139 research outputs found
Colossal magnetostriction and negative thermal expansion in the frustrated antiferromagnet ZnCr2Se4
A detailed investigation of ZnCr2Se4 is presented which is dominated by
strong ferromagnetic exchange but orders antiferromagnetically at T_N = 21 K.
Specific heat C and thermal expansion Delta L/L exhibit sharp first-order
anomalies at the antiferromagnetic transition. T_N is strongly reduced and
shifted to lower temperatures by external magnetic fields and finally is fully
suppressed suggesting a field induced quantum critical behavior close to 60
kOe. Delta L/L(T) is unusually large and exhibits negative thermal expansion
below 75 K down to T_N indicating strong frustration of the lattice.
Magnetostriction Delta L/L(H) reveals colossal values (0.5x10^{-3}) comparable
to giant magnetostriction materials. Electron-spin resonance, however, shows
negligible spin-orbital coupling excluding orbitally induced Jahn-Teller
distortions. The obtained results point to a spin-driven origin of the
structural instability at T_N explained in terms of competing ferromagnetic and
antiferromagnetic exchange interactions yielding strong bond frustration.Comment: 5 pages 4 figure
Spin-driven Phonon Splitting in Bond-frustrated ZnCr2S4
Utilizing magnetic susceptibility, specific heat, thermal expansion and IR
spectroscopy we provide experimental evidence that the two subsequent
antiferromagnetic transitions in ZnCr_2S_4 at T_N1 = 15 K and T_N2= 8 K are
accompanied by significant thermal and phonon anomalies. The anomaly at T_N2
reveals a strong temperature hysteresis typical for a first-order
transformation. Due to strong spin-phonon coupling both magnetic phase
transitions induce a splitting of phonon modes, where at T_N1 the
high-frequency and at T_N2 the low-frequency modes split. The anomalies and
phonon splitting observed at T_N2 are strongly suppressed by magnetic field.
Regarding the small positive Curie-Weiss temperature Theta= 8 K, we argue that
this scenario of two different magnetic phases with concomitant different
magneto-elastic couplings results from the strong competition of ferromagnetic
and antiferromagnetic exchange of equal strength.Comment: 4 pages, 4 figure
Spin-driven Phase Transitions in ZnCrSe and ZnCrS Probed by High Resolution Synchrotron X-ray and Neutron Powder Diffraction
The crystal and magnetic structures of the spinel compounds ZnCrS and
ZnCrSe were investigated by high resolution powder synchrotron and
neutron diffraction. ZnCrSe exhibits a first order phase transition at
K into an incommensurate helical magnetic structure. Magnetic
fluctuations above are coupled to the crystal lattice as manifested by
negative thermal expansion. Both, the complex magnetic structure and the
anomalous structural behavior can be related to magnetic frustration.
Application of an external magnetic field shifts the ordering temperature and
the regime of negative thermal expansion towards lower temperatures. Thereby,
the spin ordering changes into a conical structure. ZnCrS shows two
magnetic transitions at K and K that are accompanied by
structural phase transitions. The crystal structure transforms from the cubic
spinel-type (space group \={3}) at high temperatures in the paramagnetic
state, via a tetragonally distorted intermediate phase (space group /
) for into a low temperature orthorhombic phase
(space group ) for . The cooperative displacement of
sulfur ions by exchange striction is the origin of these structural phase
transitions. The low temperature structure of ZnCrS is identical to the
orthorhombic structure of magnetite below the Verwey transition. When applying
a magnetic field of 5 T the system shows an induced negative thermal expansion
in the intermediate magnetic phase as observed in ZnCrSe.Comment: 11 pages, 13 figures, to be published in PR
Real Time Hand Movement Trajectory Tracking for Enhancing Dementia Screening in Ageing Deaf Signers of British Sign Language
Real time hand movement trajectory tracking based on machine learning approaches may assist the early identification of dementia in ageing Deaf individuals who are users of British Sign Language (BSL), since there are few clinicians with appropriate communication skills, and a shortage of sign language interpreters. Unlike other computer vision systems used in dementia stage assessment such as RGB-D video with the aid of depth camera, activities of daily living (ADL) monitored by information and communication technologies (ICT) facilities, or X-Ray, computed tomography (CT), and magnetic resonance imaging (MRI) images fed to machine learning algorithms, the system developed here focuses on analysing the sign language space envelope(sign trajectories/depth/speed) and facial expression of deaf individuals, using normal 2D videos. In this work, we are interested in providing a more accurate segmentation of objects of interest in relation to the background, so that accurate real-time hand trajectories (path of the trajectory and speed) can be achieved. The paper presents and evaluates two types of hand movement trajectory models. In the first model, the hand sign trajectory is tracked by implementing skin colour segmentation. In the second model, the hand sign trajectory is tracked using Part Afinity Fields based on the OpenPose Skeleton Model [1, 2]. Comparisons of results between the two different models demonstrate that the second model provides enhanced improvements in terms of tracking accuracy and robustness of tracking. The pattern differences in facial and trajectory motion data achieved from the presented models will be beneficial not only for screening of deaf individuals for dementia, but also for assessment of other acquired neurological impairments associated with motor changes, for example, stroke and Parkinsons disease
The Cytosolic Tail of the Golgi Apyrase Ynd1 Mediates E4orf4-Induced Toxicity in Saccharomyces cerevisiae
The adenovirus E4 open reading frame 4 (E4orf4) protein contributes to regulation of the progression of virus infection. When expressed individually, E4orf4 was shown to induce non-classical transformed cell-specific apoptosis in mammalian cells. At least some of the mechanisms underlying E4orf4-induced toxicity are conserved from yeast to mammals, including the requirement for an interaction of E4orf4 with protein phosphatase 2A (PP2A). A genetic screen in yeast revealed that the Golgi apyrase Ynd1 associates with E4orf4 and contributes to E4orf4-induced toxicity, independently of Ynd1 apyrase activity. Ynd1 and PP2A were shown to contribute additively to E4orf4-induced toxicity in yeast, and to interact genetically and physically. A mammalian orthologue of Ynd1 was shown to bind E4orf4 in mammalian cells, confirming the evolutionary conservation of this interaction. Here, we use mutation analysis to identify the cytosolic tail of Ynd1 as the protein domain required for mediation of the E4orf4 toxic signal and for the interaction with E4orf4. We also show that E4orf4 associates with cellular membranes in yeast and is localized at their cytoplasmic face. However, E4orf4 is membrane-associated even in the absence of Ynd1, suggesting that additional membrane proteins may mediate E4orf4 localization. Based on our results and on a previous report describing a collection of Ynd1 protein partners, we propose that the Ynd1 cytoplasmic tail acts as a scaffold, interacting with a multi-protein complex, whose targeting by E4orf4 leads to cell death
Structure and magnetism in the bond-frustrated spinel
The crystal and magnetic structures of stoichiometric have been investigated using synchrotron x-ray and neutron powder diffraction, muon spin relaxation (), and inelastic neutron scattering. Synchrotron x-ray diffraction shows a spin-lattice distortion from the cubic spinel to a tetragonal lattice below , where powder neutron diffraction confirms the formation of a helical magnetic structure with magnetic moment of at 1.5 K, close to that expected for high-spin . measurements show prominent local spin correlations that are established at temperatures considerably higher (100 ΞΌs^{-1}\)) muon relaxation rates are suggestive of rapid site hopping of the muons in static field. Inelastic neutron scattering measurements show a gapless mode at an incommensurate propagation vector of k = [000.4648(2)] in the low-temperature
magnetic ordered phase that extends to 0.8 meV. The dispersion is modeled by a two-parameter Hamiltonian, containing ferromagnetic nearest-neighbor and antiferromagnetic next-nearest-neighbor interactions with a
A Steered Molecular Dynamics Study of Binding and Translocation Processes in the GABA Transporter
The entire substrate translocation pathway in the human GABA transporter (GAT-1) was explored for the endogenous substrate GABA and the anti-convulsive drug tiagabine. Following a steered molecular dynamics (SMD) approach, in which a harmonic restraining potential is applied to the ligand, dissociation and re-association of ligands were simulated revealing events leading to substrate (GABA) translocation and inhibitor (tiagabine) mechanism of action. We succeeded in turning the transporter from the outward facing occluded to the open-to-out conformation, and also to reorient the transporter to the open-to-in conformation. The simulations are validated by literature data and provide a substrate pathway fingerprint in terms of which, how, and in which sequence specific residues are interacted with. They reveal the essential functional roles of specific residues, e.g. the role of charged residues in the extracellular vestibule including two lysines (K76 (TM1) and K448 (TM10)) and a TM6-triad (D281, E283, and D287) in attracting and relocating substrates towards the secondary/interim substrate-binding site (S2). Likewise, E101 is highlighted as essential for the relocation of the substrate from the primary substrate-binding site (S1) towards the cytoplasm
Directed Evolution Generates a Novel Oncolytic Virus for the Treatment of Colon Cancer
Background Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term βDirected Evolutionβ for creating highly potent oncolytic viruses. Methodology/Principal Findings Taking the βDirected Evolutionβ approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2β3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1's efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent. Conclusions/Significance Using the βDirected Evolutionβ methodology, we have generated ColoAd1, a novel chimeric oncolytic virus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Furthermore, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies
FUS and TARDBP but Not SOD1 Interact in Genetic Models of Amyotrophic Lateral Sclerosis
Mutations in the SOD1 and TARDBP genes have been commonly identified in Amyotrophic Lateral Sclerosis (ALS). Recently, mutations in the Fused in sarcoma gene (FUS) were identified in familial (FALS) ALS cases and sporadic (SALS) patients. Similarly to TDP-43 (coded by TARDBP gene), FUS is an RNA binding protein. Using the zebrafish (Danio rerio), we examined the consequences of expressing human wild-type (WT) FUS and three ALSβrelated mutations, as well as their interactions with TARDBP and SOD1. Knockdown of zebrafish Fus yielded a motor phenotype that could be rescued upon co-expression of wild-type human FUS. In contrast, the two most frequent ALSβrelated FUS mutations, R521H and R521C, unlike S57Ξ, failed to rescue the knockdown phenotype, indicating loss of function. The R521H mutation caused a toxic gain of function when expressed alone, similar to the phenotype observed upon knockdown of zebrafish Fus. This phenotype was not aggravated by co-expression of both mutant human TARDBP (G348C) and FUS (R521H) or by knockdown of both zebrafish Tardbp and Fus, consistent with a common pathogenic mechanism. We also observed that WT FUS rescued the Tardbp knockdown phenotype, but not vice versa, suggesting that TARDBP acts upstream of FUS in this pathway. In addition we observed that WT SOD1 failed to rescue the phenotype observed upon overexpression of mutant TARDBP or FUS or upon knockdown of Tardbp or Fus; similarly, WT TARDBP or FUS also failed to rescue the phenotype induced by mutant SOD1 (G93A). Finally, overexpression of mutant SOD1 exacerbated the motor phenotype caused by overexpression of mutant FUS. Together our results indicate that TARDBP and FUS act in a pathogenic pathway that is independent of SOD1
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