Summary
Proper generalized decomposition (PGD) is often used for multiquery and fast‐response simulations. It is a powerful tool alleviating the curse of dimensionality affecting multiparametric ...partial differential equations. Most implementations of PGD are intrusive extensions based on in‐house developed FE solvers. In this work, we propose a nonintrusive PGD scheme using off‐the‐shelf FE codes (such as certified commercial software) as an external solver. The scheme is implemented and monitored by in‐house flow‐control codes. A typical implementation is provided with downloadable codes. Moreover, a novel parametric separation strategy for the PGD resolution is presented. The parametric space is split into two‐ or three‐dimensional subspaces, to allow PGD technique solving problems with constrained parametric spaces, achieving higher convergence ratio. Numerical examples are provided. In particular, a practical example in biomechanics is included, with potential application to patient‐specific simulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aims
Despite the research on orchid in insular conditions, few studies are focused on the spatial distribution of their reproductive syndromes across complex insular systems. By using island ...species–area relationships (ISAR), we explore orchid biogeography in the Central Western‐Mediterranean islands. In this study, we aim to investigate variation in ISARs using orchid pollination mechanisms as proxies to establish permanent populations explaining how the c and z parameters of ISARs vary among island types and pollination strategies and defining the most influential factors in shaping orchids' distribution.
Location
Mediterranean Basin.
Taxon
Orchidaceae.
Methods
Checklist of native orchids was obtained for 112 islands of Central‐Western Mediterranean Basin. The Arrhenius power function (S=c·Az) was used to fit ISARs for the total number of orchids as well as for functional groups defined by the pollination strategies, across different island types. We used GLM to investigate the relation between pollination syndromes with area and isolation as well as elevation, island origin, taxa richness of the source area and habitat diversity.
Results
We found that ISARs differ between continental and volcanic islands depending on isolation. The z‐value was found to be higher for more specialized strategies while the c‐value increases from autogamy to allogamy, supporting the role of these two parameters in understanding distributional dynamics. Distance from the mainland is a negative predictor for all the strategies except when deception is decoupled; island area is a positive predictor only for allogamic, deceptive and food deceptive strategies, while habitat diversity is a positive predictor for allogamic, rewarding and deceptive strategies.
Main Conclusions
Pollination syndromes contribute in explaining the distribution of orchids in insular conditions. Furthermore, we identified differences in ISARs across pollination syndromes in which the intercept increases when the pollination shifts from a generalist to a more specialized one.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The prevalence of off-label anticancer drug use is not well characterized. The extent of off-label use is a policy concern because the clinical benefits of such use to patients may not outweigh costs ...or adverse health outcomes.
Prescribing data from IntrinsiQ Intellidose data systems, a pharmacy software provider maintaining a population-based cohort database of medical oncologists, was analyzed. Use of the most commonly prescribed anticancer drugs ("chemotherapies") that were patent protected and administered intravenously to patients in 2010 was examined. Use was classified as "on-label" if the cancer site, stage, and therapy line met the US Food and Drug Administration (FDA)-approved indication. All other use was "off-label." Off-label use was divided by whether it conformed to National Comprehensive Care Network (NCCN) Compendium recommendations, a basis of insurer coverage policies. IMS Health National Sales Perspectives was used to estimate national spending by use category.
Ten chemotherapies met inclusion criteria. On-label use amounted to 70%, and off-label use amounted to 30%. Fourteen percent of use conformed to an NCCN-supported off-label indication, and 10% of off-label use was associated with an FDA-approved cancer site, but an NCCN-unsupported cancer stage and/or line of therapy. Total national spending on these chemotherapies amounted to $12 billion (B; $7.3B on-label, $2B off-label and NCCN supported; $2.5B off-label and NCCN unsupported).
Commonly used, novel chemotherapies are more often used on-label than off-label in contemporary practice. Off-label use is composed of a roughly equal mix of chemotherapy applied in clinical settings supported by the NCCN and those that are not.
The Fifth Generation of Communication Networks (5G) envisions a broader range of services compared to previous generations, supporting an increased number of use cases and applications. The broader ...application domain leads to increase in consumer use and, in turn, increased hacker activity. Due to this chain of events, strong and efficient security measures are required to create a secure and trusted environment for users. In this paper, we provide an objective overview of 5G security issues and the existing and newly proposed technologies designed to secure the 5G environment. We categorize security technologies using Open Systems Interconnection (OSI) layers and, for each layer, we discuss vulnerabilities, threats, security solutions, challenges, gaps and open research issues. While we discuss all seven OSI layers, the most interesting findings are in layer one, the physical layer. In fact, compared to other layers, the physical layer between the base stations and users' device presents increased opportunities for attacks such as eavesdropping and data fabrication. However, no single OSI layer can stand on its own to provide proper security. All layers in the 5G must work together, providing their own unique technology in an effort to ensure security and integrity for 5G data.
Subcellular distribution of mitochondria in neurons is crucial for meeting the energetic demands, as well as the necessity to buffer Ca2+ within the axon, dendrites and synapses. Mitochondrial ...impairment is an important feature of Parkinson disease (PD), in which both familial parkinsonism genes DJ‐1 and PINK1 have a great impact on mitochondrial function. We used differentiated human dopaminergic neuroblastoma cell lines with stable PINK1 or DJ‐1 knockdown to study live motility of mitochondria in neurites. The frequency of anterograde and retrograde mitochondrial motility was decreased in PINK1 knockdown cells and the frequency of total mitochondrial motility events was reduced in both cell lines. However, neither the distribution nor the size of mitochondria in the neurites differed from the control cells even after downregulation of the mitochondrial fission protein, Drp1. Furthermore, mitochondria from PINK1 knockdown cells, in which motility was most impaired, had increased levels of GSK3βSer9 and higher release of mitochondrial Ca2+ when exposed to CCCP‐induced mitochondrial uncoupling. Further analysis of the ER‐mitochondria contacts involved in Ca2+ shuttling showed that PINK1 knockdown cells had reduced contacts between the two organelles. Our results give new insight on how PINK1 and DJ‐1 influence mitochondria, thus providing clues to novel PD therapies.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Despite concerns about drug safety, current information on older adults' use of prescription and over-the-counter medications and dietary supplements is limited.
To estimate the prevalence and ...patterns of medication use among older adults (including concurrent use), and potential major drug-drug interactions.
Three thousand five community-residing individuals, aged 57 through 85 years, were drawn from a cross-sectional, nationally representative probability sample of the United States. In-home interviews, including medication logs, were administered between June 2005 and March 2006. Medication use was defined as prescription, over-the-counter, and dietary supplements used "on a regular schedule, like every day or every week." Concurrent use was defined as the regular use of at least 2 medications.
Population estimates of the prevalence of medication use, concurrent use, and potential major drug-drug interactions, stratified by age group and gender.
The unweighted survey response rate was 74.8% (weighted response rate, 75.5%). Eighty-one percent (95% confidence interval CI, 79.4%-83.5%) used at least 1 prescription medication, 42% (95% CI, 39.7%-44.8%) used at least 1 over-the-counter medication, and 49% (95% CI, 46.2%-52.7%) used a dietary supplement. Twenty-nine percent (95% CI, 26.6%-30.6%) used at least 5 prescription medications concurrently; this was highest among men (37.1%; 95% CI, 31.7%-42.4%) and women (36.0%; 95% CI, 30.2%-41.9%) aged 75 to 85 years. Among prescription medication users, concurrent use of over-the-counter medications was 46% (95% CI, 43.4%-49.1%) and concurrent use of dietary supplements was 52% (95% CI, 48.8%-55.5%). Overall, 4% of individuals were potentially at risk of having a major drug-drug interaction; half of these involved the use of nonprescription medications. These regimens were most prevalent among men in the oldest age group (10%; 95% CI, 6.4%-13.7%) and nearly half involved anticoagulants. No contraindicated concurrent drug use was identified.
In this sample of community-dwelling older adults, prescription and nonprescription medications were commonly used together, with nearly 1 in 25 individuals potentially at risk for a major drug-drug interaction.
The 5G ecosystem is radically shifting Information and Communication Technologies (ICT) towards a system directly tailored and optimised to support vertical markets and services. In order to design ...and implement the ambitious 5G network, Satellite Communications (SatCom) have been recognised as a promising solution to extend and complement terrestrial networks in unserved or under-served areas, as reflected by recent commercial and standardisation endeavours. Within 3GPP, this is reflected in the novel Study Item on Non-Terrestrial Networks to introduce 5G (New Radio, as per 3GPP nomenclature) technologies in SatCom. However, typical satellite channel impairments, as large path losses, delays, and Doppler shifts, pose severe challenges to the realisation of a satellite-based 5G network. In this paper, we thoroughly review the standardisation process performed within 3GPP from Rel. 15 to the present, discussing the different technologies and the related system architectures and interfaces. Based on these discussions, we assess the impact of the satellite channel characteristics on the major physical and medium access control layers, i.e., Downlink Synchronisation, Random Access, and Hybrid Automatic Repeat reQuest. A set of potential solutions to the identified shortcomings is finally discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of the present study was to synthesize mixture solutions which can accurately mimic the dielectric properties of biological tissues, specifically muscle and adipose tissues between 500 MHz ...and 50 GHz. Mixtures utilizing concentrations of bovine serum albumin (BSA) dissolved in phosphate buffered saline (PBS) and Ringer's solutions were synthesized to mimic in vivo and ex vivo muscle tissues. Solutions consisting of concentrations of peanut oil and Triton X-100 (TX) in PBS and Ringer's solutions were also synthesized to mimic in vivo and ex vivo adipose tissue. Results were then analysed and compared to measured dielectric properties of in vivo and ex vivo biological tissues from another previous study. Good agreement with said dielectric property measurements were obtained since the solutions from this study yielded low RMSE and RMSRE values. This implied that such solutions can be utilized in the construction of human body phantoms for narrowband and ultra-wideband microwave devices for near field breast cancer imaging.
Time-of-flight (TOF) positron emission tomography (PET) has the potential to improve signal-to-noise ratio (SNR). In the literature, this improvement has been estimated as proportional to the square ...root of D//spl Delta/x, where D is the radial dimension of the object to be imaged, and /spl Delta/x is the spatial uncertainty associated with the time resolution of the scanner. This estimate does not include the effect of the randoms. In this paper we discuss the role of random coincidence in TOF PET; in particular, the improvement in SNR due to random reduction in TOF PET. We introduce and discuss a simple model for this improvement, modify the traditional estimate for SNR gain, and compare it to experimental data from a Siemens Hi-Rez PET scanner with TOF capability.
Ordered cell cycle progression is coordinated by cyclin dependent kinases (CDKs). CDKs often phosphorylate substrates at multiple sites clustered within disordered regions. However, for most ...substrates, it is not known which phosphosites are functionally important. We developed a high-throughput approach, Phosphosite Scanning, that tests the importance of each phosphosite within a multisite phosphorylated domain. We show that Phosphosite Scanning identifies multiple combinations of phosphosites that can regulate protein function and reveals specific phosphorylations that are required for phosphorylation at additional sites within a domain. We applied this approach to the yeast transcription factor Hcm1, a conserved regulator of mitotic genes that is critical for accurate chromosome segregation. Phosphosite Scanning revealed a complex CDK-regulatory circuit that mediates Cks1-dependent phosphorylation of key activating sites in vivo. These results illuminate the mechanism of Hcm1 activation by CDK and establish Phosphosite Scanning as a powerful tool for decoding multisite phosphorylated domains.
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