Projection Domain Research Articles

The Generic Methodology for Verification and Validation to support acceptance of models, simulations and data

The Generic Methodology for Verification and Validation (GM-VV) is a generic and comprehensive methodology for structuring, organizing and managing the verification and validation (V&V) of modelling and simulation (M&S) assets. The GM-VV is an emerging recommended practice within the Simulation Interoperability Standards Organization (SISO). The GM-VV provides a technical framework to efficiently develop arguments to justify why M&S assets are acceptable or unacceptable for a specific intended use. This argumentation supports M&S stakeholders in their acceptance decision-making process regarding the development, application and reuse of such M&S assets. The GM-VV technical framework assures that during the execution of the V&V work the decisions, actions, information and evidence underlying such acceptance arguments will be traceable, reproducible, transparent and documented. Since the GM-VV is a generic (i.e. abstract) methodology it must be tailored to fit the specific V&V needs of a M&S organization, project or application domain. Therefore, V&V practitioners must incorporate specific V&V techniques within the generic architectural template offered by the GM-VV in order to properly assess the M&S assets under review. The first part of this paper provides an introductory overview of the GM-VV basic principles, concepts, methodology components and their interrelationships. The second part of the paper focuses on how the GM-VV may be tailored for a specific simulation application. This effort is illustrated with some results and lessons learned from several technology demonstration programs of the Dutch Ministry of Defence.

Guiding Principles for the Care of Older Adults with Multimorbidity: An Approach for Clinicians

Guiding Principles for the Care of Older Adults with Multimorbidity: An Approach for Clinicians

Continuous Thermal Collapse of the Intrinsically Disordered Protein Tau Is Driven by Its Entropic Flexible Domain

The tau protein belongs to the category of Intrinsically Disordered Proteins (IDP), which in their native state lack a folded structure and fluctuate between many conformations. In its physiological state, tau helps nucleating and stabilizing the microtubules' (MTs) surfaces in the axons of the neurons. Tau is mainly composed by two domains: (i) the binding domain that tightly bounds the MT surfaces and (ii) the projection domain that exerts a long-range entropic repulsive force and thus provides the proper spacing between adjacent MTs. Tau is also involved in the genesis and in the development of the Alzheimer disease when it detaches from MT surfaces and aggregates in paired helical filaments. Unfortunately, the molecular mechanisms behind these phenomena are still unclear. Temperature variation, rarely considered in biological studies, is here used to provide structural information on tau correlated to its role as an entropic spacer between adjacent MTs surfaces. In this paper, by means of small-angle X-ray scattering and molecular dynamics simulation, we demonstrate that tau undergoes a counterintuitive collapse phenomenon with increasing temperature. A detailed analysis of our results, performed by the Ensemble Optimization Method, shows that the thermal collapse is coupled to the occurrence of a transient long-range contact between a region encompassing the end of the proline-rich domain P2 and the first part of the repeats domain, and the region of the N-terminal domain entailing residues 80-150. Interestingly these two regions involved in the tau temperature collapse belong to the flexible projection domain that acts as an entropic bristle and regulates the MTs' architecture. Our results show that temperature is an important parameter that influences the dynamics of the tau projection domain, and hence its entropic behavior.

Statistical CT noise reduction with multiscale decomposition and penalized weighted least squares in the projection domain

The suppression of noise in x-ray computed tomography (CT) imaging is of clinical relevance for diagnostic image quality and the potential for radiation dose saving. Toward this purpose, statistical noise reduction methods in either the image or projection domain have been proposed, which employ a multiscale decomposition to enhance the performance of noise suppression while maintaining image sharpness. Recognizing the advantages of noise suppression in the projection domain, the authors propose a projection domain multiscale penalized weighted least squares (PWLS) method, in which the angular sampling rate is explicitly taken into consideration to account for the possible variation of interview sampling rate in advanced clinical or preclinical applications. The projection domain multiscale PWLS method is derived by converting an isotropic diffusion partial differential equation in the image domain into the projection domain, wherein a multiscale decomposition is carried out. With adoption of the Markov random field or soft thresholding objective function, the projection domain multiscale PWLS method deals with noise at each scale. To compensate for the degradation in image sharpness caused by the projection domain multiscale PWLS method, an edge enhancement is carried out following the noise reduction. The performance of the proposed method is experimentally evaluated and verified using the projection data simulated by computer and acquired by a CT scanner. The preliminary results show that the proposed projection domain multiscale PWLS method outperforms the projection domain single-scale PWLS method and the image domain multiscale anisotropic diffusion method in noise reduction. In addition, the proposed method can preserve image sharpness very well while the occurrence of "salt-and-pepper" noise and mosaic artifacts can be avoided. Since the interview sampling rate is taken into account in the projection domain multiscale decomposition, the proposed method is anticipated to be useful in advanced clinical and preclinical applications where the interview sampling rate varies.

TU-A-213CD-06: A Cone Beam CT Scatter Reduction Method with Piecewise Prior Image Knowledge

Purpose: In cone beam computerized tomography (CBCT), the reconstructed image contains significant image artifacts induced by scatter effects. The purpose of this study is to develop a scatter reduction method to improve CBCT image quality with piecewise prior image knowledge. Methods: The hypothesis of the proposed method is that in scatter-free CBCT image, the image intensities of different kind of materials are approximately globally uniform, i.e. piecewise property. However, the scatter induced image artifacts diminish the piecewise property of the CBCT image. In the proposed scatter reduction method, an extended fuzzy C-mean (EFCM) function is used to describe the degree of piecewise property of the CBCT image. Since the scatter components in projection domain can be characterized as low frequency, by minimizing the EFCM function in image domain, the proposed method removes an appropriate low frequency component from projection domain so that the reconstructed CBCT image achieves a piecewise property. Results: The performance of the proposed scatter reduction algorithm was tested using both digital phantom and pelvis CBCT images. In a phantom study, the proposed method reduced the maximum HU errors from 420HU to about 80HU; in a pelvis case, the HU errors were reduced from 580HU to 150HU. All those maximum HU errors occur around area with high image contrast. For soft tissues, the proposed method reduced the HU errors to less than 60HU. In addition, there are severe shading-artifacts that appeared in the uncorrected CBCT images in which the proposed method significantly improved the image intensity uniformity of different tissue types in the corrected CBCT image. Conclusions: For an object with piecewise property, the proposed scatter reduction method demonstrated substantial reductions in scatter-induced image artifacts commonly encountered in CBCT imaging. This methodology may be an avenue to significantly improve the image quality of clinical CBCT images.

Networks in engineering: an emerging approach to project organization studies

The field of social science has introduced a number of qualitative and quantitative approaches that have been adopted in the engineering project organization research domain. One such approach that is receiving increasing attention is social network analysis (SNA). Introduced in the 1930s and refined in multiple domains since the introduction, SNA has become a fundamental tool for social scientists over the past eight decades. Recently, engineering project organization researchers have begun to explore the application of this tool within the engineering project domain. This paper introduces both the historical development of SNA within the social science community and the recent adoption of this approach within the engineering community. The paper traces the recent trend in papers published by the engineering community to illustrate the increasing attention paid to SNA by researchers and the evolution of its use. This background is used to propose several paths forward for future researchers to expand and...

Two Surfaces of a Conserved Interdomain Linker Differentially Affect Output from the RST Sensing Module of the Bacillus subtilis Stressosome

The stressosome is a 1.8-MDa cytoplasmic complex that conveys environmental signals to the σ(B) stress factor of Bacillus subtilis. A functionally irreducible complex contains multiple copies of three proteins: the RsbRA coantagonist, RsbS antagonist, and RsbT serine-threonine kinase. Homologues of these proteins are coencoded in different genome contexts in diverse bacteria, forming a versatile sensing and transmission module called RST after its common constituents. However, the signaling pathway within the stressosome itself is not well defined. The N-terminal, nonheme globin domains of RsbRA project from the stressosome and are presumed to channel sensory input to the C-terminal STAS domains that form the complex core. A conserved, 13-residue α-helical linker connects these domains. We probed the in vivo role of the linker using alanine scanning mutagenesis, assaying stressosome output in B. subtilis via a σ(B)-dependent reporter fusion. Substitutions at four conserved residues increased output 4- to 30-fold in unstressed cells, whereas substitutions at four nonconserved residues significantly decreased output. The periodicity of these effects supports a model in which RsbRA functions as a dimer in vivo, with the linkers forming parallel paired helices via a conserved interface. The periodicity further suggests that the opposite, nonconserved faces make additional contacts important for efficient stressosome operation. These results establish that the linker influences stressosome output under steady-state conditions. However, the stress response phenotypes of representative linker substitutions provide less support for the notion that the N-terminal globin domain senses acute environmental challenge and transmits this information via the linker helix.

Integrating the Project with the Product for Applied Systems Engineering Management

Abstract Systems engineering planning and control are the essentials of systems engineering management. While the project management is concerned with such concepts as tasks, milestones, and budget, systems engineering is concerned with the product, requirements is needs to meet, its architecture, and its performance. In spite of the clear difference in the ontology used, both managers and engineers are equally required in order for the project-product ensemble to succeed. This underlines the need for a language and model as common bases for communication between managers and engineers. Based on this observation, we propose Project-Product Lifecycle Management (PPLM) as a combined model-based approach for planning project-product ensembles. Utilizing Object Process Methodology (OPM), the PPLM model integrates the project domain with the product domain via shared ontology that explicitly relates project to product entities within a unifying frame of reference.

Abstract LB-26: The N-terminal projection domain of the microtubule associated protein Tau inhibits TNFα signaling

Abstract Tumor Necrosis Factor-alpha (TNFα) is a multifunctional pro-inflammatory cytokine implicated in inducing both tumor promotion and tumor inhibition. This paradoxical effect can be partly explained by the fact that TNFα acts as a regulator of both proliferation and apoptosis; however the mechanisms and factors associated with how or whether a tumor cell responds to a microenvironment rich in TNFα have not been fully resolved. Here we provide evidence that the microtubule associate protein Tau inhibits TNFα signaling through its N-terminal domain and implicate it as a novel regulator of the cellular response to this key cytokine. Our findings indicate that over-expression of Tau in the human breast cancer cell lines MCF7, SkBr3 and in the pheochromocytoma cell line PC12 suppresses TNFα-induced apoptosis evident in the control cells. TNFα-induced cell apoptosis in control cells is triggered as early as 6 hrs post-treatment with hallmark features of cell shrinkage, membrane blebbing, disruption of tubulin architecture and caspase-3 activation. While over-expression of wild type full length Tau isoform in these cell lines, completely abrogates all TNFα-associated apoptotic phenotypes. Aside from inhibiting TNFα-induced apoptosis, Tau over-expression also interferes with TNFα-induced NFKB activation. This is evident by a significant decrease in NFKB nuclear translocation in Tau over-expressed cells compared to controls. Suppression of TNFα-signaling by Tau is not associated with its tubulin interaction since a truncated N-terminal projection domain lacking all microtubule binding domains still provides resistance to TNFα-induced apoptosis and NFKB activation. These findings lead us to conclude that the functional domain of Tau that regulates TNFα response lies within its N-terminal region and current studies investigating regions within this domain are ongoing. Our data provide direct evidence that the N-terminal domain of the microtubule associated protein Tau can inhibit TNFα signaling in tumor cells. These findings indicate a novel function for Tau and add to our knowledge of how a tumor cell responds to TNFα-signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-26. doi:1538-7445.AM2012-LB-26

A Capstone Course on Agile Software Development Using Scrum

In this paper, an undergraduate capstone course in software engineering is described that not only exposes students to agile software development, but also makes it possible to observe the behavior of developers using Scrum for the first time. The course requires students to work as Scrum Teams, responsible for the implementation of a set of user stories defined by a project domain expert playing the role of the Product Owner. During the course, data on project management activities are collected in order to analyze the amount of work completed, compliance with the release and iteration plans, productivity, ability in effort estimation, and the like. The paper discusses the achievement of teaching goals and provides empirical evaluation of students' progress in estimation and planning skills. A summary of lessons learned and recommendations is given, reflecting the issues to be considered when teaching courses in agile software development. Surveys of students have shown that they were overwhelmingly positive about the course, indicating that the course fully met or even exceeded their expectations.

Software release planning challenges in software development: An empirical study

Software development is a complicated process and requires careful planning to produce high quality software. In large software development projects, release planning may involve a lot of unique challenges. Due to time, budget and some other constraints, potentially there are many problems that may possibly occur. Subsequently, project managers have been trying to identify and understand release planning, challenges and possible resolutions which might help them in developing more effective and successful software products. This paper presents the findings from an empirical study which investigates release planning challenges. It takes a qualitative approach using interviews and observations with practitioners and project managers at five large software banking projects in Informatics Services Corporation (ISC) in Iran. The main objective of this study is to explore and increase the understanding of software release planning challenges in several software companies in a developing country. A number of challenges were elaborated and discussed in this study within the domain of software banking projects. These major challenges are classified into two main categories: the human-originated including people cooperation, disciplines and abilities; and the system-oriented including systematic approaches, resource constraints, complexity, and interdependency among the systems. Key words: Challenges, qualitative research, release planning, software developments.

Removing high contrast artifacts via digital inpainting in cryo-electron tomography: An application of compressed sensing

To cope with poor quality in cryo-electron tomography images, electron-dense markers, such as colloidal goldbeads, are often used to assist image registration and analysis algorithms. However, these markers can create artifacts that occlude a specimen due to their high contrast, which can also cause failure of some image processing algorithms. One way of reducing these artifacts is to replace high contrast objects with pixel densities that blend into the surroundings in the projection domain before volume reconstruction. In this paper, we propose digital inpainting via compressed sensing (CS) as a new method to achieve this goal. We show that cryo-ET projections are sparse in the discrete cosine transform (DCT) domain, and, by finding the sparsest DCT domain decompositions given uncorrupted pixels, we can fill in the missing pixel values that are occluded by high contrast objects without discontinuities. Our method reduces visual artifacts both in projections and in tomograms better than conventional algorithms, such as polynomial interpolation and random noise inpainting.

The I domain of the AAA+ HslUV protease coordinates substrate binding, ATP hydrolysis, and protein degradation

In the AAA+ HslUV protease, substrates are bound and unfolded by a ring hexamer of HslU, before translocation through an axial pore and into the HslV degradation chamber. Here, we show that the N-terminal residues of an Arc substrate initially bind in the HslU axial pore, with key contacts mediated by a pore loop that is highly conserved in all AAA+ unfoldases. Disordered loops from the six intermediate domains of the HslU hexamer project into a funnel-shaped cavity above the pore and are positioned to contact protein substrates. Mutations in these I-domain loops increase K(M) and decrease V(max) for degradation, increase the mobility of bound substrates, and prevent substrate stimulation of ATP hydrolysis. HslU-ΔI has negligible ATPase activity. Thus, the I domain plays an active role in coordinating substrate binding, ATP hydrolysis, and protein degradation by the HslUV proteolytic machine.

Analysis of the Projection Domain of the Microtubule Associated Protein Tau using Force Spectroscopy

Microtubule associated proteins (MAPs) are an important class of biological molecules that stabilize and organize microtubules. The MAP tau has been the subject of particular attention recently because it plays a role in some neurodegenerative diseases. This study focused on tau's projection domain in order to gain a better understanding of how the functional properties of this region of the protein affect its behavior. Using force spectroscopy of tau immobilized on mica substrates, we evaluated three versions of the protein where the projection domain had been modified, and compared long-range interactions between proteins. We found that as increasingly larger portions of tau's projection domain are removed, the range of long-range interactions decreases. Varying experimental conditions also changed the behavior of the projection domain, which is evident when the measurements are conducted in a high ionic strength buffer. This condition essentially removed the long-range interactions and provided strong evidence that the observed interactions are primarily electrostatic in nature. We also demonstrate that careful control of the experimental system allows us to measure tau-tau interactions or the behavior of tau alone on the mica. Our data confirms that the projection domain can exert strictly (entropic) repulsive interactions and can take part in more specific electrostatic interactions, depending on the geometry of the system.

Towards a Hermeneutics of Ambiguity: The Book of Esther and the Silence of Signs

The “accidental” does not seem to have any place in modern literary theory. In narrative, everything is meant to have a function and therefore signify. Indeed, contingency, fortuitous coincidences, belongs rather to the domain of hermeneutics and interpretive projections. The Book of Esther confronts us with such a kind of “causality” which is both plausible and “unexpected.” It tells the story of an extermination plot in Ahasuerus’ court, which is finally undone via an “astonishingly” favorable series of circumstances. Still, the text remains silent about the presumed logic of these coincidences. It simply points out a concomitancy of events, without indicating any superior intelligibility. More generally speaking, both Midrash and Talmud insist on these textual “signs” being opaque and deceiving — as if the rabbis wished to raise the (literary) devices of ambiguity to an ontological level, and open with the Book of Esther an enigmatic, essentially ambivalent, hermeneutics of destiny.

A Structure-Function Study of Map Tau: Analyzing Distinct Map Tau Domains in Mediating Microtubule Assembly and Bundling using Synchrotron SAXS

The microtubule-associated protein tau (MAP tau) promotes the assembly of tubulin into microtubules, a major component of the eukaryotic cytoskeleton. In neurons, MAP tau is especially abundant in the axon and plays a critical role in axonogenesis [1]. However, aberrant tau function has been implicated in many neurodegenerative diseases, such as Alzheimer's and supranuclear palsy [2,3]. Thus, there is a clear need to understand the structure of MAP tau with regards to its interactions with microtubules and its role in neuropathies. The six isoforms of MAP tau are often described as sequentially having a N-terminal (consisting of a projection domain and a proline-rich region), microtubule-binding repeats, and a C-terminal. While the function of the microtubule-binding repeats is well understood, the N- and C- terminals have been particularly difficult to characterize structurally and functionally due to the presence of intrinsically disordered domains. Using synchrotron small-angle X-ray scattering (SAXS), we examined the higher-order assembly of microtubules induced by varying concentrations of wild-type MAP tau under cell-free solution conditions. The functional dependence of the projection-domain, proline-rich region, and C-terminal were also examined by utilizing distinct constructs resulting in MAP tau with deletion domains. Not only do these results correspond well to axonal microtubule-tau bundles in vivo, we find that the modulation of the bundling of MAP tau is isoform-dependent. Surprisingly, the N-terminal tail of MAP tau is not necessary for higher-order assembly, as some models have suggested [4].Funded by DOE-BES-DE-FG-02-06ER46314 and NSF-DMR-11019001. B. Esmaeli-Azad et al. J. Cell Sci. 107; 869 (1994).2. J.G. Wood et al. PNAS. 83; 4040 (1986).3. P.M. Sanford et al. Brain. 123; 880 (2000).4. Y. Kanai et al. J. Cell Bio. 109; 1173 (1989).

Last House on the Hill

The aim of our project, Last House on the Hill (LHotH), is to holistically reconstitute the rich multimedia and primary research data with the impressive texts of the monograph, the printed final report of the Berkeley Archaeologists at Çatalhöyük (BACH) project, in which a team from UC Berkeley excavated a group of Neolithic 9000-year old buildings at this famous cultural heritage location in Central Anatolia, Turkey. The Last House on the Hill brings together the published text, complete project database (including all media formats such as photographs, videos, maps, line drawings), related Web sites, data and media outside the direct domain of the BACH project, and recontextualized presentations of the data as remixes, movies, and other interpretive works by BACH team members and many others. We are achieving this through an event-centered, CIDOC-CRM-compatible implementation ontology, expressed through an open-source Web publishing platform, providing open access, transparency and open-endedness to what is normally the closed and final process of monograph publication. The idea of embedding, interweaving, entangling, and otherwise linking the data and media from archaeological excavations with their interpretation and meaningful presentation in an open access sharable platform has long been an ambition of those of us working in the digital documentation of archaeological research and the public presentation of cultural heritage. Formidable barriers still exist to making it possible for projects to achieve these aims, ranging from intellectual property concerns to providing commitments to the long-term sustainability of the digital content. We believe that our event-centered implementation ontology will make it far easier for archaeologists and researchers in other disciplines to organize, manage, and share their data while gaining the significant benefits of the CIDOC-CRM framework. This article describes the strategy, goals, architecture, and implementation for the project, emphasizing the novel and innovative approaches that were required to make the project successful.

Estimation of affine transformations directly from tomographic projections in two and three dimensions

This paper presents a new approach to estimate two- and three-dimensional affine transformations from tomographic projections. Instead of estimating the deformation from the reconstructed data, we introduce a method which works directly in the projection domain, using parallel and fan beam projection geometries. We show that any affine deformation can be analytically compensated, and we develop an efficient multiscale estimation framework based on the normalized cross correlation. The accuracy of the approach is verified using simulated and experimental data, and we demonstrate that the new method needs less projection angles and has a much lower computational complexity as compared to approaches based on the standard reconstruction techniques.

A distributed multi-model-based Management Information System for simulation and decision-making on construction projects

The conceptual development of a Management Information System to support decision making on construction projects across all management levels within the owner and the contractor organizations is introduced. The system is designed as a distributed information and service platform. The backbone of the system is a layered ontology framework. Along with the information system, a novel approach to process and multi-model driven construction management is developed that allows for sharing distributed, yet interrelated, engineering and management application models in so called multi-models. A major challenge of the system is the management of the information and model logistics as well as the interdependencies among the application models. In order to support the retrieval of information from different project phases, domains and organizations and their combination in coherent multi-models, an ontology framework is developed. It defines the overall information space of the application models describing the application models content and their links in multi-models as well as the collaboration processes within the virtual organization of the project. The proposed system represents a paradigm shift. The information space is no longer product-model-centric. Central to the model-based information space is the process model that interrelates application model views contained in multi-models required for specific planning, production and analysis tasks. The activities are considered the enabler to semi-automatically combine dedicated information pieces of existing application models in new multi-models. Therefore we have identified the instantiation of activities and their combination to valid process chains to be the bottleneck to make the process and multi-model driven construction management efficient. As a consequence, we develop a new process and multi-model generation method, which is based on process modules formalized in description logics. The process modules combine distinct methods of Reference Process Modelling and Business Process Objects. In the generated processes, related application models, and populated multi-models are hierarchically structured (1) to support the utilization of project information by different actors of the hierarchical project organization and (2) to handle engineering and management knowledge and decisions piecewise during process generation in accordance to the hierarchy levels of the involved decision makers, thereby reducing the overall complexity of decision making. The paper discusses: (1) the main components of the system for interlinking and sharing models and information, (2) the ontology-based multi-model framework and the basics for the hierarchical structuring of the models, and (3) the generation of integrated process models.

Crystal structure of the human astrovirus capsid spike.

Astroviruses are single-stranded, plus-sense RNA viruses that infect both mammals and birds, causing gastroenteritis and other extraintestinal diseases. Clinical studies have established astroviruses as the second leading cause of viral diarrhea in young children. Here we report the crystal structure of the human astrovirus dimeric surface spike determined to 1.8-Å resolution. The overall structure of each spike/projection domain has a unique three-layered β-sandwiches fold, with a core, six-stranded β-barrel structure that is also found in the hepatitis E virus capsid protrusions, suggesting a closer phylogenetic relationship between these two viruses than previously acknowledged. Based on a hepatitis E virus capsid model, we performed homology modeling and produced a complete, T = 3 astrovirus capsid model with features remarkably similar to those observed in a cryoelectron microscopy reconstruction image of a human astrovirus. Mapping conserved residues onto the astrovirus projection domain revealed a putative receptor binding site with amino acid compositions characteristic for polysaccharide recognition. Our results will have an important impact on future characterization of astrovirus structure and function, and will likely have practical applications in the development of vaccines and antivirals.