Multi-functionalised graphene nanoflakes as tumour-targeting theranostic drug-delivery vehicles

Graphene nanoflakes (GNFs) consist of a graphene sheet approximately 30 nm in diameter with a pristine aromatic system and an edge terminated with carboxylic acid groups. Their high water solubility and relative ease of functionalisation using carboxylate chemistry means that GNFs are potential scaffolds for the synthesis of theranostic agents. In this work, GNFs were multi-functionalised with derivatives of (i) a peptide-based Glu-NH-C(O)-NH-Lys ligand that binds prostate-specific membrane antigen (PSMA), (ii) a potent anti-mitotic drug (R)-ispinesib, (iii) the chelate desferrioxamine B (DFO), and (iv) an albumin-binding tag reported to extend pharmacokinetic half-life in vivo. Subsequent 68Ga radiochemistry and experiments in vitro and in vivo were used to evaluate the performance of GNFs in theranostic drug design. Efficient 68Ga-radiolabelling was achieved and the particle-loading of (R)-ispinesib and Glu-NH-C(O)-NH-Lys was confirmed using cellular assays. Using dose–response curves and FACS analysis it was shown that GNFs loaded with (R)-ispinesib inhibited the kinesin spindle protein (KSP) and induced G2/M-phase cell cycle arrest. Cellular uptake and blocking experiments demonstrated that GNFs functionalised with the Glu-NH-C(O)-NH-Lys ligand showed specificity toward PSMA expressing cells (LNCaP). The distribution profile and excretion rates of 68Ga-radiolabelled GNFs in athymic nude mice was evaluated using time–activity curves derived from dynamic positron-emission tomography (PET). Image analysis indicated that GNFs have low accumulation and retention in background tissue, with rapid renal clearance. In summary, our study shows that GNFs are suitable candidates for use in theranostic drug design

Probable detection of starlight reflected from the giant exoplanet orbiting tau Bootis

Giant planets orbiting stars other than the Sun are clearly detectable through precise radial-velocity measurements of the orbital reflex motion of the parent star. In the four years since the discovery of the companion to the star 51 Peg, similar low-amplitude ``Doppler star wobbles'' have revealed the presence of some 20 planets orbiting nearby solar-type stars. Several of these newly-discovered planets are very close to their parent stars, in orbits with periods of only a few days. Being an indirect technique, however, the reflex-velocity method has little to say about the sizes or compositions of the planets, and can only place lower limits on their masses. Here we report the use of high-resolution optical spectroscopy to achieve a probable detection of the Doppler-shifted signature of starlight reflected from one of these objects, the giant exoplanet orbiting the star tau Bootis. Our data give the planet's orbital inclination i=29 degrees, indicating that its mass is some 8 times that of Jupiter, and suggest strongly that the planet has the size and reflectivity expected for a gas-giant planet.Comment: 15 pages, 4 figures. (Fig 1 and equation for epsilon on p1 para 2 revised; changed from double to single spacing

Quantization of Midisuperspace Models

We give a comprehensive review of the quantization of midisuperspace models. Though the main focus of the paper is on quantum aspects, we also provide an introduction to several classical points related to the definition of these models. We cover some important issues, in particular, the use of the principle of symmetric criticality as a very useful tool to obtain the required Hamiltonian formulations. Two main types of reductions are discussed: those involving metrics with two Killing vector fields and spherically symmetric models. We also review the more general models obtained by coupling matter fields to these systems. Throughout the paper we give separate discussions for standard quantizations using geometrodynamical variables and those relying on loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit

The 2017 Magnetism Roadmap

Building upon the success and relevance of the 2014 Magnetism Roadmap, this 2017 Magnetism Roadmap edition follows a similar general layout, even if its focus is naturally shifted, and a different group of experts and, thus, viewpoints are being collected and presented. More importantly, key developments have changed the research landscape in very relevant ways, so that a novel view onto some of the most crucial developments is warranted, and thus, this 2017 Magnetism Roadmap article is a timely endeavour. The change in landscape is hereby not exclusively scientific, but also reflects the magnetism related industrial application portfolio. Specifically, Hard Disk Drive technology, which still dominates digital storage and will continue to do so for many years, if not decades, has now limited its footprint in the scientific and research community, whereas significantly growing interest in magnetism and magnetic materials in relation to energy applications is noticeable, and other technological fields are emerging as well. Also, more and more work is occurring in which complex topologies of magnetically ordered states are being explored, hereby aiming at a technological utilization of the very theoretical concepts that were recognised by the 2016 Nobel Prize in Physics. Given this somewhat shifted scenario, it seemed appropriate to select topics for this Roadmap article that represent the three core pillars of magnetism, namely magnetic materials, magnetic phenomena and associated characterization techniques, as well as applications of magnetism. While many of the contributions in this Roadmap have clearly overlapping relevance in all three fields, their relative focus is mostly associated to one of the three pillars. In this way, the interconnecting roles of having suitable magnetic materials, understanding (and being able to characterize) the underlying physics of their behaviour and utilizing them for applications and devices is well illustrated, thus giving an accurate snapshot of the world of magnetism in 2017. The article consists of 14 sections, each written by an expert in the field and addressing a specific subject on two pages. Evidently, the depth at which each contribution can describe the subject matter is limited and a full review of their statuses, advances, challenges and perspectives cannot be fully accomplished. Also, magnetism, as a vibrant research field, is too diverse, so that a number of areas will not be adequately represented here, leaving space for further Roadmap editions in the future. However, this 2017 Magnetism Roadmap article can provide a frame that will enable the reader to judge where each subject and magnetism research field stands overall today and which directions it might take in the foreseeable future. The first material focused pillar of the 2017 Magnetism Roadmap contains five articles, which address the questions of atomic scale confinement, 2D, curved and topological magnetic materials, as well as materials exhibiting unconventional magnetic phase transitions. The second pillar also has five contributions, which are devoted to advances in magnetic characterization, magneto-optics and magneto-plasmonics, ultrafast magnetization dynamics and magnonic transport. The final and application focused pillar has four contributions, which present non-volatile memory technology, antiferromagnetic spintronics, as well as magnet technology for energy and bio-related applications. As a whole, the 2017 Magnetism Roadmap article, just as with its 2014 predecessor, is intended to act as a reference point and guideline for emerging research directions in modern magnetism

Quantitative nanoscale vortex-imaging using a cryogenic quantum magnetometer

Microscopic studies of superconductors and their vortices play a pivotal role in our understanding of the mechanisms underlying superconductivity. Local measurements of penetration depths or magnetic stray-fields enable access to fundamental aspects of superconductors such as nanoscale variations of superfluid densities or the symmetry of their order parameter. However, experimental tools, which offer quantitative, nanoscale magnetometry and operate over the large range of temperature and magnetic fields relevant to address many outstanding questions in superconductivity, are still missing. Here, we demonstrate quantitative, nanoscale magnetic imaging of Pearl vortices in the cuprate superconductor YBCO, using a scanning quantum sensor in form of a single Nitrogen-Vacancy (NV) electronic spin in diamond. The sensor-to-sample distance of ~10nm we achieve allows us to observe striking deviations from the prevalent monopole approximation in our vortex stray-field images, while we find excellent quantitative agreement with Pearl's analytic model. Our experiments yield a non-invasive and unambiguous determination of the system's local London penetration depth, and are readily extended to higher temperatures and magnetic fields. These results demonstrate the potential of quantitative quantum sensors in benchmarking microscopic models of complex electronic systems and open the door for further exploration of strongly correlated electron physics using scanning NV magnetometry.Comment: Main text (5 pages, 4 figures) plus supplementary material (5 pages, 6 figures). Comments welcome. Further information under http://www.quantum-sensing.c

Development and evaluation of a hand held computer based on-call pack for health protection out of hours duty: A pilot study

BACKGROUND: The on call service for health protection in most parts of the UK is provided by general public health consultants, registrars and nurses as the first tier of response backed up by medical consultants in health protection. The first tier responder usually carries a large bag of papers containing both local and national guidance on the management of common cases/incidents. An electronic on call pack may provide a suitable practical alternative to large paper based systems and help professionals deliver out of hours health protection advice and response to incidents. METHODS: We developed and piloted an electronic on call pack in Hertfordshire for use at the health protection unit level containing key local and national guidelines, contact information and useful references. The on-call pack was initially piloted using a laptop and more recently using a personal digital assistant (PDA). The use of the on-call pack was evaluated. RESULTS: Key advantages of the electronic system include reduced size, faster access to information that is clearly indexed and the relative ease of updating information. As part of the pilot, the electronic on call pack was presented to a local and regional training meeting with good response from participants using qualitative and quantitative methods. CONCLUSION: It is anticipated that with suitable evaluation this system can be adapted and utilised by other health protection practitioners. This system provides a fast, reliable and easily maintained source of information for the public health on-call team

Mucosal atrophy in collagenous colitis: a case report

<p>Abstract</p> <p>Background</p> <p>Mucosal atrophy as a potential cause of impaired colonic compliance has not yet been described as a complication in Collagenous Colitis (CC).</p> <p>Case presentation</p> <p>We present a 51-year-old female patient with a 20-year history of diarrhea and diagnosed with CC ten years prior to her presentation. We reviewed reports from three colonoscopies performed after the diagnosis. Overall 12 biopsies obtained in the last two colonoscopies were re-analyzed by two pathologists blinded to the aim of the study. Besides the typical histological findings of CC, the endoscopic appearance was normal, and no histological signs of atrophy were found during the first colonoscopy. Surprisingly, the second and third colonoscopy revealed a region of advanced segmental mucosal atrophy in the cecum with the mucosal height normalizing toward the transverse colon. This pattern of atrophy was inversely related to the pattern of sub-epithelial collagen deposition, which increased toward the rectum.</p> <p>Conclusion</p> <p>If no chance occurrence, our observation supports the idea that additional factors, probably luminal in nature, may be co-responsible for the mucosal atrophy in this case. Thus, mucosal atrophy in the proximal colon appears to be a new candidate among the growing list of rare complications associated with long standing CC.</p

Limiting problems for a nonstandard viscous Cahn--Hilliard system with dynamic boundary conditions

This note is concerned with a nonlinear diffusion problem of phase-field type, consisting of a parabolic system of two partial differential equations, complemented by boundary and initial conditions. The system arises from a model of two-species phase segregation on an atomic lattice and was introduced by Podio-Guidugli in Ric. Mat. 55 (2006), pp.105--118. The two unknowns are the phase parameter and the chemical potential. In contrast to previous investigations about this PDE system, we consider here a dynamic boundary condition for the phase variable that involves the Laplace-Beltrami operator and models an additional nonconserving phase transition occurring on the surface of the domain. We are interested to some asymptotic analysis and first discuss the asymptotic limit of the system as the viscosity coefficient of the order parameter equation tends to 0: the convergence of solutions to the corresponding solutions for the limit problem is proven. Then, we study the long-time behavior of the system for both problems, with positive or zero viscosity coefficient, and characterize the omega-limit set in both cases