Multi Analysis Research Articles

Multiregion expression profiling of prostate cancer from men randomized in the STAMPEDE trial: Stage I results of a multistage biomarker analysis.

153 Background: The PAM50 gene expression classifier stratifies localized prostate cancer into luminal A/B and basal subtypes: luminal A have superior prognosis compared to luminal B and basal. Drug response scores built using the NCI-60 cell lines predict luminal subtypes are more taxane sensitive compared to basal; luminal B is hypothesized to be the most proliferative and hormone responsive compared to the basal subtype. The STAMPEDE trial provides a framework to validate prognostic and predictive associations of the PAM50 test in tumors from men randomized to androgen deprivation therapy (ADT) alone or with docetaxel or abiraterone. We here present multi-region whole-transcriptome expression array data at completion of Stage I designed to confirm the feasibility of molecular subtyping STAMPEDE tumor blocks. Methods: In collaboration with Decipher Biosciences we generated clinical-grade whole-transcriptome expression array data (Human Exon 1.0 ST GeneChip) performed to CLIA standards on mRNA (from three 10 micron slides) from cancer-enriched areas and applied the PAM50 classifier. Results: As of January 2019, we retrieved blocks from 2012 men from an ITT population of 3879. For Stage I feasibility assessment, we sectioned diagnostic trans-rectal biopsies of the prostate from 50 randomly selected men treated with ADT. We extracted mRNA from 109 cores; > 92% cores (101) from > 94% patients (47/50) passed quality control. The prevalence of PAM50 subtypes was: 31 basal cases (62%), 18 luminal B (36%) and 1 luminal A (2%). 26 cases (52%) were identified as ETS-related gene (ERG) positive. More than one core was interrogated from 35/50 cases (range: 1-6 cores). ERG positive cores were homogeneous across cores from the same patient but PAM50 subtyping identified intra-patient variability across cores from the same case. Conclusions: We confirm the feasibility of expression profiling STAMPEDE tumor blocks and identify a low prevalence of luminal A subtype. Whereas ERG status is consistent across multiple cores, basal and luminal subtypes co-exist in the same prostate. Multi-region analysis will enable further refinement for individual patient classification.

Multi-stage optimization and meta-model analysis with sequential parameter range adjustment for the low-energy house in Korea

The demand for low-energy building in the market is growing in Korea. However, transition of the market is slow mainly due to shortage of relevant information regarding the selection of energy saving design and technical elements with their subsequent impact on energy performance. Recent development of optimization tools has tried to integrate energy performance simulation with conventional architectural design process. However, these new optimization techniques such as stochastic optimization, sensitivity analysis, and meta-model analysis failed to provide sufficient knowledge base for all stakeholders during the design process despite their potentials. The objective of this study was to test an integrated process of optimization analysis and information production. An integrated automatic simulation framework was established with Passive House Planning Package (PHPP) and modeFrontier. Sequential adjustment of ranges of influential parameters was then performed until the median value of heating demand in randomly constructed design of experiment (DOE) cases reached two target performance levels. 2D plot charts for influential parameters in each target performance level were obtained based on meta-model analysis satisfying low-energy target objects.Main findings of this study are as follows: 1) Technical parameters are more influential than design parameters. Thus, it is necessary to establish technical levels for selected primary parameters such as SHGC and linear thermal transmittance; 2) The influential priority of parameters changes through eight simulation phases. Thus, the reliability of the sensitivity analysis is largely dependent on the defining realistic and feasible ranges for every planning parameter; 3) In the case of newly-introduced parameters and technologies, the proposed methodology of multi-stage optimization analysis for advising technical level has potential to provide enough information regarding the selection of appropriate technical levels and the interrelationship among other parameters.Comparative analysis of simulation results and experts’ cognition was conducted. Results of analysis show that education for thermal bridge free design is required and solar heat gain coefficient (SHGC) of glazing should be addressed more seriously. The final design decision advisory 2D charts of influential parameters in two performance target levels showed potential of knowledge platform for all stakeholders during the design process. Although this study simulated and tested the potential of multi-stage optimization based on heating demand of the prototype rural house, the methodology could be expanded to the multi-objective optimization, including cooling and lighting consumptions.

Multi-stage Sensitivity Analysis of Distributed Energy Systems: A Variance-based Sobol Method

In the face of the pressing environmental issues, the past decade witnessed the booming development of the distributed energy systems (DESs). A notable problem of DESs is the inevitable uncertainty that may make DESs deviate significantly from the deterministically obtained expectations, in both aspects of optimal design and economic operation. It thus necessitates the sensitivity analysis to quantify the impacts of the massive parametric uncertainties. This paper aims to give a comprehensive quantification, and carries out a multi-stage sensitivity analysis on DESs from the perspectives of evaluation criteria, optimal design and economic operation. First, a mathematical model of a DES is developed to present the solutions to the three stages of the DES. Second, the Monte-Carlo simulation is carried out subject to the probabilistic distributions of the energy, technical and economic parameters. Based on the simulation results, the variance-based Sobol method is applied to calculate the individual importance, interactional importance and total importance of various parameters. The comparison of the multi-stage results shows that only a few parameters play critical roles while the uncertainty of most of the massive parameters has little impact on the system performance. In addition, the influence of parameter interactions in the optimal design stage are much stronger than that in the evaluation criteria and operation strategy stages.

Process design for the forming of semi-tubular self-piercing rivets made of high nitrogen steel

The aim to reduce pollutant emission has led to a trend towards lightweight construction in car body development during the last years. As a consequence of the resulting need for multi-material design, mechanical joining technologies become increasingly important. Mechanical joining allows for the combination of dissimilar materials, while thermic joining techniques reach their limits. Self-piercing riveting enables the joining of dissimilar materials by using semi-tubular rivets as mechanical fasteners. The rivet production, however, is costly and time-consuming, as the rivets generally have to be hardened, tempered and coated after forming, in order to achieve an adequate strength and corrosion resistance. A promising approach to improve the efficiency of the rivet manufacturing is the use of high-strength high nitrogen steel as rivet material because these additional process steps would not be necessary anymore. As a result of the comparatively high nitrogen content, such steels have various beneficial properties like higher strength, good ductility and improved corrosion resistance. By cold bulk forming of high nitrogen steels high-strength parts can be manufactured due to the strengthening which is caused by the high strain hardening. However, high tool loads thereby have to be expected and are a major challenge during the production process. Consequently, there is a need for appropriate forming strategies. This paper presents key aspects concerning the process design for the manufacturing of semi-tubular self-piercing rivets made of high-strength steel. The aim is to produce the rivets in several forming stages without intermediate heat treatment between the single stages. Due to the high strain hardening of the material, a two stage forming concept will be investigated. Cup-backward extrusion is chosen as the first process step in order to form the rivet shank without forming the rivet foot. Thus, the strain hardening effects in the area of the rivet foot are minimized and the tool loads during the following process step can be reduced. During the second and final forming stage the detailed geometry of the rivet foot and the rivet head is formed. In this context, the effect of different variations, for example concerning the final geometry of the rivet foot, on the tool load is investigated using multistage numerical analysis. Furthermore, the influence of the process temperature on occurring stresses is analysed. Based on the results of the investigations, an adequate forming strategy and a tool concept for the manufacturing of semi-tubular self-piercing rivets made of high-strength steel are presented.

Performance of women dairy self-help groups in Rajasthan: A multistage principal component analysis approach

Performance of women dairy self-help groups in Rajasthan: A multistage principal component analysis approach

In search of mediators in the relationship between entrepreneurial orientation and performance: the mediating role of technology park support

Purpose – The aim of this paper is to determine the role of the technology park support in the relationship between entrepreneurial orientation (EO) and enterprise performance. Research method – A multi-stage statistical analysis with elements of econometrics was utilised. The reliability of individual scales by Cronbach’s alpha test was performed. Variables were treated as reflective and latent and exploratory and confirmatory factor analysis was performed. The relationship between the variables studied (analysis of Pearson correlation and Tau-B Kendall) was assessed. The Structural Equation Modelling (SEM) technique was used, including mediation analysis. Results – Technology park support is not a significant mediator of the relationship between EO and performance. Originality / value / implications / recommendations – The study results are a good starting point for further research to identify the variables which mediate the EO-performance relationship. They are also an inspiration to examine why companies in technology parks do not use the offer of support from these centres.

Systemic Assessment and Selection of Material and Joining Technology Exemplarily Applied on the Automotive Bodywork

Due to the increasingly stringent environmental regulations for more sustainable products and processes, as well as the enhanced pressure on competition and costs, in particular the automotive industry is currently facing various challenges. The trend towards a system-efficient lightweight engineering is one solution that leads to the future-oriented concept of multi-material design and its growing variety of heterogeneous combinations of materials and possible joining technologies. However, such a systemically even more necessitated inherent consideration of certain material/joining-correlations causes a highly complex, multi-dimensional decision-making on component and subsystem level, which has not been investigated sufficiently in the scientific literature yet. Thus, this research work provides a multi-criteria (technically, economically and ecologically oriented) approach to an integrated cross-component material and joining concept evaluation supporting the concurrent decision-making in the early phase of product development. Here, and apart from the individual view on a functional, economic and sustainable joining of different material combinations, the overall methodology works with a set-based choice of alternative solutions ultimately to detect a holistic optimum with respect to the full assembly line with its material throughput, utilization rates, and cycle times of the needed joining systems in one subassembly step. Based on the detailed scientific considerations, an example from the automotive industry is applied to validate the usability of the prototypically software-supported procedure in an industrial context for a future multistage potential analysis.

Nonlinear Fault Detection Based on Fault-related Multiphase Principle Polynomial Analysis for Al Stack Etch Process

In integrated circuit manufacturing industry, etch process is a complex nonlinear batch process. Al stack etch is the penultimate layer of dry etch. Based on the specific steps of the recipe, it has the multiphase characteristic and the can exhibit significantly different behaviors over different phases. However, conventional fault detection methods cannot effectively monitor Al stack etch process due to nonlinear and multiphase characteristics. Moreover, they are usually modeled by normal process data. In Al stack etch process, fault process data can be obtained from the datalog of equipments. In order to utilize these data, a novel nonlinear fault detection method called fault-related multistage principal polynomial analysis (FMPPA) is proposed in this work. FMPPA is efficient to deal with nonlinearity of the multiphase batch process. Furthermore, it can make full use of fault data by decomposing original feature space into three subspaces. FMPPA is applied to monitoring the Al stack etch process. Simulation results demonstrate that FMPPA is superior to other methods.

Introducing microeconomic foundation in DEA: the average-based approach

ABSTRACTAlthough recent developments focused on the multi-stage and multilevel data envelopment analysis (DEA) exhibit a high degree of mathematical sophistication, they are also characterized by the absence of a microeconomic foundation. This study proposes a novel approach called average-based DEA, which is conceived to overcome such a concern through the application of the Spence distortion principle to the hierarchy of a system. Theoretical and empirical results demonstrate that the proposed methodology reduces the distortion of efficiency scores observed in alternative multilevel extensions.

Structure elucidation and formation mechanistic study of a methylene-bridged pregabalin dimeric degradant in pregabalin extended-release tablets.

During the pharmaceutical development of pregabalin extended-release tablets, an unknown degradant at a relative retention time (RRT) of 11.7 was observed and its nominal amount exceeded the ICH identification threshold in an accelerated stability study. The aim of this study is to identify the structure and investigate the formation mechanism of this impurity for the purpose of developing a chemically stable pharmaceutical product. By utilizing multi-stage LC-MS analysis in conjunction with mechanism-based stress study, the structure of the RRT 11.7 impurity was rapidly identified as a dimeric degradant that is caused by dimerization of two pregabalin molecules with a methylene bridging the two pregabalin moieties. The structure of the dimer was confirmed by 1D and 2D NMR measurement. The formation pathway of the dimeric degradant was also inferred from the mechanism-based stress study, which implicated that the bridging methylene could originate from formaldehyde which might be the culprit that triggers the dimerization in the first place. The subsequent API-excipients compatibility study indicated that the degradant was indeed formed in the compatibility experiments between pregabalin API and two polymeric excipients (PEO and PVPP) that are known to contain residual formaldehyde, but only in the co-presence of another excipient, colloidal silicon dioxide (SiO2). The kinetic behavior of the degradant formation was also investigated and two kinetic models were utilized based on the Arrhenius and Eyring equations, respectively, to calculate the activation energy (Ea) as well as the enthalpy of activation (△H‡), entropy of activation (△S‡), and Gibbs free energy (△G‡) of the degradation reaction. The results of this study would be useful for the understanding of similar dimeric degradant formation in finished products of drug substances containing primary or secondary amine moieties.

Multistage Analysis of Abnormal Human Behavior in Complex Scenes

Effective abnormal human behavior analysis serves as a warning signal before emergencies. However, most abnormal human behavior detections rely on manual monitoring at present. This method is criticized for being subjective and lack of timeliness. In response to the problems above, this paper proposes a multistage analysis method of abnormal human behavior in complex scenes. This paper firstly differentiates the abnormal behavior roughly from a large monitoring area with similarity measurement applied to the social force model, and precise analysis is conducted thereafter. The multistage analysis, based on the three-frame difference algorithm, is used for intrusion, left-behind baggage detection, and motion trajectory identification. The experimental result demonstrates the superiority of the proposed method in UMV, CAVIAR, and datasets. To demonstrate the adaptability and generalization ability of the proposed method, this paper selects the CVC and JAAD driving anomaly detection data sets to test the method. Experimental results show that the proposed method is superior to the existing methods.

Technological and behavioural complexity in expedient industries: The importance of use-wear analysis for understanding flake assemblages

Expedient lithic technology has been described as unchanging and without or very limited presence of formal tool types. However, this premise seems to limit the discussion on technological and behavioural complexity when studying amorphous flake industries. To address this issue, we employed multi-stage use-wear analysis to identify features that are not detectable through macroscopic approach. Our analysis of chert tools from Leang Sarru, North Sulawesi indicated the use of both unmodified flakes and retouched tools for plant processing, and we detected evidence for the manufacture of composite tools. Microscopic wear traces on unretouched flakes show that these were attached to shafts for possible use as hafted tools, but not necessarily as projectiles. Our results suggest that simple flake assemblages can be part of complex tool production and present an alternative view on the seemingly unchanging lithic technology from the Late Pleistocene to the Holocene. Furthermore, our current understanding of expedient lithic technology should be reassessed as features that are not observable with standard morphological and technological analyses may be detected through use-wear analysis. Overall, the applied methodology and results of this study are relevant to Pleistocene and Early Holocene archaeological sites and assemblages that exhibit the dilemma of inferring technological and behavioural complexity through the analysis of simple stone tools.

Pharmacodynamics of Siwu Decoction on blood supply based on factor analysis

To evaluate the pharmacodynamic effect of Siwu Decoction in treating blood deficiency in mice under multidimensional pharmacodynamic indexes by factor analysis. The mouse blood deficiency model was established with cyclophosphamide combined with acetophenone; and mouse organ index,white blood cells,red blood cell,hemoglobin,platelet counts in whole blood,serum granulocyte-macrophage colony-stimulating factor,macrophagecolony-stimulating factor,promotion erythropoietin,interleukin-3 and interleukin-6 were used as indicators to characterize the blood-enriching effect of Siwu Decoction; the pharmacodynamic effect of Siwu Decoction on blood deficiency model was evaluated comprehensively by factor analysis. Four common factors were extracted from 14 pharmacodynamics indexes through the factor analysis,namely blood phase factor,viscera index,hematopoietic regulatory factor 1-spleen index and hematopoietic regulatory factor 2-viscera index. The cumulative contribution rate of variance reached 86. 581%. The comprehensive score of factor analysis showed that Siwu Decoction had the best effect on blood replenishment,and it is significant compared with the model group( P<0. 01). The effect of alcohol precipitation of Siwu Decoction was slightly decreased. The study showed that Siwu Decoction has the best blood-enriching effect,followed by water decoction and traditional decoction. Alcohol precipitation had the worst effect. Factor analysis can be used for the comprehensive evaluation of blood deficiency mice model,and is a suitable evaluation method for animal model for multi-dimensional multistage complex data analysis. It provides a new model to evaluate the efficacy of multidimensional data in the future.

Human caudate nucleus exhibits a highly complex ganglioside pattern as revealed by high-resolution multistage Orbitrap MS

Caudate nucleus (CN) is a specialized part of the dorsal striatum of each brain hemisphere involved in numerous cognitive processes. Caudate dysfunctions are associated with Alzheimer’s, Parkinson’s and Huntington’s disease, autism, and even schizophrenia. Most of the studies upon CN and related diseases were conducted using neuroimaging techniques, which, in some instances have reached contradictory conclusions. This state-of-the-art technique triggered the development of methods able to provide information at the molecular level. In this context, here we have implemented high resolution (HR) mass spectrometry (MS) and multistage MS (MSn), for mapping and structural analysis of gangliosides in human CN. Due to the high resolution and mass accuracy (average value: 1.5 ppm), 100 distinct species, of which 90 were di-, tri-, tetra-, and pentasialylated and 17 fucosylated and acetylated and, for the first time, species modified by CH3COO−, were reliably identified in the native CN ganglioside extract. Additionally, two structurally-relevant species, GD2 (d18:1/18:0) and GD2 (d18:1/16:2), were characterized with MS2–MS3 by collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD). The set of data collected by high-resolution mass spectrometry (HR-MS) revealed a much higher complexity of the CN ganglioside pattern than ever reported, and the species associated to this brain region, potentially implicated in many of its functions.

Supermodel of the World: The Influence of Legitimacy on Genre and Creativity in Drag Music Videos

Who gets to define what counts as art when a genre is in flux? In the present analysis, I find that legitimated artists may also be able to act as intermediaries, such as critics and gatekeepers. In doing so, these artists-as-intermediaries, under certain conditions, can shift the meaning of the genre as it transitions. Using the current transition of drag performance from scene-based to industry-based genre as a case, I present a multistage qualitative analysis of televised and digital drag performance. I report three key findings from this analysis: (1) some legitimated artists can become intermediaries when their genre is in transition, (2) these legitimated artists-as-intermediaries can influence genre expectations, and (3) legitimated artists-as-intermediaries’ influence on genre expectations can, in turn, influence the creative expression of other artists. Each of the three findings, however, has the effect of limiting creativity of the artist-as-intermediary and future artists within the industry-based genre.

A multi-stage analysis of network slicing architecture for 5G mobile networks

Recently, the increasing demand for low latency, the explosive growth in the volume of network traffic, the large and growing number of connected devices, and diversified multimedia applications have paved the way for a new era of mobile networks. To meet these diverse requirements of different businesses in network virtualization, network slicing has emerged as a promising paradigm of upcoming 5G mobile networks. Network slicing is a major technology, based on network function virtualization and software defined network technologies, which aims to achieve more efficient utilization of available network traffic and reduce operating costs. In this paper, we propose a network slicing architecture for 5G mobile networks involving cloud radio access network (C-RAN), mobile edge computing (MEC), and cloud data center. We model the proposed network slicing system based on queueing theory, which can be used to derive the main performance metrics such as the CPU utilization, system throughput, system drop rate, average number of message requests, average response time, and average waiting time. We provide quantitative examples to show how this proposed model could be applied to estimate the system performance and cost for a network slicing system in 5G mobile networks and the number of C-RAN and MEC cores required under diverse 5G traffic conditions. The analytical results and simulation models indicate that the proposed model has a powerful ability to assign the number of C-RAN and MEC cores required to achieve the quality of service targets of 5G slices.

An exploration of SSA’s disability determination process based on efficiency analysis

Purpose This paper aims to estimate the performance of the social security administration (SSA) in dealing with disability benefits applications in American. Design/methodology/approach The authors propose a multi-stage data envelopment analysis (DEA) method to analyze the efficiency of 167 hearing offices (HOs) to find the best performed HOs and inefficient ones and detect total improvement of inefficient and weak efficient offices. Findings The results show that totally 299,711 applications were processed and more applications will be processed if all offices can work efficiently. To the best of the authors’ knowledge, this paper is the first one to analyze the performance of SSA HOs using the multi-stage DEA method. Originality/value To the best of the authors’ knowledge, this paper is the first one to analyze the performance of SSA HOs using the multi-stage DEA method.

Screening of monoterpene indole alkaloids in six Rauwolfia species by ultra‐high performance liquid chromatography orbitrap velos pro mass spectrometer

AbstractMonoterpene indole alkaloids have gained significant interest due to their important medicinal properties and unique skeletal characteristics. There is an urgent need to develop simple, fast and suitable method for identification and characterization of monoterpene indole alkaloids in plant extracts. Therefore, ajmaline, ajmalicine and serpentine were analyzed by direct infusion into electrospray ionization source under high‐resolution mass spectrometric conditions using orbitrap velos pro mass spectrometer in collision‐induced dissociation mode. The diagnostic fragment ions were identified and established fragmentation pathways on the basis of multistage mass spectrometry. Multistage mass spectrometric analysis showed C‐ring cleavage in ajmaline and ajmalicine whereas in serpentine E‐ring cleavage took place by retro Diels Alder. Optimized multistage mass spectrometric conditions for ajmaline, ajmalicine and serpentine were applied along with developed ultra high performance liquid chromatography with orbitrap velos pro multistage mass spectrometry method for ammoniacal chloroform root extracts of six Rauwolfia species. In total, 17 alkaloids were identified and characterized on the basis of their chromatographic, mass spectrometric and multistage mass spectrometric analysis in the ammoniacal chloroform root extracts of six Rauwolfia species. This method could be used to speed up dereplication of these bioactive monoterpene indole alkaloids in extracts.

The construction and validation of a geometric reasoning test item to support the development of learning progression

This article presents preliminary analysis of a test item in a large-scale study design to promote the development of geometric reasoning progression. Two sets of data were analysed to validate the item designed to assess secondary school students’ knowledge of a rectangle. The first data set involved 155 Year 4–10 students from seven trial schools across social strata. The second data set involved 585 Year 7–10 students from eleven project schools situated in lower socio-economic areas. The aim was to audit Australian students’ knowledge of hierarchy of shapes and document the process of validating a test item. The findings indicated that an iterative process of design, test and redesign, incorporating Sfard’s mathematical discourse framework and a multi-stage Rasch analysis, is vital in validating the results. A distinct change in students’ reasoning about rectangle is observed and this is not due to age. Moreover, Rasch analysis identified eight distinct thinking zones to assist in mapping out a learning progression for developing geometric reasoning.

The association of early linear growth and haemoglobin concentration with later cognitive, motor, and social–emotional development at preschool age in Ghana

It is important to identify the periods during childhood when exposure to environmental risk factors results in long‐term neurodevelopmental deficits. Stunting and anaemia may be sensitive indicators of exposure to such risks. In a prospective cohort enrolled before birth, we investigated the association of developmental scores at 4–6 years with (a) birth length and linear growth during three postnatal periods and (2) haemoglobin (Hb) concentration at three time points. Children were participants in a follow‐up study of a randomized controlled trial of nutritional supplementation in Ghana. At 4–6 years, cognitive, motor, and social–emotional developments were assessed using standard tests adapted for this population. We estimated the associations of length‐for‐age z‐score (LAZ) at birth and postnatal linear growth (n = 710) and Hb (n = 617) with developmental scores in regression models, using multistage least squares analysis to calculate uncorrelated residuals for postnatal growth. Cognitive development at 4–6 years was significantly associated with LAZ at birth (β = 0.12, 95% CI = 0.05, 0.19), ΔLAZ from 6 to 18 months (β = 0.16, 95% CI = 0.04, 0.28), and Hb at 18 months (β = 0.13, 95% CI = 0.06, 0.20), but not with ΔLAZ during 0–6 months, ΔLAZ from 18 months to 4–6 years, Hb at 6 months, or Hb at 4–6 years. No evidence of associations with motor or social–emotional development were found. These results suggest that in similar contexts, the earlier periods prior to birth and up to 18 months are more sensitive to risk factors for long‐term cognitive development associated with LAZ and Hb compared with later childhood. This may inform the optimal timing of interventions targeting improved cognitive development.