bluuebunny/crossref_metadata_2025 huggingface dataset:
Active phase compensation technique for buried target extraction
Authors: Cho Y.‐S. , Jung S. , Chung Y.‐S.
Published: January 2017

A novel method for buried target extraction, the active phase compensation technique is proposed. The range migration algorithm (RMA) is the conventional method for synthetic aperture radar (SAR) image reconstruction, but if targets exist in different media, identification of the target can be difficult because of losses and the significant reflection from the boundary face. In this regard, the matrix pencil method is utilised to actively find the boundary point and buried target responses. Then, the reflection effect can be eliminated, and range cells corresponding to estimated target responses can be compensated by applying newly created compensation functions. It improves the detection accuracy of buried targets. Finally, experimental results demonstrated that the proposed technique performs better than the classic RMA.
Discrete higher order sliding mode: concept to validation
Authors: Sharma Nalin Kumar , Janardhanan Sivaramakrishnan
Published: January 2017

A formal definition and design methodology for discrete‐time higher‐order sliding mode (DHOSM) based on finite difference method is proposed. A generalised reaching law is proposed to achieve r ‐order sliding mode in discrete time, and its behaviour and stability are analysed. The proposed reaching law is used to design a higher‐order sliding mode control for an uncertain LTI system. The concept is experimentally validated on a real‐time rectilinear plant and is compared with the existing algorithms on the basis of sensitivity function and ‐continuity. The results and comparison show that the proposed sliding algorithm has superior disturbance rejection capability as well as better continuity. This work is the first attempt to formally define and design DHOSM as opposed to discretisation of continuous time higher‐order sliding mode.
Terahertz frequency generation with monolithically integrated dual wavelength distributed Bragg reflector semiconductor laser diode
Authors: Gwaro Jared O. , Brenner Carsten , Sumpf Bernd , Klehr Andreas , Fricke Jörg , Hofmann Martin R.
Published: January 2017

Optoelectronic terahertz (THz) generation techniques have helped to narrow the THz gap and have opened up a wealth of new applications for THz technology. However, the development of THz systems into mass market is a major technical challenge, which is attributed to high cost of THz hardware components including sources and detectors. Here, the authors report THz generation from a distributed Bragg reflector (DBR) semiconductor laser diode together with fibre coupled photoconducting antennas. Two fibre coupled ion‐implanted gallium arsenide photoconducting antennas were employed to generate and detect THz radiation. Two DBR lasers connected with a Y‐shaped waveguide structure were monolithically integrated and used to simultaneously emit two wavelengths in the range of 785 nm. These lasers were employed as pumping source for the photomixers. An optical beat frequency of 286 GHz of the dual wavelengths was obtained from optical characterisation. A corresponding THz frequency was confirmed via photomixing in a homodyne set up. By variation of the operation parameters of the laser, the difference frequency was tuned in the range between 286 GHz to 320 GHz. In summary, they report the implementation of a compact and cost effective fiber coupled Terahertz source based on a monolithically integrated dual wavelength DBR semiconductor laser diode.
Tamper‐aware authentication framework for wireless sensor networks
Authors: Nunoo‐Mensah Henry , Boateng Kwame Osei , Gadze James Dzisi
Published: January 2017

Sensor nodes once deployed onto the field are mostly provided with little or no attention making them prone to physical attacks by adversaries. Various security frameworks have been proposed to mitigate tampering; others also ensure authentication of sensor nodes. Energy is a limited resource and as such, the need to develop energy efficient frameworks that ensure authentication and thwart tampering of deployed sensor nodes. In this study, a framework comprising an authentication algorithm with a hardware‐based tamper detection and recovery procedure is proposed. An interrupt‐driven tamper detection and recovery mechanism is employed to aid the isolation of compromised nodes. MD‐5, SHA‐1, SHA‐224, SHA‐256, SHA‐384 and SHA‐512 hash functions were reviewed and simulation done to select the most energy‐efficient option (SHA‐224) for use with the authentication algorithm. The proposed framework was compared with other existing authentication frameworks in the area of energy efficiency. The result show that the proposed framework is the most energy‐efficient. The proposed framework, TinySec, SenSec and MiniSec were analysed against node subversion and false node attacks; the proposed framework can detect compromised nodes in all two attacks but the rest were only potent against false nodes and not against node subversion.
Quantitative anisotropic isoperimetric and Brunn−Minkowski inequalities for convex sets with improved defect estimates
Authors: Harutyunyan Davit
Published: January 2017

In this paper we revisit the anisotropic isoperimetric and the Brunn−Minkowski inequalities for convex sets. The best known constantC(n) =Cn7depending on the space dimensionnin both inequalities is due to Segal [A. Segal,Lect. Notes Math., Springer, Heidelberg2050(2012) 381–391]. We improve that constant toCn6for convex sets and toCn5for centrally symmetric convex sets. We also conjecture, that the best constant in both inequalities must be of the formCn2,i.e., quadratic inn. The tools are the Brenier’s mapping from the theory of mass transportation combined with new sharp geometric-arithmetic mean and some algebraic inequalities plus a trace estimate by Figalli, Maggi and Pratelli.
Efficacy
and safety of novel digital single-operator peroral cholangioscopy-guided laser
lithotripsy for complicated biliary stones
Authors: Wong John , Tang Raymond , Teoh Anthony , Sung Joseph , Lau James
Published: January 2017

Background/study aims Laser lithotripsy can effectively fragment
complicated biliary stones, but current cholangioscopes are limited by
fragility, restricted mobility or moderate visual resolution. The efficacy and
safety of a new digital single-operator peroral cholangioscope to guide laser
lithotripsy were evaluated.

Patients and methods In this prospective single-center series, consecutive
patients with complicated biliary stones, defined as impacted stones > 1.5 cm
in size and wider than the more distal common bile duct, or stones that failed
extraction by basket mechanical lithotripsy, underwent ERCP and SpyGlass DS
peroral cholangioscope (Boston Scientific, Marlborough, United States)-guided
laser lithotripsy. Stone clearance rate and incidence of adverse events were
determined.

Results Seventeen patients (10 men, 7 women; median age 76 years) with a
median biliary stone size of 2 cm underwent predominantly holmium:yttrium
aluminum garnet laser lithotripsy, achieving a 94 % stone clearance rate over 1
median procedure. Lithotripsy was performed in 8 of 17 patients due to an
impacted biliary stone. The remaining patients underwent lithotripsy due to
prior failure of the basket mechanical lithotripter to capture or crush their
stones. Post lithotripsy, 2 patients developed cholangitis and 1 patient with
underlying COPD developed respiratory distress, all resolved with conservative
management. There were no hemobilia, perforations, pancreatitis nor any deaths.

Conclusion SpyGlass DS peroral cholangioscopy-guided laser lithotripsy is
an efficient and safe modality for management of complicated biliary
stones.
Design analysis and simulation study of an efficiency enhanced L-band MILO
Authors: Dixit Gargi , Kumar Arjun , Jain P. K.
Published: January 2017

In this article, an experimental L-band compact magnetically insulated transmission line oscillator (MILO) has been simulated using the 3D PIC simulation code “Particle Studio,” and an improvement in the device efficiency has been obtained. The detailed interaction and operating mechanism describing the role of sub-assemblies have been explained. The performance of the device was found to be the function of the distance between the end-surface of the cathode and the beam-dump disk. During simulation, a high power microwave of the TM01 mode is generated with the peak RF-power of 6 GW and the power conversion efficiency of 19.2%, at the operating voltage of ∼600 kV and at the current of 52 kA. For better impedance matching or maximum power transfer, four stubs have been placed at the λg/4 distance from the extractor cavity, which results in the stable RF power output. In this work, an improved L-band MILO along with a new type beam-dump disk is selected for performance improvement with typical design parameters and beam parameters. The total peak power of improved MILO is 7 GW, and the maximum power conversion efficiency is 22.4%. This improvement is achieved due to the formation of the virtual cathode at the load side, which helps in modulating the energy of electrons owing to maximum reflection of electrons from the mesh or foil.
Global classical solutions to the 1-D vacuum free boundary problem for full compressible Navier-Stokes equations with large data
Authors: Ou Yaobin
Published: January 2017

The vacuum free boundary problem of one-dimensional non-isentropic compressible Navier-Stokes equations with large initial data is investigated in this paper. The fluid is initially assumed to occupy a finite interval and connect to the vacuum continuously at the free boundary, which is often considered in the gas-vacuum interface problem. Using the method of Lagrangian particle path, we derive some point-wise estimates and weighted spatial and time energy estimates for the classical solutions. Then the global existence and uniqueness of classical solutions are shown, and the expanding speed for the free boundary is proved to be finite. The main difficulty of this problem is the degeneracy of the system near the free boundary. Previous results are only for the solutions with low regularity (cf. [G. Q. Chen and M. Kratka, Commun. Partial Differ. Equations. 27 907–943 (2002)]).
Superconductivity of monolayer Mo2C: The key role of functional groups
Authors: Zhang Jun-Jie , Dong Shuai
Published: January 2017

Monolayer Mo2C is a new member of two-dimensional materials. Here the electronic structure and lattice dynamics of monolayer Mo2C are calculated. According to the electron-phonon interaction, it is predicted that monolayer Mo2C could be a quasi-two-dimensional superconductor and the effects of functional-groups are crucially important considering its unsaturated surface. Despite the suppressed superconductivity by chalcogen adsorption, our most interesting prediction is that the electron-phonon interaction of monolayer Mo2C can be greatly enhanced by bromine absorption, suggesting that Mo2CBr2 as a good candidate for a nanoscale superconductor.
Influence of the poloidal equilibrium flow and flow shear on the tearing mode instabilities in tokamak plasmas
Authors: Ming Yue , Zhou Deng
Published: January 2017

The effect of the poloidal equilibrium flow and flow shear on the tearing mode instabilities for tokamak plasmas is investigated. The vorticity equation is derived and approximately solved for large poloidal mode numbers (m). Asymptotic matching of the inner solution to the outer solution can approximately give the classical tearing mode stability index Δ′. For typical plasma parameters with positive flow shear, we notice that the poloidal mean flows have a beneficial effect on the classical tearing mode and vice versa. To study the modes with arbitrary poloidal mode numbers, we numerically solve the vorticity equation for delta prime (Δ′) for typical plasma parameters with positive flow shear at the rational surface and the resulting Δ′ with large m also decreases with increasing poloidal flow velocity, consistent with the approximate analytical large m results. Our numerical calculations indicate that the poloidal mean flow with positive flow shear has beneficial influence on the stabilization of classical tearing modes in tokamak plasmas.
Effects of two-mode transverse optical phonons in bulk wurtzite AlGaN on electronic mobility in AlGaN/GaN quantum wells
Authors: Gu Z. , Ban S. L. , Jiang D. D. , Qu Y.
Published: January 2017

The two-mode property of bulk transverse optical (TO) phonons in ternary mixed crystals of wurtzite AlxGa1-xN has been investigated by introducing impurity modes in a modified random-element isodisplacement model. Based on the dielectric continuous model, the uniaxial model, and the Lei-Ting balance equation, the effects of the two-mode property on electrostatic potentials of interface optical and confined optical phonons in AlGaN/GaN quantum wells, as well as their influences on the electronic mobility (EM), are discussed by a component-dependent weight model. Our results indicate that the total EM decreases to a minimum at first and then increases slowly with x under the influences of the competitions from the eight branches of phonons. The further calculation shows that the total EM decreases with the increment of temperature in the range of 200 K < T < 400 K and reduction of well width d. As a comparison, the EM is calculated for an Al0.58Ga0.42N/GaN quantum well at room temperature, and our result is 1263.0 cm2/Vs, which is 1.44 times of the experiment value. Our result is expected since the difference between our theory and the experiment is mainly due to the neglect of interface-roughness and other secondary scattering mechanisms. Consequently, the two-mode property of bulk TO phonons in ternary mixed crystals does affect obviously on the electron transport in the quantum wells. And our component-dependent weight model could be extended to study the electric properties influenced by optical phonons in other related heterostructures.
Electronic structure of the CsPbBr3/polytriarylamine (PTAA) system
Authors: Endres James , Kulbak Michael , Zhao Lianfeng , Rand Barry P. , Cahen David , Hodes Gary , Kahn Antoine
Published: January 2017

The inorganic lead halide perovskite CsPbBr3 promises similar solar cell efficiency to its hybrid organic-inorganic counterpart CH3NH3PbBr3 but shows greater stability. Here, we exploit this stability for the study of band alignment between perovskites and carrier selective interlayers. Using ultraviolet, X-ray, and inverse photoemission spectroscopies, we measure the ionization energy and electron affinities of CsPbBr3 and the hole transport polymer polytriarylamine (PTAA). We find that undoped PTAA introduces a barrier to hole extraction of 0.2–0.5 eV, due to band bending in the PTAA and/or a dipole at the interface. p-doping the PTAA eliminates this barrier, raising PTAA's highest occupied molecular orbital to 0.2 eV above the CsPbBr3 valence band maximum and improving hole transport. However, IPES reveals the presence of states below the PTAA lowest unoccupied molecular level. If present at the CsPbBr3/PTAA interface, these states may limit the polymer's efficacy at blocking electrons in solar cells with wide band gap materials like CsPbBr3 and CH3NH3PbBr3.
Polarization-asymmetric bidirectional random laser emission from a twisted nematic liquid crystal
Authors: Chen Chun-Wei , Huang Huai-Ping , Jau Hung-Chang , Wang Cheng-Yu , Wu Chih-Wei , Lin Tsung-Hsien
Published: January 2017

This paper reports on the observation and detailed investigation of the bidirectional random lasing emitted from an active twisted nematic liquid crystal, of which the polarization states are asymmetric (non-parallel to each other). In such a laser, the liquid crystal acts as a random distributed feedback cavity with an inherently built-in polarization rotator. While propagating in the anisotropic cavity, the polarization of the dye-emitted light rotates with the gently twisted optic axis. The output polarization states are, therefore, parallel to each of the surface alignment directions. The mode stability and electrical switchability of the laser were also examined. Moreover, correlations between the lasing threshold, alignment direction, dye concentration, and film thickness were established. The findings not only suggest an optimum concentration for low-threshold random lasing operation but also disclose the threshold inversion behavior of nematic random lasers.
Asymmetric transmission of linearly polarized waves in terahertz chiral metamaterials
Authors: Fang Shenying , Luan Kang , Ma Hui Feng , Lv Wenjin , Li Yuxiang , Zhu Zheng , Guan Chunying , Shi Jinhui , Cui Tie Jun
Published: January 2017

We experimentally demonstrate the asymmetric transmission of linearly polarized waves in a multilayer chiral metamaterial in the terahertz (THz) regime. The chiral metamaterial is constructed by two stacked orthogonal metallic layers embedded in polyimide dielectric layers. Simulated and measured results show that the proposed multilayer chiral metamaterial can achieve dual-band direction-dependent cross-polarization conversions for both x- and y-polarized THz waves. The polarized wave passing through the metamaterial will be converted into its orthogonal polarization state, while the same polarized wave is blocked along the reversed propagation direction. In addition, the asymmetric transmission band may be effectively engineered to other frequencies by slightly adjusting the gap width. We believe that our findings are beneficial in manipulating the polarization state of THz waves and exploring polarization-sensitive THz devices.
Single-ion microwave near-field quantum sensor
Authors: Wahnschaffe M. , Hahn H. , Zarantonello G. , Dubielzig T. , Grondkowski S. , Bautista-Salvador A. , Kohnen M. , Ospelkaus C.
Published: January 2017

We develop an intuitive model of 2D microwave near-fields in the unusual regime of centimeter waves localized to tens of microns. Close to an intensity minimum, a simple effective description emerges with five parameters that characterize the strength and spatial orientation of the zero and first order terms of the near-field, as well as the field polarization. Such a field configuration is realized in a microfabricated planar structure with an integrated microwave conductor operating near 1 GHz. We use a single 9Be+ ion as a high-resolution quantum sensor to measure the field distribution through energy shifts in its hyperfine structure. We find agreement with simulations at the sub-micron and few-degree level. Our findings give a clear and general picture of the basic properties of oscillatory 2D near-fields with applications in quantum information processing, neutral atom trapping and manipulation, chip-scale atomic clocks, and integrated microwave circuits.
Influence of emission threshold and current increase rate on microwave starting time in relativistic backward wave oscillator
Authors: Wu Ping , Sun Jun , Song Zhimin , Teng Yan
Published: January 2017

Explosive emission cathodes (EECs) are widely used in high power microwave generators. This paper researches the influence of the emission threshold and the current increase rate of annular EECs on the microwave starting time of a relativistic backward wave oscillator (RBWO) when the current amplitude is not affected. The results show that a moderate delay in explosive emission, as long as it's not too long and the current increase rate keeps fast enough, won't bring about a corresponding delay in the starting time of microwave, but inversely, may suppress the mode competition and thus expedite the starting process slightly. The current increase rate, however, has more prominent influence on the starting time of the RBWO. A slower current increase rate will delay the time when the beam current reaches the starting current and lead to a longer starting time.
Measurement of axial radiation properties in Z-pinch dynamic hohlraum at Julong-1
Authors: Meng Shijian , Hu Qingyuan , Ning Jiaming , Ye Fan , Huang Zhanchang , Qin Yi , Wang Dong , Xu Zeping , Xu Rongkun
Published: January 2017

Axial radiation properties in Z-pinch dynamic hohlraum is investigated experimentally for the first time at Julong-1 facility in China, employing a load that contains a cylindrical CHO foam placed at the central axis position of the nested tungsten wire array. Time-resolved axially radiating images indicate that the velocity of the radiating shock is 31.9 ± 5.6 cm/μs in shot 0181. At t = −6.5 ns with respect to the peak of radially radiated power at stagnation, the annular width is estimated to be ∼1 mm and the intensities distribution in the shock implies a good azimuthal symmetry of radiation pressure. Axial power is found to peak prior to the arrival of the shock to the axis, which is explained by the balance between shock heating and radiating cooling. Utilizing the end-on radiation images and axial power, the peak radiation temperature in dynamic hohlraum is obtained to be ∼65 eV.
Epitaxial growth of BiFeO3 films on TiN under layers by sputtering deposition
Authors: Wang Yue , Li Tianjun , Wang Jian , Harumoto Takashi , Jia Tingting , Kimura Hideo , Nakada Katsuyuki , Nakagawa Shigeki , Nakamura Yoshio , Shi Ji
Published: January 2017

BiFeO3/TiN/MgO (001) films have been prepared by magneton sputtering, where TiN serves as a conductive under layer. X-ray diffraction profiles and cross-sectional transmission electron microscopy images reveal that not only (001)-epitaxial BiFeO3 films are obtained, but also both tetragonal and rhombohedral phases co-exist in BiFeO3 films. Their crystallographic relationship is shown as following: tetragonal-BiFeO3 (001) [100]//TiN (001) [100]//MgO (001) [100] and rhombohedral-BiFeO3 (001) [100]//TiN (001) [100]//MgO (001) [100]. Besides, an oxidized TiN layer (∼ 20 nm) has also been detected between BiFeO3 and TiN layers and its formation may originate from oxygen inter-diffusion from BiFeO3 layer. Despite of the existence of the oxidized TiN layer, it does not affect the epitaxial growth of BiFeO3 films. On the other hand, the coercivity electric field obtained in ferroelectric loop of BiFeO3 is greatly enhanced to 49 MV/cm due to the existence of oxidized TiN layer.
Sexual health knowledge and behaviour of young Sudanese Queenslanders: a cross-sectional study
Authors: Dean Judith , Mitchell Marion , Stewart Donald , Debattista Joseph
Published: January 2017

Background
Forced migration is associated with sexual vulnerability. However, little is known about the sexual health literacy and needs of refugee-background youth post resettlement. Methods: Conducted in partnership with the Queensland Sudanese community, this study used a cross-sectional survey to explore the sexual health knowledge, attitudes and behaviours of a convenience sample of 16- to 24-year-old Sudanese-background youth in Australia (n = 229). Results: Sexually transmissible infection (STI) and HIV knowledge scores were generally low, although they were found to significantly improve the longer participants had lived in Australia (P < 0.001). Female participants reported significantly higher levels of both STI and HIV knowledge compared with the male cohort (P < 0.001). The aggregated sexual risk behaviour score suggests generally low levels of risk-taking behaviour. However, of the 140 sexually active participants, 3.1% reported a STI diagnosis, 9.0% reported sex leading to a pregnancy and 33.1% reported they had experienced unwanted sex. Participants also reported engaging in behaviours such as anal sex (33%) and sharing injecting drug equipment. Conclusions: Patterns of sexual behaviour among this predominately refugee-background group are not dissimilar to those of other young Australians. Nonetheless, the self-reported patterns of risk behaviour combined with the low and inaccurate levels of sexual health knowledge suggest this group of young people remain sexually vulnerable, particularly early within their resettlement experience. Culturally and contextually informed sexual health interventions are needed early within the resettlement experience.
Structure and activation of C1, the complex initiating the classical pathway of the complement cascade
Authors: Mortensen Simon A. , Sander Bjoern , Jensen Rasmus K. , Pedersen Jan Skov , Golas Monika M. , Jensenius Jens C. , Hansen Annette G. , Thiel Steffen , Andersen Gregers R.
Published: January 2017

Significance

The complement system is an essential arm within the innate immune defense. Complement contributes to elimination of objects presenting danger signals such as pathogens, dying host cells, and abnormal molecular structures and is capable of inducing an inflammatory response stimulating further immune responses. The C1 complex is a giant proteolytic enzyme, which plays a leading role, because it is the first component in a proteolytic cascade initiated when complement is activated. On the basis of structural characterization of the C1 complex with X-rays and electron microscopy, we suggest that the first proteolytic reaction in the cascade, activation of the C1 complex itself, involves neighboring C1 complexes located near each other rather than a reaction within individual C1 complexes.
Genetics and insect pest management in agriculture.
Authors: Haymer D.
Published: January 2017

Genetics has long played a role in the history of insect pest management, and changes in the genetic methods used reflect changes that have occurred in the field itself over time. Beginning from simple collections of mutations and the development of chromosome linkage maps, many of the early applications of genetic technology were focused on the development of new strains for the sterile insect technique as a form of biological control. Since that time, and as the field of genetics underwent a true merger with molecular biology, the focus shifted almost entirely to methods using molecular technology. These methods had the advantage of being more broadly applicable to control of a wide range of pest species, and this did much to move the field away from the frustrations often associated with attempts to transfer genetic tools developed in
Drosophila
directly to these species. The latest applications of molecular genetic technologies in the area of genetically based control methods now also include cutting-edge systems for genome editing and the use of RNA inhibition for selectively knocking out the expression of individual genes. Finally, as the field of genetics has shifted its focus from the analysis of individual genes to that of entire genomes, new and exciting prospects are opening up for improvements in use of genetic technology for the management of insect pests.
Stabilization of freeze-dried Lactobacillus paracasei subsp. paracasei JCM 8130T with the addition of disaccharides, polymers, and their mixtures
Authors: Teng Da , Kawai Kiyoshi , Mikajiri Shuto , Hagura Yoshio
Published: January 2017

Although freeze-drying is a widely used dehydration technique for the stabilizing of unstable lactic acid bacteria, Lactobacillus paracasei subsp. paracasei JCM 8130T (L. paracasei) is destabilized after freeze-drying and subsequent storage. In order to improve the stability of freeze-dried L. paracasei, effects of disaccharides (sucrose and trehalose), polymers (maltodextrin; MD and bovine serum albumin; BSA), and their mixtures on the survival rate of freeze-dried L. paracasei were investigated. The survival rate of non-additive sample decreased slightly after freeze-drying but decreased drastically after subsequent storage at 37 °C for 4 weeks. The reduction was diminished by the addition of disaccharides and polymers. The stabilizing effect of disaccharides was not affected by the co-addition of MD. In contrast, the disaccharide–BSA mixtures had a synergistic stabilizing effect, and the survival rates were largely maintained even after storage. It is suggested that the synergistic effect originates from the conformational stabilization of the dehydrated bacteria.
4E-BP is a target of the GCN2–ATF4 pathway during Drosophila development and aging
Authors: Kang Min-Ji , Vasudevan Deepika , Kang Kwonyoon , Kim Kyunggon , Park Jung-Eun , Zhang Nan , Zeng Xiaomei , Neubert Thomas A. , Marr Michael T. , Ryoo Hyung Don
Published: January 2017

Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation–activated kinase GCN2 mediates this response in part by phosphorylating eIF2α. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids. The 4E-BP intron contains ATF4-binding sites that not only respond to stress but also show inherent ATF4 activity during normal development. Analysis of the newly synthesized proteome through metabolic labeling combined with click chemistry shows that certain stress-responsive proteins are resistant to inhibition by 4E-BP, and gcn2 mutant flies have reduced levels of stress-responsive protein synthesis. These results indicate that GCN2 and ATF4 are important regulators of 4E-BP transcription during normal development and aging.
Robust gap repair in the contractile ring ensures timely completion of cytokinesis
Authors: Silva Ana M. , Osório Daniel S. , Pereira Antonio J. , Maiato Helder , Pinto Inês Mendes , Rubinstein Boris , Gassmann Reto , Telley Ivo Andreas , Carvalho Ana Xavier
Published: January 2017

Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an actin polymerization–dependent manner. An open ring is able to constrict, and rings repair from successive cuts. After gap repair, an increase in constriction velocity allows cytokinesis to complete at the same time as controls. Our analysis demonstrates that tension in the ring increases while net cortical tension at the site of ingression decreases throughout constriction and suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure.
Fine-tuning of ULK1 mRNA and protein levels is required for autophagy oscillation
Authors: Nazio Francesca , Carinci Marianna , Valacca Cristina , Bielli Pamela , Strappazzon Flavie , Antonioli Manuela , Ciccosanti Fabiola , Rodolfo Carlo , Campello Silvia , Fimia Gian Maria , Sette Claudio , Bonaldo Paolo , Cecconi Francesco
Published: January 2017

Autophagy is an intracellular degradation pathway whose levels are tightly controlled to secure cell homeostasis. Unc-51–like kinase 1 (ULK1) is a conserved serine–threonine kinase that plays a central role in the initiation of autophagy. Here, we report that upon autophagy progression, ULK1 protein levels are specifically down-regulated by the E3 ligase NEDD4L, which ubiquitylates ULK1 for degradation by the proteasome. However, whereas ULK1 protein is degraded, ULK1 mRNA is actively transcribed. Upon reactivation of mTOR-dependent protein synthesis, basal levels of ULK1 are promptly restored, but the activity of newly synthesized ULK1 is inhibited by mTOR. This prepares the cell for a new possible round of autophagy stimulation. Our results thus place NEDD4L and ULK1 in a key position to control oscillatory activation of autophagy during prolonged stress to keep the levels of this process under a safe and physiological threshold.
Activating the nuclear piston mechanism of 3D migration in tumor cells
Authors: Petrie Ryan J. , Harlin Heather M. , Korsak Lulu I T. , Yamada Kenneth M.
Published: January 2017

Primary human fibroblasts have the remarkable ability to use their nucleus like a piston, switching from low- to high-pressure protrusions in response to the surrounding three-dimensional (3D) matrix. Although migrating tumor cells can also change how they migrate in response to the 3D matrix, it is not clear if they can switch between high- and low-pressure protrusions like primary fibroblasts. We report that unlike primary fibroblasts, the nuclear piston is not active in fibrosarcoma cells. Protease inhibition rescued the nuclear piston mechanism in polarized HT1080 and SW684 cells and generated compartmentalized pressure. Achieving compartmentalized pressure required the nucleoskeleton–cytoskeleton linker protein nesprin 3, actomyosin contractility, and integrin-mediated adhesion, consistent with lobopodia-based fibroblast migration. In addition, this activation of the nuclear piston mechanism slowed the 3D movement of HT1080 cells. Together, these data indicate that inhibiting protease activity during polarized tumor cell 3D migration is sufficient to restore the nuclear piston migration mechanism with compartmentalized pressure characteristic of nonmalignant cells.
Podosome assembly is controlled by the GTPase ARF1 and its nucleotide exchange factor ARNO
Authors: Rafiq Nisha Bte Mohd , Lieu Zi Zhao , Jiang Tingting , Yu Cheng-han , Matsudaira Paul , Jones Gareth E. , Bershadsky Alexander D.
Published: January 2017

Podosomes represent a class of integrin-mediated cell-matrix adhesions formed by migrating and matrix-degrading cells. We demonstrate that in macrophage-like THP1 cells and fibroblasts stimulated to produce podosomes, down-regulation of the G-protein ARF1 or the ARF1 guanine nucleotide exchange factor, ARNO, by small, interfering RNA or pharmacological inhibitors led to striking podosome elimination. Concomitantly, treatments inducing podosome formation increased the level of guanosine triphosphate (GTP)–bound ARF1. ARNO was found to colocalize with the adhesive rings of podosomes, whereas ARF1 was localized to vesicular structures transiently contacting podosome rings. Inhibition of ARF1 led to an increase in RhoA-GTP levels and triggered assembly of myosin-IIA filaments in THP1 cells, whereas the suppression of myosin-IIA rescued podosome formation regardless of ARF1 inhibition. Finally, expression of constitutively active ARF1 in fibroblasts induced formation of putative podosome precursors: actin-rich puncta coinciding with matrix degradation sites and containing proteins of the podosome core but not of the adhesive ring. Thus, ARNO-ARF1 regulates formation of podosomes by inhibition of RhoA/myosin-II and promotion of actin core assembly.
GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration
Authors: Wakatsuki Shuji , Tokunaga Shinji , Shibata Megumi , Araki Toshiyuki
Published: January 2017

Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)–mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration. Phosphorylated MCL1 is ubiquitinated by the FBXW7 ubiquitin ligase and degraded by the proteasome, thereby releasing BECLIN1 to induce axonal autophagy. Axonal autophagy contributes to local adenosine triphosphate production in degenerating axons and the exposure of phosphatidylserine—an “eat-me” signal for phagocytes—on transected axons and is required for normal recruitment of phagocytes to axonal debris in vivo. These results suggest that GSK3B–MCL1 signaling to regulate autophagy might be important for the successful completion of Wallerian degeneration.
Spatial and temporal signal processing and decision making by MAPK pathways
Authors: Atay Oguzhan , Skotheim Jan M.
Published: January 2017

Mitogen-activated protein kinase (MAPK) pathways are conserved from yeast to man and regulate a variety of cellular processes, including proliferation and differentiation. Recent developments show how MAPK pathways perform exquisite spatial and temporal signal processing and underscores the importance of studying the dynamics of signaling pathways to understand their physiological response. The importance of dynamic mechanisms that process input signals into graded downstream responses has been demonstrated in the pheromone-induced and osmotic stress–induced MAPK pathways in yeast and in the mammalian extracellular signal-regulated kinase MAPK pathway. Particularly, recent studies in the yeast pheromone response have shown how positive feedback generates switches, negative feedback enables gradient detection, and coherent feedforward regulation underlies cellular memory. More generally, a new wave of quantitative single-cell studies has begun to elucidate how signaling dynamics determine cell physiology and represents a paradigm shift from descriptive to predictive biology.
Watching real-time endocytosis in living cells
Authors: Frazier Meredith N. , Jackson Lauren P.
Published: January 2017

The precise sequence of events promoting clathrin-coated vesicle assembly is still debated. In this issue, Kadlecova et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608071) test structural models using quantitative microscopy in living cells to investigate the hierarchy and temporal importance of molecular events required for clathrin-coated pit initiation.
Cyclic AMP reverses the effects of aging on pacemaker activity and If in sinoatrial node myocytes
Authors: Sharpe Emily J. , Larson Eric D. , Proenza Catherine
Published: January 2017

Aerobic capacity decreases with age, in part because of an age-dependent decline in maximum heart rate (mHR) and a reduction in the intrinsic pacemaker activity of the sinoatrial node of the heart. Isolated sinoatrial node myocytes (SAMs) from aged mice have slower spontaneous action potential (AP) firing rates and a hyperpolarizing shift in the voltage dependence of activation of the “funny current,” If. Cyclic AMP (cAMP) is a critical modulator of both AP firing rate and If in SAMs. Here, we test the ability of endogenous and exogenous cAMP to overcome age-dependent changes in acutely isolated murine SAMs. We found that maximal stimulation of endogenous cAMP with 3-isobutyl-1-methylxanthine (IBMX) and forskolin significantly increased AP firing rate and depolarized the voltage dependence of activation of If in SAMs from both young and aged mice. However, these changes were insufficient to overcome the deficits in aged SAMs, and significant age-dependent differences in AP firing rate and If persisted in the presence of IBMX and forskolin. In contrast, the effects of aging on SAMs were completely abolished by a high concentration of exogenous cAMP, which restored AP firing rate and If activation to youthful levels in cells from aged animals. Interestingly, the age-dependent differences in AP firing rates and If were similar in whole-cell and perforated-patch recordings, and the hyperpolarizing shift in If persisted in excised inside-out patches, suggesting a limited role for cAMP in causing these changes. Collectively, the data indicate that aging does not impose an absolute limit on pacemaker activity and that it does not act by simply reducing the concentration of freely diffusible cAMP in SAMs.
“Opt Out” and Access to Anesthesia Care for Elective and Urgent Surgeries among U.S. Medicare Beneficiaries
Authors: Sun Eric C. , Dexter Franklin , Miller Thomas R. , Baker Laurence C.
Published: January 2017

Background

In 2001, the Centers for Medicare and Medicaid Services issued a rule allowing U.S. states to “opt out” of the regulations requiring physician supervision of nurse anesthetists in an effort to increase access to anesthesia care. Whether “opt out” has successfully achieved this goal remains unknown.

Methods

Using Medicare administrative claims data, we examined whether “opt out” reduced the distance traveled by patients, a common measure of access, for patients undergoing total knee arthroplasty, total hip arthroplasty, cataract surgery, colonoscopy/sigmoidoscopy, esophagogastroduodenoscopy, appendectomy, or hip fracture repair. In addition, we examined whether “opt out” was associated with an increase in the use of anesthesia care for cataract surgery, colonoscopy/sigmoidoscopy, or esophagogastroduodenoscopy. Our analysis used a difference-in-differences approach with a robust set of controls to minimize confounding.

Results

“Opt out” did not reduce the percentage of patients who traveled outside of their home zip code except in the case of total hip arthroplasty (2.2% point reduction; P = 0.007). For patients travelling outside of their zip code, “opt out” had no significant effect on the distance traveled among any of the procedures we examined, with point estimates ranging from a 7.9-km decrease for appendectomy (95% CI, −19 to 3.4; P = 0.173) to a 1.6-km increase (95% CI, −5.1 to 8.2; P = 0.641) for total hip arthroplasty. There was also no significant effect on the use of anesthesia for esophagogastroduodenoscopy, appendectomy, or cataract surgery.

Conclusions

“Opt out” was associated with little or no increased access to anesthesia care for several common procedures.
Lymphocyte Phospho-Ser-9-GSK-3β/Total GSK-3β Protein Levels Ratio Is Not Affected by Chronic Lithium or Valproate Treatment in Euthymic Patients With Bipolar Disorder
Authors: Azab Abed N. , Vainer Ella , Agam Galila , Bersudsky Yuly
Published: January 2017

Background

Glycogen synthase kinase-3 (GSK-3) inhibition by lithium has been well established in vitro, but proof that this biochemical effect mediates lithium's beneficial action in patients with bipolar disorder is lacking. We studied whether lymphocyte GSK-3β activity measured indirectly in lithium- or valproate (VPA)-treated euthymic patients with bipolar disorder is different from controls.

Methods

Lymphocyte total and Ser-9-phospho-GSK-3β (inactive) levels were measured by Western blotting. Forty-seven patients with bipolar disorder and 32 age- and sex-matched control subjects were studied.

Results

No significant differences were found between lithium- and VPA-treated patients and controls in phospho-GSK-3β, total GSK-3β, or their ratio.

Conclusions

The data do not support the concept that in vivo, during chronic treatment of bipolar illness, GSK-3β is inhibited either by lithium or by VPA.
Contribution of Oxidative Stress to Non-AIDS Events in HIV-Infected Patients
Authors: Masiá Mar , Padilla Sergio , Fernández Marta , Barber Xavier , Moreno Santiago , Iribarren José Antonio , Portilla Joaquín , Peña Alejandro , Vidal Francesc , Gutiérrez Félix ,   CoRIS
Published: January 2017

Objective:

Recognition of potentially modifiable mechanisms implicated in the pathogenesis of non-AIDS events (NAEs) might help improve outcomes of HIV-infected individuals. HIV infection has been associated with increased oxidative stress. We assessed the association between F2-isoprostanes and serious NAEs, and whether they improve the predictive performance of inflammation and coagulation biomarkers.

Methods:

Prospective multicenter cohort. Individuals who had an incident serious NAE and 2 sex- and age-matched participants with no events were selected. Measurement of F2-isoprostanes, highly sensitive C-reactive protein, interleukin-6, D-dimer, sCD14, sCD40, sCD163, and neopterin levels was performed in successive plasma samples collected from cohort inclusion.

Results:

Biomarkers were measured in 78 participants developing serious NAEs or death, and 151 subjects with no events. Adjusted levels of F2-isoprostanes, and also of highly sensitive C-reactive protein, sCD14, and D-dimer were higher in individuals who developed serious NAEs, including or not non-AIDS deaths. The same results were observed when only samples collected since the time of achieving virological suppression were analyzed. The additive incorporation of each biomarker, ending with F2-isoprostanes, in an adjusted model was associated with a graded and significant increase in the quality of model fitting, and 94% sensitivity, 33% specificity, and 0.77 accuracy to predict serious NAEs including non-AIDS–related death.

Conclusion:

Oxidative stress is associated with a higher risk of serious NAEs, including non-AIDS deaths. This effect is independent and additive to biomarkers of inflammation, monocyte activation, and coagulation. Our results suggest that oxidative stress should be included among mechanisms to deal with to improve prognosis of HIV-infected individuals.
Structural Level Differences in the Mother-to-Child HIV Transmission Rate in South Africa: A Multilevel Assessment of Individual-, Health Facility-, and Provincial-Level Predictors of Infant HIV Transmission
Authors: Woldesenbet Selamawit A. , Jackson Debra J. , Lombard CJ , Dinh Thu-Ha , Ramokolo Vundli , Doherty Tanya , Sherman Gayle G. , Pillay Yogan , Goga Ameena E.
Published: January 2017

Objectives:

In 2010, South Africa reported an early mother-to-child transmission (MTCT) rate of 3.5% at 4–8 weeks postpartum. Provincial early MTCT rates ranged from 1.4% [95% confidence interval (CI): 0.1 to 3.4] to 5.9% (95% CI: 3.8 to 8.0). We sought to determine reasons for these geographic differences in MTCT rates.

Methods:

This study used multilevel modeling using 2010 South African prevention of mother-to-child transmission (PMTCT) evaluation (SAPMTCTE) data from 530 facilities. Interview data and blood samples of infants were collected from 3085 mother–infant pairs at 4–8 weeks postpartum. Facility-level data on human resources, referral systems, linkages to care, and record keeping were collected through facility staff interviews. Provincial level data were gathered from publicly available data (eg, health professionals per 10,000 population) or aggregated at province-level from the SAPMTCTE (PMTCT maternal-infant antiretroviral (ARV) coverage). Variance partition coefficients and odds ratios (for provincial facility- and individual-level factors influencing MTCT) from multilevel modeling are reported.

Results:

The provincial- (5.0%) and facility-level (1.4%) variance partition coefficients showed no substantive geographic variation in early MTCT. In multivariable analysis accounting for the multilevel nature of the data, the following were associated with early MTCT: individual-level—low maternal–infant ARV uptake [adjusted odds ratio (AOR) = 2.5, 95% CI: 1.7 to 3.5], mixed breastfeeding (AOR = 1.9, 95% CI: 1.3 to 2.9) and maternal age <20 years (AOR 1.8, 95% CI: 1.1 to 3.0); facility-level–insufficient (≤2) health care-personnel for HIV-testing services (AOR = 1.8, 95% CI: 1.1 to 3.0); provincial-level PMTCT ARV (maternal–infant) coverage lower than 80% (AOR = 1.4, 95% CI: 1.1 to 1.9), and number of health professionals per 10,000 population (AOR = 0.99, 95% CI: 0.98 to 0.99).

Conclusions:

There was no substantial province-/facility-level MTCT difference. This could be due to good overall performance in reducing early MTCT. Disparities in human resource allocation (including allocation of insufficient health care personnel for testing and care at facility level) and PMTCT coverage influenced overall PMTCT programme performance. These are long-standing systemic problems that impact quality of care.