Controlled beat-wave Brillouin scattering in the ionosphere.

Stimulated Brillouin scattering experiments in the ionospheric plasma using a single electromagnetic pump wave have previously been observed to generate an electromagnetic sideband wave, emitted by the plasma, together with an ion- acoustic wave. Here we report results of a controlled, pump and probe beat-wave driven Brillouin scattering experiment, in which an ion-acoustic wave generated by the beating of electromagnetic pump and probe waves, results in electromagnetic sideband waves that are recorded on the ground. The experiment used the EISCAT facility in northern Norway, which has several high power electromagnetic wave transmitters and receivers in the radio frequency range. An electromagnetic pump consisting of large amplitude radio waves with ordinary (O) or extraordinary (X) mode polarization was injected into the overhead ionosphere, along with a less powerful probe wave, and radio sideband emissions observed on the ground clearly show stimulated Brillouin emissions at frequencies agreeing with, and changing with, the pump and probe frequencies. The experiment was simulated using a numerical full-scale model which clearly supports the interpretation of the experimental results. Such controlled beat-wave experiments demonstrate a way of remotely investigating the ionospheric plasma parameters.

Collisionless shock acceleration in the corona of an inertial confinement fusion pellet with possible application to ion fast ignition.

Two-dimensional particle-in-cell simulations are used to explore collisionless shock acceleration in the corona plasma surrounding the compressed core of an inertial confinement fusion pellet. We show that an intense laser pulse interacting with the long scale-length plasma corona is able to launch a collisionless shock around the critical density. The nonlinear wave travels up-ramp through the plasma reflecting and accelerating the background ions. Our results suggest that protons with characteristics suitable for ion fast ignition may be achieved in this way. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

New criteria for efficient Raman and Brillouin amplification of laser beams in plasma.

Raman or Brillouin amplification of a laser beam in plasma has long been seen as a way to reach multi-PW powers in compact laser systems. However, no significant plasma-based Raman amplification of a laser pulse beyond 0.1 TW has been achieved in nearly 20 years, and only one report of Brillouin amplification beyond 1 TW. In this paper, we reveal novel non-linear criteria for the initial seed pulse that will finally open the door to efficient Raman and Brillouin amplification to petawatt powers and Joule-level energies. We show that the triple product of the coupling constant [Formula: see text], seed pulse duration [Formula: see text] and seed pulse amplitude a for the Raman seed pulse (or [Formula: see text] for Brillouin) must exceed a specific minimum threshold for efficient amplification. We also analyze the plasma-based Raman and Brillouin amplification experiments to date, and show that the seed pulses used in nearly all experiments are well below our new threshold, which explains the poor efficiency obtained in them. Finally, we analyze a recent Brillouin amplification experiment that used increased seed pulse power to obtain Joule-level amplification, and find excellent agreement with our theory.

Idh1 protects murine hepatocytes from endotoxin-induced oxidative stress by regulating the intracellular NADP(+)/NADPH ratio.

Isocitrate dehydrogenase-1 (Idh1) is an important metabolic enzyme that produces NADPH by converting isocitrate to α-ketoglutarate. Idh1 is known to reduce reactive oxygen species (ROS) induced in cells by treatment with lipopolysaccharide (LPS) in vitro. Here, we used Idh1-deficient knockout (Idh1 KO) mice to investigate the role of Idh1 in antioxidant defense in vivo. Idh1 KO mice showed heightened susceptibility to death induced by LPS and exhibited increased serum levels of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The serum of LPS-injected Idh1 KO mice also contained elevated levels of AST, a marker of inflammatory liver damage. Furthermore, after LPS injection, livers of Idh1 KO mice showed histological evidence of elevated oxidative DNA damage compared with livers of wild-type (WT) mice. Idh1 KO livers showed a faster and more pronounced oxidative stress than WT livers. In line with that, Idh1 KO hepatocytes showed higher ROS levels and an increase in the NADP(+)/NADPH ratio when compared with hepatocytes isolated from WT mice. These results suggest that Idh1 has a physiological function in protecting cells from oxidative stress by regulating the intracellular NADP(+)/NADPH ratio. Our findings suggest that stimulation of Idh1 activity may be an effective therapeutic strategy for reducing oxidative stress during inflammatory responses, including the early stages of septic shock.

Backward wave cyclotron-maser emission in the auroral magnetosphere.

In this Letter, we present theory and particle-in-cell simulations describing cyclotron radio emission from Earth's auroral region and similar phenomena in other astrophysical environments. In particular, we find that the radiation, generated by a down-going electron horseshoe distribution is due to a backward-wave cyclotron-maser emission process. The backward wave nature of the radiation contributes to upward refraction of the radiation that is also enhanced by a density inhomogeneity. We also show that the radiation is preferentially amplified along the auroral oval rather than transversely. The results are in agreement with recent Cluster observations.

Cancer cell metabolism.

Although the generation of a distinctive metabolic profile is a well-known aspect of cancer, the significance of these adaptations and their potential for exploitation for anticancer therapy has not been fully appreciated until recently. Many oncogenic changes known to affect intracellular signaling pathways play an active role in mediating these metabolic changes, which, in turn, function to support cancer cell growth and replication. In this chapter, we discuss the most current findings in cancer cell metabolism in terms of their impact on tumor cell growth as well as their potential for identifying new targets for therapeutic intervention.

Production of picosecond, kilojoule, and petawatt laser pulses via Raman amplification of nanosecond pulses.

Raman amplification in plasma has been promoted as a means of compressing picosecond optical laser pulses to femtosecond duration to explore the intensity frontier. Here we show for the first time that it can be used, with equal success, to compress laser pulses from nanosecond to picosecond duration. Simulations show up to 60% energy transfer from pump pulse to probe pulse, implying that multikilojoule ultraviolet petawatt laser pulses can be produced using this scheme. This has important consequences for the demonstration of fast-ignition inertial confinement fusion.

Dust-acoustic shock waves due to strong correlation among arbitrarily charged dust.

The nonlinear propagation of the dust-acoustic (DA) waves in a strongly coupled dusty plasma containing strongly correlated arbitrarily (positively or negatively) charged dust and weakly correlated Boltzmann electrons and ions has been investigated by employing the generalized hydrodynamic model and the reductive perturbation method. It has been shown that the strong correlation among the charged dust is a source of dissipation and is responsible for the formation of the DA shock waves in such a strongly coupled dusty plasma. It has also been found that the DA shock waves with positive (negative) potential are formed for positively (negatively) charged dust. The basic features of such DA shock waves have been identified. It has been suggested that a laboratory experiment be performed to test the theory presented here.

Cyclotron maser radiation from an inhomogeneous plasma.

Cyclotron maser radiation is important in both laboratory devices such as gyrotrons and in space physics applications to phenomena such as auroral kilometric radiation. To understand the behavior, especially in the latter case where there is generally a localized region of instability, requires an understanding of how such instabilities behave in an inhomogeneous plasma. Here we consider, for simplicity, a simple ring distribution of electrons in either a step function variation of magnetic field or a continuous gradient. In each case we show that there can exist localized regions of instability from which waves, growing in time, can be radiated outwards.

Efficiency and energy spread in laser-wakefield acceleration.

The theoretical limits on efficiency and energy spread of the laser-wakefield accelerator are investigated using a one-dimensional model. Modifications, both of the wakefield due to the electron bunch, and of the laser pulse shape due to the varying permittivity of the plasma, are described self-consistently. It is found that a short laser pulse gives a higher efficiency than a long laser pulse with the same initial energy. Energy spread can be minimized by optimizing bunch length and bunch charge such that the variation of the accelerating force along the length of the bunch is minimized. An inherent trade-off between energy spread and efficiency exists.

Molecular mechanisms of tumor invasion and metastasis: an integrated view.

As tumors progress to increased malignancy, cells within them develop the ability to invade into surrounding normal tissues and through tissue boundaries to form new growths (metastases) at sites distinct from the primary tumor. The molecular mechanisms involved in this process are incompletely understood but those associated with cell-cell and cell-matrix adhesion, with the degradation of extracellular matrix, and with the initiation and maintenance of early growth at the new site are generally accepted to be critical. This article discusses current knowledge of molecular events involved in these various processes. The potential role of adhesion molecules (eg. integrins and cadherins) has undergone a major transition over the last ten years, as it has become apparent that such molecules play a major role in signaling from outside to inside a cell, thereby controlling how a cell is able (or not) to sense and interact with its local environment. Similarly the roles of proteolytic enzymes and their inhibitors (eg. matrix metalloproteinases and TIMPs) have also expanded as it has become apparent that they not only have the abilities to break down the components of the extracellular matrix but also are involved in the release of factors which can affect the growth of the tumor cells positively or negatively. Recent work has highlighted the importance of the later, post-extravasational stages of metastasis, where adhesion and proteolysis are now known to play a role along with other processes such as apoptosis, dormancy, growth factor-receptor interactions and signal transduction. Recent work has also demonstrated that not only the immediate cellular microenvironment, in terms of specific cell-cell and cell-matrix interactions, but also the extended cellular microenvironment, in terms of vascular insufficiency and hypoxia in the primary tumor, can modify cellular gene expression and enhance metastasis. Mechanisms of metastasis appear to involve a complex array of genetic and epigenetic changes many of which appear to be specific both for different types of tumors and for different sites of metastasis. Our improved understanding of the expanded roles of the individual molecules involved has resulted in a mechanistic blurring of the previously described discrete stages of the metastatic process.

Role of parallel flow in the improved mode on the STOR-M tokamak.

A novel feature of the H-mode induced by compact torus injection on the STOR-M tokamak is observed. There is almost no change in the radial electric field profiles during and after the L-H transition. The usual hypothesis of the E x B shear stabilization mechanism is therefore unlikely to play a role in this transition. A new mechanism of the stabilization of microinstabilities by parallel flow is suggested as the plausible cause for the transition to this improved regime.

Acute (cyclic) hypoxia enhances spontaneous metastasis of KHT murine tumors.

Hypoxia exists in most human and rodent solid tumors and has been shown to correlate with poor survival in carcinoma of the cervix, carcinoma of the head and neck, and soft tissue sarcoma. It exists both chronically, due to the poorly organized vasculature of solid tumors, and acutely, due to fluctuations in blood flow. It has been found that tumors that are more hypoxic are more likely to metastasize in humans and in rodent models, and it has been demonstrated that exposure of tumor cells to hypoxia in vitro can transiently enhance their metastatic potential when they are reinjected i.v. into mice. The purpose of the present study was to determine whether experimentally imposed hypoxic stress in vivo, either chronic or acute, affects the process of spontaneous metastasis in tumor-bearing mice. We exposed mice bearing KHT tumors to low oxygen conditions (5-7% O(2) breathing) daily during tumor growth in an attempt to induce additional chronic (2 h/day) and acute (12 x 10 min/day) hypoxia in their tumors. By monitoring tumor pO(2) levels over the course of treatment, we demonstrated that these treatments produce acute and chronic hypoxia within the tumor tissue. The acute but not the chronic hypoxia treatment significantly increased the number of spontaneous microscopic lung metastases in the mice by a factor of about 2, and the results suggest that this effect was due to the changes induced in the primary tumor. This study describes a novel method for studying the effects of hypoxia in solid tumors and demonstrates that acute and chronic hypoxia can have different effects on tumor cell behavior in vivo.

Knee magnetic resonance imaging in childhood chronic monarthritis.

OBJECTIVE: To describe the usefulness of magnetic resonance imaging (MRI) of the knee in the evaluation of chronic monarthritis of uncertain cause in childhood. METHODS: We retrospectively reviewed 21 children referred to our clinic with a putative diagnosis of chronic inflammatory monarthritis of the knee who had MRI performed between May 1993 and June 1997. The median age was 13 years (range 2-17) and 11 were girls. RESULTS: The clinical diagnosis prior to MRI assessment was inflammatory arthritis in 16 patients, and a primary noninflammatory cause in 5. MRI was done in the patients with presumptive inflammatory arthritis when there were atypical symptoms, signs, or radiographs (n = 14), or when they failed to respond to therapy (n = 2). In the patients with a presumptive noninflammatory diagnosis, MRI was performed to clarify the diagnosis. Twelve children (57%) had MRI evidence of a noninflammatory diagnosis. In 4 children (19%) the MRI study indicated the presence of arthritis, and in 5 children (24%) the MRI studies were normal. The noninflammatory diagnoses included: lipoma arborescens (n = 1), vascular malformation [intraarticular (n = 1), extraarticular (n = 1)], synovial chondromatosis (n = 2), partial anterior cruciate ligament tear (n = 2), traumatic bone contusion (n = 2), possible meniscal tear (n = 1), osteochondritis dissecans (n = 1), and a soft tissue mass of uncertain significance in the suprapatellar pouch (n = 1). CONCLUSION: Inflammatory arthritis is usually diagnosed by clinical assessment alone. Uncommonly, when a single joint is involved, and atypical features are identified by a pediatric rheumatologist, other causes of chronic pain and swelling need to be excluded. In this selected patient population, MRI is a useful tool either to confirm the presence of inflammatory arthritis or to investigate a wide range of pathology that can mimic knee joint arthritis.

Congenital-infantile fibrosarcoma: magnetic resonance imaging findings.

Congenital-infantile, fibrosarcoma is a rare tumour presenting at birth or in the neonatal period. Few such tumours have been reported, and imaging details in particular are scant. The authors describe two neonates with congenital-infantile fibrosarcoma, the first case involving the right thigh and extending into the pelvis, and the second involving the calf and the ankle. In both cases magnetic resonance imaging (MRI) demonstrated well-demarcated, low-signal-intensity soft-tissue masses with t1-weighting and inhomogeneous, high-signal-intensity masses with T2-weighting. MRI was superior to other imaging modalities in the assessment of soft-tissue involvement and proved especially useful in planning therapy and monitoring chemotherapeutic response.

Osteosarcoma in a 19-month-old girl.

Osteosarcoma develops only rarely in patients under 6 years of age. The authors describe a 19-month-old girl who presented with proximal humeral metaphyseal osteosarcoma. To the authors' knowledge, this report represents the youngest patient with this bone lesion.

An unusual case of mixed sclerosing bone dystrophy presenting with morning stiffness and joint swelling in childhood: a case report.

We describe a case of a 16 year old native Indian girl with pain, morning stiffness and foot swelling who had radiographic changes consistent with mixed sclerosing bone dystrophy (MSBD) combined with fibrous dysplasia.

Atlantoaxial subluxation in children with seronegative enthesopathy and arthropathy syndrome: 2 case reports and a review of the literature.

We describe 2 HLA-B27 positive children with seronegative enthesopathy and arthropathy (SEA) syndrome who developed spontaneous (nontraumatic) atlantoaxial subluxation early in their disease course. Neither child had evidence of spinal cord compression but both had progressive atlantoaxial subluxation in spite of conservative treatment. Both underwent elective posterior cervical (C1-C2) fusion.

Obstructive lung disease in children after allogeneic bone marrow transplantation: evaluation with high-resolution CT.

OBJECTIVE: Obstructive lung disease is a major complication of bone marrow transplantation related to graft-versus-host disease. The purpose of this study was to determine the usefulness of high-resolution CT to evaluate obstructive lung disease occurring in children after bone marrow transplantation. MATERIALS AND METHODS: Ten high-resolution CT scans of the lungs were obtained in seven children who developed chronic obstructive lung disease after bone marrow transplantation. All seven patients had chronic graft-versus-host disease. Spirometry, the gold standard test, confirmed airflow obstruction in each case, five prior to high-resolution CT. Two patients were too young to have spirometry until 10 and 15 months respectively after successful high-resolution CT. Selected images from these studies were randomized with similar images from five control subjects and reviewed blindly. All images from scans in patients with obstructive lung disease were analyzed retrospectively for parenchymal hypoattenuation, bronchial dilatation, bronchial wall thickening, and abnormal parenchymal opacity. Expiratory air-trapping was assessed on cine high-resolution CT done in four cases. RESULTS: Three blinded observers each correctly identified all five controls among 15 high-resolution CT examinations. No scan from a patient with obstructive lung disease was considered normal. Areas of parenchymal hypoattenuation affected 35 of 35 lobes of the lung. Expiratory air-trapping was shown by cine high-resolution CT. Subsegmental or segmental bronchial dilatation was seen in 23 of 25 lobes in five patients. Bronchial wall thickening was not a prominent feature. Increasing abnormality was demonstrated in three patients on follow-up high-resolution CT. The high-resolution CT abnormalities were similar to those reported in patients with bronchiolitis obliterans. CONCLUSION: High-resolution CT of the lungs can show extensive abnormality in children who develop chronic obstructive lung disease after bone marrow transplantation. High-resolution CT is a useful noninvasive technique in the evaluation of this disease.