Graphene Nanoflake Antibody Conjugates for Multimodal Imaging of Tumors

Graphene-based materials are promising scaffolds for use in the design of tailored-made nanomedicines. Herein, the synthesis and characterization of a series of multifunctional carboxylated graphene nanoflakes (GNFs) conjugated to monoclonal antibodies (mAbs) for tumor-specific binding and modulation of pharmacokinetics is presented. GNF–mAb constructs are coupled to a fluorophore (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene [BODIPY]) for applications in optical imaging, a paramagnetic Gd3+ complex, [GdDOTAGA(H2O)]−, and the hexadentate chelate desferrioxamine B (DFO) for radiolabeling with 89Zr4+ (t1/2 = 78.41 h) ions and applications in dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI). Experimental properties of [89Zr]GdDOTAGA–ZrDFO–GNF–trastuzumab are tested in extensive chemical, spectroscopic, radiochemical, and cellular assays in vitro, and assessment of the pharmacokinetics by PET imaging in mice bearing a human ovarian cancer model illustrates the potential of using GNF–mAbs to develop multifunctional PET/MRI probes

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

Multifrequency Strategies for the Identification of Gamma-Ray Sources

More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd

A novel approach using potable diagnostic ultrasound to inform treatment choices for hemiplegic shoulder pain – A case study

Introduction: Hemiplegic shoulder pain (HSP) has a reported incidence of up to 84% of patients. The purpose of this case study is to report findings from a patient with HSP who received problem specific treatment and underwent real-time scanning of shoulder region with a portable diagnostic ultrasound. Treatment was modified to address the problems. Methods/Case Description:The patient was a 45 year-old woman with right sided-hemiparesis resulting from a clot. Patient was undergoing rehabilitation in a private clinic and reported shoulder pain. Patient was undergoing rehabilitation (over-arm exercises, electrical stimulation, stretches, Saebo exercises) however, continued to complain of shoulder pain (VAS-7). Ultrasound scanning was undertaken and following observations were made on both affected (AF) and unaffected (UAF) shoulders. Acromion-greater tuberosity (AGT) distance (AF-3.35 cm, UAF-2.04 cm), diameter of supraspinatus in resting state (AF -1.16 cm, UAF-1.42cm) and contracted state (AF-1.14cm, UAF-1.63cm). Modified treatment included: 1) Isometric exercises to supraspinatus muscle 2) Trigger point release for trapezius 3) Electrical stimulation to lateral deltoid and supraspinatus 4) avoid over-arm activitiesResults: Ultrasound measurement suggested reduction in AGT immediately following treatment. 8 weeks later, VAS score was 3 and patient reported using her arm more for various functional tasks. Diameter of supraspinatus in resting state (AF -1.30 cm, UAF-1.45cm) and contracted state (AF-1.42cm, UAF-1.70cm) suggested some improvement.Conclusions: Real-time ultrasound has potential benefits as an assessment tool to inform treatment choices for HSP. Further studies are required in this area

Northern Ireland’s longstanding record wind gust is almost certainly incorrect

Accurate assessment of record extreme wind gusts is important for building design standards and for industries such as insurance and forestry. Re‐inspection of archived anemograph records, together with indirect supporting evidence, shows that the current record wind gust for Northern Ireland – a gust of 108 kn (56 m/s) recorded at Kilkeel on 12 January 1974 – is almost certainly incorrect. We recommend that other longstanding UK record wind gusts should also be independently reassessed for veracity by an independent Climate Extremes Committee, following WMO and US best practice examples

Soliton pair dynamics in patterned ferromagnetic ellipses

Confinement alters the energy landscape of nanoscale magnets, leading to the appearance of unusual magnetic states, such as vortices, for example. Many basic questions concerning dynamical and interaction effects remain unanswered, and nanomagnets are convenient model systems for studying these fundamental physical phenomena. A single vortex in restricted geometry, also known as a non-localized soliton, possesses a characteristic translational excitation mode that corresponds to spiral-like motion of the vortex core around its equilibrium position. Here, we investigate, by a microwave reflection technique, the dynamics of magnetic soliton pairs confined in lithographically defined, ferromagnetic Permalloy ellipses. Through a comparison with micromagnetic simulations, the observed strong resonances in the subgigahertz frequency range can be assigned to the translational modes of vortex pairs with parallel or antiparallel core polarizations. Vortex polarizations play a negligible role in the static interaction between two vortices, but their effect dominates the dynamics.Comment: supplemental movies on http://www.nature.com/nphys/journal/v1/n3/suppinfo/nphys173_S1.htm

Maximising response to postal questionnaires – A systematic review of randomised trials in health research

Background Postal self-completion questionnaires offer one of the least expensive modes of collecting patient based outcomes in health care research. The purpose of this review is to assess the efficacy of methods of increasing response to postal questionnaires in health care studies on patient populations. Methods The following databases were searched: Medline, Embase, CENTRAL, CDSR, PsycINFO, NRR and ZETOC. Reference lists of relevant reviews and relevant journals were hand searched. Inclusion criteria were randomised trials of strategies to improve questionnaire response in health care research on patient populations. Response rate was defined as the percentage of questionnaires returned after all follow-up efforts. Study quality was assessed by two independent reviewers. The Mantel-Haenszel method was used to calculate the pooled odds ratios. Results Thirteen studies reporting fifteen trials were included. Implementation of reminder letters and telephone contact had the most significant effect on response rates (odds ratio 3.7, 95% confidence interval 2.30 to 5.97 p = <0.00001). Shorter questionnaires also improved response rates to a lesser degree (odds ratio 1.4, 95% confidence interval 1.19 to 1.54). No evidence was found that incentives, re-ordering of questions or including an information brochure with the questionnaire confer any additional advantage. Conclusion Implementing repeat mailing strategies and/or telephone reminders may improve response to postal questionnaires in health care research. Making the questionnaire shorter may also improve response rates. There is a lack of evidence to suggest that incentives are useful. In the context of health care research all strategies to improve response to postal questionnaires require further evaluation

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201