Internal transport barriers in the National Spherical Torus Experiment

In the National Spherical Torus Experiment [M. Ono , Nucl. Fusion 41, 1435 (2001)], internal transport barriers (ITBs) are observed in reversed (negative) shear discharges where diffusivities for electron and ion thermal channels and momentum are reduced. While neutral beam heating can produce ITBs in both electron and ion channels, high harmonic fast wave heating can also produce electron ITBs (e-ITBs) under reversed magnetic shear conditions without momentum input. Interestingly, the location of the e-ITB does not necessarily match that of the ion ITB (i-ITB). The e-ITB location correlates best with the magnetic shear minima location determined by motional Stark effect constrained equilibria, whereas the i-ITB location better correlates with the location of maximum ExB shearing rate. Measured electron temperature gradients in the e-ITB can exceed critical gradients for the onset of electron thermal gradient microinstabilities calculated by linear gyrokinetic codes. A high-k microwave scattering diagnostic shows locally reduced density fluctuations at wave numbers characteristic of electron turbulence for discharges with strongly negative magnetic shear versus weakly negative or positive magnetic shear. Reductions in fluctuation amplitude are found to be correlated with the local value of magnetic shear. These results are consistent with nonlinear gyrokinetic simulations predicting a reduction in electron turbulence under negative magnetic shear conditions despite exceeding critical gradients.X1128sciescopu

The Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH) can measure the impairment, activity limitations and participation restriction constructs from the International Classification of Functioning, Disability and Health (ICF)

Background The International Classification of Functioning, Disability and Health (ICF) model of the consequences of disease identifies three health outcomes, impairment, activity limitations and participation restrictions. However, few orthopaedic health outcome measures were developed with reference to the ICF. This study examined the ability of a valid and frequently used measure of upper limb function, namely the Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), to operationalise the ICF. Methods Twenty-four judges used the method of Discriminant Content Validation to allocate the 38 items of the DASH to the theoretical definition of one or more ICF outcome. One-sample t-tests classified each item as measuring, impairment, activity limitations, participation restrictions, or a combination thereof. Results The DASH contains items able to measure each of the three ICF outcomes with discriminant validity. The DASH contains five pure impairment items, 19 pure activity limitations items and three participation restriction items. In addition, seven items measured both activity limitations and participation restrictions. Conclusions The DASH can measure the three health outcomes identified by the ICF. Consequently the DASH could be used to examine the impact of trauma and subsequent interventions on each health outcome in the absence of measurement confound

Matrix-Bound PAI-1 Supports Cell Blebbing via RhoA/ROCK1 Signaling

The microenvironment of a tumor can influence both the morphology and the behavior of cancer cells which, in turn, can rapidly adapt to environmental changes. Increasing evidence points to the involvement of amoeboid cell migration and thus of cell blebbing in the metastatic process; however, the cues that promote amoeboid cell behavior in physiological and pathological conditions have not yet been clearly identified. Plasminogen Activator Inhibitor type-1 (PAI-1) is found in high amount in the microenvironment of aggressive tumors and is considered as an independent marker of bad prognosis. Here we show by immunoblotting, activity assay and immunofluorescence that, in SW620 human colorectal cancer cells, matrix-associated PAI-1 plays a role in the cell behavior needed for amoeboid migration by maintaining cell blebbing, localizing PDK1 and ROCK1 at the cell membrane and maintaining the RhoA/ROCK1/MLC-P pathway activation. The results obtained by modeling PAI-1 deposition around tumors indicate that matrix-bound PAI-1 is heterogeneously distributed at the tumor periphery and that, at certain spots, the elevated concentrations of matrix-bound PAI-1 needed for cancer cells to undergo the mesenchymal-amoeboid transition can be observed. Matrix-bound PAI-1, as a matricellular protein, could thus represent one of the physiopathological requirements to support metastatic formation

PAI-1 and functional blockade of SNAI1 in breast cancer cell migration

12 pages, 5 figures.-- PMID: 19055748 [PubMed].-- et al.[Introduction]: Snail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasion. The Plasminogen Activation (PA) system, including urokinase plasminogen activator (uPA), its receptor and its inhibitor, plasminogen activator inhibitor type 1(PAI-1), also plays a key role in cancer invasion and metastasis, either through proteolytic degradation or by non-proteolytic modulation of cell adhesion and migration. Thus, Snail and the PA system are both over-expressed in cancer and influence this process. In this study we aimed to determine if the activity of SNAI1 (a member of the Snail family) is correlated with expression of the PA system components and how this correlation can influence tumoural cell migration.[Methods]: We compared the invasive breast cancer cell-line MDA-MB-231 expressing SNAI1 (MDA-mock) with its derived clone expressing a dominant-negative form of SNAI1 (SNAI1-DN). Expression of PA system mRNAs was analysed by cDNA microarrays and real-time quantitative RT-PCR. Wound healing assays were used to determine cell migration. PAI-1 distribution was assessed by immunostaining.[Results]: We demonstrated by both cDNA microarrays and realtime quantitative RT-PCR that the functional blockade of SNAI1 induces a significant decrease of PAI-1 and uPA transcripts. After performing an in vitro wound-healing assay, we observed that SNAI1-DN cells migrate more slowly than MDA-mock cells and in a more collective manner. The blockade of SNAI1 activity resulted in the redistribution of PAI-1 in SNAI1-DN cells decorating large lamellipodia, which are commonly found structures in these cells.[Conclusions]: In the absence of functional SNAI1, the expression of PAI-1 transcripts is decreased, although the protein is redistributed at the leading edge of migrating cells in a manner comparable with that seen in normal epithelial cells.This work was supported by the CNRS ACI Program "Complexité du vivant" (grant # 050009DR11) and by the Evry Genopole grant "Aide à l'acquisition d'équipement semi-lourd" 2007 and 2008.Peer reviewe

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Validation of the theoretical domains framework for use in behaviour change and implementation research

Background An integrative theoretical framework, developed for cross-disciplinary implementation and other behaviour change research, has been applied across a wide range of clinical situations. This study tests the validity of this framework. Methods Validity was investigated by behavioural experts sorting 112 unique theoretical constructs using closed and open sort tasks. The extent of replication was tested by Discriminant Content Validation and Fuzzy Cluster Analysis. Results There was good support for a refinement of the framework comprising 14 domains of theoretical constructs (average silhouette value 0.29): 'Knowledge', 'Skills', 'Social/Professional Role and Identity', 'Beliefs about Capabilities', 'Optimism', 'Beliefs about Consequences', 'Reinforcement', 'Intentions', 'Goals', 'Memory, Attention and Decision Processes', 'Environmental Context and Resources', 'Social Influences', 'Emotions', and 'Behavioural Regulation'. Conclusions The refined Theoretical Domains Framework has a strengthened empirical base and provides a method for theoretically assessing implementation problems, as well as professional and other health-related behaviours as a basis for intervention development