Repetitive Application Research Articles

Chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in rats.

BackgroundPreclinical experimental studies revealed an acute alteration of pituitary adenylate cyclase-activating polypeptide in response to a single activation of the trigeminovascular system, which suggests a potential role of pituitary adenylate cyclase-activating polypeptide in the pathogenesis of migraine. However, changes in pituitary adenylate cyclase-activating polypeptide after repeated migraine-like attacks in chronic migraine are not clear. Therefore, the present study investigated chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulations in the rat.MethodsA rat model of chronic migraine was established by repeated chemical dural stimulations using an inflammatory soup for a different numbers of days. The pituitary adenylate cyclase-activating polypeptide levels were quantified in plasma, the trigeminal ganglia, and the trigeminal nucleus caudalis using radioimmunoassay and Western blotting in trigeminal ganglia and trigeminal nucleus caudalis tissues. Western blot analysis and real-time polymerase chain reaction were used to measure the protein and mRNA expression of pituitary adenylate cyclase-activating polypeptide-related receptors (PAC1, VPAC1, and VPAC2) in the trigeminal ganglia and trigeminal nucleus caudalis to identify changes associated with repetitive applications of chemical dural stimulations.ResultsAll rats exhibited significantly decreased periorbital nociceptive thresholds to repeated inflammatory soup stimulations. Radioimmunoassay and Western blot analysis demonstrated significantly decreased pituitary adenylate cyclase-activating polypeptide levels in plasma and trigeminal ganglia after repetitive chronic inflammatory soup stimulation. Protein and mRNA analyses of pituitary adenylate cyclase-activating polypeptide-related receptors demonstrated significantly increased PAC1 receptor protein and mRNA expression in the trigeminal ganglia, but not in the trigeminal nucleus caudalis, and no significant differences were found in the expression of the VPAC1 and VPAC2 receptors.ConclusionsThis study demonstrated the chronic alteration of pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in the rat, which suggests the crucial involvement of pituitary adenylate cyclase-activating polypeptide in the development of migraine. The selective increase in pituitary adenylate cyclase-activating polypeptide-related receptors suggests that the PAC1 receptor pathway is a novel target for the treatment of migraine.

Prophylactic topical paeoniflorin prevents mechanical allodynia caused by paclitaxel in mice through adenosine A1 receptors

BackgroundThe chemotherapeutic agent paclitaxel (PTX) causes refractory peripheral neuropathy as a side effect. Prophylactic oral administration of the traditional herbal medicine Shakuyakukanzoto containing Paeoniae Radix and Glycyrrhizae Radix prevents the development of PTX-induced mechanical allodynia in mice via peripheral effects, mostly due to Paeoniae Radix. However, the bioactive component responsible for the prevention of PTX-induced neuropathic pain remains unknown. PurposeTo determine whether a monoterpene glycoside paeoniflorin (PF), which is the principal bioactive constituent of Paeoniae Radix, has inhibitory effects on PTX-induced mechanical allodynia and investigate the underlying mechanisms. MethodsC57BL/6NCr mice received a single intraperitoneal injection of PTX and then were topically administered PF to the planar surface twice daily for 13 days. Mechanical allodynia was evaluated by the von Frey filament test, peripheral nerve activity was recorded using bipolar electrodes, and demyelination in peripheral nerves was analysed by electron microscopy. Schwann cell line LY-PPB6 pre-treated with PF and then treated with PTX was used to analyse the expression of the transcription factor CHOP, a marker of endoplasmic reticulum (ER) stress, by western blotting. ResultsPTX caused mechanical allodynia and increased both spontaneous and mechanical stimuli-evoked peripheral nerve activities, whereas repetitive topical application of PF significantly attenuated PTX-induced allodynia, suppressed saphenous nerve firing, and inhibited demyelination in the plantar nerve. Moreover, in cultured Schwann cells, PF downregulated PTX-induced expression of CHOP, indicating the inhibition of ER stress. The attenuation of mechanical allodynia in mice and downregulation of CHOP levels in cell cultures was inhibited by adenosine A1 receptor (A1R) antagonist 8-cyclopentyl-1,3-diprooylxanrhine, suggesting the involvement of A1R in PF-associated analgesic effects. ConclusionThese results suggest that prophylactic topical application of PF is effective in alleviating PTX-induced mechanical allodynia by protecting sensory nerves from demyelination via activation of the A1R.

A unifying hypothesis for M1 muscarinic receptor signalling in pyramidal neurons.

Phasic release of acetylcholine (ACh) in the neocortex facilitates attentional processes. Acting at a single metabotropic receptor subtype, ACh exerts two opposing actions in cortical pyramidal neurons: transient inhibition and longer-lasting excitation. Cholinergic inhibitory responses depend on calcium release from intracellular calcium stores, and run down rapidly at resting membrane potentials when calcium stores become depleted. We demonstrate that cholinergic excitation promotes calcium entry at subthreshold membrane potentials to rapidly refill calcium stores, thereby maintaining the fidelity of inhibitory cholinergic signalling. We propose a 'unifying hypothesis' for M1 receptor signalling whereby inhibitory and excitatory responses to ACh in pyramidal neurons represent complementary mechanisms governing rapid calcium cycling between the endoplasmic reticulum, the cytosol and the extracellular space. Gq -coupled M1-type muscarinic acetylcholine (ACh) receptors (mAChRs) mediate two distinct electrophysiological responses in cortical pyramidal neurons: transient inhibition driven by calcium-dependent small conductance potassium ('SK') channels, and longer-lasting and voltage-dependent excitation involving non-specific cation channels. Here we examine the interaction of these two cholinergic responses with respect to their contributions to intracellular calcium dynamics, testing the 'unifying hypothesis' that rundown of inhibitory SK responses at resting membrane potentials (RMPs) reflects depletion of intracellular calcium stores, while mAChR-driven excitation acts to refill those stores by promoting voltage-dependent entry of extracellular calcium. We report that fidelity of cholinergic SK responses requires the continued presence of extracellular calcium. Inhibitory responses that diminished after repetitive ACh application at RMPs were immediately rescued by pairing mAChR stimulation with subthreshold depolarization (∼10mV from RMPs) initiated with variable delay (up to 500ms) after ACh application, but not by subthreshold depolarization preceding mAChR stimulation. Further, rescued SK responses were time-locked to ACh application, rather than to the timing of subsequent depolarizing steps, suggesting that cholinergic signal transduction itself is not voltage-sensitive, but that depolarization facilitates rapid cycling of extracellular calcium through the endoplasmic reticulum to activate SK channels. Consistent with this prediction, rescue of SK responses by subthreshold depolarization required the presence of extracellular calcium. Our results demonstrate that, in addition to gating calcium release from intracellular stores, mAChR activation facilitates voltage-dependent refilling of calcium stores, thereby maintaining the ongoing fidelity of SK-mediated inhibition in response to phasic release of ACh.

A Modular High-Voltage Pulse-Generator With Sequential Charging for Water Treatment Applications

High-voltage pulse-generators can be used effectively for bacterial decontamination in water treatment applications. Applying a pulsed electric field to the infected water sample guarantees killing of harmful germs and bacteria. In this paper, a modular high-voltage pulse-generator with sequential charging is proposed for water treatment via underwater pulsed streamer corona discharge. The proposed generator consists of series-connected modules similar to an arm of a modular multilevel converter. The modules’ capacitors are charged sequentially from a relatively low-voltage dc supply, then they are connected in series and discharged into the load. Two configurations are proposed in this paper, one for low repetitive pulse rate applications, and the other for high repetitive pulse rates. In the first topology, the equivalent resistance of the infected water sample is used as a charging resistance for the generator’s capacitors during the charging process. While in the second topology, the water resistance is bypassed during the charging process, and an external charging resistance with proper value is used instead. In this paper, detailed designs for the proposed pulse-generators are presented and validated by simulation results using MATLAB. A scaled down experimental setup has been built to show the viability of the proposed concept.

Simplified analysis of sub-wavelength triangular gratings by simplified modal method.

A phase-equivalence of a triangular grating and a "corresponding" blazed structure is proposed. This equivalence is used to simplify the analysis of the grating, which otherwise would require the repetitive application of the simplified modal method to each lamellar grating that constitutes the triangular grating. The concept is used to arrive at an equation for the phase introduced by the triangular grating. The proposed model is verified by finite element simulations. A method of fabricating a triangular grating in quartz is presented. The proposed theory, along with optical testing, can be used as a non-destructive means by which to estimate the height of the triangular grating during the dry etching process.

Release of heavy metals during long-term land application of sewage sludge compost: Percolation leaching tests with repeated additions of compost

Leaching assessment procedures have been used to determine the leachability of heavy metals as input for evaluating the risk from sewage sludge compost land application. However, relatively little attention has been paid to understanding leaching from soils with repeated application of sewage sludge compost with elevated levels of heavy metals. In this paper, leaching assessment is extended to evaluate the potential leaching of heavy metals during repetitive application of composted sewage sludge to soils. Four cycling of compost additions and percolation leaching were conducted to investigate how leaching behavior of heavy metals changed with repeated additions of compost. Results showed that repetitive additions of compost to soil significantly increased the content of organic matter, which favored the formation of reducing condition due to improved microbial activities and oxygen consumption. Establishment of reducing conditions can enhance the leaching concentrations of As by approximately 1 order of magnitude, especially for the soil rich in organic matter. For Cd, Cr, Cu, and Pb, repeated additions of compost will cause accumulation in total contents but not enhancement in leaching concentrations. The infiltration following compost additions will leach out the mobile fraction and the residual fraction might not release in the next cycling of compost addition and infiltration. The cumulative release of Cd, Cr, Cu, and Pb accounted for less than 5% of the total contents during four times of compost applications.

Pilot-scale removal and recovery of dissolved phosphate from secondary wastewater effluents with reusable ZnFeZr adsorbent @ Fe3O4/SiO2 particles with magnetic harvesting

Advanced nanocomposite magnetic particles functionalized with ZnFeZr-adsorbent are developed, characterized and tested for the removal and recovery of phosphate directly from spiked secondary wastewater effluent (∼10 mg/L PO4–P). The phosphate loaded particles can be extracted from the liquid phase via magnetic separation, regenerated in a NaOH solution where phosphate desorption takes place, and reused in numerous cycles. Laboratory experiments demonstrate their reusability and stability in 60 consecutive adsorption/desorption runs where under optimal conditions > 90% total P-recovery efficiency is reached. In addition, pilot tests are performed to verify the proof-of-concept by upscaling the technology and maintain high efficiency of phosphate removal and recovery after treating 1.5 m3 wastewater in 20 cycles. Effluent concentrations <0.05 mg/L PO4–P can be achieved in the treated wastewater. The reclaimed desorption solution is concentrated with phosphate ions through its repetitive application, attaining up to 38-times enrichment (∼380 mg/L PO4–P) compared to the initial concentration in wastewater. The P-rich eluate is used as a source for subsequent precipitation of a solid fertilizer product such as struvite.

Combined maceration procedure permits advanced microsurgical dissection of Thiel-embalmed specimens

IntroductionDue to the realistic colour, texture conservation and preservation of biomechanical properties, Thiel-embalming is becoming the main embalming procedure for clinical courses and research based on human cadaver material. The aim of this study is to establish a new procedure that allows advanced microdissection of small vessels and intraorganic nerves in Thiel-embalmed material. Material and methods/resultsAfter a classical gross anatomical dissection, human hemipelves underwent repetitive application of 3 consecutive steps: (i) maceration with alloy of nitric acid and MiliQ water 1:10 for 24–48h. (ii) Immersion: the hemipelves were rinsed under tap water for 20–30min. and placed in a water bath for 1h. The nerves become more prominent due to the swelling and increased water content. (iii) microdissection under surgical microscope. To facilitate the organ visualization perfusion with polyurethane (Pu4ii, VasQtec®, Switzerland) in red/blue for arteries/veins respectively has been performed. ConclusionBy using the proposed procedure, we performed satisfactory microdissection on Thiel-embalmed samples. The combination with polyurethane vascular casting permits visualization of small arterioles and venules in a range of 20–25μm. The method is very suitable for demonstration of somatic and vegetative nerves. Branches of the sacral plexuses and autonomic nerves from the superior and inferior hypogastric plexus have been tracked up to the smallest intraorganic branches in a range of 12.5–15μm.In conclusion, the established combined procedure offers a new possibility for advanced microdissection, which will allow acquisition of clinically relevant information about organ specific micro- vascularization and innervation.

A high-power subterahertz surface wave oscillator with separated overmoded slow wave structures**Project supported by the National Natural Science Foundation of China (Grant No. 61231003).

A megawatt-level subterahertz surface wave oscillator (SWO) is proposed to obtain high conversion efficiency by using separated overmoded slow wave structures (SWSs). Aiming at the repetitive operation and practical applications, the device driven by electron beam with modest energy and current is theoretically analyzed and verified. Then, the functions of the two SWS sections and the effect of the drift tube are investigated by using a particle-in-cell code to reveal how the proposed device achieves high efficiency. The mode analysis of the beam-wave interaction region in the device is also carried out, and the results indicate that multi-modes participate in the premodulation of the electron beam in the first SWS section, while the TM01 mode surface wave is successfully and dominantly excited and amplified in the second SWS section. Finally, a typical simulation result demonstrates that at a beam energy of 313 keV, beam current of 1.13 kA, and guiding magnetic field of above 3.5 T, a high-power subterahertz wave is obtained with an output power of about 70 MW at frequency 146.3 GHz, corresponding to the conversion efficiency of 20%. Compared with the results of the previous subterahertz overmoded SWOs with integral SWS and similar beam parameters, the efficiency increases almost 50% in the proposed device.

Non-target effect of continuous application of chlorpyrifos on soil microbes, nematodes and its persistence under sub-humid tropical rice-rice cropping system

Application of pesticide in agricultural fields is “unnecessary evil” for non-target microflora and fauna. Hence, to identify the safer pesticide molecules against non-target microbes, a long-term pesticide experiment was initiated at National Rice Research Institute, Cuttack, India. In the present study, the effect of continuous application of chlorpyrifos (0.5kgha−1) in rice fields on non-target groups of soil microbes and nematodes was studied for seven seasons (four wet and three dry seasons) during 2009–2013. Treatments were arranged in a randomized complete block design with four replications of chlorpyrifos-treated (0.5kg a.i. ha−1) (CT) and untreated control (UT) plots. During seven seasons of experimentation, regular application of chlorpyrifos had no significant effect on population of heterotrophic aerobic, anaerobic, oligotrophic and copiotrophic bacteria in CT compared to UT, whereas, population of asymbiotic aerobic nitrogen fixer, nitrifiers, denitrifiers, gram positive and spore-forming bacteria were significantly reduced by nearly 0.25–2 fold in CT than UT. However, comparatively less deviation in population of actinomycetes, fungi, phosphate solubilizing and sulfur oxidizing bacteria were observed in CT than UT. Significant interactions were found between effects of chlorpyrifos with time in population dynamics of microbes. In plant parasitic nematode species, Meloidogyne graminicola (RRKN) and Hirschmanniella spp. (RRN), were significantly lower (p<0.01) in CT compared to UT after first year onwards. The overall observation of five years data indicated that the RRKN population showed a decreasing trend (R2=0.644) whereas RRN showed increasing trend (R2=0.932) in CT. The drastic chlorpyrifos dissipation was noticed after 15 days of application from the initial residue of 0.25mgkg−1 soil, which indicated that chlorpyrifos residue in rice field soil was not persistent and its half-life was found to be 4.02 days. Overall, the present findings revealed that non-target effect of repetitive application of chloropyrifos (0.5kgha−1) on soil microbes and nematodes was found less under rice-rice cropping system.

Düşük doz risperidon tedavisine yanıt veren delüzyonel parazitoz vakası

Delusional parasitosis is a somatic type delusional disorder encountered in presenile women who suffer from a fixed false belief that they are infested with parasites. Despite a detailed examination and assurance, patients are not convinced that they have no parasitic infection. Repetitive applications and tests increases the treatment cost very much. In this article, we present a 76 years-old woman who had persistent thoughts about being infested by parasites for two years, and made deep scars widely distributed on her body, and was refusing any psychiatric diagnosis. Our aim was to draw attention to the delusional disorder which was a rare disease with poor prognosis, and to report results of low dose risperidone treatment with favorable outcomes of given psycho-education to the patient and her family.

Cathepsin G Controls Arterial But Not Venular Myeloid Cell Recruitment.

Therapeutic targeting of arterial leukocyte recruitment in the context of atherosclerosis has been disappointing in clinical studies. Reasons for such failures include the lack of knowledge of arterial-specific recruitment patterns. Here we establish the importance of the cathepsin G (CatG) in the context of arterial myeloid cell recruitment. Intravital microscopy of the carotid artery, the jugular vein, and cremasteric arterioles and venules in Apoe-/-and CatG-deficient mice (Apoe-/-Ctsg-/-) was used to study site-specific myeloid cell behavior after high-fat diet feeding or tumor necrosis factor stimulation. Atherosclerosis development was assessed in aortic root sections after 4 weeks of high-fat diet, whereas lung inflammation was assessed after inhalation of lipopolysaccharide. Endothelial deposition of CatG and CCL5 was quantified in whole-mount preparations using 2-photon and confocal microscopy. Our observations elucidated a crucial role for CatG during arterial leukocyte adhesion, an effect not found during venular adhesion. Consequently, CatG deficiency attenuates atherosclerosis but not acute lung inflammation. Mechanistically, CatG is immobilized on arterial endothelium where it activates leukocytes to firmly adhere engaging integrin clustering, a process of crucial importance to achieve effective adherence under high-shear flow. Therapeutic neutralization of CatG specifically abrogated arterial leukocyte adhesion without affecting myeloid cell adhesion in the microcirculation. Repetitive application of CatG-neutralizing antibodies permitted inhibition of atherogenesis in mice. Taken together, these findings present evidence of an arterial-specific recruitment pattern centered on CatG-instructed adhesion strengthening. The inhibition of this process could provide a novel strategy for treatment of arterial inflammation with limited side effects.

Algorithmic Differentiation for Callable Exotics

In this article, we study the algorithmic calculation of present values greeks for callable exotic instruments. The speed of greeks evaluations becomes important with recent initial margin rules, including the ISDA standard model SIMM, requiring sensitivity calculations for non-cleared deals (e.g. callable exotic/structured products) for a large set of risk factors and on a daily basis.In general, present values of callable trades are obtained by the backward repetitive application of conditional expectation via least-squares Monte Carlo (regression) and arithmetic operations encoded in so called pricing (payoff) script. By nature, this pricing procedure is known to be computationally intensive leading to very slow greeks, if computed by a simple bump-and-reprice. The fast alternative is the adjoint differentiation (AD) method. However, a direct application of the AD is not straightforward because regressions introduce path interdependency, whereas traditional AD is applied on a path-by-path basis. We describe how to extend the traditional AD method to include the regressions. Usually, the procedure must include the recording of information in a data structure, often referred to as the instrument tape, during the backward pricing. This is followed by a subsequent playback of the tape in which the recorded information is used to compute the greeks. The tape adds a significant complexity to the AD implementation and can introduce memory issues (due to the significant storage demands), coding and debugging difficulties, etc.Next, we propose a new tapeless differentiation method, called backward differentiation (BD), for exotic deals. It is applied during the backward pricing procedure following the payoff script. Importantly, it completely avoids the tape and all of its related complications.We demonstrate the efficiency of the BD on the example of a Bermudan swaption calculated with a one-factor Hull-White model. For 50-100 greeks, the BD calculation time is only 2-6 times slower than a single pricing which leads to up 20 times acceleration with respect to the bump-and-reprice. We also give a numerical convergence analysis demonstrating the high quality of the BD greeks.

Options of biological substances application in rectal fistulas treatment (Review of the literature)

Aim of review. To present literature data of the treatment of incomplete rectal fistulas with application of biological substances. Summary. Treatment of rectal fistulas remains burning issue in coloproctology due to unsatisfactory results of surgery resulting in high relapse rate, usually regardless of applied surgical method and high risk of severe complications as anal sphincter incompetence. This is why development of sparing methods of rectal fistula treatment that will allow to decrease intraoperative trauma of the anal sphincter at minimal risk of disease recurrence and, therefore, to prevent development of sphincter incompetence is important. Application of biological materials in rectal fistulas treatment result in reduction of the wound size, accelerates reparative processes and decreases degree of traumatization. Minimization of surgical impact on the anal sphincter allows repetitive application of biological materials up to the achievement of positive effect. Conclusion. Application of biological materials at sphincter-preserving technique provides decreased risk of development of postoperative anal sphincter incompetence.

Meta-learning recommendation of default size of classifier pool for META-DES

Dynamic ensemble selection (DES) is a mechanism for selecting an ensemble of competent classifiers from a pool of base classifiers, in order to classify a particular test sample. The size of this pool is user-defined, and yet is crucial for controlling the computational complexity and performance of a DES. An appropriate pool size depends on the choice of base classifiers, the underlying DES method used, and more importantly, the characteristics of the given problem. After the DES method and the base classifiers are selected, an appropriate pool size for a given problem can be obtained by the repetitive application of the DES with a variety of sizes, after which a selection is performed. Since this brute force approach is computationally expensive, researchers set the pool size to a pre-specified value. This strategy, may, however further complicate and reduce the performance of the DES method. Instead, we propose a framework that is akin to meta-learning, in order to predict a suitable pool size based on the intrinsic classification complexity of a problem. In our strategy, we collect meta-features corresponding to classification complexity from a number of data sets. Additionally, we obtain the best pool sizes for these data sets using the brute force approach. The association between these two pieces of information is captured using meta-regression models. Finally, for an unseen problem, we predict the pool size using this model and the classification complexity information. We carry out experiments on 65 two-class data sets and with a recent DES method, namely, META-DES. We also consider variants of meta-regression techniques and report prediction results, after which we carry out a statistical comparison among them. Moreover, we investigate the performance of META-DES and observe that it performs equivalently for both the predicted and the best pool sizes.

The Geometry of Plasticity-Induced Sensitization in Isoinhibitory Rate Motifs.

A well-known phenomenon in sensory perception is desensitization, wherein behavioral responses to persistent stimuli become attenuated over time. In this letter, our focus is on studying mechanisms through which desensitization may be mediated at the network level and, specifically, how sensitivity changes arise as a function of long-term plasticity. Our principal object of study is a generic isoinhibitory motif: a small excitatory-inhibitory network with recurrent inhibition. Such a motif is of interest due to its overrepresentation in laminar sensory network architectures. Here, we introduce a sensitivity analysis derived from control theory in which we characterize the fixed-energy reachable set of the motif. This set describes the regions of the phase-space that are more easily (in terms of stimulus energy) accessed, thus providing a holistic assessment of sensitivity. We specifically focus on how the geometry of this set changes due to repetitive application of a persistent stimulus. We find that for certain motif dynamics, this geometry contracts along the stimulus orientation while expanding in orthogonal directions. In other words, the motif not only desensitizes to the persistent input, but heightens its responsiveness (sensitizes) to those that are orthogonal. We develop a perturbation analysis that links this sensitization to both plasticity-induced changes in synaptic weights and the intrinsic dynamics of the network, highlighting that the effect is not purely due to weight-dependent disinhibition. Instead, this effect depends on the relative neuronal time constants and the consequent stimulus-induced drift that arises in the motif phase-space. For tightly distributed (but random) parameter ranges, sensitization is quite generic and manifests in larger recurrent E-I networks within which the motif is embedded.

Timing Analysis of Robotic Neuromodulatory Rehabilitation System for Paired Associative Stimulation

In this paper, the timing accuracy of a tapping motion is analyzed for a robotic neuromodulatory rehabilitation system (RNRS). Paired associative stimulation (PAS) refers to repetitive application of conditioned transcranial magnetic stimulation (TMS) with peripheral stimulation at appropriate interstimulus intervals. When overlapped properly, this pairing can be used for rehabilitation through the rebuilding of neural pathways. Therefore in PAS, providing peripheral stimulation at the right time is crucial. The common procedure of PAS in the literature is to use electrical stimulation as peripheral stimulation. However, inspired by the repetitive facilitation exercise (RFE), mechanical stimulation is adopted in this RNRS experiment. Experiments show that RNRS can give mechanical stimulation accurately within a standard deviation of 5 ms. This stimulation is accurate enough when considering a 50 ms overlapping time window, the effective time range over which the overlap happens. The overlapping time window of mechanical stimulation is longer than that of electrical stimulation and it is expected to relax timing requirements in PAS by using RNRS. In addition, fMRI-compatible RNRS will allow further research on how mechanical stimulation itself affects on brain by observing brain activity through fMRI, where a general electrical stimulation device and TMS are not allowed. These results will help to get a consistent neural plasticity effect with RNRS for individuals with stroke and allow performing further research on brain plasticity in fMRI, contributing to the neuromodulation research.

A note on efficient performance evaluation of the Cumulative Sum chart and the Sequential Probability Ratio Test

We establish a simple connection between certain in‐control characteristics of the Cumulative Sum (CUSUM) Run Length and their out‐of‐control counterparts. The connection is in the form of paired integral (renewal) equations. The derivation exploits Wald's likelihood ratio identity and the well‐known fact that the CUSUM chart is equivalent to repetitive application of Wald's Sequential Probability Ratio Test (SPRT). The characteristics considered include the entire Run Length distribution and all of the corresponding moments, starting from the zero‐state average run length. A particular practical benefit of our result is that it enables the in‐control and out‐of‐control characteristics of the CUSUM Run Length to be computed concurrently. Moreover, owing to the equivalence of the CUSUM chart to a sequence of SPRTs, the Average Sample Number and Operating Characteristic functions of an SPRT under the null and under the alternative can all be computed simultaneously as well. This would double up the efficiency of any numerical method that one may choose to devise to carry out the actual computations. Copyright © 2016 John Wiley &amp; Sons, Ltd.

A Closed-Form Dynamics of a Novel Fully Wrist Driven by Revolute Motors

AbstractThis paper proposes a systematic methodology to obtain a closed-form formulation for dynamics analysis of a novel spherical robot that is called a 3(RPSP)-S parallel manipulator. The proposed manipulator provides high rotational displacement of the moving platform for low angular displacement of the motors. The advised robot is suitable for repetitive oscillatory applications (for example, wrist and ankle rehabilitation and table of autopilot and gyroscope life test, etc.). First, we describe the structure of the proposed manipulator and solve the inverse kinematics problem of the manipulator. Next, based on the principle of virtual work, a methodology for deriving the dynamical equations of motion is developed. The elaborated approach shows that the inverse dynamics of the manipulator can be reduced to solving a system of three linear equations in three unknowns. Finally, a computational algorithm to solve the inverse dynamics of the manipulator is advised and several trajectories of the moving platform are simulated and verified by a special dynamics modeling commercial software (MSC ADAMS).

F8-SIP mediated targeted photodynamic therapy leads to microvascular dysfunction and reduced glioma growth

The extra domain A (ED A) of fibronectin has been identified as a tumor vessel specific neovascular marker in glioma. Antibody based vascular targeting against ED A of fibronectin allows precise accumulation of photosensitizer in glioma microvasculature and thereby promises to overcome drawbacks of current photodynamic therapy (PDT) for glioma treatment. Our aim was to characterize microcirculatory consequences of F8-small immunoprotein (SIP) mediated PDT by intravital microscopy (IVM) and to analyze the effects on glioma growth. For IVM SF126 glioma cells were implanted into dorsal skinfold-chamber of nude mice. PDT was performed after intravenous injection of photosensitizer (PS)-coupled F8-SIP or PBS (n=4). IVM was performed before and after PDT for 4days. Analysis included total and functional (TVD, FVD) vessel densities, perfusion index (PI), microvascular permeability and blood flow rate (Q). To assess tumor growth SF126 glioma cells were implanted subcutaneously. PDT was performed as a single and repetitive treatment after PS-F8-SIP injection (n=5). Subcutaneous tumors were treated after uncoupled F8-SIP injection as control group (n=5). PDT induced microvascular stasis and thrombosis with reduced FVD (24h: 115.98±0.7 vs. 200.8±61.9cm/cm(2)) and PI (39±11 vs. 70±10%), whereas TVD was not altered (298±39.2 vs. 278.2±51cm/cm(2)). Microvascular dysfunction recovered 4days after treatment. Microvascular dysfunction led to a temporary reduction of glioma growth in the first 48h after treatment with complete recovery 5days after treatment. Repetitive PDT resulted in sustained reduction of tumor growth. F8-SIP mediatedPDT leads to microvascular dysfunction and reduced glioma growth in a preclinical glioma model with recovery of microcirculation 4days after treatment. Repetitive application of PDT overcomes microvascular recovery and leads to prolonged antiglioma effects.