General Framework For Analysis Research Articles

Digitally Enabled Generic Analytical Framework Accelerating the Pace of Liquid Chromatography Method Development for Vaccine Adjuvant Formulations.

The growing use of adjuvants in the fast-paced formulation of new vaccines has created an unprecedented need for meaningful analytical assays that deliver reliable quantitative data from complex adjuvant and adjuvant-antigen mixtures. Due to their complex chemical and physical properties, method development for the separation of vaccine adjuvants is considered a highly challenging and laborious task. Reversed-phase liquid chromatography (RPLC) is among the most important tests in the (bio)pharmaceutical industry for release and stability indicating measurements including adjuvant content, identity, and purity profile. However, the time constraints of developing "on-demand" robust quantitative methods prior to each change in formulation can easily lead to sample analysis becoming a bottleneck in vaccine development. Herein, a simple and efficient generic analytical framework capable of chromatographically resolving the most commonly used non-aluminum-based adjuvants across academic and industrial sectors is introduced. This was designed to seek a more proactive approach for fast-paced assay development endeavors that evolved from extensive stationary phase screening in conjunction with multifactorial in silico simulations of adjuvant retention time (RT) as a function of gradient time, temperature, organic modifier blending, and buffer concentration. The multifactorial retention models yield 3D resolution maps with excellent baseline separation of all adjuvants in a single run, which was found to be very accurate, with differences between experimental and simulated retention times of less than 1%. The analytical framework described here also includes the introduction of a more versatile approach to method development by introducing a dynamic RT database for adjuvants covering the entire library of adjuvants with broad mechanisms of action across numerous vaccine formulations with excellent linearity, accuracy, precision, and specificity. The power of this framework was also demonstrated with numerous analytical assays that can be generated rapidly from simulations guiding vaccine processes in the development of new adjuvant formulations. Analytical assay in this work covers content, purity profile by LC with diode array detector (DAD) and charged aerosol detector (CAD), and component identification by LC with mass spectrometry (MS) across complex vaccine formulations, including the use of surfactants (e.g., polysorbates) as well as their separation from adjuvant targets.

Self‐supervised representation learning of metro interior noise based on variational autoencoder and deep embedding clustering

AbstractThe noise within train is a paradox; while harmful to passenger health, it is useful to operators as it provides insights into the working status of vehicles and tracks. Recently, methods for identifying defects based on interior noise signals are emerging, among which representation learning is the foundation for deep neural network models to understand the key information and structure of the data. To provide foundational data for track fault detection, a representation learning framework for interior noise, named the interior noise representation framework, is introduced. The method includes: (i) using wavelet transform to represent the original noise signal and designing a soft and hard denoising module for dataset denoising; (ii) deep residual convolutional denoising variational autoencoder (VAE) module performs representation learning with a VAE and deep residual convolutional neural networks, enabling richer data augmentation for sparsely labeled samples by manipulating the embedding space; (iii) deep embedding clustering submodule balances the representation of reconstruction and clustering features through the joint optimization of these aspects, categorizing metro noise into three distinct classes and effectively discriminating significantly different features. The experimental results show that, compared to traditional mechanism‐based models for characterizing interior noise, this approach offers a data‐driven general analysis framework, providing a foundational model for downstream tasks.

How to Assess Rule-of-Law Violations in a State of Emergency? Towards a General Analytical Framework

How to Assess Rule-of-Law Violations in a State of Emergency? Towards a General Analytical Framework

FedCut: A Spectral Analysis Framework for Reliable Detection of Byzantine Colluders.

This paper proposes a general spectral analysis framework that thwarts a security risk in federated Learning caused by groups of malicious Byzantine attackers or colluders, who conspire to upload vicious model updates to severely debase global model performances. The proposed framework delineates the strong consistency and temporal coherence between Byzantine colluders' model updates from a spectral analysis lens, and, formulates the detection of Byzantine misbehaviours as a community detection problem in weighted graphs. The modified normalized graph cut is then utilized to discern attackers from benign participants. Moreover, the Spectral heuristics is adopted to make the detection robust against various attacks. The proposed Byzantine colluder resilient method, i.e., FedCut, is guaranteed to converge with bounded errors. Extensive experimental results under a variety of settings justify the superiority of FedCut, which demonstrates extremely robust model accuracy (MA) under various attacks. It was shown that FedCut's averaged MA is 2.1% to 16.5% better than that of the state of the art Byzantine-resilient methods. In terms of the worst-case model accuracy (MA), FedCut is 17.6% to 69.5% better than these methods.

Genetic Architecture and Analysis Practices of Circulating Metabolites in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program.

Circulating metabolite levels partly reflect the state of human health and diseases, and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single study analyses. Leveraging the rich metabolomics resources generated by the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally-diverse samples. We provided recommendations for outlier and imputation handling to process metabolite data, as well as a general analytical framework. We further performed a pooled analysis following our practical recommendations and discovered 1,778 independent loci associated with 667 metabolites. Among 108 novel locus - metabolite pairs, we detected not only novel loci within previously implicated metabolite associated genes, but also novel genes (such as GAB3 and VSIG4 located in the X chromosome) that have putative roles in metabolic regulation. In the sex-stratified analysis, we revealed 85 independent locus-metabolite pairs with evidence of sexual dimorphism, including well-known metabolic genes such as FADS2 , D2HGDH , SUGP1 , UTG2B17 , strongly supporting the importance of exploring sex difference in the human metabolome. Taken together, our study depicted the genetic contribution to circulating metabolite levels, providing additional insight into the understanding of human health.

Analysis of Nonconcurrent Controls in Adaptive Platform Trials: Separating Randomized and Nonrandomized Information.

Adaptive platform trials allow treatments to be added or dropped during the study, meaning that the control arm may be active for longer than the experimental arms. This leads to nonconcurrent controls, which provide nonrandomized information that may increase efficiency but may introduce bias from temporal confounding and other factors. Various methods have been proposed to control confounding from nonconcurrent controls, based on adjusting for time period. We demonstrate that time adjustment is insufficient to prevent bias in some circumstances where nonconcurrent controls are present in adaptive platform trials, and we propose a more general analytical framework that accounts for nonconcurrent controls in such circumstances. We begin by defining nonconcurrent controls using the concept of a concurrently randomized cohort, which is a subgroup of participants all subject to the same randomized design. We then use cohort adjustment rather than time adjustment. Due to flexibilities in platform trials, more than one randomized design may be in force at any time, meaning that cohort-adjusted and time-adjusted analyses may be quite different. Using simulation studies, we demonstrate that time-adjusted analyses may be biased while cohort-adjusted analyses remove this bias. We also demonstrate that the cohort-adjusted analysis may be interpreted as a synthesis of randomized and indirect comparisons analogous to mixed treatment comparisons in network meta-analysis. This allows the use of network meta-analysis methodology to separate the randomized and nonrandomized components and to assess their consistency. Whenever nonconcurrent controls are used in platform trials, the separate randomized and indirect contributions to the treatment effect should bepresented.

Methodological Considerations in Evaluating Breast Cancer Screening Studies.

In evidence-based medicine frameworks, the highest level of evidence is derived from quantitative synthesis of double-masked, high-quality, randomly assigned controlled trials. Meta-analyses of randomly assigned controlled trials have demonstrated that screening mammography reduces breast cancer deaths. In the United States, every major guideline-producing organization has recommended screening mammography in average-risk women; however, there are controversies about age and frequency. Carefully controlled observational research studies and statistical modeling studies can address evidence gaps and inform evidence-based, contemporary screening practices. As breast imaging radiologists develop and evaluate existing and new screening tests and technologies, they will need to understand the key methodological considerations and scientific criteria used by policy makers and health service researchers to support dissemination and implementation of evidence-based screening tests. The Wilson and Jungner principles and the U.S. Preventive Services Task Force general analytic framework provide structured evaluations of the effectiveness of screening tests. Key considerations in both frameworks include public health significance, natural history of disease, cost-effectiveness, and characteristics of screening tests and treatments. Rigorous evaluation of screening tests using analytic frameworks can maximize the benefits of screening tests while reducing potential harms. The purpose of this article is to review key methodological considerations and analytic frameworks used to evaluate screening studies and develop evidence-based recommendations.

Multistability of segmented rings by programming natural curvature

Multistable structures have widespread applications in the design of deployable aerospace systems, mechanical metamaterials, flexible electronics, and multimodal soft robotics due to their capability of shape reconfiguration between multiple stable states. Recently, the snap-folding of rings, often in the form of circles or polygons, has shown the capability of inducing diverse stable configurations. The natural curvature of the rod segment (curvature in its stress-free state) plays an important role in the elastic stability of these rings, determining the number and form of their stable configurations during folding. Here, we develop a general theoretical framework for the elastic stability analysis of segmented rings (e.g., polygons) based on an energy variational approach. Combining this framework with finite element simulations, we map out all planar stable configurations of various segmented rings and determine the natural curvature ranges of their multistable states. The theoretical and numerical results are validated through experiments, which demonstrate that a segmented ring with a rectangular cross-section can show up to six distinct planar stable states. The results also reveal that, by rationally designing the segment number and natural curvature of the segmented ring, its one- or multiloop configuration can store more strain energy than a circular ring of the same total length. We envision that the proposed strategy for achieving multistability in the current work will aid in the design of multifunctional, reconfigurable, and deployable structures.

Directional integration and pathway enrichment analysis for multi-omics data

Omics techniques generate comprehensive profiles of biomolecules in cells and tissues. However, a holistic understanding of underlying systems requires joint analyses of multiple data modalities. We present DPM, a data fusion method for integrating omics datasets using directionality and significance estimates of genes, transcripts, or proteins. DPM allows users to define how the input datasets are expected to interact directionally given the experimental design or biological relationships between the datasets. DPM prioritises genes and pathways that change consistently across the datasets and penalises those with inconsistent directionality. To demonstrate our approach, we characterise gene and pathway regulation in IDH-mutant gliomas by jointly analysing transcriptomic, proteomic, and DNA methylation datasets. Directional integration of survival information in ovarian cancer reveals candidate biomarkers with consistent prognostic signals in transcript and protein expression. DPM is a general and adaptable framework for gene prioritisation and pathway analysis in multi-omics datasets.

Aging dynamics of d-dimensional locally activated random walks.

Locally activated random walks are defined as random processes, whose dynamical parameters are modified upon visits to given activation sites. Such dynamics naturally emerge in living systems as varied as immune and cancer cells interacting with spatial heterogeneities in tissues, or, at larger scales, animals encountering local resources. At the theoretical level, these random walks provide an explicit construction of strongly non-Markovian and aging dynamics. We propose a general analytical framework to determine various statistical properties characterizing the position and dynamical parameters of the random walker on d-dimensional lattices. Our analysis applies in particular to both passive (diffusive) and active (run and tumble) dynamics, and quantifies the aging dynamics and potential trapping of the random walker; it finally identifies clear signatures of activated dynamics for potential use in experimental data.

A General Analysis of Resonant Switched-Capacitor Converters Using Peak Energy Storage and Switch Stress Including Ripple

This work presents a general analytical framework enabling large-signal characterization of resonant switched-capacitor (ReSC) power converters that accounts for passive component voltage and current ripple, for operation at and above resonance. From this, appropriate phase durations for minimized rms currents are derived, in addition to expressions for total passive component volume using an intuitive peak energy method. An example hardware prototype validates both the derived waveforms and timings—as well as total passive volume—through three comparable hardware configurations, one of which minimizes passive component volume. In addition, the proposed technique formulates analytical expressions for both rms currents and peak blocking voltages, facilitating refined loss estimation and component selection. Subsequent calculation of the large-signal Volt–Amp (VA) switch stress metric allows a more accurately quantified trade-off between active and passive components compared to prior work, which has not fully accounted for ripple. Four common ReSC topologies are exemplified throughout, with topology specific parameters documented for reference.

Formation tracking control in open multiagent systems with general linear dynamics

This paper studies the formation tracking problem of the so-called open multiagent systems. In these systems, agents can freely join or leave at any time, i.e. the system sizes are changeable. To achieve formation tracking control in these systems, we propose a general theoretical analysis framework that consists of a formation adjustment strategy and a formation tracking protocol. Therein, the former is used to adjust the predefined task-oriented formation shape to the varying size of the system. This strategy is built on the existing scalable self-healing idea and then modified by a size estimation method. The latter is used to drive the present followers to form the adjusted formation and track a leader. To accommodate undirected and directed graphs, two distributed formation tracking protocols are designed respectively. Due to possible agent migration, the designed tracking protocols are endowed with self-adaptive ability, i.e. without depending on global topology information. Then, their convergence properties are analysed using the Lyapunov theory. Finally, two simulations are presented to verify the effectiveness of the proposed framework.

The Crosswise Model for Surveys on Sensitive Topics: A General Framework for Item Selection and Statistical Analysis

When surveys contain direct questions about sensitive topics, participants may not provide their true answers. Indirect question techniques incentivize truthful answers by concealing participants’ responses in various ways. The Crosswise Model aims to do this by pairing a sensitive target item with a non-sensitive baseline item, and only asking participants to indicate whether their responses to the two items are the same or different. Selection of the baseline item is crucial to guarantee participants’ perceived and actual privacy and to enable reliable estimates of the sensitive trait. This research makes the following contributions. First, it describes an integrated methodology to select the baseline item, based on conceptual and statistical considerations. The resulting methodology distinguishes four statistical models. Second, it proposes novel Bayesian estimation methods to implement these models. Third, it shows that the new models introduced here improve efficiency over common applications of the Crosswise Model and may relax the required statistical assumptions. These three contributions facilitate applying the methodology in a variety of settings. An empirical application on attitudes toward LGBT issues shows the potential of the Crosswise Model. An interactive app, Python and MATLAB codes support broader adoption of the model.

On the security risk of pre-image attack on cancelable biometrics

Over the years, a number of biometric template protection schemes, often based on the notion of “cancelable biometrics”, have been proposed. An ideal cancelable biometric algorithm complies with four criteria: irreversibility, revocability, unlinkability, and performance preservation. Cancelable biometrics employs an irreversible but distance preserving transformation to convert the original biometric templates into protected templates. Matching in the transform domain can be accomplished due to the property of distance preservation. However, distance preservation also entails security issues, a point often overlooked in existing research. In this paper, we have conducted a comprehensive security analysis of distance preservation in cancelable biometrics for the first time. The analysis is based on a pre-image attack, which is launched to break the security of cancelable biometrics under Kerckhoffs’s assumption. Furthermore, we propose a general security analysis framework under the single and cross-transformation attacks, which also employs an information leakage estimation strategy based on mutual information as a complement. The experimental results performed on real face, iris, and fingerprint data demonstrate that the risks originating from the matching scores computed from the distance/similarity of two cancelable templates greatly compromise the security of cancelable biometric schemes, including the classic Biohashing, Index-of-max hashing, Non-linear multi-dimensional spectral hashing, Indexing-First-One hashing, Bloom Filter and Two-factor Protected Minutia Cylinder-Code. The security versus accuracy trade-off is discussed and recommendations for designing a biometric system secure against pre-image attacks are also proposed. The source code is available at github.com/biometricsecurity/CBrisks.

Exploring Blockchain Technology through a Modular Lens: A Survey

Blockchain has attracted significant attention in recent years due to its potential to revolutionize various industries by providing trustlessness. To comprehensively examine blockchain systems, this article presents both a macro-level overview on the most popular blockchain systems, and a micro-level analysis on a general blockchain framework and its crucial components. The macro-level exploration provides a big picture on the endeavors made by blockchain professionals over the years to enhance the blockchain performance while the micro-level investigation details the blockchain building blocks for deep technology comprehension. More specifically, this article introduces a general modular blockchain analytic framework that decomposes a blockchain system into interacting modules and then examines the major modules to cover the essential blockchain components of network, consensus, and distributed ledger at the micro-level. The framework as well as the modular analysis jointly build a foundation for designing scalable, flexible, and application-adaptive blockchains that can meet diverse requirements. Additionally, this article explores popular technologies that can be integrated with blockchain to expand functionality and highlights major challenges. Such a study provides critical insights to overcome the obstacles in designing novel blockchain systems and facilitates the further development of blockchain as a digital infrastructure to service new applications.

A General Analytical Framework for the Resolution of Near-Field Beamforming

A General Analytical Framework for the Resolution of Near-Field Beamforming

Effects of linear landscape elements on multiple ecosystem services in contrasting agricultural landscapes

Linear landscape elements, such as field margins, are agricultural practices whose adoption is supported by agri-environmental climate measures (AECMs). AECMs are meant to improve ecological conditions on farms and surrounding areas. The effectiveness of AECMs to enhance the supply of multiple ecosystem services (ESs) is still debated and knowledge on the resulting ESs bundles under different practices stemming from AECMs is still lacking. We aimed at assessing the potential of AECMs that promote the implementation of linear landscape elements to provide high levels of multiple ESs and at analyzing bundles at landscape level in different geographical contexts. We assessed the potential effects of linear landscape elements (woody, grassy, flower and a mix) on six ESs (food and feed provision, pollination, pest control, climate regulation, aesthetics, and habitat maintenance), combining scenarios and spatially explicit modelling approaches. Our results showed the positive effects of linear landscape elements on all regulating and cultural ESs. The more abundant the linear elements, the higher the overall ESs supply. However, the effect of linear landscape elements on multiple ESs depended on the types of linear elements and the geographical context of their implementation. When the supply of the ES was already high in the baseline situation, the changes induced by the implementation of the linear elements were much lower than when the baseline situation showed a lower initial supply of one or several of the ESs. Our analyses give insights on the efficiency of AECMs on multiple environmental targets. Our approach is a first step towards a general framework for an ex-ante integrated analysis of AECMs that can be used to design agri-environmental policies. From a more practical perspective, our results can form a basis for additional payments for AECMs. Our study also confirms the relevance of the EU biodiversity strategy that commits to ensure at least 10% of agricultural area as high-biodiversity landscape features such as linear landscape elements, and the relevance of the enhanced conditionality and eco-schemes in the reformed Common agricultural Policy targeting non-productive elements and biodiversity.

Behavioral selection in structured populations

The multilevel model of behavioral selection (MLBS) by Borgstede and Eggert (Behav Process 186:104370. 10.1016/j.beproc.2021.104370, 2021) provides a formal framework that integrates reinforcement learning with natural selection using an extended Price equation. However, the MLBS is so far only formulated for homogeneous populations, thereby excluding all sources of variation between individuals. This limitation is of primary theoretical concern because any application of the MLBS to real data requires to account for variation between individuals. In this paper, I extend the MLBS to account for inter-individual variation by dividing the population into homogeneous sub-populations and including class-specific reproductive values as weighting factors for an individual’s evolutionary fitness. The resulting formalism closes the gap between the theoretical underpinnings of behavioral selection and the application of the theory to empirical data, which naturally includes inter-individual variation. Furthermore, the extended MLBS is used to establish an explicit connection between the dynamics of learning and the maximization of individual fitness. These results expand the scope of the MLBS as a general theoretical framework for the quantitative analysis of learning and evolution.

Molecular sexing of birds using quantitative PCR (qPCR) of sex-linked genes and logistic regression models.

The ability to sex individuals is an important component of many behavioural and ecological investigations and provides information for demographic models used in conservation and species management. However, many birds are difficult to sex using morphological characters or traditional molecular sexing methods. In this study, we developed probabilistic models for sexing birds using quantitative PCR (qPCR) data. First, we quantified distributions of gene copy numbers at a set of six sex-linked genes, including the sex-determining gene DMRT1, for individuals across 17 species and seven orders of birds (n = 150). Using these data, we built predictive logistic models for sex identification and tested their performance with independent samples from 51 species and 13 orders (n = 209). Models using the two loci most highly correlated with sex had greater accuracy than models using the full set of sex-linked loci, across all taxonomic levels of analysis. Sex identification was highly accurate when individuals to be assigned were of species used in model building. Our analytical approach was widely applicable across diverse neognath bird lineages spanning millions of years of evolutionary divergence. Unlike previous methods, our probabilistic framework incorporates uncertainty around qPCR measurements as well as biological variation within species into decision-making rules. We anticipate that this method will be useful for sexing birds, including those of high conservation concern and/or subsistence value, that have proven difficult to sex using traditional approaches. Additionally, the general analytical framework presented in this paper may also be applicable to other organisms with sex chromosomes.

A General Materials Data Science Framework for Quantitative 2D Analysis of Particle Growth from Image Sequences

Phase transformations are a challenging problem in materials science, which lead to changes in properties and may impact performance of material systems in various applications. We introduce a general framework for the analysis of particle growth kinetics by utilizing concepts from machine learning and graph theory. As a model system, we use image sequences of atomic force microscopy showing the crystallization of an amorphous fluoroelastomer film. To identify crystalline particles in an amorphous matrix and track the temporal evolution of the particle dispersion, we have developed quantitative methods of 2D analysis. 700 image sequences were analyzed using a neural network architecture, achieving 0.97 pixel-wise classification accuracy as a measure of the correctly classified pixels. The growth kinetics of isolated and impinged particles were tracked throughout time using these image sequences. The relationship between image sequences and spatiotemporal graph representations was explored to identify the proximity of crystallites from each other. The framework enables the analysis of all image sequences without the requirement of sampling for specific particles or timesteps for various materials systems.