Strongly Anisotropic Transport in Higher Two-Dimensional Landau Levels

Low-temperature, electronic transport in Landau levels N>1 of a two-dimensional electron system is strongly anisotropic. At half-filling of either spin level of each such Landau level the magnetoresistance either collapses to form a deep minimum or is peaked in a sharp maximum, depending on the in-plane current direction. Such anisotropies are absent in the N=0 and N=1 Landau level, which are dominated by the states of the fractional quantum Hall effect. The transport anisotropies may be indicative of a new many particle state, which forms exclusively in higher Landau levels.Comment: 12 pages, 3 Postscript figure

Genetic Assimilation and Canalisation in the Baldwin Effect

The Baldwin Effect indicates that individually learned behaviours acquired during an organism’s lifetime can influence the evolutionary path taken by a population, without any direct Lamarckian transfer of traits from phenotype to genotype. Several computational studies modelling this effect have included complications that restrict its applicability. Here we present a simplified model that is used to reveal the essential mechanisms and highlight several conceptual issues that have not been clearly defined in prior literature. In particular, we suggest that canalisation and genetic assimilation, often conflated in previous studies, are separate concepts and the former is actually not required for non-heritable phenotypic variation to guide genetic variation. Additionally, learning, often considered to be essential for the Baldwin Effect, can be replaced with a more general phenotypic plasticity model. These simplifications potentially permit the Baldwin Effect to operate in much more general circumstances

Inhibition of NF-κB Activity by Thalidomide through Suppression of IκB Kinase Activity

The sedative and anti-nausea drug thalidomide, which causes birth defects in humans, has been shown to have both anti-inflammatory and anti-oncogenic properties. The anti-inflammatory effect of thalidomide is associated with suppression of cytokine expression and the anti-oncogenic effect with inhibition of angiogenesis. It is presently unclear whether the teratogenic properties of thalidomide are connected in any way to the beneficial, anti-disease characteristics of this drug. The transcription factor NF-κB has been shown to be a key regulator of inflammatory genes such as tumor necrosis factor-α and interleukin-8. Inhibition of NF-κB is associated with reduced inflammation in animal models, such as those for rheumatoid arthritis. We show here that thalidomide can block NF-κB activation through a mechanism that involves the inhibition of activity of the IκB kinase. Consistent with the observed inhibition of NF-κB, thalidomide blocked the cytokine-induced expression of NF-κB-regulated genes such as those encoding interleukin-8, TRAF1, and c-IAP2. These data indicate that the therapeutic potential for thalidomide may be based on its ability to block NF-κB activation through suppression of IκB kinase activity

Experimental Evidence for a Spin-Polarized Ground State in the \nu=5/2 Fractional Quantum Hall Effect

We study the \nu=5/2 even-denominator fractional quantum Hall effect (FQHE) over a wide range of magnetic (B) field in a heterojunction insulated gate field-effect transistor (HIGFET). The electron density can be tuned from n=0 to 7.6 \times 10^{11} cm^{-2} with a peak mobility \mu = 5.5 \times 10^6 cm^2/Vs. The \nu=5/2 state shows a strong minimum in diagonal resistance and a developing Hall plateau at magnetic fields as high as 12.6T. The strength of the energy gap varies smoothly with B-field. We interpret these observations as strong evidence for a spin-polarized ground state at \nu=5/2.Comment: new references adde

Chemotherapy-induced muscle wasting: Association with NF-κB and cancer cachexia

A compounding feature of greater than 50% of all cancers is the high incidence of the cachexia syndrome, a complex metabolic disorder characterized by extreme weight loss due mainly to the gross depletion of skeletal muscle tissue. Although studies into the cause of cancer cachexia has spanned over multiple decades, little is known about the effects of various cancer treatments themselves on cachexia. For example, chemotherapy agents induce side effects such as nausea and anorexia, but these symptoms do not fully account for the changes seen with cancer cachexia. In this study we examine the effects of chemotherapeutic compounds, specifically, cisplatin in the colon-26 adenocarcinoma model of cancer cachexia. We find that although cisplatin is able to reduce tumor burden as expected, muscle wasting in mice nevertheless persists. Strikingly, cisplatin alone was seen to regulate muscle atrophy, which was independent of the commonly implicated ubiquitin proteasome system. Finally, we show that cisplatin is able to induce NF-κB activity in both mouse muscles and myotube cultures, suggesting that an additional side effect of cancer treatment is the regulation of muscle wasting that may be mediated through activation of the NF-κB signaling pathway

Iκbα gene transfer is cytotoxic to squamous-cell lung cancer cells and sensitizes them to tumor necrosis factor-α-mediated cell death

Current paradigms in cancer therapy suggest that activation of nuclear factor-κB (NF-κB) by a variety of stimuli, including some cytoreductive agents, may inhibit apoptosis. Thus, inhibiting NF-κB activation may sensitize cells to anticancer therapy, thereby providing a more effective treatment for certain cancers. E-1-deleted adenoviral (Ad) vectors encoding a "superrepressor" form of the NF-κB inhibitor IκBα (AdIκBαSR) or β-galactosidase (AdLacZ) were tested alone and in combination with tumor necrosis factor-α (TNF-α) in lung cancer cells for sensitization of the cells to death. Following transduction with AdIκBαSR, lung cancer cells expressed IκBαSR in a dose-dependent manner. Probing nuclear extracts of lung cancer cells with NF-κB-sequence-specific oligonucleotides indicated that there was a minimal amount of NF-κB in the nucleus at baseline and an expected and dramatic increase in nuclear NF-κB following exposure of cells to TNF-α. Control E-1-deleted AdLacZ did not promote NF-κB activation. Importantly, AdIκBαSR-mediated gene transfer resulted in the complete block of nuclear translocation of NF-κB by specific binding of its p65/relA component with transgenic IκBαSR. At the cellular level, transduction with AdIκBαSR resulted in increased cytotoxicity in lung cancer cells as opposed to transduction with equivalent doses of AdLacZ. In addition, whereas the parental cells were resistant to TNF-α-mediated cytotoxicity, IκBαSR-transduced cells could be sensitized to TNF-α. Consequently, AdIκBαSR transduction followed by exposure to TNF-α uniformly resulted in the death of non-small-cell lung cancer cells. These data suggest that novel approaches incorporating IκBα gene therapy may have a role in the treatment of lung cancer

NF-κB and IκBα are found in the mitochondria. Evidence for regulation of mitochondrial gene expression by NF-κB

The transcription factor NF-κB has been shown to be predominantly cytoplasmically localized in the absence of an inductive signal. Stimulation of cells with inflammatory cytokines such as tumor necrosis factor α or interleukin-1 induces the degradation of IκB, the inhibitor of NF-κB, allowing nuclear accumulation of NF-κB and regulation of specific gene expression. The degradation of IκB is controlled initially by phosphorylation induced by the IκB kinase, which leads to ubiquitination and subsequent proteolysis of the inhibitor by the proteasome. We report here that NF-κB and IκBα (but not IκBβ) are also localized in the mitochondria. Stimulation of cells with tumor necrosis factor α leads to the phosphorylation of mitochondrial IκBα and its subsequent degradation by a nonproteasome-dependent pathway. Interestingly, expression of the mitochondrially encoded cytochrome c oxidase III and cytochrome b mRNAs were reduced by cytokine treatment of cells. Inhibition of activation of mitochondrial NF-κB by expression of the superrepressor form of IκBα inhibited the loss of expression of both cytochrome c oxidase III and cytochrome b mRNA. These data indicate that the NF-κB regulatory pathway exists in mitochondria and that NF-κB can negatively regulate mitochondrial mRNA expression

Reflection and Ducting of Gravity Waves Inside the Sun

Internal gravity waves excited by overshoot at the bottom of the convection zone can be influenced by rotation and by the strong toroidal magnetic field that is likely to be present in the solar tachocline. Using a simple Cartesian model, we show how waves with a vertical component of propagation can be reflected when traveling through a layer containing a horizontal magnetic field with a strength that varies with depth. This interaction can prevent a portion of the downward-traveling wave energy flux from reaching the deep solar interior. If a highly reflecting magnetized layer is located some distance below the convection zone base, a duct or wave guide can be set up, wherein vertical propagation is restricted by successive reflections at the upper and lower boundaries. The presence of both upward- and downward-traveling disturbances inside the duct leads to the existence of a set of horizontally propagating modes that have significantly enhanced amplitudes. We point out that the helical structure of these waves makes them capable of generating an alpha-effect, and briefly consider the possibility that propagation in a shear of sufficient strength could lead to instability, the result of wave growth due to over-reflection.Comment: 23 pages, 5 figures. Accepted for publication in Solar Physic

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students