New High-Confinement Regime with Fast Ions in the Core of Fusion Plasmas.

The key result of the present work is the theoretical prediction and observation of the formation of a new type of transport barrier in fusion plasmas, called F-ATB (fast ion-induced anomalous transport barrier). As demonstrated through state-of-the-art global electrostatic and electromagnetic simulations, the F-ATB is characterized by a full suppression of the turbulent transport-caused by strongly sheared, axisymmetric E×B flows-and an increase of the neoclassical counterpart, albeit keeping the overall fluxes at significantly reduced levels. The trigger mechanism is shown to be a mainly electrostatic resonant interaction between suprathermal particles, generated via ion-cyclotron-resonance heating, and plasma microturbulence. These findings are obtained by realistic simulations of the ASDEX Upgrade discharge No. 36637-properly designed to maximized the beneficial role of the wave-particle resonance interaction-which exhibits the expected properties of improved confinement produced by energetic particles.

Mean and oscillating plasma flows and turbulence interactions across the L-H confinement transition.

A complex interaction between turbulence driven E × B zonal flow oscillations, i.e., geodesic acoustic modes (GAMs), the turbulence, and mean equilibrium flows is observed during the low to high (L-H) plasma confinement mode transition in the ASDEX Upgrade tokamak. Below the L-H threshold at low densities a limit-cycle oscillation forms with competition between the turbulence level and the GAM flow shearing. At higher densities the cycle is diminished, while in the H mode the cycle duration becomes too short to sustain the GAM, which is replaced by large amplitude broadband flow perturbations. Initially GAM amplitude increases as the H-mode transition is approached, but is then suppressed in the H mode by enhanced mean flow shear.

Intrinsic toroidal rotation, density peaking, and turbulence regimes in the core of tokamak plasmas.

Observations in the ASDEX Upgrade tokamak show a correlation between the gradient of the intrinsic toroidal rotation profile and the logarithmic gradient of the electron density profile. The intrinsic toroidal rotation in the center of the plasma reverses from co- to countercurrent when the logarithmic density gradients are large, and the turbulence is either dominated by trapped electron modes or is at the transition between ion temperature gradient and trapped electron modes. A study based on local gyrokinetic calculations suggests that the dominant trend in the observations can be explained by the combination of residual stresses produced by E × B and profile shearing mechanisms.

A key to improved ion core confinement in the JET tokamak: ion stiffness mitigation due to combined plasma rotation and low magnetic shear.

New transport experiments on JET indicate that ion stiffness mitigation in the core of a rotating plasma, as described by Mantica et al. [Phys. Rev. Lett. 102, 175002 (2009)] results from the combined effect of high rotational shear and low magnetic shear. The observations have important implications for the understanding of improved ion core confinement in advanced tokamak scenarios. Simulations using quasilinear fluid and gyrofluid models show features of stiffness mitigation, while nonlinear gyrokinetic simulations do not. The JET experiments indicate that advanced tokamak scenarios in future devices will require sufficient rotational shear and the capability of q profile manipulation.

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle.

Prostaglandins (PGs) are important regulators of reproductive processes including early embryonic development. We analyzed the most relevant PG in bovine uteri at different preimplantation pregnancy stages when compared with non-pregnant controls. Additionally, endometrium and trophoblast tissues were examined regarding specific enzymes and receptors involved in PG generation and function. Simmental heifers were artificially inseminated or received seminal plasma only. At days 12, 15, or 18, post-estrus uteri were flushed for PG determination by liquid chromatography-tandem mass spectrometry. Endometrium and trophoblast tissues were sampled for RNA extraction and quantitative real-time PCR analysis. At all days and points of time examined, the concentration of 6-keto PGF(1alpha) (stable metabolite of PGI(2)) was predominant followed by PGF(2alpha)>PGE(2)>PGD(2) approximately TXB(2) (stable metabolite of TXA(2)). At days 15 and 18, PG increased from overall low levels at day 12, with a much more pronounced increase during pregnancy. The PGF(2alpha)/PGE(2) ratio was not influenced by status. The highest PG concentration was measured at day 15 with 6-keto PGF(1alpha) (6.4 ng/ml) followed by PGF(2alpha) (1.1 ng/ml) and PGE(2) (0.3 ng/ml). Minor changes in endometrial PG biosynthesis enzymes occurred due to pregnancy. Trophoblasts revealed high transcript abundance of general and specific PG synthases contributing to uterine PG. As PGI(2) and PGF(2alpha) receptors were abundantly expressed by the trophoblast, abundant amounts of PGI(2) and PGF(2alpha) in the uterine lumen point towards an essential role of PG for the developing embryo. High amounts of PG other than PGE(2) in the preimplantation uterus may be essential rather than detrimental for successful reproduction.

Prognostic factors in prosthetic rehabilitation of bilateral dysvascular above-knee amputee: is the stump condition an influencing factor?

AIM: The aim of this study was to evaluate the prognostic factors for rehabilitation outcome in bilateral dysvascular lower limb amputees, specifically to ascertain how the stump condition can influence the mobility outcome. METHODS: A retrospective study of 30 selected bilateral above-knee amputees for vascular disease was carried out. Barthel Index (BI) was given and stump condition was assessed at admission and at discharge. Influence of age, comorbidities and stump condition on effectiveness of BI was evaluated. Locomotor Capability Index (LCI) was performed at discharge. Influence of stump problems (pain, flexion, pain with flexion) on LCI was evaluated. RESULTS: At discharge, 25 patients were able to ambulate. Age and pathological conditions of stumps correlated negatively with BI effectiveness. LCI values were higher for patients with ideal stumps and lower for patients with combined stump pain and flexion deformities. Post hoc analysis showed that the principal factor negatively influencing the LCI score was the presence of stump flexion deformities. CONCLUSIONS: In our homogeneous group of bilateral amputees, age reduced the possibility of improving the level of autonomy. Good stump quality is one of the major determinants of mobility outcome. Efforts should be made to minimize stump complications. In particular, incorrect positioning of the stump, which is responsible for hip flexor retraction, should be avoided after surgery.

PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells.

AIM: Platelet-activating factor acetyl hydrolase 1B1 (PAFAH1B1, also known as Lis1) is a protein essentially involved in neurogenesis and mostly studied in the nervous system. As we observed a significant expression of PAFAH1B1 in the vascular system, we hypothesized that PAFAH1B1 is important during angiogenesis of endothelial cells as well as in human vascular diseases. METHOD: The functional relevance of the protein in endothelial cell angiogenic function, its downstream targets and the influence of NONHSAT073641, a long non-coding RNA (lncRNA) with 92% similarity to PAFAH1B1, were studied by knockdown and overexpression in human umbilical vein endothelial cells (HUVEC). RESULTS: Knockdown of PAFAH1B1 led to impaired tube formation of HUVEC and decreased sprouting in the spheroid assay. Accordingly, the overexpression of PAFAH1B1 increased tube number, sprout length and sprout number. LncRNA NONHSAT073641 behaved similarly. Microarray analysis after PAFAH1B1 knockdown and its overexpression indicated that the protein maintains Matrix Gla Protein (MGP) expression. Chromatin immunoprecipitation experiments revealed that PAFAH1B1 is required for active histone marks and proper binding of RNA Polymerase II to the transcriptional start site of MGP. MGP itself was required for endothelial angiogenic capacity and knockdown of both, PAFAH1B1 and MGP, reduced migration. In vascular samples of patients with chronic thromboembolic pulmonary hypertension (CTEPH), PAFAH1B1 and MGP were upregulated. The function of PAFAH1B1 required the presence of the intact protein as overexpression of NONHSAT073641, which was highly upregulated during CTEPH, did not affect PAFAH1B1 target genes. CONCLUSION: PAFAH1B1 and NONHSAT073641 are important for endothelial angiogenic function.

Steady-state fully noninductive current driven by electron cyclotron waves in a magnetically confined plasma

A steady-state, fully noninductive plasma current has been sustained for the first time in a tokamak using electron cyclotron current drive only. In this discharge, 123 kA of current have been sustained for the entire gyrotron pulse duration of 2 s. Careful distribution across the plasma minor radius of the power deposited from three 0. 5-MW gyrotrons was essential for reaching steady-state conditions. With central current drive, up to 153 kA of current have been fully replaced transiently for 100 ms. The noninductive scenario is confirmed by the ability to recharge the Ohmic transformer. The dependence of the current drive efficiency on the minor radius is also demonstrated.

Prognostic factors in rehabilitation of above knee amputees for vascular diseases.

PURPOSE: This study was undertaken to predict rehabilitation potential and prognostic factors of patients undergoing above knee amputation for vascular diseases. METHOD: In a prospective study on 144 patients consecutively admitted to our rehabilitation unit for above knee amputation, multiple regression analyses were used to assess the relationship between nine independent variables and a battery of outcome measures: the Rivermead Mobility Index (RMI) and Barthel Index (BI) effectiveness on discharge, length of hospital stay. Two multiple logistic regressions were performed, using as dependent variable the occurrence of good or partial autonomy in mobility, quantified as RMI scores. RESULTS: Advanced age was the most powerful prognostic factor influencing effectiveness expressed as both mobility (RMI) and BI. Patients aged < 65 years had a greater probability (odds ratio 2.92) of good autonomy in mobility than older patients. The absence of vascular impairment of the residual limb and timely admission to the rehabilitation hospital correlated positively with effectiveness of mobility. CONCLUSIONS: These findings indicate that relevant prognostic factors can be identified at the beginning of rehabilitation treatment.

[Intraoperative ultrasonography in the diagnosis of liver metastasis from gastrointestinal neoplasms]. / L'ecografia intraoperatoria nella diagnosi di metastasi epatiche da neoplasia gastrointestinale.

The authors illustrate their experience in the systematic use of intraoperative ultrasonography of the liver in patients undergoing surgery due to gastrointestinal cancer. The liver is the organ in which metastases from colorectal, stomach, pancreatic, and biliary cancer are most often localised. Between January 1991 and April 1992 95 patients underwent intraoperative ultrasonographic controls of the liver. In all cases the liver was studied using traditional image diagnosis: standard ultrasonography and CAT. On the basis of their experience the authors observed 12 cases negative for metastases using CAT and traditional ultrasonography which were positive using intraoperative ultrasonography, 2 cases which were positive for secondary hepatic lesions using traditional diagnostic tools but negative following histological tests guided by intraoperative ultrasonography. In the case of false negatives using traditional methods, those metastases revealed by intraoperative ultrasonography were above all located deep down and in segments which are difficult to explore, or were so small that they were not visible or palpable during intraoperative controls of the viscera. Intraoperative ultrasonography of the liver has been found to be a more sensitive test (97% of the best series) than standard ultrasonography (65%) or CAT (43%). Higher resolution due to the characteristics of the method is coupled with the possibility that intraoperative ultrasonography may be used to guide biopsies of the metastases revealed, thus allowing histological confirmation to be obtained: for this reason the risk of false positives is virtually zero.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Lipoxygenase inhibitors induce potent anti-proliferative and cytotoxic effects in human tumour cells independently of suppression of 5-lipoxygenase activity.

BACKGROUND AND PURPOSE: Certain 5-lipoxygenase (5-LO) inhibitors exhibit anti-carcinogenic activities against 5-LO overexpressing tumour types and cultured tumour cells. It has been proposed therefore that 5-LO products significantly contribute to tumour cell proliferation. To date, the relationship between the inhibitory mechanisms of 5-LO inhibitors, which vary widely, and tumour cell viability has not been evaluated. This study addresses the anti-proliferative and cytotoxic potency of a number of 5-LO inhibitors with different inhibitory mechanisms in 5-LO-positive and 5-LO-negative tumour cells. EXPERIMENTAL APPROACH: Cell viability was measured by the WST-1 assay; cell proliferation was assessed using the bromodeoxyuridine (BrdU) incorporation assay. Cell death was analysed by annexin V staining, Western blot analysis of PARP (poly ADP-ribose polymerase) cleavage and a cytotoxicity assay. 5-LO product formation was quantified by a 5-LO activity assay. KEY RESULTS: The common 5-LO inhibitors AA-861, Rev-5901 and MK-886 induced cytotoxic and anti-proliferative effects in 5-LO-positive Capan-2 pancreatic cancer cells; BWA4C and CJ-13,610 only caused anti-proliferative effects, while zileuton failed to impair cell viability. Moreover, the concentrations of the 5-LO inhibitors required to induce anti-proliferation and cytotoxicity highly exceeded those for suppression of 5-LO. Supplementation with mitogenic 5-LO products failed to protect Capan-2 cells from the effects of 5-LO inhibitors. Finally, the cytotoxic and anti-proliferative 5-LO inhibitors also potently reduced the viability of 5-LO-deficient tumour cell lines (HeLa, Panc-1 and U937). CONCLUSIONS AND IMPLICATIONS: Certain 5-LO inhibitors cause cytotoxic and anti-proliferative effects independently of suppression of 5-LO activity. Thus, the role of 5-LO overexpression in tumour cell viability remains unclear and requires further elucidation.

Prostaglandin D2 produced by hematopoietic prostaglandin D synthase contributes to LPS-induced fever.

A large body of evidence has implicated prostaglandin E(2) (PGE(2)) in fever production. However, the role of PGD(2) in this context is only poorly understood. We therefore determined by LC-MS/MS analyses the content of PGD(2) and PGE(2) in cerebrospinal fluid (CSF), plasma and lungs of rats over 5 hours after fever induction by intraperitoneal injection of lipopolysaccharide (LPS, 50 microg/kg). Both PGD(2) and PGE(2) were detected in CSF, plasma and lungs of saline-treated control animals. The injection of LPS evoked fever and an increase of PGE(2) in the CSF, while the CSF content of PGD(2) was not significantly altered. However, both PGE(2) and PGD(2) levels were elevated in plasma and lungs after LPS injection. Interestingly, pretreatment with a novel selective inhibitor of hematopoietic prostaglandin D synthase (H-PGDS), EDJ300520 (10-40 mg/kg p.o.), selectively and dose-dependently prevented the LPS-induced increase of PGD(2) in plasma and lungs but did not affect the PGE(2) content. Most remarkably, EDJ300520 pretreatment led to an hypothermic response after LPS injection during the first 3 h and prevented fever induction. These data indicate that PGD(2) produced peripherally by H-PGDS essentially contributes to LPS-induced fever.

Transport of parallel momentum induced by current-symmetry breaking in toroidal plasmas.

The symmetry of a physical system strongly impacts on its properties. In toroidal plasmas, the symmetry along a magnetic field line usually constrains the radial flux of parallel momentum to zero in the absence of background flows. By breaking the up-down symmetry of the toroidal currents, this constraint can be relaxed. The parallel asymmetry in the magnetic configuration then leads to an incomplete cancellation of the turbulent momentum flux across a flux surface. The magnitude of the subsequent toroidal rotation increases with the up-down asymmetry and its sign depends on the direction of the toroidal magnetic field and plasma current. Such a mechanism offers new insights in the interpretation and control of the intrinsic toroidal rotation in present day experiments.

Toroidal momentum pinch velocity due to the coriolis drift effect on small scale instabilities in a toroidal plasma.

In this Letter, the influence of the "Coriolis drift" on small scale instabilities in toroidal plasmas is shown to generate a toroidal momentum pinch velocity. Such a pinch results because the Coriolis drift generates a coupling between the density and temperature perturbations on the one hand and the perturbed parallel flow velocity on the other. A simple fluid model is used to highlight the physics mechanism and gyro-kinetic calculations are performed to accurately assess the magnitude of the pinch. The derived pinch velocity leads to a radial gradient of the toroidal velocity profile even in the absence of a torque on the plasma and is predicted to generate a peaking of the toroidal velocity profile similar to the peaking of the density profile. Finally, the pinch also affects the interpretation of current experiments.

Direction of impurity pinch and auxiliary heating in tokamak plasmas.

A mechanism of particle pinch for trace impurities in tokamak plasmas, arising from the effect of parallel velocity fluctuations in the presence of a turbulent electrostatic potential, is identified analytically by means of a reduced fluid model and verified numerically with a gyrokinetic code for the first time. The direction of such a pinch reverses as a function of the direction of rotation of the turbulence in agreement with the impurity pinch reversal observed in some experiments when moving from dominant auxiliary ion heating to dominant auxiliary electron heating.

Experimental study of trapped-electron-mode properties in tokamaks: threshold and stabilization by collisions.

Trapped electron modes are one of the candidates to explain turbulence driven electron heat transport observed in tokamaks. This instability has two characteristics: a threshold in normalized gradient and stabilization by collisions. Experiments using modulated electron cyclotron heating in the ASDEX Upgrade tokamak demonstrate explicitly the existence of the threshold. The stabilization with increasing collisionality is evidenced by a strong decrease of the propagation of heat pulses, explained by a transition to ion temperature gradient driven transport. These results are supported by linear gyrokinetic calculations.

Turbulent particle transport in magnetized plasmas.

Particle transport in magnetized plasmas is investigated with a fluid model of drift wave turbulence. An analytical calculation shows that magnetic field curvature and thermodiffusion drive an anomalous pinch. The curvature driven pinch velocity is consistent with the prediction of turbulence equipartition theory. The thermodiffusion flux is found to be directed inward for a small ratio of electron to ion pressure gradient, and it reverses its sign when increasing this ratio. Numerical simulations confirm that a turbulent particle pinch exists. It is mainly driven by curvature for equal ion and electron heat sources. The sign and relative weights of the curvature and thermodiffusion pinches are consistent with the analytical calculation.

Density peaking, anomalous pinch, and collisionality in tokamak plasmas.

The existence of an anomalous particle pinch in magnetized tokamak plasmas is still questioned. Contradictory observations have been collected so far in tokamaks. Clear experimental evidence that density peaking in tokamak plasmas drops with increasing collisionality is provided for the first time. This phenomenon is explained by means of existing theoretical models based on the fluid description of drift wave instabilities, provided that such models include the dissipative effects introduced by collisions on the mentioned instabilities. These results reconcile the apparent contradictions found so far in the experiments.

Long-pulse improved central electron confinement in the TCV tokamak with electron cyclotron heating and current drive.

Current profile tailoring by electron cyclotron heating (ECH) and current drive (ECCD) is used to improve central electron energy confinement in the TCV tokamak. Counter-ECCD on axis alone achieves this goal in a transient manner only. A stable scenario is obtained by a two-step sequence of off-axis ECH, which stabilizes magnetohydrodynamics modes, and on-axis counter-ECCD, which generates a flat or inverted current profile. This high-confinement regime, with central temperatures up to 9 keV (at a normalized beta(N) approximately 0.6), has been sustained for the entire duration of the heating pulse, or over 200 electron energy confinement times and 5 current redistribution times.