bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed Lysis Confers Resistance to the Nucleoside Analogue 5-Fluorouracil and Alleviates Mutation Accumulation in the Single-Stranded DNA Bacteriophage ϕX174
Authors: Pereira-Gómez Marianoel , Sanjuán Rafael
Published: February 2014

Rates of spontaneous mutation determine viral fitness and adaptability. In RNA viruses, treatment with mutagenic nucleoside analogues selects for polymerase variants with increased fidelity, showing that viral mutation rates can be adjusted in response to imposed selective pressures. However, this type of resistance is not possible in viruses that do not encode their own polymerases, such as single-stranded DNA viruses. We previously showed that serial passaging of bacteriophage ϕX174 in the presence of the nucleoside analogue 5-fluorouracil (5-FU) favored substitutions in the lysis protein E (P. Domingo-Calap, M. Pereira-Gomez, and R. Sanjuán, J. Virol.
86:
9640–9646, 2012, doi:10.1128/JVI.00613–12). Here, we found that approximately half (6/12) of the amino acid replacements in the N-terminal region of this protein led to delayed lysis, and two of these changes (V2A and D8A) also conferred partial resistance to 5-FU. By delaying lysis, the V2A and D8A substitutions allowed the virus to increase the burst size per cell in the presence of 5-FU. Furthermore, these substitutions tended to alleviate drug-induced mutagenesis by reducing the number of rounds of copying required for population growth, revealing a new mechanism of resistance. This form of mutation rate regulation may also be utilized by other viruses whose replication mode is similar to that of bacteriophage ϕX174.

IMPORTANCE
Many viruses display high rates of spontaneous mutations due to defects in proofreading or postreplicative repair, allowing them to rapidly adapt to changing environments. Viral mutation rates may have been optimized to achieve high adaptability without incurring an excessive genetic load. Supporting this, RNA viruses subjected to chemical mutagenesis treatments have been shown to evolve higher-fidelity polymerases. However, many viruses cannot modulate replication fidelity because they do not encode their own polymerase. Here, we show a new mechanism for regulating viral mutation rates. We found that, under mutagenic conditions, the single-stranded bacteriophage ϕX174 evolved delayed lysis, and that this allowed the virus to increase the amount of progeny produced per cell. As a result, the viral population was amplified in fewer infection cycles, reducing the chances for mutation appearance.
Loss of a Conserved N-Linked Glycosylation Site in the Simian Immunodeficiency Virus Envelope Glycoprotein V2 Region Enhances Macrophage Tropism by Increasing CD4-Independent Cell-to-Cell Transmission
Authors: Yen Po-Jen , Herschhorn Alon , Haim Hillel , Salas Ignacio , Gu Christopher , Sodroski Joseph , Gabuzda Dana
Published: February 2014

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. Thus, CD4-independent phenotypes were detected only in the context of cell-to-cell contact. Similar results were obtained in SIVmac251 with and without N173. N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. This mechanism may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses
in vivo
.

IMPORTANCE
In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. The same genetic determinant also affects the sensitivity of these viruses to inhibition by neutralizing antibodies. Most macrophage-tropic HIV/SIV strains are known to be neutralization sensitive. Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4
in vivo
.
Contribution of PDZD8 to Stabilization of the Human Immunodeficiency Virus Type 1 Capsid
Authors: Guth Charles Alexander , Sodroski Joseph
Published: February 2014

Following human immunodeficiency virus type 1 (HIV-1) entry into the host cell, the viral capsid gradually disassembles in a process called uncoating. A proper rate of uncoating is important for reverse transcription of the HIV-1 genome. Host restriction factors such as TRIM5α and TRIMCyp bind retroviral capsids and cause premature disassembly, leading to blocks in reverse transcription. Other host factors, such as cyclophilin A, stabilize the HIV-1 capsid and are required for efficient infection in some cell types. Here, we show that a heat-labile factor greater than 100 kDa in the cytoplasm of cells from multiple vertebrate species slows the spontaneous disassembly of HIV-1 capsid-nucleocapsid (CA-NC) complexes
in vitro
. We identified the PDZ domain-containing protein 8 (PDZD8) as a critical component of the capsid-stabilizing activity in the cytoplasmic extracts. PDZD8 has been previously reported to bind the HIV-1 Gag polyprotein and to make a positive contribution to the efficiency of HIV-1 infection (M. S. Henning, S. G. Morham, S. P. Goff, and M. H. Naghavi, J. Virol.
84:
8990–8995, 2010, doi:10.1128/JVI.00843–10). PDZD8 knockdown accelerated the disassembly of HIV-1 capsids in infected cells, resulting in decreased reverse transcription. The PDZD8 coiled-coil domain is sufficient for HIV-1 capsid binding, but other parts of the protein, including the PDZ domain, are apparently required for stabilizing the capsid and supporting HIV-1 infection. In summary, PDZD8 interacts with and stabilizes the HIV-1 capsid and thus represents a potentially targetable host cofactor for HIV-1 infection.

IMPORTANCE
After human immunodeficiency virus type 1 (HIV-1) gains access to the interior of the target cell, host cell factors can influence virus infection in either a positive or negative way. HIV-1 depends upon certain host cell factors to assist processes that are required for virus replication. One example of such a host factor is PDZD8. This work shows that PDZD8 helps to stabilize the HIV-1 capsid, a huge complex of the viral RNA, enzymes, and protein. When PDZD8 is prevented from interacting with the HIV-1 capsid, the capsid becomes unstable and HIV-1 infection is inhibited. These results show that PDZD8 regulates the uncoating of the HIV-1 capsid. Interfering with the interaction of PDZD8 and capsid could prove to be a useful strategy for intervening in HIV-1 infection and transmission.
Posterior shoulder dislocation while lifting weights: a missed diagnosis
Authors: Cuffolo Giulio , Coomber Ross , Burtt Simon , Gray Jim
Published: February 2014

We present a case of a 24-year-old man who suffered acute shoulder pain and subsequent inability to move his arm while lifting weights in the bench-press position. He attended A&E where he was examined and X-rays were performed. He was diagnosed with presumed pectoralis major tendon rupture and was discharged to fracture clinic the following day with analgesia. On review in clinic he was found to have a posterior shoulder dislocation and was taken to theatre for relocation under anaesthesia. This case report examines the mechanism, investigations and management of posterior shoulder dislocation.
Widespread skin rash following travel to South-East Asia
Authors: Creamer Andrew
Published: February 2014

A 21-year-old man presented with a widespread, intensely pruritic skin rash, which developed acutely 5 days after returning from a backpacking holiday in Thailand. On initial presentation to his general practitioner, an erythematous, papular rash was noted in the upper right back, with smaller clusters of lesions on the buttocks and right arm. Based on the anatomical distribution of the lesions, a preliminary diagnosis of shingles was made. Over the following 2 weeks, the lesions failed to improve, and new snake-like lesions appeared. A dermatologist made the diagnosis of cutaneous larva migrans. The skin lesions rapidly resolved following oral albendazole therapy.
Reticular schwannoma mimicking myxoid sarcoma
Authors: Chaurasia Jai Kumar , Afroz Nishat , Sahoo Biswajit , Naim Mohammed
Published: February 2014

Reticular/microcystic schwannoma is a recently described rare distinctive variant of schwannoma with a predilection for gastrointestinal tract. Its occurrence in soft tissue is extremely rare. We report a case of reticular/microcystic variant of schwannoma in a 55-year-old Indian woman who presented with a painless slow-growing swelling in the right forearm for the past 6 months. MRI findings suggested myxoid sarcoma. However, histological and immunohistochemical findings in the excised specimen were consistent with reticular/microcystic variant of schwannoma. This case report emphasises that the diagnosis of reticular/microcystic schwannoma should always be considered in cases where myxoid sarcomas are suspected as it can mimic malignant myxoid sarcomas, clinically and radiologically, thereby avoiding aggressive intervention and overtreatment.
Modelling the blast environment and relating this to clinical injury: experience from the 7/7 inquest
Authors: Hepper Alan E , Pope D J , Bishop M , Kirkman E , Sedman A , Russell R , Mahoney P F , Clasper J
Published: February 2014

This paper addresses the computational modelling of a series of specific blast-related incidents and the relationships of clinical and engineering interpretations. The Royal Centre for Defence Medicine and the Defence Science and Technology Laboratory were tasked in 2010 by the UK Ministry of Defence to assist the Coroner's inquests into the 7 July 2005 London bombings. A three phase approach was taken. The first phase included an engineering expert in blast effects on structures reviewing photographs of the damaged carriages and bus to give a view on the likely physical effects on people close to the explosions. The second phase was a clinical review of the evidence by military clinicians to assess blast injury in the casualties. The third phase was to model the blast environment by structural dynamics experts to assess likely blast loading on victims to evaluate the potential blast loading on individuals. This loading information was then assessed by physiology experts. Once all teams (engineering, clinical and modelling/physiological) had separately arrived at their conclusions, the information streams were integrated to arrive at a consensus. The aim of this paper is to describe the methodology used as a potential model for others to consider if faced with a similar investigation, and to show the benefit of the transition of military knowledge to a civilian environment.
Safety and performance of the Penumbra Liberty stent system in a rabbit aneurysm model
Authors: Chavan Rajendra , Pons Stephen , Gupta Vikas , Hui Delilah , Bose Arani
Published: February 2014

Background

Endovascular treatment of wide necked and large/giant intracranial aneurysms is challenging. The goal of this study was to evaluate the Liberty stent system in the rabbit elastase aneurysm model for 30, 90, and 180 days.

Methods

The Altes elastase model was used to create aneurysms in the right common carotid artery in New Zealand White rabbits. Safety was assessed by angiographic and histopathological data from treated wide necked aneurysms, treated subclavian arteries, and related vasculature immediately post-treatment and at scheduled end points.

Results

In this study, stenting of wide necked aneurysms demonstrated excellent results in all 35 animals. The Liberty could be tracked to the final position across an aneurysm neck precisely, without changing microcatheter position. After device deployment, no significant changes in vessel contour and no stent migration were observed. Coil mass was well supported in all aneurysms and high packing densities were achieved. In addition, follow-up angiograms showed stable coil masses and persistent occlusion in all animals, without any recanalization of the neck or aneurysmal sac. Furthermore, there was no evidence of coil compaction or protrusion of coil loop through the stent struts. None of the immediate post-coiling angiograms revealed evidence of vasospasm, dissection, or in-stent thrombosis.

Discussion

This animal study demonstrated promising results with the novel Liberty stent system. The Liberty showed consistent precise positioning and accurate deployment. The stent revealed good compatibility with embolic coiling procedures, while morbidity and mortality were negligible. In addition, persistent occlusion of aneurysms without recanalization or in-stent stenosis was observed at the 180 day follow-up.
Optical transition in nanocrystalline Si doped SiO2 thin films formed by cosputtering
Authors: Hirata Katsuya , Hara Hiroki , Katsumata Hiroshi
Published: February 2014

Optical transition properties of nanocrystalline silicon (nc-Si) doped SiO2 thin films prepared by cosputtering with SiO2 target and Si-chips followed by high temperature annealing were investigated as a function of ratio of target area (Si/SiO2) in the range of 0 to 0.19. Optical transmission measurements revealed that the indirect band-gap of nc-Si decreased from 4.87 to 2.32 eV with increasing Si/SiO2 from 0.04 to 0.19, whereas no noticeable absorption was observed for the samples with Si/SiO2 = 0.00. Photoluminescence (PL) measurements showed that considerably weak emissions due to oxygen deficient center (ODC) in SiO2 films were observed at 514–539 nm for samples with lower Si/SiO2 of 0.0–0.09, while the strong emissions due to an interfacial layer between the nc-Si core and the SiO2 surface layer were observed at 746–808 nm for samples with higher Si/SiO2 of 0.13–0.19. PL excitation spectrum monitored at 800 nm showed that the PL at 800 nm was excited through nc-Si. On the other hand, cathodoluminesncence peaks were observed at 455 and 465 nm for the samples with 0.04 and 0.13, respectively, in which both peaks were assigned to originate from oxygen vacancies created during electron beam irradiation. The mechanisms of three types of luminescence, due to the ODC in SiO2, band-to-band transition of nc-Si, and the interfacial layer between the nc-Si core and the SiO2 surface layer, are discussed.
Bifurcations Leading to Nonlinear Oscillations in a 3D Piecewise Linear Memristor Oscillator
Authors: Scarabello Marluce da Cruz , Messias Marcelo
Published: February 2014

In this paper, we make a bifurcation analysis of a mathematical model for an electric circuit formed by the four fundamental electronic elements: one memristor, one capacitor, one inductor and one resistor. The considered model is given by a discontinuous piecewise linear system of ordinary differential equations, defined on three zones in ℝ3, determined by |z| < 1 (called the central zone) and |z| > 1 (the external zones). We show that the z-axis is filled by equilibrium points of the system, and analyze the linear stability of the equilibria in each zone. Due to the existence of this line of equilibria, the phase space ℝ3 is foliated by invariant planes transversal to the z-axis and parallel to each other, in each zone. In this way, each solution is contained in a three-piece invariant set formed by part of a plane contained in the central zone, which is extended by two half planes in the external zones. We also show that the system may present nonlinear oscillations, given by the existence of infinitely many periodic orbits, each one belonging to one such invariant set and passing by two of the three zones or passing by the three zones. These orbits arise due to homoclinic and heteroclinic bifurcations, obtained varying one parameter in the studied model, and may also exist for some fixed sets of parameter values. This intricate phase space may bring some light to the understanding of these memristor properties. The analytical and numerical results obtained extend the analysis presented in [Itoh & Chua, 2009; Messias et al., 2010].
Competing Responses in a Discrete Mechanical System
Authors: Waite J. J. , Virgin L. N. , Wiebe R.
Published: February 2014

This short paper takes a close look at a relatively simple harmonically-excited mechanical oscillator. Throughout the range of forcing frequencies the basins of attraction are investigated by applying strong perturbations to steady-state behavior. In this way, a more general solution space is mapped out. Numerical simulation of the equation of motion agrees very closely with data generated from a laboratory experiment.
Bifurcation Analysis in a Digitally Controlled H-Bridge Grid-Connected Inverter
Authors: Lei Bo , Xiao Guochun , Wu Xuanlv , Kafle Yuba-Raj , Zheng Lifu
Published: February 2014

The bifurcation behavior of a digitally controlled H-bridge grid-connected inverter is studied in this paper. The discrete-time model of this time-varying system is derived for inherent time delay in a digitally controlled system. Theoretical analyses indicate that only Hopf bifurcation can take place when the system loses its stability. The analytical expression of oscillation frequency is also derived in this paper. Moreover, the stability and instability boundaries for all switching cycles within a line cycle are described by analytical expressions. Finally, the theoretical results are verified by numerical simulations, circuit simulations and experimental measurements. These aforementioned conclusions provide an insight into the design process of the inverter system in terms of stability behavior and instability phenomenon.
On the Exact Traveling Wave Solutions of (2 + 1)-Dimensional Higher Order Broer–Kaup Equation
Authors: Li Jibin
Published: February 2014

In this paper, we study the dynamical behavior and exact parametric representations of all traveling wave solutions for (2 + 1)-dimensional higher order Broer–Kaup equation. By using the method of dynamical systems, under different parametric conditions, for the solution component U, exact monotonic and nonmonotonic kink wave solutions, two-peak wave solutions, periodic wave solutions, as well as unbounded traveling wave solutions are obtained. Exact wave profiles of traveling wave solutions for all solution components U, V, W, P are shown.
Splitting-particle methods for structured population models: Convergence and applications
Authors: Carrillo J. A. , Gwiazda P. , Ulikowska A.
Published: February 2014

We propose a new numerical scheme designed for a wide class of structured population models based on the idea of operator splitting and particle approximations. This scheme is related to the Escalator Boxcar Train (EBT) method commonly used in biology, which is in essence an analogue of particle methods used in physics. Our method exploits the split-up technique, thanks to which the transport step and the nonlocal integral terms in the equation can be separately considered. The order of convergence of the proposed method is obtained in the natural space of finite non-negative Radon measures equipped with the flat metric. This convergence is studied even adding reconstruction and approximation steps in the particle simulation to keep the number of approximation particles under control. We validate our scheme in several test cases showing the theoretical convergence error. Finally, we use the scheme in situations in which the EBT method does not apply showing the flexibility of this new method to cope with the different terms in general structured population models.
Computation of the effective slip of rough hydrophobic surfaces via homogenization
Authors: Bonnivard Matthieu , Dalibard Anne-Laure , Gérard-Varet David
Published: February 2014

We present a quantitative analysis of the effect of rough hydrophobic surfaces on viscous Newtonian flows. We use a model introduced by Ybert and coauthors in [Achieving large with superhydrophobic surfaces: Scaling laws for generic geometries, Phys. Fluids 19 (2007) 123601], in which the rough surface is replaced by a flat plane with alternating small areas of slip and no-slip. We investigate the averaged slip generated at the boundary, depending on the ratio between these areas. This problem reduces to the homogenization of a nonlocal system, involving the Dirichlet to Neumann map of the Stokes operator, in a domain with small holes. Pondering on the works of Allaire [Homogenization of the Navier–Stokes equations in open sets perforated with tiny holes. I. Abstract framework, a volume distribution of holes, Arch. Rational Mech. Anal. 113 (1990) 209–259; Homogenization of the Navier–Stokes equations in open sets perforated with tiny holes. II. Noncritical sizes of the holes for a volume distribution and a surface distribution of holes, Arch. Rational Mech. Anal. 113 (1990) 261–298]. We compute accurate scaling laws of the averaged slip for various types of roughness (riblets, patches). Numerical computations complete and confirm the analysis.
Analysis of models for quantum transport of electrons in graphene layers
Authors: El Hajj Raymond , Méhats Florian
Published: February 2014

We present and analyze two mathematical models for the self-consistent quantum transport of electrons in a graphene layer. We treat two situations. First, when the particles can move in all the plane ℝ2, the model takes the form of a system of massless Dirac equations coupled together by a self-consistent potential, which is the trace in the plane of the graphene of the 3D Poisson potential associated to surface densities. In this case, we prove local in time existence and uniqueness of a solution in Hs(ℝ2), for [Formula: see text] which includes in particular the energy space H1/2(ℝ2). The main tools that enable to reach [Formula: see text] are the dispersive Strichartz estimates that we generalized here for mixed quantum states. Second, we consider a situation where the particles are constrained in a regular bounded domain Ω. In order to take into account Dirichlet boundary conditions which are not compatible with the Dirac Hamiltonian H0, we propose a different model built on a modified Hamiltonian displaying the same energy band diagram as H0 near the Dirac points. The well-posedness of the system in this case is proved in [Formula: see text], the domain of the fractional order Dirichlet Laplacian operator, for [Formula: see text].
A hydrodynamic model for the interaction of Cucker–Smale particles and incompressible fluid
Authors: Ha Seung-Yeal , Kang Moon-Jin , Kwon Bongsuk
Published: February 2014

We present a new hydrodynamic model for the interactions between collision-free Cucker–Smale flocking particles and a viscous incompressible fluid. Our proposed model consists of two hydrodynamic models. For the Cucker–Smale flocking particles, we employ the pressureless Euler system with a non-local flocking dissipation, whereas for the fluid, we use the incompressible Navier–Stokes equations. These two hydrodynamic models are coupled through a drag force, which is the main flocking mechanism between the particles and the fluid. The flocking mechanism between particles is regulated by the Cucker–Smale model, which accelerates global flocking between the particles and the fluid. We show that this model admits the global-in-time classical solutions, and exhibits time-asymptotic flocking, provided that the initial data is appropriately small. In the course of our analysis for the proposed system, we first consider the hydrodynamic Cucker–Smale equations (the pressureless Euler system with a non-local flocking dissipation), for which the global existence and the time-asymptotic behavior of the classical solutions are also investigated.
Role of shape and quadrupole deformation of parents in the cluster emission of rare earth nuclei
Authors: Girija K. K. , Joseph Antony
Published: February 2014

The nuclear structure effects on α decay and cluster emission are investigated in the case of even–even rare earth nuclei150–160Dy ,150–160Er ,150–160Yb ,158,162,166–176Hf ,160,164–178W and162,166,170–180Os . The role of shape and deformation of parent nuclei in the decay rate is studied by taking the Coulomb and proximity potentials as the interacting barrier for the post scission configuration. The quadrupole deformation of parent nuclei causes a slight change in the half-life of α emissions, but it affects the rate of heavy cluster emissions significantly. Prolate deformation of parents enhances cluster emission, while an oblate deformation slows down the decay. Shape and deformation of parent nuclei causes change in the branching ratio also. A prolate deformation increases the branching ratio, whereas an oblate deformation reduces it. Highest branching ratio is predicted at N ~ 90.
Weighing the neutrino
Authors: Jentschura U. D. , Horváth D. , Nagy S. , Nándori I. , Trócsányi Z. , Ujvári B.
Published: February 2014

We investigate the potential of short-baseline experiments in order to measure the dispersion relation of the (muon) neutrino, with a prospect of eventually measuring the neutrino mass. As a byproduct, the experiment would help to constrain parameters of Lorentz-violating effects in the neutrino sector. The potential of a high-flux laser-accelerated proton beam (e.g., at the upcoming ELI facility), incident on a thick target composed of a light element to produce pions, with a subsequent decay to muons and muon-neutrinos, is discussed. We find a possibility for a muon neutrino mass measurement of unprecedented accuracy.
Vibration Analysis of Complete Conical Shells with Variable Thickness
Authors: Kang Jae-Hoon
Published: February 2014

A three-dimensional (3D) method of analysis is presented for determining the free vibration frequencies of complete (not truncated) conical shells with linearly varying thickness. The complete conical shells free or clamped at the bottom edge with a free vertex are investigated. Unlike conventional shell theories, which are mathematically 2D, the present method is based upon the 3D dynamic equations of elasticity. Displacement components ur, uθ and uz in the radial, circumferential and axial directions, respectively, are taken to be periodic in θ and in time, and expressed by algebraic polynomials in the r- and z-directions. Potential (strain) and kinetic energies of the complete conical shell are formulated. The Ritz method is used to solve the eigenvalue problem, yielding the upper bound values of the frequencies by minimization. As the degree of the polynomials is increased, frequencies converge to the exact values, with four-digit exactitude demonstrated for the first five frequencies. The frequencies from the present 3D method are compared with those from other 3D approaches and 2D shell theory by previous researchers.
Experimental Assessment of Noncontact Type Laser-Based Force Measurement Technique for Impulsive Loading
Authors: Ramesh Pallekonda , Bommana Divakar , Kulkarni Vinayak , Sahoo Niranjan , Dwivedy S. K.
Published: February 2014

Force measurement is an essential element in the design of mechanical or nonmechanical systems. The choice of a particular technique, among the numerous measurement techniques available, depends on various parameters within which the nature of force is an important one. The measurement of impulse force is considered in this study using two techniques. In view of this, an experimental setup has been developed to understand the applicability and assessment of a laser-based extrusive technique, along with the established intrusive accelerometer-based technique for impulsive force measurement. The accelerometer-based measurements can be used to precisely predict the magnitude and temporal nature of the force. However, the velocity-based impulse prediction shows some limitation on complete representation of the system. In addition, the indirect measurement of acceleration from the velocity measured seems to have better prediction of the force.
Feeding and growth of a dyke–laccolith system (Elba Island, Italy) from AMS and mineral fabric data
Authors: Roni Emanuele , Westerman David Scott , Dini Andrea , Stevenson Carl , Rocchi Sergio
Published: February 2014

Dykes feed laccoliths and sills; however, the link between feeder and intrusion is rarely observed. The felsic San Martino laccolith displays a clear feeder–intrusion link, allowing reconstruction of the influence of the size and location of feeder dykes on magma flow during formation of subhorizontal intrusions. This work uses anisotropy of magnetic susceptibility (AMS) combined with mineral shape-preferred orientations of sanidine megacrysts to examine magma flow pathways through feeders into a laccolith. Strong correlation between AMS and K-feldspar datasets indicates that alteration affecting the paramagnetic mineralogy did not influence AMS results. The well-established field relationships between feeder and laccolith provided a robust ‘geo-logical’ model for flow pathways that we have used as a framework to aid interpretation of AMS data. The position and size of the main feeder dyke helped to predict the flow paths in the overlying laccolith. Our results show that magma spread laterally from the feeding system and built the laccolith layers with propagating and inflating divergent flow where tabular particles became aligned perpendicular to the magma displacement direction. The lack of internal discontinuities indicates that the magma was injected as a single pulse or a series of quickly coalescing pulses.

Supplementary material:

AMS methods, AMS data and detailed fabric maps are available at
www.geolsoc.org.uk/SUP18717
.
Quantifying the impacts of climate change on groundwater in an unconfined aquifer that is strongly influenced by surface water
Authors: Scibek J. , Allen D. M. , Whitfield P. H.
Published: February 2014

A three-dimensional transient groundwater flow model, implemented in MODFLOW, is used to quantify the impacts of climate change on groundwater in an unconfined aquifer with demonstrated strong connection to surface water (Kettle and Granby Rivers). The Grand Forks aquifer is located in a semi-arid region of south-central British Columbia, Canada. Distributed recharge is modelled using HELP, driven by the LARS-WG stochastic weather generator, and stage–discharge curves for rivers are modelled using BRANCH and calibrated to historical data. For recharge modelling, three year-long climate scenarios were run, each representing one typical year in the present, and future (2020s and 2050s), by perturbing the historical weather according to the downscaled CGCM1 global climate model results. By the 2050s the largest increase in recharge relative to present occurs in late spring, by a factor of three or more, a 50% increase in summer months in most areas of the aquifer, a 10–25% increase in autumn, and a reduction in recharge in winter. CGCM1 downscaling was also used to predict basin-scale runoff for the Kettle River. Future climate scenarios suggest a shift in the hydrograph peak to an earlier date, although the peak flow remains the same, and baseflow level is lower and of longer duration. Groundwater levels near the river floodplain are predicted to be higher earlier in the year due to an earlier onset of peak flow, but considerably lower during the summer months. Away from rivers, groundwater levels increase slightly due to the predicted increase in recharge.
Historical damage and earthquake environmental effects related to shallow intraplate seismicity of central western Argentina
Authors: Moreiras Stella Maris , Páez María Solange
Published: February 2014

Central western Argentina is identified as the most hazardous seismic zone in the country. Historical earthquakes with magnitudes greater than M
s
>6.0 frequently occur in this territory and are associated with the subduction of the Nazca plate. However, seismic hazards have not been fully assessed in this region. No secondary seismic effects of a potential earthquake with destructive consequences have been considered, nor has the existence of shallow Quaternary blind faults been identified by seismic surveys. Neotectonic studies performed up to the present describe only those Quaternary faults with some surficial expression. Lacking proper hazard assessment limits strategies to reduce the economic impact of drastic seismic events. This chapter is focused on the impact of major destructive earthquakes that have occurred in central western Argentina in order to understand the incidence of these phenomena in the past and to consider the vulnerability of the region in light of its increased urbanization and changing agricultural practices.
Chromatin Contributions to the Regulation of Innate Immunity
Authors: Smale Stephen T. , Tarakhovsky Alexander , Natoli Gioacchino
Published: February 2014

A fundamental property of cells of the innate immune system is their ability to elicit a transcriptional response to a microbial stimulus or danger signal with a high degree of cell type and stimulus specificity. The selective response activates effector pathways to control the insult and plays a central role in regulating adaptive immunity through the differential regulation of cytokine genes. Selectivity is dictated by signaling pathways and their transcription factor targets. However, a growing body of evidence supports models in which different subsets of genes exhibit distinct chromatin features that play active roles in shaping the response. Chromatin also participates in innate memory mechanisms that can promote tolerance to a stimulus or prime cells for a more robust response. These findings have generated interest in the capacity to modulate chromatin regulators with small-molecule compounds for the treatment of diseases associated with innate or adaptive immunity.
State Transformations in OECD Countries
Authors: Genschel Philipp , Zangl Bernhard
Published: February 2014

Is the state still the basic unit of political authority in OECD countries? International relations scholars discuss whether international institutions undermine or buttress state authority. Students of comparative political economy argue about the extent to which political authority has migrated to private market actors. We inventory and compare the main arguments in both debates. Our findings suggest a different pattern of state transformation than most participants in the debates implicitly assume. The key feature is not a zero-sum shift of political authority to nonstate actors but an unbundling and reconfiguration of authority. The segmental differentiation into largely self-contained national states is overlaid by a functionally differentiated order in which different dimensions of authority are exercised by different state and nonstate actors. The state remains focal, but its role changes from virtual monopolist to manager of political authority.
Cardiovascular responses to water immersion in humans: impact on cerebral perfusion
Authors: Carter Howard H. , Spence Angela L. , Pugh Christopher J. A. , Ainslie Philip , Naylor Louise H. , Green Daniel J.
Published: February 2014

Episodic increases in cerebrovascular perfusion and shear stress may have beneficial impacts on endothelial function that improve brain health. We hypothesized that water immersion to the level of the right atrium in humans would increase cerebral perfusion. We continuously measured, in 9 young (means ± SD, 24.6 ± 2.0 yr) healthy men, systemic hemodynamic variables along with blood flows in the common carotid and middle and posterior cerebral arteries during controlled filling and emptying of a water tank to the level of the right atrium. Mean arterial pressure (80 ± 9 vs. 91 ± 12 mmHg, P < 0.05), cardiac output (4.8 ± 0.7 vs. 5.1 ± 0.6 l/min, P < 0.05) and end-tidal carbon dioxide (PetCO2, 39.5 ± 2.0 vs. 44.4 ± 3.5 mmHg, P < 0.05) increased with water immersion, along with middle (59 ± 6 vs. 64 ± 6 cm/s, P < 0.05) and posterior cerebral artery blood flow velocities (41 ± 9 vs. 44 ± 10 cm/s, P < 0.05). These changes were reversed when the tank was emptied. Water immersion is associated with hemodynamic and PetCO2 changes, which increase cerebral blood velocities in humans. This study provides an evidence base for future studies to examine the potential additive effect of exercise in water on improving cerebrovascular health.
Modulation of angiotensin II-induced inflammatory cytokines by the Epac1-Rap1A-NHE3 pathway: implications in renal tubular pathobiology
Authors: Xie Ping , Joladarashi Darukeshwara , Dudeja Pradeep , Sun Lin , Kanwar Yashpal S.
Published: February 2014

Besides the glomerulus, the tubulointerstitium is often concomitantly affected in certain diseases, e.g., diabetic nephropathy, and activation of the renin-angiotensin system, to a certain extent, worsens its outcome because of perturbations in hemodynamics and possibly tubuloglomerular feedback. Certain studies suggest that pathobiology of the tubulointerstitium is influenced by small GTPases, e.g., Rap1. We investigated the effect of ANG II on inflammatory cytokines, while at the same time focusing on upstream effector of Rap1, i.e., Epac1, and some of the downstream tubular transport molecules, i.e., Na/H exchanger 3 (NHE3). ANG II treatment of LLC-PK1cells decreased Rap1a GTPase activity in a time- and dose-dependent manner. ANG II treatment led to an increased membrane translocation of NHE3, which was reduced with Epac1 and PKA activators. ANG II-induced NHE3 translocation was notably reduced with the transfection of Rap1a dominant positive mutants, i.e., Rap1a-G12V or Rap1a-T35A. Transfection of cells with dominant negative Rap1a mutants, i.e., Rap1a-S17A, or Epac1 mutant, i.e., EPAC-ΔcAMP, normalized ANG II-induced translocation of NHE3. In addition, ANG II treatment led to an increased expression of inflammatory cytokines, i.e., IL-1β, IL-6, IL-8, and TNF-α, which was reduced with Rap1a-G12V or Rap1a-T35A transfection, while it reverted to previous comparable levels following transfection of Rap1a-S17A or EPAC-ΔcAMP. ANG II-induced expression of cytokines was reduced with the treatment with NHE3 inhibitor S3226 or with Epac1 and PKA activators. These data suggest that this novel Epac1-Rap1a-NHE3 pathway conceivably modulates ANG II-induced expression of inflammatory cytokines, and this information may yield the impetus for developing strategies to reduce tubulointertstitial inflammation in various renal diseases.
Renal-specific and inducible depletion of NaPi-IIc/Slc34a3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice
Authors: Myakala Komuraiah , Motta Sarah , Murer Heini , Wagner Carsten A. , Koesters Robert , Biber Jürg , Hernando Nati
Published: February 2014

The proximal renal epithelia express three different Na-dependent inorganic phosphate (Pi) cotransporters: NaPi-IIa/SLC34A1, NaPi-IIc/SLC34A3, and PiT2/SLC20A2. Constitutive mouse knockout models of NaPi-IIa and NaPi-IIc suggested that NaPi-IIa mediates the bulk of renal reabsorption of Pi whereas the contribution of NaPi-IIc to this process is minor and probably restricted to young mice. However, many reports indicate that mutations of NaPi-IIc in humans lead to hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report the generation of a kidney-specific and inducible NaPi-IIc-deficient mouse model based on the loxP-Cre system. We found that the specific removal of the cotransporter from the kidneys of young mice does not impair the capacity of the renal epithelia to transport Pi. Moreover, the levels of Pi in plasma and urine as well as the circulating levels of parathyroid hormone, FGF-23, and vitamin D3 remained unchanged. These findings are in agreement with the data obtained with the constitutive knockout model and suggest that, under steady-state conditions of normal dietary Pi, NaPi-IIc is not an essential Na-Pi cotransporter in murine kidneys. However, and unlike the constitutive mutants, the kidney-specific depletion of NaPi-IIc does not result in alteration of the homeostasis of calcium. This suggests that the calcium-related phenotype observed in constitutive knockout mice may not be related to inactivation of the cotransporter in kidney.
Dominant factors that govern pressure natriuresis in diuresis and antidiuresis: a mathematical model
Authors: Moss Robert , Layton Anita T.
Published: February 2014

We have developed a whole kidney model of the urine concentrating mechanism and renal autoregulation. The model represents the tubuloglomerular feedback (TGF) and myogenic mechanisms, which together affect the resistance of the afferent arteriole and thus glomerular filtration rate. TGF is activated by fluctuations in macula densa [Cl−] and the myogefnic mechanism by changes in hydrostatic pressure. The model was used to investigate the relative contributions of medullary blood flow autoregulation and inhibition of transport in the proximal convoluted tubule to pressure natriuresis in both diuresis and antidiuresis. The model predicts that medullary blood flow autoregulation, which only affects the interstitial solute composition in the model, has negligible influence on the rate of NaCl excretion. However, it exerts a significant effect on urine flow, particularly in the antidiuretic kidney. This suggests that interstitial washout has significant implications for the maintenance of hydration status but little direct bearing on salt excretion, and that medullary blood flow may only play a signaling role for stimulating a pressure-natriuresis response. Inhibited reabsorption in the model proximal convoluted tubule is capable of driving pressure natriuresis when the known actions of vasopressin on the collecting duct epithelium are taken into account.
Angiotensin 1–7 mediates renoprotection against diabetic nephropathy by reducing oxidative stress, inflammation, and lipotoxicity
Authors: Mori Jun , Patel Vaibhav B. , Ramprasath Tharmarajan , Alrob Osama Abo , DesAulniers Jessica , Scholey James W. , Lopaschuk Gary D. , Oudit Gavin Y.
Published: February 2014

The renin-angiotensin system, especially angiotensin II (ANG II), plays a key role in the development and progression of diabetic nephropathy. ANG 1–7 has counteracting effects on ANG II and is known to exert beneficial effects on diabetic nephropathy. We studied the mechanism of ANG 1–7-induced beneficial effects on diabetic nephropathy in db/db mice. We administered ANG 1–7 (0.5 mg·kg−1·day−1) or saline to 5-mo-old db/db mice for 28 days via implanted micro-osmotic pumps. ANG 1–7 treatment reduced kidney weight and ameliorated mesangial expansion and increased urinary albumin excretion, characteristic features of diabetic nephropathy, in db/db mice. ANG 1–7 decreased renal fibrosis in db/db mice, which correlated with dephosphorylation of the signal transducer and activator of transcription 3 (STAT3) pathway. ANG 1–7 treatment also suppressed the production of reactive oxygen species via attenuation of NADPH oxidase activity and reduced inflammation in perirenal adipose tissue. Furthermore, ANG 1–7 treatment decreased lipid accumulation in db/db kidneys, accompanied by increased expressions of renal adipose triglyceride lipase (ATGL). Alterations in ATGL expression correlated with increased SIRT1 expression and deacetylation of FOXO1. The upregulation of angiotensin-converting enzyme 2 levels in diabetic nephropathy was normalized by ANG 1–7. ANG 1–7 treatment exerts renoprotective effects on diabetic nephropathy, associated with reduction of oxidative stress, inflammation, fibrosis, and lipotoxicity. ANG 1–7 can represent a promising therapy for diabetic nephropathy.
Novel cardiolipin therapeutic protects endothelial mitochondria during renal ischemia and mitigates microvascular rarefaction, inflammation, and fibrosis
Authors: Liu Shaoyi , Soong Yi , Seshan Surya V. , Szeto Hazel H.
Published: February 2014

Microvascular rarefaction, or loss of microvascular density, is increasingly implicated in the progression from acute ischemic kidney injury to chronic kidney disease. Microvascular dropout results in chronic tissue hypoxia, interstitial inflammation, and fibrosis. There is currently no therapeutic intervention for microvascular rarefaction. We hypothesize that capillary dropout begins with ischemic damage to endothelial mitochondria due to cardiolipin peroxidation, resulting in loss of cristae and the failure to regenerate ATP upon reperfusion. SS-31 is a cell-permeable peptide that targets the inner mitochondrial membrane and binds selectively to cardiolipin. It was recently shown to inhibit cardiolipin peroxidation by cytochrome c peroxidase activity, and it has been shown to protect mitochondrial cristae in proximal tubular cells during ischemia, and accelerated ATP recovery upon reperfusion. We found mitochondrial swelling and loss of cristae membranes in endothelial and medullary tubular epithelial cells after 45-min ischemia in the rat. The loss of cristae membranes limited the ability of these cells to regenerate ATP upon reperfusion and led to loss of vascular integrity and to tubular cell swelling. SS-31 prevented mitochondria swelling and protected cristae membranes in both endothelial and epithelial cells. By minimizing endothelial and epithelial cell injury, SS-31 prevented “no-reflow” after ischemia and significantly reduced the loss of peritubular capillaries and cortical arterioles, interstitial inflammation, and fibrosis at 4 wk after ischemia. These results suggest that mitochondria protection represents an upstream target for pharmacological intervention in microvascular rarefaction and fibrosis.