961 resultados para Calcium channel blockers


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This paper presents the details of experimental studies on the shear behaviour and strength of lipped channel beams (LCBs). The LCB sections are commonly used as flexural members in residential, industrial and commercial buildings. To ensure safe and efficient designs of LCBs, many research studies have been undertaken on the flexural behaviour of LCBs. To date, however, limited research has been conducted into the strength of LCB sections subject to shear actions. Therefore a detailed experimental study involving 20 tests was undertaken to investigate the shear behaviour and strength of LCBs. This research has shown the presence of increased shear capacity of LCBs due to the additional fixity along the web to flange juncture, but the current design rules (AS/NZS 4600 and AISI) ignore this effect and were thus found to be conservative. Therefore they were modified by including a higher elastic shear buckling coefficient. Ultimate shear capacity results obtained from the shear tests were compared with the modified shear capacity design rules. It was found that they are still conservative as they ignore the presence of post-buckling strength. Hence the AS/NZS 4600 and AISI design rules were further modified to include the available post-buckling strength. Suitable design rules were also developed under the direct strength method (DSM) format. This paper presents the details of this study and the results including the modified shear design rules.

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Cold-formed steel members are increasingly used as primary structural elements in the building industries around the world due to the availability of thin and high strength steels and advanced cold-forming technologies. Cold-formed lipped channel beams (LCB) are commonly used as flexural members such as floor joists and bearers. However, their shear capacities are determined based on conservative design rules. Current practice in flooring systems is to include openings in the web element of floor joists or bearers so that building services can be located within them. Shear behaviour of LCBs with web openings is more complicated while their shear strengths are considerably reduced by the presence of web openings. However, limited research has been undertaken on the shear behaviour and strength of LCBs with web openings. Hence a detailed experimental study involving 40 shear tests was undertaken to investigate the shear behaviour and strength of LCBs with web openings. Simply supported test specimens of LCBs with aspect ratios of 1.0 and 1.5 were loaded at midspan until failure. This paper presents the details of this experimental study and the results of their shear capacities and behavioural characteristics. Experimental results showed that the current design rules in cold-formed steel structures design codes are very conservative for the shear design of LCBs with web openings. Improved design equations have been proposed for the shear strength of LCBs with web openings based on the experimental results from this study.

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Cold-formed steel Lipped Channel Beams (LCB) with web openings are commonly used as floor joists and bearers in building structures. The shear behaviour of these beams is more complicated and their shear capacities are considerably reduced by the presence of web openings. However, limited research has been undertaken on the shear behaviour and strength of LCBs with web openings. Hence a detailed numerical study was undertaken to investigate the shear behaviour and strength of LCBs with web openings. Finite element models of simply supported LCBs under a mid-span load with aspect ratios of 1.0 and 1.5 were developed and validated by comparing their results with test results. They were then used in a detailed parametric study to investigate the effects of various influential parameters. Experimental and numerical results showed that the current design rules in cold-formed steel structures design codes are very conservative. Improved design equations were therefore proposed for the shear strength of LCBs with web openings based on both experimental and numerical results. This paper presents the details of finite element modelling of LCBs with web openings, validation of finite element models, and the development of improved shear design rules. The proposed shear design rules in this paper can be considered for inclusion in the future versions of cold-formed steel design codes.

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The methodology undertaken, the channel model and the system model created for developing a novel adaptive equalization method and a novel channel tracking method for uplink of MU-MIMO-OFDM systems is presented in this paper. The results show that the channel tracking method works with 97% accuracy, while the training-based initial channel estimation method shows poor performance in estimating the actual channel comparatively.

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The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

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The purpose of this study is to identify the impact of individual differences on service channel selection for e-government services. In a comparative survey of citizens in Germany and Australia (n=1205), we investigate the impact of age, gender, and mobility issues on the selection of personal or mobile communication as channels for service consumption. The results suggest that Australians are more likely to want to use new technology-oriented channels as internet or mobile applications while Germans tend to use classical channels as telephone or in person. Moreover, differences with respect to age, gender, and mobility exist. Implications for practice and issues for future research are discussed.

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Objectives The aim of this study was to evaluate the role of cardiac K+ channel gene variants in families with atrial fibrillation (AF). Background The K+ channels play a major role in atrial repolarization but single mutations in cardiac K+ channel genes are infrequently present in AF families. The collective effect of background K+ channel variants of varying prevalence and effect size on the atrial substrate for AF is largely unexplored. Methods Genes encoding the major cardiac K+ channels were resequenced in 80 AF probands. Nonsynonymous coding sequence variants identified in AF probands were evaluated in 240 control subjects. Novel variants were characterized using patch-clamp techniques and in silico modeling was performed using the Courtemanche atrial cell model. Results Nineteen nonsynonymous variants in 9 genes were found, including 11 rare variants. Rare variants were more frequent in AF probands (18.8% vs. 4.2%, p < 0.001), and the mean number of variants was greater (0.21 vs. 0.04, p < 0.001). The majority of K+ channel variants individually had modest functional effects. Modeling simulations to evaluate combinations of K+ channel variants of varying population frequency indicated that simultaneous small perturbations of multiple current densities had nonlinear interactions and could result in substantial (>30 ms) shortening or lengthening of action potential duration as well as increased dispersion of repolarization. Conclusions Families with AF show an excess of rare functional K+ channel gene variants of varying phenotypic effect size that may contribute to an atrial arrhythmogenic substrate. Atrial cell modeling is a useful tool to assess epistatic interactions between multiple variants.

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Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.

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Migraine with aura (MA) is a subtype of typical migraine. Migraine with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2) susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at this site have recently been implicated. We have previously provided evidence of linkage of typical migraine (predominantly MA) to microsatellite markers on chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a large genomic investigation involving candidate genes that lie within the chromosome 1q23 and 1q31 regions using an association analysis approach. Methods We have genotyped a large population of case-controls (243 unrelated Caucasian migraineurs versus 243 controls) examining a set of 5 single nucleotide polymorphisms (SNPs) and the Fas Ligand dinucleotide repeat marker, located within the chromosome 1q23 and 1q31 regions. Results Several genes have been studied including membrane protein (ATP 1 subtype A4 and FasL), cytoplasmic glycoprotein (CASQ 1) genes and potassium (KCN J9 and KCN J10) and calcium (CACNA1E) channel genes in 243 migraineurs (including 85% MA and 15% of migraine without aura (MO)) and 243 matched controls. After correction for multiple testing, chi-square results showed non-significant P values (P > 0.008) across all SNPs (and a CA repeat) tested in these different genes, however results with the KCN J10 marker gave interesting results (P = 0.02) that may be worth exploring further in other populations. Conclusion These results do not show a significant role for the tested candidate gene variants and also do not support the hypothesis that a common chromosome 1 defective gene influences both FHM and the more common forms of migraine.

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Migraine is a frequent familial disorder that, in common with most multifactorial disorders, has an unknown etiology. The authors identified several families with multiple individuals affected by typical migraine using a single set of diagnostic criteria and studied these families for cosegregation between the disorder and markers on chromosome 19, the location of a mutation that causes a rare form of familial hemiplegic migraine (FHM). One large tested family showed both cosegregation and significant allele sharing for markers situated within or adjacent to the FHM locus. Multipoint GENEHUNTER results indicated significant excess allele sharing across a 12.6- cM region containing the FHM Ca2+ channel gene, CACNL1A4 (maximum nonparametric linkage Z score = 6.64, p = 0.0026), with a maximum parametric lod score of 1.92 obtained for a (CAG)(n) triplet repeat polymorphism situated in exon 47 of this gene. The CAG expansion did not, however, appear to be the cause of migraine in this pedigree. Other tested families showed neither cosegregation nor excess allele sharing to chromosome 19 markers. HOMOG analysis indicated heterogeneity, generating a maximum HLOD score of 3.6. It was concluded that Chr19 mutations either in the CACNL1A4 gene or a closely linked gene are implicated in some pedigrees with familial typical migraine, and that the disorder is genetically heterogeneous.

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Solution chemistry plays a significant role in the rate and type of foulant formed on heated industrial surfaces. This paper describes the effect of sucrose, silica (SiO2), Ca2+ and Mg2+ ions, and trans-aconitic acid on the kinetics and solubility of SiO2 and calcium oxalate monohydrate (COM) in mixed salt solutions containing sucrose and refines models previously proposed. The developed SiO2 models show that sucrose and SiO2 concentrations are the main parameters that determine apparent order (n) and apparent rate of reaction (k) and SiO2 solubility over a 24 h period. The calcium oxalate solubility model shows that while increasing [Mg2+] increases COM solubility, the reverse is so with increasing sucrose concentrations. The role of solution species on COM crystal habit is discussed and the appearance of the uncommon (001) face is explained.

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Cell-based therapy is considered a promising approach to achieving predictable periodontal regeneration. In this study, the regenerative potential of cell sheets derived from different parts of the periodontium (gingival connective tissue, alveolar bone and periodontal ligament) were investigated in an athymic rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC) and gingival margin-derived cells (GMC) were obtained from human donors. The osteogenic potential of the primary cultures was demonstrated in vitro. Cell sheets supported by a calcium phosphate coated melt electrospun polycaprolactone (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL scaffold alone was able to promote alveolar bone formation within the defect after 4 weeks. The addition of ABC and PDLC sheets resulted in significant periodontal attachment formation. The GMC sheets did not promote periodontal regeneration on the root surface and inhibited bone formation within the CaP-PCL scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP-PCL scaffold could promote periodontal regeneration, but ABC sheets were not as effective as PDLC sheets in promoting new attachment formation.

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Cold-formed steel Lipped Channel Beams (LCB) with web openings are commonly used as floor joists and bearers in building structures. Shear behaviour of these beams is more complicated and their shear capacities are considerably reduced by the presence of web openings. Hence detailed numerical and experimental studies of simply supported LCBs under a mid-span load with aspect ratios of 1.0 and 1.5 were undertaken to investigate the shear behaviour and strength of LCBs with web openings. Experimental and numerical results showed that the current design rules in cold-formed steel structures design codes are very conservative. Improved design equations were therefore proposed for the shear strength of LCBs with web openings based on both experimental and numerical results. This research showed a significant reduction in shear capacities of LCBs when large web openings are included for the purpose of locating building services. A cost effective method of eliminating such detrimental effects of large circular web openings was also therefore investigated using experimental and numerical studies. For this purpose LCBS were reinforced using plate, stud, transverse and sleeve stiffeners with varying sizes and thicknesses that were welded and screw-fastened to the web of LCBs. These studies showed that plate stiffeners were the most suitable. Suitable screw-fastened plate stiffener arrangements with optimum thicknesses were then proposed for LCBs with web openings to restore their original shear capacities. This paper presents the details of finite element analyses and experiments of LCBs with web openings in shear, and the development of improved shear design rules. It then describes the experimental and numerical studies to determine the optimum plate stiffener arrangements and the results. The proposed shear design rules in this paper can be considered for inclusion in the future versions of cold-formed steel design codes.

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This paper presents the details of an experimental study of a cold-formed steel hollow flange channel beam known as LiteSteel Beam (LSB) subject to combined bending and shear actions. The LSB sections are produced by a patented manufacturing process involving simultaneous cold-forming and electric resistance welding. Due to the geometry of the LSB, as well as its unique residual stress characteristics and initial geometric imperfections resultant of manufacturing processes, much of the existing research for common cold-formed steel sections is not directly applicable to LSB. Experimental and numerical studies have been carried out to evaluate the behaviour and design of LSBs subject to pure bending actions and predominant shear actions. To date, however, no investigation has been conducted into the strength of LSB sections under combined bending and shear actions. Combined bending and shear is especially prevalent at the supports of continuous span and cantilever beams, where the interaction of high shear force and bending moment can reduce the capacity of a section to well below that for the same section subject only to pure shear or moment. Hence experimental studies were conducted to assess the combined bending and shear behaviour and strengths of LSBs. Eighteen tests were conducted and the results were compared with current AS/NZS 4600 and AS 4100 design rules. AS/NZS 4600 design rules were shown to grossly underestimate the combined bending and shear capacities of LSBs and hence two lower bound design equations were proposed based on experimental results. Use of these equations will significantly improve the confidence and cost-effectiveness of designing LSBs for combined bending and shear actions.

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Neuromuscular electrical stimulation (NMES) has been consistently demonstrated to improve skeletal muscle function in neurological populations with movement disorders, such as poststroke and incomplete spinal cord injury (Vanderthommen and Duchateau, 2007). Recent research has documented that rapid, supraspinal central nervous system reorganisation/neuroplastic mechanisms are also implicated during NMES (Chipchase et al., 2011). Functional neuroimaging studies have shown NMES to activate a network of sub-cortical and cortical brain regions, including the sensorimotor (SMC) and prefrontal (PFC) cortex (Blickenstorfer et al., 2009; Han et al., 2003; Muthalib et al., 2012). A relationship between increase in SMC activation with increasing NMES current intensity up to motor threshold has been previously reported using functional MRI (Smith et al., 2003). However, since clinical neurorehabilitation programmes commonly utilise NMES current intensities above the motor threshold and up to the maximum tolerated current intensity (MTI), limited research has determined the cortical correlates of increasing NMES current intensity at or above MTI (Muthalib et al., 2012). In our previous study (Muthalib et al., 2012), we assessed contralateral PFC activation using 1-channel functional near infrared spectroscopy (fNIRS) during NMES of the elbow flexors by increasing current intensity from motor threshold to greater than MTI and showed a linear relationship between NMES current intensity and the level of PFC activation. However, the relationship between NMES current intensity and activation of the motor cortical network, including SMC and PFC, has not been clarified. Moreover, it is of scientific and clinical relevance to know how NMES affects the central nervous system, especially in comparison to voluntary (VOL) muscle activation. Therefore, the aim of this study was to utilise multi-channel time domain fNIRS to compare SMC and PFC activation between VOL and NMESevoked wrist extension movements.