bluuebunny/crossref_metadata_2025 huggingface dataset:
Filamentation induced by collinear femtosecond double pulses with different wavelengths in air
Authors: Li Suyu , Sui Laizhi , Li Shuchang , Liu Dunli , Li He , Li Qingyi , Zhang Fangjian , Chen Anmin , Jiang Yuanfei , Jin Mingxing
Published: September 2015

Filamentation induced by collinear femtosecond double pulses with different wavelengths (400 nm + 800 nm) in air is investigated by measuring the filament spectra along the propagation axis. By changing their energies and the time delay between them, the role of each pulse in the filamentation is investigated. Though the two pulses do not overlap in time, the filament generated by the previous pulse will interact with the latter one, thus affecting the filamentation process. Each pulse plays a different role when the time delay and input energy are different: As the energy of the 800 nm pulse is relative high (∼600 μJ), the 400 nm pulse has inhibitory and supplementary effects on the filament generated by the 800 nm one as it is prior to and behind the 800 nm one, respectively, which ultimately influences the filament length and strength; however, as energy of the 800 nm pulse decreases to 340 μJ, the filament mainly results from the 400 nm pulse and the 800 nm one just plays an auxiliary role. This study provides an effective way to control filamentation.
Structure and electronic properties of Cu nanoclusters supported on Mo2C(001) and MoC(001) surfaces
Authors: Posada-Pérez Sergio , Viñes Francesc , Rodríguez José A. , Illas Francesc
Published: September 2015

The atomic structure and electronic properties of Cun nanoclusters (n = 4, 6, 7, and 10) supported on cubic nonpolar δ-MoC(001) and orthorhombic C- or Mo-terminated polar β-Mo2 C(001) surfaces have been investigated by means of periodic density functional theory based calculations. The electronic properties have been analyzed by means of the density of states, Bader charges, and electron localization function plots. The Cu nanoparticles supported on β-Mo2 C(001), either Mo- or C-terminated, tend to present a two-dimensional structure whereas a three-dimensional geometry is preferred when supported on δ-MoC(001), indicating that the Mo:C ratio and the surface polarity play a key role determining the structure of supported clusters. Nevertheless, calculations also reveal important differences between the C- and Mo-terminated β-Mo2 C(001) supports to the point that supported Cu particles exhibit different charge states, which opens a way to control the reactivity of these potential catalysts.
Influence of interface roughness in quantum cascade lasers
Authors: Krivas K. A. , Winge D. O. , Franckié M. , Wacker A.
Published: September 2015

We use a numerical model based on non-equilibrium Green's functions to investigate the influence of interface roughness (IFR) scattering in terahertz quantum cascade lasers. We confirm that IFR is an important phenomenon that affects both current and gain. The simulations indicate that IFR causes a leakage current that transfers electrons from the upper to the lower laser state. In certain cases, this current can greatly reduce gain. In addition, individual interfaces and their impact on the renormalized single particle energies are studied and shown to give both blue- and red-shifts of the gain spectrum.
Electrical and structural properties of group-4 transition-metal nitride (TiN, ZrN, and HfN) contacts on Ge
Authors: Yamamoto Keisuke , Noguchi Ryutaro , Mitsuhara Masatoshi , Nishida Minoru , Hara Toru , Wang Dong , Nakashima Hiroshi
Published: September 2015

Electrical and structural properties were investigated for group-4 transition-metal nitride contacts on Ge (TiN/Ge, ZrN/Ge, and HfN/Ge), which were prepared by direct sputter depositions using nitride targets. These contacts could alleviate the intrinsic Fermi-level pinning (FLP) position toward the conduction band edge. It was revealed that this phenomenon is induced by an amorphous interlayer (a-IL) containing nitrogen atoms at the nitride/Ge interfaces. The strength of FLP alleviation positively depended on the thickness of a-IL. TiN/Ge and ZrN/Ge contacts with ∼2 nm-thick a-ILs showed strong FLP alleviations with hole barrier heights (ΦBP) in the range of 0.52–56 eV, and a HfN/Ge contact with an ∼1 nm-thick a-IL showed a weaker one with a ΦBP of 0.39 eV. However, TaN/Ge contact without a-IL did not show such FLP alleviation. Based on the results of depth distributions for respective elements, we discussed the formation kinetics of a-ILs at TiN/Ge and ZrN/Ge interfaces. Finally, we proposed an interfacial dipole model to explain the FLP alleviation.
Negative ion properties of trans 2,2′,6,6′-tetrafluoroazobenzene: Experiment and theory
Authors: Rezaee Mohammadreza , Wang Yi , Zhang Xinxing , Liu Gaoxiang , Bowen Kit , Bayer Andrew M. , Best Michel D. , Compton Robert N.
Published: September 2015

Chemical bonding and the electronic structure of the trans 2,2′,6,6′-tetrafluoroazobenzene negative ion have been studied using collision-induced dissociation as well as photodetachment-photoelectron spectroscopy and the experimental results for different properties were compared with the corresponding values calculated using ab initio quantum chemistry methods. The trans 2,2′,6,6′-tetrafluoroazobenzene anion was prepared by atmospheric pressure chemical ionization for the collision induced dissociation (CID) experiment and through thermal electron attachment in the photodetachment-photoelectron spectroscopy experiments. The adiabatic electron affinity of trans 2,2′,6,6′-tetrafluoroazobenzene was measured to be 1.3 ± 0.10 eV using 355 nm, 488 nm, and 532 nm photodetachment photons and the vertical detachment energy was measured to be 1.78 ± 0.10 eV, 2.03 ± 0.10 eV, and 1.93 ± 0.10 eV, respectively. The adiabatic electron affinity was calculated employing different ab initio methods giving values in excellent agreement with experimental results. Energy resolved collision induced dissociation experiment study of the precursor anion resulted in 1.92 ± 0.15 eV bond dissociation energy for the collision process yielding C6H3F2− fragment ion at 0 K. Calculations using different ab initio methods resulted in a bond dissociation energy ranging from 1.79 to 2.1 eV at 0 K. Two additional CID fragment ions that appear at higher energies, C6H2F− and C6H−, are not results of a single bond cleavage. The occurrence of C6H− is of particular interest since it is the first anion to be observed in the interstellar medium.
Tandem ion mobility spectrometry coupled to laser excitation
Authors: Simon Anne-Laure , Chirot Fabien , Choi Chang Min , Clavier Christian , Barbaire Marc , Maurelli Jacques , Dagany Xavier , MacAleese Luke , Dugourd Philippe
Published: September 2015

This manuscript describes a new experimental setup that allows to perform tandem ion mobility spectrometry (IMS) measurements and which is coupled to a high resolution time-of-flight mass spectrometer. It consists of two 79 cm long drift tubes connected by a dual ion funnel assembly. The setup was built to permit laser irradiation of the ions in the transfer region between the two drift tubes. This geometry allows selecting ions according to their ion mobility in the first drift tube, to irradiate selected ions, and examine the ion mobility of the product ions in the second drift tube. Activation by collision is possible in the same region (between the two tubes) and between the second tube and the time-of-flight. IMS-IMS experiments on Ubiquitin are reported. We selected a given isomer of charge state +7 and explored its structural rearrangement following collisional activation between the two drift tubes. An example of IMS-laser-IMS experiment is reported on eosin Y, where laser irradiation was used to produce radical ions by electron photodetachment starting from doubly deprotonated species. This allowed measuring the collision cross section of the radical photo-product, which cannot be directly produced with an electrospray source.
Octonic formulations of Maxwell type fluid equations
Authors: Tanışlı Murat , Demir Süleyman , Şahin Neslihan
Published: September 2015

Although the origins of electromagnetic theory and the fluid mechanics are completely different, the compressible ideal fluid equations can be expressed in a form analogous to that of electromagnetism. In this paper, the Maxwell type fluid equations are rewritten in terms of octons. Using the analogies between electromagnetism and fluid mechanics, the compact and elegant formulations are derived. It is proved that single octonic expression describes Maxwell-type fluid equations. The octonic fluid wave equations and fluid Poynting theorem are also formulated in a similar form to electromagnetism and linear gravity.
Effects of nitrogen-related defects on visible light photocatalytic response in N+ implanted TiO2: A first-principles study
Authors: Senga Junya , Tatsumi Kazuyoshi , Muto Shunsuke , Yoshida Tomoko
Published: September 2015

It was found that the visible-light responsiveness of a nitrogen ion-implanted TiO2 photocatalyst was attributable to the predominant chemical states of nitrogen, depending on the local nitrogen concentration near the surface. In the present study, we examined the effects of conceivable nitrogen-related defects on the visible light responsiveness, based on electronic structures calculated from first principles. Possible chemical states were proposed by comparing previously reported experiments with the present theoretical N-K X-ray absorption spectra. The theoretically predicted visible light absorption spectra and carrier trap states due to the bandgap states associated with the defects well explained the relationship between the catalytic reactivity and the proposed chemical states.
Solution and displacement in monolayer and multilayer binary films of SF6 and CF4 on graphite
Authors: Thomas Petros , Grogan Michael D. W. , Hess George B.
Published: September 2015

Infrared reflection absorption spectroscopy is used to study the evolution of binary physisorbed films on graphite. A predeposited monolayer of SF6 is exposed to slowly increasing pressure of CF4 at constant temperature between 80 and 113 K. Shifts in the frequencies of the dominant vibrational mode of each species due to resonant dipole-dipole coupling serve as proxies for the areal density of each species in the monolayer. If the initial SF6 film is far below saturation (coexistence with bulk solid), the SF6 can be largely displaced by continuous solution of CF4. However, if the initial SF6 layer is at or near saturation, a layer of CF4 condenses on top at a well defined CF4 pressure after only 2%-3% dilution of the SF6 layer. Simultaneously, most of the dissolved CF4 is withdrawn from the SF6 layer. With further increase in CF4 pressure, the CF4 layer is compressed and additional layers condense, while the SF6 layer is again diluted. Still, the SF6 layer retains about 90% concentration until the CF4 pressure is very close to saturation, at which point the SF6 is rapidly displaced, apparently going into dilute solution in the rapidly growing CF4 multilayer. Monte Carlo simulations are used to quantitatively relate measured frequency shifts to concentrations in the binary monolayer.
Correlation functions of main-chain polymer nematics constrained by tensorial and vectorial conservation laws
Authors: Svenšek Daniel , Podgornik Rudolf
Published: September 2015

We present and analyze correlation functions of a main-chain polymer nematic in a continuum worm-like chain description for two types of constraints formalized by the tensorial and vectorial conservation laws, both originating in the microscopic chain integrity, i.e., the connectivity of the polymer chains. In particular, our aim is to identify the features of the correlation functions that are most susceptible to the differences between the two constraints. Besides the density and director autocorrelations in both the tensorial and vectorial cases, we calculate also the density-director correlation functions, the latter being a direct signature of the presence of a specific constraint. Its amplitude is connected to the strength of the constraint and is zero if none of the constraints are present, i.e., for a standard non-polymeric nematic. Generally, the correlation functions with the constraints differ substantially from the correlation functions in the non-polymeric case, if the constraints are strong which in practice requires long chains. Moreover, for the tensorial conservation law to be well distinguishable from the vectorial one, the chain persistence length should be much smaller than the total length of the chain, so that hairpins (chain backfolding) are numerous and the polar order is small.
Relaxation channels of multi-photon excited xenon clusters
Authors: Serdobintsev P. Yu. , Rakcheeva L. P. , Murashov S. V. , Melnikov A. S. , Lyubchik S. , Timofeev N. A. , Pastor A. A. , Khodorkovskii M. A.
Published: September 2015

The relaxation processes of the xenon clusters subjected to multi-photon excitation by laser radiation with quantum energies significantly lower than the thresholds of excitation of atoms and ionization of clusters were studied. Results obtained by means of the photoelectron spectroscopy method showed that desorption processes of excited atoms play a significant role in the decay of two-photon excited xenon clusters. A number of excited states of xenon atoms formed during this process were discovered and identified.
Shock melting method to determine melting curve by molecular dynamics: Cu, Pd, and Al
Authors: Liu Zhong-Li , Zhang Xiu-Lu , Cai Ling-Cang
Published: September 2015

A melting simulation method, the shock melting (SM) method, is proposed and proved to be able to determine the melting curves of materials accurately and efficiently. The SM method, which is based on the multi-scale shock technique, determines melting curves by preheating and/or prepressurizing materials before shock. This strategy was extensively verified using both classical and ab initio molecular dynamics (MD). First, the SM method yielded the same satisfactory melting curve of Cu with only 360 atoms using classical MD, compared to the results from the Z-method and the two-phase coexistence method. Then, it also produced a satisfactory melting curve of Pd with only 756 atoms. Finally, the SM method combined with ab initio MD cheaply achieved a good melting curve of Al with only 180 atoms, which agrees well with the experimental data and the calculated results from other methods. It turned out that the SM method is an alternative efficient method for calculating the melting curves of materials.
Spectral modification of the laser emission of a terahertz quantum cascade laser induced by broad-band double pulse injection seeding
Authors: Markmann Sergej , Nong Hanond , Pal Shovon , Hekmat Negar , Scholz Sven , Kukharchyk Nadezhda , Ludwig Arne , Dhillon Sukhdeep , Tignon Jérôme , Marcadet Xavier , Bock Claudia , Kunze Ulrich , Wieck Andreas D. , Jukam Nathan
Published: September 2015

We demonstrate by injection seeding that the spectral emission of a terahertz (THz) quantum cascade laser (QCL) can be modified with broad-band THz pulses whose bandwidths are greater than the QCL bandwidth. Two broad-band THz pulses delayed in time imprint a modulation on the single THz pulse spectrum. The resulting spectrum is used to injection seed the THz QCL. By varying the time delay between the THz pulses, the amplitude distribution of the QCL longitudinal modes is modified. By applying this approach, the QCL emission is reversibly switched from multi-mode to single mode emission.
Surface modifications with Lissajous trajectories using atomic force microscopy
Authors: Cai Wei , Yao Nan
Published: September 2015

In this paper, we report a method for atomic force microscopy surface modifications with single-tone and multiple-resolution Lissajous trajectories. The tip mechanical scratching experiments with two series of Lissajous trajectories were carried out on monolayer films. The scratching processes with two scan methods have been illustrated. As an application, the tip-based triboelectrification phenomenon on the silicon dioxide surface with Lissajous trajectories was investigated. The triboelectric charges generated within the tip rubbed area on the surface were characterized in-situ by scanning Kelvin force microscopy. This method would provide a promising and cost-effective approach for surface modifications and nanofabrication.
Direct observation of a resolvable spin separation in the spin Hall effect of light at an air-glass interface
Authors: Ren Jin-Li , Wang Bo , Xiao Yun-Feng , Gong Qihuang , Li Yan
Published: September 2015

We theoretically and experimentally demonstrate that it is possible to directly observe the resolvable spin separation in the spin Hall effect of light at an air-glass interface by choosing optimal parameters. When a P-polarized light with a beam waist of 10 μm is incident around Brewster's angle, the two spin components of the reflected beam can be completely separated by eliminating the influence of the in-plane wavevector spread. This not only obviously reveals the strong impacts of the polarization state, the incident angle, the beam waist, and the in-plane wavevector spread, but also intuitively visualizes the observation of the spin Hall effect of light.
Existence of three-dimensional ideal-magnetohydrodynamic equilibria with current sheets
Authors: Loizu J. , Hudson S. R. , Bhattacharjee A. , Lazerson S. , Helander P.
Published: September 2015

We consider the linear and nonlinear ideal plasma response to a boundary perturbation in a screw pinch. We demonstrate that three-dimensional, ideal-MHD equilibria with continuously nested flux-surfaces and with discontinuous rotational-transform across the resonant rational-surfaces are well defined and can be computed both perturbatively and using fully nonlinear equilibrium calculations. This rescues the possibility of constructing MHD equilibria with current sheets and continuous, smooth pressure profiles. The results predict that, even if the plasma acts as a perfectly conducting fluid, a resonant magnetic perturbation can penetrate all the way into the center of a tokamak without being shielded at the resonant surface.
Reducing the carbon footprint of Australian milk production by mitigation of enteric methane emissions
Authors: Moate Peter J. , Deighton Matthew H. , Williams S. Richard O. , Pryce Jennie E. , Hayes Ben J. , Jacobs Joe L. , Eckard Richard J. , Hannah Murray C. , Wales William J.
Published: September 2015

This review examines research aimed at reducing enteric methane emissions from the Australian dairy industry. Calorimeter measurements of 220 forage-fed cows indicate an average methane yield of 21.1 g methane (CH4)/kg dry matter intake. Adoption of this empirical methane yield, rather than the equation currently used in the Australian greenhouse gas inventory, would reduce the methane emissions attributed to the Australian dairy industry by ~10%. Research also indicates that dietary lipid supplements and feeding high amounts of wheat substantially reduce methane emissions. It is estimated that, in 1980, the Australian dairy industry produced ~185 000 t of enteric methane and total enteric methane intensity was ~33.6 g CH4/kg milk. In 2010, the estimated production of enteric methane was 182 000 t, but total enteric methane intensity had declined ~40% to 19.9 g CH4/kg milk. This remarkable decline in methane intensity and the resultant improvement in the carbon footprint of Australian milk production was mainly achieved by increased per-cow milk yield, brought about by the on-farm adoption of research findings related to the feeding and breeding of dairy cows. Options currently available to further reduce the carbon footprint of Australian milk production include the feeding of lipid-rich supplements such as cottonseed, brewers grains, cold-pressed canola, hominy meal and grape marc, as well as feeding of higher rates of wheat. Future technologies for further reducing methane emissions include genetic selection of cows for improved feed conversion to milk or low methane intensity, vaccines to reduce ruminal methanogens and chemical inhibitors of methanogenesis.
A steady-state physiological model for intracellular dimethylsulfoxide in marine phytoplankton
Authors: Lavoie Michel , Levasseur Maurice , Sunda William G.
Published: September 2015

Environmental context
Dimethylsulfoxide (DMSO) is important in the biogeochemical cycle of sulfur. Using a mathematical flux model of DMSO production and loss rates, we find that the high intracellular DMSO concentrations measured in phytoplankton cannot be produced without invoking unrealistically high intracellular concentrations of the precursor dimethylsulfoniopropionate, or much lower phytoplankton cellular efflux rates than currently reported. Our study emphasises the need for further investigations of DMSO fluxes across intracellular and outer cell membranes.

Abstract
Despite 20+ years of research, the mechanisms whereby marine phytoplankton accumulate high dimethylsulfoxide (DMSO) concentrations (up to 1–70mmol per litre of cell volume) are still puzzling. In order to evaluate reported intracellular DMSO concentrations, we constructed a kinetic steady-state rate model of intracellular DMSO concentrations in microalgae based on reported DMSO production from the oxidation of dimethylsulfoniopropionate (DMSP) and loss by diffusion out of the cell. Based on measured rates of DMSO diffusion across the outer cell membrane of model algal species, the steady-state model indicates that sustaining intracellular DMSO concentrations in the millimolar range by the oxidation of intracellular DMSP would require steady-state intracellular DMSP concentrations that are 40 to 10000 times higher than values measured in prymnesiophytes and diatoms, high- and low-DMSP algal groups. However, if DMSO is mainly produced within the chloroplast by the oxidation of DMSP by photosynthetically produced reactive oxygen species, it would have to diffuse through multiple chloroplast membranes before being lost from the cell across the outer membrane. Consequently, its loss rate might be considerably slower than our model predicts, allowing the build-up of higher intracellular DMSO concentrations. Possible biases in sample handling and DMSO analyses could also explain the discrepancy between modelled and measured intracellular DMSO.
Dietary change among hominins and cercopithecids in Ethiopia during the early Pliocene
Authors: Levin Naomi E. , Haile-Selassie Yohannes , Frost Stephen R. , Saylor Beverly Z.
Published: September 2015

Significance

Dietary change among hominins is a critical aspect of human evolution. Here we use carbon isotope data from fossil teeth of hominins, monkeys, and other mammals from Ethiopia to document C4food consumption by both hominins and the baboon,Theropithecus oswaldi, during the early Pliocene. The expansion of hominin diet and the appearance of theTheropithecus oswaldilineage as early as 3.76 Ma mark a major ecological change within African primate communities. The ability to eat a range of C3and C4foods indicates that early Pliocene hominins were likely generalists who could thrive in different and perhaps varying environments.
Melting of iron determined by X-ray absorption spectroscopy to 100 GPa
Authors: Aquilanti Giuliana , Trapananti Angela , Karandikar Amol , Kantor Innokenty , Marini Carlo , Mathon Olivier , Pascarelli Sakura , Boehler Reinhard
Published: September 2015

Significance

There is a long-standing controversy over the melting curve of Fe at high pressure as determined from static laser heated diamond anvil cell and dynamic compression studies. X-ray absorption spectroscopy measurements are used here as a criterion to detect melting under pressure. Confronted with a diversity of obtained melting curves, this technique, used at such pressure and temperature conditions, is eligible to be at the forefront to probe Earth's deep interior. Furthermore, the experiment reported here holds promise for addressing important issues related to the structure and phase diagram of compressed melts, such as the existence of structural complexity (polyamorphism) in the liquid phase or the extent of icosahedral ordering whose investigation has been limited until now to ambient conditions.
Complex constraints on allometry revealed by artificial selection on the wing ofDrosophila melanogaster
Authors: Bolstad Geir H. , Cassara Jason A. , Márquez Eladio , Hansen Thomas F. , van der Linde Kim , Houle David , Pélabon Christophe
Published: September 2015

Significance

Many traits scale precisely with size, but it is unknown whether this is due to selection for optimal function or due to evolutionary constraint. We use artificial selection to demonstrate that wing-shape scaling in fruit flies can respond to selection. This evolved response in scaling was lost during a few generations after selection ended, but other selected changes in wing shape persisted. Shape–size scaling in fly wings is therefore evolvable, but adaptation is apparently constrained by selection that may not be on wings. This may explain why scaling relationships are often evolutionarily conserved.
Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest
Authors: Moreau Hélène D. , Lemaître Fabrice , Garrod Kym R. , Garcia Zacarias , Lennon-Duménil Ana-Maria , Bousso Philippe
Published: September 2015

Significance

To mount an efficient immune response, T cells need to recognize foreign antigen to become activated, proliferate, and acquire their effector functions. We show that T cells can adopt two behaviors depending on the strength of the antigen stimulation. Upon suboptimal stimulation, T cells adopt a scanning behavior that promotes local exploration of the microenvironment. Stronger stimulation triggers specific mechanisms that induce complete T-cell arrest. We propose that these distinct behaviors may represent an optimal strategy for T cells to find the strongest antigenic stimulation.
Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis
Authors: Hsu Lea Chia-Ling , Nam Sean , Cui Yi , Chang Ching-Pu , Wang Chia-Fang , Kuo Hung-Chih , Touboul Jonathan D. , Chou Shen-Ju
Published: September 2015

Significance

The cerebral cortex is the most highly evolved structure in the human brain. Generating the correct number and types of neurons is crucial for brain function. We show a central role of the Lhx2 homeoprotein in this task: deleting Lhx2 in cortical progenitors leads to a temporal shift of neurogenesis initiation, resulting in a much smaller cortex with decreased numbers of neurons in all cortical layers. Further, we found that Lhx2 is required for the Wnt/β-catenin pathway to maintain progenitor proliferation. Using a parsimonious mathematical model, we demonstrated that such disruptions of neurogenesis timing are enough to explain the cortical size and thickness modifications observed. Our findings enlighten how neurogenesis timing is regulated molecularly and how it affects cortical size and organization.
Climate change and physical disturbance cause similar community shifts in biological soil crusts
Authors: Ferrenberg Scott , Reed Sasha C. , Belnap Jayne
Published: September 2015

Significance

In drylands worldwide, where plant cover is sparse, large amounts of the ground surface are covered by specialized organisms that form biological soil crusts (biocrusts). Biocrusts fix carbon and nitrogen, stabilize soils, and influence hydrology. Extensive physical disturbance from livestock/human trampling and off-road vehicles is known to destroy biocrusts and alter ecosystem function. More recent work also indicates that climate change can affect biocrust communities. Contrary to our expectations, experimental climate change and physical disturbance had strikingly similar impacts on biocrust communities, with both promoting a shift to degraded, early successional states. These results herald ecological state transitions in drylands as temperatures rise, calling for management strategies that consider risks from both physical disturbances and climate change.
Amelioration of inflammation and tissue damage in sickle cell model mice by Nrf2 activation
Authors: Keleku-Lukwete Nadine , Suzuki Mikiko , Otsuki Akihito , Tsuchida Kouhei , Katayama Saori , Hayashi Makiko , Naganuma Eriko , Moriguchi Takashi , Tanabe Osamu , Engel James Douglas , Imaizumi Masue , Yamamoto Masayuki
Published: September 2015

Significance

Sickle cell disease (SCD) is one of the most common inherited disorders. A mutation in the β-globin gene causes deformation of red blood cells into a sickle shape, which in turn causes intravascular hemolysis and vaso-occlusion resulting in damage to multiple organs. Most studies that propose to develop new SCD therapies include the induction of fetal γ-globin expression to inhibit sickle cell formation as their ultimate goal. In contrast, we demonstrate here that activation of nuclear factor erythroid 2-related factor 2 (Nrf2) ameliorates the development of inflammation and tissue damage that strongly affect the morbidity of SCD patients. Notably, several compounds that serve as Nrf2 inducers have been developed or are under development. The data indicate that Nrf2 activation could improve the prognosis for SCD patients.
EBS7 is a plant-specific component of a highly conserved endoplasmic reticulum-associated degradation system in
Arabidopsis
Authors: Liu Yidan , Zhang Congcong , Wang Dinghe , Su Wei , Liu Linchuan , Wang Muyang , Li Jianming
Published: September 2015

Significance

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a well-studied cellular process in yeast and mammalian systems. Recent molecular and genetic studies in the reference plant
Arabidopsis
have revealed that ERAD also is conserved in plants. Here we report that an
Arabidopsis
ERAD process for degrading misfolded/mutant receptor-like kinases requires a plant-specific protein, ethyl methanesulfonate-mutagenized brassinosteroid-insensitive 1 suppressor 7 (EBS7), that is localized to the ER membrane and is induced by ER stress. Our biochemical studies suggest that EBS7 functions as a key regulator of this
Arabidopsis
ERAD process by maintaining the protein stability of its core component, a membrane-anchored E3 ligase,
Arabidopsis thaliana
HMG-CoA reductase degradation 1a (AtHrd1a).
Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity
Authors: Zhang Peng , Sun Fang , Tsao Caroline , Liu Sijun , Jain Priyesh , Sinclair Andrew , Hung Hsiang-Chieh , Bai Tao , Wu Kan , Jiang Shaoyi
Published: September 2015

Significance

A protein modification technology has been developed in this study to overcome current problems faced by protein therapy. After being individually encapsulated in a super-hydrophilic zwitterionic gel, a therapeutic protein showed exceptional stability and long in vivo circulation half-life. More importantly, no immune response against either the protein or the polymer was observed following repeated injections. This technology will benefit patients by reducing administration frequency and mitigating adverse reactions and could allow more immunogenic proteins to enter into human therapeutic or protective applications.
MYB36 regulates the transition from proliferation to differentiation in the
Arabidopsis
root
Authors: Liberman Louisa M. , Sparks Erin E. , Moreno-Risueno Miguel A. , Petricka Jalean J. , Benfey Philip N.
Published: September 2015

Significance

The process by which cells differentiate is central to multicellular development and cancer. Dramatic gene expression changes mediate this complex process, which involves the termination of proliferation and the acquisition of distinct cell-specific features. We identified a transcription factor, MYB DOMAIN PROTEIN 36 (MYB36), that regulates this developmental transition in the
Arabidopsis thaliana
root endodermis. Differentiated endodermis forms a protective waxy barrier called the Casparian strip. We found that MYB36 activates genes involved in Casparian strip formation and represses genes involved in proliferation. Our results suggest that MYB36 is a critical regulator of developmental timing in the root endodermis.
Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity
Authors: Paterson Alison M. , Lovitch Scott B. , Sage Peter T. , Juneja Vikram R. , Lee Youjin , Trombley Justin D. , Arancibia-Cárcamo Carolina V. , Sobel Raymond A. , Rudensky Alexander Y. , Kuchroo Vijay K. , Freeman Gordon J. , Sharpe Arlene H.
Published: September 2015

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4+Foxp3− (T conv) and regulatory Foxp3+ (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA-4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells.
Reconciling depressed Ca2+ sparks occurrence with enhanced RyR2 activity in failing mice cardiomyocytes
Authors: Ruiz-Hurtado Gema , Li Linwei , Fernández-Velasco María , Rueda Angélica , Lefebvre Florence , Wang Yueyi , Mateo Philippe , Cassan Cécile , Gellen Barnabas , Benitah Jean Pierre , Gómez Ana María
Published: September 2015

Abnormalities in cardiomyocyte Ca2+ handling contribute to impaired contractile function in heart failure (HF). Experiments on single ryanodine receptors (RyRs) incorporated into lipid bilayers have indicated that RyRs from failing hearts are more active than those from healthy hearts. Here, we analyzed spontaneous Ca2+ sparks (brief, localized increased in [Ca2+]i) to evaluate RyR cluster activity in situ in a mouse post-myocardial infarction (PMI) model of HF. The cardiac ejection fraction of PMI mice was reduced to ∼30% of that of sham-operated (sham) mice, and their cardiomyocytes were hypertrophied. The [Ca2+]i transient amplitude and sarcoplasmic reticulum (SR) Ca2+ load were decreased in intact PMI cardiomyocytes compared with those from sham mice, and spontaneous Ca2+ sparks were less frequent, whereas the fractional release and the frequency of Ca2+ waves were both increased, suggesting higher RyR activity. In permeabilized cardiomyocytes, in which the internal solution can be controlled, Ca2+ sparks were more frequent in PMI cells (under conditions of similar SR Ca2+ load), confirming the enhanced RyR activity. However, in intact cells from PMI mice, the Ca2+ sparks frequency normalized by the SR Ca2+ load in that cell were reduced compared with those in sham mice, indicating that the cytosolic environment in intact cells contributes to the decrease in Ca2+ spark frequency. Indeed, using an internal “failing solution” with less ATP (as found in HF), we observed a dramatic decrease in Ca2+ spark frequency in permeabilized PMI and sham myocytes. In conclusion, our data show that, even if isolated RyR channels show more activity in HF, concomitant alterations in intracellular media composition and SR Ca2+ load may mask these effects at the Ca2+ spark level in intact cells. Nonetheless, in this scenario, the probability of arrhythmogenic Ca2+ waves is enhanced, and they play a potential role in the increase in arrhythmia events in HF patients.
From orthogonal polynomials on the unit circle to functional equations via generating functions
Authors: Cantero María , Iserles Arieh
Published: September 2015

We explore orthogonal polynomials on the unit circle whose Schur parameters are

{
c

α
n

}

n
=
1

∞

\{c\alpha ^n\}_{n=1}^\infty

, where

0
>

|

α

|

,

|

c

|

>
1

0>|\alpha |,|c|>1

. Specifically, we derive two different generating functions. The first can be represented explicitly in terms of sums of a

q
q

-hypergeometric type and used to derive explicitly the underlying orthogonal polynomials, while the second obeys a functional differential equation and can be used to determine the asymptotic behaviour of these polynomials. Extending these constructs to orthogonal polynomials of the second kind, we are able to construct the Carathéodory function and examine the underlying orthogonality measure.
Renormalization and blow-up for wave maps from 𝑆²×ℝ to 𝕊²
Authors: Shahshahani Sohrab
Published: September 2015

We construct a one parameter family of finite time blow-ups to the co-rotational wave maps problem from

S
2

×

R

S^2\times \mathbb {R}

to

S
2

,

S^2,

parameterized by

ν
∈
(

1
2

,
1
]
.

\nu \in (\frac {1}{2},1].

The longitudinal function

u
(
t
,
α
)

u(t,\alpha )

which is the main object of study will be obtained as a perturbation of a rescaled harmonic map of rotation index one from

R

2

\mathbb {R}^2

to

S
2

.

S^2.

The domain of this harmonic map is identified with a neighborhood of the north pole in the domain

S
2

S^2

via the exponential coordinates

(
α
,
θ
)
.

(\alpha ,\theta ).

In these coordinates

u
(
t
,
α
)
=
Q
(
λ
(
t
)
α
)
+

R

(
t
,
α
)
,

u(t,\alpha )=Q(\lambda (t)\alpha )+\mathcal {R}(t,\alpha ),

where

Q
(
r
)
=
2
arctan
⁡

r

Q(r)=2\arctan {r}

is the standard co-rotational harmonic map to the sphere,

λ
(
t
)
=

t

−
1
−
ν

,

\lambda (t)=t^{-1-\nu },

and

R

(
t
,
α
)

\mathcal {R}(t,\alpha )

is the error with local energy going to zero as

t
→
0.

t\rightarrow 0.

Blow-up will occur at

(
t
,
α
)
=
(
0
,
0
)

(t,\alpha )=(0,0)

due to energy concentration, and up to this point the solution will have regularity

H

1
+
ν
−

.

H^{1+\nu -}.
Hip Dysplasia in Children With Osteogenesis Imperfecta: Association With Collagen Type I C-Propeptide Mutations
Authors: Kishta Waleed , Abduljabbar Fahad H. , Gdalevitch Marie , Rauch Frank , Hamdy Reggie , Fassier François
Published: September 2015

Background:

Osteogenesis imperfecta (OI) is a heritable skeletal disorder characterized by bone fragility and short stature that is usually due to mutations in 1 of the 2 genes that code for collagen type I α-chains. The association between hip dysplasia and OI has not been systematically investigated. In this single-center study, we retrospectively reviewed all cases of OI associated with hip dysplasia to describe clinical characteristics and the effect of therapy.

Methods:

We reviewed the charts of 687 patients with OI who were seen at the Shriners Hospital for Children in Montreal between 1999 and 2013 to identify patients with a diagnosis of hip dysplasia. Clinical characteristics and the course after therapeutic interventions were extracted from the charts.

Results:

Hip dysplasia was diagnosed in 8 hips of 5 patients (4 boys, 1 girl; age at diagnosis ranged between 3 wk and 27 mo old). The prevalence of hip dysplasia and OI was therefore 0.87% (per patient). In 4 of the 5 patients (80%), OI was caused by mutations affecting the C-propeptide of collagen type I, which is otherwise rare in OI. Among the 26 patients with C-propeptide mutations followed at our institution, 4 (15%) had hip dysplasia. Pavlik harness treatment was attempted in 2 patients (3 hips) but was not effective in either case and resulted in avascular necrosis of 1 hip. Femoral varus derotational shortening osteotomies using a telescopic rod were performed in all 8 hips along with a closed reduction in 4 hips and an open reduction in 4 hips. Concomitant pelvic osteotomies were performed in 2 hips (1 patient). Surgery resulted in redislocation of 1 hip; all other surgically treated hips remained reduced.

Conclusions:

Clinical screening for hip dysplasia is difficult in OI owing to the bowing of the proximal femur and the risk of causing fractures. OI patients with positive C-propeptide mutation should therefore be screened for hip dysplasia by use of ultrasound. Presence of a C-propeptide mutation appears to be a risk factor for hip dysplasia (80%). It appears that Pavlik harness treatment is not useful in children with OI. The usual treatment of children with OI who pull to stand or started walking with femoral deformity is femoral osteotomy and rodding. In case of associated hip dysplasia with a dislocation, open reduction of the hip and a possible concomitant pelvic osteotomy appears to be a valid management option.

Level of Evidence:

Level IV.
Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review
Authors: Guzman-Aranguez Ana , Fonseca Begoña , Carracedo Gonzalo , Martin-Gil Alba , Martinez-Aguila Alejandro , Pintor Jesús
Published: September 2015

Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.
Deep Sclerectomy With Mitomycin C and Injectable Cross-linked Hyaluronic Acid Implant: Long-term Results
Authors: Bettin Paolo , Di Matteo Federico , Rabiolo Alessandro , Fiori Marina , Ciampi Carlo , Bandello Francesco
Published: September 2015

Purpose:

To evaluate the long-term efficacy and safety of deep sclerectomy (DS) augmented with mitomycin C (MMC) and injectable cross-linked hyaluronic acid implant (Healaflow) in medically refractory glaucoma patients.

Materials and Methods:

Our study included 96 eyes of 83 consecutive patients with open-angle glaucoma undergoing MMC-DS with injectable cross-linked hyaluronic acid implant. Mean follow-up was 28.6±20.0 months. Variables analyzed were: intraocular pressure (IOP), best-corrected visual acuity, mean number of antiglaucomatous drugs, execution of postoperative maneuvres (goniopuncture, bleb needling, and laser lysis of scleral flap sutures). Tonometric success was defined by 2 different thresholds, specifically IOP≤21 mm Hg (criterion A) and ≤15 mm Hg (criterion B). The procedure was defined as a qualified success if reached with medication and as a complete success if reached without.

Results:

For criterion A, qualified and complete success rates were 96% and 94%, respectively, at 12 months, 95% and 92% at 24 months, and 92% and 89% at 36 months. For criterion B, qualified and complete success rates were 75% and 75%, respectively, at 12 months, 62% and 60% at 24 months, and 59% and 58% at 36 months. Goniopuncture was performed in 56 eyes (58%), bleb needling with 5-fluorouracil injection in 4 eyes (5.1%), and laser release of scleral flap sutures in 4 eyes (4%). Six eyes required additional filtering surgery.

Conclusion:

DS with Healaflow and MMC seems to be an effective and safe technique to lower IOP in patients affected by open-angle glaucoma, with few postoperative complications.
Cost-Utility Analysis of Cataract Surgery in Advanced Glaucoma Patients
Authors: Xu Xian , Ma Ying-Yan , Zou Hai-Dong
Published: September 2015

Purpose:

To assess the cost-effectiveness of cataract surgery in advanced glaucoma (AG) patients.

Materials and Methods:

A total of 93 patients with AG who underwent cataract surgeries were collected prospectively from June 2010 through June 2013 in Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai, and were followed up for at least 3 months. A standard phacoemulsification technique was used to remove cataract(s). No complications occurred intraoperatively or postoperatively. Costs associated with surgery were recorded. Utility values of cataract surgery were obtained by using time trade-off method. Quality-adjusted life-years (QALYs) were calculated using the patients’ life expectancy at a 3% discounted rate. Incremental cost-utility analysis was performed (compared with no treatment) by calculating the incremental cost-effectiveness ratio (ICER), that is, the mean incremental cost for each QALY. The bootstrap method was used for statistical analysis, and sensitivity analyses were performed to test robustness of the results.

Results:

The mean incremental cost of cataract surgery was 9876 Chinese yuan (CNY) [1593 US dollar (USD)] [95% confidence interval (CI), 9144-10,570 CNY (1475-1705 USD)].The mean additional QALYs gained were 2.20 (95% CI, 1.85-2.54), and the incremental cost for each additional QALY was 4508 CNY (727 USD) [95% CI, 3890-5234 CNY (627-844 USD)], far lower than the per capita annual disposable income in Shanghai, 40,188 CNY (6482 USD).

Conclusion:

For AG patients, cataract surgery does help obtain more QALYs and was highly cost effective.