bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated cerebrovascular resistance index is associated with cognitive dysfunction in the very-old
Authors: Clark Lindsay R , Nation Daniel A , Wierenga Christina E , Bangen Katherine J , Dev Sheena I , Shin David D , Delano-Wood Lisa , Liu Thomas T , Rissman Robert A , Bondi Mark W
Published: January 2015

Introduction

Age-related vascular changes, including blood pressure elevation and cerebral blood flow (CBF) reduction, are associated with cognitive decline and Alzheimer’s disease (AD). Evidence suggests that the relationship between blood pressure and dementia risk varies between younger and older samples within the elderly population.

Methods

We examined the relationship between mean arterial pressure (MAP), CBF, and cognition in young-old (60 to 75 years of age) versus very-old (80+ years of age) adults. Fifty-eight non-demented older adults completed an arterial spin labeling MRI scan, and an index of cerebrovascular resistance (CVRi) was estimated for each participant by calculating the ratio of MAP and CBF.

Results

Results demonstrated a similar negative relationship between MAP and CBF across both age groups. However, very-old participants exhibited elevated CVRi and reduced CBF compared to young-old participants in regions implicated in AD and cerebral small vessel disease. Furthermore, significant age by CVRi interactions revealed that elevated CVRi in the thalamus was inversely related to verbal fluency performance in the very-old group.

Conclusions

Findings support CVRi as a potential vascular biomarker and suggest that regionally-specific vascular changes may contribute to cognitive decline, particularly in the very-old.
Neural correlates of visual hallucinations in dementia with Lewy bodies
Authors: Heitz Camille , Noblet Vincent , Cretin Benjamin , Philippi Nathalie , Kremer Laurent , Stackfleth Mélanie , Hubele Fabrice , Armspach Jean Paul , Namer Izzie , Blanc Frédéric
Published: January 2015

Introduction

The aim of this study was to investigate the association between visual hallucinations in dementia with Lewy bodies (DLB) and brain perfusion using single-photon emission computed tomography.

Methods

We retrospectively included 66 patients with DLB, 36 of whom were having visual hallucinations (DLB-hallu) and 30 of whom were not (DLB-c). We assessed visual hallucination severity on a 3-point scale of increasing severity: illusions, simple visual hallucinations and complex visual hallucinations. We performed voxel-level comparisons between the two groups and assessed correlations between perfusion and visual hallucinations severity.

Results

We found a significant decrease in perfusion in the left anterior cingulate cortex, the left orbitofrontal cortex and the left cuneus in the DLB-hallu group compared with the DLB-c group. We also found a significant correlation between decreased bilateral anterior cingulate cortex, left orbitofrontal cortex, right parahippocampal gyrus, right inferior temporal cortex and left cuneus perfusion with the severity of hallucinations.

Conclusions

Visual hallucinations seem to be associated with the impairment of anterior and posterior regions (secondary visual areas, orbitofrontal cortex and anterior cingulate cortex) involved in a top-down and bottom-up mechanism, respectively. Furthermore, involvement of the bilateral anterior cingulate cortex and right parahippocampal gyrus seems to lead to more complex hallucinations.
Three-dimensional gravity inversion using graph theory to delineate the skeleton of homogeneous sources
Authors: Bijani Rodrigo , Ponte-Neto Cosme F. , Carlos Dionisio U. , Silva Dias Fernando J. S.
Published: January 2015

We developed a new strategy, based on graph theory concepts, to invert gravity data using an ensemble of simple point masses. Our method consisted of a genetic algorithm with elitism to generate a set of possible solutions. Each estimate was associated to a graph to solve the minimum spanning tree (MST) problem. To produce unique and stable estimates, we restricted the position of the point masses by minimizing the statistical variance of the distances of an MST jointly with the data-misfit function during the iterations of the genetic algorithm. Hence, the 3D spatial distribution of the point masses identified the skeleton of homogeneous gravity sources. In addition, our method also gave an estimation of the anomalous mass of the source. So, together with the anomalous mass, the skeleton could aid other 3D methods with promising geometric a priori parameters. Several tests with different values of regularizing parameter were made to bespeak this new regularizing strategy. The inversion results applied to noise-corrupted synthetic gravity data revealed that, regardless of promising starting models, the estimated distribution of point masses and the anomalous mass offered valuable information about the homogeneous sources in the subsurface. Tests on real data from a portion of Quadrilátero Ferrífero, Minas Gerais state, Brazil, were performed for complementary analysis of the proposed inversion method.
Comparison of Measured and Proxy-Based VS30 Values in California
Authors: Yong Alan
Published: January 2015

This study was prompted by the recent availability of a significant amount of openly accessible measured V S30 values and the desire to investigate the trend of using proxy-based models to predict V S30 in the absence of measurements. Comparisons between measured and model-based values were performed. The measured data included 503 V S30 values collected from various projects for 482 seismographic station sites in California. Six proxy-based models—employing geologic mapping, topographic slope, and terrain classification—were also considered. Included was a new terrain class model based on the Yong et al. (2012) approach but recalibrated with updated measured V S30 values. Using the measured V S30 data as the metric for performance, the predictive capabilities of the six models were determined to be statistically indistinguishable. This study also found three models that tend to underpredict V S30 at lower velocities (NEHRP Site Classes D–E) and overpredict at higher velocities (Site Classes B–C).
Modelling and Control of an Overhead Crane System with a Flexible Cable and Large Swing Angle
Authors: Fatehi Mohammad H. , Eghtesad Mohammad , Amjadifard Roya
Published: January 2015

This paper deals with modelling and control of an overhead crane with a flexible cable. The developed dynamical model includes both transverse vibrations of the flexible cable and large swing angles of cable while the trolley is moving horizontally. To carry out the modelling, Rayleigh-Ritz discretization method is used to achieve an ordinary differential equation (ODE) model for transverse deflection of the cable with finite generalized degrees of freedom. Using the Euler–Lagrange formulation, a nonlinear dynamic model of the crane system with a flexible cable is obtained. The control objective is to move the payload position to the desired point and at the same time, to reduce the payload swing and to suppress the cable's transverse vibration. To this end, a static state feedback control combined with integral error feedback is proposed. Simulations are performed using the developed nonlinear model under various conditions to illustrate the effectiveness of the proposed control system.
Feedback Control of Rijke-Type Thermo-Acoustic Instability
Authors: Zhang Zhiguo , Guan Di
Published: January 2015

Thermo-acoustic instabilities are characterized by large-amplitude pressure oscillations, which are detrimental to land-based gas turbine and aero-engines. In this work, a real-time monitoring and feedback control strategy is developed, which involves two algorithms. One is an identification algorithm, which is used to ‘sense’ the condition of a combustion system and to conduct system identification. The algorithm performs somewhat similar to short-time Fourier transform, but is suitable for real-time computation and is able to more accurately estimate frequency using a shorter sample length. Furthermore it can output a reconstructed signal whose frequency is twice of the input signal, which has great potential to be used for system identification. The other algorithm is a revised infinite impulse response (IIR) filter; its efficiency is optimized by using LMS (least mean square). Finally, the control strategy is then experimentally implemented on a Rijke tube. It is found that approximately 50 dB sound reduction is achieved by actuating a loudspeaker. In addition, the control strategy is demonstrated to be able to track and prevent the onset of new limit cycle results from changes of fuel flow rate.
Reference Cases for Verification of Operation and Maintenance Simulation Models for Offshore Wind Farms
Authors: Dinwoodie Iain , Endrerud Ole-Erik V. , Hofmann Matthias , Martin Rebecca , Sperstad Iver Bakken
Published: January 2015

Due to lack of operating experience in the field of offshore wind energy and large costs associated with maintaining offshore wind farms, there is a need to develop accurate operation and maintenance models for strategic planning purposes. This paper provides an approach for verifying such simulation models and demonstrates it by describing the verification process for four models. A reference offshore wind farm is defined and simulated using these models to provide test cases and benchmark results for verification for wind farm availability and O&M costs. This paper also identifies key modelling assumptions that impact the results. The calculated availabilities for the four models show good agreement apart from cases where maintenance resources are heavily constrained. There are also larger discrepancies between the cost results. All the differences in the results can be explained by different modelling assumptions. Therefore, the models can be regarded as verified based on the presented approach.
Routing and Scheduling of Maintenance Fleet for Offshore Wind Farms
Authors: Dai Lijuan , Stålhane Magnus , Utne Ingrid B.
Published: January 2015

Reducing the operation and maintenance (O&M) cost is a necessity in current offshore wind farms so that the produced power can achieve a competitive price in the market. An offshore wind farm normally comprises a large number of turbines which demand frequent maintenance visits. In addition to making maintenance plans that avoid downtime and production losses, it is important to utilize the expensive resources, such as service vessels, in an efficient way. This article introduces the routing and scheduling problem of a maintenance fleet for offshore wind farms (RSPMFOWF), which is to determine the optimal assignments of turbines and routes to the vessels in terms of cost. Simultaneously considering the characteristics and limitations in this problem, we present the mathematical formulations for the RSPMFOWF. A computational case study is also carried out. The results provide both the optimized cost and detailed arrangements, which can be directly used in maintenance planning.
Investigation of Optimum Crew Transfer Vessel Fleet for Offshore Wind Farm Maintenance Operations
Authors: Dalgic Yalcin , Lazakis Iraklis , Turan Osman
Published: January 2015

The offshore wind industry, which aims to reduce the operational costs, usually achieved through learning curves and supply chain improvements, has seen drastic cost increase over the last five years. In order to sustain the competitiveness of the offshore wind industry against other renewable energy sources, the cost of offshore wind needs to come down to today's onshore cost. This cost reduction target can be achieved through optimising the offshore related operations which contribute the most to the operating expenditures (OPEX) of the offshore wind farms. In this paper, the investigation of optimum crew transfer vessel fleet, which indicates the influence of fleet size and characteristics of the vessels involved in the operations, is introduced with a focus on power production, total cost of the Operation and Maintenance (O&M) and revenue loss. A time domain Monte-Carlo approach is adopted while taking into consideration the climate parameters, failure characteristics of turbine components, the specification of crew transfer vessels, and the composition of vessel fleet. Through this extensive study, it is concluded the O&M related costs can be reduced significantly while the availability and the productivity of the turbines can be increased by optimising the use of the O&M vessel fleet in terms of fleet size and vessel capabilities.
Comparative Environmental Sustainability Assessment of Bio-Based Fibre Reinforcement Materials for Wind Turbine Blades
Authors: Corona A. , Markussen C.M. , Birkved M. , Madsen B.
Published: January 2015

Over the recent decades biomaterials have been marketed successfully supported by the common perception that biomaterials and environmental sustainability de facto represents two sides of the same coin. The development of sustainable composite materials for wind turbine blades for small-scale wind turbines have therefore partially been focused on substitution of conventional fibre materials with bio-fibres assuming that this substitution was in the better for the environment and human health. The major question is if this material substitution, taking into account a multitude of environmental impact categories, not only climate change, actually is supporting sustainable development or if the development of sustainable composite materials is more complex and perhaps even contra-intuitive due to complex trade-offs. Based on a case study 4 different types of fibres and fibre mixtures (flax, carbon, glass and flax/carbon, flax/glass mixed fibres) are compared in terms of environmental sustainability. Applying one of the most recent life cycle impact assessment methods, we demonstrate that the environmental sustainability of natural fibre based composite materials is similar or even lower, within certain impact categories, than the conventional materials. This observation may seem contra-intuitive (i.e. most people would expect the bio-based to be most sustainable), but is primarily caused by the fact that the resin demand of biobased reinforcement materials is by far larger than that of conventional reinforcement materials. Since the environmental burden of the resin in addition is comparable to that of the fibres (especially in terms human health related impacts), the higher resin demand counterbalances the environmental sustainability improvements, obtained with the application of natural fibres.
Backup Control of Wind Power Generation System Based on Voltage-Sensorless and LCL Active Damping Scheme
Authors: Zhang Jianwen , Wang Haisong , Wang Han , Zhu Miao , Cai Xu
Published: January 2015

Under the fault condition of voltage sensors, the wind power generation system requests an effective backup control scheme without voltage sensors. In order to save sensors for the grid-connected inverter (GCI) with LCL-filter in the full-scale wind power converter, a grid-side voltage-sensorless solution scheme is presented in this paper. A frequency-adaptive SOGI (FA-SOGI) is introduced to realize the virtual flux (VF) estimation. A grid-side voltage observer is thus designed to acquire the phase angle and amplitude, which can realize voltage orientation control (VOC) for the GCI system. With an improved feedback damping method for LCL filter, a full control strategy of the full-scale wind power generation system is given and explained in detail. All theoretical results have been validated by the simulation, followed by analysis and discussion.
Analysis and Control of Wind-Driven Stand-Alone Doubly-Fed Induction Generator with Reactive Power Support from Stator and Rotor Side
Authors: Sam K. Navin , Kumaresan N. , Gounden N. Ammasai , Katyal Rajesh
Published: January 2015

Hybrid-excited system has been formulated for the operation of wind-driven Doubly-Fed Induction Generators (DFIGs) for stand-alone power supplies. Here, apart from the rotor side excitation of DFIG employing SPWM inverter supplied through set of batteries, the generator is partially excited by fixed capacitor at the stator terminals. The steady-state equivalent circuit and its analysis for the proposed system have been devised and presented. The selection of stator capacitor has clearly been brought out. An attempt is also made for sizing of various components such as inverter and battery for the given machine rating and other operating conditions. Phasor diagram representation of the proposed system for typical operating conditions is also furnished. The stator voltage magnitude and frequency are maintained constant by closed loop control developed using TMS320LF2407A Digital Signal Processor (DSP) controller. Efficacy of the proposed hybrid-excited stand-alone DFIG system has been demonstrated under steady-state and dynamic operating conditions with experimental results obtained on a 3-phase, 4-pole, 415 V, 50 Hz, 5 kVA generator in the laboratory.
Flow-Sound Interaction Mechanisms in the Wake of Two Side-By-Side Cylinders
Authors: Arthurs David , Bolduc Michael , Ritcey Adam , Ziada Samir
Published: January 2015

The phenomenon of flow-excited acoustic resonance, where periodic flow oscillations are enhanced by a resonant sound field, is a design concern in many engineering applications such as in heat exchangers, piping systems, and cavity flows. This study experimentally examines the phenomenon of flow-excited acoustic resonance for two side-by-side cylinders in a duct with cross-flow. This geometry has been investigated for three cylinder spacing ratios, defined as the center-to-center distance between the cylinders normalized by their diameter, of T/D = 1.25, 1.46 and 2.5, and for a range of acoustic pressure amplitudes. Intermediate and small spacing ratios have been given special attention, as these cases have been found to exhibit bistable flow in the wake in the absence of acoustic resonance. Phase-locked PIV measurements reveal that the self-excited sound field produces a strong oscillatory flow pattern in the cylinder wakes, which is symmetric for large spacing ratios and high acoustic amplitudes, but remains bistable for small spacing ratios, even during very intense acoustic resonances. The aeroacoustic sources and sinks within the flow field, computed using Howe's theory of vortex sound, are compared for the range of spacing ratios and acoustic pressure amplitudes examined in this study.
Radiated Sound from a Circular Cylinder in a Turbulent Shear Layer
Authors: Bilka Michael J. , Kerrian Peter , Ross Mark H. , Morris Scott C.
Published: January 2015

The effect of turbulent approach flow on the radiated sound from a circular cylinder was studied experimentally. The approach flow turbulence was provided by a single stream shear layer produced by an open jet anechoic tunnel facility. An instrumented cylinder was used to measure steady and unsteady surface pressure. The sound radiated from the cylinder placed in both an irrotational approach flow and the highly turbulent approach flow of the shear-layer was measured and compared. The cylinders located within the shear layer produced a less tonal sound with a higher broadband amplitude when compared to that of the free-stream approach flow. Secondly, the radiated sound from cylinders of different diameters was investigated to assess the effect of the ratio of cylinder diameter to approach flow length scale. It was found that as this ratio decreased, the broadband sound levels decreased as well. A simple theoretical model was then used to provide a prediction of the radiated sound for the cylinder within the shear layer. The theoretical model used statistics of the velocity field of the approach shear layer and the radiated sound spectrum the cylinder placed in a free stream. It was found that this method provided a similar spectral shape to the measured radiated sound.
Flow Simulation and Aerodynamic Noise Prediction for a High-Speed Train Wheelset
Authors: Zhu J. Y. , Hu Z. W. , Thompson D. J.
Published: January 2015

Aerodynamic noise becomes significant for high-speed trains and its prediction in an industrial context is hard to achieve. The aerodynamic and aeroacoustic behaviour of the flow past a high-speed train wheelset, one of the main components of a bogie, are investigated at a scale 1:10 using a two-stage hybrid method of computational fluid dynamics and acoustic analogy. The near-field unsteady flow is obtained by solving the Navier-Stokes equations numerically through delayed detached-eddy simulations and the results are fed to predict the far-field noise signals using the Ffowcs Williams-Hawkings acoustic analogy. Far-field sound radiated from the scaled model is also measured in a low noise open-jet anechoic wind tunnel. Good agreement is achieved between numerical and experimental results for the dominant frequency of tonal noise and the shape of the spectra. Results show that turbulent flow past the wheelset is characterized by three-dimensional streamwise and spanwise vortices with various scales and orientations. Vortex shedding and flow separation around the wheelset are the key factors for the aerodynamic noise generation. It is found that the radiated tonal noise corresponds to the dominant frequencies of the oscillating lift and drag forces from the wheelset. The directivity of the noise radiated exhibits a typical dipole pattern. As the inflow velocity increases, the shedding frequency scales with the freestream velocity and the axle diameter to yield a Strouhal number of 0.18 while the noise levels increase noticeably. For the current wheelset case investigated without considering the ground effect, the inclusion of wheelset rotation increases the radiated noise levels slightly with similar directivity.
On a Generalized Multipole Expansion with Application to Propeller Design Synthesis
Authors: Campos L.M.B.C. , Lau F.J.P.
Published: January 2015

The radiation of sound by surfaces in motion in a non-uniform flow, including the effects of reflections from obstacles on noise, is specified by an extension of the Kirchhoff integral that leads to a generalized multipole expansion that extends the classical series of spherical harmonics to account for the effects of ( i) the moving medium and ( ii) the rotating sound sources. The corresponding radiation integrals are evaluated analytically for an arbitrary source distribution along the blades of a propeller at an angular inflow. The effects of the incident flow and propeller rotation on the amplitude and phase of sound, e.g. through the retarded time, lead to an extension of the generating function for Legendre polynomials; this provides the representation of the acoustic field as the generalized multipolar series. Each generalized multipole sound field is shown to consist of a fundamental blade passng frequency (BPF) plus all harmonics, with directivities specified by integrals of Bessel functions, that are evaluated analytically. The theory is validated by comparison with noise measurements using two different model propellers in two distinct aeroacoustic wind tunnels. The experimental results are used to illustrate the principle of propeller noise synthesis, relating the radiated sound field to the sound source distribution.
Structural basis for recognition of intron branchpoint RNA by yeast Msl5 and selective effects of interfacial mutations on splicing of yeast pre-mRNAs
Authors: Jacewicz Agata , Chico Lidia , Smith Paul , Schwer Beate , Shuman Stewart
Published: January 2015

Saccharomyces cerevisiae Msl5 orchestrates spliceosome assembly by binding the intron branchpoint sequence 5′-UACUAAC and, with its heterodimer partner protein Mud2, establishing cross intron-bridging interactions with the U1 snRNP at the 5′ splice site. Here we define the central Msl5 KH-QUA2 domain as sufficient for branchpoint RNA recognition. The 1.8 Å crystal structure of Msl5-(KH-QUA2) bound to the branchpoint highlights an extensive network of direct and water-mediated protein–RNA and intra-RNA atomic contacts at the interface that illuminate how Msl5 recognizes each nucleobase of the UACUAAC element. The Msl5 structure rationalizes a large body of mutational data and inspires new functional studies herein, which reveal how perturbations of the Msl5·RNA interface impede the splicing of specific yeast pre-mRNAs. We also identify interfacial mutations in Msl5 that bypass the essentiality of Sub2, a DExD-box ATPase implicated in displacing Msl5 from the branchpoint in exchange for the U2 snRNP. These studies establish an atomic resolution framework for understanding splice site selection and early spliceosome dynamics.
A new record of Actinobacteria isolated from soil in Jerusalem and their enzymatic potential
Authors: Mansour Samira R. , Abdel-Azeem Ahmed M. , Abo-Deraz Samy Salem Soliman
Published: January 2015

Actinobacteria are well recognized for their bioactive compounds.They are considered as a promising source of wide range of important enzymes, some of which are produced on an industrial scale. In this study, 35 isolates of actinomycetes were isolated from soil samples collected in the area of Al-Aqsa Mosque in Jerusalem, Israel. To our knowledge, this is the first study of actinomycetes from this terrestrial environment. The efficiency of the isolated actinobacteria in the production of amylase, cellulase, protease, tyrosinase, lipase, catalase and phosphatase was studied. Isolates obtained showed some activity and other completely failed to produce such enzymes. From total 35 isolates, only three isolates (8.6%) showed ability to produce protease, four isolates (11.4%) for lipase, five isolates (14.3%) for tyrosinase and two isolates (5.7%) for phosphatase enzymes. However, all isolates were positive for amylase and catalase enzymes; vice versa for cellulase enzyme all isolates failed to degrade cellulose in the form of carboxymethylcellulose.
Safety, efficacy and utility of methods of transferring adhesive and cohesive Escherichia coli cells to microplates to avoid aerosols
Authors: Ericksen Bryan
Published: January 2015

The virtual colony count (VCC) microbiological assay has been utilized for over a decade to measure the antimicrobial activity of peptides such as defensins and LL-37 against biosafety level (BSL)-1 and BSL-2 bacteria including Escherichia coli, Staphylococcus aureus, Bacillus cereus, and Enterobacter aerogenes.  In addition, a modified pipetting technique was presented in a 2011 study of defensin activity against the BSL-3 pathogen Bacillus anthracis.  Both studies were published in the journal Antimicrobial Agents and Chemotherapy.  Here I report that the method can also detect cross-contamination caused by aerosols utilizing the VCC method of data analysis by quantitative growth kinetics (QGK).  The QGK threshold time, or Tt, equivalent to the cycle time Ct reported in 1996 by Heid et al., precisely identifies when wells were inoculated.
Class, politics, gender and the marriage divide in the United States
Authors: Carbone June , Cahn Naomi
Published: January 2015

In this article we use the idea of the ‘marriage divide’ to describe the transformation of the family to meet the needs of the information economy and the divisions that the transformation has created. In doing so, we emphasise three types of ‘marriage divides’ in the United States: class and racial, ideological and political, and family law/gender ideology.
A Meta-Analysis of Electronic Word-of-Mouth Elasticity
Authors: You Ya , Vadakkepatt Gautham G. , Joshi Amit M.
Published: January 2015

The authors conduct a meta-analysis on the effect of electronic word of mouth on sales by examining 51 studies (involving 339 volume and 271 valence elasticities) and primary data collected on product characteristics (durability, trialability, and usage condition), industry characteristics (industry growth and competition), and platform characteristics (expertise and trustworthiness). Their analysis reveals that electronic word-of-mouth volume (valence) elasticity is .236 (.417). More importantly, the findings show that volume and valence elasticities are higher for privately consumed, low-trialability products that operate in less competitive industries and whose reviews are carried on independent review sites. Furthermore, volume elasticities are higher for durable goods and for reviews on specialized review sites, whereas valence elasticities are greater for community-based sites. Drawing on the results, they discuss several implications for managers and researchers and explain why valence elasticities are often found to be insignificant. Finally, they propose numerous directions for future research in the area on the basis of their findings.
Orientierungsschätzung mit einem Sliding Mode-Beobachter auf Basis Body Sensor Network-integrierter Inertialsensorik
Authors: Rüschen Daniel , Kim Saim , Leonhardt Steffen , J. E. Misgeld Berno
Published: January 2015

Dieser Beitrag beschreibt einen Sliding Mode-Beobachter, der auf einem Prozessmodell der menschlichen Bewegung basiert und dazu genutzt wird, die räumliche Orientierung von Körpersegmenten unter dynamischen Bedingungen zu bestimmen. Dazu kommt eine in ein Body Sensor Network integrierte Inertialsensorik zum Einsatz, mit der die Leistungsfähigkeit des Gesamtsystems in Laufband-Versuchen evaluiert wird.
Regelung eines Prüfstands für Beinprothesen
Authors: Gallinger Simon , Wulff Wulf , Thiele Julius , Kraft Marc
Published: January 2015

Zur Funktions- und Betriebsfestigkeitsprüfung moderner Beinprothesen für aktive amputierte Menschen wurde am Fachgebiet
Medizintechnik der TU Berlin ein servohydraulischer Prüfstand entwickelt. Mithilfe einer robusten, adaptiven Regelungsstragie ist
der Gangsimulator in der Lage, komplexe, hochdynamische Bewegungsabläufe mit Beinprothesen mit großer Genauigkeit
durchzuführen.
Prozessanalyse zur Ex-vivo Nierenperfusion – Fokus: Autoregulation
Authors: Gransow Marian , Koch Susanne , Tetschke Florian , Aschenbrenner Ulf , Thiele Christine , Malberg Hagen
Published: January 2015

Normotherme ex-vivo Nierenperfusion ist eine vielversprechende Technik zur Erhaltung und Bewertung der Vitalität und Viabilität von Organen. In diesem Beitrag wird eine qualitative Prozessanalyse durchgeführt und nierenspezifische Funktionalitäten werden aufgezeigt. Zusätzlich wird eine Methode vorgestellt, die Autoregulation einer isolierten ex-vivo perfundierten Niere automatisiert zu charakterisieren.
Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
Authors: Schröder Matthias , Arlt Olga , Schmidt Helmut , Huwiler Andrea , Angioni Carlo , Pfeilschifter Josef M. , Schwiebs Anja , Radeke Heinfried H.
Published: January 2015

FTY720 (Fingolimod; Gilenya®) is an immune-modulatory prodrug which, after intracellular phosphorylation by sphingosine kinase 2 (SphK2) and export, mimics effects of the endogenous lipid mediator sphingosine-1-phosphate. Fingolimod has been introduced to treat relapsing-remitting multiple sclerosis. However, little has been published about the immune cell membrane penetration and subcellular distribution of FTY720 and FTY720-P. Thus, we applied a newly established LC-MS/MS method to analyze the subcellular distribution of FTY720 and FTY720-P in subcellular compartments of spleen cells of wild type, SphK1- and SphK2-deficient mice. These studies demonstrated that, when normalized to the original cell volume and calculated on molar basis, FTY720 and FTY720-P dramatically accumulated several hundredfold within immune cells reaching micromolar concentrations. The amount and distribution of FTY720 was differentially affected by SphK1- and SphK2-deficiency. On the background of recently described relevant intracellular FTY720 effects in the nanomolar range and the prolonged application in multiple sclerosis, this data showing a substantial intracellular accumulation of FTY720, has to be considered for benefit/risk ratio estimates.
CCR2 Antagonism Alters Brain Macrophage Polarization and Ameliorates Cognitive Dysfunction Induced by Traumatic Brain Injury
Authors: Morganti Josh M. , Jopson Timothy D. , Liu Sharon , Riparip Lara-Kirstie , Guandique Cristian K. , Gupta Nalin , Ferguson Adam R. , Rosi Susanna
Published: January 2015

Traumatic brain injury (TBI) is a major risk factor for the development of multiple neurodegenerative diseases. With respect to the increasing prevalence of TBI, new therapeutic strategies are urgently needed that will prevent secondary damage to primarily unaffected tissue. Consistently, neuroinflammation has been implicated as a key mediator of secondary damage following the initial mechanical insult. Following injury, there is uncertainty regarding the role that accumulating CCR2+macrophages play in the injury-induced neuroinflammatory sequelae and cognitive dysfunction. UsingCX3CR1GFP/+CCR2RFP/+reporter mice, we show that TBI initiated a temporally restricted accumulation of peripherally derived CCR2+macrophages, which were concentrated in the hippocampal formation, a region necessary for learning and memory. Multivariate analysis delineated CCR2+macrophages' neuroinflammatory response while identifying a novel therapeutic treatment window. As a proof of concept, targeting CCR2+macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there was a significant reduction in multiple proinflammatory and neurotoxic mediators with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing of TBI-induced hippocampal-dependent cognitive dysfunction and reduced proinflammatory activation profile 1 month after injury. Thus, therapeutically targeting the CCR2+subset of monocytes/macrophages may provide a new avenue of clinical intervention following TBI.
Inflammasome-Induced IL-1β Secretion in Microglia Is Characterized by Delayed Kinetics and Is Only Partially Dependent on Inflammatory Caspases
Authors: Burm Saskia M. , Zuiderwijk-Sick Ella A. , ‘t Jong Anke E.J. , van der Putten Céline , Veth Jennifer , Kondova Ivanela , Bajramovic Jeffrey J.
Published: January 2015

Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1β (IL-1β). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques. We analyzed the expression profile of NOD (nucleotide-binding oligomerization domain)-like receptors, adaptor proteins, and caspases and characterized inflammasome activation and regulation in detail. We here demonstrate that primary microglia can respond to the same innate stimuli as hematopoietic macrophages. However, microglial responses are more persistent due to lack of negative regulation on pro-IL-1β expression. In addition, we show that while caspase 1, 4, and 5 activation is pivotal for inflammasome-induced IL-1β secretion by hematopoietic macrophages, microglial secretion of IL-1β is only partially dependent on these inflammatory caspases. These results identify key cell type-specific differences that may aid the development of strategies to modulate innate immune responses in the brain.
Hypoxia Silences Retrotrapezoid Nucleus Respiratory Chemoreceptors via Alkalosis
Authors: Basting Tyler M. , Burke Peter G.R. , Kanbar Roy , Viar Kenneth E. , Stornetta Daniel S. , Stornetta Ruth L. , Guyenet Patrice G.
Published: January 2015

In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (ΔfR) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔVT) followed the same trend. The effect of hypoxia on ΔfRwas not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). ΔfRwas highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN.
Motor Cortex Layer V Pyramidal Neurons Exhibit Dendritic Regression, Spine Loss, and Increased Synaptic Excitation in the Presymptomatic hSOD1G93AMouse Model of Amyotrophic Lateral Sclerosis
Authors: Fogarty Matthew J. , Noakes Peter G. , Bellingham Mark C.
Published: January 2015

Motor cortex layer V pyramidal neurons (LVPNs) regulate voluntary control of motor output and selectively degenerate (along with lower motor neurons) in amyotrophic lateral sclerosis. Using dye-filling and whole-cell patch clamping in brain slices, together with high-resolution spinning disk confocalz-stack mosaics, we characterized the earliest presymptomatic cortical LVPN morphologic and electrophysiological perturbations in hSOD1G93A(SOD1) mice to date. Apical dendritic regression occurred from postnatal day (P) 28, dendritic spine loss from P21, and increased EPSC frequency from P21 in SOD1 LVPNs. These findings demonstrate extensive early changes in motor cortex of the SOD1 mouse model, which thus recapitulates clinically relevant cortical pathophysiology more faithfully than previously thought.
Biomarkers of Traumatic Injury Are Transported from Brain to Blood via the Glymphatic System
Authors: Plog Benjamin A. , Dashnaw Matthew L. , Hitomi Emi , Peng Weiguo , Liao Yonghong , Lou Nanhong , Deane Rashid , Nedergaard Maiken
Published: January 2015

The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity.
Genetic regulation of murine pituitary development
Authors: Rizzoti Karine
Published: January 2015

Significant progress has been made recently in unravelling the embryonic events leading to pituitary morphogenesis, bothin vivoandin vitro. This includes dissection of the molecular mechanisms controlling patterning of the ventral diencephalon that regulate formation of the pituitary anlagen or Rathke's pouch. There is also a better characterisation of processes that underlie maintenance of pituitary progenitors, specification of endocrine lineages and the three-dimensional organisation of newly differentiated endocrine cells. Furthermore, a population of adult pituitary stem cells (SCs), originating from embryonic progenitors, have been described and shown to have not only regenerative potential, but also the capacity to induce tumour formation. Finally, the successful recapitulationin vitroof embryonic events leading to generation of endocrine cells from embryonic SCs, and their subsequent transplantation, represents exciting advances towards the use of regenerative medicine to treat endocrine deficits. In this review, an up-to-date description of pituitary morphogenesis will be provided and discussed with particular reference to pituitary SC studies.
Predictive Factors of Supraventricular Arrhythmias after Noncardiac Thoracic Surgery: A Multicenter Study
Authors: Elrakhawy Hany M. , Alassal Mohamed A. , Elsadeck Nabil , Shaalan Ayman , Ezeldin Tamer H. , Shalabi Ali
Published: January 2015

Background: Supraventricular cardiac arrhythmias are the most common rhythm disturbances in patients following thoracic surgery. The purpose of our study was to determine which of the clinical parameters are the most valuable in predicting postoperative atrial fibrillation (AF) after lung surgery.

Methods: Retrospective analysis was carried out on 987 patients after noncardiac thoracic surgery to define the prevalence, associated risk factors, and clinical course of postoperative arrhythmias. There were 822 men and 165 women, age 34 to 78 years (mean age: 61 � 8 years). The patients were divided into two groups depending on the occurrence or absence of supraventricular arrhythmia. Group I consisted of 876 patients who were free from rhythm disturbances. The remaining 111 patients exhibited episodes of supraventricular arrhythmia (29 supraventricular tachycardia; 82 AF). These 111 patients were placed in Group II. Preoperative, operative, and postoperative data were reviewed. Statistical analysis was performed.

Results: A statistically significant difference was found between the two groups in age, previous history of heart disease, and lung resection, especially pneumonectomy. Conclusion: Age, history of prior heart disease, lung resection, and the extent of pulmonary resection are the main risk factors for postoperative supraventricular arrhythmia in patients undergoing major thoracic operations.
Frontal Planar QRS/T Angle Can Be a Prognostic Factor in the Early Postoperative Period of Patients Undergoing Coronary Bypass Surgery
Authors: Karabacak Kubilay , Celik Murat , Gokoglan Yalcin , Kadan Murat , Kaya Erkan , Doganci Suat , Yildirim Vedat , Demirkilic Ufuk
Published: January 2015

Background: Wide QRS/T angle reflects the ventricular repolarization heterogeneity and has been found in association with cardiac morbidity and mortality in various study populations. However, literature data about the availability of QRS/T angle in patients undergoing cardiac surgery has not yet been available.

Methods: A total of 157 patients who underwent isolated coronary artery bypass surgery were included in this study. A preoperative 12-lead ECG was obtained one day before surgical procedure. The absolute difference between the frontal QRS wave axes and T-wave axes was defined as frontal planar QRS/T angle. Afterwards, patients were divided into two groups according to their frontal planar QRS/T angle (the cut-off value as 90�).

Results: Group 1 consisted of 109 patients with frontal planar QRS/T angle of <90, and the remaining 48 patients with frontal planar QRS/T angle 90 were placed into group 2. Mean EuroSCORE was much higher in group 2. There were significant differences for positive inotropic agent usage (27.5% for group 1 versus 58.3% for group 2, P < .001) and the prevalence of postoperative atrial fibrillation (11.9% for group 1 versus 31.2% for group 2, P = .004) between the two groups. In multivariate logistic regression analysis, used to determine the independent predictors of positive inotropic usage in the early postoperative period, only frontal planar QRS/T angle (OR: 0.989, 95% CI: 0.981-0.997, P = .008) and EuroSCORE (OR: 0.792, 95% CI: 0.646-0.971, P = .025) were found to be statistically significant.

Conclusion: We found that frontal planar QRS/T angle might be an important preoperative parameter in predicting the need for inotropic drugs in the early postoperative period following coronary artery bypass surgery.
Assessing Gene-Environment Interactions for Common and Rare Variants with Binary Traits Using Gene-Trait Similarity Regression
Authors: Zhao Guolin , Marceau Rachel , Zhang Daowen , Tzeng Jung-Ying
Published: January 2015

Accounting for gene–environment (G×E) interactions in complex trait association studies can facilitate our understanding of genetic heterogeneity under different environmental exposures, improve the ability to discover susceptible genes that exhibit little marginal effect, provide insight into the biological mechanisms of complex diseases, help to identify high-risk subgroups in the population, and uncover hidden heritability. However, significant G×E interactions can be difficult to find. The sample sizes required for sufficient power to detect association are much larger than those needed for genetic main effects, and interactions are sensitive to misspecification of the main-effects model. These issues are exacerbated when working with binary phenotypes and rare variants, which bear less information on association. In this work, we present a similarity-based regression method for evaluating G×E interactions for rare variants with binary traits. The proposed model aggregates the genetic and G×E information across markers, using genetic similarity, thus increasing the ability to detect G×E signals. The model has a random effects interpretation, which leads to robustness against main-effect misspecifications when evaluating G×E interactions. We construct score tests to examine G×E interactions and a computationally efficient EM algorithm to estimate the nuisance variance components. Using simulations and data applications, we show that the proposed method is a flexible and powerful tool to study the G×E effect in common or rare variant studies with binary traits.
The ways of implementing interactive methods in the educational process of students of higher educational institutions
Authors: Vaskov Y.V. , Sizonenko I.E.
Published: January 2015

Purpose : theoretical basis and practical implementation of interactive methods in the educational process of higher education institutions. Material : еhe study involved 50 students of the Kharkiv humanitarian-pedagogical Academy. Results : ыhowing the possibility of introducing interactive teaching method "Joint project." The theoretical study and practical implementation of the method is the process of inclusion of all students in the joint study group (in the form of small groups) work on mastering the content of teaching material. Also, the presentation of educational options to solve their own problems, discussion of the results of joint activities, making optimal decisions. Conclusions : еhe development of theoretical foundations and practical implementation of an interactive method improved the quality of the educational process of students. This is reflected in the involvement of all students in active joint work on learning. Also provide an opportunity for each student to express their own opinions on those tasks. This increased level of theoretical knowledge of each student.