Mapping patterns of multiple deprivation using self-organising maps: An application to EU-SILC data for Ireland

The development of conceptual frameworks for the analysis of social exclusion has somewhat out-stripped related methodological developments. This paper seeks to contribute to filling this gap through the application of self-organising maps (SOMs) to the analysis of a detailed set of material deprivation indicators relating to the Irish case. The SOM approach allows us to offer a differentiated and interpretable picture of the structure of multiple deprivation in contemporary Ireland. Employing this approach, we identify 16 clusters characterised by distinct profiles across 42 deprivation indicators. Exploratory analyses demonstrate that, controlling for equivalised household income, SOM cluster membership adds substantially to our ability to predict subjective economic stress. Moreover, in comparison with an analogous latent class approach, the SOM analysis offers considerable additional discriminatory power in relation to individuals' experience of their economic circumstances. The results suggest that the SOM approach could prove a valuable addition to a 'methodological platform' for analysing the shape and form of social exclusion. (c) 2009 Elsevier Inc. All rights reserved.

PBOX-15, a novel microtubule targeting agent, induces apoptosis, upregulates death receptors, and potentiates TRAIL-mediated apoptosis in multiple myeloma cells

Background: In recent years, much progress has been made in the treatment of multiple myeloma. However, a major limitation of existing chemotherapeutic drugs is the eventual emergence of resistance; hence, the development of novel agents with new mechanisms of action is pertinent. Here, we describe the activity and mechanism of action of pyrrolo-1,5-benzoxazepine-15 (PBOX-15), a novel microtubule-targeting agent, in multiple myeloma cells.

Methods: The anti-myeloma activity of PBOX-15 was assessed using NCI-H929, KMS11, RPMI8226, and U266 cell lines, and primary myeloma cells. Cell cycle distribution, apoptosis, cytochrome c release, and mitochondrial inner membrane depolarisation were analysed by flow cytometry; gene expression analysis was carried out using TaqMan Low Density Arrays; and expression of caspase-8 and Bcl-2 family of proteins was assessed by western blot analysis.

Results: Pyrrolo-1,5-benzoxazepine-15 induced apoptosis in ex vivo myeloma cells and in myeloma cell lines. Death receptor genes were upregulated in both NCI-H929 and U266 cell lines, which displayed the highest and lowest apoptotic responses, respectively, following treatment with PBOX-15. The largest increase was detected for the death receptor 5 (DR5) gene, and cotreatment of both cell lines with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the DR5 ligand, potentiated the apoptotic response. In NCI-H929 cells, PBOX-15-induced apoptosis was shown to be caspase-8 dependent, with independent activation of extrinsic and intrinsic apoptotic pathways. A caspase-8-dependent decrease in expression of Bim(EL) preceded downregulation of other Bcl-2 proteins (Bid, Bcl-2, Mcl-1) in PBOX-15-treated NCI-H929 cells.

Conclusion: PBOX-15 induces apoptosis and potentiates TRAIL-induced cell death in multiple myeloma cells. Thus, PBOX-15 represents a promising agent, with a distinct mechanism of action, for the treatment of this malignancy. British Journal of Cancer (2011) 104, 281-289. doi: 10.1038/sj.bjc.6606035 www.bjcancer.com Published online 21 December 2010 (C) 2011 Cancer Research UK

Transmit Antenna Selection in Cognitive MIMO Relaying with Multiple Primary Transceivers

We consider transmit antenna selection (TAS) in cognitive multiple-input multiple-output (MIMO) relay networks, as an interference-aware design for secondary users (SUs) to ensure power and interference constraints of multiple primary users (PUs). In doing so, we derive new exact and asymptotic expressions for the outage probability of TAS with maximal ratio combining (TAS/MRC) and with selection combining (TAS/SC) over Rayleigh fading. The proposed analysis and simulations highlight that TAS/MRC and TAS/SC with decode-and-forward relaying achieve the same diversity order in cognitive MIMO networks, which scales with the minimum number of antennas at the SUs. Furthermore, we accurately characterize the outage gap between TAS/MRC and TAS/SC relaying as a concise ratio of their array gains.

Endocrine disruptor activity of multiple environmental food chain contaminants

Industrial chemicals, antimicrobials, drugs and personal care products have been reported as global pollutants which enter the food chain. Some of them have also been classified as endocrine disruptors based on results of various studies employing a number of in vitro/. vivo tests. The present study employed a mammalian reporter gene assay to assess the effects of known and emerging contaminants on estrogen nuclear receptor transactivation.Out of fifty-nine compounds assessed, estrogen receptor agonistic activity was observed for parabens (. n= 3), UV filters (. n= 6), phthalates (. n= 4) and a metabolite, pyrethroids (. n= 9) and their metabolites (. n= 3). Two compounds were estrogen receptor antagonists while some of the agonists enhanced 17β-estradiol mediated response.This study reports five new compounds (pyrethroids and their metabolites) possessing estrogen agonist activity and highlights for the first time that pyrethroid metabolites are of particular concern showing much greater estrogenic activity than their parent compounds.

Partial shoeprint retrieval using multiple point-of-interest detectors and SIFT descriptors

Shoeprint evidence collected from crime scenes can play an important role in forensic investigations. Usually, the analysis of shoeprints is carried out manually and is based on human expertise and knowledge. As well as being error prone, such a manual process can also be time consuming; thus affecting the usability and suitability of shoeprint evidence in a court of law. Thus, an automatic system for classification and retrieval of shoeprints has the potential to be a valuable tool. This paper presents a solution for the automatic retrieval of shoeprints which is considerably more robust than existing solutions in the presence of geometric distortions such as scale, rotation and scale distortions. It addresses the issue of classifying partial shoeprints in the presence of rotation, scale and noise distortions and relies on the use of two local point-of-interest detectors whose matching scores are combined. In this work, multiscale Harris and Hessian detectors are used to select corners and blob-like structures in a scale-space representation for scale invariance, while Scale Invariant Feature Transform (SIFT) descriptor is employed to achieve rotation invariance. The proposed technique is based on combining the matching scores of the two detectors at the score level. Our evaluation has shown that it outperforms both detectors in most of our extended experiments when retrieving partial shoeprints with geometric distortions, and is clearly better than similar work published in the literature. We also demonstrate improved performance in the face of wear and tear. As matter of fact, whilst the proposed work outperforms similar algorithms in the literature, it is shown that achieving good retrieval performance is not constrained by acquiring a full print from a scene of crime as a partial print can still be used to attain comparable retrieval results to those of using the full print. This gives crime investigators more flexibility is choosing the parts of a print to search for in a database of footwear.

Multiple configurations of the two excess 4f electrons on defective CeO2(111):Origin and implications

Density-functional theory calculations have been carried out to systematically study single surface oxygen vacancies on CeO2(111). It is surprisingly found that multiple structures with the two excess electrons localized at different positions can exist. We show that the origin of the multiconfigurations of 4f electrons is a result of geometric relaxation on the surface and strong localization characteristic of 4f electrons in ceria. The importance of 4f electron structures is also presented and discussed. These results may possess implications for our understanding of materials with f electrons.

Deletions of CDKN2C in Multiple Myeloma: Biological and Clinical Implications

Purpose: Deletions of chromosome 1 have been described in 7% to 40% of cases of myeloma with inconsistent clinical consequences. CDKN2C at 1p32.3 has been identified in myeloma cell lines as the potential target of the deletion. We tested the clinical impact of 1p deletion and used high-resolution techniques to define the role of CDKN2C in primary patient material.Experimental Design: We analyzed 515 cases of monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and newly diagnosed multiple myeloma using fluorescence in situ hybridization (FISH) for deletions of CDKN2C. In 78 myeloma cases, we carried out Affymetrix single nucleotide polymorphism mapping and U133 Plus 2.0 expression arrays. In addition, we did mutation, methylation, and Western blotting analysis.Results: By FISH we identified deletion of 1p32.3 (CDKN2C) in 3 of 66 MGUS (4.5%), 4 of 39 SMM (10.3%), and 55 of 369 multiple myeloma cases (15%). We examined the impact of copy number change at CDKN2C on overall survival (OS), and found that the cases with either hemizygous or homozygous deletion of CDKN2C had a worse OS compared with cases that were intact at this region (22 months versus 38 months; P = 0.003). Using gene mapping we identified three homozygous deletions at 1p32.3, containing CDKN2C, all of which lacked expression of CDKN2C. Cases with homozygous deletions of CDKN2C were the most proliferative myelomas, defined by an expression-based proliferation index, consistent with its biological function as a cyclin-dependent kinase inhibitor.Conclusions: Our results suggest that deletions of CDKN2C are important in the progression and clinical outcome of myeloma.

Incomplete DJH rearrangements of the IgH gene are frequent in multiple myeloma patients: immunobiological characteristics and clinical implications.

DH-JH rearrangements of the Ig heavy-chain gene (IGH) occur early during B-cell development. Consequently, they are detected in precursor-B-cell acute lymphoblastic leukemias both at diagnosis and relapse. Incomplete DJH rearrangements have also been occasionally reported in mature B-cell lymphoproliferative disorders, but their frequency and immunobiological characteristics have not been studied in detail. We have investigated the frequency and characteristics of incomplete DJH as well as complete VDJH rearrangements in a series of 84 untreated multiple myeloma (MM) patients. The overall detection rate of clonality by amplifying VDJH and DJH rearrangements using family-specific primers was 94%. Interestingly, we found a high frequency (60%) of DJH rearrangements in this group. As expected from an immunological point of view, the vast majority of DJH rearrangements (88%) were unmutated. To the best of our knowledge, this is the first systematic study describing the incidence of incomplete DJH rearrangements in a series of unselected MM patients. These results strongly support the use of DJH rearrangements as PCR targets for clonality studies and, particularly, for quantification of minimal residual disease by real-time quantitative PCR using consensus JH probes in MM patients. The finding of hypermutation in a small proportion of incomplete DJH rearrangements (six out of 50) suggests important biological implications concerning the process of somatic hypermutation. Moreover, our data offer a new insight in the regulatory development model of IGH rearrangements.

Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.

The detection of contaminating clonal cells in apheresis products is related to response and outcome in multiple myeloma undergoing autologous peripheral blood stem cell transplantation.

In the present paper, we report on the use of the heteroduplex PCR technique to detect the presence of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) in the apheresis products of patients with multiple myeloma (MM) undergoing autologous peripheral blood stem cell (APBSC) transplantation. Twenty-three out of 31 MM patients undergoing APBSC transplantation with VDJH segments clonally rearranged detected at diagnosis were included in the study. Samples of the apheresis products were PCR amplified using JH and VH (FRIII and FRII) consensus primers and subsequently analyzed with the heteroduplex technique, and compared with those obtained at diagnosis. 52% of cases yielded positive results (presence of clonally rearranged VDJH segments in at least one apheresis). The presence of positive results in the apheresis products was not related to any pretransplant characteristics with the exception of response status at transplant. Thus, while no one patient with positive apheresis products was in complete remission (CR), negative immunofixation, before the transplant, five cases (46%) with negative apheresis were already in CR at transplant (P = 0.01). The remaining six cases with heteroduplex PCR negative apheresis were in partial remission before transplant. Patients with clonally free products were more likely to obtain CR following transplant (64% vs 17%, P= 0.02) and a longer progression-free survival, (40 months in patients transplanted with polyclonal products vs 20 with monoclonal ones, P = 0.03). These results were consistent when the overall survival was considered, since it was better in those patients with negative apheresis than it was in those with positive (83% vs 36% at 5 years from diagnosis, P= 0.01). These findings indicate that the presence of clonality rearranged VDJH segments is related to the response and outcome in MM transplanted patients.

Beam division multiple access for massive MIMO downlink transmission

We study a multiuser multicarrier downlink communication system in which the base station (BS) employs a large number of antennas. By assuming frequency-division duplex operation, we provide a beam domain channel model as the number of BS antennas grows asymptotically large. With this model, we first derive a closed-form upper bound on the achievable ergodic sum-rate before developing necessary conditions to asymptotically maximize the upper bound, with only statistical channel state information at the BS. Inspired by these conditions, we propose a beam division multiple access (BDMA) transmission scheme, where the BS communicates with users via different beams. For BDMA transmission, we design user scheduling to select users within non-overlapping beams, work out an optimal pilot design under a minimum mean square error criterion, and provide optimal pilot sequences by utilizing the Zadoff-Chu sequences. The proposed BDMA scheme reduces significantly the pilot overhead, as well as, the processing complexity at transceivers. Simulations demonstrate the high spectral efficiency of BDMA transmission and the advantages in the bit error rate performance of the proposed pilot sequences.

Secure Multiple Amplify-and-Forward Relaying with Co-Channel Interference

We investigate the impact of co-channel interference on the security performance of multiple amplify-and-forward (AF) relaying networks, where N intermediate AF relays assist the data transmission from the source to the destination. The relays are corrupted by multiple co-channel interferers, and the information transmitted from the relays to destination can be overheard by the eavesdropper. In order to deal with the interference and wiretap, the best out of N relays is selected for security enhancement. To this end, we derive a novel lower bound on the secrecy outage probability (SOP), which is then utilized to present two best relay selection criteria, based on the instantaneous and statistical channel information of the interfering links. For these criteria and the conventional maxmin criterion, we quantify the impact of co-channel interference and relay selection by deriving the lower bound on the SOP. Furthermore, we derive the asymptotic SOP for each criterion, to explicitly reveal the impact of transmit power allocation among interferers on the secrecy performance, which offers valuable insights into practical design. We demonstrate that all selection criteria achieve full secrecy diversity order N, while the proposed in this paper two criteria outperform the conventional max-min scheme.