bluuebunny/crossref_metadata_2025 huggingface dataset:
Decentralised adaptive fuzzy control of coordinated multiple mobile manipulators interacting with non‐rigid environments
Authors: Li Zhijun , Yang Chenguang , Tang Yong
Published: June 2013

Many robotic applications involve the tasks in which multiple coordinated mobile manipulators system interacts with rigid or non‐rigid environments. In this study, we study the topic of multiple mobile manipulators grasping a rigid common object in contact with a deformable working environment, for which few investigations have been made. To solve the difficulty. We first develop the decentralised dynamics of the inter‐connected system, including the dynamics of the mobile manipulators, the internal forces between end‐effectors and the object and the interaction forces between the object and the environments. Then, we design decentralised adaptive fuzzy control based on impedance approach for coordinated multiple mobile manipulators using Lyapunov synthesis. Rigourous stability and performance analysis have been established, and simulation are presented to figuratively demonstrate that the motion/force‐tracking errors converge to zero, whereas the internal force‐tracking error remains bounded and can be made arbitrarily small.
Delay and data packet dropout separately related stability and state feedback stabilisation of networked control systems
Authors: Sun Jiandong , Jiang Jingping
Published: June 2013

There exist bounded transmission delay and data packet dropout in the networked control systems (NCSs). When the sensors and actuators are time‐driven and controllers are event‐driven, the NCSs can be modelled as a class of discrete‐time systems with time‐varying input delay. Most of similar articles simply combine delay and packet dropout to analyse and synthesise NCSs without distinguishing their different impacts, which leads to conservative results. In this study, the authors summarise that the number of consecutive data packet dropout increases gradually in case of packet dropout. A novel Lyapunov–Krasovskii functional is constructed based on this increment property, so less conservative results are obtained through the Lyapunov–Krasovskii functional approach. In addition, the upper bound of a Lyapunov functional difference cross term is reasonably estimated to further reduce the conservativeness. Stability and stabilisation criteria which are separately related to the transmission delay and data packet dropout are presented. The obtained conditions are based on linear matrix inequalities, which can be solved easily by MATLAB or other numerical software.
Global stabilisation of large‐scale hydraulic networks with quantised and positive proportional controls
Authors: Jensen Tom Nørgaard , Wisniewski Rafał
Published: June 2013

The problem considered here is output regulation of a large‐scale hydraulic network where the structure of the network is subject to change and where the actuation is subject to a non‐negativity constraint. Previous results have shown that semi‐global practical output regulation is achievable using a set of decentralised, logarithmic quantised and constrained control actions with properly designed quantisation parameters. That is, an attractor set with a compact basin of attraction exists. Subsequently, the basin can be increased by increasing the control gains. In our work, this result is extended by showing that an attractor set with a global basin of attraction exists for arbitrary values of positive control gains, given that the upper level of the quantiser is properly designed. Furthermore, the proof is given for general monotone quantisation maps. Since the basin of attraction is global and the result is independent on the size of the network, this shows that structural changes can be implemented without destabilising the closed‐loop system.
Integrated trade‐off design of fault detection system for linear discrete time‐varying systems
Authors: Wan Yiming , Dong Wei , Ye Hao
Published: June 2013

In this study, the problem of fault detection (FD) system design for linear discrete time‐varying systems is addressed. Different from most existing methods which separately handle residual generator and evaluator, this study focuses on integrated design of residual generator and evaluator. Instead of traditional trade‐off design between sensitivity to faults and robustness to disturbances, this study aims at maximising FD rate given a predefined false alarm rate. The proposed approach in this study follows two steps: first, in the norm‐based framework, the parity relation‐based offline FD system achieves maximal FD rate by minimising the set of undetectable faults; then the optimal offline FD system is equivalently transformed into a recursive FD algorithm for online use. Relationship between the obtained solution in this study and the existing ones is analysed. The performance improvement of the proposed approach is illustrated by comparing against existing methods through Monte Carlo simulations.
Feedback control for switched positive linear systems
Authors: Zhang Junfeng , Han Zhengzhi , Zhu Fubo , Huang Jun
Published: June 2013

This study investigates the feedback control for a class of switched positive linear systems (SPLSs). By means of the linear programming approach, output‐feedback and state‐feedback controllers for the underlying systems with average dwell time are designed, respectively. Under these controllers, the closed‐loop systems are positive and asymptotically stable. These results obtained provide a way to solve the control synthesis problems of SPLSs by multiple linear copositive Lyapunov functions. Finally, an example is given to illustrate the validity of the present design.
Observer‐based H∞ control for discrete‐time stochastic systems with quantisation and random communication delays
Authors: Yan Huaicheng , Su Zhenzhen , Zhang Hao , Yang Fuwen
Published: June 2013

In this study, the authors are concerned with the observer‐based quantised H∞ control problem for a class of discrete‐time stochastic systems with random communication delays. The system under consideration involves signals quantisation, state‐dependent disturbance as well as random communication delays. The measured output and the control input quantisation are considered simultaneously by using the sector bound approach, while the random communication delays from the sensor to the controller and from the controller to the plant are modelled by a linear function of the stochastic variable satisfying Bernoulli random binary distribution. It is aimed at designing an observer‐based controller such that the dynamics of the closed‐loop system is guaranteed to be exponentially stable in the mean square, and a prescribed H∞ disturbance attenuation level is also achieved. Finally, a simulation example is given to illustrate the effectiveness of the proposed method.
Iterative learning control for a class of non‐linear switched systems
Authors: Bu Xuhui , Hou Zhongsheng , Yu Fashan , Fu Ziyi
Published: June 2013

In this study, the problem of iterative learning control for a class of non‐linear switched systems with arbitrary switched rules is considered. It is assumed that the considered switched systems are operated during a finite‐time interval repetitively, and then the iterative learning control scheme can be introduced. It is also shown that under some given conditions, the D‐type iterative learning control law can guarantee the asymptotic convergence of the tracking error between the desired output and the actual output for the entire time interval through the iterative learning process. Two examples are given to illustrate the effectiveness of the proposed approach.
Gyroscopic destabilisation in polyatomic molecules: Rotational structure of the low-frequency bending vibrational states ν23 and ν11 of dimethylsulfoxide
Authors: Cuisset Arnaud , Sadovskií Dmitrií A.
Published: June 2013

We give details of the spectroscopic observation of the gyroscopic destabilisation in the ν23 vibrational state of dimethylsulfoxide (DMSO) announced by Cuisset, Pirali, and Sadovskií [Phys. Rev. Lett. 109, 094101 (2012)]10.1103/PhysRevLett.109.094101. Following the first successful high-resolution spectroscopic study of the rotational structure of the “perpendicular” band of DMSO at 324 cm−1 associated with the ν23 bending vibrational mode, the rare subsystem of ν23 rotational levels consisting of a series of fourfold quasidegenerate levels (4-clusters) was identified. Our complete analysis of the underlying rotational dynamics uncovered a bifurcation leading to the gyroscopic destabilisation of one of the two stable principal axes of inertia, a phenomenon known previously only in a few triatomic molecules.
Contractions of AdS brane algebra and superGalileon Lagrangians
Authors: Kamimura Kiyoshi , Onda Seiji
Published: June 2013

We examine AdS Galileon Lagrangians using the method of nonlinear realization. By contractions (1) flat curvature limit, (2) non-relativistic brane algebra limit, and (3) (1) + (2) limits we obtain DBI, Newton-Hoock, and Galilean Galileons, respectively. We make clear how these Lagrangians appear as invariant 4-forms and/or pseudo-invariant Wess-Zumino (WZ) terms using Maurer-Cartan (MC) equations on the coset G/SO(3, 1). We show the equations of motion are written in terms of the MC forms only and explain why the inverse Higgs condition is obtained as the equation of motion for all cases. The supersymmetric extension is also examined using a supercoset SU(2, 2|1)/(SO(3, 1) × U(1)) and five WZ forms are constructed. They are reduced to the corresponding five Galileon WZ forms in the bosonic limit and are candidates for supersymmetric Galileon action.
Diagnosing suprathermal ion populations in Z-pinch plasmas using fusion neutron spectra
Authors: Knapp P. F. , Sinars D. B. , Hahn K. D.
Published: June 2013

The existence of suprathermal ion populations gives rise to significant broadening of and modifications to the fusion neutron spectrum. We show that when this population takes the form of a power-law at high energies, specific changes occur to the spectrum which are diagnosable. In particular, the usual Gaussian spectral shape produced by a thermal plasma is replaced by a Lorentz-like spectrum with broad wings extending far from the spectral peak. Additionally, it is found that the full width at half maximum of the spectrum depends on both the ion temperature and the power-law exponent. This causes the use of the spectral width for determination of the ion temperature to be unreliable. We show that these changes are distinguishable from other broadening mechanisms, such as temporal and motional broadening, and that detailed fitting of the spectral shape is a promising method for extracting information about the state of the ions.
A piezoelectric pseudo-bimorph actuator
Authors: Shi Huaduo , Chen Jianguo , Liu Guoxi , Xiao Wenlei , Dong Shuxiang
Published: June 2013

We report a piezoelectric pseudo-bimorph actuator, which is made of only one single plate with interdigitated electrodes on both sides and polarized alternately in longitudinal direction. Like a bimorph actuator, it can also produce a large bending actuation based on anti-symmetrically longitudinal piezoelectric d33 strain effect under an applied electric field. The presented pseudo-bimorph actuator shows much better temperature stability than conventional piezoelectric bimorph actuators from room temperature to the depolarization temperature of the material due to lacking of interface strain loss.
Enhanced interface perpendicular magnetic anisotropy in Ta|CoFeB|MgO using nitrogen doped Ta underlayers
Authors: Sinha Jaivardhan , Hayashi Masamitsu , Kellock Andrew J. , Fukami Shunsuke , Yamanouchi Michihiko , Sato Hideo , Ikeda Shoji , Mitani Seiji , Yang See-hun , Parkin Stuart S. P. , Ohno Hideo
Published: June 2013

We show that the magnetic characteristics of Ta|CoFeB|MgO magnetic heterostructures are strongly influenced by doping the Ta underlayer with nitrogen. In particular, the saturation magnetization drops upon doping the Ta underlayer, suggesting that the doped underlayer acts as a boron diffusion barrier. In addition, the thickness of the magnetic dead layer decreases with increasing nitrogen doping. Surprisingly, the interface magnetic anisotropy increases to ∼1.8 erg/cm2 when an optimum amount of nitrogen is introduced into the Ta underlayer. These results show that nitrogen doped Ta serves as a good underlayer for spintronic applications including magnetic tunnel junctions and domain wall devices.
Parallel generation of uniform fine droplets at hundreds of kilohertz in a flow-focusing module
Authors: Bardin David , Kendall Michael R. , Dayton Paul A. , Lee Abraham P.
Published: June 2013

Droplet-based microfluidic systems enable a variety of biomedical applications from point-of-care diagnostics with third world implications, to targeted therapeutics alongside medical ultrasound, to molecular screening and genetic testing. Though these systems maintain the key advantage of precise control of the size and composition of the droplet as compared to conventional methods of production, the low rates at which droplets are produced limits translation beyond the laboratory setting. As well, previous attempts to scale up shear-based microfluidic systems focused on increasing the volumetric throughput and formed large droplets, negating many practical applications of emulsions such as site-specific therapeutics. We present the operation of a parallel module with eight flow-focusing orifices in the dripping regime of droplet formation for the generation of uniform fine droplets at rates in the hundreds of kilohertz. Elevating the capillary number to access dripping, generation of monodisperse droplets of liquid perfluoropentane in the parallel module exceeded 3.69 × 105 droplets per second, or 1.33 × 109 droplets per hour, at a mean diameter of 9.8 μm. Our microfluidic method offers a novel means to amass uniform fine droplets in practical amounts, for instance, to satisfy clinical needs, with the potential for modification to form massive amounts of more complex droplets.
Optical emission spectroscopic diagnostics of a non-thermal atmospheric pressure helium-oxygen plasma jet for biomedical applications
Authors: Thiyagarajan Magesh , Sarani Abdollah , Nicula Cosmina
Published: June 2013

In this work, we have applied optical emission spectroscopy diagnostics to investigate the characteristics of a non-thermal atmospheric pressure helium plasma jet. The discharge characteristics in the active and afterglow region of the plasma jet, that are critical for biomedical applications, have been investigated. The voltage-current characteristics of the plasma discharge were analyzed and the average plasma power was measured to be around 18 W. The effect of addition of small fractions of oxygen at 0.1%–0.5% on the plasma jet characteristics was studied. The addition of oxygen resulted in a decrease in plasma plume length due to the electronegativity property of oxygen. Atomic and molecular lines of selected reactive plasma species that are considered to be useful to induce biochemical reactions such as OH transitions A2Σ+(ν=0,1)→X2Π(Δν=0) at 308 nm and A2Σ+(ν=0,1)→X2Π(Δν=1) at 287 nm, O I transitions 3p5P→3s5S0 at 777.41 nm, and 3p3P→3s3S0 at 844.6 nm, N2(C-B) second positive system with electronic transition C3Πu →B3Πg  in the range of 300–450 nm and N2+(B-X) first negative system with electronic transition B2Σu+→X2Σg+(Δν=0) at 391.4 nm have been studied. The atomic emission lines of helium were identified, including the He I transitions 3p3P0→2s3S at 388.8 nm, 3p1P0→ 2s1S at 501.6 nm, 3d3D→2p3P0 at 587.6 nm, 3d1D→2p1P0 at 667.8 nm, 3s3S1→2p3P0 at 706.5 nm, 3s1S0→2p1P0 at 728.1 nm, and Hα transition 2p-3d at 656.3 nm. Using a spectral fitting method, the OH radicals at 306–312 nm, the rotational and vibrational temperatures equivalent to gas temperatures of the discharge was measured and the effective non-equilibrium nature of the plasma jet was demonstrated. Our results show that, in the entire active plasma region, the gas temperature remains at 310 ± 25 K and 340 ± 25 K and it increases to 320 ± 25 K and 360 ± 25 K in the afterglow region of the plasma jet for pure helium and helium/oxygen (0.1%) mixture, respectively. Additionally, the vibrational temperatures range from 2200 ± 100 K and 2500 ± 100 K for pure helium and helium/oxygen (0.1%) mixture, respectively. The plasma jet was tested on heat sensitive polymer films used in biomedical applications such as polyethylene terephthalate and poly-L-lactide samples continuously for several minutes without causing any physical or thermal damage to the films. The plasma jet produces significant reactive species of interest while the gas temperatures remain very low demonstrating its potential for a range of biomedical applications.
Functional properties of ZnO films prepared by thermal oxidation of metallic films
Authors: Rambu A. P. , Tiron V. , Nica V. , Iftimie N.
Published: June 2013

We have prepared ZnO films by thermal oxidation of Zn metallic films and analyzed their structure, morphology, wettability, and gas sensing properties. Films structure and surface morphology were derived from X-ray diffraction and atomic force microscopy data. XRD analysis indicates that obtained ZnO films posses a crystalline structure. An increase of the surface roughness was observed, once the oxidation time increases. Surface wettability investigations showed that under UV-illumination, ZnO films present a reversible switching between hydrophobic and hydrophilic states. The gas response to methane, acetone, and formaldehyde was investigated, and experimental results indicate that tested films are selective to methane. Also, the gas response was found to increase, as the oxidation time of metallic films increases. This behavior was attributed to the structural changes (crystallite sizes, surface roughness), which take place during oxidation process.
Noise analysis of broadband active metamaterials with non-Foster loads
Authors: Fan Yifeng , Rajab Khalid Z. , Hao Yang
Published: June 2013

Active metamaterials loaded with non-Foster inclusions may exhibit broadband and low-loss material properties, as compared to their passive counterparts. However, the study of their noise performance still remains to be explored. In addition to the Johnson-Nyquist noise from lossy conductors, nonlinear materials used for the design of negative impedance converters (NICs) will give rise to noise as well. In this paper, a general analytical model is developed for the prediction of the noise performance of broadband, stable active metamaterials based on NICs. The noise performance is analyzed in relation to stability, and the effective material properties. The techniques developed in this paper can be applied generally to metamaterials for which equivalent circuit models exist, and results are shown demonstrating the power spectral density and the noise figure of the specific case of an active metamaterial consisting of loaded loop arrays. Results are compared to and verified with circuit simulations.
Doping dependence of self-diffusion in germanium and the charge states of vacancies
Authors: Südkamp T. , Bracht H. , Impellizzeri G. , Lundsgaard Hansen J. , Nylandsted Larsen A. , Haller E. E.
Published: June 2013

Self-diffusion in boron-doped germanium has been studied at temperatures between 526 and 749 °C with secondary ion mass spectrometry. Self-diffusion under acceptor doping is retarded compared to intrinsic conditions. This demonstrates the contribution of charged vacancies in self-diffusion. Taking into account the dominance of doubly negatively charged vacancies under donor doping, the doping dependence of self-diffusion is best described with an inverse level ordering for singly and doubly negatively charged vacancies for all doping conditions. The level ordering explains the dominance of doubly charged vacancies under donor doping and their decreasing contribution with increasing acceptor doping until neutral vacancies mediate self-diffusion.
C60/N,N′-bis(1-naphthyl)-N,N′-diphenyl-1,1′-biphenyl-4,4′-diamine:MoO3 as the interconnection layer for high efficient tandem blue fluorescent organic light-emitting diodes
Authors: Wu Xiaoming , Bi Wentao , Hua Yulin , Sun Jin'e , Xiao Zhihui , Wang Li , Yin Shougen
Published: June 2013

The high efficient tandem blue fluorescent organic light emitting diodes (OLEDs) with the transparent interconnection layer (ICL) of fullerence (C60)/Molybdenum oxide (MoO3)-doped N,N′-bis(1-naphthyl)-N,N′-diphenyl-1,1′-biphenyl-4,4′-diamine (NPB) were presented. A stack consisting of 0.5 nm of LiF and 1 nm of Ca, which is located from C60 to adjacent electron transporting layer is used as an electron injection layer. The experiment results indicate that the luminance of the tandem device is basically equal to that of the traditional single-unit device, but the current density of the tandem device is much less than that of the single-unit device under a same luminance. The current efficiency and the maximal power efficiency of tandem device with LiF/Ca/C60/NPB:MoO3/MoO3-based interconnection layer have been approximately enhanced by 250% and 126%, respectively. In addition, we also analyze that the mechanism of the efficiency enhancement is ascribed to the effective charge separation and transport of the ICL in tandem OLEDs.
Wavelength limits for InGaN quantum wells on GaN
Authors: Pristovsek Markus
Published: June 2013

The emission wavelength of coherently strained InGaN quantum wells (QW) is limited by the maximum thickness before relaxation starts. For high indium contents x>40% the resulting wavelength decreases because quantum confinement dominates. For low indium content x<40% the electron hole wave function overlap (and hence radiative emission) is strongly reduced with increasing QW thickness due to the quantum confined Stark effect and imposes another limit. This results in a maximum usable emission wavelength at around 600 nm for QWs with 40%-50% indium content. Relaxed InGaN buffer layers could help to push this further, especially on non- and semi-polar orientations.
Carbon dioxide photolysis from 150 to 210 nm: Singlet and triplet channel dynamics, UV-spectrum, and isotope effects
Authors: Schmidt Johan A. , Johnson Matthew S. , Schinke Reinhard
Published: June 2013

We present a first principles study of the carbon dioxide (CO2) photodissociation process in the 150- to 210-nm wavelength range, with emphasis on photolysis below the carbon monoxide +singlet channel threshold at ∼167 nm. The calculations reproduce experimental absorption cross-sections at a resolution of ∼0.5 nm without scaling the intensity. The observed structure in the 150- to 210-nm range is caused by excitation of bending motion supported by the deep wells at bent geometries in theandpotential energy surfaces. Predissociation below the singlet channel threshold occurs via spin-orbit coupling to nearby repulsive triplet states. Carbon monoxide vibrational and rotational state distributions in the singlet channel as well as the triplet channel for excitation at 157 nm satisfactorily reproduce experimental data. The cross-sections of individual CO2isotopologues (12C16O2,12C17O16O,12C18O16O,13C16O2, and13C18O16O) are calculated, demonstrating that strong isotopic fractionation will occur as a function of wavelength. The calculations provide accurate, detailed insight into CO2photoabsorption and dissociation dynamics, and greatly extend knowledge of the temperature dependence of the cross-section to cover the range from 0 to 400 K that is useful for calculations of propagation of stellar light in planetary atmospheres. The model is also relevant for the interpretation of laboratory experiments on mass-independent isotopic fractionation. Finally, the model shows that the mass-independent fractionation observed in a series of Hg lamp experiments is not a result of hyperfine interactions making predissociation of17O containing CO2more efficient.
Phosphorylation-triggered CUEDC2 degradation promotes UV-induced G
1
arrest through APC/C
Cdh1
regulation
Authors: Zhang Wei-Na , Zhou Jie , Zhou Tao , Li Ai-Ling , Wang Na , Xu Jin-Jing , Chang Yan , Man Jiang-Hong , Pan Xin , Li Tao , Li Wei-Hua , Mu Rui , Liang Bing , Chen Liang , Jin Bao-Feng , Xia Qing , Gong Wei-Li , Zhang Xue-Min , Wang Li , Li Hui-Yan
Published: June 2013

DNA damage triggers cell cycle arrest to provide a time window for DNA repair. Failure of arrest could lead to genomic instability and tumorigenesis. DNA damage-induced G
1
arrest is generally achieved by the accumulation of Cyclin-dependent kinase inhibitor 1 (p21). However, p21 is degraded and does not play a role in UV-induced G
1
arrest. The mechanism of UV-induced G
1
arrest thus remains elusive. Here, we have identified a critical role for CUE domain-containing protein 2 (CUEDC2) in this process. CUEDC2 binds to and inhibits anaphase-promoting complex/cyclosome-Cdh1 (APC/C
Cdh1
), a critical ubiquitin ligase in G
1
phase, thereby stabilizing Cyclin A and promoting G
1
–S transition. In response to UV irradiation, CUEDC2 undergoes ERK1/2-dependent phosphorylation and ubiquitin-dependent degradation, leading to APC/C
Cdh1
-mediated Cyclin A destruction, Cyclin-dependent kinase 2 inactivation, and G
1
arrest. A nonphosphorylatable CUEDC2 mutant is resistant to UV-induced degradation. Expression of this stable mutant effectively overrides UV-induced G
1
–S block. These results establish CUEDC2 as an APC/C
Cdh1
inhibitor and indicate that regulated CUEDC2 degradation is critical for UV-induced G
1
arrest.
Acoustic echoes reveal room shape
Authors: Dokmanić Ivan , Parhizkar Reza , Walther Andreas , Lu Yue M. , Vetterli Martin
Published: June 2013

Imagine that you are blindfolded inside an unknown room. You snap your fingers and listen to the room’s response. Can you hear the shape of the room? Some people can do it naturally, but can we design computer algorithms that hear rooms? We show how to compute the shape of a convex polyhedral room from its response to a known sound, recorded by a few microphones. Geometric relationships between the arrival times of echoes enable us to “blindfoldedly” estimate the room geometry. This is achieved by exploiting the properties of Euclidean distance matrices. Furthermore, we show that under mild conditions, first-order echoes provide a unique description of convex polyhedral rooms. Our algorithm starts from the recorded impulse responses and proceeds by learning the correct assignment of echoes to walls. In contrast to earlier methods, the proposed algorithm reconstructs the full 3D geometry of the room from a single sound emission, and with an arbitrary geometry of the microphone array. As long as the microphones can hear the echoes, we can position them as we want. Besides answering a basic question about the inverse problem of room acoustics, our results find applications in areas such as architectural acoustics, indoor localization, virtual reality, and audio forensics.
MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations
Authors: Fan Chengpeng , Rajasekaran Deepa , Syed Mansoor Ali , Leng Lin , Loria J. Patrick , Bhandari Vineet , Bucala Richard , Lolis Elias J.
Published: June 2013

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. In addition to its known receptor-mediated biological activities, MIF possesses a catalytic site of unknown function between subunits of a homotrimer. Each subunit contributes three β-strands to adjacent subunits to form a core seven-stranded β-sheet for each monomer. MIF monomers, dimers, or trimers have been reported, but the active form that binds and activates the MIF receptor (CD74) is still a matter of debate. A cysteine mutant (N110C) that covalently locks MIF into a trimer by forming a disulfide with Cys-80 of an adjacent subunit is used to study this issue. Partial catalytic activity and receptor binding to CD74 are retained by N110C (locked trimer), but there is no cellular signaling. Wild-type MIF-induced cellular signaling, in vivo lung neutrophil accumulation, and alveolar permeability are inhibited with a fivefold excess of N110C. NMR and size-exclusion chromatography with light scattering reveal that N110C can form a higher-order oligomer in equilibrium with a single locked trimer. The X-ray structure confirms a local conformational change that disrupts the subunit interface and results in global changes responsible for the oligomeric form. The structure also confirms these changes are consistent for the partial catalytic and receptor binding activities. The absence of any potential monomer and the retention of partial catalytic and receptor binding activities despite changes in conformation (and dynamics) in the mutant support an endogenous MIF trimer that binds and activates CD74 at nanomolar concentrations. This conclusion has implications for therapeutic development.
Genetic reconstitution of tumorigenesis in primary intestinal cells
Authors: Onuma Kunishige , Ochiai Masako , Orihashi Kaoru , Takahashi Mami , Imai Toshio , Nakagama Hitoshi , Hippo Yoshitaka
Published: June 2013

Animal models for human colorectal cancer recapitulate multistep carcinogenesis that is typically initiated by activation of the Wnt pathway. Although potential roles of both genetic and environmental modifiers have been extensively investigated in vivo, it remains elusive whether epithelial cells definitely require interaction with stromal cells or microflora for tumor development. Here we show that tumor development could be simply induced independently of intestinal microenvironment, even with WT murine primary intestinal cells alone. We developed an efficient method for lentiviral transduction of intestinal organoids in 3D culture. Despite seemingly antiproliferative effects by knockdown of adenomatous polyposis coli (
APC
), we managed to reproducibly induce
APC
-inactivated intestinal organoids. As predicted, these organoids were constitutively active in the Wnt signaling pathway and proved tumorigenic when injected into nude mice, yielding highly proliferative tubular epithelial glands accompanied by prominent stromal tissue. Consistent with cellular transformation, tumor-derived epithelial cells acquired sphere formation potential, gave rise to secondary tumors on retransplantation, and highly expressed cancer stem cell markers. Inactivation of
p53
or phosphatase and tensin homolog deleted from chromosome 10, or activation of
Kras,
promoted tumor development only in the context of
APC
suppression, consistent with earlier genetic studies. These findings clearly indicated that genetic cooperation for intestinal tumorigenesis could be essentially recapitulated in intestinal organoids without generating gene-modified mice. Taken together, this in vitro model for colon cancer described herein could potentially provide unique opportunities for carcinogenesis studies by serving as a substitute or complement to the currently standard approaches.
Liposome division by a simple bacterial division machinery
Authors: Osawa Masaki , Erickson Harold P.
Published: June 2013

We previously reconstituted Z rings in tubular multilamellar liposomes with FtsZ-YFP-mts, where mts is a membrane-targeting amphiphilic helix. These reconstituted Z rings generated a constriction force but did not divide the thick-walled liposomes. Here we developed a unique system to observe Z rings in unilamellar liposomes. FtsZ-YFP-mts incorporated inside large, unilamellar liposomes formed patches that produced concave distortions when viewed at the equator of the liposome. When viewed en face at the top of the liposome, many of the patches were seen to be small Z rings, which still maintained the concave depressions. We also succeeded in reconstituting the more natural, two-protein system, with FtsA and FtsZ-YFP (having the FtsA-binding peptide instead of the mts). Unilamellar liposomes incorporating FtsA and FtsZ-YFP showed a variety of distributions, including foci and linear arrays. A small fraction of liposomes had obvious Z rings. These Z rings could constrict the liposomes and in some cases appeared to complete the division, leaving a clear septum between the two daughter liposomes. Because complete liposome divisions were not seen with FtsZ-mts, FtsA may be critical for the final membrane scission event. We demonstrate that reconstituted cell division machinery apparently divides the liposome in vitro.
Nonlinear effects of group size on collective action and resource outcomes
Authors: Yang Wu , Liu Wei , Viña Andrés , Tuanmu Mao-Ning , He Guangming , Dietz Thomas , Liu Jianguo
Published: June 2013

For decades, scholars have been trying to determine whether small or large groups are more likely to cooperate for collective action and successfully manage common-pool resources. Using data gathered from the Wolong Nature Reserve since 1995, we examined the effects of group size (i.e., number of households monitoring a single forest parcel) on both collective action (forest monitoring) and resource outcomes (changes in forest cover) while controlling for potential confounding factors. Our results demonstrate that group size has nonlinear effects on both collective action and resource outcomes, with intermediate group size contributing the most monitoring effort and leading to the biggest forest cover gain. We also show how opposing effects of group size directly and indirectly affect collective action and resource outcomes, leading to the overall nonlinear relationship. Our findings suggest why previous studies have observed differing and even contradictory group-size effects, and thus help guide further research and governance of the commons. The findings also suggest that it should be possible to improve collective action and resource outcomes by altering factors that lead to the nonlinear group-size effect, including punishing free riding, enhancing overall and within-group enforcement, improving social capital across groups and among group members, and allowing self-selection during the group formation process so members with good social relationships can form groups autonomously.
Underconnectivity between voice-selective cortex and reward circuitry in children with autism
Authors: Abrams Daniel A. , Lynch Charles J. , Cheng Katherine M. , Phillips Jennifer , Supekar Kaustubh , Ryali Srikanth , Uddin Lucina Q. , Menon Vinod
Published: June 2013

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.
Structure of the human cohesin inhibitor Wapl
Authors: Ouyang Zhuqing , Zheng Ge , Song Jianhua , Borek Dominika M. , Otwinowski Zbyszek , Brautigam Chad A. , Tomchick Diana R. , Rankin Susannah , Yu Hongtao
Published: June 2013

Cohesin, along with positive regulators, establishes sister-chromatid cohesion by forming a ring to circle chromatin. The wings apart-like protein (Wapl) is a key negative regulator of cohesin and forms a complex with precocious dissociation of sisters protein 5 (Pds5) to promote cohesin release from chromatin. Here we report the crystal structure and functional characterization of human Wapl. Wapl contains a flexible, variable N-terminal region (Wapl-N) and a conserved C-terminal domain (Wapl-C) consisting of eight HEAT (Huntingtin, Elongation factor 3, A subunit, and target of rapamycin) repeats. Wapl-C folds into an elongated structure with two lobes. Structure-based mutagenesis maps the functional surface of Wapl-C to two distinct patches (I and II) on the N lobe and a localized patch (III) on the C lobe. Mutating critical patch I residues weaken Wapl binding to cohesin and diminish sister-chromatid resolution and cohesin release from mitotic chromosomes in human cells and
Xenopus
egg extracts. Surprisingly, patch III on the C lobe does not contribute to Wapl binding to cohesin or its known regulators. Although patch I mutations reduce Wapl binding to intact cohesin, they do not affect Wapl–Pds5 binding to the cohesin subcomplex of sister chromatid cohesion protein 1 (Scc1) and stromal antigen 2 (SA2) in vitro, which is instead mediated by Wapl-N. Thus, Wapl-N forms extensive interactions with Pds5 and Scc1–SA2. Wapl-C interacts with other cohesin subunits and possibly unknown effectors to trigger cohesin release from chromatin.
Archaeological shellfish size and later human evolution in Africa
Authors: Klein Richard G. , Steele Teresa E.
Published: June 2013

Approximately 50 ka, one or more subgroups of modern humans expanded from Africa to populate the rest of the world. Significant behavioral change accompanied this expansion, and archaeologists commonly seek its roots in the African Middle Stone Age (MSA; ∼200 to ∼50 ka). Easily recognizable art objects and “jewelry” become common only in sites that postdate the MSA in Africa and Eurasia, but some MSA sites contain possible precursors, especially including abstractly incised fragments of ocher and perforated shells interpreted as beads. These proposed art objects have convinced most specialists that MSA people were behaviorally (cognitively) modern, and many argue that population growth explains the appearance of art in the MSA and its post-MSA florescence. The average size of rocky intertidal gastropod species in MSA and later coastal middens allows a test of this idea, because smaller size implies more intense collection, and more intense collection is most readily attributed to growth in the number of human collectors. Here we demonstrate that economically important Cape turban shells and limpets from MSA layers along the south and west coasts of South Africa are consistently and significantly larger than turban shells and limpets in succeeding Later Stone Age (LSA) layers that formed under equivalent environmental conditions. We conclude that whatever cognitive capacity precocious MSA artifacts imply, it was not associated with human population growth. MSA populations remained consistently small by LSA standards, and a substantial increase in population size is obvious only near the MSA/LSA transition, when it is dramatically reflected in the Out-of-Africa expansion.
Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2
Authors: Sprowl Jason A. , Ciarimboli Giuliano , Lancaster Cynthia S. , Giovinazzo Hugh , Gibson Alice A. , Du Guoqing , Janke Laura J. , Cavaletti Guido , Shields Anthony F. , Sparreboom Alex
Published: June 2013

Oxaliplatin is an integral component of colorectal cancer therapy, but its clinical use is associated with a dose-limiting peripheral neurotoxicity. We found that the organic cation transporter 2 (OCT2) is expressed on dorsal root ganglia cells within the nervous system where oxaliplatin is known to accumulate. Cellular uptake of oxaliplatin was increased by 16- to 35-fold in cells overexpressing mouse Oct2 or human OCT2, and this process was associated with increased DNA platination and oxaliplatin-induced cytotoxicity. Furthermore, genetic or pharmacologic knockout of Oct2 protected mice from hypersensitivity to cold or mechanical-induced allodynia, which are established tests to assess acute oxaliplatin-induced neurotoxicity. These findings provide a rationale for the development of targeted approaches to mitigate this debilitating toxicity.
Pesticides reduce regional biodiversity of stream invertebrates
Authors: Beketov Mikhail A. , Kefford Ben J. , Schäfer Ralf B. , Liess Matthias
Published: June 2013

The biodiversity crisis is one of the greatest challenges facing humanity, but our understanding of the drivers remains limited. Thus, after decades of studies and regulation efforts, it remains unknown whether to what degree and at what concentrations modern agricultural pesticides cause regional-scale species losses. We analyzed the effects of pesticides on the regional taxa richness of stream invertebrates in Europe (Germany and France) and Australia (southern Victoria). Pesticides caused statistically significant effects on both the species and family richness in both regions, with losses in taxa up to 42% of the recorded taxonomic pools. Furthermore, the effects in Europe were detected at concentrations that current legislation considers environmentally protective. Thus, the current ecological risk assessment of pesticides falls short of protecting biodiversity, and new approaches linking ecology and ecotoxicology are needed.
General approach to reversing ketol-acid reductoisomerase cofactor dependence from NADPH to NADH
Authors: Brinkmann-Chen Sabine , Flock Tilman , Cahn Jackson K. B. , Snow Christopher D. , Brustad Eric M. , McIntosh John A. , Meinhold Peter , Zhang Liang , Arnold Frances H.
Published: June 2013

To date, efforts to switch the cofactor specificity of oxidoreductases from nicotinamide adenine dinucleotide phosphate (NADPH) to nicotinamide adenine dinucleotide (NADH) have been made on a case-by-case basis with varying degrees of success. Here we present a straightforward recipe for altering the cofactor specificity of a class of NADPH-dependent oxidoreductases, the ketol-acid reductoisomerases (KARIs). Combining previous results for an engineered NADH-dependent variant of
Escherichia coli
KARI with available KARI crystal structures and a comprehensive KARI-sequence alignment, we identified key cofactor specificity determinants and used this information to construct five KARIs with reversed cofactor preference. Additional directed evolution generated two enzymes having NADH-dependent catalytic efficiencies that are greater than the wild-type enzymes with NADPH. High-resolution structures of a wild-type/variant pair reveal the molecular basis of the cofactor switch.
Species-specific factors mediate extensive heterogeneity of mRNA 3′ ends in yeasts
Authors: Moqtaderi Zarmik , Geisberg Joseph V. , Jin Yi , Fan Xiaochun , Struhl Kevin
Published: June 2013

Most eukaryotic genes express mRNAs with alternative polyadenylation sites at their 3′ ends. Here we show that polyadenylated 3′ termini in three yeast species (
Saccharomyces cerevisiae
,
Kluyveromyces lactis
, and
Debaryomyces hansenii
) are remarkably heterogeneous. Instead of a few discrete 3′ ends, the average yeast gene has an “end zone,” a >200 bp window with >60 distinct poly(A) sites, the most used of which represents only 20% of the mRNA molecules. The pattern of polyadenylation within this zone varies across species, with
D. hansenii
possessing a higher focus on a single dominant point closer to the ORF terminus. Some polyadenylation occurs within mRNA coding regions with a strong bias toward the promoter. The polyadenylation pattern is determined by a highly degenerate sequence over a broad region and by a local sequence that relies on A residues after the cleavage point. Many dominant poly(A) sites are predicted to adopt a common secondary structure that may be recognized by the cleavage/polyadenylation machinery. We suggest that the end zone reflects a region permissive for polyadenylation, within which cleavage occurs preferentially at the A-rich sequence. In
S. cerevisiae
strains,
D. hansenii
genes adopt the
S. cerevisiae
polyadenylation profile, indicating that the polyadenylation pattern is mediated primarily by species-specific factors.
Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake
Authors: Feng Shengjie , Li Hongyu , Tai Yilin , Huang Junbo , Su Yujuan , Abramowitz Joel , Zhu Michael X. , Birnbaumer Lutz , Wang Yizheng
Published: June 2013

Mitochondrial Ca
2+
homeostasis is fundamental to regulation of mitochondrial membrane potential, ATP production, and cellular Ca
2+
homeostasis. It has been known for decades that isolated mitochondria can take up Ca
2+
from the extramitochondrial solution, but the molecular identity of the Ca
2+
channels involved in this action is largely unknown. Here, we show that a fraction of canonical transient receptor potential 3 (TRPC3) channels is localized to mitochondria, a significant fraction of mitochondrial Ca
2+
uptake that relies on extramitochondrial Ca
2+
concentration is TRPC3-dependent, and the up- and down-regulation of TRPC3 expression in the cell influences the mitochondrial membrane potential. Our findings suggest that TRPC3 channels contribute to mitochondrial Ca
2+
uptake. We anticipate our observations may provide insights into the mechanisms of mitochondrial Ca
2+
uptake and advance understanding of the physiological role of TRPC3.
Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction
Authors: Plaks Vicki , Rinkenberger Julie , Dai Joanne , Flannery Margaret , Sund Malin , Kanasaki Keizo , Ni Wei , Kalluri Raghu , Werb Zena
Published: June 2013

The pregnancy complication preeclampsia (PE), which occurs in approximately 3% to 8% of human pregnancies, is characterized by placental pathologies that can lead to significant fetal and maternal morbidity and mortality. Currently, the only known cure is delivery of the placenta. As the etiology of PE remains unknown, it is vital to find models to study this common syndrome. Here we show that matrix metalloproteinase-9 (MMP9) deficiency causes physiological and placental abnormalities in mice, which mimic features of PE. As with the severe cases of this syndrome, which commence early in gestation, MMP9-null mouse embryos exhibit deficiencies in trophoblast differentiation and invasion shortly after implantation, along with intrauterine growth restriction or embryonic death. Reciprocal embryo transfer experiments demonstrated that embryonic MMP9 is a major contributor to normal implantation, but maternal MMP9 also plays a role in embryonic trophoblast development. Pregnant MMP9-null mice bearing null embryos exhibited clinical features of PE as VEGF dysregulation and proteinuria accompanied by preexisting elevated blood pressure and kidney pathology. Thus, our data show that fetal and maternal MMP9 play a role in the development of PE and establish the MMP9-null mice as a much-needed model to study the clinical course of this syndrome.