bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations underlying Episodic Ataxia type-1 antagonize Kv1.1 RNA editing
Authors: Ferrick-Kiddie Elizabeth A. , Rosenthal Joshua J. C. , Ayers Gregory D. , Emeson Ronald B. 
Published: February 2017

AbstractAdenosine-to-inosine RNA editing in transcripts encoding the voltage-gated potassium channel Kv1.1 converts an isoleucine to valine codon for amino acid 400, speeding channel recovery from inactivation. Numerous Kv1.1 mutations have been associated with the human disorder Episodic Ataxia Type-1 (EA1), characterized by stress-induced ataxia, myokymia, and increased prevalence of seizures. Three EA1 mutations, V404I, I407M, and V408A, are located within the RNA duplex structure required for RNA editing. Each mutation decreased RNA editing both in vitro and using an in vivo mouse model bearing the V408A allele. Editing of transcripts encoding mutant channels affects numerous biophysical properties including channel opening, closing, and inactivation. Thus EA1 symptoms could be influenced not only by the direct effects of the mutations on channel properties, but also by their influence on RNA editing. These studies provide the first evidence that mutations associated with human genetic disorders can affect cis-regulatory elements to alter RNA editing.
Massively augmented hippocampal dentate granule cell activation accompanies epilepsy development
Authors: Dengler Christopher G. , Yue Cuiyong , Takano Hajime , Coulter Douglas A. 
Published: February 2017

AbstractIn a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development. Pharmacological blockade of outward chloride transport had no effect during epilepsy development, and significantly increased granule cell activation in both control and chronically epileptic animals. This apparent occlusion effect implicates reduction in chloride extrusion as a mechanism contributing to granule cell hyperactivation specifically during early epilepsy development. Glutamine plays a significant role in local synthesis of GABA in synapses. In epileptic mice, sparse granule cell activation could be restored by glutamine application, implicating compromised GABA synthesis. Glutamine had no effect on granule cell activation earlier, during epilepsy development. We conclude that compromised feedforward inhibition within the local circuit generates the massive dentate gyrus circuit hyperactivation evident in animals during and following epilepsy development. However, the mechanisms underlying this disinhibition diverge significantly as epilepsy progresses.
Durability-enhanced two-dimensional hole gas of C-H diamond surface for complementary power inverter applications
Authors: Kawarada Hiroshi , Yamada Tetsuya , Xu Dechen , Tsuboi Hidetoshi , Kitabayashi Yuya , Matsumura Daisuke , Shibata Masanobu , Kudo Takuya , Inaba Masafumi , Hiraiwa Atsushi 
Published: February 2017

AbstractComplementary power field effect transistors (FETs) based on wide bandgap materials not only provide high-voltage switching capability with the reduction of on-resistance and switching losses, but also enable a smart inverter system by the dramatic simplification of external circuits. However, p-channel power FETs with equivalent performance to those of n-channel FETs are not obtained in any wide bandgap material other than diamond. Here we show that a breakdown voltage of more than 1600 V has been obtained in a diamond metal-oxide-semiconductor (MOS) FET with a p-channel based on a two-dimensional hole gas (2DHG). Atomic layer deposited (ALD) Al2O3 induces the 2DHG ubiquitously on a hydrogen-terminated (C-H) diamond surface and also acts as both gate insulator and passivation layer. The high voltage performance is equivalent to that of state-of-the-art SiC planar n-channel FETs and AlGaN/GaN FETs. The drain current density in the on-state is also comparable to that of these two FETs with similar device size and VB.
The X-like shaped spatiotemporal structure of the biphoton entangled state in a cold two-level atomic ensemble
Authors: Zhang Dasen , Zhang Zhiming 
Published: February 2017

AbstractWe study the spatiotemporal structure of the biphoton entangled state generated by the four-wave mixing (FWM) process in a cold two-level atomic ensemble. We analyze, for the first time, the X-like shaped structure of the biphoton entangled state and the geometry of the biphoton correlation for different lengths and densities of the cold atomic ensemble. The propagation equations of the photon pairs generated from FWM process are derived in a spatiotemporal framework. By means of the input-output relations of the propagation equations, the biphoton amplitude function is obtained in a spatiotemporal domain. In the given frequency range, the biphoton amplitude displays an X-like shaped geometry, nonfactorizable in the space-time domain. Such an X-like shaped spatiotemporal structure is caused by the phase matching and the FWM gain. The former leads to the X-like shaped envelope of the biphoton correlation, while the latter gives rise to the oscillations around the X-like shaped envelope.
Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization
Authors: Degani-Katzav Nurit , Klein Moshe , Har-Even Moran , Gortler Revital , Tobi Ruthi , Paas Yoav 
Published: February 2017

AbstractIvermectin (IVM) is a broad-spectrum anthelmintic drug used to treat human parasitic diseases like river blindness and lymphatic filariasis. By activating invertebrate pentameric glutamate-gated chloride channels (GluCl receptors; GluClRs), IVM induces sustained chloride influx and long-lasting membrane hyperpolarization that inhibit neural excitation in nematodes. Although IVM activates the C. elegans heteromeric GluClα/β receptor, it cannot activate a homomeric receptor composed of the C. elegans GluClβ subunits. To understand this incapability, we generated a homopentameric α7-GluClβ chimeric receptor that consists of an extracellular ligand-binding domain of an α7 nicotinic acetylcholine receptor known to be potentiated by IVM, and a chloride-selective channel domain assembled from GluClβ subunits. Application of IVM prior to acetylcholine inhibited the responses of the chimeric α7-GluClβR. Adding IVM to activated α7-GluClβRs, considerably accelerated the decline of ACh-elicited currents and stabilized the receptors in a non-conducting state. Determination of IVM association and dissociation rate constants and recovery experiments suggest that, following initial IVM binding to open α7-GluClβRs, the drug induces a conformational change and locks the ion channel in a closed state for a long duration. We further found that IVM also inhibits the activation by glutamate of a homomeric receptor assembled from the C. elegans full-length GluClβ subunits.
Nonlinear infrared spectroscopy free from spectral selection
Authors: Paterova Anna , Lung Shaun , Kalashnikov Dmitry A. , Krivitsky Leonid A. 
Published: February 2017

AbstractInfrared (IR) spectroscopy is an indispensable tool for many practical applications including material analysis and sensing. Existing IR spectroscopy techniques face challenges related to the inferior performance and the high cost of IR-grade components. Here, we develop a new method, which allows studying properties of materials in the IR range using only visible light optics and detectors. It is based on the nonlinear interference of entangled photons, generated via Spontaneous Parametric Down Conversion (SPDC). In our interferometer, the phase of the signal photon in the visible range depends on the phase of an entangled IR photon. When the IR photon is traveling through the media, its properties can be found from observations of the visible photon. We directly acquire the SPDC signal with a visible range CCD camera and use a numerical algorithm to infer the absorption coefficient and the refraction index of the sample in the IR range. Our method does not require the use of a spectrometer and a slit, thus it allows achieving higher signal-to-noise ratio than the earlier developed method.
Multi-Constituent Simulation of Thrombus Deposition
Authors: Wu Wei-Tao , Jamiolkowski Megan A. , Wagner William R. , Aubry Nadine , Massoudi Mehrdad , Antaki James F. 
Published: February 2017

AbstractIn this paper, we present a spatio-temporal mathematical model for simulating the formation and growth of a thrombus. Blood is treated as a multi-constituent mixture comprised of a linear fluid phase and a thrombus (solid) phase. The transport and reactions of 10 chemical and biological species are incorporated using a system of coupled convection-reaction-diffusion (CRD) equations to represent three processes in thrombus formation: initiation, propagation and stabilization. Computational fluid dynamic (CFD) simulations using the libraries of OpenFOAM were performed for two illustrative benchmark problems: in vivo thrombus growth in an injured blood vessel and in vitro thrombus deposition in micro-channels (1.5 mm × 1.6 mm × 0.1 mm) with small crevices (125 μm × 75 μm and 125 μm × 137 μm). For both problems, the simulated thrombus deposition agreed very well with experimental observations, both spatially and temporally. Based on the success with these two benchmark problems, which have very different flow conditions and biological environments, we believe that the current model will provide useful insight into the genesis of thrombosis in blood-wetted devices, and provide a tool for the design of less thrombogenic devices.
Rapid and sensitive diagnoses of dry root rot pathogen of chickpea (Rhizoctonia bataticola (Taub.) Butler) using loop-mediated isothermal amplification assay
Authors: Ghosh Raju , Tarafdar Avijit , Sharma Mamta 
Published: February 2017

AbstractDry root rot (DRR) caused by the fungus Rhizoctonia bataticola (Taub.) Butler, is an emerging disease in chickpea. The disease is often mistaken with other root rots like Fusarium wilt, collar rot and black root rot in chickpea. Therefore, its timely and specific detection is important. Current detection protocols are either based on mycological methods or on protocols involving DNA amplification by polymerase chain reaction (PCR). Here we report the rapid and specific detection of R. bataticola using loop-mediated isothermal amplification (LAMP) assay targeting fungal specific 5.8S rDNA sequence for visual detection of R. bataticola. The reaction was optimized at 63 °C for 75 min using minimum 10 fg of DNA. After adding SYBR Green I in LAMP products, the amplification was found to be highly specific in all the 94 isolates of R. bataticola collected from diverse geographical regions as well as DRR infected plants and sick soil. No reaction was found in other pathogenic fungi infecting chickpea (Fusarium oxysporum f. sp. ciceris, Rhizoctonia solani, Sclerotium rolfsii and Fusarium solani) and pigeonpea (Fusarium udum and Phytophthora cajani). The standardised LAMP assay with its simplicity, rapidity and specificity is very useful for the visual detection of this emerging disease in chickpea.
Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening
Authors: Temml Veronika , Garscha Ulrike , Romp Erik , Schubert Gregor , Gerstmeier Jana , Kutil Zsofia , Matuszczak Barbara , Waltenberger Birgit , Stuppner Hermann , Werz Oliver , Schuster Daniela 
Published: February 2017

AbstractLeukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer of AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. The soluble epoxide hydrolase (sEH) converts AA-derived anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatetraenoic acids (di-HETEs). Its inhibition consequently also counteracts inflammation. Targeting both LT biosynthesis and the conversion of EETs with a dual inhibitor of FLAP and sEH may represent a novel, powerful anti-inflammatory strategy. We present a pharmacophore-based virtual screening campaign that led to 20 hit compounds of which 4 targeted FLAP and 4 were sEH inhibitors. Among them, the first dual inhibitor for sEH and FLAP was identified, N-[4-(benzothiazol-2-ylmethoxy)-2-methylphenyl]-N’-(3,4-dichlorophenyl)urea with IC50 values of 200 nM in a cell-based FLAP test system and 20 nM for sEH activity in a cell-free assay.
Development of in vitro and in vivo rabies virus neutralization assays based on a high-titer pseudovirus system
Authors: Nie Jianhui , Wu Xiaohong , Ma Jian , Cao Shouchun , Huang Weijin , Liu Qiang , Li Xuguang , Li Yuhua , Wang Youchun 
Published: February 2017

AbstractPseudoviruses are useful virological tools because of their safety and versatility; however the low titer of these viruses substantially limits their wider applications. We developed a highly efficient pseudovirus production system capable of yielding 100 times more rabies pseudovirus than the traditional method. Employing the high-titer pseudoviruses, we have developed robust in vitro and in vivo neutralization assays for the evaluation of rabies vaccine, which traditionally relies on live-virus based assays. Compared with current rapid fluorescent focus inhibition test (RFFIT), our in vitro pseudovirus-based neutralization assay (PBNA) is much less labor-intensive while demonstrating better reproducibility. Moreover, the in vivo PBNA assay was also found to be superior to the live virus based assay. Following intravenous administration, the pseudovirus effectively infected the mice, with dynamic viral distributions being sequentially observed in spleen, liver and brain. Furthermore, data from in vivo PBNA showed great agreement with those generated from the live virus model but with the experimental time significantly reduced from 2 weeks to 3 days. Taken together, the effective pseudovirus production system facilitated the development of novel PBNA assays which could replace live virus-based traditional assays due to its safety, rapidity, reproducibility and high throughput capacity.
Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control
Authors: Valenza Gaetano , Citi Luca , Garcia Ronald G. , Taylor Jessica Noggle , Toschi Nicola , Barbieri Riccardo 
Published: February 2017

AbstractThe application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.
Calcium spikes, waves and oscillations in a large, patterned epithelial tissue
Authors: Balaji Ramya , Bielmeier Christina , Harz Hartmann , Bates Jack , Stadler Cornelia , Hildebrand Alexander , Classen Anne-Kathrin 
Published: February 2017

AbstractWhile calcium signaling in excitable cells, such as muscle or neurons, is extensively characterized, calcium signaling in epithelial tissues is little understood. Specifically, the range of intercellular calcium signaling patterns elicited by tightly coupled epithelial cells and their function in the regulation of epithelial characteristics are little explored. We found that in Drosophila imaginal discs, a widely studied epithelial model organ, complex spatiotemporal calcium dynamics occur. We describe patterns that include intercellular waves traversing large tissue domains in striking oscillatory patterns as well as spikes confined to local domains of neighboring cells. The spatiotemporal characteristics of intercellular waves and oscillations arise as emergent properties of calcium mobilization within a sheet of gap-junction coupled cells and are influenced by cell size and environmental history. While the in vivo function of spikes, waves and oscillations requires further characterization, our genetic experiments suggest that core calcium signaling components guide actomyosin organization. Our study thus suggests a possible role for calcium signaling in epithelia but importantly, introduces a model epithelium enabling the dissection of cellular mechanisms supporting the initiation, transmission and regeneration of long-range intercellular calcium waves and the emergence of oscillations in a highly coupled multicellular sheet.
Organic/Organic Heterointerface Engineering to Boost Carrier Injection in OLEDs
Authors: Fathollahi Mohammadreza , Ameri Mohsen , Mohajerani Ezeddin , Mehrparvar Ebrahim , Babaei Mohammadrasoul 
Published: February 2017

AbstractWe investigate dynamic formation of nanosheet charge accumulations by heterointerface engineering in double injection layer (DIL) based organic light emitting diodes (OLEDs). Our experimental results show that the device performance is considerably improved for the DIL device as the result of heterointerface injection layer (HIIL) formation, in comparison to reference devices, namely, the current density is doubled and even quadrupled and the turn-on voltage is favorably halved, to 3.7 V, which is promising for simple small-molecule OLEDs. The simulation reveals the (i) formation of dynamic p-type doping (DPD) region which treats the quasi Fermi level at the organic/electrode interface, and (ii) formation of dynamic dipole layer (DDL) and the associated electric field at the organic/organic interface which accelerates the ejection of the carriers and their transference to the successive layer. HIIL formation proposes alternate scenarios for device design. For instance, no prerequisite for plasma treatment of transparent anode electrode, our freedom in varying the thicknesses of the organic layers between 10 nm and 60 nm for the first layer and between 6 nm and 24 nm for the second layer. The implications of the present work give insight into the dynamic phenomena in OLEDs and facilitates the development of their inexpensive fabrication for lighting applications.
Matrix attachment region combinations increase transgene expression in transfected Chinese hamster ovary cells
Authors: Zhao Chun-Peng , Guo Xiao , Chen Si-Jia , Li Chang-Zheng , Yang Yun , Zhang Jun-He , Chen Shao-Nan , Jia Yan-Long , Wang Tian-Yun 
Published: February 2017

AbstractMatrix attachment regions (MARs) are cis-acting DNA elements that can increase transgene expression levels in a CHO cell expression system. To investigate the effects of MAR combinations on transgene expression and the underlying regulatory mechanisms, we generated constructs in which the enhanced green fluorescent protein (eGFP) gene flanked by different combinations of human β-interferon and β-globin MAR (iMAR and gMAR, respectively), which was driven by the cytomegalovirus (CMV) or simian virus (SV) 40 promoter. These were transfected into CHO-K1 cells, which were screened with geneticin; eGFP expression was detected by flow cytometry. The presence of MAR elements increased transfection efficiency and transient and stably expression of eGFP expression under both promoters; the level was higher when the two MARs differed (i.e., iMAR and gMAR) under the CMV but not the SV40 promoter. For the latter, two gMARs showed the highest activity. We also found that MARs increased the ratio of stably transfected positive colonies. These results indicate that combining the CMV promoter with two different MAR elements or the SV40 promoter with two gMARs is effective for inducing high expression level and stability of transgenes.
Discrete Element Model for Suppression of Coffee-Ring Effect
Authors: Xu Ting , Lam Miu Ling , Chen Ting-Hsuan 
Published: February 2017

AbstractWhen a sessile droplet evaporates, coffee-ring effect drives the suspended particulate matters to the droplet edge, eventually forming a ring-shaped deposition. Because it causes a non-uniform distribution of solid contents, which is undesired in many applications, attempts have been made to eliminate the coffee-ring effect. Recent reports indicated that the coffee-ring effect can be suppressed by a mixture of spherical and non-spherical particles with enhanced particle-particle interaction at air-water interface. However, a model to comprehend the inter-particulate activities has been lacking. Here, we report a discrete element model (particle system) to investigate the phenomenon. The modeled dynamics included particle traveling following the capillary flow with Brownian motion, and its resultant 3D hexagonal close packing of particles along the contact line. For particles being adsorbed by air-water interface, we modeled cluster growth, cluster deformation, and cluster combination. We found that the suppression of coffee-ring effect does not require a circulatory flow driven by an inward Marangoni flow at air-water interface. Instead, the number of new cluster formation, which can be enhanced by increasing the ratio of non-spherical particles and the overall number of microspheres, is more dominant in the suppression process. Together, this model provides a useful platform elucidating insights for suppressing coffee-ring effect for practical applications in the future.