Bifurcations and chaos in semiconductor superlattices with a tilted magnetic field

We study the effects of dissipation on electron transport in a semiconductor superlattice with an applied bias voltage and a magnetic field that is tilted relative to the superlattice axis.In previous work, we showed that although the applied fields are stationary,they act like a THz plane wave, which strongly couples the Bloch and cyclotron motion of electrons within the lowest miniband. As a consequence,the electrons exhibit a unique type of Hamiltonian chaos, which creates an intricate mesh of conduction channels (a stochastic web) in phase space, leading to a large resonant increase in the current flow at critical values of the applied voltage. This phase-space patterning provides a sensitive mechanism for controlling electrical resistance. In this paper, we investigate the effects of dissipation on the electron dynamics by modifying the semiclassical equations of motion to include a linear damping term. We demonstrate that even in the presence of dissipation,deterministic chaos plays an important role in the electron transport process. We identify mechanisms for the onset of chaos and explore the associated sequence of bifurcations in the electron trajectories. When the Bloch and cyclotron frequencies are commensurate, complex multistability phenomena occur in the system. In particular, for fixed values of the control parameters several distinct stable regimes can coexist, each corresponding to different initial conditions. We show that this multistability has clear, experimentally-observable, signatures in the electron transport characteristics.Comment: 14 pages 11 figure

Endoscopic tri-modal imaging for surveillance in ulcerative colitis: randomised comparison of high-resolution endoscopy and autofluorescence imaging for neoplasia detection; and evaluation of narrow-band imaging for classification of lesions

Background: Endoscopic tri-modal imaging (ETMI) incorporates white light endoscopy (WLE), autofluorescence imaging (AFI) and narrow-band imaging (NBI). Aims: To assess the value of ETMI for the detection and classification of neoplasia in patients with longstanding ulcerative colitis. Design: Randomised comparative trial of tandem colonoscopies. Setting: Academic Medical Centre Amsterdam, Netherlands. Patients and methods: Fifty patients with ulcerative colitis underwent surveillance colonoscopy with ETMI. Each colonic segment was inspected twice, once with AFI and once with WLE, in random order. All detected lesions were inspected by NBI for Kudo pit pattern analysis and additional random biopsies were taken. Main outcome measures: Neoplasia miss-rates of AFI and WLE, and accuracy of the Kudo classification by NBI. Results: Among patients assigned to inspection with AFI first (n = 25), 10 neoplastic lesions were primarily detected. Subsequent WLE detected no additional neoplasia. Among patients examined with WLE first (n = 25), three neoplastic lesions were detected; subsequent inspection with AFI added three neoplastic lesions. Neoplasia miss-rates for AFI and WLE were 0% and 50% (p = 0.036). The Kudo classification by NBI had a sensitivity and specificity of 75% and 81%; however, all neoplasia was coloured purple on AFI (sensitivity 100%). No additional patients with neoplasia were detected by random biopsies. Conclusion: Autofluorescence imaging improves the detection of neoplasia in patients with ulcerative colitis and decreases the yield of random biopsies. Pit pattern analysis by NBI has a moderate accuracy for the prediction of histology, whereas AFI colour appears valuable in excluding the presence of neoplasia. Trial registration number: ISRCTN0527274

A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

OBJECTIVES: To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. METHODS: The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. RESULTS: Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. CONCLUSIONS: This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis

Kinome-wide analysis of the effect of statins in colorectal cancer

Background Epidemiological studies and meta-analyses show an association between statin use and a reduced incidence of colorectal cancer (CRC). We have shown that statins act on CRC through bone morphogenetic protein (BMP) signalling, but the exact cellular targets and underlying mechanism of statin action remain elusive. In this study, we set out to assess the influence of statins on global cancer cell signalling by performing an array-based kinase assay using immobilised kinase substrates spanning the entire human kinome. Methods CRC cells with or without Lovastatin treatment were used for kinome analysis. Findings on kinome arrays were further confirmed by immunoblotting with activity-specific antibodies. Experiments in different CRC cell lines using immunoblotting, siRNA-mediated knockdown and treatment with specific BMP inhibitor Noggin were performed. The relevance of in vitro findings was confirmed in xenografts and in CRC patients treated with Simvastatin. Results Kinome analysis can distinguish between non-specific, toxic effects caused by 10 mu M of Lovastatin and specific effects on cell signalling caused by 2 mu M Lovastatin. Statins induce upregulation of PTEN activity leading to downregulation of the PI3K/Akt/mTOR signalling. Treatment of cells with the specific BMP inhibitor Noggin as well as PTEN knockdown and transfection of cells with a constitutively active form of AKT abolishes the effect of Lovastatin on mTOR phosphorylation. Experiments in xenografts and in patients treated with Simvastatin confirm statin-mediated BMP pathway activation, activation of PTEN and downregulation of mTOR signalling. Conclusions Statins induce BMP-specific activation of PTEN and inhibition of PI3K/Akt/mTOR signalling in CRC

Evaluation of Model Predictions of the Unsteady Tidal Stream Resource and Turbine Fatigue Loads Relative to Multi-Point Flow Measurements at Raz Blanchard

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Measured ADCP data were gathered during the Interreg TIGER project. Further information on the deployment campaigns and underlying ADCP data can be found in T1.7.3 (https://interregtiger.com/download/tiger-tidal-test-procedure-reports/, accessed on 26 June 2023). Overview of models used is given in [36]. Underlying model data are provided in the references given. Variation in the flow properties with disk-averaged velocity as reported in this study and employed for fatigue load analysis is available from https://doi.org/10.48420/24236593 (accessed on 28 September 2023). We are grateful to the French navy SHOM (”Service Hydrographique et Océanographique de la Marine”) for providing access to bathymetric data (http://data.shom.fr/, accessed on 6 June 2023).The next stage of development of the tidal stream industry will see a focus on the deployment of tidal turbines in arrays of increasing device numbers and rated power. Successful array development requires a thorough understanding of the resource within potential deployment sites. This is predictable in terms of flow speeds, based upon tidal constituents. However, the operating environment for the turbine is more complex than the turbine experiencing a uniform flow, with turbulence, shear and wave conditions all affecting the loading on the turbine components. This study establishes the accuracy with which several alternative modelling tools predict the resource characteristics which define unsteady loading—velocity shear, turbulence and waves—and assesses the impact of the model choice on predicted damage equivalent loads. In addition, the predictions of turbulence are compared to a higher fidelity model and the occurrence of flow speeds to a Delft3D model for currents and waves. These models have been run for a specific tidal site, the Raz Blanchard, one of the major tidal stream sites in European waters. The measured resource and predicted loading are established using data collected in a recent deployment of acoustic Doppler current profilers (ADCPs) as part of the Interreg TIGER project. The conditions are measured at three locations across the site, with transverse spacing of 145.7 m and 59.3 m between each device. Turbine fatigue loading is assessed using measurements and model predictions based on an unsteady blade element momentum model applied to near-surface and near-bed deployment positions. As well as across-site spatial variation of loading, the through life loading over a 5-year period results in an 8% difference to measured loads for a near-surface turbine, using conditions purely defined from a resource model and to within 3% when using a combination of modelled shear with measured turbulence characteristics.European Regional Development Fund (ERDF

Bub1 Is a Fission Yeast Kinetochore Scaffold Protein, and Is Sufficient to Recruit other Spindle Checkpoint Proteins to Ectopic Sites on Chromosomes

The spindle checkpoint delays anaphase onset until all chromosomes have attached in a bi-polar manner to the mitotic spindle. Mad and Bub proteins are recruited to unattached kinetochores, and generate diffusible anaphase inhibitors. Checkpoint models propose that Mad1 and Bub1 act as stable kinetochore-bound scaffolds, to enhance recruitment of Mad2 and Mad3/BubR1, but this remains untested for Bub1. Here, fission yeast FRAP experiments confirm that Bub1 stably binds kinetochores, and by tethering Bub1 to telomeres we demonstrate that it is sufficient to recruit anaphase inhibitors in a kinase-independent manner. We propose that the major checkpoint role for Bub1 is as a signalling scaffold

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies