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It has been frequently reported that myostatin inhibition increases muscle mass, but decreases muscle quality (i.e., strength/muscle mass). Resistance exercise training (RT) and essential amino acids (EAAs) are potent anabolic stimuli that synergistically increase muscle mass through changes in muscle protein turnover. In addition, EAAs are known to stimulate mitochondrial biogenesis. We have investigated if RT amplifies the anabolic potential of myostatin inhibition while EAAs enhance muscle quality through stimulations of mitochondrial biogenesis and/or muscle protein turnover. Mice were assigned into ACV (myostatin inhibitor), ACV+EAA, ACV+RT, ACV+EAA +RT, or control (CON) over 4 weeks. RT, but not EAA, increased muscle mass above ACV. Despite differences in muscle mass gain, myofibrillar protein synthesis was stimulated similarly in all vs. CON, suggesting a role for changes in protein breakdown in muscle mass gains. There were increases in MyoD expression but decreases in Atrogin-1/MAFbx expression in ACV+EAA, ACV+RT, and ACV+EAA+RT vs. CON. EAA increased muscle quality (e.g., grip strength and maximal carrying load) without corresponding changes in markers of mitochondrial biogenesis and neuromuscular junction stability. In conclusion, RT amplifies muscle mass and strength through changes in muscle protein turnover in conjunction with changes in implicated signaling, while EAAs enhance muscle quality through unknown mechanisms.

Importance of dedicated webservers and specialized software for simulations of protein-protein interactions is well established. The purpose of our study was to examine the protein-protein interaction that occurred under physiological and stress conditions between peroxiredoxin II and the creatine kinase brain-type using protein-docking server ClusPro 2.0. To predict the particular site of aminoacid docking, computer software analyzes various protein conformations and chooses the most profitable energy state, therefore selecting a number of possible combinations that would fit the correct profile. By coimmunoprecipitation assay, we demonstrated that two molecules Prx II and CKBB have interacted with further attenuation of this specific binding by pretreatment with selected stress factors. In previous study, we showed that the enzymatic activity of CKBB was recovered by different concentration ratios of Prx II. The specific binding models were generated by ClusPro 2.0 protein docking server and studied using PyMol software. It was shown that a number of amino acid residues including Lys 11, Arg 13, Ala 204, Arg 209 for creatine kinase, and Asp 181, Glu 192, Lys 196, Glu 162, Gln 163 for Prx II have participated in the complex formation throughout the first ten conformations.

This paper introduces a dual-arm robot painter system which is capable of sketching a camera-captured image with short line segments. To express various curved edges in the image by combining line segments, we first apply edge detection algorithm to the entire image, split the edged image into small boxed pieces, and then apply Hough Transformation to each piece so that the edges inside the piece can be approximated with short line segments. To draw the picture within a reasonable time, we designed a simple dual-arm robot system and controlled both arms concurrently according to linear interpolation algorithm. From the experiments, we could verify that simple linear motions can describe various images effectively with a unique brush style.

In today's business environment, competition within industries is becoming more and more intense. To survive in this fast-paced competitive environment, it's important to know what the core patents are and how the patents can be grouped. This study focuses on discovering core patents and clustering patents using a patent citation network in which core patents are represented as an influential node and patent groups as a cluster of nodes. Existing methods have discovered influential nodes and cluster nodes separately, especially in a citation network. This study develops a method used to detect influential nodes (that is, core patents) and clusters (that is, patent groups) in a patent citation network simultaneously rather than separately. The method allows a core patent in each patent group to be discovered easily and the distribution of similar patents around a core patent to be recognized. For this study, kernel k-means clustering with a graph kernel is introduced. A graph kernel helps to compute implicit similarities between patents in a high-dimensional feature space.

Centrality measures such as degree centrality have been utilized to identify influential and important patents in a citation network. However, no existing centrality measures take into consideration information from the change of the similarity matrix. This paper presents a new centrality measure based on the change of a node similarity matrix. The proposed approach gives more intuitive understanding of the finding of the influential nodes. The present study starts off with the assumption that the change of matrix that may result from removing a given node would assess the importance of the node since each node make a contribution to the given similarity matrix between nodes. The various matrix norms using the singular values such as nuclear norm which is the sum of all singular values, are used for calculating the contribution of a given node to a node similarity matrix. In other words, we can obtain the change of matrix norms for a given node after we calculate the singular values for the case of the nonexistence and the case of existence of the node. Then, the node resulting in the largest change (i.e., decrease) of matrix norms can be considered as the most important node. Computation of singular values can be computationally intensive when the similarity matrix size is large. Therefore, the singular value update technique is also developed for the case of the network with large nodes. We compare the performance of our proposed approach with other widely used centrality measures using U.S. patents data in the area of information and security. Experimental results show that our proposed approach is competitive or even performs better compared to existing approaches.

Thermal expanded core (TEC) fiber can reduce, being advantaged from thermal diffusion technology, connection loss by expanding the tolerance in relation to axial offset and gap when making optical connection having mode field diameter (MFD) of optical fiber expanded locally. In this paper, TEC fiber fabrication system based on the frame brushing techniques using twin-torch tip was designed and developed in order to maintain a stable thermal diffusion and single-mode when manufacturing TEC fiber. We were able to obtain that varied kinds of TEC fibers of which MFD could have been extended between and by TEC fiber fabrication system. In addition, the characteristic of connection loss was measured by alignment two TEC fibers of which MFD was .

The development of simple radiofrequency (RF) coils for magnetic resonance (MR) of the human brain is still of high interest in the engineering of systems for which phased arrays are not yet available. Particularly, high-field MR studies will benefit from configurations with simple coils that are easy to build and require only a few RF parts for operation (e.g., quadrature hybrids). In this article we describe selected simple transmit/receive (transceive) partial volume coil assemblies for human brain studies at high magnetic fields of 3, 4, and 7 T (130, 170, and 300 MHz). To characterize coil performance, the experimental results of MRI of phantoms, anatomical MRI, and single-voxel MRS of healthy human volunteers are presented. © 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 31B: 71–85, 2007.

A novel selective multiple quantum filtering-based chemical shift imaging method was developed for acquiring GABA images in the human brain at 3 T. This method allows a concomitant acquisition of an interleaved total creatine image with the same spatial resolution. Using T1-based image segmentation and a nonlinear least square regression analysis of GABA-to-total creatine concentration ratios in frontal and parietal lobes of healthy adult volunteers as a function of the tissue gray matter fraction, the mean GABA concentration in gray and white matter was determined to be 1.30 ± 0.36 μmol/g and 0.16 ± 0.16 μmol/g (mean ± SD, n = 13), respectively. It is expected that this method will become a useful tool for studying GABAergic function in the human brain in vivo.

Pinus densiflora belongs to the Pinaceae family which has been widely used for health promoting purposes as folk medicine or as a food. Various curative effects of different parts of the pine have been reported including as a remedy for carcinoma. We examined the effects of pine needle water extracts (PNE) on macrophage function using peritoneal macrophage, pre-osteoclast bone macrophage (Raw 264.7 cell) and brain macrophage (C6 microglia). When peritoneal macrophages were treated with various concentrations of PNE (1～100 ㎍/mL) for 24 hours, phagocytic activity was significantly increased, whereas it had no effect on tumoricidal activity and NO production. However, the treatment of Raw 264.7 with PNE resulted in the enhancement of NO production at high concentration (100 ㎍/mL). Furthermore, the treatment of C6 with PNE increased the production of NO in a concentration-dependent manner, whereas PNE suppressed NO production in LPS/IFN-γ-stimulated microglia. These results suggest that PNE has differential immunomodulatory effects on macrophages.

The human DnaJ homolog Hdj2 is a cochaperone containing a cysteine-rich zinc finger domain. We identified a specific interaction of Hdj2 with the cellular redox enzyme thioredoxin using a yeast two-hybrid assay and a coimmunoprecipitation assay, thereby investigating how the redox environment of the cell regulates Hdj2 function. In reconstitution experiments with Hsc70, we found that treatment with H2O2 caused the oxidative inactivation of Hdj2 cochaperone activity. Hdj2 inactivation paralleled the oxidation of cysteine thiols and concomitant release of coordinated zinc, suggesting a role of cysteine residues in the zinc finger domain of Hdj2 as a redox sensor of chaperone-mediated protein-folding machinery. H2O2-induced negative regulation of Hdj2 cochaperone activity was also confirmed in mammalian cells using luciferase as a foreign reporter cotransfected with Hsc70 and Hdj2. The in vivo oxidation of cysteine residues in Hdj2 was detected only in thioredoxin-knockdown cells, implying that thioredoxin is involved in the in vivo reduction. The oxidative inactivation of Hdj2 was reversible. Wild-type thioredoxin notably recovered the oxidatively inactivated Hdj2 activity accompanied by the reincorporation of zinc, whereas the catalytically inactive mutant thioredoxin (Cys32Ser/Cys35Ser) did not. Taken together, we propose that oxidation and reduction reversibly regulate Hdj2 function in response to the redox states of the cell.

Transgenic mouse models have been essential for understanding the pathogenesis of Alzheimer's disease (AD) including those that model the deposition process of beta-amyloid (Abeta). Several laboratories have focused on research related to the non-invasive detection of early changes in brains of transgenic mouse models of Alzheimer's pathology. Most of this work has been performed using regional image analysis of individual mouse brains and pooling the results for statistical assessment. Here we report the implementation of a non-linear image registration algorithm to register anatomical and transverse relaxation time (T2) maps estimated from MR images of transgenic mice. The algorithm successfully registered mouse brain magnetic resonance imaging (MRI) volumes and T2 maps, allowing reliable estimates of T2 values for different regions of interest from the resultant combined images. This approach significantly reduced the data processing and analysis time, and improved the ability to statistically discriminate between groups. Additionally, 3D visualization of intra-regional distributions of T2 of the resultant registered images provided the ability to detect small changes between groups that otherwise would not be possible to detect.

This study confirms the presence of iron, co-localized with Abeta plaques, in PS/APP mouse brain, using Perls' stain for Fe3+ supplemented by 3,3'-diaminobenzidine (DAB) and Abeta immunohistochemistry in histological brains sections fixed with formalin or methacarn. In this study, the fixation process and the slice thickness did not interfere with the Perls' technique. The presence of iron in beta-amyloid plaques in PS/APP transgenic mice, a model of Alzheimer's disease (AD) pathology, may explain previous reports of reductions of transverse relaxation time (T2) in MRI studies and represent the source of the intrinsic Abeta plaque MR contrast in this model.

A single-shot multiple quantum filtering method is developed that uses two double-band frequency selective pulses for enhanced spectral selectivity in combination with a slice-selective 90 degrees, a slice-selective universal rotator 90 degrees, and a spectral-spatial pulse composed of two slice-selective universal rotator 45 degrees pulses for single-shot three-dimensional localization. The use of this selective multiple quantum filtering method for C(3) and C(4) methylene protons of GABA resulted in improved spectral selectivity for GABA and effective suppression of overlapping signals such as creatine and glutathione in each single scan, providing reliable measurements of the GABA doublet in all subjects. The concentration of GABA was measured to be 0.7 +/- 0.2 micromol/g (means +/- SD, n = 15) in the fronto-parietal region of the human brain in vivo.

Hemodynamic-based brain mapping techniques have been extensively used. However, spatial accuracy and extents of those techniques to neuronal active sites are poorly understood because most of the techniques are contaminated by signals from non-specific large blood vessels. To accurately determine the intrinsic cerebral blood flow (CBF) responses induced by neural activity, large vessel-free and tissue-specific CBF imaging techniques should be utilized. For this, the arterial spin labeling MRI technique with flow-crushing bipolar gradients was applied in the rat brain to examine contributions of large blood vessels to CBF MRI. It was found that the majority (80–90%) of signals of arterial spin labeled MRI originated from tissue and capillaries. The arterial spin labeling technique with minimal sensitivity to large vessels was used to determine whether signal changes induced by neural activity are laminar-specific. During somatosensory stimulation, the highest neural activities and metabolic responses were expected to be located at the middle layer (i.e., layer 4) in the rat somatosensory cortex. Functional foci in CBF fMRI were located at the middle of the somatosensory cortex, suggesting that the response of CBF MRI signals is specific to sites of neural activity.

A single-shot, two-echo method for the simultaneous detection of multiple-quantum (MQ)-filtered γ-aminobutyric acid (GABA) and creatine (Cr) was developed and demonstrated in the human brain in vivo at 3 Tesla. The simultaneously measured Cr singlet served as a navigator for the spectral phase of GABA and any frequency shift during measurements due to drift in the static magnetic field (B0) or subject movement, as well as an internal concentration reference. In addition, the use of a double-band frequency-selective MQ filter for C3 and C4 methylene protons of GABA provided a very robust measurement of GABA, with excellent suppression of overlapping metabolites such as Cr and glutathione (GSH) in each single scan. Contamination from overlapping macromolecules was also demonstrated to be negligible with this method. The GABA-to-Cr ratio was 0.09 ± 0.03 (mean ± SD, N = 17) and the estimated concentration of GABA in the frontoparietal region of the human brain in vivo was 0.66 ± 0.19 μmol/g (mean ± SD, N = 17) with the internal reference method, and 0.69 ± 0.18 μmol/g (mean ± SD, N = 17) with the external reference method. The observed pattern of GABA doublet was consistent among all subjects, with a frequency separation of ∼13 Hz. Magn Reson Med 51:1115–1121, 2004. © 2004 Wiley-Liss, Inc.

The development of a noninvasive method to detect early, subtle changes in the brains of patients with Alzheimer's disease (AD) would have considerable clinical value as therapy. This therapy is most likely to be successful if intervention could occur before neurons were irreversibly damaged or lost. An ideal biological neuroimaging marker would be an early, sensitive, and valid indicator of brain changes, capable of discriminating the effects of normal aging. The introduction of high field-strength clinical magnetic resonance imaging (MRI) systems now offer a powerful new noninvasive tool that may be capable of detecting brain pathology resulting from AD. Here we present results from high field-strength MRI in transgenic mice along with a new MRI technique for imaging brain iron. The successful translation of this research to the clinic could prove important to both the early diagnosis and monitoring of the efficacy of potential therapies in humans.

The visualization of β-amyloid plaque deposition in brain, a key feature of Alzheimer’s disease (AD), is important for the evaluation of disease progression and the efficacy of therapeutic interventions. In this study, β-amyloid plaques in the PS/APP transgenic mouse brain, a model of human AD pathology, were detected using MR microscopy without contrast reagents. β-Amyloid plaques were clearly visible in the cortex, thalamus, and hippocampus of fixed brains of PS/APP mice. The distribution of plaques identified by MRI was in excellent agreement with those found in the immunohistological analysis of the same brain sections. It was also demonstrated that image contrast for β-amyloid plaques was present in freshly excised nonfixed brains. Furthermore, the detection of β-amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging. Magn Reson Med 52:538–544, 2004.

The cerebral deposition of amyloid -peptide, a central event in Alzheimer’s disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1) transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of -amyloid in several brain regions, starting from 10 weeks of age; 2) transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of A-peptide without -amyloid deposition; and 3) nontransgenic (NTg) littermates as controls. The transverse relaxation time T2, an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T1 values or proton density were detected between any groups of mice. These results indicate that T2 may be a sensitive marker of abnormalities in this transgenic mouse model of AD. Magn Reson Med 51:794 –798, 2004. © 2004 Wiley-Liss, Inc.

In vivo magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide unique quality to attain neurochemical, physiological, anatomical, and functional information non-invasively. These techniques have been increasingly applied to biomedical research and clinical usage in diagnosis and prognosis of diseases. The ability of MRS to detect early yet subtle changes of neurochemicals in vivo permits the use of this technology for the study of cerebral metabolism in physiological and pathological conditions. Recent advances in MR technology have further extended its use to assess the etiology and progression of neurodegeneration. This review focuses on the current technical advances and the applications of MRS and MRI in the study of neurodegenerative disease animal models including amyotrophic lateral sclerosis, Alzheimer's, Huntington's, and Parkinson's diseases. Enhanced MR measurable neurochemical parameters in vivo are described in regard to their importance in neurodegenerative disorders and their investigation into the metabolic alterations accompanying the pathogenesis of neurodegeneration.

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level—dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the postitive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.

Six distinct peroxiredoxin (Prx) proteins (Prx I-VI) from distinct genes have been identified in mammalian tissues. Prxs are members of a group of peroxidases that have conserved reactive cysteine residue(s) in the active site(s). An immediate physiological electron donor for the peroxidase catalysis for five Prx proteins (Prx I-V) has been identified as thioredoxin (Trx), but that for Prx VI (1-Cys Prx) is still unclear. To identify an immediate electron donor and a binding protein for Prx VI, we performed a Prx VI protein overlay assay. A 20-kDa binding protein was identified by the Prx VI protein overlay assay with flow-through fractions from a High-Q column with rat lung crude extracts. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and MS-Fit, we identified the 20-kDa Prx VI-binding protein as a cyclophilin A (CyP-A). The binding of recombinant human CyP-A (hCyP-A) to Prx VI was confirmed by using the hCyP-A protein overlay assay and Western immunoblot analysis with hCyP-A-specific antibodies. hCyP-A enhanced the antioxidant activity of Prx VI, as well as the other known mammalian Prx isotypes. hCyP-A supported antioxidant activity of Prx II and Prx VI both against thiol (dithiothreitol)-containing metal-catalyzed oxidation (MCO) systems and ascorbate-containing MCO systems. Prx II was reduced by hCyP-A without help from any other reductant, and the reduction was cyclosporin A-independent. These results strongly suggest that CyP-A not only binds to Prx proteins but also supports its peroxidase activity as an immediate electron donor. In addition, Cys(115) and Cys(161) of hCyP-A were found to be involved in the activation and the reduction of Prx.

Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood–brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in α-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma glucose, which is consistent with the reversible Michaelis–Menten model. When the model was fitted to the brain glucose measurements, the apparent Michaelis-Menten constant, Kt, was 3.3 ± 1.0 mmol/L, and the ratio of the maximal transport rate relative to CMRglc, Tmax/CMRglc, was 2.7 ± 0.1. This Kt is comparable to the authors' previous human data, suggesting that glucose transport kinetics in humans and rats are similar. Cerebral blood flow (CBF) was simultaneously assessed and constant above 2 mmol/L plasma glucose at 73 ± 6 mL 100 g−1 min−1. Extrapolation of the reversible Michaelis–Menten model to hypoglycemia correctly predicted the plasma glucose concentration (2.1 ± 0.6 mmol/L) at which brain glucose concentrations approached zero. At this point, CBF increased sharply by 57% ± 22%, suggesting that brain glucose concentration is the signal that triggers defense mechanisms aimed at improving glucose delivery to the brain during hypoglycemia.

Measurement of cerebral arterial and venous blood volumes during increased cerebral blood flow can provide important information regarding hemodynamic regulation under normal, pathological, and neuronally active conditions. In particular, the change in venous blood volume induced by neural activity is one critical component of the blood oxygenation level-dependent (BOLD) signal because BOLD contrast is dependent only on venous blood, not arterial blood. Thus, relative venous and arterial blood volume (rCBV) and cerebral blood flow (rCBF) in alpha-chlorolase-anesthetized rats under hypercapnia were measured by novel diffusion-weighted (19)F NMR following an i.v. administration of intravascular tracer, perfluorocarbons, and continuous arterial spin labeling methods, respectively. The relationship between rCBF and total rCBV during hypercapnia was rCBV(total) = rCBF(0.40), which is consistent with previous PET measurement in monkeys. This relationship can be linearized in a CBF range of 50-130 ml/100 g/min as DeltarCBV(total)/ DeltarCBF = 0.31 where DeltarCBV and DeltarCBF represent rCBV and rCBF changes. The average arterial volume fraction was 0.25 at a basal condition with CBF of approximately 60 ml/100 g/min and increased up to 0.4 during hypercapnia. The change in venous rCBV was 2-fold smaller than that of total rCBV (DeltarCBV(vein)/DeltarCBF = 0.15), while the arterial rCBV change was 2.5 times larger than that of total rCBV (DeltarCBV(artery)/DeltarCBF = 0.79). These NMR results were confirmed by vessel diameter measurements with in vivo videomicroscopy. The absolute venous blood volume change contributes up to 36% of the total blood volume change during hypercapnia. Our findings provide a quantitative physiological model of BOLD contrast.

A novel europium complex, Eu(TTA) 3 (TPPO) was synthesized and its photoluminescent and electroluminescent characteristics were investigated with a device structure of ITO/TPD/Eu(TTA) 3 (TPPO)/Alq 3 /Al, where a sharp emission at the wavelength of 615 nm was observed, ed.

The thermodynamical estimation of the interfacial reaction and the impact properties of Nb/MoSi2 laminate composites containing SiC, NbSi2 or ZrO2 particles are investigated. Laminate composites, which comprise alternating layers of MoSi2 with the particle and Nb foil, were fabricated by the hot press process. It is clearly found out that the interfacial reaction of Nb/MoSi2 can be controlled by the addition of ZrO2 particle to the MoSi2 phase. The addition of ZrO2 particle increases both the impact value and the sintered density of Nb/MoSi2. The suppression of the interfacial reaction is caused by the formation of ZrSiO4 in MoSi2−ZrO2 matrix mixture.

Nb/MoSi2 laminate composites have been successfully fabricated by hot pressing in a graphite mould. Lamination of Nb foil and MoSi2 layer showed a sufficient improvement in the absorbed impact energy compared to that of monolithic MoSi2 material. The impact value of Nb/MoSi2 laminate composites obviously is reduced when sintered at temperatures higher than 1523K, even if the composite density contributing to impact load increased along with fabricating temperatures. Impact value of laminate composites was also drastically decreased with the growth of reaction layer after the heat treatment. However, it was effective to increase the pressure at the same sintering temperature for the improvement of the impact value.

Spatial specificities of the calcium-dependent synaptic activity, hemodynamic-based blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) fMRI were quantitatively compared in the same animals. Calcium-dependent synaptic activity was imaged by exploiting the manganese ion (Mn 11 ) as a calcium analog and an MRI contrast agent at 9.4 T. Following forepaw stimulation in a-chloralose anesthetized rat, water T1 of the contralateral forepaw somatosensory cortex (SI) was focally and markedly reduced from 1.99 6 0.03 sec to 1.30 6 0.18 sec (mean 6 SD, N 5 7), resulting from the preferential intracellular Mn 11 accumulation. Based on an in vitro calibration, the estimated contralateral somatosensory cortex [Mn 11 ] was ;100mM, which was 2‐5-fold higher than the neighboring tissue and the ipsilateral SI. Regions with the highest calcium activities were localized around cortical layer IV. Stimulus-induced BOLD and CBF changes were 3.4 6 1.6% and 98 6 33%, respectively. The T1 synaptic activity maps extended along the cortex, whereas the hemodynamic-based activation maps extended radially along the vessels. Spatial overlaps among the synaptic activity, BOLD, and CBF activation maps showed excellent co-registrations. The center-of-mass offsets between any two activation maps were less than 200 mm, suggesting that hemodynamic-based fMRI techniques (at least at high field) can be used to accurately map the spatial loci of synaptic activity. Magn Reson Med 43:383‐392, 2000. © 2000 Wiley-Liss, Inc.

The nature of vascular contribution to blood oxygenation level dependent (BOLD) contrast used in functional MRI (fMRI) is poorly understood. To investigate vascular contributions at an ultrahigh magnetic field of 9.4 T, diffusion-weighted fMRI techniques were used in a rat forepaw stimulation model. Tissue and blood T2 values were measured to optimize the echo time for fMRI. The T2 of arterial blood was 40.8 6 3.4 msec (mean 6 SD; n 5 5), similar to the tissue T2 of 38.6 6 2.1 msec (n 5 16). In comparison, the T2 of venous blood at an oxygenation level of 79.6 6 6.1% was 9.2 6 2.3 msec (n 5 11). The optimal spin-echo time of 40 msec was confirmed from echo-time dependency fMRI studies. The intravascular contribution was examined using a graded diffusion-weighted spin-echo echo-planar imaging technique with diffusion weighting factor (b )v alues of up to 1200 sec/mm2. Relative BOLD signal changes induced by forepaw stimulation showed no dependence on the strength or direction of the diffusion-sensitizing gradients, suggesting that the large vessel contribution to the BOLD signal is negligible at 9.4 T. However, gradient-echo fMRI performed with bipolar diffusion sensitizing gradients, which suppress intravascular components from large vessels, showed higher percent signal changes in the surface of the brain. This effect was attributed to the extravascular contribution from large vessels. These find

Hand and wrist injuries commonly occur and can be debilitating. Scapholunate dissociation generally requires surgery, and if left untreated, can lead to scapholunate advanced collapse (SLAC wrist) and associated osteoarthritis [1]. The overall goal of this research is to make a positive impact on the assessment and treatment of wrist injuries and on prevention of osteoarthritis as a result of injury.Copyright © 2011 by ASME

Scapholunate dissociation (SL ligament disruption) due to trauma can cause changes in joint kinematics and contact patterns, which can lead to scapholunate advanced collapse (SLAC wrist) with secondary radiocarpal osteoarthritis (OA) [1]. The relationship between consequent abnormal mechanics and the onset of OA is not clearly understood, however elevated joint contact pressure is believed to be an associated factor. Knowing how injuries affect joint physiology and mechanics and how well surgical repairs restore the mechanics may improve surgical efficacy and help predict OA risk. Recently a method was proposed to measure joint contact mechanics from in vivo imaging data during functional loading [2]. The objective of this study was to compare radiocarpal joint mechanics (contact forces, contact areas, peak and average contact pressures) of injured and post-operative wrists to contralateral controls using MRI-based contact modeling. We hypothesized that average contact pressures and peak contact pressures would be higher in the injured wrists, and that these measures would decrease post-operatively.Copyright © 2011 by ASME

The wrist is one of the most complicated multibody joints in the human body. It can be subject to many injuries. Scapholunate (SL) dissociation is a relatively common injury that is particularly difficult to diagnose and treat. Without treatment, SL dissociation is known to progress to scapholunate advance collapse (SLAC wrist) and associated osteoarthritis (OA) [1]. Traumatic arthropathy of the wrist due to scapholunate dissociation has a definitive pattern from onset to severe bone and joint degeneration. The altered radiocarpal and SL mechanics with SL dissociation may be accompanied by a secondary carpal collapse between the capitate and lunate [2]. The initial SL disruption causes apparent changes in joint kinematics and contact patterns. Thus, understanding normal and abnormal in vivo contact mechanics as a result of SL ligament injury may lead to more effective treatments that may even prevent the onset of OA. In addition, in vivo contact mechanics data after surgical treatment may help determine the effectiveness of various surgical techniques which are used to correct SL injury.Copyright © 2011 by ASME

The distal radioulnar joint (DRUJ) is a joint of the wrist which allows forearm rotation and force transmission in the upper limb while preserving stability independent of flexion and extension of the forearm and wrist. The DRUJ is a frequently injured joint in the body. Conditions affecting the joint could be positive ulnar variance (Ulnar Impaction Syndrome) or negative ulnar variance (ulnar impingement), which may be congenital or may result from a poorly reduced distal radius fracture or both bone forearm fracture. The DRUJ is also adversely affected by other injuries near the joint. In fact, a significant correlation has been found between negative ulnar variance and scapholunate dissociation [1, 2, 3]. While this could be a predisposing factor, the associate also leads to the question of whether or not scapholunate dissociation may cause changes in the radioulnar joint mechanics. Altered joint mechanics are highly associated with onset of secondary osteoarthritis. An understanding of in vivo distal radioulnar joint contact mechanics in the normal and pathological wrist could help physicians make better clinical recommendations and improve treatment for the primary injury and avoid DRUJ pathology. Successful treatment may possibly reduce risk of or prevent the onset of osteoarthritis.Copyright © 2011 by ASME

Background: Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T2 lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. Objective: To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. Methods: Seventeen patients with SPMS (Expanded Disability Status Scale = 4.0–7.0; length of MS diagnosis = 19.4 ± 7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. Results: The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region ( p = 0.001). Conclusion: The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS.

Studies of the neural control of movement often rely on the ability to record EMG activity during natural behavioral tasks over long periods of time. Increasing the number of recorded muscles and the time over which recordings are made allows more rigorous answers to many questions related to the descending control of motor output. Chronic recording of EMG activity from multiple hindlimb muscles has been reported in the cat but few studies have been done in non-human primates. This paper describes two chronic EMG implant methods that are minimally invasive, relatively non-traumatic and capable of recording from large numbers of hindlimb muscles simultaneously for periods of many months to years.

In this study, forelimb organizations and output properties of the supplementary motor area (SMA) and the dorsal cingulate motor area (CMAd) were assessed and compared with primary motor cortex (M1). Stimulus-triggered averages of electromyographic activity from 24 muscles of the forelimb were computed from layer V sites of 2 rhesus monkeys performing a reach-to-grasp task. No clear segregation of the forelimb representation of proximal and distal muscles was found in SMA. In CMAd, sites producing poststimulus effects in proximal muscles tended to be located caudal to distal muscle sites, although the number of effects was limited. For both SMA and CMAd, facilitation effects were more prevalent in distal than in proximal muscles. At an intensity of 60 microA, the mean latencies of M1 facilitation effects were 8 and 12.1 ms shorter and the magnitudes approximately 10 times greater than those from SMA and CMAd. Our results show that corticospinal neurons in SMA and CMAd provide relatively weak input to spinal motoneurons compared with the robust effects from M1. However, a small number of facilitation effects from SMA and CMAd had latencies as short as the shortest ones from M1 suggesting a minimum linkage to motoneurons as direct as that from M1.

In this paper, the dynamic stability of a rotating cantilever pipe conveying fluid with a crack and tip mass is investigated by numerical method. That is, the effects of the rotating the rotating angular velocity, the mass ratio, the crack and tip mass on the critical flow velocity for flutter instability of system are studied. The equations of motion of rotating pipe are derived by using the extended Hamilton's principle. The crack section of pipe is represented by a local flexibility matrix connecting two undamaged pipe segments. The crack is assumed to be in the first mode of fracture and always opened during the vibrations. Finally, the stability maps of the cracked rotating pipe system as a rotating angular velocity and mass ratio β are presented.

In this study, we used MRI to analyze quantitative parametric maps of transverse (T(2)) relaxation times in a longitudinal study of transgenic mice expressing mutant forms of amyloid precursor protein (APP), presenilin (PS1), or both (PS/APP), modeling aspects of Alzheimer's disease (AD). The main goal was to characterize the effects of progressive beta-amyloid accumulation and deposition on the biophysical environment of water and to investigate if these measurements would provide early indirect evidence of AD pathological changes in the brains of these mice. Our results demonstrate that at an early age before beta-amyloid deposition, only PS/APP mice show a reduced T(2) in the hippocampus and cortex compared with wild-type non-transgenic (NTg) controls, whereas a statistically significant within-group aging-associated decrease in T(2) values is seen in the cortex and hippocampus of all three transgenic genotypes (APP, PS/APP, and PS) but not in the NTg controls. In addition, for animals older than 12 months, we confirmed our previous report that only the two genotypes that form amyloid plaques (APP and PS/APP) have significantly reduced T(2) values compared with NTg controls. Thus, T(2) changes in these AD models can precede amyloid deposition or even occur in AD models that do not deposit beta-amyloid (PS mice), but are intensified in the presence of amyloid deposition.