Regulation of proteins mediating neurodegeneration in experimental autoimmune encephalomyelitis and multiple sclerosis

Multiple sclerosis is characterized by inflammatory demyelination and axonal loss as pathophysiological correlates of relapsing activity and progressive development of clinical disability. The molecular processes involved in this pathogenesis are still unclear as they are quite complex and heterogeneous. In this article we present protein expression analysis of brain and spinal cord tissues from different models of murine experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for multiple sclerosis. We observed a number of EAE-specific protein expression and PTM differences. Proteome analysis was extended to multiple sclerosis specimens in order to validate the EAE findings. Our findings suggest the regulation of a number of proteins that shed light on the molecular mechanisms of the disease processes taking place in EAE and multiple sclerosis. We found consistent modulation of proteins including serum amyloid P component, sirtuin 2, dihydropyrimidinase-related protein family proteins, stathmin 1, creatine kinase B and chloride intracellular channel protein 1. Functional classification of the proteins by database and the literature mining reveals their association with neuronal development and myelinogenesis, suggesting possible disease processes that mediate neurodegeneration.     

How can I help you? Design principles for task-oriented speech dialog systems in customer service

Organizations are increasingly delegating customer inquiries to speech dialog systems (SDSs) to save personnel resources. However, customers often report frustration when interacting with SDSs due to poorly designed solutions. Despite these issues, design knowledge for SDSs in customer service remains elusive. To address this research gap, we employ the design science approach and devise a design theory for SDSs in customer service. The design theory, including 14 requirements and five design principles, draws on the principles of dialog theory and undergoes validation in three iterations using five hypotheses. A summative evaluation comprising a two-phase experiment with 205 participants yields positive results regarding the user experience of the artifact. This study contributes to design knowledge for SDSs in customer service and supports practitioners striving to implement similar systems in their organizations.

     

In vitro studies of PDR brachytherapy

BACKGROUND: Calculations on the basis of the LQ-model have been focussed on the possible radiobiological equivalence between common continuous low dose rate irradiation (CLDR) and a superfractionated irradiation (PDR = pulsed dose rate) provided that the same total dose will be prescribed in the same overall time as with the low doserate. A clinically usable fractionation scheme for brachytherapy was recommended by Brenner and Hall and should replace the classical CLDR brachytherapy with line sources with an afterloading technique using a stepping source. The hypothes is that LDR equivalency can be achieved by superfractionation was tested by means of in vitro experiments on V79 cells in monolayer and spheroid cultures as well as on HeLa monolayers. MATERIALS AND METHODS: Simulating the clinical situation in PDR brachytherapy, fractionation experiments were carried out in the dose rate gradient of afterloading sources. Different dose levels were produced with the same number of fractions in the same overall incubation time. The fractionation schedules which were to be compared with a CLDR reference curve were: 40 x 0.47 Gy, 20 x 0.94 Gy, 10 x 1.88 Gy, 5 x 3.76 Gy, 2 x 9.4 Gy given in a period of 20 h and 1 x 18.8 Gy as a "single dose" exposition. As measured by flow cytometry, the influence of the dose rate in the pulse on cell survival and on cell cycle distribution under superfractionation was examined on V79 cells. RESULTS: V79 spheroids as a model for a slowly growing tumor, reacted according to the radiobiological calculations, as a CLDR equivalency was achieved with increasing fractionation. Rapidly growing V79 monolayer cells showed an inverse fractionation effect. A superfractionated irradiation with pulses of 0.94 Gy/h respectively 0.47 Gy/0.5 h was significantly more effective than the CLDR irradiation. This inverse fractionation effect in log-phase V79 cells could be attributed to the accumulation of cycling cells in the radiosensitive G2/M phase (G2 block) during protected exposure which was drastically more pronounced for the pulsed scheme. HeLa cells were rather insensitive to changes of fractionation. Superfractionation as well as hypofractionation yielded CLDR equivalent survival curves. CONCLUSIONS: The fractionation scheme, derived from the PDR theory to achieve CLDR equivalent effects, is valid for many cell lines, however not for all. Proliferation and dose rate dependend cell cycle effects modify predictions derived from the sublethal damage recovery model and can influence acute irradiation effects significantly. Dose rate sensitivity and rapid proliferation favour cell cycle effects and substantiate, applied to the clinical situation, the possibility of a higher effectiveness of the pulsed irradiation on rapidly growing tumors.     

How can the success of a glaucoma operation be predicted?

PURPOSE: The effect of glaucoma surgery can simply be measured in terms of intraocular pressure (IOP) reduction. However, IOP reduction is not the final goal of glaucoma surgery, but rather long-term visual field preservation. Visual field preservation, on the other hand, can only be judged many years after surgery. Therefore, a formula that could be used to define the success of a pressure-lowering operation soon after surgery should take account of IOP reduction, but the correlation between "successful IOP reduction" and "long-term visual field preservation" should be as high as possible. METHODS: In an attempt to find such a formula, we examined the long-term course with reference to both IOP and visual field in 108 patients (mean follow-up 7.9 years). Several criteria were tested for their ability to predict the long-term visual field preservation. RESULT: The best correlation was obtained by a combined criterion specifying both an absolute upper limit and a relative IOP decrease (i.e. IOP postoperatively < 0.8*IOP preoperatively and IOP postoperatively < 21 mmHg). CONCLUSION: We recommend use of this criterion whenever the effect of a pressure-lowering operation has to be estimated shortly after surgery.     

Integratable non-clogging microconcentrator based on counter-flow principle for continuous enrichment of CaSki cells sample

This study addresses the need to reduce the risk of clogging when preparing samples for cell concentration, i.e., the CaSki Cell-lines (epidermoid cervical carcinoma cells). Aiming to develop a non-clogging microconcentrator, we proposed a new counter-flow concentration unit characterized by the directions of penetrating flows being at an obtuse angle to the main flow, due to employment of streamlined turbine blade-like micropillars. Based on the optimization results of the counter-flow unit profile, a fractal arrangement for the counter-flow concentration unit was developed. A counter-flow microconcentrator chip was then designed and fabricated, with both the processing layer and collecting layer arranged in terms of the honeycomb structure. Visualized experiments using CaSki cell samples on the microconcentrator chip demonstrated that no cell-clogging phenomena occurred during the test and that no cells were found in the final filtrate. The test results show an excellent concentration performance for the microconcentrator chip, while a concentrating ratio of >4 with the flow rate being below 1.0 ml/min. As only geometrical structure is employed in the passive device, the counter-flow microconcentrator can be easily integrated into advanced microfluidic systems. Owing to the merit of non-clogging and continuous processing ability, the counter-flow microconcentrator is not only suitable for the sample preparation within biomedical field, but also applicable in water-particle separation.     

Editorial: Special issue on approximate dynamic programming and reinforcement learning

We are extremely pleased to present this special issue of the Journal of Control Theory and Applications.Approximate dynamic programming (ADP) is a general and effective approach for solving optimal control and estimation problems by adapting to uncertain environments over time.ADP optimizes the sensing objectives accrued over a future time interval with respect to an adaptive control law,conditioned on prior knowledge of the system,its state,and uncertainties.A numerical search over the present value of the control minimizes a Hamilton-Jacobi-Bellman (HJB) equation providing a basis for real-time,approximate optimal control.     

RF/wireless-interconnect: The next wave of connectivity

In the era of the nanometer CMOS technology, due to stringent system requirements in power, performance and other fundamental physical limitations (such as mechanical reliability, thermal constraints, overall system form factor, etc.), future VLSI systems are relying more on ultra-high data rates (up to 100 Gbps/pin or 20 Tbps aggregate), scalable, re-configurable, highly compact and reliable interconnect fabric. To overcome such challenges, we first explore the use of multiband RF/wireless-interconnects wh...     

GeodesicViewer - A tool for exploring geodesics in the theory of relativity

The GeodesicViewer realizes exocentric two- and three-dimensional illustrations of lightlike and timelike geodesics in the general theory of relativity. By means of an intuitive graphical user interface, all parameters of a spacetime as well as the initial conditions of the geodesics can be modified interactively. This makes the GeodesicViewer a useful instrument for the exploration of geodesics in four-dimensional Lorentzian spacetimes.

Program summary

Program title: GeodesicViewerCatalogue identifier: AEFP_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEFP_v1_0.htmlProgram obtainable from: CPC Program Library, Queen's University, Belfast, N. IrelandLicensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.htmlNo. of lines in distributed program, including test data, etc.: 168 868No. of bytes in distributed program, including test data, etc.: 6 076 202Distribution format: tar.gzProgramming language: C++, Qt, Qwt, OpenGLComputer: All platforms with a C++ compiler, Qt, Qwt, OpenGLOperating system: Linux, Mac OS XRAM: 24 MbytesClassification: 1.5External routines:

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Gnu Scientific Library (GSL) (http://www.gnu.org/software/gsl/)

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Motion4D (included in the package). The Motion4D library can also be downloaded from CPC. Catalogue identifier: AEEX

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Qt (http://qt.nokia.com/downloads)

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Qwt (http://qwt.sourceforge.net/)

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OpenGL (http://www.opengl.org/)

Nature of problem: Illustrate geodesics in four-dimensional Lorentzian spacetimes.Solution method: Integration of ordinary differential equations. 3D-Rendering via OpenGL.Running time: Interactive. The examples given take milliseconds.     

Evaluation of artery visualizations for heart disease diagnosis

Heart disease is the number one killer in the United States, and finding indicators of the disease at an early stage is critical for treatment and prevention. In this paper we evaluate visualization techniques that enable the diagnosis of coronary artery disease. A key physical quantity of medical interest is endothelial shear stress (ESS). Low ESS has been associated with sites of lesion formation and rapid progression of disease in the coronary arteries. Having effective visualizations of a patient's ESS data is vital for the quick and thorough non-invasive evaluation by a cardiologist. We present a task taxonomy for hemodynamics based on a formative user study with domain experts. Based on the results of this study we developed HemoVis, an interactive visualization application for heart disease diagnosis that uses a novel 2D tree diagram representation of coronary artery trees. We present the results of a formal quantitative user study with domain experts that evaluates the effect of 2D versus 3D artery representations and of color maps on identifying regions of low ESS. We show statistically significant results demonstrating that our 2D visualizations are more accurate and efficient than 3D representations, and that a perceptually appropriate color map leads to fewer diagnostic mistakes than a rainbow color map.