bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite size suppression of the weak field magnetoresistance of lightly phosphorous-doped silicon
Authors: Porter Nicholas A. , Marrows Christopher H.
Published: March 2012

We report magnetoresistance measurements of lightly phosphorous doped silicon in samples that are fabricated from silicon-on-insulator wafers and so confined in one dimension. All three principal magnetic field orientations were studied at 50 and 270 K for thicknesses between 1.5−530 μm, and as thin as 150 nm at 270 K. The weak field magnetoresistance was suppressed in the orientations with the field in the sample plane when the sample is thinner than ∼1 μm at 270 K (∼10 μm at 50 K). This suppression occurred for samples that are much thicker than the carrier mean free path and the Debye screening length, and the relevant lengthscale is instead the energy relaxation length.
Microcavity enhanced single photon emission from an electrically driven site-controlled quantum dot
Authors: Schneider C. , Heindel T. , Huggenberger A. , Niederstrasser T. A. , Reitzenstein S. , Forchel A. , Höfling S. , Kamp M.
Published: March 2012

In this work we report on the integration of single site-controlled quantum dots (SCQDs) into electrically driven micropillar cavities. The electroluminescence of these devices features emission of single SCQDs with inhomogeneous broadenings down to 170 µeV. The enhancement of electroluminescence by quantum dot-cavity coupling is demonstrated by temperature dependent investigations. Single photon emission from a spatially and spectrally coupled SCQD-resonator system is confirmed by photon autocorrelation measurements under electrical excitation yielding a g(2)(0) value of 0.42.
Instrumentation of a compact random-access photostimulator based on acousto-optic deflectors
Authors: Liu Yafeng , Zhao Yuan , Lv Xiaohua , Li Yiding , Zhang Xiaohui , Zhang Jie , Wang Liping , Zeng Shaoqun
Published: March 2012

Recently developed optogenetics provides a fast, non-invasive, and efficient method for cell activation. However, it is difficult for the optical stimulators used for optogenetics to realize selective multi-site fast activation. In this paper, we developed a random-access photostimulator based on a pair of perpendicularly oriented acousto-optic deflectors. Precise laser targeting in the x-y plane was verified, and the lateral spatial resolution of laser intensity after the objective was measured as ∼1.38 μm. Photostimulaton of ChETA-expressing astrocytes induced reliable inward currents only if the laser beam was directed onto the targeted cell. In the ChR2-expresing neuron, multiple locations along two dendrites were stimulated, and spatiotemporal integration was observed in the soma with fast multi-site activation. These results demonstrated that this random-access photostimulator would be a powerful tool for selective multi-site fast activation. The compact and modular design of this photostimulator makes it easily integrated with different commercial microscopes, and thus widely popularized in many laboratories.
Ab initio properties of MgAlk (Alk = Li, Na, K, Rb, Cs)
Authors: Augustovičová L. , Soldán P.
Published: March 2012

High level ab initio calculations are performed on the ground electronic state of diatomic molecules MgAlk (Alk = Li, Na, K, Rb, Cs). Potential energy curves and dipole moment functions are determined making use of the single-reference unrestricted and restricted coupled-cluster methods with large basis sets. Basic spectroscopic properties of the ground electronic states are derived from ro-vibrational bound state calculations.
How does folding modulate thermal conductivity of graphene?
Authors: Yang Nuo , Ni Xiaoxi , Jiang Jin-Wu , Li Baowen
Published: March 2012

We study thermal transport in folded graphene nanoribbons using molecular dynamics simulations and the non-equilibrium Green’s function method. It is found that the thermal conductivity of flat graphene nanoribbons can be modulated by folding and changing interlayer couplings. The analysis of transmission reveals that the reduction of thermal conductivity is due to scattering of low frequency phonons by the folds. Our results suggest that folding can be utilized in the modulation of thermal transport properties in graphene and other two dimensional materials.
High room-temperature optical gain in Ga(NAsP)/Si heterostructures
Authors: Koukourakis N. , Bückers C. , Funke D. A. , Gerhardt N. C. , Liebich S. , Chatterjee S. , Lange C. , Zimprich M. , Volz K. , Stolz W. , Kunert B. , Koch S. W. , Hofmann M. R.
Published: March 2012

We analyze the modal gain of Ga(NAsP) multi quantum-well heterostructures pseudomorphically grown on (001) silicon substrate by metal-organic vapor-phase epitaxy. Using the variable stripe length method, we obtain high modal gain values up to 78 cm−1 at room temperature that are comparable to the values of common high quality III-V laser material. We find good agreement between experimental results and theoretically calculated gain spectra obtained using a microscopic model. The results underline the high potential of Ga(NAsP) as an active material for directly electrically pumped lasers on silicon substrate.
Magnetoelectric manipulation of domain wall configuration in thin film Ni/[Pb(Mn1/3Nb2/3)O3]0.68-[PbTiO3]0.32 (001) heterostructure
Authors: Hsu Chin-Jui , Hockel Joshua L. , Carman Gregory P.
Published: March 2012

This paper reports experimental observations of partial and reversible out-of-plane magnetization change in a thin film Ni/[Pb(Mn1/3Nb2/3)O3]0.68-[PbTiO3]0.32 (001) heterostructure. Electric-field-induced isotropic in-plane compressive strain (∼1000 ppm) eliminates the stripe domain pattern in a 60-nm-thick Ni thin film. When the electric field is removed, the stripe domains are returned to their original configurations with some domain wall pinning perturbations due to ferroelectric domain texturing. The observed domain structure change is attributed to the transition from Bloch wall to Néel wall and the broadening of the Bloch wall. This out-of-plane magnetization change does not occur in thicker (100-nm-thick) Ni thin film.
Stabilizer design based on flywheel energy storage system with multiple operations for multi-machine power systems
Authors: Xu Qingshan , Zang Haixiang , Shi Linjun
Published: March 2012

Due to the issue of no guarantee of robustness for the flywheel energy storage system (FESS)-based stabilizer designed at one special operation level, an improved method concerning multiple operations was proposed to select the best installing location, damping control loop, feedback signal robustly and to tune FESS-based stabilizer parameters. Based on linearized model with FESS and application of damping torque analysis, the maximum of all of the minimum damping torque indices under multi-operation conditions is the selection index of FESS installing location, damping control loop and feedback signal, and the operation that had little change on the real part of eigenvalue is the condition to tune FESS-based stabilizer parameters. Moreover, a four-machine power system with FESS was investigated. The results indicate that power system oscillations are suppressed effectively by FESS-based stabilizer designed by the method under multiple operations. It is also seen that the proposed method is effective and robust.
Electrochromic switchable mirror glass with controllable reflectance
Authors: Tajima Kazuki , Hotta Hiromi , Yamada Yasusei , Okada Masahisa , Yoshimura Kazuki
Published: March 2012

An electrochromic switchable mirror glass with controllable reflectance was developed. The conditions for fabricating InGaZnO4 (IGZO) thin film, which serves as a transparent conductor, were investigated. The mirror glass with IGZO thin film exhibited multiple colors arising from interference between multilayers. The mirror glass with IGZO thin film fabricated at a working pressure of 0.4 Pa showed high transmittance (63%) in the transparent state and low reflectance (16%) in the reflective state at a wavelength of 670 nm. Moreover, the developed mirror glass had low glare in the reflective state because the reflection of direct, bright light was reduced.
The influence of Mg doping on the nucleation of self-induced GaN nanowires
Authors: Limbach F. , Caterino R. , Gotschke T. , Stoica T. , Calarco R. , Geelhaar L. , Riechert H.
Published: March 2012

GaN nanowires were grown without any catalyst by plasma-assisted molecular beam epitaxy. Under supply of Mg, nanowire nucleation is faster, the areal density of wires increases to a higher value, and nanowire coalescence is more pronounced than without Mg. During nanowire nucleation the Ga desorption was monitored in-situ by line-of-sight quadrupole mass spectrometry for various substrate temperatures. Nucleation energies of 4.0±0.3 eV and 3.2±0.3 eV without and with Mg supply were deduced, respectively. This effect has to be taken into account for the fabrication of nanowire devices and could be employed to tune the NW areal density.
Hot spin spots in the laser-induced demagnetization
Authors: Si M. S. , Zhang G. P.
Published: March 2012

Laser-induced femtosecond magnetism or femtomagnetism simultaneously relies on two distinctive contributions: (a) the optical dipole interaction (ODI) between a laser field and a magnetic system and (b) the spin expectation value change (SEC) between two transition states. Surprisingly, up to now, no study has taken both contributions into account simultaneously. Here we do so by introducing a new concept of the optical spin generator, a product of SEC and ODI between transition states. In ferromagnetic nickel, our first-principles calculation demonstrates that the larger the value of optical spin generator is, the larger the dynamic spin moment change is. This simple generator directly links the time-dependent spin moment change \documentclass[12pt]{minimal}\begin{document}$\Delta M_{z}^{\bf k}(t)$\end{document}ΔMzk(t) at every crystal-momentum k point to its intrinsic electronic structure and magnetic properties. Those hot spin spots are a direct manifestation of the optical spin generator, and should be the focus of future research.
Linear and nonlinear intraband optical properties of ZnO quantum dots embedded in SiO2 matrix
Authors: Maikhuri Deepti , Purohit S. P. , Mathur K. C.
Published: March 2012

In this work we investigate some optical properties of semiconductor ZnO spherical quantum dot embedded in an amorphous SiO2 dielectric matrix. Using the framework of effective mass approximation, we have studied intraband S-P, and P-D transitions in a singly charged spherical ZnO quantum dot. The optical properties are investigated in terms of the linear and nonlinear photoabsorption coefficient, the change in refractive index, and the third order nonlinear susceptibility and oscillator strengths. Using the parabolic confinement potential of electron in the dot these parameters are studied with the variation of the dot size, and the energy and intensity of incident radiation. The photoionization cross sections are also obtained for the different dot radii from the initial ground state of the dot. It is found that dot size, confinement potential, and incident radiation intensity affects intraband optical properties of the dot significantly.
Two copies of the SecY channel and acidic lipids are necessary to activate the SecA translocation ATPase
Authors: Dalal Kush , Chan Catherine S. , Sligar Stephen G. , Duong Franck
Published: March 2012

The SecA ATPase associates with the SecY complex to push preproteins across the bacterial membrane. Because a single SecY is sufficient to create the conducting channel, the function of SecY oligomerization remains unclear. Here, we have analyzed the translocation reaction using nanodiscs. We show that one SecY copy is sufficient to bind SecA and the preprotein, but only the SecY dimer together with acidic lipids supports the activation of the SecA translocation ATPase. In discs, the dimer is predominantly arranged in a back-to-back manner and remains active even if a constituent SecY copy is defective for SecA binding. In membrane vesicles and in intact cells, the coproduction of two inactive SecYs, one for channel gating and the other for SecA binding, recreates a functional translocation unit. These results indisputably argue that the SecY dimer is crucial for the activation of SecA, which is necessary for preprotein transport.
Endorsement of sexist ideology in Taiwan and the United States: Social dominance orientation, right‐wing authoritarianism, and deferential family norms
Authors: Lee I‐Ching
Published: March 2012

Despite close relationships between men and women in daily lives, gender inequality is ubiquitous and often supported by sexist ideology. The understanding of potential bases of sexist ideology is thus important. According to Duckitt's dual‐process model (2001), different worldviews may explain different types of sexist ideology. Individuals who hold a “competitive world” worldview tend to endorse group‐based dominance. This lends itself to the endorsement of hostile sexism, because hostile sexism is an obvious form of male dominance. Conversely, individuals who hold a “dangerous world” worldview tend to adhere to social cohesion, collective security, and social traditions. This lends itself to the endorsement of benevolent sexism, because benevolent sexism values women who conform to gender norms. As predicted by Duckitt's model, research has shown that social dominance orientation, a general orientation towards the endorsement of group‐based dominance, is closely associated with hostile sexism. Furthermore, right‐wing authoritarianism, which measures adherence to social traditions, is closely associated with benevolent sexism. Due to the interdependent nature of gender relationships, the current research proposed that a relationship‐based belief in hierarchy, deferential family norms, and norms depicting proper manners among family members should predict the endorsement of hostile and benevolent sexism, after controlling for social dominance orientation and right‐wing authoritarianism. As predicted, according to student samples collected in Taiwan and the US, the endorsement of deferential family norms predicted the endorsement of hostile sexism and of benevolent sexism, respectively. In addition, among men and women, social dominance orientation predicted hostile sexism more strongly (as opposed to benevolent sexism), whereas right‐wing authoritarianism predicted benevolent sexism more strongly (as opposed to hostile sexism). Implications regarding relationship norms, social dominance orientation, right‐wing authoritarianism, and sexist ideology are discussed.
Socioeconomical and sociopolitical correlates of interpersonal forgiveness: A three‐level meta‐analysis of the Enright Forgiveness Inventory across 13 societies
Authors: Hanke Katja , Fischer Ronald
Published: March 2012

We report a meta‐analysis on the country‐level correlates of the Enright Forgiveness Inventory (EFI), to address (1) whether there are differences in forgiveness between societies, (2) what society‐level context variables can account for these differences, and (3) whether conceptual relationships of forgiveness found at the individual level can be replicated at the societal level. We found sizeable differences between societies that are associated with democracy, peacefulness, socioeconomic development, and postmaterialism indices of a society. Replicating individual‐level results, subjective wellbeing was positively related to forgiveness. We discuss the importance of macro‐level contextual variables for understanding levels of forgiveness.
European athletes dominate performances in Double Iron ultra‐triathlons – A retrospective data analysis from 1985 to 2010
Authors: Rüst Christoph Alexander , Knechtle Beat , Knechtle Patrizia , Lepers Romuald , Rosemann Thomas , Onywera Vincent
Published: March 2012

We investigated the participation and performance trends of ultra‐endurance triathletes from all nationalities competing in a Double Iron ultra‐triathlon (7.6‐km swim, 360‐km cycle and 84.4‐km run) from 1985 to 2010. A total of 1854 athletes participated in 92 Double Iron ultra‐triathlons. The majority of the winners came from Europe with 72 victories, followed by North America with 17 victories. The race time for the European ultra‐triathletes was 1340 (s=95.3) min, decreasing highly significantly (r 2=0.28; P<0.0001) across the years. North American ultra‐triathletes finished the races within 1556 (s=124.5) min; their race time showed no changes across the years (r 2=0.045; P=0.07). The race time for the Europeans was highly significantly faster compared to the North Americans (P<0.0001). Future studies should investigate each country in Europe and North America in order to find the country with the largest participation of athletes and their best performance.
Inactivity‐induced oxidative stress: A central role in age‐related sarcopenia?
Authors: Derbré Frédéric , Gratas‐Delamarche Arlette , Gómez‐Cabrera Mari Carmen , Viña José
Published: March 2012

Ageing causes a progressive decline in skeletal muscle mass that may lead to decreased strength and functionality. The term sarcopenia is especially used to characterise this geriatric syndrome. Numerous conditions and behaviours are considered to accelerate the progression of sarcopenia such as chronic diseases, malnutrition and physical inactivity. As people in modern countries are more and more sedentary, the impact of physical inactivity on the prevalence of sarcopenia might be more and more important in the future. In this review, we discuss how reactive oxygen species (ROS) could mediate the effects of lifelong inactivity in the onset and progression of age‐related sarcopenia. Although the cellular mechanisms responsible for muscle ROS production are not necessarily the same, both inactivity and ageing are indeed known to increase basal ROS concentrations in skeletal muscle. New data and literature review are provided showing that chronic ROS overproduction induced by physical inactivity may exacerbate the activation of some redox‐sensitive signalling pathways involved in age‐related sarcopenia. We also address the scientific evidences implicating the role of ROS overproduction in the precocious failure of aged muscles to activate intracellular signalling responses to contractions.
The effects of air travel on performance measures of elite Australian rugby league players
Authors: McGuckin Teneale Alyce , Sinclair Wade Heath , Sealey Rebecca Maree , Bowman Paul
Published: March 2012

The current study explored the effects of short haul air travel within the same country on elite Australian rugby league (RL) players (n=12) during two away and two home games of elite competition. Physiological tests of handgrip strength and leg power were assessed along with psychological tests and perceptions of leg soreness and tiredness on the day before the game (Time 1 and Time 2) and on game day (Time 3). Game statistics of tackles and metres gained were assessed for the games analysed. Significant differences were found for daily analyses of life demands for athletes (DALDA) worse than normal responses at Time 2 (2.50±3.23 vs. 3.50±3.93; P=0.04), Karolinska Sleepiness Scale (KSS) at Time 2 (2.88±1.51 vs. 3.71±1.37; P=0.011) and leg tiredness at Time 3 (3.38±1.66 vs. 2.35±1.70; P=0.004) between home and away games. The analysis of game statistics identified that more metres were gained during home games (83.6±49.1 vs. 63.0±30.1; P=0.02) and more tackles made while playing away (18.4±9.2 vs. 14.3±6.7; P=0.016). The results suggest that short haul air travel without crossing time zones results in symptoms of travel fatigue but does not appear to negatively impact on elite RL players ability to perform strength and power tasks. Different game tactics (attacking vs. defensive) occurred between home and away games however, it is unclear whether travel fatigue or a home advantage (HA) is associated with this finding.
Pointwise error estimates of finite element approximations to the Stokes problem on convex polyhedra
Authors: Guzmán J. , Leykekhman D.
Published: March 2012

The aim of the paper is to show the stability of the finite element solution for the Stokes system in

W
∞
1

W^1_\infty

norm on general convex polyhedral domain. In contrast to previously known results,

W
r
2

W^2_r

regularity for

r
>
3

r>3

, which does not hold for general convex polyhedral domains, is not required. The argument uses recently available sharp Hölder pointwise estimates of the corresponding Green’s matrix together with novel local energy error estimates, which do not involve an error of the pressure in a weaker norm.
AUF1/hnRNP D represses expression of VEGF in macrophages
Authors: Fellows Abigail , Griffin Mary E. , Petrella Brenda L. , Zhong Lihui , Parvin-Nejad Fatemeh P. , Fava Roy , Morganelli Peter , Robey R. Brooks , Nichols Ralph C.
Published: March 2012

Vascular endothelial growth factor (VEGF) is a regulator of vascularization in development and is a key growth factor in tissue repair. In disease, VEGF contributes to vascularization of solid tumors and arthritic joints. This study examines the role of the mRNA-binding protein AUF1/heterogeneous nuclear ribonucleoprotein D (AUF1) in VEGF gene expression. We show that overexpression of AUF1 in mouse macrophage-like RAW-264.7 cells suppresses endogenous VEGF protein levels. To study 3′ untranslated region (UTR)–mediated regulation, we introduced the 3′ UTR of VEGF mRNA into a luciferase reporter gene. Coexpression of AUF1 represses VEGF-3′ UTR reporter expression in RAW-264.7 cells and in mouse bone marrow–derived macrophages. The C-terminus of AUF1 contains arginine–glycine–glycine (RGG) repeat motifs that are dimethylated. Deletion of the RGG domain of AUF1 eliminated the repressive effects of AUF1. Surprisingly, expression of an AUF1-RGG peptide reduced endogenous VEGF protein levels and repressed VEGF-3′ UTR reporter activity in RAW-264.7 cells. These findings demonstrate that AUF1 regulates VEGF expression, and this study identifies an RGG peptide that suppresses VEGF gene expression.
A mechanosensory system governs myosin II accumulation in dividing cells
Authors: Kee Yee-Seir , Ren Yixin , Dorfman Danielle , Iijima Miho , Firtel Richard , Iglesias Pablo A. , Robinson Douglas N.
Published: March 2012

The mitotic spindle is generally considered the initiator of furrow ingression. However, recent studies suggest that furrows can form without spindles, particularly during asymmetric cell division. In Dictyostelium, the mechanoenzyme myosin II and the actin cross-linker cortexillin I form a mechanosensor that responds to mechanical stress, which could account for spindle-independent contractile protein recruitment. Here we show that the regulatory and contractility network composed of myosin II, cortexillin I, IQGAP2, kinesin-6 (kif12), and inner centromeric protein (INCENP) is a mechanical stress–responsive system. Myosin II and cortexillin I form the core mechanosensor, and mechanotransduction is mediated by IQGAP2 to kif12 and INCENP. In addition, IQGAP2 is antagonized by IQGAP1 to modulate the mechanoresponsiveness of the system, suggesting a possible mechanism for discriminating between mechanical and biochemical inputs. Furthermore, IQGAP2 is important for maintaining spindle morphology and kif12 and myosin II cleavage furrow recruitment. Cortexillin II is not directly involved in myosin II mechanosensitive accumulation, but without cortexillin I, cortexillin II's role in membrane–cortex attachment is revealed. Finally, the mitotic spindle is dispensable for the system. Overall, this mechanosensory system is structured like a control system characterized by mechanochemical feedback loops that regulate myosin II localization at sites of mechanical stress and the cleavage furrow.
Molecular imaging of nuclear factor-Y transcriptional activity maps proliferation sites in live animals
Authors: Goeman Frauke , Manni Isabella , Artuso Simona , Ramachandran Balaji , Toietta Gabriele , Bossi Gianluca , Rando Gianpaolo , Cencioni Chiara , Germoni Sabrina , Straino Stefania , Capogrossi Maurizio C. , Bacchetti Silvia , Maggi Adriana , Sacchi Ada , Ciana Paolo , Piaggio Giulia
Published: March 2012

In vivo imaging involving the use of genetically engineered animals is an innovative powerful tool for the noninvasive assessment of the molecular and cellular events that are often targets of therapy. On the basis of the knowledge that the activity of the nuclear factor-Y (NF-Y) transcription factor is restricted in vitro to proliferating cells, we have generated a transgenic reporter mouse, called MITO-Luc (for mitosis-luciferase), in which an NF-Y–dependent promoter controls luciferase expression. In these mice, bioluminescence imaging of NF-Y activity visualizes areas of physiological cell proliferation and regeneration during response to injury. Using this tool, we highlight for the first time a role of NF-Y activity on hepatocyte proliferation during liver regeneration. MITO-Luc reporter mice should facilitate investigations into the involvement of genes in cell proliferation and provide a useful model for studying aberrant proliferation in disease pathogenesis. They should be also useful in the development of new anti/proproliferative drugs and assessment of their efficacy and side effects on nontarget tissues.
Binding of Autoantibodies to the Core Region of Tissue Transglutaminase Is a Feature of Paediatric Coeliac Disease
Authors: Comerford Ross , Byrne Greg , Feighery Conleth , Kelly Jacinta
Published: March 2012

Objectives:

Production of autoantibodies to the enzyme tissue transglutaminase (tTG) is a hallmark of coeliac disease (CD). We have previously demonstrated that the immumoglobulin (Ig) A response to tTG in adult CD specifically targets its catalytic core region, containing the active‐site triad of amino acids. The aim of the present study was to investigate this phenomenon in paediatric patients with CD, and to elucidate the contribution of each active‐site residue to epitopes recognised. The specificity of the IgG anti‐tTG response was also investigated and compared with that of the IgA anti‐tTG response, in both paediatric and adult patients with CD.

Methods:

Wild‐type and novel variants of tTG were generated via site‐directed mutagenesis and expressed as glutathione‐S‐transferase–fusion proteins in Escherichia coli BL‐21. The mutagenic variants of tTG had substitutions of 1, 1, or all of the 3 of the catalytic triad amino acids. All of the recombinant tTGs were tested for their antigenicity in IgA and IgG enzyme‐linked immunosorbent assays with cohorts of paediatric (n = 63) and adult (n = 30) CD sera.

Results:

Substitution of even 1 amino acid in the catalytic triad resulted in a significant reduction of CD IgA and IgG anti‐tTG binding, with all of the mutant proteins displaying diminished antigenicity compared with the wild‐type protein.

Conclusions:

The core region of tTG is specifically targeted from early on in disease course by CD patient autoantibodies of both the IgA and IgG class.
Impact of deficiency in CCR2 and CX3CR1 receptors on monocytes trafficking in herpes simplex virus encephalitis
Authors: Boivin Nicolas , Menasria Rafik , Gosselin David , Rivest Serge , Boivin Guy
Published: March 2012

The role played by resident microglia and by the infiltration of peripheral monocytes/macrophages in the innate immune response during herpes simplex virus type 1 (HSV-1) encephalitis was evaluated in mice deficient for the CCR2 and CX3CR1 receptors. CCR2−/−, CX3CR1−/−and C57BL/6 wild-type (WT) male mice were infected intranasally with 7×105p.f.u. of an HSV-1 clinical strain and monitored for signs of encephalitis and survival. In addition, brain viral DNA load and cytokine levels were evaluated by RT-PCR and magnetic bead-based immunoassay, respectively. The cellular response was assessed by fluorescence-activated cell sorting of blood and brain leukocytes. Infected CX3CR1−/−mice had a significantly lower mean life expectancy than WT mice (P<0.05, log-rank test) and demonstrated an increased infiltration of Ly-6Chigh‘inflammatory’ macrophages in the brain (P<0.05). Infected CCR2−/−mice had fewer monocytes (P<0.05), with a lower proportion of Ly-6Chigh‘inflammatory’ monocytes in the blood than the other groups (P<0.05). Brain viral DNA loads were only slightly higher in knockout mice than in WT mice (P-value not significant). These data suggest that CCR2 and especially CX3CR1 receptors are necessary to initiate a proper immune response during HSV encephalitis. More precisely, CCR2 is crucial for the emigration of monocytes from the bone marrow to the blood, whereas CX3CR1 is mostly implicated in the regulation of infiltrating cells from the blood to the site of infection and in the control of the immune homeostasis of the brain.
After the bottleneck: Genome-wide diversification of the Mycobacterium tuberculosis complex by mutation, recombination, and natural selection
Authors: Namouchi Amine , Didelot Xavier , Schöck Ulrike , Gicquel Brigitte , Rocha Eduardo P.C.
Published: March 2012

Many of the most virulent bacterial pathogens show low genetic diversity and sexual isolation. Accordingly, Mycobacterium tuberculosis, the deadliest human pathogen, is thought to be clonal and evolve by genetic drift. Yet, its genome shows few of the concomitant signs of genome degradation. We analyzed 24 genomes and found an excess of genetic diversity in regions encoding key adaptive functions including the type VII secretion system and the ancient horizontally transferred virulence-related regions. Four different approaches showed evident signs of recombination in M. tuberculosis. Recombination tracts add a high density of polymorphisms, and many are thus predicted to arise from outside the clade. Some of these tracts match Mycobacterium canettii sequences. Recombination introduced an excess of non-synonymous diversity in general and even more in genes expected to be under positive or diversifying selection, e.g., cell wall component genes. Mutations leading to non-synonymous SNPs are effectively purged in MTBC, which shows dominance of purifying selection. MTBC mutation bias toward AT nucleotides is not compensated by biased gene conversion, suggesting the action of natural selection also on synonymous changes. Together, all of these observations point to a strong imprint of recombination and selection in the genome affecting both non-synonymous and synonymous positions. Hence, contrary to some other pathogens and previous proposals concerning M. tuberculosis, this lineage may have come out of its ancestral bottleneck as a very successful pathogen that is rapidly diversifying by the action of mutation, recombination, and natural selection.
Extraction of High-Quality Genomic DNA from Ectocarpus
Authors: Coelho Susana M. , Scornet Delphine , Rousvoal Sylvie , Peters Nick , Dartevelle Laurence , Peters Akira F. , Cock J. Mark
Published: March 2012

For some applications, such as genome sequencing and high-throughput genotyping with multiple markers, it is necessary to use high-quality genomic DNA. This article describes how to obtain several micrograms of high-quality, cesium chloride-purified DNA from 1 g of Ectocarpus filaments. We also recommend using DNA of this quality for quantitative RT–PCR control reactions. However, simpler, more rapid, kit-based methods are preferable for experiments that involve the treatment of large numbers of individuals, such as genotyping large populations with a small number of markers or PCR screening of large populations.
Formation of Solid Lipid Nanoparticle (SLN)–Gene Vector Complexes for Transfection of Mammalian Cells In Vitro: Figure 1.
Authors: Rudolph Carsten , Rosenecker Joseph
Published: March 2012

Solid lipid nanoparticles (SLNs) offer several technological advantages over standard DNA carriers such as cationic lipids or cationic polymers. However, in the absence of endosomolytic agents such as chloroquine, gene-transfer efficiency mediated by SLN-derived gene vectors consisting of optimized lipid composition remains lower compared to those achieved with standard transfection agents. This protocol describes the incorporation of a dimeric human immunodeficiency virus type-1 (HIV-1) TAT peptide into SLN gene vectors to increase gene-transfer efficiency. This results in higher transfection rates than for standard transfection agents in vitro; the ternary SLN–gene vector complexes usually result in transfection levels equal to or higher than those observed with gene vector complexes formulated with branched polyethylenimine (PEI) 25 kDa. One significant advantage of using this method is the low cytotoxicity of the SLN gene vectors. The application of the gene-transfer technique is limited to relatively low plasmid DNA (pDNA) concentrations of the resulting complexes (10 µg/mL). At higher concentrations, the particles tend to aggregate and precipitate. Therefore, their use for in vivo application, which generally requires high pDNA concentrations, is limited.
Scoring and Analyzing Aggression in Drosophila
Authors: Certel Sarah J. , Kravitz Edward A.
Published: March 2012

Aggression is an innate behavior that has likely evolved in the framework of defending or obtaining resources. This complex social behavior is influenced by genetic, hormonal, and environmental factors. In many organisms, aggression is critical to survival, but the ability to control and suppress aggression in distinct contexts also is necessary. Invertebrate organisms, with their relatively simple nervous systems and a multiplicity of powerful tools available to examine their often elaborate and complex behavioral displays, have become increasingly valuable models for investigating the genetic and systems biological roots of social behavior. In this protocol, we outline methods for analyzing aggression in Drosophila: The design encompasses eco-ethological constraints that emphasize an understanding of normal aggression. The details include steps for constructing a fight arena, isolating and painting flies, introducing flies to an arena, and videotaping and scoring fights. These experimental protocols are in current use to identify candidate genes important in aggression and to elaborate the neuronal circuitry underlying the display of aggression and other social behaviors.
In Vivo Labeling of Cortical Astrocytes with Sulforhodamine 101 (SR101)
Authors: Nimmerjahn Axel , Helmchen Fritjof
Published: March 2012

Fluorescent markers that stain particular cell types in the intact brain are essential tools for fluorescence microscopy because they enable studies of structure and function of cells identified in this way. Although cell type-specific fluorescence staining can be achieved through promoter-driven expression of fluorescent proteins, this genetic approach is generally labor- and cost-intensive. Alternative viral approaches for targeted fluorophore expression are relatively invasive. For astrocytes, there is a simple alternative. This protocol describes an easy and robust method for rapid (within minutes) and high-contrast staining of astrocytes in defined regions of the intact rodent cortex using the synthetic, water-soluble but non-fixable red fluorescent dye sulforhodamine 101 (SR101). Selective staining is achieved through local uptake and gap junction-mediated spread of SR101 following its topical application or injection into tissue. Applications, technical pitfalls, and limitations of the SR101-staining technique are discussed. Given its simplicity and reliability, SR101 staining is a valuable tool for the study of astrocyte function in the intact brain and for in vivo fluorescence microscopy in general.
Introduction to Genetic Association Studies
Authors: Lewis Cathryn M. , Knight Jo
Published: March 2012

Genetic association studies are used to find candidate genes or genome regions that contribute to a specific disease by testing for a correlation between disease status and genetic variation. This article provides a broad outline of the design and analysis of such studies, focusing on case–control studies in candidate genes or regions.
Population PK/PD analysis of metformin using the signal transduction model
Authors: Chae Jung‐woo , Baek In‐hwan , Lee Byung‐yo , Cho Seong‐kwon , Kwon Kwang‐il
Published: March 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Metformin, a biguanide glucose lowering agent, is commonly used to manage type 2 diabetes.

• The molecular mechanisms of metformin have not been fully identified, but turnover of biomarkers such as glucose and signalling pathways or translocation of glucose transporters are closely related to the glucose‐lowering effects of metformin.

• The PK/PD of metformin have been investigated in healthy humans and patients with type 2 diabetes mellitus and modelling has been performed using an indirect response model.

WHAT THIS STUDY ADDS

• The purpose of this investigation was to develop a population PK/PD model for metformin using a signal transduction model in healthy humans and predict the PK/PD profile in patients with type 2 diabetes.

• The aim was to compare a previous model (a biophase model) with the signal transduction model, and use a more appropriate model to follow the actions of metformin.

• Additionally, our developed model was appropriate to predict the time course of plasma metformin and fasting plasma glucose (FPG) concentrations in patients with type 2 diabetes.

• To our knowledge, this is the first published population PK/PD analysis using the signal transduction model for metformin.

AIMS To develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for metformin (500 mg) using the signal transduction model in healthy humans and to predict the PK/PD profile in patients with type 2 diabetes.

METHODS Following the oral administration of 500 mg metformin to healthy humans, plasma concentrations of metformin were measured using LC‐MS/MS. A sequential modelling approach using NONMEM VI was used to facilitate data analysis. Monte Carlo simulation was performed to predict the antihyperglycaemic effect in patients with type 2 diabetes.

RESULTS Forty‐two healthy humans were included in the study. Population mean estimates (relative standard error, RSE) of apparent clearance, apparent volume of distribution and the absorption rate constant were 52.6 l h−1 (4.18%), 113 l (56.6%) and 0.41 h−1, respectively. Covariate analyses revealed that creatinine clearance (CLCR) significantly influenced metformin: CL/F= 52.6 × (CLcr/106.5)0.782. The signal transduction model was applied to describe the antihyperglycaemic effect of metformin. The population means for efficacy, potency, transit time and the Hill coefficient were estimated to be 19.8 (3.17%), 3.68 µg ml−1 (3.89%), 0.5 h (2.89%) and 0.547 (9.05%), respectively. The developed model was used to predict the antihyperglycaemic effect in patients with type 2 diabetes. The predicted plasma glucose concentration value was similar to previous values.

CONCLUSIONS The population signal transduction model was developed and evaluated for metformin use in healthy volunteers. Model evaluation by non‐parametric bootstrap analysis suggested that the proposed model was robust and parameter values were estimated with good precision.
Predation by introduced fish constrains the thermal distribution of aquatic Coleoptera in mountain lakes
Authors: DE MENDOZA GUILLERMO , RICO EUGENIO , CATALAN JORDI
Published: March 2012

1. Most high mountain lakes were free of fish until humans stocked them. This provides the opportunity to study the extent to which predation constrains the thermal distribution of large macroinvertebrates, among lakes of a suitable temperature for them.

2. We analysed the distribution of aquatic beetles (Coleoptera, Dytisicidae, including the genera Agabus, Platambus, Hydroporus and Boreonectes) in a set of 82 lakes in the Pyrenees. Temperature was the most important variable explaining the overall distribution of dytiscids (out of 29 environmental variables considered). The presence of fish (i.e. salmonids) and macrophyte cover (plants provide refuge from predators) was also important. Indeed, either salmonids or macrophytes as single factors explained more of the variance in dytiscid distribution than temperature.

3. Further analysis showed that the presence of salmonids was particularly important for the medium‐sized dytiscid Agabus bipustulatus. This species is generally eurythermic, although in the Pyrenees it is found mainly in cold lakes. This is attributed to predation pressure from fish, since the latter are more likely to be present in warm lakes. As a consequence, salmonids increase fragmentation of A. bipustulatus with respect to populations occupying lowland habitats.

4. Predation can therefore constrain the distribution of species to a fraction of habitats that appear suitable based on simple thermal responses. As humans also facilitate the dispersal of non‐native fish, the consequent modification of distribution patterns in fresh waters could make it difficult to predict how distributions might change in relation to climate warming.
Inheritance and memory of stress‐induced epigenome change: roles played by the ATF‐2 family of transcription factors
Authors: Seong Ki‐Hyeon , Maekawa Toshio , Ishii Shunsuke
Published: March 2012

Data on the inheritance‐of‐stress effect have been accumulating and some mechanistic insights, such as epigenetic regulation, have also been suggested. In particular, the modern view of Lamarckian inheritance appears to be affected by the finding that stress‐induced epigenetic changes can be inherited. This review summarizes the current data on the inheritance of stress effect and possible mechanisms involved in this process. In particular, we focus on the stress‐induced epigenetic changes mediated by the ATF‐2 family of transcription factors.
Niche models tell half the story: spatial context and life‐history traits influence species responses to global change
Authors: Swab Rebecca M. , Regan Helen M. , Keith David A. , Regan Tracey J. , Ooi Mark K. J.
Published: March 2012

Aim  While niche models are typically used to assess the vulnerability of species to climate change, they have been criticized for their limited assessment of threats other than climate change. We attempt to evaluate this limitation by combining niche models with life‐history models to investigate the relative influence of climate change and a range of fire regimes on the viability of a long‐lived plant population. Specifically, we investigate whether range shift due to climate change is a greater threat to an obligate seeding fire‐prone shrub than altered fire frequency and how these two threatening processes might interact.

Location  Australian sclerophyll woodland and heathland.

Methods  The study species is Leucopogon setiger, an obligate seeding fire‐prone shrub. A spatially explicit stochastic matrix model was constructed for this species and linked with a dynamic niche model and fire risk functions representing a suite of average fire return intervals. We compared scenarios with a variety of hypothetical patches, a patch framework based upon current habitat suitability and one with dynamic habitat suitability based on climate change scenarios A1FI and A2.

Results  Leucopogon setiger was found to be sensitive to fire frequency, with shorter intervals reducing expected minimum abundances (EMAs). Spatial decoupling of fires across the landscape reduced the vulnerability of the species to shortened fire frequencies. Shifting habitat, while reducing EMAs, was less of a threat to the species than frequent fire.

Main conclusions  Altered fire regime, in particular more frequent fires relative to the historical regime, was predicted to be a strong threat to this species, which may reflect a vulnerability of obligate seeders in general. Range shifts induced by climate change were a secondary threat when habitat reductions were predicted. Incorporating life‐history traits into habitat suitability models by linking species distribution models with population models allowed for the population‐level evaluation of multiple stressors that affect population dynamics and habitat, ultimately providing a greater understanding of the impacts of global change than would be gained by niche models alone. Further investigations of this type could elucidate how particular bioecological factors can affect certain types of species under global change.
Modification of fatigue strain‐life equation for sheet metals considering anisotropy due to crystallographic texture
Authors: HARIHARAN K. , PRAKASH R. V.
Published: March 2012

The fatigue behaviour of cold rolled and annealed sheet metals are influenced by the anisotropy of mechanical properties due to crystallographic texture. However, the existing fatigue strain‐life models are primarily meant for isotropic material behaviour. In the present work, the Coffin‐Manson equation for strain‐life is modified to include the effect of anisotropy using phenomenological plasticity models. It is observed that the variation of strain hardening exponent is critical to model the strain‐life behaviour. Variation of strain hardening exponent with orientation is modelled using existing anisotropic yield criteria. The prediction of fatigue life using the proposed model correlates well with the experimental results of Al6061‐T6 along different orientations. The proposed model can be used to predict the fatigue properties along any orientation from the fatigue data along one orientation and monotonic mechanical properties along longitudinal, transverse and diagonal directions.
Recoverability of renal functions after relief of partial ureteric obstruction of solitary kidney: impact of ferulic acid
Authors: Shokeir Ahmed A. , Hussein Abdel‐Aziz M. , Soliman Shady A. , Kamal Mohamed M. , Abdel‐Aziz Azza , Awadalla Amira , Rahim Mona Abdel , Barakat Nashwa
Published: March 2012

What's known on the subject? and What does the study add?

It is known that the kidney damage continues even after release of ureteric obstruction. This study found that giving ferulic acid, antioxidant, after release of ureteric obstruction enhanced the recovery of kidney functions in solitary kidney.

OBJECTIVE

To evaluate the effect of ferulic acid (FA) on the recovery of renal function and renal damage after relief of partial ureteric obstruction (PUO) of a solitary kidney.

METHODS

Male mongrel dogs (n= 32) were classified into three groups: sham (eight), control (12) and study (12).

A right nephrectomy was carried out and dogs in the study and control groups were subjected to 4 weeks of PUO.

Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC) were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief of obstruction.

Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial fibrosis in the kidney were evaluated at the end of experiment.

RESULTS

Ferulic acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26% and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks' obstruction.

In addition, FA caused a significant decrease in MDA and a significant increase in GSH and SOD.

Ferulic acid also significantly reduced the interstitial fibrosis, and caspase 3 expression, and significantly increased the expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the obstruction.

CONCLUSION

Ferulic acid enhances the recoverability of renal function and minimizes the renal damage through reduction of oxidative stress, tubular apoptosis and the interstitial fibrosis in the solitary kidney after relief of PUO.