Intelligent tutoring systems for systems engineering methodologies

The general goal is to provide the technology required to build systems that can provide intelligent tutoring in IDEF (Integrated Computer Aided Manufacturing Definition Method) modeling. The following subject areas are covered: intelligent tutoring systems for systems analysis methodologies; IDEF tutor architecture and components; developing cognitive skills for IDEF modeling; experimental software; and PC based prototype

Sensitivity analysis of energy performance and thermal comfort throughout building design process

In a traditional building design process (TDP), design variables are fixed sequentially, as opposed to integrated design process (IDP) which tends to avoid sequential design phases to create more sustainable buildings. First, a reference building is introduced and an energy model based on TRNSYS is presented to determine the energy consumption and comfort in the building. The model is validated based on energy bills, certified simulations and literature. Then, the paper performs an extended sensitivity analysis (SA) of 30 design variables with respect to different performance criteria related to energy consumption and comfort, based on a TRNSYS model. Three SA techniques were used, namely standard regression coefficients (SRC), partial rank correlation coefficients (PRCC) and Sobol indices. Results show that all three techniques yielded a similar ranking of the importance of the variables for most model outputs. Interactions between variables were identified with second-order Sobol indices. In the second part of this paper, a traditional design framework was adopted in which sets of variables were fixed sequentially. A SA was performed at each phase of the process, assuming fixed values for parameters chosen in previous design phases. Results show that fixing variables during the phases of a traditional design process tends to reduce the probabilities of finding low-energy consumption designs. Moreover, the influence of some variables was found to change during the design phases

Performance of a sequential versus holistic building design approach using multi-objective optimization

Integrated design processes are currently pushed forward in order to achieve net-zero energy building designs at affordable cost. Through a case study of a residential building, this paper compares a sequential versus a holistic design approach based on multi-objective optimization. In the holistic approach, 39 design variables related to the architecture and HVAC systems are simultaneously optimized. In the sequential approach, the architecture variables are first optimized; several optimal solutions are then selected for the second phase optimization of the heating system parameters. Carbon footprint, life cycle cost and thermal comfort are optimized by the algorithm NSGA-II. With only 100 computational hours, the holistic approach found 59% of the optimal solutions, whereas it took 765 h to find 41% of the optimal solutions with the sequential approach. This comparison shows the negative effects of making irreversible variable selections in the early phase of a design process, as it reduces the ability to find optimal solutions in the end

Comparison between two genetic algorithms minimizing carbon footprint of energy and materials in a residential building

The emergence of building performance optimization is recognized as a way to achieve sustainable building designs. In this paper, the problem consists in minimizing simultaneously the emissions of greenhouse gases (GHG) related to building energy consumption and those related to building materials. This multi-objective optimization problem involves variables with different hierarchical levels, i.e. variables that can become obsolete depending on the value of the other variables. To solve it, NSGA-II is compared with an algorithm designed specifically to deal with hierarchical variables, namely sNSGA. Evaluation metrics such as convergence, diversity and hypervolume show that both algorithms handle hierarchical variables, but the analysis of the Pareto front confirms that in the present case, NSGA-II is better to identify optimal solutions than sNSGA. All the optimal solutions are made of buildings with wooden envelopes and relied either on heat pumps or on electrical heaters for proving heating

Analysis of methods

Information is one of an organization's most important assets. For this reason the development and maintenance of an integrated information system environment is one of the most important functions within a large organization. The Integrated Information Systems Evolution Environment (IISEE) project has as one of its primary goals a computerized solution to the difficulties involved in the development of integrated information systems. To develop such an environment a thorough understanding of the enterprise's information needs and requirements is of paramount importance. This document is the current release of the research performed by the Integrated Development Support Environment (IDSE) Research Team in support of the IISEE project. Research indicates that an integral part of any information system environment would be multiple modeling methods to support the management of the organization's information. Automated tool support for these methods is necessary to facilitate their use in an integrated environment. An integrated environment makes it necessary to maintain an integrated database which contains the different kinds of models developed under the various methodologies. In addition, to speed the process of development of models, a procedure or technique is needed to allow automatic translation from one methodology's representation to another while maintaining the integrity of both. The purpose for the analysis of the modeling methods included in this document is to examine these methods with the goal being to include them in an integrated development support environment. To accomplish this and to develop a method for allowing intra-methodology and inter-methodology model element reuse, a thorough understanding of multiple modeling methodologies is necessary. Currently the IDSE Research Team is investigating the family of Integrated Computer Aided Manufacturing (ICAM) DEFinition (IDEF) languages IDEF(0), IDEF(1), and IDEF(1x), as well as ENALIM, Entity Relationship, Data Flow Diagrams, and Structure Charts, for inclusion in an integrated development support environment

Factors affecting individual foraging specialization and temporal diet stability across the range of a large “generalist” apex predator

Individual niche specialization (INS) is increasingly recognized as an important component of ecological and evolutionary dynamics. However, most studies that have investigated INS have focused on the effects of niche width and inter- and intraspecific competition on INS in small-bodied species for short time periods, with less attention paid to INS in large-bodied reptilian predators and the effects of available prey types on INS. We investigated the prevalence, causes, and consequences of INS in foraging behaviors across different populations of American alligators (Alligator mississippiensis), the dominant aquatic apex predator across the southeast US, using stomach contents and stable isotopes. Gut contents revealed that, over the short term, although alligator populations occupied wide ranges of the INS spectrum, general patterns were apparent. Alligator populations inhabiting lakes exhibited lower INS than coastal populations, likely driven by variation in habitat type and available prey types. Stable isotopes revealed that over longer time spans alligators exhibited remarkably consistent use of variable mixtures of carbon pools (e.g., marine and freshwater food webs). We conclude that INS in large-bodied reptilian predator populations is likely affected by variation in available prey types and habitat heterogeneity, and that INS should be incorporated into management strategies to efficiently meet intended goals. Also, ecological models, which typically do not consider behavioral variability, should include INS to increase model realism and applicability

Grant Proposal for the Continuation of the Voyager Interstellar Mission: LECP Investigation

This proposal documents the plans of the Low Energy Charged Particle (LECP) investigation team for participation in NASA's Voyager Interstellar Mission (VIM) as the Voyager 1 and 2 spacecraft explore the outer reaches of the heliosphere and search for the termination shock and the heliopause. The proposal covers the four year period from 1 January 1997 to 31 December 2000. The LECP instruments on Voyager 1 and 2 measure in situ intensities of charged particles with energies from about 30 keV to 100 MeV for ions, and about 20 keV to greater than 10 MeV for electrons. The instruments provide detailed spectral, angular, and compositional information about the particles. Composition is available for greater than 200 keV/nuc using multi-parameter measurements. Angular information is obtained by a mechanically scanned platform that rotates at various commanded rates. Measurements of low energy ion and electron intensities versus time and spatial location within the heliosphere contain an abundance of information regarding various transport and acceleration processes on both local (approx. 1 hr, approx. 0.01 AU) and global (approx. 11 yrs, approx. 100 AU) scales. The LECP instruments provide unique observations of such dynamical processes, and we anticipate that it will return critical information regarding the boundaries of the heliosphere. Several recent and exciting discoveries based on LECP measurements emphasize the important role that low energy charged particle distributions play in physical processes in the interplanetary medium. Yet, at the same time, these discoveries also underscore the fact that our understanding of processes in the outer heliosphere is, in most cases, incomplete, and in others, only rudimentary at best. Among the discoveries referred to above are the following: (1) Shocks: Examination of greater than 30 keV ion intensities have revealed: (a) a total absence of acceleration beyond only -100-200 keV at a strong transient shock in May 1991 at 35 AU, despite an enhanced level of seed particles; (b) a large transient shock in September 1991 of global scale, with intensities of shock-accelerated ions greater than or equal to 30 keV to approx. 30 MeV showing complex, highly energy-dependent spatial evolution, and small-scale (approx. few gyroradii), often anisotropic, micro-structures; (c) recurrent intensity increases in greater than or equal to 30 keV to -few MeV ions, with structures that, in some cases, show no correlation with the associated corotating shock. (2) Superthermal ion pressure: A global merged interaction region with a leading shock, downstream of which the superthermal ion (greater than or equal to 30 keV to approx. 4 MeV) pressure is comparable to that of the thermal plasma, and the total particle pressure yields a plasma beta of order unity. (3) Pickup ions: Measurements of the C/O ratio within transient structures at 35-45 AU showing the first clear evidence that transient shocks can pre-accelerate interstellar pickup ions from approx. 1 keV/nuc to at least 1 MeV/nuc. (4) Seed particles: Injection of ions for acceleration to high energies at the termination shock is unlikely to be a problem, since interplanetary transient and recurrent shocks are continually accelerating ions, of solar wind or interstellar origin, to highly superthermal energies. (5) Precursor electrons: Ambient solar electrons (greater than or equal to few tens of keV) that exist in the outer heliosphere ca form a broad precursor, several days wide, that is upstream of the termination shock and potentially observable a few months prior to the shock crossing. (6) Solar wind velocity at Voyager 1: We can use LECP ion data to obtain the solar wind velocity at Voyager 1, enabling us to provide critical measurement of the plasma flow as we approach and encounter the termination shock and other regions (necessary due to the partial failure of the Voyager 1 PLS experiment). The work of the LECP investigator team during the VIM will include: (1) Continuing operations with regard to the receipt, processing, verification, cataloging, display, and distribution of the data from the LECP instruments on Voyager 1 and 2, (2) Monitoring the health and performance of the LECP instruments, and evaluating and characterizing the response of the LECP instruments to various energetic particle and plasma environments, (3) Participating in, and supporting Voyager Project planning exercises and other coordinated activities relevant to exploration of the outer heliosphere, (4) Developing analysis techniques and operational procedures suitable for searching for and characterizing the boundaries and unique regions of the outher heliosphere, (5) Continuing the preparation of data sets appropriate for submission to the National Space Sciences Data Center (NSSDC) and, where appropriate, the Planetary Data System (PDS), (6) Maintaining direct Web access to online LECP data through the JHU/APL Voyager LECP home page, (7) Performing scientific evaluations of the Voyager 1 and 2 LECP data sets in conjunction with other data sets and other investigators, with particular focus on the outer regions of the heliosphere, and (8) Publishing the results of these evaluations in the scientific literature and presenting the results in scientific conferences

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

COVID-19 progression and convalescence in common variable immunodeficiency patients shows incomplete adaptive responses and persistent inflammasome activation

Patients with common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, are characterized by hypogammaglobulinemia, poorly protective vaccine titers and increased susceptibility to infections. New pathogens such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), might constitute a particular threat to these immunocompromised patients since many of them experience a slower recovery and do not achieve full response to SARS-CoV-2 vaccines. To define the molecular basis of the altered immune responses caused by SARS-CoV-2 infection in CVID patients, we generated longitudinal single-cell datasets of peripheral blood immune cells along viral infection and recovery. We sampled the same individuals before, during and after SARS-CoV-2 infection to model their specific immune response dynamics while removing donor variability. We observed that COVID-19 CVID patients show defective canonical NF-κB pathway activation and dysregulated expression of BCR-related genes in naïve B cells, as well as enhanced cytotoxic activity but incomplete cytokine response in NK and T cells. Moreover, monocytes from COVID-19 CVID patients show persistent activation of several inflammasome-related genes, including the pyrin and NLRC4 inflammasomes. Our results shed light on the molecular basis of the prolonged clinical manifestations observed in these immunodeficient patients upon SARS-CoV-2 infection, which might illuminate the development of tailored treatments for COVID-19 CVID patients.We thank the CERCA Program/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This publication is part of the Human Cell Atlas: www.humancellatlas.org/publications. This study was funded by ”la Caixa” Foundation under the grant agreement LCF/PR/HR22/52420002, Spanish Ministry of Science and Innovation (grant number PID2020-117212RB-I00/AEI/10.13038/501100011033) (E.B.), by the Wellcome Trust Grant 206194 and 108413/A/15/D (R.V.-T.), Instituto de Salud Carlos III (ISCIII), Ref. AC18/00057, associated with i-PAD project (ERARE European Union program) (E.B.), and the Chan Zuckerberg Initiative (grant 2020-216799) (R.V.-T. and E.B.). This publication has also been supported by the Unstoppable campaign of the Josep Carreras Leukaemia Foundation. We are indebted to the donors for participating in this research.N

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

Orientia tsutsugamushi is the causal agent of scrub typhus, a public health problem in the Asia-Pacific region and a life-threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushi altered the expression of more than 4,500 genes, as demonstrated by microarray analysis. The expression of type I interferon, interferon-stimulated genes and genes associated with the M1 polarization of macrophages was significantly upregulated. O. tsutsugamushi also induced the expression of apoptosis-related genes and promoted cell death in a small percentage of monocytes. Live organisms were indispensable to the type I interferon response and apoptosis and enhanced the expression of M1-associated cytokines. These data were related to the transcriptional changes detected in mononuclear cells isolated from patients with scrub typhus. Here, the microarray analyses revealed the upregulation of 613 genes, which included interferon-related genes, and some features of M1 polarization were observed in these patients, similar to what was observed in O. tsutsugamushi-stimulated monocytes in vitro. This is the first report demonstrating that monocytes are clearly polarized in vitro and ex vivo following exposure to O. tsutsugamushi. These results would improve our understanding of the pathogenesis of scrub typhus, during which interferon-mediated activation of monocytes and their subsequent polarization into an M1 phenotype appear critical. This study may give us a clue of new tools for the diagnosis of patients with scrub typhus