Surface charge, fluidity, and calcium uptake by rat intestinal brush-border vesicles

AbstractBiological membrane outer surfaces are negatively charged and interact with positively charged calcium ion during calcium uptake. Positively charged polycations such as polyarginine bind to membranes with high affinity, displacing bound calcium from the membrane. We tested the effect of polyarginine on uptake of calcium by brush-border membrane vecicles and examined the responses in terms of membrane fluidity by electron paramagnetic resonance (EPR). Polyarginine inhibited the saturable component of calcium uptake by a mechanism combining inhibition characteristics of strontium (competitive) and magnesium (non-competitive). Unlike the inhibition of non-saturable calcium uptake by strontium and magnesium, polyarginine increased kD, the rate constant for non-saturable calcium uptake, by a concentration dependent mechanism. These effects of polyarginine on calcium uptake were associated with decreased membrane fluidity at the uptake temperature. These findings are consistent with a role for surface negative charge in determining both saturable and non-saturable calcium uptake. Increased membrane fluidity is associated with decreased saturable and increased non-saturable calcium uptake. Although increased fluidity might be involved in the increased kD for non-saturable uptake, the concentration-specific stimulating effect of polyarginine suggests a gating mechanism

Switching dynamics of surface stabilized ferroelectric liquid crystal cells: effects of anchoring energy asymmetry

We study both theoretically and experimentally switching dynamics in surface stabilized ferroelectric liquid crystal cells with asymmetric boundary conditions. In these cells the bounding surfaces are treated differently to produce asymmetry in their anchoring properties. Our electro-optic measurements of the switching voltage thresholds that are determined by the peaks of the reversal polarization current reveal the frequency dependent shift of the hysteresis loop. We examine the predictions of the uniform dynamical model with the anchoring energy taken into account. It is found that the asymmetry effects are dominated by the polar contribution to the anchoring energy. Frequency dependence of the voltage thresholds is studied by analyzing the properties of time-periodic solutions to the dynamical equation (cycles). For this purpose, we apply the method that uses the parameterized half-period mappings for the approximate model and relate the cycles to the fixed points of the composition of two half-period mappings. The cycles are found to be unstable and can only be formed when the driving frequency is lower than its critical value. The polar anchoring parameter is estimated by making a comparison between the results of modelling and the experimental data for the shift vs frequency curve. For a double-well potential considered as a deformation of the Rapini-Papoular potential, the branch of stable cycles emerges in the low frequency region separated by the gap from the high frequency interval for unstable cycles.Comment: 35 pages, 15 figure

Searching for physics beyond the Standard Model through the dipole interaction

The magnetic dipole interaction played a central role in the development of QED, and continued in that role for the Standard Model. The muon anomalous magnetic moment has served as a benchmark for models of new physics, and the present experimental value is larger than the standard-model value by more than three standard deviations. The electric dipole moment (EDM) violates parity ({$P$}) and time-reversal ({$T$}) symmetries, and in the context of the $CPT$ theorem, the combination of charge conjugation and parity ($CP$). Since a new source of {$CP$} violation outside of that observed in the $K$ and $B$ meson systems is needed to help explain the baryon asymmetry of the universe, searches for EDMs are being carried out worldwide on a number of systems. The standard-model value of the EDM is immeasurably small, so any evidence for an EDM would signify the observation of new physics. Unique opportunities exist for EDM searches using polarized proton, deuteron or muon beams in storage rings. This talk will provide an overview of the theory of dipole moments, and the relevant experiments. The connection to the transition dipole moment that could produce lepton flavor violating interactions such as $\mu^+ \rightarrow e^+ \gamma$ is also mentioned.Comment: Invited Plenary talk at the 19th International Spin Physics Symposium, Juelic

A Fully Nonmetallic Gas Turbine Engine Enabled by Additive Manufacturing, Part II: Additive Manufacturing and Characterization of Polymer Composites

This publication is the second part of the three part report of the project entitled "A Fully Nonmetallic Gas Turbine Engine Enabled by Additive Manufacturing" funded by NASA Aeronautics Research Institute (NARI). The objective of this project was to conduct additive manufacturing to produce aircraft engine components by Fused Deposition Modeling (FDM), using commercially available polyetherimides-Ultem 9085 and experimental Ultem 1000 mixed with 10% chopped carbon fiber. A property comparison between FDM-printed and injection molded coupons for Ultem 9085, Ultem 1000 resin and the fiber-filled composite Ultem 1000 was carried out. Furthermore, an acoustic liner was printed from Ultem 9085 simulating conventional honeycomb structured liners and tested in a wind tunnel. Composite compressor inlet guide vanes were also printed using fiber-filled Ultem 1000 filaments and tested in a cascade rig. The fiber-filled Ultem 1000 filaments and composite vanes were characterized by scanning electron microscope (SEM) and acid digestion to determine the porosity of FDM-printed articles which ranged from 25 to 31%. Coupons of Ultem 9085, experimental Ultem 1000 composites and XH6050 resin were tested at room temperature and 400F to evaluate their corresponding mechanical properties. A preliminary modeling was also initiated to predict the mechanical properties of FDM-printed Ultem 9085 coupons in relation to varied raster angles and void contents, using the GRC-developed MAC/GMC program

Statistical Properties of Share Volume Traded in Financial Markets

We quantitatively investigate the ideas behind the often-expressed adage `it takes volume to move stock prices', and study the statistical properties of the number of shares traded $Q_{\Delta t}$ for a given stock in a fixed time interval $\Delta t$. We analyze transaction data for the largest 1000 stocks for the two-year period 1994-95, using a database that records every transaction for all securities in three major US stock markets. We find that the distribution $P(Q_{\Delta t})$ displays a power-law decay, and that the time correlations in $Q_{\Delta t}$ display long-range persistence. Further, we investigate the relation between $Q_{\Delta t}$ and the number of transactions $N_{\Delta t}$ in a time interval $\Delta t$, and find that the long-range correlations in $Q_{\Delta t}$ are largely due to those of $N_{\Delta t}$. Our results are consistent with the interpretation that the large equal-time correlation previously found between $Q_{\Delta t}$ and the absolute value of price change $| G_{\Delta t} |$ (related to volatility) are largely due to $N_{\Delta t}$.Comment: 4 pages, two-column format, four figure

A pilot study of eye movement during mammography interpretation: Eyetracker results and workstation design implications

Digital mammography can potentially improve mammography image and interpretation quality. On-line interpretation from a workstation may improve interpretation logistics and increase availability of comparison images. Interpretation of eight 4k- x 5k-pixel mammograms on two to four 2k- x 2.5k-pixel monitors is problematic because of the time spent in choosing which images display on which monitors, and zooming and roaming on individual images that are too large to display completely at full resolution. The authors used an eyetracker to measure radiologists viewing behavior during mammography interpretation with film on a viewbox. It was observed that a significant portion of the mammographers' time is spent viewing "comparison pairs" (typically two or more comparisons per case), such as the left mediolateral and craniocaudal images or old and new images. From the eyetracker measurements, we estimated that the number of image display, roam, and zoom operations decreases from an average of 64 for one monitor to 31 for four monitors, with the largest change going from one to two monitors. We also show that fewer monitors with a faster response time is superior to more monitors with a slower response time. Finally, the authors demonstrate the applicability of time-motion analysis to mammographic workstation design

Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases.

High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52-kb intronic deletion 3'). Family members were assessed for HBM segregation with identified variants. Three-dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM (∼prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non-LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5-HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST-LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z-scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z-scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion (∼3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance.This study was supported by The Wellcome Trust and NIHR CRN (portfolio number 5163). CLG was funded by a Wellcome Trust Clinical Research Training Fellowship (080280/Z/06/Z), the EU 7th Framework Programme under grant agreement number 247642 (GEoCoDE), a British Geriatric Society travel grant, and is now funded by Arthritis Research UK (grant ref 20000). SH acknowledges Arthritis Research UK support (grant ref 19580). KESP acknowledges the support of Cambridge NIHR Biomedical Research Centre. KAW is supported by the core programme of the MRC Nutrition and Bone Health group at MRC Human Nutrition Research, funded by the UK Medical Research Council (Grant code U10590371). EM acknowledges support of the Sheffield Teaching Hospitals Foundation Trust Clinical Research Facility. The SGC is a registered charity (no. 1097737) that receives funds from AbbVie, Bayer, Boehringer Ingelheim, Genome Canada (Ontario Genomics Institute OGI- 055), GlaxoSmithKline, Janssen, Lilly Canada, Novartis Research Foundation, Ontario Ministry of Economic Development & Innovation, Pfizer, Takeda, and Wellcome Trust (092809/Z/10/Z).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.270

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Human G Protein–Coupled Receptor Gpr-9-6/Cc Chemokine Receptor 9 Is Selectively Expressed on Intestinal Homing T Lymphocytes, Mucosal Lymphocytes, and Thymocytes and Is Required for Thymus-Expressed Chemokine–Mediated Chemotaxis

TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein–coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti–GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory α4β7high intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen–positive (CLA+) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic α4β7−CLA− memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti–GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response