Dynamic Pattern Formation in Electron-Beam-Induced Etching

© 2015 American Physical Society. We report highly ordered topographic patterns that form on the surface of diamond, span multiple length scales, and have a symmetry controlled by the precursor gas species used in electron-beam-induced etching (EBIE). The pattern formation dynamics reveals an etch rate anisotropy and an electron energy transfer pathway that is overlooked by existing EBIE models. We, therefore, modify established theory such that it explains our results and remains universally applicable to EBIE. The patterns can be exploited in controlled wetting, optical structuring, and other emerging applications that require nano- and microscale surface texturing of a wide band-gap material

Gas-mediated charged particle beam processing of nanostructured materials

Gas mediated processing under a charged particle (electron or ion) beam enables direct-write, high resolution surface functionalization, chemical dry etching and chemical vapor deposition of a wide range of materials including catalytic metals, optoelectronic grade semiconductors and oxides. Here we highlight three recent developments of particular interest to the optical materials and nanofabrication communities: fabrication of self-supporting, three dimensional, fluorescent diamond nanostructures, electron beam induced deposition (EBID) of high purity materials via activated chemisorption, and post-growth purification of nanocrystalline EBID-grown platinum suitable for catalysis applications. © 2014 SPIE

Automatic classification of takeaway food outlet cuisine type using machine (deep) learning

Background and purpose Neighbourhood exposure to takeaway (‘fast’-) food outlets selling different cuisines may be differentially associated with diet, obesity and related disease, and contributing to population health inequalities. However research studies have not disaggregated takeaways by cuisine type. This is partly due to the substantial resource challenge of de novo manual classification of unclassified takeaway outlets at scale. We describe the development of a new model to automatically classify takeaway food outlets, by 10 major cuisine types, based on business name alone. Material and methods We used machine (deep) learning, and specifically a Long Short Term Memory variant of a Recurrent Neural Network, to develop a predictive model trained on labelled outlets (n=14,145), from an online takeaway food ordering platform. We validated the accuracy of predictions on unseen labelled outlets (n=4000) from the same source. Results Although accuracy of prediction varied by cuisine type, overall the model (or ‘classifier’) made a correct prediction approximately three out of four times. We demonstrated the potential of the classifier to public health researchers and for surveillance to support decision-making, through using it to characterise nearly 55,000 takeaway food outlets in England by cuisine type, for the first time. Conclusions Although imperfect, we successfully developed a model to classify takeaway food outlets, by 10 major cuisine types, from business name alone, using innovative data science methods. We have made the model available for use elsewhere by others, including in other contexts and to characterise other types of food outlets, and for further development.This study is funded by the National Institute of Health Research (NIHR) School of Public Health Research (Grant Reference Number PD-SPH-2015). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This work was also supported by the MRC Epidemiology Unit, University of Cambridge (Grant Reference Number MC/UU/00006/7). TBu is funded by the Centre for Diet and Activity Research (CEDAR), a UK Clinical Research Collaboration (UKCRC) Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute of Health Research, and the Wellcome Trust (Grant Reference Number MR/K023187/1), under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. These funders played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication

Nuclear receptors in vascular biology

Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma.

Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem-like cells, a source of post-treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM-infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)-β-mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single-cell transcriptomics demonstrated that both tumour and haematopoietic-derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co-expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti-tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways

Quantum Non-demolition Detection of Single Microwave Photons in a Circuit

Thorough control of quantum measurement is key to the development of quantum information technologies. Many measurements are destructive, removing more information from the system than they obtain. Quantum non-demolition (QND) measurements allow repeated measurements that give the same eigenvalue. They could be used for several quantum information processing tasks such as error correction, preparation by measurement, and one-way quantum computing. Achieving QND measurements of photons is especially challenging because the detector must be completely transparent to the photons while still acquiring information about them. Recent progress in manipulating microwave photons in superconducting circuits has increased demand for a QND detector which operates in the gigahertz frequency range. Here we demonstrate a QND detection scheme which measures the number of photons inside a high quality-factor microwave cavity on a chip. This scheme maps a photon number onto a qubit state in a single-shot via qubit-photon logic gates. We verify the operation of the device by analyzing the average correlations of repeated measurements, and show that it is 90% QND. It differs from previously reported detectors because its sensitivity is strongly selective to chosen photon number states. This scheme could be used to monitor the state of a photon-based memory in a quantum computer.Comment: 5 pages, 4 figures, includes supplementary materia

Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Nonlinear response of the vacuum Rabi resonance

On the level of single atoms and photons, the coupling between atoms and the electromagnetic field is typically very weak. By employing a cavity to confine the field, the strength of this interaction can be increased many orders of magnitude to a point where it dominates over any dissipative process. This strong-coupling regime of cavity quantum electrodynamics has been reached for real atoms in optical cavities, and for artificial atoms in circuit QED and quantum-dot systems. A signature of strong coupling is the splitting of the cavity transmission peak into a pair of resolvable peaks when a single resonant atom is placed inside the cavity - an effect known as vacuum Rabi splitting. The circuit QED architecture is ideally suited for going beyond this linear response effect. Here, we show that increasing the drive power results in two unique nonlinear features in the transmitted heterodyne signal: the supersplitting of each vacuum Rabi peak into a doublet, and the appearance of additional peaks with the characteristic sqrt(n) spacing of the Jaynes-Cummings ladder. These constitute direct evidence for the coupling between the quantized microwave field and the anharmonic spectrum of a superconducting qubit acting as an artificial atom.Comment: 6 pages, 4 figures. Supplementary Material and Supplementary Movies are available at http://www.eng.yale.edu/rslab/publications.htm

Oldest pathology in a tetrapod bone illuminates the origin of terrestrial vertebrates

The origin of terrestrial tetrapods was a key event in vertebrate evolution, yet how and when it occurred remains obscure, due to scarce fossil evidence. Here, we show that the study of palaeopathologies, such as broken and healed bones, can help elucidate poorly understood behavioural transitions such as this. Using high-resolution finite element analysis, we demonstrate that the oldest known broken tetrapod bone, a radius of the primitive stem tetrapod Ossinodus pueri from the mid-Viséan (333 million years ago) of Australia, fractured under a high-force, impact-type loading scenario. The nature of the fracture suggests that it most plausibly occurred during a fall on land. Augmenting this are new osteological observations, including a preferred directionality to the trabecular architecture of cancellous bone. Together, these results suggest that Ossinodus, one of the first large (>2m length) tetrapods, spent a significant proportion of its life on land. Our findings have important implications for understanding the temporal, biogeographical and physiological contexts under which terrestriality in vertebrates evolved. They push the date for the origin of terrestrial tetrapods further back into the Carboniferous by at least two million years. Moreover, they raise the possibility that terrestriality in vertebrates first evolved in large tetrapods in Gondwana rather than in small European forms, warranting a re-evaluation of this important evolutionary event