Mesenchymal stem cells expressing TRAIL lead to tumour growth inhibition in an experimental lung cancer model

AbstractLung cancer is a major public health problem in the western world, and gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumour tissue. Some of the main factors inhibiting systemic delivery are found in the blood stream in the form of red and white blood cells (WBCs) and serum components. Mesenchymal stem cells (MSCs) have been shown to home to tumour sites and could potentially act as a shield and vehicle for a tumouricidal gene therapy vector. Here, we describe the ability of an adenoviral vector expressing TRAIL (Ad.TR) to transduce MSCs and show the apoptosis‐inducing activity of these TRAIL‐carrying MSCs on A549 lung carcinoma cells. Intriguingly, using MSCs transduced with Ad.enhanced‐green‐fluorescent‐protein (EGFP) we could show transfer of viral DNA to cocultured A549 cells resulting in transgenic protein production in these cells, which was not inhibited by exposure of MSCs to human serum containing high levels of adenovirus neutralizing antibodies. Furthermore, Ad.TR‐transduced MSCs were shown not to induce T‐cell proliferation, which may have resulted in cytotoxic T‐cell‐mediated apoptosis induction in the Ad.TR‐transduced MSCs. Apoptosis was also induced in A549 cells by Ad.TR‐transduced MSCs in the presence of physiological concentrations of WBC, erythrocytes and sera from human donors that inhibit or neutralize adenovirus alone. Moreover, we could show tumour growth reduction with TRAIL‐loaded MSCs in an A549 xenograft mouse model. This is the first study that demonstrates the potential therapeutic utility of Ad.TR‐transduced MSCs in cancer cells and the stability of this vector in the context of the blood environment.</jats:p

Optical Nanotransmission Lines: Synthesis of Planar Left-Handed Metamaterials in the Infrared and Visible Regimes

Following our recent theoretical development of the concept of nano-inductors, nano-capacitors and nano-resistors at optical frequencies and the possibility of synthesizing more complex nano-scale circuits, here we theoretically investigate in detail the problem of optical nano-transmission-lines (NTL) that can be envisioned by properly joining together arrays of these basic nano-scale circuit elements. We show how, in the limit in which these basic circuit elements are closely packed together, the NTLs can be regarded as stacks of plasmonic and non-plasmonic planar slabs, which may be designed to effectively exhibit the properties of planar metamaterials with forward (right-handed) or backward (left-handed) operation. With the proper design, negative refraction and left-handed propagation are shown to be possible in these planar plasmonic guided-wave structures, providing possibilities for sub-wavelength focusing and imaging in planar optics, and laterally-confined waveguiding at IR and visible frequencies. The effective material parameters for such NTLs are derived, and the connection and analogy between these optical NTLs and the double-negative and double-positive metamaterials are also explored. Physical insights and justification for the results are also presented.Comment: 26 pages, 12 figures, accepted for publication in JOSA B, scheduled to appear March 200

'A hard-won capability': the experiences of parents managing their babies' medicines after discharge from a neonatal unit.:'A hard-won capability'

IntroductionParents of babies who required neonatal care are responsible for managing their medicines after they are discharged home. There is wide variation in the information and amount of preparation given to parents prior to assuming this challenging task. The aim of the Parent co-Designed Drug Information for parents and Guardians Taking Neonates home (PADDINGToN) study was to explore parents' experiences of managing their babies' medicines post discharge from a neonatal unit and to use this information to develop suitable resources for future families.MethodsA qualitative participatory interpretative approach using a mixture of remote and face-to-face small group interviews or one-to-one interviews was used. Parents were recruited using social media advertisements and convenience sampling from five study sites (four neonatal units in England and one in Ireland). Parents from other neonatal units were invited to take part through social media advertisement. The interviews were audio-recorded and inductive reflexive thematic analysis was used to analyze the data.Results17 parents (14 mothers, 3 fathers) participated. One over-arching theme, 'A hard won capability', and four major interpretive themes were generated from the analysis of the data: Being in NICU and the prospect of going home: emotional and practical challenges; Living the reality of being at home: the uncertainty associated with giving medicines; Being at home: battling the system and a lack of support/knowledge; and Suggesting ways forward: parents' lived insights into improving information and resources.ConclusionDespite the challenges they faced, parents developed strategies for safely and reliably managing medicines administration and they assimilated knowledge, built their confidence and achieved a capability in medicines administration. Their experiences have been used to build a suite of medicines administration resources to support future parents.</jats:sec

All Optical Implementation of Multi-Spin Entanglement in a Semiconductor Quantum Well

We use ultrafast optical pulses and coherent techniques to create spin entangled states of non-interacting electrons bound to donors (at least three) and at least two Mn2+ ions in a CdTe quantum well. Our method, relying on the exchange interaction between localized excitons and paramagnetic impurities, can in principle be applied to entangle a large number of spins.Comment: 17 pages, 3 figure

Impact of HIV-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010

Pliocene Diatom Biomarkers in Sabrina Coast. EAIS Continental Marginal Dynamics

PNRA Tytan project, supported by the National Institute of Oceanography and Applied Geophysics (OGS), focused on the advances and retreats dynamics of the ice sheet and on variations in the glacial regime. Unit 2 focused on Diatom biomarkers and assemblages analysis on sediments of core PC03, collected during the IN2017-V01 cruise on the eastern flank of the Minang-a (or Whale) submarine Canyon. The project aims at reconstructing the depositional environment of the continental margin off the Totten Glacier and diatom data remained a key tools to constrain past ice-sheet dynamics and to forecasting future behaviour in a warming world. Preliminary dataset from diatom biostratigraphic tools allows to refer the base of the core to Pliocene while the upper part of the core records more modern EAIS dynamics, indicative of minor sedimentary evolution steps of the continental margin. Diatom assemblage analyses highlight Eocene-Oligocene reworked material and freshwater diatom inputs in Pliocene sequence, strengthening the debate about ice-sheet and paleoceanographic models, WAIS cyclic collapse and suspected Pliocene EAIS retreat into major subglacial Antarctic basins