Exploring 4D Quantum Hall Physics with a 2D Topological Charge Pump

The discovery of topological states of matter has profoundly augmented our understanding of phase transitions in physical systems. Instead of local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example thereof is the two-dimensional integer quantum Hall effect. It is characterized by the first Chern number which manifests in the quantized Hall response induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional systems leads to the appearance of a novel non-linear Hall response that is quantized as well, but described by a 4D topological invariant - the second Chern number. Here, we report on the first observation of a bulk response with intrinsic 4D topology and the measurement of the associated second Chern number. By implementing a 2D topological charge pump with ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small atom cloud as a local probe, we fully characterize the non-linear response of the system by in-situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probe higher-dimensional quantum Hall systems, where new topological phases with exotic excitations are predicted

Death from colonic disease in epidermolysis bullosa dystrophica

BACKGROUND: Squamous cell carcinomas and renal failure were reported the causes of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Death from colonic disease in epidermolysis bullosa (EB) is never reported. CASE PRESENTATION: We demonstrate a male patient with RDEB. He suffered megacolon due to fecal impaction and died from sigmoid colon perforation with peritonitis at age 35 years. CONCLUSION: Constipation is a common clinical feature of RDEB, but fetal complications of chronic constipation are rarely reported. To the author's best knowledge, it has not been reported or recognized in the English literature previously. The aggressive assessment of constipation with fecal impaction is recommended in patients with RDEB

Emergent quantum confinement at topological insulator surfaces

Bismuth-chalchogenides are model examples of three-dimensional topological insulators. Their ideal bulk-truncated surface hosts a single spin-helical surface state, which is the simplest possible surface electronic structure allowed by their non-trivial $\mathbb{Z}_2$ topology. They are therefore widely regarded ideal templates to realize the predicted exotic phenomena and applications of this topological surface state. However, real surfaces of such compounds, even if kept in ultra-high vacuum, rapidly develop a much more complex electronic structure whose origin and properties have proved controversial. Here, we demonstrate that a conceptually simple model, implementing a semiconductor-like band bending in a parameter-free tight-binding supercell calculation, can quantitatively explain the entire measured hierarchy of electronic states. In combination with circular dichroism in angle-resolved photoemission (ARPES) experiments, we further uncover a rich three-dimensional spin texture of this surface electronic system, resulting from the non-trivial topology of the bulk band structure. Moreover, our study reveals how the full surface-bulk connectivity in topological insulators is modified by quantum confinement.Comment: 9 pages, including supplementary information, 4+4 figures. A high resolution version is available at http://www.st-andrews.ac.uk/~pdk6/pub_files/TI_quant_conf_high_res.pd

NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes

<p>Abstract</p> <p>Background</p> <p>Lipoteichoic acid (LTA) is a component of gram-positive bacterial cell walls and may be elevated in the cerebrospinal fluid of patients suffering from meningitis. Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Moreover, several studies have suggested that increased oxidative stress is implicated in the pathogenesis of brain inflammation and injury. However, the molecular mechanisms underlying LTA-induced redox signal and MMP-9 expression in brain astrocytes remain unclear.</p> <p>Objective</p> <p>Herein we explored whether LTA-induced MMP-9 expression was mediated through redox signals in rat brain astrocytes (RBA-1 cells).</p> <p>Methods</p> <p>Upregulation of MMP-9 by LTA was evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways were investigated by pretreatment with pharmacological inhibitors or transfection with small interfering RNAs (siRNAs), Western blotting, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover, we determined the cell functional changes by migration assay.</p> <p>Results</p> <p>These results showed that LTA induced MMP-9 expression via a PKC(α)-dependent pathway. We further demonstrated that PKCα stimulated p47^phox/NADPH oxidase 2 (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9 promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co-activator p300 also contributed to these responses. Functionally, LTA-induced MMP-9 expression enhanced astrocytic migration.</p> <p>Conclusion</p> <p>These results demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(α)-mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell migration enhanced by LTA.</p

Human factors for dementia: Evidence based design

Designing care environments for people living with dementia is a complex challenge as the key stakeholder may have difficulty communicating their capabilities, limitations and preferences. This paper describes the use of evidence-based design personas in a multi-disciplinary team with architects and chartered human factors specialists. Four individual personas (Alison, Barry, Christine and David) and a couple persona (Chris and Sally) were used to bring the voices of the people living with different stages of dementia to the design process. Their changing/fluctuating symptoms were communicated in two formats (wheel and matrix) within an inclusive design process to adapt a Victorian semi-detached house. The demonstrator house presents evidence based design, adaptation and support solutions to support people living with dementia to age well at home

Matrix Metalloproteinase-8 Mediates the Unfavorable Systemic Impact of Local Irradiation on Pharmacokinetics of Anti-Cancer Drug 5-Fluorouracil

Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for cancer treatment. However, the interactions between radiation and 5-FU remain unclear. Here, we evaluated the influence of local irradiation on the pharmacokinetics of 5-FU in rats. The single-fraction radiation was delivered to the whole pelvic fields of Sprague-Dawley rats after computerized tomography-based planning. 5-FU at 100 mg/kg was prescribed 24 hours after radiation. A high-performance liquid chromatography system was used to measure 5-FU in the blood. Matrix metalloproteinase-8 (MMP-8) inhibitor I was administered to examine whether or not RT modulation of 5-FU pharmacokinetic parameters could be blocked. Compared with sham-irradiated controls, whole pelvic irradiation reduced the area under the concentration versus time curve (AUC) of 5-FU in plasma and, in contrast, increased in bile with a radiation dose-dependent manner. Based on protein array analysis, the amount of plasma MMP-8 was increased by whole pelvic irradiation (2.8-fold by 0.5 Gy and 5.3-fold by 2 Gy) in comparison with controls. Pretreatment with MMP-8 inhibitor reversed the effect of irradiation on AUC of 5-FU in plasma. Our findings first indicate that local irradiation modulate the systemic pharmacokinetics of 5-FU through stimulating the release of MMP-8. The pharmacokinetics of 5-FU during concurrent chemoradiaiton therapy should be rechecked and the optimal 5-FU dose should be reevaluated, and adjusted if necessary, during CCRT

The persistence of epiphyseal scars in the distal radius in adult individuals

The use of radiographic imaging in the estimation of chronological age facilitates the analysis of structures not visible on gross morphological inspection. Following the completion of epiphyseal fusion, a thin radio-opaque band, the epiphyseal scar, may be observed at the locus of the former growth plate. The obliteration of this feature has previously been interpreted as the final stage of skeletal maturation and consequently has been included as a criterion in several methods of age estimation, particularly from the distal radius. Due to the recommendations relating to age estimation in living individuals, accurate assessment of age from the distal radius is of great importance in human identification; however, the validity of the interpretation of the obliteration of the epiphyseal scar as an age-related process has not been tested. A study was undertaken to assess the persistence of epiphyseal scars in adults between 20 and 50 years of age through the assessment of 616 radiographs of left and right distal radii from a cross-sectional population. This study found that 86 % of females and 78 % of males retained some remnant of the epiphyseal scar in the distal radius. The relationships between chronological age, biological sex and the persistence of the epiphyseal scar were not statistically significant. The findings of this study indicate that the epiphyseal scars may persist in adult individuals until at least 50 years of age. No maximum age should therefore be applied to the persistence of an epiphyseal scar in the distal radius

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Dementia-friendly communities: challenges and strategies for achieving stakeholder involvement.

Dementia-friendly communities (DFCs) are a UK policy initiative that aims to enable people with dementia to feel supported and included within their local community. Current approaches to DFC creation rely on stakeholder involvement, often requiring volunteer assistance. There is though a lack of evidence that examines the reality of achieving this. This paper critically assesses the challenges and strategies for achieving stakeholder involvement in DFCs. The evidence base is drawn from an inter-agency project funded by the National Health Service in the South of England where seven DFCs were developed by steering group partners and four part-time project workers (PWs). Data from the independent evaluation undertaken in the first year (2013-2014) of the project were analysed: 14 semi-structured interviews and a focus group examined PWs' experiences; while progress and key milestones are determined from monthly progress forms, good news stories, locality steering group minutes and press releases. Analysis was undertaken using a directed content analysis method, whereby data content for each locality was matched to the analytical framework that was drawn from Alzheimer's Society guidance. Challenges to achieving stakeholder involvement were identified as: establishing networks and including people representative of the local community; involving people affected by dementia; and gaining commitment from organisations. Strategies for achieving stakeholder involvement were recognised as: a sustainable approach; spreading the word; and sharing of ideas. By highlighting these challenges and the approaches that have been used within communities to overcome them, these findings form the foundation for the creation of DFC initiatives that will become embedded within communities. Stakeholder involvement is unpredictable and changeable; therefore, reliance on this approach questions the long-term sustainability of DFCs, and must be considered in future policies designed to enhance quality of life for people affected by dementia

Estimation of colorectal adenoma recurrence with dependent censoring

<p>Abstract</p> <p>Background</p> <p>Due to early colonoscopy for some participants, interval-censored observations can be introduced into the data of a colorectal polyp prevention trial. The censoring could be dependent of risk of recurrence if the reasons of having early colonoscopy are associated with recurrence. This can complicate estimation of the recurrence rate.</p> <p>Methods</p> <p>We propose to use midpoint imputation to convert interval-censored data problems to right censored data problems. To adjust for potential dependent censoring, we use information from auxiliary variables to define risk groups to perform the weighted Kaplan-Meier estimation to the midpoint imputed data. The risk groups are defined using two risk scores derived from two working proportional hazards models with the auxiliary variables as the covariates. One is for the recurrence time and the other is for the censoring time. The method described here is explored by simulation and illustrated with an example from a colorectal polyp prevention trial.</p> <p>Results</p> <p>We first show that midpoint imputation under an assumption of independent censoring will produce an unbiased estimate of recurrence rate at the end of the trial, which is often the main interest of a colorectal polyp prevention trial, and then show in simulations that the weighted Kaplan-Meier method using the information from auxiliary variables based on the midpoint imputed data can improve efficiency in a situation with independent censoring and reduce bias in a situation with dependent censoring compared to the conventional methods, while estimating the recurrence rate at the end of the trial.</p> <p>Conclusion</p> <p>The research in this paper uses midpoint imputation to handle interval-censored observations and then uses the information from auxiliary variables to adjust for dependent censoring by incorporating them into the weighted Kaplan-Meier estimation. This approach can handle a situation with multiple auxiliary variables by deriving two risk scores from two working PH models. Although the idea of this approach might appear simple, the results do show that the weighted Kaplan-Meier approach can gain efficiency and reduce bias due to dependent censoring.</p