Design and results of a dual-gas Quasi-Phase matching (QPM) foil target

Quasi-phase matching (QPM) can be used to increase the conversion efficiency of the high harmonic generation (HHG) process. We observed QPM with an improved dual-gas foil target with a 1 kHz, 10 mJ, 30 fs laser system. Phase tuning and enhancement were possible within a spectral range from 17 nm to 30 nm. Furthermore analytical calculations and numerical simulations were carried out to distinguish QPM from other effects, such as the influence of adjacent jets on each other or the laser gas interaction. The simulations were performed with a 3 dimensional code to investigate the phase matching of the short and long trajectories individually over a large spectral range.

Dual targeting of tumour cells and host endothelial cells by novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines

PURPOSE: Some members of a novel series of pyrrolo-1,5-benzoxazepines (PBOXs) are microtubule-targeting agents capable of inducing apoptosis in a variety of human cancerous cells, hence, they are currently being developed as potential anti-cancer agents. The purpose of this study was to first characterise the activities of a novel PBOX analogue, PBOX-16 and then investigate the anti-angiogenic potential of both PBOX-16 and its prototype PBOX-6.

METHODS: The effects of PBOX-6 and -16 on cancerous cells (chronic myeloid leukaemia K562 cells and ovarian carcinoma A2780 cells) and primary cultured human umbilical vein endothelial cells (HUVECs) were examined by assessing cell proliferation, microtubular organisation, DNA analysis of cell cycle progression and caspase-3/7 activity. Their anti-angiogenic properties were then investigated by examining their ability to interfere with HUVEC differentiation into capillary-like structures and vascular endothelial growth factor (VEGF)-stimulated HUVEC migration.

RESULTS: PBOX-6 and -16 inhibited proliferation of K562, A2780 and HUVEC cells in a concentration-dependent manner. PBOX-16, confirmed as a novel depolymerising agent, was approximately tenfold more potent than PBOX-6. Inhibition of cell proliferation was mediated by G(2)/M arrest followed by varying degrees of apoptosis depending on the cell type; endothelial cells underwent less apoptosis than either of the cancer cell lines. In addition to the antitumourigenic properties, we also describe a novel antiangiogenic function for PBOXs: treatment with PBOXs inhibited the spontaneous differentiation of HUVECs into capillary-like structures when grown on a basement membrane matrix preparation (Matrigel™) and also significantly reduced VEGF-stimulated HUVEC migration.

CONCLUSION: Dual targeting of both the tumour cells and the host endothelial cells by PBOX compounds might enhance the anti-cancer efficacy of these drugs.

Workplace accommodation for older teachers in Japan and Germany: The role of the institutional context in supporting late career options for teachers with ill-health

Due to population ageing, Japan and Germany have to extend individuals´ working lives. However, disability increases with old-age. Workplace accommodation is a means to enable disabled individuals to remain productively employed. Drawing on qualitative interview data, this paper explores how School Authorities in these countries use workplace accommodation to support ill teachers, a white-collar profession strongly affected by (mental) ill-health. It furthermore explores how such measures influence older teachers´ career expectations and outcomes. It finds that even though the institutional contexts are similar, career options and expectations vary, though with similar (negative) outcomes for national strategies to extend working lives.

Dual interfacial modifications of hierarchically structured iodine-doped ZnO photoanodes for high-efficiency dye-sensitized solar cells

A nanocomposite porous electrode structure consisting of hierarchical iodine-doped zinc oxide (I-ZnO) aggregates combined with the two simple solution-processed interfacial modifications i.e. a ZnO compact layer (CL) and a TiO2 protective layer (PL) has been developed in order to understand electron transport and recombination in the photoanode matrix, together with boosting the conversion efficiency of I-ZnO based dye-sensitized solar cells (DSCs). Electrochemical impedance spectra demonstrate that ZnO CL pre-treatment and TiO2 PL post-treatment synergistically reduce charge-transfer resistance and suppress electron recombination. Furthermore, the electron lifetime in two combined modifications of IZnO + CL + PL photoelectrode is the longest in comparison with the other three photoelectrodes. As a consequence, the overall conversion efficiency of I-ZnO + CL + PL DSC is significantly enhanced to 6.79%, with a 36% enhancement compared with unmodified I-ZnO DSC. Moreover, the stability of I-ZnO + CL + PL cell is improved as compared to I-ZnO one. The mechanism of electron transfer and recombination upon the introduction of ZnO CL and TiO2 PL is also proposed in this work.

Dual-Hop Cognitive Amplify-and-Forward Relaying Networks over η− μ Fading Channels

This paper presents a thorough performance analysis of dual-hop cognitive amplify-and-forward (AF) relaying networks under spectrum-sharing mechanism over independent non-identically distributed (i.n.i.d.) 􀀀 fading channels. In order to guarantee the quality-of-service (QoS) of primary networks, both maximum tolerable peak interference power Q at the primary users (PUs) and maximum allowable transmit power P at secondary users (SUs) are considered to constrain transmit power at the cognitive transmitters. For integer-valued fading parameters, a closed-form lower bound for the outage probability (OP) of the considered networks is obtained. Moreover, assuming arbitrary-valued fading parameters, the lower bound in integral form for the OP is derived. In order to obtain further insights on the OP performance, asymptotic expressions for the OP at high SNRs are derived, from which the diversity/coding gains and the diversity-multiplexing gain tradeoff (DMT) of the secondary network can be readily deduced. It is shown that the diversity gain and also the DMT are solely determined by the fading parameters of the secondary network whereas the primary network only affects the coding gain. The derived results include several others available in previously published works as special cases, such as those for Nakagami-m fading channels. In addition, performance evaluation results have been obtained by Monte Carlo computer simulations which have verified the accuracy of the theoretical analysis.

Lanthanide luminescent logic gate mimics in soft matter: [H(+)] and [F(-)] dual-input device in a polymer gel with potential for selective component release

The non-covalent incorporation of responsive luminescent lanthanide, Ln(iii), complexes with orthogonal outputs from Eu(iii) and Tb(iii) in a gel matrix allows for in situ logic operation with colorimetric outputs. Herein, we report an exemplar system with two inputs ([H(+)] and [F(-)]) within a p(HEMA-co-MMA) polymer organogel acting as a dual-responsive device and identify future potential for such systems.

The impact of organisational factors and government policy on psychiatric nurses family focused practice with parents who have mental illness, their dependent children and families in Ireland

Government policy and organizational factors influence family focused practice in adult mental health services. However, how these aspects shape psychiatric nurses’ practice with parents who have mental illness, their dependent children and families is less well understood. Drawing on the findings of a qualitative study, this article explores the way in which Irish policy and organizational factors might influence psychiatric nurses’ family focused practice, and whether (and how) family focused practice might be further promoted. A purposive sample of 14 psychiatric nurses from eight mental health services completed semi-structured interviews in 2013. The analysis was inductive and presented as thematic networks. Both groups described how policies and organizational culture enabled and/or hindered family focused practice, with differences between community and acute participants seen. The need to develop national and international policies along with practices to embed information and support regarding parenting into ongoing care is implicated in this study.

The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models

As key molecules that drive progression and chemoresistance in gastrointestinal cancers, epidermal growth factor receptor (EGFR) and HER2 have become efficacious drug targets in this setting. Lapatinib is an EGFR/HER2 kinase inhibitor suppressing signaling through the RAS/RAF/MEK (MAP/ERK kinase)/MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase)/AKT pathways. Histone deacetylase inhibitors (HDACi) are a novel class of agents that induce cell cycle arrest and apoptosis following the acetylation of histone and nonhistone proteins modulating gene expression and disrupting HSP90 function inducing the degradation of EGFR-pathway client proteins. This study sought to evaluate the therapeutic potential of combining lapatinib with the HDACi panobinostat in colorectal cancer (CRC) cell lines with varying EGFR/HER2 expression and KRAS/BRAF/PIK3CA mutations. Lapatinib and panobinostat exerted concentration-dependent antiproliferative effects in vitro (panobinostat range 7.2-30 nmol/L; lapatinib range 7.6-25.8 μmol/L). Combined lapatinib and panobinostat treatment interacted synergistically to inhibit the proliferation and colony formation in all CRC cell lines tested. Combination treatment resulted in rapid induction of apoptosis that coincided with increased DNA double-strand breaks, caspase-8 activation, and PARP cleavage. This was paralleled by decreased signaling through both the PI3K and MAPK pathways and increased downregulation of transcriptional targets including NF-κB1, IRAK1, and CCND1. Panobinostat treatment induced downregulation of EGFR, HER2, and HER3 mRNA and protein through transcriptional and posttranslational mechanisms. In the LoVo KRAS mutant CRC xenograft model, the combination showed greater antitumor activity than either agent alone, with no apparent increase in toxicity. Our results offer preclinical rationale warranting further clinical investigation combining HDACi with EGFR and HER2-targeted therapies for CRC treatment.

The dual EGFR/HER-2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38

Members of the human epidermal receptor (HER) family are frequently associated with aggressive disease and poor prognosis in multiple malignancies. Lapatinib is a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and HER-2. This study evaluated the therapeutic potential of lapatinib, alone and in combination with SN-38, the active metabolite of irinotecan (CPT-11), in colon and gastric cancer cell lines. Concentration-dependent antiproliferative effects of both lapatinib and SN-38 were observed in all colon and gastric cancer cell lines tested but varied significantly between individual cell lines (lapatinib range 0.08-11.7 muM; SN-38 range 3.6-256 nM). Lapatinib potently inhibited the growth of a HER-2 overexpressing gastric cancer cell line and demonstrated moderate activity in gastric and colon cancer cells with detectable HER-2 expression. The combination of lapatinib and SN-38 interacted synergistically to inhibit cell proliferation in all colon and gastric cancer cell lines tested. Cotreatment with lapatinib and SN-38 also resulted in enhanced cell cycle arrest and the induction of apoptosis with subsequent cellular pharmacokinetic analysis demonstrating that lapatinib promoted the increased intracellular accumulation and retention of SN-38 when compared to SN-38 treatment alone. Finally, the combination of lapatinib and CPT-11 demonstrated synergistic antitumor efficacy in the LoVo colon cancer mouse xenograft model with no apparent increase in toxicity compared to CPT-11 monotherapy. These results provide compelling preclinical rationale indicating lapatinib to be a potentially efficacious chemotherapeutic combination partner for irinotecan in the treatment of gastrointestinal carcinomas.

Social Work Home Visits to Children and Families in the UK: A Foucauldian Perspective

The home visit is at the heart of social work practice with children and families; it is what children and families' social workers do more than any other single activity (except for recording), and it is through the home visit that assessments are made on a daily basis about risk, protection and welfare of children. And yet it is, more than any other activity, an example of what Pithouse has called an ‘invisible trade’: it happens behind closed doors, in the most secret and intimate spaces of family life. Drawing on conceptual tools associated with the work of Foucault, this article sets out to provide a critical, chronological review of research, policy and practice on home visiting. We aim to explain how and in what ways changing discourses have shaped the emergence, legitimacy, research and practice of the social work home visit to children and families at significant time periods and in a UK context. We end by highlighting the importance for the social work profession of engagement and critical reflection on the identified themes as part of their daily practice.

How useful is dual energy lateral vertebral assessment in a clinic setting?

Screening for osteoporotic vertebral fractures traditionally involves X-ray of the thoracic and lumbar spine. We evaluated use of dual energy X-ray technology in patients with osteoporosis. We found this technology useful in the clinic setting and it has advantages in that less radiation is delivered to the patient.