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Meddling Kids
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Description: Scooby doo where are you? There is no time to lose for Daphne and Velma, all the paranormal mystery solving has worn them out and all they need now is each other to play with and solve the mystery of what is under that purple dress and that orange turtle-neck sweater!
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Models: Harmony Reigns Elouise


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The Factors that affect enzyme reaction rate
The above. All that is required :)
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- Created on: 10-12-09 11:54
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Factors affecting the rate of enzyme reactions
Enzymes have an optimum temperature which is the temperature at which they work fastest. For most this
is around 40 degrees, but there are ones at 90 and some below 0 degrees,
Leading up to the optimum temperature, the rate increases steadily, because the enzyme and substrate
molecules have more kinetic energy and so collisions happen more often and because there is enough
energy to bypass the activation energy (already greatly reduced thanks to the enzyme.…read more
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Thu, 11/02/2010 - 16:05
Och-Ziff Capital Management has reported a GAAP net loss for the fourth quarter and full year ended 31 December 2009 of USD47.2m, or USD0.58 per basic and diluted class A share, and USD297.4m, or USD3.79 per basic and diluted class A share, respectively.
Thu, 11/02/2010 - 15:22
DB Climate Change Advisors, the climate change investment and research business of Deutsche Bank's asset management business, and Nasdaq OMX Group have introduced the DB Nasdaq OMX Clean Tech Index.
Thu, 11/02/2010 - 14:27
Kohlberg Kravis Roberts and Premier Natural Resources have formed a partnership to pursue investments in oil and gas properties in North America.
Thu, 11/02/2010 - 14:10
Partners Capital, a London and Boston based private investment office, has appointed Ethan Hall as director of research and Sean Farrell as an investment principal.
Thu, 11/02/2010 - 12:25
The DMX - Directional Markets Index heads the list of investable Alternative Investment Indices with a return of 0.18 per cent in February.
Thu, 11/02/2010 - 12:23
The beginning of a new year always provides a moment for reflection on the previous 12 months as well as looking toward the year to come, and 2009 was certainly an interesting and transitiona
Thu, 11/02/2010 - 12:10
What a difference a year has made. In 2009, hedge funds posted record gains, reversing steep declines from the year prior, and capital, coveting those impressive returns, is returning.
Thu, 11/02/2010 - 12:08
Peak Ridge Capital, an alternative asset management firm, has added Gary King as a senior strategic adviser to the firm.
Thu, 11/02/2010 - 12:05
In the midst of last year's global financial crisis, many fund executives and managers were not prepared for what lay ahead.
Thu, 11/02/2010 - 11:30
The concerns about Eurozone markets are being reflected in the actions of hedge funds and investors, an expert has asserted.
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Lunch Walks Among Us
By (author) Jim Benton
Illustrated by Jim Benton
Format: Hardback
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Lunch Walks Among Us by Jim Benton
Book DescriptionFranny K. Stein is not your average girl -- she's a mad scientist. She prefers poison ivy to daisies, and when Franny jumps rope, she uses her pet snake. The kids in Franny's class think she's weird, wacky, and just plain creepy.Tired of being stared at, Franny decides to attempt her most dangerous experiment yet -- she's going to "fit in." but when a giant Monstrous Fiend attacks the class, everyone knows it's up to a "mad scientist" to save the day. But has Franny lost her creepy, crawly ways?
Buy Lunch Walks Among Us book by Jim Benton from Australia's Online Bookstore, Boomerang Books.
Book DetailsISBN: 9780756976521
(201mm x 130mm x 14mm)
Imprint: Perfection Learning
Publisher: Perfection Learning
Publish Date: 1-Sep-2004
Country of Publication: United States
Other Editions...
Books By Author Jim Benton
Quite a Mountain, Hardback (June 2017)
Award-winning cartoonist Jim Benton presents an all-ages book about following your dreams and the ups and downs of friendship.
Dumbness Is a Dish Best Served Cold (Dear Dumb Diary: Deluxe), Hardback (September 2016)
Includes an excerpt from: Dear dumb diary, Let's pretend this never happened.
Live Each Day to the Dumbest (Dear Dumb Diary Year Two #6), Paperback / softback (August 2015)» View all books by Jim Benton
When Jamie inherits her grandmother's trunk, she discovers an old diary and, after reading it, realizes that everyone's the same--deep down.
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Blukacz E.A.,Canadian Department of Fisheries and Oceans |
Koops M.A.,Canadian Department of Fisheries and Oceans |
Sutton T.M.,Purdue University |
Sutton T.M.,University of Alaska Fairbanks |
And 9 more authors.
Journal of Great Lakes Research | Year: 2010
Sexual-selection theory predicts males will increase investment in ejaculates if there is an increase in the level of sperm competition. Production of ejaculates is energetically costly, so males in better condition should be able to produce ejaculates of higher quality than individuals in poorer condition. We examined how ejaculate investment (i.e., relative testes mass) and sperm quality (i.e., sperm swimming speed) in lake whitefish (Coregonus clupeaformis) were related to residual soma mass, fork length, and fish age using data collected from Lake Michigan and Bay of Quinte (Lake Ontario). Populations from both lakes had positive relationships between relative testes mass and residual soma mass. Fork length was the most important predictor of sperm swimming speed with larger males from both lakes tending to have faster swimming sperm than smaller fish. Testis asymmetry, which is a commonly observed phenomenon in other animals but which has only recently been reported in fishes, was found to occur in the majority of examined lake whitefish with the left testes typically larger than the right. © 2010. Source
Andvik R.T.,University of Wisconsin - Stevens Point |
Sloss B.L.,University of Wisconsin - Stevens Point |
VanDeHey J.A.,University of Wisconsin - Stevens Point |
Claramunt R.M.,Charlevoix Research Station |
Isermann D.A.,University of Wisconsin - Stevens Point
Journal of Great Lakes Research | Year: 2016
Lake whitefish (Coregonus clupeaformis) support the primary commercial fishery in Lake Michigan. Discrete genetic stocks of lake whitefish have been identified and tagging data suggest stocks are mixed throughout much of the year. Our objectives were to determine if (1) differential stock harvest occurs in the commercial catch, (2) spatial differences in genetic composition of harvested fish were present, and (3) seasonal differences were present in the harvest by commercial fisheries that operate in management zones WI-2 and WFM-01 (Green Bay, Lake Michigan). Mixed stock analysis was conducted on 17 commercial harvest samples (n = 78-145/sample) collected from various ports lake-wide during 2009-2010. Results showed significant mixing with variability in stock composition across most samples. Samples consisted of two to four genetic stocks each accounting for ≥. 10% the catch. In 10 of 17 samples, the stock contributing the largest proportion made up <. 60% of the harvest. In general, seasonal and annual differences existed in the proportional stock contribution at a single capture location. Samples from Wisconsin's primary commercial fishing management zone (WI-2) were composed predominately of fish from the Big Bay de Noc (Michigan) stock as opposed to the geographically proximate, North-Moonlight Bay (Wisconsin) stock. These findings have implications for management and allocation of fish to various quotas. Specifically, geographic location of harvest, the current means of allocating harvest quotas, is not the best predictor of genetic stock harvest. © 2016. Source
How to manage data to enhance their potential for synthesis, preservation, sharing, and reuse-a Great Lakes case study [Cómo manejar datos para incrementar el potencial para su síntesis, preservación, intercambio y reutilización -los Grandes Lagos como caso de estudio]
Kolb T.L.,Charlevoix Research Station |
Agnes Blukacz-Richards E.,Canadian Department of Fisheries and Oceans |
Muir A.M.,Great Lakes Fish Commission |
Muir A.M.,Michigan State University |
And 6 more authors.
Fisheries | Year: 2013
Proper data management (applying coordinated standards and structures to data collection, maintenance, retrieval, and documentation) is essential for complex projects to ensure data accuracy and accessibility. In this article, we used a recent project evaluating changes in Lake Whitefish (Coregonus clupeaformis) growth, condition, and recruitment in the Great Lakes as a case study to illustrate how thoughtful data management approaches can enhance and improve research. Data management best practices described include dedicating personnel to data curation, setting data standards, building a relational database, managing data updates, checking for and trapping errors, extracting data, documenting data sets, and coordinating with project collaborators. The data management actions taken ultimately resulted in a rich body of scientific publication and a robust database available for future studies. Investing in data management allowed this project to serve as a model for taking the first steps toward a common goal of sharing, documenting, and preserving data that are collected and reported during the scientific research process. Source
Claramunt R.M.,Charlevoix Research Station |
Muir A.M.,Purdue University |
Muir A.M.,Golder Associates |
Johnson J.,Charlevoix Research Station |
And 2 more authors.
Journal of Great Lakes Research | Year: 2010
We compared diets of juvenile lake whitefish among six sites in Lake Michigan and one in Lake Superior during 2005 and 2006 to assess spatial and temporal patterns in food habits and evaluate if ontogenetic diet shifts occur that may influence growth and survival. A total of 262 and 496 juveniles were captured in 2005 and 2006, the majority of which were captured during June and July. Sites in southern Lake Michigan tended to have larger juveniles, and the smallest juveniles were observed at Naubinway, northern Lake Michigan, and Whitefish Point, Lake Superior. The mean number of prey items per stomach differed among sampling sites and years. Copepods were the most prevalent prey item, and were present in greater than 70% of juvenile stomachs from most sites. However, the percent by number of copepods decreased during July as chironomids and other benthic macroinvertebrates increased in number. There was a significant positive relationship between percent of benthic prey items and mean length of juvenile lake whitefish. A substantial increase in the percent of benthic prey consumed after 40 mm (total length) was observed and likely resulted from juvenile lake whitefish crossing a size threshold for benthic feeding relating to morphological changes (i.e., transition of mouth opening from terminal to sub-terminal) in addition to a potential increase in the availability of emergent macroinvertebrates. Timing of the transition to benthic feeding is likely regulated by the number of prey per juvenile and the overlap with peak emergence of important benthic aquatic invertebrates such as chironomids. A better understanding of these factors will increase our understanding of juvenile lake whitefish growth and survival, which are necessary for improving year-class strength predictions. © 2010. Source


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The neural control of "cooperative" hand movements reflecting "opening a bottle" was explored in human subjects by electromyographic (EMG) and functional magnetic resonance imaging (fMRI) recordings. EMG responses to unilateral nonnoxious ulnar nerve stimulation were analyzed in the forearm muscles of both sides during dynamic movements against a torque applied by the right hand to a device which was compensated for by the left hand. For control, stimuli were applied while task was performed in a static/isometric mode and during bilateral synchronous pro-/supination movements. During the dynamic cooperative task, EMG responses to stimulations appeared in the right extensor and left flexor muscles, regardless of which side was stimulated. Under the control conditions, responses appeared only on the stimulated side. fMRI recordings showed a bilateral extra-activation and functional coupling of the secondary somatosensory cortex (S2) during the dynamic cooperative, but not during the control, tasks. This activation might reflect processing of shared cutaneous input during the cooperative task. Correspondingly, it is assumed that stimulation-induced unilateral volleys are processed in S2, leading to a release of EMG responses to both forearms. This indicates a task-specific neural coupling during cooperative hand movements, which has consequences for the rehabilitation of hand function in poststroke patients.
In contrast to the lower limbs, a great variety of uni- and bimanual functional hand/arm movements exist that requires a specific neural control. In monkeys, it was suggested that the supplementary motor area (SMA) of one hemisphere influences the motor outflow of both hemispheres (Jenny 1979; Rouiller et al. 1994). Furthermore, the primary (Donchin et al. 1998; Kermadi et al. 1998) and nonprimary motor cortex (Tanji et al. 1987) as well as the prefrontal cortex (Theorin and Johansson 2010) are assumed to play an essential role in the execution of bimanual tasks. Previous research has indicated that distributed neural networks coordinate interlimb coordination including cortical and subcortical areas (Kazennikov et al. 1999; Stephan et al. 1999; Kermadi et al. 2000; Debaere et al. 2001; Swinnen 2002), and their involvement might be task-specific (Ohki and Johansson 1999; Bracewell et al. 2003; Wiesendanger and Serrien 2004; White et al. 2008; Alberts and Wolf 2009; Heitger et al. 2012).
Most human studies on bimanual tasks involve the performance of bilateral separate, symmetrical, or reciprocal movements (Kelso et al. 1979; Marteniuk et al. 1984; Fowler et al. 1991; Donchin et al. 1998; Swinnen 2002; McCombe Waller and Whitall 2008; Liuzzi et al. 2011), or object manipulation tasks (Johansson et al. 2006; Theorin and Johansson 2007), while cooperative hand movements are rarely studied (for review, see Obhi 2004). So far it has been demonstrated by functional magnetic resonance imaging (fMRI; Puttemans et al. 2005; Johansson et al. 2006; Theorin and Johansson 2007; Grefkes et al. 2008; Goble et al. 2010) and magnetoencephalography (Disbrow et al. 2001), the brain activation pattern during bimanual hand movements is task- and condition-dependent. This includes the activation of the SMA, the primary motor cortex (M1), the premotor cortex (PMC), and the secondary somatosensory cortex (S2). However, the role of these cortical areas has not yet been investigated during cooperative hand movements.
The task investigated here, that is, a "bottle opening" movement against a defined resistance, requires bimanual "cooperative" movements, in which one hand supports the action of the other one in order to complete the task. Although many daily tasks involve cooperative hand movements, little is known about the underlying neural mechanisms.
The distribution of electromyographic (EMG) responses in arm muscles evoked by nerve stimulation allows analysis of the connectivity of neural circuits involved in a specific task (Michel et al. 2008; Dietz et al. 2011). In cases of uni- or bilateral separate arm movements, this approach is known to evoke EMG responses in the forearm muscles ipsilateral to the stimulation site (Zehr and Kido 2001). It is expected that, during cooperative hand movements, a neural coupling is reflected in reflex EMG responses to unilateral nerve stimulation in the forearm muscles of both sides.
Additionally, we used fMRI in order to identify brain areas involved in the cooperative hand movement task as complementary information. This includes the assumption that the supraspinal pathways and centers, mediating the bilateral reflex EMG responses, can be detected by the imaging study. The aim was to identify the cortical areas involved in the cooperative hand movements and whether they differ from those activated in the control conditions. We hypothesize that the neural coupling during cooperative hand movements is achieved by an exchange of information from each hand to both hemispheres at a brainstem level, followed by a processing of the afferent input in specific cortical sensori-motor areas (e.g., SMA, PMC, and S2), which leads to an appropriate control of cooperative hand movements. Since S2 is suggested to be involved in the integration of information from the 2 sides of the body (Lin and Forss 2002) and is modulated by task effort (Heuninckx et al. 2005; Goble et al. 2010), we hypothesize that neural processing of cooperative hand movements can be achieved by an involvement of S2. Subsequently, we performed psycho-physiological interactions (PPIs) and functional connectivity (FC) analyses to estimate the functional coupling between brain regions of interest (ROIs) with relation to task performance.
General Procedures and Experimental Conditions
This study was approved by the Ethics Committee of the Canton of Zurich and conformed to the standards set by the Declaration of Helsinki. All subjects were informed about the experiment and gave written consent for their participation. The "electrophysiological" recordings were performed in 12 right-handed (Oldfield 1971) healthy volunteers (mean age 27.3 years, range 25–32 years; 4 males). Twenty right-handed healthy volunteers (mean age: 33 ± 9.8 years; 13 males) participated in the "fMRI study." Four of the volunteers participated in both studies. Only right-handed subjects were chosen in order to avoid an additional variable that could influence the results.
Electrophysiological Study
A device that allows the performance of cooperative movement tasks of the upper limbs was constructed together with the Swiss Federal Institute of Technology Zurich (ETHZ) for the electrophysiological experiments (patent registration number E 11167554). The device comprises 2 handles representing a bottle that is placed horizontally in front of the subject (Fig. 1A). The diameters of the 2 handles corresponded approximately to the 2 ends of a normal bottle (right 5 and left 7 cm). Torque and angular rotation sensors allowed the recording of torsional moments and the position of the handles on both sides. For the cooperative movement task, the 2 ends of the "bottle" were mechanically connected, that is, when a torque was applied on one side it became transmitted to the other side. Therefore, the resistance was constant throughout a movement cycle on both sides. This cooperative mode was either used dynamically (the handles could be turned in opposite directions against a predefined resistance) or statically (the handles were blocked for reciprocal rotation).
The maximum torque (MaxT) of each subject was determined in the static mode of the device. The highest value of 3 attempts was taken. For the 2 experimental conditions, the resistance of the device was set to 20% MaxT. In the dynamic task (dyn-coop), subjects performed rhythmic "opening" movements, that is, extension of the right wrist and flexion of the left wrist (frequency of 45/min, indicated by a metronome), with the right hand counteracted by the left hand, that is, both hands were free to rotate during the dynamic task. A visual feedback about the torques applied to the device by both hands was provided through a potentiometer. In one control task (stat-coop), subjects exerted a bimanual reciprocal isometric/static torque of 20% MaxT on the handles (indicated again on a screen placed in front of the subject), with the right forearm extensors counteracted by the left flexor muscles thus mimicking the opening task. An additional control task consisted in a frequently investigated upper limb task (Swinnen 2002), that is, bilateral synchronous pro-/supination movements (pro-sup; frequency of 40–50/min) with freely held dumb-bells (1 or 2 kg, depending on the EMG background activity which had to match the EMG activity during the dynamic task as good as possible). This task was chosen for control as we expected a similar dynamic proprioceptive input becomes generated as during the dyn-coop task. Each of the 3 motor tasks was performed approximately 80 times. Figure 1B shows an overview over the setups for the different experimental conditions.
Recording of Biomechanical and Electromyographic Signals
The angular position and torque signals were measured separately for both sides. EMG recordings were made using surface electrodes placed over the forearm flexor (Musculus flexor carpi ulnaris) and extensor (M. extensor carpi radialis) muscles and over the M. deltoideus pars clavicularis muscles of both arms. All signals were sampled at 1000 Hz and recorded using Soleasy v. 4.1 (ALEA Solutions GmbH Software and Instrumentation, Switzerland). EMG signals were amplified (10 000-fold) and band-pass filtered (30–300 Hz). Afterwards, the signals were transferred together with biomechanical signals to a personal computer via an analog-to-digital converter. Further processing of the data was done using Soleasy v. 4.1. EMG signals were offset corrected, rectified, and band-stop filtered (45–55 Hz) before root mean square (RMS) values, averages, and grand averages were calculated.
Ulnar Nerve Stimulation
The distal part of the ulnar nerve was randomly stimulated 15 times per side at the onset of movement cycles at the right or left forearm for the release of reflex responses in the arm muscles. The stimulation electrodes (2.63 cm2 in size; Neuroline 700, Ambu, Ballerup, Denmark) were placed over the ulnar nerve at both wrists with an interelectrode space of 2 cm.
Electrical pulses were administered by an Electro Stimulator (AS 100, Alea Solutions, Zurich, Switzerland). Each electrical stimulus consisted of a train of 4 biphasic pulses with 2 ms duration per pulse and a frequency of 200 Hz resulting in total stimulus duration of 17 ms. The intensity was set on 1.5 times motor threshold (MT). MT was defined as the lowest intensity leading to a visible twitch of the M. abductor digiti minimi. It was determined by stepwise increasing the intensity. This nonnoxious stimulation intensity (1.5 MT) is known to evoke cutaneous reflexes (Yang and Stein 1990). A similar stimulus paradigm has previously been used to investigate neural limb coupling during locomotion in healthy subjects (Michel et al. 2008; Dietz et al. 2009) and poststroke patients (Kloter et al. 2011).
In a pilot study, we compared the effects of median, radial, and ulnar nerve stimulation. The bilateral responses to ulnar nerve stimulation were more reproducible, and the stimuli were less painful than median nerve stimulation. Superficial radial nerve stimulation was more difficult to perform (perception threshold is a quite subjective measure). Therefore, we used ulnar nerve stimulation in our study. The stimulation electrodes were attached with a surgical tape after determining the optimal stimulation site. The MT of each person was checked to confirm that it was constant during and after the experiment.
The stimuli were randomly released every third to sixth cyclic movement triggered by a change in torque of 0.035 Nm, that is, about 100 ms after the start of the opening (dyn-coop) movement of the right hand and every 5–9 s during the control tasks. A dummy signal was released at the same time point without stimulation and was used to record the nonstimulated EMG, that is, background activity.
Reflex Data Analysis
Reflex responses were analyzed by calculating the RMS of EMG signals including all samples within a time window of 50–200 ms after the start of stimulation. The window was chosen according to the appearance of the main components of the reflex responses. The responses were compared with the RMS of background EMG activity within the same time window following "dummy" stimulations using a multivariate General Linear Model (GLM) with post hoc paired t-test with Bonferroni correction. The factors for the GLM were condition, stimulation side, and recording site.
The responses were mostly suppressive. The amplitude of the reflex response (maximal negativity/suppression; maximal positivity/facilitation) was compared with that of background activity in the nonstimulated recordings. The onset of reflex responses was determined manually. The differences in latency were also compared by a GLM with post hoc paired t-test with Bonferroni correction. Pearson correlations were applied in order to evaluate the similarities between the shape of the EMG response patterns recorded from the right forearm extensors and left forearm flexor muscles during the dyn-coop opening task, following unilateral nerve stimulation on the ipsilateral and contralateral sides, respectively.
fMRI Study
For the fMRI study, a hand-held MR-compatible device was used corresponding to the bottle device used in the EMG experiment, constructed by the ETHZ. In total, 20 volunteers performed the dyn-coop condition with the left hand resisting the opening movements guided by the right hand (ca. 20% MaxT) with a frequency of 45/min, so that the right extensors and left flexors were activated.
For control, the same participants performed a bilateral synchronous pro-sup movement task of both arms, with a frequency of 45/min while holding fMRI-compatible dumb-bells of 500 g. Additionally, 13 (out of 20) randomly selected volunteers performed 2 additional "non- coop" tasks. During the "non-coop-1" task, they held the device and executed symmetrical wrist extension and flexion movements (cf. Fig. 1B, non-coop-1). The rationale for this choice of task was to have a control task in which subjects performed synchronized (in-phase) but noncooperative wrist movements. This control was included to see whether activation of a brain region is exclusively influenced by the factor "cooperative movement" or by the factor wrist movement during extension and flexion movements in the dyn-coop task. During the "non-coop-2" task, subjects performed the same reciprocal hand wrist movements during the dyn-coop condition but without holding the device (cf. Fig. 1B, non-coop-2). Thus, the factor "bimanual hand movement" was kept constant, but the factor "hand cooperation" was minimized.
For all tasks, pacing was achieved by visual cues, which were shown via a mirror system, indicating the start of the requested movement (movement onset was further controlled by the experimenter). The synchronization between the fMRI clock and the temporal onset of the visual cues was controlled by Presentation (www.neurobs.com/presentation). Each task was performed separately (6 min duration) and was arranged in a block design: During each block, 7 opening-closing or pronation-supination movements were followed by rest periods of 8–10 s. For each experimental condition, participants performed 10 blocks (=70 trials). Task presentation was randomized across subjects to avoid order effects. To prevent head movements during the fMRI scan, a neck-pad was used to fixate the head. In addition, subjects were only included if overall head motion was <1.5 mm in translation and 1.5° in rotation. We therefore believe that any task-related activity was not influenced by head motion.
fMRI Acquisition
For all tasks, fMRI was performed at the University Hospital of Zurich on a Philips Ingenia 3-T whole-body MRI system (Philips Medical Systems, Best, The Netherlands) and an 8-channel head coil. Functional data were obtained in 180 scans per run using 30 transverse slices covering the whole brain in oblique orientation. Slices were acquired in an interleaved order, using a sensitivity-encoded (SENSE, factor 1.8), single-shot, echo planar imaging (EPI) technique (echo time = 35 ms, repetition time = 2000 ms, field of view = 220 × 220 mm, voxel size: 2.75 × 2.75 × 4 mm, resliced: 1.72 × 1.72 × 4 mm, flip angle: 78°). SENSE imaging was applied to shorten readout trains in a single shot in EPI, to reduce susceptibility artifacts, and to improve spatial resolution (Boujraf et al. 2009). Four dummy scans were acquired at the beginning of each run and discarded in order to establish a steady state in T1 relaxation for all functional scans.
Data were analyzed using MATLAB 7.9 (Mathworks, Inc., Natick, MA, USA) and SPM8 (Wellcome Department of Cognitive Neurology, London, UK). For each subject, functional images were realigned, normalized to the EPI template provided by the Montreal Neurological Institute (MNI brain), resliced to 2 × 2 × 2 mm voxel size, and smoothed using 8-mm full-width at half-maximum Gaussian kernel. An autoregressive model of the first order was used to account for serial correlations. High-pass filtering with standard 128 s cutoff eliminated slow signal drifts. The Anatomical Automatic Labeling Toolbox for SPM8 was used to identify activated regions (Tzourio-Mazoyer et al. 2002).
Regions of Interest Analysis
Before testing for fMRI signal changes related to cooperative hand movements (i.e., dyn-coop vs. pro-sup), we first estimated the average activation strength (i.e., parameter estimates) across the dyn-coop and pro-sup tasks (F-contrast, P < 0. 05, family-wise error [FWE] corrected for multiple comparisons) in ROIs known to be involved in bimanual hand movements (Puttemans et al. 2005; Grefkes et al. 2008). The spatial coordinates of the individuals ROIs were determined following the definition of Grefkes et al. (2008): the M1 region has to be located in the precentral gyrus and central sulcus near the hand knob (MNI coordinates in this study: left M1: −34 −26 56 and right M1: 36 −26 56), the PMC in the lateral precentral sulcus (MNI coordinates: left PMC: −50 −2 44 and right PMC: 52 −2 46), the SMA in the dorsal medial wall within the interhemispheric fissure (MNI coordinates: 0 −19 48), and the S2 region in the upper bank of the Sylvian fissure (MNI coordinates: left S2: −56 −16 14 and right S2: 54 −14 18). Subsequent analyses were performed for ROIs, placed in S1 and in the insular cortex. For each subject, the time series of all ROIs were extracted in a sphere region (radius = 4 mm).
fMRI Data Analysis
A standard hemodynamic response function was used for convolution of the model regressors. First-level analyses were conducted using a voxel-wise GLM, which reflects a flexible generalization of an ordinary/simple linear regression (Friston et al. 1995). Each task was entered as regressors into 4 separate GLMs: dyn-coop and pro-sup (n = 20), and non-coop-1 and non-coop-2 (n = 13). Session-specific motion parameters were modeled as covariates of no interest. Second-level random effect analyses were conducted using a full-factorial design. The following 2 contrasts were estimated: "dyn-coop versus pro-sup" (n = 20) and "dyn-coop versus average (pro-sup and non-coop-1/2)" (n = 13). All fMRI results were shown on a cluster-corrected (Forman et al. 1995; Slotnick et al. 2003) voxel threshold of P < 0.001 (spatial extent: k ≥ 42 voxels). The cluster size threshold for the selected P-values was estimated using Monte Carlo simulations (http://afni.nimh.nih.gov/pub/dist/doc/program_help/AlphaSim.html). The cluster threshold method was applied to control for the overall type I error. Only gray matter-related fMRI signal changes will be reported.
Psycho-Physiological Interactions and Functional Connectivity
PPI is a brain imaging method of estimating the functional coupling between a brain region and the rest of the brain with relation to the performance of a particular cognitive task (Friston et al. 1997). In this study, the psychological vector was separately modeled for 2 types of bimanual hand movements: (1) dyn-coop and (2) pro-sup. For example, the PPI-specific GLM for the dyn-coop task contains 3 regressors: The interaction term (blood oxygen level-dependent [BOLD] response × psychological vector), main effect of BOLD activity from a given ROI, and main effect of psychological vector (e.g., dyn-coop). To extend the concept of factorial designs to PPI's, the basic idea is to substitute (neural) activity from one cerebral region for one of the factors:
We used the SPM toolbox conn (v13i, http://www.nitrc.org/projects/conn/) to perform the FC analysis. White matter, cerebrospinal fluid, and the 6 motion parameters were used as covariates of no interest. Only the white matter and cerebrospinal fluid signals were removed to avoid any bias introduced by removing the global signal (i.e., gray matter) (Behzadi et al. 2007; Murphy et al. 2009). This approach should "normalize" the distribution of voxel-to-voxel connectivity values as effectively as including the global signal as a covariate of no interest, but without the potential problems of the latter method. Although we did not record respiration and cardiac responses, it has been demonstrated that nonneuronal physiological noise (e.g., cardiac and respiratory signal) can successfully be removed by the CompCor algorithm (Behzadi et al. 2007) as implemented in the conn toolbox. Bivariate correlations were calculated as a measure of strength of FC, to examine cross-correlations of BOLD signal time series between ROIs. For each individual, the fMRI time series were extracted for each ROI using MarsBaR (Brett et al. 2002; http://marsbar.sourceforge.net/) after the fMRI time series had been spatially smoothed, temporally filtered (0.01–0.1 Hz), normalized (to the MNI template), and motion corrected. The signal of a given ROI was then averaged for 4-mm diameter spheres. The same ROIs as for the PPI analysis were used. Task-specific (dyn-coop and pro-sup) statistical results were represented at P ≤ 0.05 (FWE-corrected for multiple comparisons).
Electrophysiological Recordings
An opening movement cycle took a mean of 485 ms. The movement onset of the left and right hands during the dyn-coop task was analyzed using the changes in hand position (angular rotation sensors) at both handles. According to this analysis, both hands started almost simultaneously with the dynamic opening torque exerted by the right-hand and the left-hand compensatory torque (difference between right and left hands: 18 ± 18 ms).
During the different tasks, reflex responses measured in proximal and distal arm muscles following unilateral ulnar nerve stimulation showed approximately the same behavior, that is, a unilateral (ipsilateral) EMG response during the control tasks and a bilateral response during the dyn-coop task. For further analysis, only the forearm flexors and extensor muscles were included.
Figure 2 shows an example of the EMG signal recordings from the right extensor muscles and the biomechanical signals of torque and position of both sides from one volunteer during the performance of the dyn-coop (Fig. 2A) and stat-coop (Fig. 2B) tasks. During the dynamic task, segmented EMG responses appeared in the right extensor muscles following right and left ulnar nerve stimulation, whereas in the nonstimulated movements they did not. In the static task, a response was only discerned in the ipsilateral muscle.
In the dyn-coop task, the reflex EMG responses evoked by the stimulation consisted mainly of suppressive responses on both sides. These were further evaluated for their similarities in terms of latency, duration, and amplitude (Fig. 3a,b). In contrast, during the stat-coop task, reflex responses appeared only ipsilateral to the same stimulation (Fig. 3c).
Figure 3 shows the overall averages of the reflex EMG responses in the right extensor and left flexor muscles to ipsilateral (Fig. 3A) and contralateral (Fig. 3B) ulnar nerve stimulation during dyn-coop movements (Fig. 3a,b). The mean background EMG activity is shown as gray area. The RMS values of all reflex responses (time window 50–200 ms) in the dyn-coop task were significantly different from background EMG activity (stimulation ipsilateral P < 0.01, contralateral P < 0.05). The same difference was found after ipsilateral stimulation in the stat-coop task (Fig. 3c; P < 0.05) and in the pro-supin task (Fig. 3d; P < 0.005) but not following contralateral stimulation, where no response could be detected.
In Figure 3, the stimulation artifact lasted for the first 17 ms on both sides. The responses in the right extensor muscles to right (ipsilateral) ulnar nerve stimulation (Fig. 3Aa) appeared with an early response (ER) that had a latency of 25 ± 3.1 ms, followed by a first suppressive response (N1) peaking at a latency of 43 ± 6.0 ms after onset of right-side stimulation and a first facilitative wave (P1) with a peak at 59 ± 7.2 ms. The peak of the second suppressive wave (N2) was reached at 86 ± 10.1 ms and the following plateau-like activity (P2) was observed at 120 ± 20.3 ms. Following left (contralateral) ulnar nerve stimulation (Fig. 3Ba), the EMG response onset in the right extensor was observed at 61 ± 8.8 ms, the peak of the suppressive wave (N2) occurred at a latency of 87 ± 7.7 ms, and the plateau-like activity (P2) was reached again at 104 ± 8.7 ms. The grand averages of late right extensor responses to ipsi- and contralateral nerve stimulation were similar in their latencies, durations, and amplitudes.
Figure 3 also shows the corresponding EMG responses in the left flexor muscles following left and right ulnar nerve stimulation (Fig. 3b). Following left (ipsilateral) ulnar nerve stimulation (Fig. 3Ab), an ER (onset 24 ± 3.7 ms) was followed by a suppressive peak (N1) with a latency of 48 ± 5.8 ms, a facilitative peak (P1) at 69 ± 10.8 ms, and a second suppressive peak (N2) at 96 ± 18.4 ms. The plateau-like activity (P2) was reached again at 121 ± 22.9 ms. Stimulation of the right (contralateral) ulnar nerve (Fig. 3Bb) was followed by a suppressive EMG response in the left flexor muscle starting at 66 ± 8.5 ms with a peak suppression (N2) at 88 ± 7.7 ms, followed by a peak facilitation (P2) at 109 ± 5.1 ms.
The background activity and EMG response amplitudes were about 3 times larger in the extensor than in the flexor muscles. In addition, the response amplitudes in the extensor muscles (suppressive peaks) were smaller following contralateral compared with ipsilateral stimulations (not significant, P = 0.057).
Figure 3c,d shows the EMG responses in the right forearm extensors following ipsilateral (Fig. 3A) and contralateral (Fig. 3B) ulnar nerve stimulation during the control tasks: Static (Fig. 3c) and pro-sup (Fig. 3d) tasks. In contrast to the responses in the right-arm muscles during the dyn-coop task (Fig. 3Ba,b), no distinct EMG responses could be detected in the right extensor muscle when the left (contralateral) ulnar nerve was stimulated (Fig. 3Bc,d). In the static task (Fig. 3c), the EMG responses in the right extensor muscle following ipsilateral nerve stimulation appeared with a suppressive peak (N1) at a latency of 47 ± 5.6 ms, followed by a facilitative peak (P1) at a latency of 66 ± 6.5 ms, a second suppressive peak (N2) at 96 ± 15.3 ms, and a late facilitative peak (P2) at 141 ± 21.7 ms. Similar responses appeared in the left flexor muscle following left ulnar nerve stimulation (not shown).
Also in the pro-sup task (Fig. 3d), EMG responses were only present in the muscles of the stimulated arm. The EMG responses in the right extensor muscle following ipsilateral nerve stimulation appeared with a suppressive peak (N1) at a latency of 52 ± 4.8 ms, followed by a facilitative peak (P1) at a latency of 73 ± 6.3 ms, a second suppressive peak (N2) at 106 ± 12.7 ms, and a late facilitative peak (P2) at 148 ± 29.8 ms.
The response pattern (early and late reflex complexes; ER to P2) to ipsilateral stimulation was similar in latency, duration, and amplitude during the dyn-coop and the control tasks (Fig. 3A). Only during the dyn-coop task, a late reflex complex (N2 and P2) appeared also at the contralateral, nonstimulated side (Fig. 3B), which again was similar in latency, duration, and amplitude to the late ipsilateral reflex complex.
The level of background activity in the extensor muscles was about 3 times larger (RMS values: 154–45 µV) in the dynamic compared with the static condition. When the amplitude of the EMG responses was compared with that of background EMG (same time interval in nonstimulated movements), it amounted to 65% in the dynamic and 60% in the static task. The difference in the background activity is thought to be due to the fact that a dynamic movement against a torque of 20% MaxT produces a stronger muscle activation compared with the static/isometric muscle contraction with a 20% MaxT.
fMRI Recordings
Figure 4A shows robust mean fMRI signal changes across the dyn-coop and pro-sup tasks in the SMA, PMC, and M1 as well as in the cerebellum and higher visual areas (including V5). However, the parameter estimates (Fig. 4B) did not differ between dyn-coop and pro-sup in these regions. The contrast dyn-coop versus pro-sup elicited exclusively bilateral activation patterns in the S2 (Brodmann area, BA, 43) at a voxel threshold of P < 0.001 (cluster-corrected, k ≥ 42 voxels) as shown in Figure 5A and Table 1A. Parameter estimates were significantly higher for the dyn-coop than for the pro-sup condition (Fig. 5A, right S2: P < 0.001 and left S2: P < 0.001). As shown in Figure 5B and Table 1B, the contrast between "dyn-coop versus average pro-sup and non-coop" still revealed bilateral S2 activation at a voxel threshold of P < 0.001 (cluster-corrected, k ≥ 42 voxels), and a weaker activation of the left insular cortex (BA 13), cerebellum (lobes 3–5), right posterior thalamus, and bilateral S1 (BA 2/3). S1 activity was especially strong if the dyn-coop task was compared with the non-coop-2 task (P < 0.0001, data not shown), that is, a task in which subjects did not hold any device but performed out-phase hand movements. At a more liberal threshold (P < 0.005, cluster-corrected) also in the contrast dyn-coop versus pro-sup, additional activations to S2 were observed bilaterally in S1 (Supplementary Fig. 1). Only the left insular cortex (MNI: −38 −14 12, Table 1B, P = 0.01) but not its homologous counterpart (MNI: 38 −14 12) or literature-based insular cortex ROIs (Heuninckx et al. 2005; MNI: −36 24 −8 and −36 −2 6) showed stronger activity for dyn-coop relative to all control conditions.
|Brodmann area
|MNI coordinates
|(A) Contrast "dyn-coop task > pro-sup task"
|Left postcentral gyrus (S2)
|Right postcentral gyrus (S2)
|(B) Contrast "dyn-coop task > average pro-sup task and noncoop tasks"
|Left postcentral gyrus (S2)
|Right postcentral gyrus (S2)
|Left insula
|Right posterior thalamus
|Left postcentral gyrus (S1)
|Right postcentral gyrus (S1)
|Brodmann area
|MNI coordinates
|(A) Contrast "dyn-coop task > pro-sup task"
|Left postcentral gyrus (S2)
|Right postcentral gyrus (S2)
|(B) Contrast "dyn-coop task > average pro-sup task and noncoop tasks"
|Left postcentral gyrus (S2)
|Right postcentral gyrus (S2)
|Left insula
|Right posterior thalamus
|Left postcentral gyrus (S1)
|Right postcentral gyrus (S1)
The age of the subjects was not correlated to the right S2 (r = −0.21, P = 0.37) or left S2 (r = 0.35, P = 0.13) activity for the dyn-coop task (assessed by Pearsons's correlations).
The PPI analysis for the between-task comparison showed significant results only for the contrast dyn-coop task versus pro-sup task (P < 0.001, cluster-corrected with k ≥ 42), but not vice versa (see Supplementary Table 1). A main finding was that a preselected seed was never "connected" to its homologous counterpart. In general, results were rather unspecific and did not show a unique pattern within intra or interregional seeds. In contrast, the FC analysis revealed that the 2 S2 ROIs were functionally connected during the dyn-coop task only (t = 3.75). In addition, the left M1 and right M1 ROIs show a functional connection (t = 6.21). At this statistical threshold, no functional coupling between any of the ROIs was observed for the pro-sup task.
The aim of this study was to explore the neural control of cooperative hand movements by electrophysiological and fMRI recordings. The main result was that only during the performance of a cooperative opening movement. EMG responses appeared in the forearm muscles of both arms, independent of which side was stimulated. Correspondingly, fMRI showed a bilateral functional coupling of the S2 regions during the dyn-coop task, but not in the control tasks. Although, in most bimanual tasks, an integrated control structure might be used. The present study suggests relevant task-specific differences in the neural control.
Task-Specific Neural Hand Coordination
In the present study, we observed a task-specific neural coupling during dynamic cooperative hand movements. Previous electrophysiological research in this field has focused mainly on the execution of unilateral or separate bimanual movements, (Donchin et al. 1998; Swinnen 2002; White et al. 2008). A task-dependent amplitude modulation of unilateral EMG responses in upper limb muscles to magnetic brain stimulation (Datta et al. 1989) and to cutaneous nerve stimulation (Zehr and Kido 2001) with larger amplitudes during a dynamic compared with a static muscle contraction (Zehr and Kido 2001) were described. Only ipsilateral EMG responses were also recorded in both control conditions investigated here.
This reflex behavior differs profoundly from that found during cooperative hand movements and represents the novel result of this study. Exclusively during the dynamic cooperative hand movements, a distinct contralateral EMG response pattern (N2–P2 complex) appeared in forearm muscles with approximately the same latency (80 ms) as the late complex (N2–P2) of the ipsilateral, stimulated side. Therefore, different neural circuitries are suggested to be involved during cooperative and noncooperative hand movements.
In the muscles ipsilateral to the nerve stimulation, the response pattern was more complex, combining early (ER and N1–P1 complex), similar to reflex responses elicited during control tasks, and long-latency (N2–P2 complex) reflex components present also on the contralateral, nonstimulated side only during the dyn-coop task. The distribution of reflex responses to a unilateral afferent volley reflects a task-specific, functionally meaningful, neural coupling of upper limbs, that is, the processing of an artificial input by (coupled) neural circuits. This coupling obviously depends on the performance of cooperative hand movements ("opening a bottle"), as the coupling did not occur when the task was mimicked in the static (stat-coop) condition or during the pro-sup task. The mostly suppressive action of the responses might reflect a transient blockage of processing the natural afferent input.
It might be argued that the high level of background EMG in the forearm extensor (compared with flexor) muscles (cf. Fig. 3a) contributes to the bilateral N2–P2 responses. However, this is rather unlikely as (1) the extensor background EMG level was similar during the pro-sup control task (Fig. 3d), but a response appeared only ipsilateral to the stimulation site and (2) the same bilateral N2–P2 pattern was obtained in the left flexors (Fig. 3b) during the dyn-coop task, although the background EMG level was low compared with the extensor activity (cf. Fig. 3c).
Task-Specific Involvement of CNS Areas
We suggest that such a task-specific neural coupling represents an operational rule, which occurs within the spinal cord, brainstem, and supraspinal circuitries. There is spinal decussation and bilateral termination of cervical corticospinal projections in the cervical cord of monkeys (Rosenzweig et al. 2009), which could account for the bilateral long-latency response pattern seen in the dyn-coop condition. Stimulation of reticulospinal cells can also lead to bilateral response patterns (Drew et al. 1996; Brocard et al. 2010). Such a mechanism was assumed to mediate bilateral arm muscle responses to unilateral leg nerve stimulation during locomotion of stroke subjects (Kloter et al. 2011). Although locomotor function differs basically from cooperative hand movements, the underlying task-dependent neural coupling of limbs might be achieved in a similar way. Nevertheless, it is not possible to conclude from the present experiments whether either one or both mechanisms are involved.
One has to be aware that the electrophysiological and fMRI recordings represent connected studies, which provide complementary information since both experimental parts examined cooperative hand movements. They can, however, not directly be linked with each other. Thus, the fMRI study does not allow direct conclusions to be drawn in relation to the electrophysiological findings. Based on our fMRI findings, we suggest that the pathways and brain areas involved in the generation of the bilateral reflex responses become reflected in the bilateral activation of S2 during cooperative hand movements (i.e., dyn-coop vs. pro-sup). Using a different set-up, this assumption is supported by observations in humans (Disbrow et al. 2001) and nonhuman primates (Whitsel et al. 1969) as S2 receives afferent inputs from receptor fields of both hands.
Earlier it was hypothesized that a single integrating center is involved in the control of bimanual movements (Wiesendanger and Miles 1982; Peters 1985; Jagacinski et al. 1988), and that the connectivity between the homologous primary motor cortices is mediated by the corpus callosum (Liuzzi et al. 2011). The latter mechanism would be in line with the observation that patients who undergo callosotomy are unable to perform these tasks (Preilowski 1972).
However, our fMRI results do not provide evidence for a single integrating center but for the existence of a brain region, that is, S2 bilaterally, which is specifically involved in the coordination of cooperative hand movements but not in the control tasks. If the contrast dyn-coop versus pro-sup task was analyzed, one could argue that we have not identified regions that are responsive to cooperative hand movements as the observed activation differences could simply be due to different proprioceptive input to S2. However, our results do not support this assumption, as bilateral S2 activation was still present after subtraction of the non-coop tasks, which involve both in-phase (non-coop-1 task) and out-phase (non-coop-2 task) bimanual hand movements. Thus, S2 activation appears to be task-dependent and might be modulated by an "additional/stronger coordinative effort" (Heuninckx et al. 2005; Wenderoth et al. 2005; Goble et al. 2010) during the dyn-coop task. Therefore, the "task-specific" bilateral activation of the S2 areas does not exclude an S2 activation in other bimanual movement tasks not investigated here.
In addition, an S1 activation was found especially in the contrast "dyn-coop versus non-coop-2", although it was weaker than S2 activation. This S1 activation has to be due to cooperative hand movements and not to out-phase wrist movements. Hence, we would conclude that successful integration of active cooperative hand movements (integration sensory information of both body parts) is primarily achieved by S2 with an additional involvement of S1.
It has been hypothesized that S2 plays a role in the human mirror system (Avikainen et al. 2002), because an active suppression of S2 occurred during action observation. Yet, this finding is unlikely to explain our results as visual observation of the hand was minimized during scanning. Furthermore, S2 seems to play an important role in proprioception (Lin et al. 2000). Although proprioception from the wrist movements was similar for both the dyn-coop and the pro-sup tasks, the shared bimanual afferent input during the dyn-coop task might be meaningful for the S2 activation. It is known that S2 activity increases during attentive cutaneous tasks (e.g., Nelson et al. 2004; Jung et al. 2012). It would thus seem reasonable that the dyn-coop condition included greater attention to the bimanual cutaneous information that signaled the activity of the opposite limb during rotation of the device.
S2 is also suggested to be involved in the exchange and integration of information from the 2 sides of the body (Lin and Forss 2002). After unilateral limb stimulation, S2 cortices of both hemispheres are activated and thus, S2 is thought to have a role in combining somatosensory information from the 2 sides of the body to allow its interhemispheric unification (Hari et al. 1998), which is in line with our fMRI results. In addition, the spatial extent of fMRI activation in the S2 (and ventral parietal areas) in humans is larger for bilateral hand stimulation than for unilateral (Disbrow et al. 2001). This further supports our suggestion that S2 is engaged and required in the interhemispheric processing of afferent input during cooperative hand movements. The functional connectivity analysis revealed that the left and right S2 areas (in addition to M1) were functionally connected only for the dyn-coop condition. Thus, a stronger connectivity between the right and the left S2 exists for the dyn-coop task relative to the pro-sup task. This finding supports the idea of an interaction and coupling between the 2 cortical areas involved in the execution of the cooperative task.
There was no specific dyn-coop-related activation of the SMA, (right) insular cortex (Heuninckx et al. 2005), or any other cortical regions (e.g., M1 and PMC) (Grefkes et al. 2008) nor an age-related increase in S2 activity within our subject sample (Heuninckx et al. 2005; Goble et al. 2010), suggested to be characteristic for other bimanual hand movements. The absence of an age-by-task correlation is not surprising, as activations (including S2) for coordinated bimanual hand movements do only show an age-dependency for the elderly (subjects > 60 years; Heuninckx et al. 2005; Goble et al. 2010), but not for young, adults. However, the nonsubtracted fMRI data show robust activation of the SMA, PMC, and M1 in all experimental hand movement tasks performed in this study, that is, these cortical areas are obviously nonspecifically involved in all bimanual movement tasks. The main difference in the neural organization of cooperative hand movements is the involvement of S2.
Consequences for Hand Rehabilitation
Task-specific training effects are well established on the basis of both animal experiments (Edgerton et al. 1997; de Leon et al. 1998a, 1998b) and studies in humans (for reviews, see Dietz 2002, 2008). An established approach for hand rehabilitation after a stroke is "constraint-induced movement therapy" (Liepert et al. 1998; for reviews, see Taub et al. 1999; Liepert 2010; Nijland et al. 2011). Using this approach, the paretic limb is trained exclusively and compensation or involvement of the unaffected limb is avoided. According to observations made here, the neural structure and interhemispheric information transfer mediating cooperative movements should additionally be trained in order to achieve an improved performance in everyday tasks that require cooperative hand movements.
On the basis of both reflex and fMRI analyses, we conclude that combining and integrating somatosensory information from dynamic cooperative hand movements is task specifically mediated by S2. Consequently, the afferent volley produced by unilateral nerve stimulation is thought to be processed by an interaction of the S2 areas through the corpus callosum. The similarity in latency of the N2–P2 complex of the reflex EMG responses indicates a joint release from supraspinal centers to the arm muscles of both sides. This together with the simultaneous start of bilateral hand movements to "open the bottle" suggests a common release of executor signals to forearm extensors and flexors. The present data provide evidence that bilateral S2 areas are involved in such cooperative bimanual actions. It remains for further studies to determine the exact pathways involved in the generation of the bilateral reflexes described.
Supplementary Material
Supplementary can be found at: http://www.cercor.oxfordjournals.org/
The device used for this study was constructed in the Sensory-Motor Systems Lab of the ETH Zürich (Prof R. Riener). We thank Dr Michelle Starkey for her helpful comments and editing of the manuscript and Amanda Genewein and Sarina Bürer for assisting in the experiments. Conflict of Interest: None declared.


text:
Brief Report
Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus
Version of Record online: 17 OCT 2003
DOI: 10.1002/mds.10639
Copyright © 2003 Movement Disorder Society
Movement Disorders
Volume 19, Issue 2, pages 196–199, February 2004
Additional Information
How to Cite
Hjort, N., Østergaard, K. and Dupont, E. (2004), Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus. Mov. Disord., 19: 196–199. doi: 10.1002/mds.10639
Publication History
- Issue online: 10 FEB 2004
- Version of Record online: 17 OCT 2003
- Manuscript Accepted: 16 JUL 2003
- Manuscript Revised: 20 JUN 2003
- Manuscript Received: 6 FEB 2003
Funded by
- Danish Parkinson Foundation
- Novo Nordisk Foundation
- Dr. Eilif and Ane Trier-Hansen's Foundation
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kirklandsJust a preview of the Southern Charm collection, in stores now! #masonjar #weddings #love #mykirklands
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- Listing Company: First Weber Inc
Property Description for 58 Ac S Wisconsin Dells Pky Lake Delton WI 53913
58 Ac S Wisconsin Dells Pky Lake Delton WI 53913 - Prime Development site at Wis. Dells most vibrant area: Exit 92 and Hwy 12-Wis. Dells Parkway. 58 acres in the heart of the water park resorts. Kalahari to the south Wilderness to the north and Great Wolf and many other thriving tourist business to the west. High visibility and over 3 million annual visitors enjoy this location. Easy access off I90/94 and Hwy 12. Fully improved frontage road with underground utilities, multi purpose pedestrian sidewalks, street lights, ready for development.
Building and Construction
- City
Land Features
- Topography: Level, Rolling
- Zoning: Industrial
- Waterfront/Access: N
|MLS Number
|New Status
|Previous Status
|Activity Date
|New List Price
|Previous List Price
|Sold Price
|Oct 27 2016 11:50AM
|Oct 27 2016 1:45AM
|Nov 3 2015 1:48PM
Estimated Monthly Payment
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Community Homes Near 58 Ac S Wisconsin Dells Pky
Buyer understands that the information which is contained on Data pages is obtained from a number of different sources and which has not been independently verified or confirmed by the various real estate brokers and agents who have been and are involved in this transaction. If any particular measurement or data element is important or material to buyer, Buyer assumes all responsibility and liability to research, verify and confirm said data element and measurement. REALTOR *MLS* Equal Housing Opportunity


text:
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JVC Home Entertainment - Reviews
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search all 100,286 blends
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home > signature blend >
Bubble, Bubble
created by: Paige Tyson
What's that you've got in your cauldron? It looks toxic.
1 reviews
1 recent reviews
click & drag the tin to rotate
blended with hojicha, green tea, natural vanilla flavor,
teas: hojicha, vanilla green
accented with cornflowers, cardamom and cloves
steep at 180° for 2 mins
This tea contains a moderate level of caffeine
this tea is part of the KITCHEN WITCH TINCTURES fandom
Love Bubble, Bubble? This is just one of 27 teas in this fandom. Check out the whole series.


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Top Definition
the current Wal-Mart craze; Wal-Mart's power and the negative consequences associated with it
Walmarimania is causing smaller businesses to shut down.
by tc1030 November 10, 2010
The Urban Dictionary Mug
One side has the word, one side has the definition. Microwave and dishwasher safe. Lotsa space for your liquids.Buy the mug
The Urban Dictionary T-Shirt
Smooth, soft, slim fit American Apparel shirt. Custom printed. 100% fine jersey cotton, except for heather grey (90% cotton).Buy the t-shirt


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Top News
Collaboration helps juvenile offenders forge a path for the future
JACKSONVILLE – A pro bono program for juvenile offenders who have completed the State Attorney's Office's diversion program, which began as a collaboration between Florida Coastal School of Law and the Center for Legal Rights, has blossomed into a new joint effort that links the city, the State Attorney's Office, Florida Coastal, the Duval County Clerk of Courts, the Jacksonville Sheriff's Office and Jacksonville Area Legal Aid.
Florida Supreme Court ruling addresses insurance payment clause debate
Professor says quality appointments key for next Constitution Revision Commission
Pacific Legal Foundation asks Florida Supreme Court to hear undertakings case
Florida Supreme Court foreclosure ruling expected to increase filings, provide clarity
Citizens group raises safety, environmental, financial concerns about rail project
Environmental groups look to stop three-state pipeline project
JUNO BEACH, FLORIDA – An attorney for Chattahoochee Riverkeeper, one of three environmental groups that have asked the U.S. Court of Appeals for the District of Columbia Circuit to stop construction on three Southeastern pipeline projects, said its primary concerns are the impacts the $3.2 billion Sabal Trail Pipeline project will have on the Chattahoochee River, its tributaries and the communities along those waterways.
McGlinchey Stafford adds three attorneys to Florida Commercial Litigation group
Environmental permit challenges latest chapter in rail project fight
Florida police chiefs, former justices call for rejection of revised marijuana proposal
Congresswoman's former attorney says publication's 'grandstanding' comments are 'rubbish'
ORLANDO – Before withdrawing from his brief tenure as a lawyer for U.S. Rep. Corrine Brown, who lost her bid for re-election in the state's Aug. 30 primary and is facing a federal fraud trial, attorney Mark NeJame took umbrage at statements made about his professional style by a Florida publication.
ACLU complaint seeks to secure hormone therapy for transgender prisoner
Courts and trademark attorneys agree: Confusion between FIU, FNU unlikely
Changing Cuba-U.S. relations could open new doors for Cuban lawyers
Rising care costs, unhappy workers left in wake of high court appeal reject
Family law attorney, Rising Star: 'Nothing in life is impossible'
Private Sarasota County hospitals' indigent care reimbursement case headed to high court
Touby: Workers' compensation rulings bring balance to 'pro-business' system
FBI halts requests for information on Orlando nightclub shooting investigation
Karlinsky: Assignment of benefits bills not approved in session, still a 'major issue'
ORLANDO – Fred Karlinsky, co-chair of the insurance regulatory and transactions practice at Greenberg Traurig, discussed noteworthy insurance-related measures before the legislature as part of his presentation at the recent Florida Hurricane Catastrophe Fund's (FHCF) annual Participating Insurers Workshop.


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The fabulous evolution of e-bikes
More and more people switch to e-bikes these days. And those electrical bikes are not just popular among those more advanced in age, they're useful companions for the sporty and adventure-seeking. Sales are not booming as a whole yet, but have been showing steady increase in America and in Europe in the past years.[1] The advantages are obvious: heavy head winds and agonizing ascents lose their threatening character when one flies over the tarmac or even off-road terrain. The progress e-bikes have been making recently is remarkable, but there's much more to come in the future.
Digital, of course!
Why do I have to get a bicycle that has an electric engine? Why can I not simply buy a bicycle and then get a portable electric engine and install it on the bicycle? Or on my friend's bicycle? Yes, many people wonder why one has to invest lots of cash in a bicycle while often it's only the engine that's new about it. Well, here's the solution: the company ShareRoller designed a portable motor that can be installed on nearly any bicycle's front wheel.[2] It only weighs around 3kg and has the size of a standard first-aid kit. Now you can electrify any bicycle, literally. However, the most promising new feature of e-bikes is the internet. Yep, e-bikes have electricity (!) so why not connect them to the digital land of possibilities? Slick, slim, and fast: Swiss e-bike company Stromer are pioneers in e-bike technologies. One of their latest models, the ST2, is the first "connected" bicycle on the market. Stromer developed its own smartphone app called OMNI, which connects to the bicycle's integrated computer as well as to the OMNI data cloud. This enables cyclers to lock their bicycles or block its engine wherever they are. If the bicycle gets stolen user's can track it via GPS on their phone. The bicycle's computer automatically saves data on the bicycle's condition making it very easy for mechanics to bring it back on its feet when it's broken. The app furthermore allows you to control the bicycle's range and speed. It's very fast, too and has an extremely long-lasting battery. No surprise then that the company says they've built something better than a car. There is one major problem, however. The bicycle's SIM card costs around 250 Euros for the first three years. Add to that a buying price of 5690 Euros and the ST2 becomes a rather expensive experience.[3]
What type do you need?
There is not just one e-bike on the market anymore. There's an e-bike for grabbing groceries, one for going off-road (check Fatbikes), and one for getting the kids home safely or transporting a small piece of furniture. Many complain about the heaviness of e-bikes. While this is true for most of them, there are plans for the first folding e-bikes weighing only around 14kg (GI Bike). It's a truly exciting moment for such an old invention – the good old bicycle.


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Indian Mud Run obstacle races, mud run, and OCR information, distance, cost, dates, calendar, discounts, obstacles, reviews, and more
The Indian Mud run is a 5K run through beautiful hills alongside spectacular rock formations. The terrain is an obstacle itself then the run will challenge you with over 30 obstacles. Some of the obstacles include 20' cargo net climb, natural rock climb with ropes, steep hills, 200' water slide, 40 foot long monkey bars across a canal, 20' high climbing wall, shock wires and a lot of mud. After the race you get a free beer and a free ride on our Blob pillow. Racers also get a cool medal, a beautiful shirt and a chance to win GoPro cameras. Shirts include the top 500 placers from the previous year's race. We also have a separate kid's course.
Upcoming Indian Mud Run EventsClick an event name to view the event details. Scroll past this, or click here to see the review section
- Race discount More info
June 24, 2017Learn MoreCoshocton Ohio Indian Mud Run 2017
Coshocton Lake Park, Coshocton, OH, United States
Browse our calendar of previous mud runs, mud races & obstacle races for Indian Mud Run
Indian Mud Run Reviews
(Scroll up to see a list of upcoming events for Indian Mud Run)
Click here to submit your review.
Best local/small OCR 5k I've done. The rugged, natural terrain was the biggest obstacle. Mud and hills galore. Obstacles themselves were top notch and had an element of danger not found at many large corporate race series. Finish line could be more organized for finding beer and swag but that's a small complaint compared to the value of this race.


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Hotfrog INDIA provides information regarding Woodside Matheran in Thane Maharashtra. Woodside Matheran is located at Babaji Niwas Baji Prabhu Deshpande Path Naupada, Thane Maharashtra 400602 and provides Gardens services. Contact them on 0 9869028568 or by visiting them on their website http://www.woodsidematheran.com.
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We have more Gardens services in Thane Maharashtra available on Hotfrog INDIA. You can update your search for Thane Gardens by location, keyword or service options.
Santosh Katvi, PO Sandoz Baug Gate No2 Kolshet Road Thane Maharashtra 400 607
VEER SAWARKAR PATH THANE (W) Thane Maharashtra 400602
THANE(W) Thane Maharashtra 400601
GOKHALE RD TAKLE COMPOUND Thane Maharashtra 400602
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Doggy Day Care in Wyoanna, PA
Drop off your dog at your sitter's home in the morning, and pick them up in the evening.
Animals are better than people!
Old Forge, PA, 18518
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Dog Loving Entrepreneur-Adventurer
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Scott Township , PA, 18411
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Wilkes barre, PA, 18705
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Scranton, PA, 18508
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Old Forge, PA, 18518
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1996 Dodge Ram shift issue.
I have a 1996 Dodge Ram 4x4 5.9ltr. The
current issue that I'm having, I'll start the
truck first time for the day and I can leave
my driveway, hit the stop sign about 1/4
mile away, and when I press the gas pedal it
pauses as though in neutral and slams into
gear. This is the only time of the day it does
this. I've driven it cold and let it warm up for
up to 10 minutes and doesn't seem to affect
the outcome.
2 Answers
I have a 99 dodge ram and my issue is that I will crank it up when it's cold then I can drive it about 5 minutes and then once the tranny gets warm it will just stop pulling. It's like it goes into neutral.
Torque converter or it's clutch, or might be a clutch pack going, specifically the one for 1st gear, or something related to that like the solenoid, valve body, or piston seal. Check the ATF level and if okay might want to take it into a tranny shop.
Your Answer
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Dania FL Real Estate & Homes for Sale
0 Properties Found
The median home value in Dania, FL is $126,200.
This is
lower than
the county median home value of $163,200.
The national median home value is $177,414.
The average price of homes sold in Dania, FL is $126,200.
Approximately 39.8% of Dania homes are owned,
compared to 35.16% rented, while
25.04% are vacant.
Dania real estate listings include condos, townhomes, and single family homes for sale.
Commercial properties are also available.
If you see a property you're interested in, contact a Dania real estate agent to arrange a tour today!
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Dania ZIPs33004 Homes for Sale


text:
Web Application Security
securing a deliberately vulnerable web app Jul 03 2011 10:51PM
Robin Wood (robin digininja org)
This is a question for anyone who runs a deliberately vulnerable web
app on a public facing site to allow people to test hacking it or to
test vulnerability scanners against it. I'm thinking of things like
http://test.acunetix.com/ .
What I'd like to know is how you go about securing the box the sites
are running on. Obviously you need the site running on its own server,
preferably airgapped from the rest of your network but how do you
protect yourself from attackers getting on the box then pivoting from
it to do a real attack to someone else? I'm guessing it is something
like a VM that is automatically rolled back periodically so even if
someone tries then they only have a limited attack window but are
there any other things people do?
I'm asking because I've got an idea for a new public service which
would involve putting up an app that is vulnerable but I'd like to
make sure that if I do I protect myself as much as possible.
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Vila Leopoldina, São Paulo, Brazil
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Looking for London and Paris for January 2016! A charming and cozy house located in a beautiful island in Brazil - Ilhabela. This house is really oceanfront,...
This is our main home, I live with my husband and two years old son. The view to Pacaembu is beautiful, 19 floor, and the neighbourhood is very peaceful and...