Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population

Myocardial infarction (MI) is divided into either ST elevation MI (STEMI) or non-ST elevation MI (NSTEMI), differing in a number of clinical characteristics. We sought to identify genetic variants conferring risk to NSTEMI or STEMI by conducting a genome-wide association study (GWAS) of MI stratified into NSTEMI and STEMI in a consecutive sample of 1,579 acute MI cases with 1,576 controls. Subsequently, we followed the results in an independent population-based sample of 562 cases and 566 controls, a partially independent prospective cohort (N = 16,627 with 163 incident NSTEMI cases), and examined the effect of disease-associated variants on gene expression in 513 healthy participants. Genetic variants on chromosome 1p13.3 near the damage-regulated autophagy modulator 2 gene DRAM2 associated with NSTEMI (rs656843; odds ratio 1.57, P = 3.11 x 10(-10)) in the case-control analysis with a consistent but not statistically significant effect in the prospective cohort (rs656843; hazard ratio 1.13, P = 0.43). These variants were not associated with STEMI (rs656843; odds ratio, 1.11, P = 0.20; hazard ratio 0.97, P = 0.87), appearing to have a pronounced effect on NSTEMI risk. A majority of the variants at 1p13.3 associated with NSTEMI were also associated with the expression level of DRAM2 in blood leukocytes of healthy controls (top-ranked variant rs325927, P = 1.50 x 10(-12)). The results suggest that genetic factors may in part influence whether coronary artery disease results in NSTEMI rather than STEMI.Peer reviewe

Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA

Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health-care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk.Peer reviewe

Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

Correction: vol 7, 13205, 2016, doi:10.1038/ncomms13205Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in Bone-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2) = 0.18, P value = 0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.Peer reviewe

Effective capacity evaluation of advanced wideband CDMA and UWB radio networks

Abstract High radio capacity is one of the main targets in wireless network planning. The characteristics of the broadband radio channel pose serious challenges for achieving this goal. This thesis views the capacity problem from two frameworks. In the first, the effective user capacity in advanced direct sequence wideband code-division multiple-access (DS-CDMA) radio networks is evaluated. Sensitivity to various imperfections in key system parameters is studied. The analysis is based on a mathematical foundation that presents complex signal models and enables evaluation of the performance losses due to parameter estimation errors and multipath fading. The effective number of users supported in a cell is restricted by the multiple access interference (MAI) in the same cell (intracell interference) and overall background noise. The studied wideband CDMA receiver structures comprise conventional rake receivers with both the maximal ratio combining (MRC) and equal gain combining (EGC) schemes that can be supplemented with either linear decorrelating or nonlinear successive cancellation-based multiuser detectors and M-antenna spatial diversity. The second framework focuses on direct sequence spread spectrum-based ultra wideband (UWB) indoor communications. Cochannel interference limited capacity is evaluated against the outage probability criterion in exponentially decaying lognormal multipath fading channels. Distance-dependence and spatial distribution of users is taken into account at different spatial cell configurations. Only moderate complexity partial rake receivers with noncoherent combining are employed. Total interference is composed of interpath, multipath, intracell, and intercell interference contributions. Lognormal sum approximations and simulations are used to evaluate distributions of the desired and interfering signals. The impact of the timing errors at the receiver monopulse correlation is studied. The numerical results for the wideband CDMA framework show that effective user capacity and sensitivity depend critically on the joint impact of nonidealities in system parameters (e.g., channel profile, severity of fading, receiver algorithms). User capacities of the studied multiuser enhanced receivers were more prone to these impairments than those of the simpler single user receivers. The results should be used for network planning and optimization. The numerical results of the UWB framework suggest that, even in the multipath rich channel, the optimal number of rake fingers can be less than half of the significant multipaths. Differences between circular, square, and hexagonal cell models proved to be minor with respect to link distance distributions. The derived link distance statistics are useful tools in the analytic piconet dimensioning and optimization

Towards 6G:getting ready for the next decade

Abstract As the wireless and mobile world is turning its interest into beyond 5G development, industry and research community are gradually taking up this colossal challenge. This paper discusses the readiness and capacity needed to develop beyond 5G (B5G) and 6G technology and their associated businesses and applications. The wireless landscape is analyzed in different timeframes covering roughly the period between 2020 and 2030, the decade where B5G and 6G are expected to be fully developed. After discussing relevant trends and key requirements needed to develop B5G and 6G in general, the paper will consider, as a particular example, the current development and readiness of Finland. With a strong background in 5G, Finland is one of the first countries to start doing 6G development following a large research project where key industrial and academic players of the country participate. Hopefully, the conceived developing path to 6G presented in this paper will serve a motivational guide to other developers

Shell-model study on event rates of lightest supersymmetric particles scattering off 83Kr and 125Te

We investigate the elastic and inelastic scattering of lightest supersymmetric particle (LSP) dark matter off two possible target nuclei, 83Kr and 125Te. For the nuclear-structure calculations, we employ the nuclear shell model using recently generated realistic interactions. We have condensed the nuclear-physics contribution to a set of nuclear-structure factors that are independent of the adopted supersymmetric (SUSY) model. Total event rates are then easily calculated by combining the nuclear-structure factors with SUSY parameters of choice. In particular, 125Te shows promise as a detector material with both the elastic and inelastic channels yielding an appreciable nuclear response.peerReviewe

Transmission strategies for throughput maximization in high speed train communications:from theoretical study to practical algorithms

Abstract This paper focuses on improving the downlink throughput of the base station (BS)-to-train communication link in a high-speed train (HST) scenario. First, we provide a theoretical study of the throughput maximization problem in a single-cell multiple-input-multiple-output orthogonal frequency-division multiplexing (MIMO-OFDM) train scenario with and without cooperation among carriages. The aim is to give fundamental insight into the problem rather than providing practically realizable algorithms. The theoretical study suggests that it is highly advantageous to exploit the size of the train by increasing the number of antennas and further allowing the carriages to cooperate. In the practical system-level study, we propose two low-complexity MIMO-OFDM transmission schemes, which are based on simple antenna selection (AS) methods with spatial multiplexing. The main idea is to select the best transmit antennas among different antenna combinations by comparing their estimated throughput performances. The simulation results show that the proposed algorithms outperform Long-Term Evolution (LTE)-based dynamic rank transmission schemes in terms of throughput and computational load in practical HST scenarios. Unlike the exhaustive search type of dynamic transmission schemes, our simple algorithms are also applicable to large antenna arrays. In conclusion, large antenna arrays with simple AS and spatial multiplexing transmission strategies seem to be potential solutions to the significant improvement of the throughput of the BS-to-train link in HST scenarios

Feasibility studies on the use of higher frequency bands and beamforming selection scheme for high speed train communication

Abstract With increasing popularity of high speed trains and traffic forecast for future cellular networks, the need to provide improved data rates using higher frequency bands (HFBs) for train passengers is becoming crucial. In this paper, we modify the OFDM frame structure for HST, taking into account the increasing sensitivity to speed at HFBs. A lower bound on the SNR/SINR for a given rate for reliable communication was derived considering the physical layer parameters from the OFDM frame. We also analyze different pathlossmodels in the context of examining the required gain needed to achieve the same performance as with microwave bands. Finally, we present a time-based analogue beamforming selection approach for HST. We observed that, irrespective of the pathloss models used, the required gains are within the same range. For the same SNR/SINR at different frequency bands, the achievable data rate varies with respect to the frequency bands. Our results show the potential of the use of HFBs. However, due to the increased sensitivity of some channel parameters, a maximum frequency band of 38GHz is suggested. Evaluation of our proposed beamforming scheme indicates a close performance to the optimal SVD scheme with a marginal rate gap of less than 2 b/s/Hz

Higher frequency band beamforming scheme for high speed train

Abstract With the increasing popularity of high speed trains (HSTs) and the traffic forecast for future cellular networks, the need to provide very high data rates using higher frequency bands (HFBs) for train passengers is becoming crucial. In this paper, we present a timer-based beamforming selection algorithm for HST, which exploits the prior knowledge of the position and direction of the HST. A sequential and hierarchical codebook is designed based on the array response vectors and linked to the line-of-sight (LOS) angle-of-arrival/departure base station (BS)-HST link. The effect of velocity feedback errors on the throughput performance was analyzed. The antenna deactivation and the sub-array approaches were considered to mitigate the effect of velocity feedback errors. Evaluation of our proposed beamforming scheme indicates a close performance to the optimal singular value decomposition (SVD) scheme when no velocity feedback error occurs and with the occurrence of velocity feedback errors, the sub-array approach proved to be an efficient way to reduce the effect of the errors