the double helix, modulates initial guanine-metal bond formation. Moreover, DNA conformational features can be linked to both similarities and distinctions in platinum drug adduct formation between the naked and nucleosomal DNA states. Notably, structures that facilitate initial platinum-guanine bond formation can oppose cross-link generation, rationalizing the occurrence of long-lived therapeutically ineffective monofunctional adducts. These findings illuminate DNA structure-dependent reactivity and provide a novel framework for understanding metal-double helix interactions, which should facilitate the development of improved chromatin-targeting medicinal agent

Platelet count and liver function tests in proteinuric and chronic hypertension in pregnancy

Platelet counts and plasma enzyme estimations were performed in 207 pregnant patients with proteinuric hypertension and in 60 patients with chronic hypertension. Patients with abruptio placentae were excluded. In the proteinuric hypertensive patients a low platelet count « 150000/mm3 ) was found in 63 (30%) and elevated transaminase levels in 50 (24%) and both abnormalities were present in 47 patients (23%). The serum lactate dehydrogenase (LDH) value was mildly elevated in most proteinuric hypertensive women, but a markedly elevated LDH level ( > 400 IU/I) was usually associated with other evidence of liver necrosis. Raised plasma alkaline phosphatase and -y-glutamyhransferase levels were not related to the occurrence or severity of liver necrosis. In proteinuric hypertensive patients a low platelet count or elevated transaminase level was associated with deteriorating renal function, increased maternal morbidity, increased incidence of low-birth-weight babies and a raised perinatal mortality rate (149/1 000). In patients with chronic hypertension, 1 had a low platelet count but none had elevated transaminase, LDH or other enzyme levels and there was no recorded perinatal mortality

Dynamic Load and Storage Integration

Modern technology combined with the desire to minimize the size and weight of a ship’s power system are leading to renewed interest in more electric or all electric ships. An important characteristic of the emerging ship power system is an increasing level of load variability, with some future pulsed loads requiring peak power in excess of the available steady– state power. This inevitably leads to the need for some additional energy storage beyond that inherent in the fuel. With the current and evolving technology, it appears that storage will be in the form of batteries, rotating machines, and capacitors. All of these are in use on ships today and all have enjoyed significant technological improvements over the last decade. Moreover all are expected to be further enhanced by today’s materials research. A key benefit of storage is that, when it can be justified for a given load, it can have additional beneficial uses such as ride-through capability to restart a gas turbine if there is an unanticipated power loss; alternatively, storage can be used to stabilize the power grid when switching large loads. Knowing when to stage gas turbine utilization versus energy storage is a key subject in this paper. The clear need for storage has raised the opportunity to design a comprehensive storage system, sometimes called an energy magazine, that can combine intermittent generation as well as any or all of the other storage technologies to provide a smaller, lighter and better performing system than would individual storage solutions for each potential application.Center for Electromechanic

Is stimulation of leaf photosynthesis by elevated carbon dioxide concentration maintained in the long term? A test with Lolium perenne grown for 10 years at two nitrogen fertilization levels under Free Air CO2 Enrichment (FACE)

Photosynthesis is commonly stimulated in grasslands with experimental increases in atmospheric CO2 concentration ([CO2]), a physiological response that could significantly alter the future carbon cycle if it persists in the long term.. Yet an acclimation of photosynthetic capacity suggested by theoretical models and short-term experiments could completely remove this effect of CO2. Perennial ryegrass (Lolium perenne L. cv. Bastion) was grown under an elevated [CO2] of 600 mumol mol(-1) for 10 years using Free Air CO2 Enrichment (FACE), with two contrasting nitrogen levels and abrupt changes in the source: sink ratio following periodic harvests. More than 3000 measurements characterized the response of leaf photosynthesis and stomatal conductance to elevated [CO2] across each growing season for the duration of the experiment. Over the 10 years as a whole, growth at elevated [CO2] resulted in a 43% higher rate of light-saturated leaf photosynthesis and a 36% increase in daily integral of leaf CO2 uptake. Photosynthetic stimulation was maintained despite a 30% decrease in stomatal conductance and significant decreases in both the apparent, maximum carboxylation velocity (V-c,V-max) and the maximum rate of electron transport (J(max)). Immediately prior to the periodic (every 4-8 weeks) cuts of the L. perenne stands, V-c,V-max and J(max), were significantly lower in elevated than in ambient [CO2] in the low-nitrogen treatment. This difference was smaller after the cut, suggesting a dependence upon the balance between the sources and sinks for carbon. In contrast with theoretical expectations and the results of shorter duration experiments, the present results provide no significant change in photosynthetic stimulation across a 10-year period, nor greater acclimation in V-c,V-max and J(max) in the later years in either nitrogen treatment

Probing the Space of Toric Quiver Theories

We demonstrate a practical and efficient method for generating toric Calabi-Yau quiver theories, applicable to both D3 and M2 brane world-volume physics. A new analytic method is presented at low order parametres and an algorithm for the general case is developed which has polynomial complexity in the number of edges in the quiver. Using this algorithm, carefully implemented, we classify the quiver diagram and assign possible superpotentials for various small values of the number of edges and nodes. We examine some preliminary statistics on this space of toric quiver theories

Effects of diamagnetic levitation on bacterial growth in liquid

Diamagnetic levitation is a technique that uses a strong, spatially-varying magnetic field to levitate diamagnetic materials, such as water and biological cells. This technique has the potential to simulate aspects of weightlessness, on the Earth. In common with all ground-based techniques to simulate weightlessness, however, there are effects introduced by diamagnetic levitation that are not present in space. Since there have been few studies that systematically investigate these differences, diamagnetic levitation is not yet being fully exploited. For the first time, we critically assess the effect of diamagnetic levitation on a bacterial culture in liquid. We used a superconducting magnet to levitate growing bacterial cultures for up to 18 hours, in a series of experiments to determine the effect of diamagnetic levitation on all phases of the bacterial growth cycle. We find that diamagnetic levitation increases the rate of population growth in a liquid culture. The speed of sedimentation of the bacterial cells to the bottom of the container is considerably reduced. Further experiments and microarray gene analysis show that the growth enhancement is due to greater oxygen availability in the magnetically levitated sample. We demonstrate that the magnetic field that levitates the cells also induces convective stirring in the liquid, an effect not present in microgravity. We present a simple theoretical model, showing how the paramagnetic force on dissolved oxygen can cause the liquid to become unstable to convection when the consumption of oxygen by the bacteria generates an oxygen concentration gradient. We propose that this convection enhances oxygen availability by transporting oxygen around the sample. Since convection is absent in space, these results are of significant importance and timeliness to researchers considering using diamagnetic levitation to explore weightless effects on living organisms and a broad range of other topics in the physical and life sciences