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 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.

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.

Multi-wavelength observations of Proxima Centauri

Aims: We report simultaneous observations of the nearby flare star Proxima Centauri with VLT/UVES and XMM-Newton over three nights in March 2009. Our optical and X-ray observations cover the star's quiescent state, as well as its flaring activity and allow us to probe the stellar atmospheric conditions from the photosphere into the chromosphere, and then the corona during its different activity stages. Methods: Using the X-ray data, we investigate variations in coronal densities and abundances and infer loop properties for an intermediate-sized flare. The optical data are used to investigate the magnetic field and its possible variability, to construct an emission line list for the chromosphere, and use certain emission lines to construct physical models of Proxima Centauri's chromosphere. Results: We report the discovery of a weak optical forbidden Fe xiii line at 3388 Å during the more active states of Proxima Centauri. For the intermediate flare, we find two secondary flare events that may originate in neighbouring loops, and discuss the line asymmetries observed during this flare in H i, He i, and Ca ii lines. The high time-resolution in the Hα line highlights strong temporal variations in the observed line asymmetries, which re-appear during a secondary flare event. We also present theoretical modelling with the stellar atmosphere code PHOENIX to construct flaring chromospheric models. Based on observations collected at the European Southern Observatory, Paranal, Chile, 082.D-0953A and on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member states and NASA.Full Table 6 is only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/534/A133

Dual-Diversity Combining for Constrained Resource Allocation and Throughput Maximization in OFDMA Networks

Al Rawi, Anas F., Emiliano Garcia-Palacios, Sonia Aissa, Charalampos C. Tsimenidis, and Bayan S. Sharif. "Dual-Diversity Combining for Constrained Resource Allocation and Throughput Maximization in OFDMA Networks." In Vehicular Technology Conference (VTC Spring), 2013 IEEE 77th, pp. 1-5. IEEE, 2013.

I/Q imbalance in AF dual-hop relaying: Performance analysis in Nakagami-m fading

We analyze the performance of amplify-and-forward dual-hop relaying systems in the presence of in-phase and quadrature-phase imbalance (IQI) at the relay node. In particular, an exact analytical expression for and tight lower bounds on the outage probability are derived over independent, non-identically distributed Nakagami-m fading channels. Moreover, tractable upper and lower bounds on the ergodic capacity are presented at arbitrary signal-to-noise ratios (SNRs). Some special cases of practical interest (e.g., Rayleigh and Nakagami-0.5 fading) are also studied. An asymptotic analysis is performed in the high SNR regime, where we observe that IQI results in a ceiling effect on the signal-to-interference-plus-noise ratio (SINR), which depends only on the level of I/Q impairments, i.e., the joint image rejection ratio. Finally, the optimal I/Q amplitude and phase mismatch parameters are provided for maximizing the SINR ceiling, thus improving the system performance. An interesting observation is that, under a fixed total phase mismatch constraint, it is optimal to have the same level of transmitter (TX) and receiver (RX) phase mismatch at the relay node, while the optimal values for the TX and RX amplitude mismatch should be inversely proportional to each other.

On the Ontological Quality and Logical Quality of Conceptual-Modeling Grammars: The Need for a Dual Perspective

A core activity in information systems development involves building a conceptual model of the domain that an information system is intended to support. Such models are created using a conceptual-modeling (CM) grammar. Just as high-quality conceptual models facilitate high-quality systems development, high-quality CM grammars facilitate high-quality conceptual modeling. This paper provides a new perspective on ways to improve the quality of the semantics of CM grammars. For many years, the leading approach to this topic has relied on ontological theory. We show, however, that the ontological approach captures only half the story. It needs to be coupled with a logical approach. We explain how the ontological quality and logical quality of CM grammars interrelate. Furthermore, we outline three contributions that a logical approach can make to evaluating the quality of CM grammars: a means of seeing some familiar conceptual-modeling problems in simpler ways; the illumination of new problems; and the ability to prove the benefit of modifying existing CM grammars in particular ways. We demonstrate these benefits in the context of the Entity-Relationship grammar. More generally, our paper opens up a new area of research with many opportunities for future research and practice.

Dual Classification Revisited: Rodney Needham and Vertical Asymmetry aboard Scottish Trawlers

Drawing on ethnographic data collected while working as a deckhand on two Scottish trawlers, this article analyses the spatialisation of social, religious and economic inequalities that marked relations between crew members while they hunted for prawns in the North Sea. Moreover, it explores these inequalities as a wider feature of life in Gamrie, Aberdeenshire, a Brethren and Presbyterian fishing village riven by disparities in wealth and religion. Inequalities identified by fishermen at sea mirrored those identified by residents onshore, resulting in fishing boats being experienced as small 'floating villages'. Drawing on the work of Rodney Needham, this article suggests that these asymmetries can be traced along a vertical axis, with greater to lesser wealth and religiosity moving from top/above to bottom/below. The article seeks to understand the presence and persistence of these hierarchies at sea and on land, by revisiting dual classification within anthropological theory.