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Sample records for sivmac239 challenge model

  1. Vaccination with Gag, Vif, and Nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239.

    Science.gov (United States)

    Martins, Mauricio A; Wilson, Nancy A; Piaskowski, Shari M; Weisgrau, Kim L; Furlott, Jessica R; Bonaldo, Myrna C; Veloso de Santana, Marlon G; Rudersdorf, Richard A; Rakasz, Eva G; Keating, Karen D; Chiuchiolo, Maria J; Piatak, Michael; Allison, David B; Parks, Christopher L; Galler, Ricardo; Lifson, Jeffrey D; Watkins, David I

    2014-07-01

    Broadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among several different vaccine constructs. Accordingly, we tested whether vaccinating rhesus macaques with "minigenes" encoding fragments of Gag, Vif, and Nef resulted in broadened cellular responses capable of controlling SIV replication. We delivered these minigenes through combinations of recombinant Mycobacterium bovis BCG (rBCG), electroporated recombinant DNA (rDNA) along with an interleukin-12 (IL-12)-expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D (rYF17D), and recombinant adenovirus serotype 5 (rAd5). Although priming with EP rDNA plus pIL-12 increased the breadth of vaccine-induced T-cell responses, this effect was likely due to the improved antigen delivery afforded by electroporation rather than modulation of immunodominance. Indeed, Mamu-A*01(+) vaccinees mounted CD8(+) T cells directed against only one subdominant epitope, regardless of the vaccination regimen. After challenge with SIVmac239, vaccine efficacy was limited to a modest reduction in set point in some of the groups and did not correlate with standard T-cell measurements. These findings suggest that broad T-cell responses elicited by conventional vectors may not be sufficient to substantially contain AIDS virus replication. Immunodominance poses a major obstacle to the generation of broadly targeted, HIV-specific cellular responses by vaccination. Here we attempted to circumvent this phenomenon and thereby broaden the repertoire of SIV-specific cellular responses by

  2. Effect of plasma viremia on apoptosis and immunophenotype of dendritic cells subsets in acute SIVmac239 infection of Chinese rhesus macaques.

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    Hou-Jun Xia

    Full Text Available Non-human primates such as Chinese rhesus macaques (Ch Rhs provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs in the peripheral blood of Ch Rhs: myeloid DCs (mDCs and plasmacytoid DCs (pDCs. In this study, two-color fluorescence-activated cell sorting (FACS analyses were used to identify the main DC subsets, namely CD1c(+ mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c(+ mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c(+ mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

  3. Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

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    Song Chen

    Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

  4. Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques

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    McDermott, Adrian B.; O'Connor, David H.; Fuenger, Sarah; Piaskowski, Shari; Martin, Sarah; Loffredo, John; Reynolds, Matthew; Reed, Jason; Furlott, Jessica; Jacoby, Timothy; Riek, Cara; Dodds, Elizabeth; Krebs, Kendall; Davies, Mary-Ellen; Schleif, William A.; Casimiro, Danilo R.; Shiver, John W.; Watkins, D. I.

    2005-01-01

    Adenovirus 5 (Ad5) vectors show promise as human immunodeficiency virus vaccine candidates. Indian rhesus macaques vaccinated with Ad5-gag controlled simian-human immunodeficiency virus SHIV89.6P viral replication in the absence of Env immunogens that might elicit humoral immunity. Here we immunized 15 macaques using either a homologous Ad5-gag/Ad5-gag (Ad5/Ad5) or a heterologous DNA-gag/Ad5-gag (DNA/Ad5) prime-boost regimen and challenged them with a high dose of simian immunodeficiency virus SIVmac239. Macaques vaccinated with the DNA/Ad5 regimen experienced a brief viral load nadir of less than 10,000 viral copies per ml blood plasma that was not seen in Mamu-A*01-negative DNA/Ad5 vaccinees, Mamu-A*01-positive Ad5/Ad5 vaccinees, or vaccine-naive controls. Interestingly, most of these animals were not durably protected from disease progression when challenged with SIVmac239. To investigate the reasons underlying this short-lived vaccine effect, we investigated breadth of the T-cell response, immunogenetic background, and viral escape from CD8+ lymphocytes that recognize immunodominant T-cell epitopes. We show that these animals do not mount unusually broad cellular immune response, nor do they express unusual major histocompatibility complex class I alleles. Viral recrudescence occurred in four of the five Mamu-A*01-positive vaccinated macaques. However, only a single animal in this group demonstrated viral escape in the immunodominant Gag181-189CM9 response. These results suggest that viral “breakthrough” in vaccinated animals and viral escape are not inextricably linked and underscore the need for additional research into the mechanisms of vaccine failure. PMID:16306626

  5. Crystallization and preliminary X-ray crystallographic analysis of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an immunodominant SIVmac239 Env epitope

    International Nuclear Information System (INIS)

    Gao, Feng; Bao, Jinku

    2013-01-01

    A primitive monoclinic crystal of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an SIVmac239 Env peptide was obtained and belonged to space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. The crystal diffracted to 2.55 Å resolution. Long-term nonprogression during simian immunodeficiency virus (SIV) infection has been strongly associated with the major histocompatibility complex (MHC) class I allele Mamu-B*17. Here, a complex of rhesus macaque Mamu-B*17 with rhesus macaque β 2 -microglobulin (β 2 m) and an immunodominant peptide (SIVmac239 Env241–251; LRCNDTNYSGF; Env LF11) derived from the SIV Env protein was crystallized by the hanging-drop method using PEG 3350 as a precipitating agent. The crystals belonged to the primitive monoclinic space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. Assuming the presence of one molecule in the asymmetric unit, the Matthews coefficient and solvent content were calculated to be 2.96 Å 3 Da −1 and 58.5%, respectively

  6. A novel SIV gag-specific CD4(+)T-cell clone suppresses SIVmac239 replication in CD4(+)T cells revealing the interplay between antiviral effector cells and their infected targets.

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    Ayala, Victor I; Trivett, Matthew T; Coren, Lori V; Jain, Sumiti; Bohn, Patrick S; Wiseman, Roger W; O'Connor, David H; Ohlen, Claes; Ott, David E

    2016-06-01

    To study CD4(+)T-cell suppression of AIDS virus replication, we isolated nine rhesus macaque SIVGag-specific CD4(+)T-cell clones. One responding clone, Gag68, produced a typical cytotoxic CD8(+)T-cell response: induction of intracellular IFN-γ, MIP-1α, MIP-1β, and CD107a degranulation. Gag68 effectively suppressed the spread of SIVmac239 in CD4(+)T cells with a corresponding reduction of infected Gag68 effector cells, suggesting that CD4(+)effectors need to suppress their own infection in addition to their targets to be effective. Gag68 TCR cloning and gene transfer into CD4(+)T cells enabled additional experiments with this unique specificity after the original clone senesced. Our data supports the idea that CD4(+)T cells can directly limit AIDS virus spread in T cells. Furthermore, Gag68 TCR transfer into CD4(+)T-cell clones with differing properties holds promise to better understand the suppressive effector mechanisms used by this important component of the antiviral response using the rhesus macaque model. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Immunogenicity of seven new recombinant yellow fever viruses 17D expressing fragments of SIVmac239 Gag, Nef, and Vif in Indian rhesus macaques.

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    Mauricio A Martins

    Full Text Available An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV. Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (rYF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIVmac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5 vectors resulted in robust expansion of SIV-specific CD8(+ T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4(+ cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D - a clinically relevant vaccine vector - can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D

  8. Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA protein in a human immunodeficiency virus type 1 (HIV-1 derivative that has simian immunodeficiency virus (SIVmac239 vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

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    Adachi Akio

    2009-08-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5 of capsid protein (CA and the entire SIVmac239 vif gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7 of HIV type 2 (HIV-2 CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α. Results In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and vif with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells. Conclusion We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys in vivo.

  9. A Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239.

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    Powell, Rebecca L R; Ouellette, Ian; Lindsay, Ross W; Parks, Christopher L; King, C Richter; McDermott, Adrian B; Morrow, Gavin

    2013-06-01

    Results from recent HIV-1 vaccine studies have indicated that high serum antibody (Ab) titers may not be necessary for Ab-mediated protection, and that Abs localized to mucosal sites might be critical for preventing infection. Enzyme-linked immunosorbent assay (ELISA) has been used for decades as the gold standard for Ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of Abs. In this study, we assessed the Bio-Plex(®) Suspension Array System for the detection of simian immunodeficiency virus (SIV)-specific Abs in rhesus macaques (RMs) chronically infected with SIV, whose serum or mucosal SIV-specific Ab titers were negative by ELISA. We developed a SIVmac239-specific 4-plex bead array for the simultaneous detection of Abs binding to Env, Gag, Pol, and Nef. The 4-plex assay was used to quantify SIV-specific serum IgG and rectal swab IgA titers from control (SIV-naive) and SIVmac239-infected RMs. The Bio-Plex assay specifically detected anti-SIV Abs in specimens from SIV-infected animals for all four analytes when compared to SIV-naive control samples (p≤0.04). Furthermore, in 70% of Env and 79% of Gag ELISA-negative serum samples, specific Ab was detected using the Bio-Plex assay. Similarly, 71% of Env and 48% of Gag ELISA-negative rectal swab samples were identified as positive using the Bio-Plex assay. Importantly, assay specificity (i.e., probability of true positives) was comparable to ELISA (94%-100%). The results reported here indicate that microsphere-based methods provide a substantial improvement over ELISA for the detection of Ab responses, aid in detecting specific Abs when analyzing samples containing low levels of Abs, such as during the early stages of a vaccine trial, and may be valuable in attempts to link protective efficacy of vaccines with induced Ab responses.

  10. A novel protective MHC-I haplotype not associated with dominant Gag-specific CD8+ T-cell responses in SIVmac239 infection of Burmese rhesus macaques.

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    Naofumi Takahashi

    Full Text Available Several major histocompatibility complex class I (MHC-I alleles are associated with lower viral loads and slower disease progression in human immunodeficiency virus (HIV and simian immunodeficiency virus (SIV infections. Immune-correlates analyses in these MHC-I-related HIV/SIV controllers would lead to elucidation of the mechanism for viral control. Viral control associated with some protective MHC-I alleles is attributed to CD8+ T-cell responses targeting Gag epitopes. We have been trying to know the mechanism of SIV control in multiple groups of Burmese rhesus macaques sharing MHC-I genotypes at the haplotype level. Here, we found a protective MHC-I haplotype, 90-010-Id (D, which is not associated with dominant Gag-specific CD8+ T-cell responses. Viral loads in five D+ animals became significantly lower than those in our previous cohorts after 6 months. Most D+ animals showed predominant Nef-specific but not Gag-specific CD8+ T-cell responses after SIV challenge. Further analyses suggested two Nef-epitope-specific CD8+ T-cell responses exerting strong suppressive pressure on SIV replication. Another set of five D+ animals that received a prophylactic vaccine using a Gag-expressing Sendai virus vector showed significantly reduced viral loads compared to unvaccinated D+ animals at 3 months, suggesting rapid SIV control by Gag-specific CD8+ T-cell responses in addition to Nef-specific ones. These results present a pattern of SIV control with involvement of non-Gag antigen-specific CD8+ T-cell responses.

  11. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

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    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  12. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    International Nuclear Information System (INIS)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

    2016-01-01

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  13. Parasites may exit immunocompromised northern pig-tailed macaques (Macaca leonina) infected with SIVmac239.

    Science.gov (United States)

    Song, Tian-Zhang; Zhang, Ming-Xu; Xia, Yu-Jie; Xiao, Yu; Pang, Wei; Zheng, Yong-Tang

    2018-01-18

    Parasites can increase infection rates and pathogenicity in immunocompromised human immunodeficiency virus (HIV) patients. However, in vitro studies and epidemiological investigations also suggest that parasites might escape immunocompromised hosts during HIV infection. Due to the lack of direct evidence from animal experiments, the effects of parasitic infections on immunocompromised hosts remain unclear. Here, we detected 14 different parasites in six northern pig-tailed macaques (NPMs) before or at the 50th week of simian immunodeficiency virus (SIV) infection by ELISA. The NPMs all carried parasites before viral injection. At the 50th week after viral injection, the individuals with negative results in parasitic detection (i.e., 08247 and 08287) were characterized as the Parasites Exit (PE) group, with the other individuals (i.e., 09203, 09211, 10205, and 10225) characterized as the Parasites Remain (PR) group. Compared with the PR group, the NPMs in the PE group showed higher viral loads, lower CD4 + T cells counts, and lower CD4/CD8 rates. Additionally, the PE group had higher immune activation and immune exhaustion of both CD4 + and CD8 + T cells. Pathological observation showed greater injury to the liver, cecum, colon, spleen, and mesenteric lymph nodes in the PE group. This study showed more seriously compromised immunity in the PE group, strongly indicating that parasites might exit an immunocompromised host.

  14. Parasites may exit immunocompromised northern pig-tailed macaques (Macaca leonina infected with SIVmac239

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    Tian-Zhang Song

    2018-01-01

    Full Text Available Parasites can increase infection rates andpathogenicity in immunocompromised humanimmunodeficiency virus (HIV patients. However, invitro studies and epidemiological investigationsalso suggest that parasites might escapeimmunocompromised hosts during HIV infection.Due to the lack of direct evidence from animalexperiments, the effects of parasitic infections onimmunocompromised hosts remain unclear. Here,we detected 14 different parasites in six northernpig-tailed macaques (NPMs before or during the50th week of post-simian immunodeficiency virus(SIV infection by ELISA. The NPMs all carriedparasites before viral injection. At the 50th week afterviral injection, the individuals with negative resultsin parasitic detection (i.e., 08247 and 08287 werecharacterized as the Parasites Exit (PE group, withthe other individuals (i.e., 09203, 09211, 10205, and10225 characterized as the Parasites Remain (PRgroup. Compared with the PR group, the NPMs in thePE group showed higher viral loads, lower CD4+ Tcells counts, and lower CD4/CD8 rates. Additionally,the PE group had higher immune activation andimmune exhaustion of both CD4+ and CD8+ T cells.Pathological observation showed greater injury tothe liver, cecum, colon, spleen, and mesentericlymph nodes in the PE group. This study showedmore seriously compromised immunity in the PEgroup, strongly indicating that parasites might exit animmunocompromised host.

  15. Hydropower Modeling Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Stoll, Brady [National Renewable Energy Lab. (NREL), Golden, CO (United States); Andrade, Juan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Cohen, Stuart [National Renewable Energy Lab. (NREL), Golden, CO (United States); Brinkman, Greg [National Renewable Energy Lab. (NREL), Golden, CO (United States); Brancucci Martinez-Anido, Carlo [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-04-19

    Hydropower facilities are important assets for the electric power sector and represent a key source of flexibility for electric grids with large amounts of variable generation. As variable renewable generation sources expand, understanding the capabilities and limitations of the flexibility from hydropower resources is important for grid planning. Appropriately modeling these resources, however, is difficult because of the wide variety of constraints these plants face that other generators do not. These constraints can be broadly categorized as environmental, operational, and regulatory. This report highlights several key issues involving incorporating these constraints when modeling hydropower operations in terms of production cost and capacity expansion. Many of these challenges involve a lack of data to adequately represent the constraints or issues of model complexity and run time. We present several potential methods for improving the accuracy of hydropower representation in these models to allow for a better understanding of hydropower's capabilities.

  16. Challenges in edge modeling

    International Nuclear Information System (INIS)

    Schneider, R.

    2007-01-01

    Fluid models like B2, UEDGE or EDGE2D are the working horses for scrape-off layer physics, both for design and experimental support. The concept of a numerical tokamak, aiming at a predictive code for ITER, triggers the need to re-assess the available tools and their necessary extensions. These additional physics issues will be summarized from a personal point-of-view. Depending on the specific problem, several complexity levels of scrape-off layer models will be needed. Therefore, a hierarchy of tools is necessary, which will be discussed. Furthermore, the experience existing in other scientific fields with multi-scale problems and modeling should be used. Here, the coupling of different length and time scales are in particular of interest for fusion problems. (author)

  17. Challenges in horizontal model integration.

    Science.gov (United States)

    Kolczyk, Katrin; Conradi, Carsten

    2016-03-11

    Systems Biology has motivated dynamic models of important intracellular processes at the pathway level, for example, in signal transduction and cell cycle control. To answer important biomedical questions, however, one has to go beyond the study of isolated pathways towards the joint study of interacting signaling pathways or the joint study of signal transduction and cell cycle control. Thereby the reuse of established models is preferable, as it will generally reduce the modeling effort and increase the acceptance of the combined model in the field. Obtaining a combined model can be challenging, especially if the submodels are large and/or come from different working groups (as is generally the case, when models stored in established repositories are used). To support this task, we describe a semi-automatic workflow based on established software tools. In particular, two frequent challenges are described: identification of the overlap and subsequent (re)parameterization of the integrated model. The reparameterization step is crucial, if the goal is to obtain a model that can reproduce the data explained by the individual models. For demonstration purposes we apply our workflow to integrate two signaling pathways (EGF and NGF) from the BioModels Database.

  18. The 24-Hour Mathematical Modeling Challenge

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    Galluzzo, Benjamin J.; Wendt, Theodore J.

    2015-01-01

    Across the mathematics curriculum there is a renewed emphasis on applications of mathematics and on mathematical modeling. Providing students with modeling experiences beyond the ordinary classroom setting remains a challenge, however. In this article, we describe the 24-hour Mathematical Modeling Challenge, an extracurricular event that exposes…

  19. Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVΔnef Vaccination.

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    Natalia Guerra-Pérez

    Full Text Available Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Δnef (SIVΔnef vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt infection even in SIVΔnef-infected animals. Rectal SIVΔnef infection/vaccination protected 7 out of 7 SIVΔnef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVΔnef-negative macaques, while 1 out of 3 animals co-infected with SIVΔnef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings.

  20. Data Modeling Challenges of Advanced Interoperability.

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    Blobel, Bernd; Oemig, Frank; Ruotsalainen, Pekka

    2018-01-01

    Progressive health paradigms, involving many different disciplines and combining multiple policy domains, requires advanced interoperability solutions. This results in special challenges for modeling health systems. The paper discusses classification systems for data models and enterprise business architectures and compares them with the ISO Reference Architecture. On that basis, existing definitions, specifications and standards of data models for interoperability are evaluated and their limitations are discussed. Amendments to correctly use those models and to better meet the aforementioned challenges are offered.

  1. Five challenges in modelling interacting strain dynamics

    DEFF Research Database (Denmark)

    Wikramaratna, Paul S; Kurcharski, Adam; Gupta, Sunetra

    2015-01-01

    population models. Next we consider the nature of so-called “strain space”. We describe two key types of host heterogeneities, and explain how models could help generate a better understanding of their effects. Finally, for diseases with many strains, we consider the challenge of modelling how immunity...

  2. Five challenges in modelling interacting strain dynamics

    Directory of Open Access Journals (Sweden)

    Paul S. Wikramaratna

    2015-03-01

    Full Text Available Population epidemiological models where hosts can be infected sequentially by different strains have the potential to help us understand many important diseases. Researchers have in recent years started to develop and use such models, but the extra layer of complexity from multiple strains brings with it many technical challenges. It is therefore hard to build models which have realistic assumptions yet are tractable. Here we outline some of the main challenges in this area. First we begin with the fundamental question of how to translate from complex small-scale dynamics within a host to useful population models. Next we consider the nature of so-called “strain space”. We describe two key types of host heterogeneities, and explain how models could help generate a better understanding of their effects. Finally, for diseases with many strains, we consider the challenge of modelling how immunity accumulates over multiple exposures.

  3. Computer Aided Modelling – Opportunities and Challenges

    DEFF Research Database (Denmark)

    Cameron, Ian; Gani, Rafiqul

    2011-01-01

    -based solutions to significant problems? The important issues of workflow and data flow are discussed together with fit-for-purpose model development. As well, the lack of tools around multiscale modelling provides opportunities for the development of efficient tools to address such challenges. The ability...

  4. Big data business models: Challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Ralph Schroeder

    2016-12-01

    Full Text Available This paper, based on 28 interviews from a range of business leaders and practitioners, examines the current state of big data use in business, as well as the main opportunities and challenges presented by big data. It begins with an account of the current landscape and what is meant by big data. Next, it draws distinctions between the ways organisations use data and provides a taxonomy of big data business models. We observe a variety of different business models, depending not only on sector, but also on whether the main advantages derive from analytics capabilities or from having ready access to valuable data sources. Some major challenges emerge from this account, including data quality and protectiveness about sharing data. The conclusion discusses these challenges, and points to the tensions and differing perceptions about how data should be governed as between business practitioners, the promoters of open data, and the wider public.

  5. Computational challenges in modeling gene regulatory events.

    Science.gov (United States)

    Pataskar, Abhijeet; Tiwari, Vijay K

    2016-10-19

    Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.

  6. Eight challenges for network epidemic models

    Directory of Open Access Journals (Sweden)

    Lorenzo Pellis

    2015-03-01

    Full Text Available Networks offer a fertile framework for studying the spread of infection in human and animal populations. However, owing to the inherent high-dimensionality of networks themselves, modelling transmission through networks is mathematically and computationally challenging. Even the simplest network epidemic models present unanswered questions. Attempts to improve the practical usefulness of network models by including realistic features of contact networks and of host–pathogen biology (e.g. waning immunity have made some progress, but robust analytical results remain scarce. A more general theory is needed to understand the impact of network structure on the dynamics and control of infection. Here we identify a set of challenges that provide scope for active research in the field of network epidemic models.

  7. Challenges in modelling nanoparticles for drug delivery

    International Nuclear Information System (INIS)

    Barnard, Amanda S

    2016-01-01

    Although there have been significant advances in the fields of theoretical condensed matter and computational physics, when confronted with the complexity and diversity of nanoparticles available in conventional laboratories a number of modeling challenges remain. These challenges are generally shared among application domains, but the impacts of the limitations and approximations we make to overcome them (or circumvent them) can be more significant one area than another. In the case of nanoparticles for drug delivery applications some immediate challenges include the incompatibility of length-scales, our ability to model weak interactions and solvation, the complexity of the thermochemical environment surrounding the nanoparticles, and the role of polydispersivity in determining properties and performance. Some of these challenges can be met with existing technologies, others with emerging technologies including the data-driven sciences; some others require new methods to be developed. In this article we will briefly review some simple methods and techniques that can be applied to these (and other) challenges, and demonstrate some results using nanodiamond-based drug delivery platforms as an exemplar. (topical review)

  8. Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

    Science.gov (United States)

    Lakhashe, Samir K; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B; Dipasquale, Janet M; Hemashettar, Girish; Yoon, John K; Rasmussen, Robert A; Yang, Feng; Lee, Sandra J; Montefiori, David C; Novembre, Francis J; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu-Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R; Robert-Guroff, Marjorie; Johnson, Welkin E; Lieberman, Judy; Ruprecht, Ruth M

    2011-08-05

    We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus > 90%; these RM also had strong SIV Gag-specific proliferation of CD8⁺ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4⁺ T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Challenges in Continuum Modelling of Intergranular Fracture

    DEFF Research Database (Denmark)

    Coffman, Valerie; Sethna, James P.; Ingraffea, A. R.

    2011-01-01

    of grain boundaries, but also in crucial ways on edges, corners and triple junctions of even greater geometrical complexity. To address the first two challenges, we explore the physical underpinnings for creating functional forms to capture the hierarchical commensurability structure in the grain boundary......Intergranular fracture in polycrystals is often simulated by finite elements coupled to a cohesive zone model for the interfaces, requiring cohesive laws for grain boundaries as a function of their geometry. We discuss three challenges in understanding intergranular fracture in polycrystals. First...... properties. To address the last challenge, we demonstrate a method for atomistically extracting the fracture properties of geometrically complex local regions on the fly from within a finite element simulation....

  10. Seven challenges in modeling vaccine preventable diseases

    Directory of Open Access Journals (Sweden)

    C.J.E. Metcalf

    2015-03-01

    Full Text Available Vaccination has been one of the most successful public health measures since the introduction of basic sanitation. Substantial mortality and morbidity reductions have been achieved via vaccination against many infections, and the list of diseases that are potentially controllable by vaccines is growing steadily. We introduce key challenges for modeling in shaping our understanding and guiding policy decisions related to vaccine preventable diseases.

  11. Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Christine M Fennessey

    2017-05-01

    Full Text Available HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART for 82 days starting on day 6 post-infection (study 1. Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2. Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound

  12. Aeronautical telecommunications network advances, challenges, and modeling

    CERN Document Server

    Musa, Sarhan M

    2015-01-01

    Addresses the Challenges of Modern-Day Air Traffic Air traffic control (ATC) directs aircraft in the sky and on the ground to safety, while the Aeronautical Telecommunications Network (ATN) comprises all systems and phases that assist in aircraft departure and landing. The Aeronautical Telecommunications Network: Advances, Challenges, and Modeling focuses on the development of ATN and examines the role of the various systems that link aircraft with the ground. The book places special emphasis on ATC-introducing the modern ATC system from the perspective of the user and the developer-and provides a thorough understanding of the operating mechanism of the ATC system. It discusses the evolution of ATC, explaining its structure and how it works; includes design examples; and describes all subsystems of the ATC system. In addition, the book covers relevant tools, techniques, protocols, and architectures in ATN, including MIPv6, air traffic control (ATC), security of air traffic management (ATM), very-high-frequenc...

  13. Eight challenges in modelling infectious livestock diseases

    Directory of Open Access Journals (Sweden)

    E. Brooks-Pollock

    2015-03-01

    Full Text Available The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock diseases suffers simultaneously from a wealth and a lack of data. On the one hand, the ability to conduct transmission experiments, detailed within-host studies and track individual animals between geocoded locations make livestock diseases a particularly rich potential source of realistic data for illuminating biological mechanisms of transmission and conducting explicit analyses of contact networks. On the other hand, scarcity of funding, as compared to human diseases, often results in incomplete and partial data for many livestock diseases and regions of the world. In this overview of challenges in livestock disease modelling, we highlight eight areas unique to livestock that, if addressed, would mark major progress in the area.

  14. Collaborative Inquiry Learning: Models, tools, and challenges

    Science.gov (United States)

    Bell, Thorsten; Urhahne, Detlef; Schanze, Sascha; Ploetzner, Rolf

    2010-02-01

    Collaborative inquiry learning is one of the most challenging and exciting ventures for today's schools. It aims at bringing a new and promising culture of teaching and learning into the classroom where students in groups engage in self-regulated learning activities supported by the teacher. It is expected that this way of learning fosters students' motivation and interest in science, that they learn to perform steps of inquiry similar to scientists and that they gain knowledge on scientific processes. Starting from general pedagogical reflections and science standards, the article reviews some prominent models of inquiry learning. This comparison results in a set of inquiry processes being the basis for cooperation in the scientific network NetCoIL. Inquiry learning is conceived in several ways with emphasis on different processes. For an illustration of the spectrum, some main conceptions of inquiry and their focuses are described. In the next step, the article describes exemplary computer tools and environments from within and outside the NetCoIL network that were designed to support processes of collaborative inquiry learning. These tools are analysed by describing their functionalities as well as effects on student learning known from the literature. The article closes with challenges for further developments elaborated by the NetCoIL network.

  15. Modeling for Ecosystem Services: Challenges and Opportunities

    Science.gov (United States)

    Guswa, A. J.; Brauman, K. A.; Ghile, Y.

    2012-12-01

    Ecosystem services are those values provided to human society by the structure and processes of ecosystems and landscapes. Water-related services include the transformation of precipitation impulses into supplies of water for hydropower, irrigation, and industrial and municipal uses, the retention and removal of applied nutrients and pollutants, flood-damage mitigation, recreation, and the provision of cultural and aesthetic values. Incorporation of changes to the value of these services in land-use planning and decision making requires identification of the relevant services, engagement of stakeholders, knowledge of how land-use changes impact water quality, quantity, and timing, and mechanisms for putting value on the hydrologic and biogeochemical changes. We present three examples that highlight the characteristics, challenges, and opportunities associated with prototypical decisions that incorporate ecosystem services values: scenario analysis, payment for ecosystem services, and optimal spatial planning. Through these examples, we emphasize the challenges of data availability, model resolution and complexity, and attribution of value. We also provide some suggestions for ways forward.

  16. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia

    2017-11-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  17. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia; Pluta, Dustin; Shen, Tong; Chen, Chuansheng; Xue, Gui; Ombao, Hernando

    2017-01-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible

  18. Integrated Environmental Modelling: Human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  19. Challenges in Modeling of the Global Atmosphere

    Science.gov (United States)

    Janjic, Zavisa; Djurdjevic, Vladimir; Vasic, Ratko; Black, Tom

    2015-04-01

    ") with significant amplitudes can develop. Due to their large scales, that are comparable to the scales of the dominant Rossby waves, such fictitious solutions are hard to identify and remove. Another new challenge on the global scale is that the limit of validity of the hydrostatic approximation is rapidly being approached. Having in mind the sensitivity of extended deterministic forecasts to small disturbances, we may need global non-hydrostatic models sooner than we think. The unified Non-hydrostatic Multi-scale Model (NMMB) that is being developed at the National Centers for Environmental Prediction (NCEP) as a part of the new NOAA Environmental Modeling System (NEMS) will be discussed as an example. The non-hydrostatic dynamics were designed in such a way as to avoid over-specification. The global version is run on the latitude-longitude grid, and the polar filter selectively slows down the waves that would otherwise be unstable. The model formulation has been successfully tested on various scales. A global forecasting system based on the NMMB has been run in order to test and tune the model. The skill of the medium range forecasts produced by the NMMB is comparable to that of other major medium range models. The computational efficiency of the global NMMB on parallel computers is good.

  20. Post-infection immunodeficiency virus control by neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Yamamoto

    Full Text Available BACKGROUND: Unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (NAbs, primary HIV infections are not met with such potent and early antibody responses. This brings into question if or how the presence of potent antibodies can contribute to primary HIV control, but protective efficacies of antiviral antibodies in primary HIV infections have remained elusive; and, it has been speculated that even NAb induction could have only a limited suppressive effect on primary HIV replication once infection is established. Here, in an attempt to answer this question, we examined the effect of passive NAb immunization post-infection on primary viral replication in a macaque AIDS model. METHODS AND FINDINGS: The inoculums for passive immunization with simian immunodeficiency virus mac239 (SIVmac239-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced T cell priming. CONCLUSIONS: Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for

  1. Toxicokinetic modeling challenges for aquatic nanotoxicology

    Directory of Open Access Journals (Sweden)

    Wei-Yu eChen

    2016-01-01

    Full Text Available Nanotoxicity has become of increasing concern since the rapid development of metal nanoparticles (NPs. Aquatic nanotoxicity depends on crucial qualitative and quantitative properties of nanomaterials that induce adverse effects on subcellular, tissue, and organ level. The dose-response effects of size-dependent metal NPs, however, are not well investigated in aquatic organisms. In order to determine the uptake and elimination rate constants for metal NPs in the metabolically active/ detoxified pool of tissues, a one-compartmental toxicokinetic model can be applied when subcellular partitioning of metal NPs data would be available. The present review is an attempt to describe the nano-characteristics of toxicokinetics and subcellular partitioning on aquatic organisms with the help of the mechanistic modeling for NP size-dependent physiochemical properties and parameters. Physiologically-based pharmacokinetic (PBPK models can provide an effective tool to estimate the time course of NP accumulation in target organs and is useful in quantitative risk assessments. NP accumulation in fish should take into account different effects of different NP sizes to better understand tissue accumulative capacities and dynamics. The size-dependent NP partition coefficient is a crucial parameter that influences tissue accumulation levels in PBPK modeling. Further research is needed to construct the effective systems-level oriented toxicokinetic model that can provide a useful tool to develop quantitatively the robustly approximate relations that convey a better insight into the impacts of environmental metal NPs on subcellular and tissue/organ responses in aquatic organisms.

  2. Theorists reject challenge to standard model

    CERN Multimedia

    Adam, D

    2001-01-01

    Particle physicists are questioning results that appear to violate the Standard Model. There are concerns that there is not sufficient statistical significance and also charges that the comparison is being made with the 'most convenient' theoretical value for the muon's magnetic moment (1 page).

  3. GEOS Atmospheric Model: Challenges at Exascale

    Science.gov (United States)

    Putman, William M.; Suarez, Max J.

    2017-01-01

    The Goddard Earth Observing System (GEOS) model at NASA's Global Modeling and Assimilation Office (GMAO) is used to simulate the multi-scale variability of the Earth's weather and climate, and is used primarily to assimilate conventional and satellite-based observations for weather forecasting and reanalysis. In addition, assimilations coupled to an ocean model are used for longer-term forecasting (e.g., El Nino) on seasonal to interannual times-scales. The GMAO's research activities, including system development, focus on numerous time and space scales, as detailed on the GMAO website, where they are tabbed under five major themes: Weather Analysis and Prediction; Seasonal-Decadal Analysis and Prediction; Reanalysis; Global Mesoscale Modeling, and Observing System Science. A brief description of the GEOS systems can also be found at the GMAO website. GEOS executes as a collection of earth system components connected through the Earth System Modeling Framework (ESMF). The ESMF layer is supplemented with the MAPL (Modeling, Analysis, and Prediction Layer) software toolkit developed at the GMAO, which facilitates the organization of the computational components into a hierarchical architecture. GEOS systems run in parallel using a horizontal decomposition of the Earth's sphere into processing elements (PEs). Communication between PEs is primarily through a message passing framework, using the message passing interface (MPI), and through explicit use of node-level shared memory access via the SHMEM (Symmetric Hierarchical Memory access) protocol. Production GEOS weather prediction systems currently run at 12.5-kilometer horizontal resolution with 72 vertical levels decomposed into PEs associated with 5,400 MPI processes. Research GEOS systems run at resolutions as fine as 1.5 kilometers globally using as many as 30,000 MPI processes. Looking forward, these systems can be expected to see a 2 times increase in horizontal resolution every two to three years, as well as

  4. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Directory of Open Access Journals (Sweden)

    Iskra Tuero

    2015-08-01

    Full Text Available Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC

  5. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

    Science.gov (United States)

    Tuero, Iskra; Mohanram, Venkatramanan; Musich, Thomas; Miller, Leia; Vargas-Inchaustegui, Diego A; Demberg, Thorsten; Venzon, David; Kalisz, Irene; Kalyanaraman, V S; Pal, Ranajit; Ferrari, Maria Grazia; LaBranche, Celia; Montefiori, David C; Rao, Mangala; Vaccari, Monica; Franchini, Genoveffa; Barnett, Susan W; Robert-Guroff, Marjorie

    2015-08-01

    Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males) was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males) received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC) in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized) remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC and ADCP

  6. Transnational nursing programs: models, advantages and challenges.

    Science.gov (United States)

    Wilson, Michael

    2002-07-01

    Conducting transnational programs can be a very rewarding activity for a School, Faculty or University. Apart from increasing the profile of the university, the conduct of transnational programs can also provide the university with openings for business opportunities, consultative activities, and collaborative research. It can also be a costly exercise placing an enormous strain on limited resources with little reward for the provider. Transnational ventures can become nonviable entities in a very short period of time due to unanticipated global economic trends. Transnational courses offered by Faculties of Business and Computing are commonplace, however, there is a growing number of health science programs, particularly nursing that are being offered transnational. This paper plans an overview of several models employed for the delivery of transnational nursing courses and discusses several key issues pertaining to conducting courses outside the host university's country.

  7. Value Creation Challenges in Multichannel Retail Business Models

    Directory of Open Access Journals (Sweden)

    Mika Yrjölä

    2014-08-01

    Full Text Available Purpose: The purpose of the paper is to identify and analyze the challenges of value creation in multichannel retail business models. Design/methodology/approach: With the help of semi-structured interviews with top executives from different retailing environments, this study introduces a model of value creation challenges in the context of multichannel retailing. The challenges are analyzed in terms of three retail business model elements, i.e., format, activities, and governance. Findings: Adopting a multichannel retail business model requires critical rethinking of the basic building blocks of value creation. First of all, as customers effortlessly move between multiple channels, multichannel formats can lead to a mismatch between customer and firm value. Secondly, retailers face pressures to use their activities to form integrated total offerings to customers. Thirdly, multiple channels might lead to organizational silos with conflicting goals. A careful orchestration of value creation is needed to determine the roles and incentives of the channel parties involved. Research limitations/implications: In contrast to previous business model literature, this study did not adopt a network-centric view. By embracing the boundary-spanning nature of the business model, other challenges and elements might have been discovered (e.g., challenges in managing relationships with suppliers. Practical implications: As a practical contribution, this paper has analyzed the challenges retailers face in adopting multichannel business models. Customer tendencies for showrooming behavior highlight the need for generating efficient lock-in strategies. Customized, personal offers and information are ways to increase customer value, differentiate from competition, and achieve lock-in. Originality/value: As a theoretical contribution, this paper empirically investigates value creation challenges in a specific context, lowering the level of abstraction in the mostly

  8. Geospace environment modeling 2008--2009 challenge: Dst index

    Science.gov (United States)

    Rastätter, L.; Kuznetsova, M.M.; Glocer, A.; Welling, D.; Meng, X.; Raeder, J.; Wittberger, M.; Jordanova, V.K.; Yu, Y.; Zaharia, S.; Weigel, R.S.; Sazykin, S.; Boynton, R.; Wei, H.; Eccles, V.; Horton, W.; Mays, M.L.; Gannon, J.

    2013-01-01

    This paper reports the metrics-based results of the Dst index part of the 2008–2009 GEM Metrics Challenge. The 2008–2009 GEM Metrics Challenge asked modelers to submit results for four geomagnetic storm events and five different types of observations that can be modeled by statistical, climatological or physics-based models of the magnetosphere-ionosphere system. We present the results of 30 model settings that were run at the Community Coordinated Modeling Center and at the institutions of various modelers for these events. To measure the performance of each of the models against the observations, we use comparisons of 1 hour averaged model data with the Dst index issued by the World Data Center for Geomagnetism, Kyoto, Japan, and direct comparison of 1 minute model data with the 1 minute Dst index calculated by the United States Geological Survey. The latter index can be used to calculate spectral variability of model outputs in comparison to the index. We find that model rankings vary widely by skill score used. None of the models consistently perform best for all events. We find that empirical models perform well in general. Magnetohydrodynamics-based models of the global magnetosphere with inner magnetosphere physics (ring current model) included and stand-alone ring current models with properly defined boundary conditions perform well and are able to match or surpass results from empirical models. Unlike in similar studies, the statistical models used in this study found their challenge in the weakest events rather than the strongest events.

  9. Challenges and opportunities for integrating lake ecosystem modelling approaches

    Science.gov (United States)

    Mooij, Wolf M.; Trolle, Dennis; Jeppesen, Erik; Arhonditsis, George; Belolipetsky, Pavel V.; Chitamwebwa, Deonatus B.R.; Degermendzhy, Andrey G.; DeAngelis, Donald L.; Domis, Lisette N. De Senerpont; Downing, Andrea S.; Elliott, J. Alex; Ruberto, Carlos Ruberto; Gaedke, Ursula; Genova, Svetlana N.; Gulati, Ramesh D.; Hakanson, Lars; Hamilton, David P.; Hipsey, Matthew R.; Hoen, Jochem 't; Hulsmann, Stephan; Los, F. Hans; Makler-Pick, Vardit; Petzoldt, Thomas; Prokopkin, Igor G.; Rinke, Karsten; Schep, Sebastiaan A.; Tominaga, Koji; Van Dam, Anne A.; Van Nes, Egbert H.; Wells, Scott A.; Janse, Jan H.

    2010-01-01

    A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and trait-based models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative

  10. Editorial: Modelling and computational challenges in granular materials

    NARCIS (Netherlands)

    Weinhart, Thomas; Thornton, Anthony Richard; Einav, Itai

    2015-01-01

    This is the editorial for the special issue on “Modelling and computational challenges in granular materials” in the journal on Computational Particle Mechanics (CPM). The issue aims to provide an opportunity for physicists, engineers, applied mathematicians and computational scientists to discuss

  11. International Students Take Up the Model Solar Car Challenge.

    Science.gov (United States)

    Wellington, Paul

    2000-01-01

    Introduces an event in which two school teams from Argentina and Vietnam joined those from each Australian state in a race of model cars powered by the sun that provides a challenging and exciting approach for students to apply their scientific and technological knowledge to design and build the most efficient vehicles possible to gain hands-on…

  12. Multiphysics software and the challenge to validating physical models

    International Nuclear Information System (INIS)

    Luxat, J.C.

    2008-01-01

    This paper discusses multi physics software and validation of physical models in the nuclear industry. The major challenge is to convert the general purpose software package to a robust application-specific solution. This requires greater knowledge of the underlying solution techniques and the limitations of the packages. Good user interfaces and neat graphics do not compensate for any deficiencies

  13. Editorial: Modelling and computational challenges in granular materials

    OpenAIRE

    Weinhart, Thomas; Thornton, Anthony Richard; Einav, Itai

    2015-01-01

    This is the editorial for the special issue on “Modelling and computational challenges in granular materials” in the journal on Computational Particle Mechanics (CPM). The issue aims to provide an opportunity for physicists, engineers, applied mathematicians and computational scientists to discuss the current progress and latest advancements in the field of advanced numerical methods and modelling of granular materials. The focus will be on computational methods, improved algorithms and the m...

  14. Modeling and Management of Big Data: Challenges and opportunities

    OpenAIRE

    Gil, David; Song, Il-Yeol

    2016-01-01

    The term Big Data denotes huge-volume, complex, rapid growing datasets with numerous, autonomous and independent sources. In these new circumstances Big Data bring many attractive opportunities; however, good opportunities are always followed by challenges, such as modelling, new paradigms, novel architectures that require original approaches to address data complexities. The purpose of this special issue on Modeling and Management of Big Data is to discuss research and experience in modellin...

  15. Crowd Sourcing for Challenging Technical Problems and Business Model

    Science.gov (United States)

    Davis, Jeffrey R.; Richard, Elizabeth

    2011-01-01

    imaging, microbial detection and even the use of pharmaceuticals for radiation protection. The internal challenges through NASA@Work drew over 6000 participants across all NASA centers. Challenges conducted by each NASA center elicited ideas and solutions from several other NASA centers and demonstrated rapid and efficient participation from employees at multiple centers to contribute to problem solving. Finally, on January 19, 2011, the SLSD conducted a workshop on open collaboration and innovation strategies and best practices through the newly established NASA Human Health and Performance Center (NHHPC). Initial projects will be described leading to a new business model for SLSD.

  16. Research Challenges in Financial Data Modeling and Analysis.

    Science.gov (United States)

    Alexander, Lewis; Das, Sanjiv R; Ives, Zachary; Jagadish, H V; Monteleoni, Claire

    2017-09-01

    Significant research challenges must be addressed in the cleaning, transformation, integration, modeling, and analytics of Big Data sources for finance. This article surveys the progress made so far in this direction and obstacles yet to be overcome. These are issues that are of interest to data-driven financial institutions in both corporate finance and consumer finance. These challenges are also of interest to the legal profession as well as to regulators. The discussion is relevant to technology firms that support the growing field of FinTech.

  17. Modelling across bioreactor scales: methods, challenges and limitations

    DEFF Research Database (Denmark)

    Gernaey, Krist

    that it is challenging and expensive to acquire experimental data of good quality that can be used for characterizing gradients occurring inside a large industrial scale bioreactor. But which model building methods are available? And how can one ensure that the parameters in such a model are properly estimated? And what......Scale-up and scale-down of bioreactors are very important in industrial biotechnology, especially with the currently available knowledge on the occurrence of gradients in industrial-scale bioreactors. Moreover, it becomes increasingly appealing to model such industrial scale systems, considering...

  18. Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities.

    Science.gov (United States)

    Bardhan, Jaydeep P

    2013-12-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

  19. Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities

    Science.gov (United States)

    Bardhan, Jaydeep P.

    2014-01-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics. PMID:25505358

  20. Gradient models in molecular biophysics: progress, challenges, opportunities

    Science.gov (United States)

    Bardhan, Jaydeep P.

    2013-12-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g., molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding nonlocal dielectric response. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain, and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost 40 years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The review concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

  1. The status and challenge of global fire modelling

    Science.gov (United States)

    Hantson, Stijn; Arneth, Almut; Harrison, Sandy P.; Kelley, Douglas I.; Prentice, I. Colin; Rabin, Sam S.; Archibald, Sally; Mouillot, Florent; Arnold, Steve R.; Artaxo, Paulo; Bachelet, Dominique; Ciais, Philippe; Forrest, Matthew; Friedlingstein, Pierre; Hickler, Thomas; Kaplan, Jed O.; Kloster, Silvia; Knorr, Wolfgang; Lasslop, Gitta; Li, Fang; Mangeon, Stephane; Melton, Joe R.; Meyn, Andrea; Sitch, Stephen; Spessa, Allan; van der Werf, Guido R.; Voulgarakis, Apostolos; Yue, Chao

    2016-06-01

    Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.

  2. Unfolding Challenges of Business Model Innovation towards Circular Economy

    DEFF Research Database (Denmark)

    Hvass, Kerli Kant

    2017-01-01

    of customers where it is important to see them as suppliers and co-producers of post-consumer value of products and materials. Finally, integrating circular economy strategies into business models may bring along radical changes to how companies perceive its products and relationships with customers and other...... model. The paper is based on empirical findings from a 34 month long qualitative case study of a leading Scandinavian fashion brand and the study followed an engaged scholarship strategy (Van de Ven, 2007). The findings identify issues and challenges that impact the successful implementation...

  3. Challenges in Materials Transformation Modeling for Polyolefins Industry

    Science.gov (United States)

    Lai, Shih-Yaw; Swogger, Kurt W.

    2004-06-01

    Unlike most published polymer processing and/or forming research, the transformation of polyolefins to fabricated articles often involves non-confined flow or so-called free surface flow (e.g. fiber spinning, blown films, and cast films) in which elongational flow takes place during a fabrication process. Obviously, the characterization and validation of extensional rheological parameters and their use to develop rheological constitutive models are the focus of polyolefins materials transformation research. Unfortunately, there are challenges that remain with limited validation for non-linear, non-isothermal constitutive models for polyolefins. Further complexity arises in the transformation of polyolefins in the elongational flow system as it involves stress-induced crystallization process. The complicated nature of elongational, non-linear rheology and non-isothermal crystallization kinetics make the development of numerical methods very challenging for the polyolefins materials forming modeling. From the product based company standpoint, the challenges of materials transformation research go beyond elongational rheology, crystallization kinetics and its numerical modeling. In order to make models useful for the polyolefin industry, it is critical to develop links between molecular parameters to both equipment and materials forming parameters. The recent advances in the constrained geometry catalysis and materials sciences understanding (INSITE technology and molecular design capability) has made industrial polyolefinic materials forming modeling more viable due to the fact that the molecular structure of the polymer can be well predicted and controlled during the polymerization. In this paper, we will discuss inter-relationship (models) among molecular parameters such as polymer molecular weight (Mw), molecular weight distribution (MWD), long chain branching (LCB), short chain branching (SCB or comonomer types and distribution) and their affects on shear and

  4. Six challenges in modelling for public health policy.

    Science.gov (United States)

    Metcalf, C J E; Edmunds, W J; Lessler, J

    2015-03-01

    The World Health Organisation's definition of public health refers to all organized measures to prevent disease, promote health, and prolong life among the population as a whole (World Health Organization, 2014). Mathematical modelling plays an increasingly important role in helping to guide the most high impact and cost-effective means of achieving these goals. Public health programmes are usually implemented over a long period of time with broad benefits to many in the community. Clinical trials are seldom large enough to capture these effects. Observational data may be used to evaluate a programme after it is underway, but have limited value in helping to predict the future impact of a proposed policy. Furthermore, public health practitioners are often required to respond to new threats, for which there is little or no previous data on which to assess the threat. Computational and mathematical models can help to assess potential threats and impacts early in the process, and later aid in interpreting data from complex and multifactorial systems. As such, these models can be critical tools in guiding public health action. However, there are a number of challenges in achieving a successful interface between modelling and public health. Here, we discuss some of these challenges. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Six challenges in modelling for public health policy

    Directory of Open Access Journals (Sweden)

    C.J.E. Metcalf

    2015-03-01

    Full Text Available The World Health Organisation's definition of public health refers to all organized measures to prevent disease, promote health, and prolong life among the population as a whole (World Health Organization, 2014. Mathematical modelling plays an increasingly important role in helping to guide the most high impact and cost-effective means of achieving these goals. Public health programmes are usually implemented over a long period of time with broad benefits to many in the community. Clinical trials are seldom large enough to capture these effects. Observational data may be used to evaluate a programme after it is underway, but have limited value in helping to predict the future impact of a proposed policy. Furthermore, public health practitioners are often required to respond to new threats, for which there is little or no previous data on which to assess the threat. Computational and mathematical models can help to assess potential threats and impacts early in the process, and later aid in interpreting data from complex and multifactorial systems. As such, these models can be critical tools in guiding public health action. However, there are a number of challenges in achieving a successful interface between modelling and public health. Here, we discuss some of these challenges.

  6. Citizen observations contributing to flood modelling: opportunities and challenges

    Directory of Open Access Journals (Sweden)

    T. H. Assumpção

    2018-02-01

    Full Text Available Citizen contributions to science have been successfully implemented in many fields, and water resources is one of them. Through citizens, it is possible to collect data and obtain a more integrated decision-making process. Specifically, data scarcity has always been an issue in flood modelling, which has been addressed in the last decades by remote sensing and is already being discussed in the citizen science context. With this in mind, this article aims to review the literature on the topic and analyse the opportunities and challenges that lie ahead. The literature on monitoring, mapping and modelling, was evaluated according to the flood-related variable citizens contributed to. Pros and cons of the collection/analysis methods were summarised. Then, pertinent publications were mapped into the flood modelling cycle, considering how citizen data properties (spatial and temporal coverage, uncertainty and volume are related to its integration into modelling. It was clear that the number of studies in the area is rising. There are positive experiences reported in collection and analysis methods, for instance with velocity and land cover, and also when modelling is concerned, for example by using social media mining. However, matching the data properties necessary for each part of the modelling cycle with citizen-generated data is still challenging. Nevertheless, the concept that citizen contributions can be used for simulation and forecasting is proved and further work lies in continuing to develop and improve not only methods for collection and analysis, but certainly for integration into models as well. Finally, in view of recent automated sensors and satellite technologies, it is through studies as the ones analysed in this article that the value of citizen contributions, complementing such technologies, is demonstrated.

  7. Citizen observations contributing to flood modelling: opportunities and challenges

    Science.gov (United States)

    Assumpção, Thaine H.; Popescu, Ioana; Jonoski, Andreja; Solomatine, Dimitri P.

    2018-02-01

    Citizen contributions to science have been successfully implemented in many fields, and water resources is one of them. Through citizens, it is possible to collect data and obtain a more integrated decision-making process. Specifically, data scarcity has always been an issue in flood modelling, which has been addressed in the last decades by remote sensing and is already being discussed in the citizen science context. With this in mind, this article aims to review the literature on the topic and analyse the opportunities and challenges that lie ahead. The literature on monitoring, mapping and modelling, was evaluated according to the flood-related variable citizens contributed to. Pros and cons of the collection/analysis methods were summarised. Then, pertinent publications were mapped into the flood modelling cycle, considering how citizen data properties (spatial and temporal coverage, uncertainty and volume) are related to its integration into modelling. It was clear that the number of studies in the area is rising. There are positive experiences reported in collection and analysis methods, for instance with velocity and land cover, and also when modelling is concerned, for example by using social media mining. However, matching the data properties necessary for each part of the modelling cycle with citizen-generated data is still challenging. Nevertheless, the concept that citizen contributions can be used for simulation and forecasting is proved and further work lies in continuing to develop and improve not only methods for collection and analysis, but certainly for integration into models as well. Finally, in view of recent automated sensors and satellite technologies, it is through studies as the ones analysed in this article that the value of citizen contributions, complementing such technologies, is demonstrated.

  8. Undergraduate students’ challenges with computational modelling in physics

    Directory of Open Access Journals (Sweden)

    Simen A. Sørby

    2012-12-01

    Full Text Available In later years, computational perspectives have become essential parts in several of the University of Oslo’s natural science studies. In this paper we discuss some main findings from a qualitative study of the computational perspectives’ impact on the students’ work with their first course in physics– mechanics – and their learning and meaning making of its contents. Discussions of the students’ learning of physics are based on sociocultural theory, which originates in Vygotsky and Bakhtin, and subsequent physics education research. Results imply that the greatest challenge for students when working with computational assignments is to combine knowledge from previously known, but separate contexts. Integrating knowledge of informatics, numerical and analytical mathematics and conceptual understanding of physics appears as a clear challenge for the students. We also observe alack of awareness concerning the limitations of physical modelling. The students need help with identifying the appropriate knowledge system or “tool set”, for the different tasks at hand; they need helpto create a plan for their modelling and to become aware of its limits. In light of this, we propose thatan instructive and dialogic text as basis for the exercises, in which the emphasis is on specification, clarification and elaboration, would be of potential great aid for students who are new to computational modelling.

  9. Models of marine molluscan diseases: Trends and challenges.

    Science.gov (United States)

    Powell, Eric N; Hofmann, Eileen E

    2015-10-01

    Disease effects on host population dynamics and the transmission of pathogens between hosts are two important challenges for understanding how epizootics wax and wane and how disease influences host population dynamics. For the management of marine shellfish resources, marine diseases pose additional challenges in early intervention after the appearance of disease, management of the diseased population to limit a decline in host abundance, and application of measures to restrain that decline once it occurs. Mathematical models provide one approach for quantifying these effects and addressing the competing goals of managing the diseased population versus managing the disease. The majority of models for molluscan diseases fall into three categories distinguished by these competing goals. (1) Models that consider disease effects on the host population tend to focus on pathogen proliferation within the host. Many of the well-known molluscan diseases are pandemic, in that they routinely reach high prevalence rapidly over large geographic expanses, are characterized by transmission that does not depend upon a local source, and exert a significant influence on host population dynamics. Models focused on disease proliferation examine the influence of environmental change on host population metrics and provide a basis to better manage diseased stocks. Such models are readily adapted to questions of fishery management and habitat restoration. (2) Transmission models are designed to understand the mechanisms triggering epizootics, identify factors impeding epizootic development, and evaluate controls on the rate of disease spread over the host's range. Transmission models have been used extensively to study terrestrial diseases, yet little attention has been given to their potential for understanding the epidemiology of marine molluscan diseases. For management of diseases of wild stocks, transmission models open up a range of options, including the application of area

  10. European Continental Scale Hydrological Model, Limitations and Challenges

    Science.gov (United States)

    Rouholahnejad, E.; Abbaspour, K.

    2014-12-01

    The pressures on water resources due to increasing levels of societal demand, increasing conflict of interest and uncertainties with regard to freshwater availability create challenges for water managers and policymakers in many parts of Europe. At the same time, climate change adds a new level of pressure and uncertainty with regard to freshwater supplies. On the other hand, the small-scale sectoral structure of water management is now reaching its limits. The integrated management of water in basins requires a new level of consideration where water bodies are to be viewed in the context of the whole river system and managed as a unit within their basins. In this research we present the limitations and challenges of modelling the hydrology of the continent Europe. The challenges include: data availability at continental scale and the use of globally available data, streamgauge data quality and their misleading impacts on model calibration, calibration of large-scale distributed model, uncertainty quantification, and computation time. We describe how to avoid over parameterization in calibration process and introduce a parallel processing scheme to overcome high computation time. We used Soil and Water Assessment Tool (SWAT) program as an integrated hydrology and crop growth simulator to model water resources of the Europe continent. Different components of water resources are simulated and crop yield and water quality are considered at the Hydrological Response Unit (HRU) level. The water resources are quantified at subbasin level with monthly time intervals for the period of 1970-2006. The use of a large-scale, high-resolution water resources models enables consistent and comprehensive examination of integrated system behavior through physically-based, data-driven simulation and provides the overall picture of water resources temporal and spatial distribution across the continent. The calibrated model and results provide information support to the European Water

  11. Challenges of model transferability to data-scarce regions (Invited)

    Science.gov (United States)

    Samaniego, L. E.

    2013-12-01

    Developing the ability to globally predict the movement of water on the land surface at spatial scales from 1 to 5 km constitute one of grand challenges in land surface modelling. Copying with this grand challenge implies that land surface models (LSM) should be able to make reliable predictions across locations and/or scales other than those used for parameter estimation. In addition to that, data scarcity and quality impose further difficulties in attaining reliable predictions of water and energy fluxes at the scales of interest. Current computational limitations impose also seriously limitations to exhaustively investigate the parameter space of LSM over large domains (e.g. greater than half a million square kilometers). Addressing these challenges require holistic approaches that integrate the best techniques available for parameter estimation, field measurements and remotely sensed data at their native resolutions. An attempt to systematically address these issues is the multiscale parameterisation technique (MPR) that links high resolution land surface characteristics with effective model parameters. This technique requires a number of pedo-transfer functions and a much fewer global parameters (i.e. coefficients) to be inferred by calibration in gauged basins. The key advantage of this technique is the quasi-scale independence of the global parameters which enables to estimate global parameters at coarser spatial resolutions and then to transfer them to (ungauged) areas and scales of interest. In this study we show the ability of this technique to reproduce the observed water fluxes and states over a wide range of climate and land surface conditions ranging from humid to semiarid and from sparse to dense forested regions. Results of transferability of global model parameters in space (from humid to semi-arid basins) and across scales (from coarser to finer) clearly indicate the robustness of this technique. Simulations with coarse data sets (e.g. EOBS

  12. Modeling and Analysis in Marine Big Data: Advances and Challenges

    Directory of Open Access Journals (Sweden)

    Dongmei Huang

    2015-01-01

    Full Text Available It is aware that big data has gathered tremendous attentions from academic research institutes, governments, and enterprises in all aspects of information sciences. With the development of diversity of marine data acquisition techniques, marine data grow exponentially in last decade, which forms marine big data. As an innovation, marine big data is a double-edged sword. On the one hand, there are many potential and highly useful values hidden in the huge volume of marine data, which is widely used in marine-related fields, such as tsunami and red-tide warning, prevention, and forecasting, disaster inversion, and visualization modeling after disasters. There is no doubt that the future competitions in marine sciences and technologies will surely converge into the marine data explorations. On the other hand, marine big data also brings about many new challenges in data management, such as the difficulties in data capture, storage, analysis, and applications, as well as data quality control and data security. To highlight theoretical methodologies and practical applications of marine big data, this paper illustrates a broad view about marine big data and its management, makes a survey on key methods and models, introduces an engineering instance that demonstrates the management architecture, and discusses the existing challenges.

  13. Challenge models for RTFS in rainbow trout fry (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Henriksen, Maya Maria Mihályi; Madsen, Lone; Dalsgaard, Inger

    2011-01-01

    forms of stress have shown to be reproducible. Bath challenge is more appropriate for vaccine testing, since natural transmission of infection is imitated and is also more suitable due to the small size of the fry. A bath-model using H2O2 as a stressor is currently being tested on 1.4g rainbow trout fry...... in four experimental groups: 1) no H2O2/no bath infection, 2) H2O2/no bath infection, 3) no H2O2/ bath infection and 4) H2O2/ bath infection. Mortality will be evaluated over approximately 25 days. The project is currently in its preliminary phase and presently focused on development of a model...

  14. Challenges in LCA modelling of multiple loops for aluminium cans

    DEFF Research Database (Denmark)

    Niero, Monia; Olsen, Stig Irving

    considered the case of closed-loop recycling for aluminium cans, where body and lid are different alloys, and discussed the abovementioned challenge. The Life Cycle Inventory (LCI) modelling of aluminium processes is traditionally based on a pure aluminium flow, therefore neglecting the presence of alloying...... elements. We included the effect of alloying elements on the LCA modelling of aluminium can recycling. First, we performed a mass balance of the main alloying elements (Mn, Fe, Si, Cu) in aluminium can recycling at increasing levels of recycling rate. The analysis distinguished between different aluminium...... packaging scrap sources (i.e. used beverage can and mixed aluminium packaging) to understand the limiting factors for multiple loop aluminium can recycling. Secondly, we performed a comparative LCA of aluminium can production and recycling in multiple loops considering the two aluminium packaging scrap...

  15. Challenges to the standard model of Big Bang nucleosynthesis

    International Nuclear Information System (INIS)

    Steigman, G.

    1993-01-01

    Big Bang nucleosynthesis provides a unique probe of the early evolution of the Universe and a crucial test of the consistency of the standard hot Big Bang cosmological model. Although the primordial abundances of 2 H, 3 He, 4 He, and 7 Li inferred from current observational data are in agreement with those predicted by Big Bang nucleosynthesis, recent analysis has severely restricted the consistent range for the nucleon-to-photon ratio: 3.7 ≤ η 10 ≤ 4.0. Increased accuracy in the estimate of primordial 4 he and observations of Be and B in Pop II stars are offering new challenges to the standard model and suggest that no new light particles may be allowed (N ν BBN ≤ 3.0, where N ν is the number of equivalent light neutrinos). 23 refs

  16. MODELLING CHALLENGES TO FORECAST URBAN GOODS DEMAND FOR RAIL

    Directory of Open Access Journals (Sweden)

    Antonio COMI

    2015-12-01

    Full Text Available This paper explores the new research challenges for forecasting urban goods demand by rail. In fact, the growing interest to find urban logistics solutions for improving city sustainability and liveability, mainly due to the reduction of urban road accessibility and environmental constraints, has pushed to explore solutions alternative to the road. Multimodal urban logistics, based on the use of railway, seem an interesting alternative solution, but it remained mainly at conceptual level. Few studies have explored the factors, that push actors to find competitive such a system with respect to the road, and modelling framework for forecasting the relative demand. Therefore, paper reviews the current literature, investigates the factors involved in choosing such a mode, and finally, recalls a recent modelling framework and hence proposes some advancements that allow to point out the rail transport alternative.

  17. Challenges of Modeling Flood Risk at Large Scales

    Science.gov (United States)

    Guin, J.; Simic, M.; Rowe, J.

    2009-04-01

    Flood risk management is a major concern for many nations and for the insurance sector in places where this peril is insured. A prerequisite for risk management, whether in the public sector or in the private sector is an accurate estimation of the risk. Mitigation measures and traditional flood management techniques are most successful when the problem is viewed at a large regional scale such that all inter-dependencies in a river network are well understood. From an insurance perspective the jury is still out there on whether flood is an insurable peril. However, with advances in modeling techniques and computer power it is possible to develop models that allow proper risk quantification at the scale suitable for a viable insurance market for flood peril. In order to serve the insurance market a model has to be event-simulation based and has to provide financial risk estimation that forms the basis for risk pricing, risk transfer and risk management at all levels of insurance industry at large. In short, for a collection of properties, henceforth referred to as a portfolio, the critical output of the model is an annual probability distribution of economic losses from a single flood occurrence (flood event) or from an aggregation of all events in any given year. In this paper, the challenges of developing such a model are discussed in the context of Great Britain for which a model has been developed. The model comprises of several, physically motivated components so that the primary attributes of the phenomenon are accounted for. The first component, the rainfall generator simulates a continuous series of rainfall events in space and time over thousands of years, which are physically realistic while maintaining the statistical properties of rainfall at all locations over the model domain. A physically based runoff generation module feeds all the rivers in Great Britain, whose total length of stream links amounts to about 60,000 km. A dynamical flow routing

  18. Challenges of Microgrids in Remote Communities: A STEEP Model Application

    Directory of Open Access Journals (Sweden)

    Daniel Akinyele

    2018-02-01

    Full Text Available There is a growing interest in the application of microgrids around the world because of their potential for achieving a flexible, reliable, efficient and smart electrical grid system and supplying energy to off-grid communities, including their economic benefits. Several research studies have examined the application issues of microgrids. However, a lack of in-depth considerations for the enabling planning conditions has been identified as a major reason why microgrids fail in several off-grid communities. This development requires research efforts that consider better strategies and framework for sustainable microgrids in remote communities. This paper first presents a comprehensive review of microgrid technologies and their applications. It then proposes the STEEP model to examine critically the failure factors based on the social, technical, economic, environmental and policy (STEEP perspectives. The model details the key dimensions and actions necessary for addressing the challenge of microgrid failure in remote communities. The study uses remote communities within Nigeria, West Africa, as case studies and demonstrates the need for the STEEP approach for better understanding of microgrid planning and development. Better insights into microgrid systems are expected to address the drawbacks and improve the situation that can lead to widespread and sustainable applications in off-grid communities around the world in the future. The paper introduces the sustainable planning framework (SPF based on the STEEP model, which can form a general basis for planning microgrids in any remote location.

  19. Ensemble models on palaeoclimate to predict India's groundwater challenge

    Directory of Open Access Journals (Sweden)

    Partha Sarathi Datta

    2013-09-01

    Full Text Available In many parts of the world, freshwater crisis is largely due to increasing water consumption and pollution by rapidly growing population and aspirations for economic development, but, ascribed usually to the climate. However, limited understanding and knowledge gaps in the factors controlling climate and uncertainties in the climate models are unable to assess the probable impacts on water availability in tropical regions. In this context, review of ensemble models on δ18O and δD in rainfall and groundwater, 3H- and 14C- ages of groundwater and 14C- age of lakes sediments helped to reconstruct palaeoclimate and long-term recharge in the North-west India; and predict future groundwater challenge. The annual mean temperature trend indicates both warming/cooling in different parts of India in the past and during 1901–2010. Neither the GCMs (Global Climate Models nor the observational record indicates any significant change/increase in temperature and rainfall over the last century, and climate change during the last 1200 yrs BP. In much of the North-West region, deep groundwater renewal occurred from past humid climate, and shallow groundwater renewal from limited modern recharge over the past decades. To make water management to be more responsive to climate change, the gaps in the science of climate change need to be bridged.

  20. Challenge

    International Nuclear Information System (INIS)

    Schwitters, R.F.

    1996-01-01

    The design of new and upgrades of existing high energy particle accelerators is reviewed in light of the current knowledge of the standard model determined from existing and past machines and funding factors. Current financing of science will delay determining unknowns, such as CP violation, proton decay, neutrino properties, and dark matter. Three options are given: (1) obtain more funding, (2) downsize scientific personnel as are private enterprises or (3) develop new technology which will reduce the high cost of building current designs of high energy accelerators. (AIP) copyright 1996 American Institute of Physics

  1. Challenges of citizen science contributions to modelling hydrodynamics of floods

    Science.gov (United States)

    Assumpção, Thaine Herman; Popescu, Ioana; Jonoski, Andreja; Solomatine, Dimitri P.

    2017-04-01

    Citizen science is an established mechanism in many fields of science, including ecology, biology and astronomy. Citizen participation ranges from collecting and interpreting data towards designing experiments with scientists and cooperating with water management authorities. In the environmental sciences, its potential has begun to be explored in the past decades and many studies on the applicability to water resources have emerged. Citizen Observatories are at the core of several EU-funded projects such as WeSenseIt, GroundTruth, GroundTruth 2.0 and SCENT (Smart Toolbox for Engaging Citizens into a People-Centric Observation Web) that already resulted in valuable contributions to the field. Buytaert et al. (2014) has already reviewed the role of citizen science in hydrology. The work presented here aims to complement it, reporting and discussing the use of citizen science for modelling the hydrodynamics of floods in a variety of studies. Additionally, it highlights the challenges that lie ahead to utilize more fully the citizen science potential contribution. In this work, focus is given to each component of hydrodynamic models: water level, velocity, flood extent, roughness and topography. It is addressed how citizens have been contributing to each aspect, mainly considering citizens as sensors and citizens as data interpreters. We consider to which kind of model (1D or 2D) the discussed approaches contribute and what their limitations and potential uses are. We found that although certain mechanisms are well established (e.g. the use of Volunteer Geographic Information for soft validation of land-cover and land-use maps), the applications in a modelling context are rather modest. Also, most studies involving models are limited to replacing traditional data with citizen data. We recommend that citizen science continue to be explored in modelling frameworks, in different case studies, taking advantage of the discussed mechanisms and of new sensor technologies

  2. Challenges and potential solutions for European coastal ocean modelling

    Science.gov (United States)

    She, Jun; Stanev, Emil

    2017-04-01

    Coastal operational oceanography is a science and technological platform to integrate and transform the outcomes in marine monitoring, new knowledge generation and innovative technologies into operational information products and services in the coastal ocean. It has been identified as one of the four research priorities by EuroGOOS (She et al. 2016). Coastal modelling plays a central role in such an integration and transformation. A next generation coastal ocean forecasting system should have following features: i) being able to fully exploit benefits from future observations, ii) generate meaningful products in finer scales e.g., sub-mesoscale and in estuary-coast-sea continuum, iii) efficient parallel computing and model grid structure, iv) provide high quality forecasts as forcing to NWP and coastal climate models, v) resolving correctly inter-basin and inter-sub-basin water exchange, vi) resolving synoptic variability and predictability in marine ecosystems, e.g., for algae bloom, vi) being able to address critical and relevant issues in coastal applications, e.g., marine spatial planning, maritime safety, marine pollution protection, disaster prevention, offshore wind energy, climate change adaptation and mitigation, ICZM (integrated coastal zone management), the WFD (Water Framework Directive), and the MSFD (Marine Strategy Framework Directive), especially on habitat, eutrophication, and hydrographic condition descriptors. This presentation will address above challenges, identify limits of current models and propose correspondent research needed. The proposed roadmap will address an integrated monitoring-modelling approach and developing Unified European Coastal Ocean Models. In the coming years, a few new developments in European Sea observations can expected, e.g., more near real time delivering on profile observations made by research vessels, more shallow water Argo floats and bio-Argo floats deployed, much more high resolution sea level data from SWOT

  3. A Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239

    OpenAIRE

    Powell, Rebecca L.R.; Ouellette, Ian; Lindsay, Ross W.; Parks, Christopher L.; King, C. Richter; McDermott, Adrian B.; Morrow, Gavin

    2013-01-01

    Abstract Results from recent HIV-1 vaccine studies have indicated that high serum antibody (Ab) titers may not be necessary for Ab-mediated protection, and that Abs localized to mucosal sites might be critical for preventing infection. Enzyme-linked immunosorbent assay (ELISA) has been used for decades as the gold standard for Ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of Abs. In this study, w...

  4. Smart services – characteristics, challenges, opportunities and business models

    Directory of Open Access Journals (Sweden)

    Marquardt Katrin

    2017-07-01

    Full Text Available “Industry 4.0”, “Digitalization”, “Internet of Things” and “Smart Services” are the today’s buzzwords when tracking economic news. It is to ask about the meaning of those phrases. The world has changed over the last decade from a mainly physical to software controlled economy and the information technology has become an integral part of our industry and society in its entirety. Nowadays it is no longer the product that matters it is the data that are generated by using the product or service. Those usage data collected and analyzed commence new business models and services. The economic future of a company will much more rely on the ability to collect and use the data to generate Smart Services for their customers and to transform from a simple product supplier to an entertainment provider. However there are not only opportunities there are also challenges on the way to that new services which needs to be known and considered. For instance the development cycles need to be faster, the business models need to be adjusted and the positive financial results will not come into the picture on the first day. Based on those thoughts and while there only a handful of researches about that new services exists, the main purpose of the present study is at first, to gain a common understanding about the meaning and the characteristics of Smart Services and their adjacencies. Secondly, the study summarizes the identified challenges and opportunities in relation to them. Thirdly, the author introduce and explain the main business models usable for those Smart Services and the requirements for starting the transformation towards those services. The aim of this paper is to set a basis for this exciting and relatively unsought topic and to produce an interest in further empirical and practical researches in this area. The methodologies used for this research are a systematic literature review and an evaluation of existing studies with the

  5. Challenges of 4D(ata Model for Electronic Government

    Directory of Open Access Journals (Sweden)

    Bogdan GHILIC-MICU

    2015-01-01

    Full Text Available Social evolution pyramid, built on the foundation of the ‘90s capitalist society, lead to the emergence of the informational society – years 1990 to 2005 – and knowledge society – years 2005 to 2020. The literature starts using a new concept, a new form of association – artificial intelligence society – foreseen to be established in the next time frame. All these developments of human society and translations or leaps (most of the times apparently timeless were, are and will be possible only due to the advancing information and communications technologies. The leap to Democracy 3.0, based on information and communication technologies prompts to a radical change in the majority of the classical concepts targeting society structure and the way it is guided and controlled. Thus, concepts become electronic concepts (or e-concepts through the use of new technologies. E-concepts keep the essence of the classical principles of liberty and democracy, adding a major aspect of the new way of communication and spreading ideas between people. The main problem is to quantify, analyze and foresee the way technological changes will influence not only the economic system, but also the daily life of the individual and the society. Unfortunately (or maybe fortunately, depending on the point of view, all these evolutions and technological and social developments are as many challenges for the governments of the world. In this paper we will highlight only four of the challenges facing the governments, grouped in a structured model with the following specific concepts: Big Data, Social Data, Linked Data and Mobile Data. This is an emerging paradigm of the information and communication technology supporting national and global eGovernment projects.

  6. Memory of irrigation effects on hydroclimate and its modeling challenge

    Science.gov (United States)

    Chen, Fei; Xu, Xiaoyu; Barlage, Michael; Rasmussen, Roy; Shen, Shuanghe; Miao, Shiguang; Zhou, Guangsheng

    2018-06-01

    Irrigation modifies land-surface water and energy budgets, and also influences weather and climate. However, current earth-system models, used for weather prediction and climate projection, are still in their infancy stage to consider irrigation effects. This study used long-term data collected from two contrasting (irrigated and rainfed) nearby maize-soybean rotation fields, to study the effects of irrigation memory on local hydroclimate. For a 12 year average, irrigation decreases summer surface-air temperature by less than 1 °C and increases surface humidity by 0.52 g kg‑1. The irrigation cooling effect is more pronounced and longer lasting for maize than for soybean. Irrigation reduces maximum, minimum, and averaged temperature over maize by more than 0.5 °C for the first six days after irrigation, but its temperature effect over soybean is mixed and negligible two or three days after irrigation. Irrigation increases near-surface humidity over maize by about 1 g kg‑1 up to ten days and increases surface humidity over soybean (~ 0.8 g kg‑1) with a similar memory. These differing effects of irrigation memory on temperature and humidity are associated with respective changes in the surface sensible and latent heat fluxes for maize and soybean. These findings highlight great need and challenges for earth-system models to realistically simulate how irrigation effects vary with crop species and with crop growth stages, and to capture complex interactions between agricultural management and water-system components (crop transpiration, precipitation, river, reservoirs, lakes, groundwater, etc.) at various spatial and temporal scales.

  7. Challenges and Opportunities in Modeling of the Global Atmosphere

    Science.gov (United States)

    Janjic, Zavisa; Djurdjevic, Vladimir; Vasic, Ratko

    2016-04-01

    are comparable to the scales of the dominant Rossby waves, such fictitious solutions are hard to identify and remove. Another new challenge on the global scale is that the limit of validity of the hydrostatic approximation is rapidly being approached. Relaxing the hydrostatic approximation requieres careful reformulation of the model dynamics and more computations and communications. The unified Non-hydrostatic Multi-scale Model (NMMB) will be briefly discussed as an example. The non-hydrostatic dynamics were designed in such a way as to avoid over-specification. The global version is run on the latitude-longitude grid, and the polar filter selectively slows down the waves that would otherwise be unstable without modifying their amplitudes. The model has been successfully tested on various scales. The skill of the medium range forecasts produced by the NMMB is comparable to that of other major medium range models, and its computational efficiency on parallel computers is good.

  8. Challenges and opportunities in land surface modelling of savanna ecosystems

    Directory of Open Access Journals (Sweden)

    R. Whitley

    2017-10-01

    Full Text Available The savanna complex is a highly diverse global biome that occurs within the seasonally dry tropical to sub-tropical equatorial latitudes and are structurally and functionally distinct from grasslands and forests. Savannas are open-canopy environments that encompass a broad demographic continuum, often characterised by a changing dominance between C3-tree and C4-grass vegetation, where frequent environmental disturbances such as fire modulates the balance between ephemeral and perennial life forms. Climate change is projected to result in significant changes to the savanna floristic structure, with increases to woody biomass expected through CO2 fertilisation in mesic savannas and increased tree mortality expected through increased rainfall interannual variability in xeric savannas. The complex interaction between vegetation and climate that occurs in savannas has traditionally challenged terrestrial biosphere models (TBMs, which aim to simulate the interaction between the atmosphere and the land surface to predict responses of vegetation to changing in environmental forcing. In this review, we examine whether TBMs are able to adequately represent savanna fluxes and what implications potential deficiencies may have for climate change projection scenarios that rely on these models. We start by highlighting the defining characteristic traits and behaviours of savannas, how these differ across continents and how this information is (or is not represented in the structural framework of many TBMs. We highlight three dynamic processes that we believe directly affect the water use and productivity of the savanna system: phenology, root-water access and fire dynamics. Following this, we discuss how these processes are represented in many current-generation TBMs and whether they are suitable for simulating savanna fluxes.Finally, we give an overview of how eddy-covariance observations in combination with other data sources can be used in model

  9. Recent European Challenges and the Danish Collective Agreement Model

    DEFF Research Database (Denmark)

    Larsen, Trine Pernille; Navrbjerg, Steen Erik

    are related to the new forms of cross-border collaboration and negotiations taking place within multi-national corporations (MNC's). This research paper examines a series of challenges facing the collective bargaining systems in Denmark, Estonia, Northern Ireland and Sweden. These countries represent four...... distinct labour market systems with different traditions of social dialogue and allow comparison of how different EU member states handled the recent challenges caused by the increased European integration....

  10. Why Is Improvement of Earth System Models so Elusive? Challenges and Strategies from Dust Aerosol Modeling

    Science.gov (United States)

    Miller, Ronald L.; Garcia-Pando, Carlos Perez; Perlwitz, Jan; Ginoux, Paul

    2015-01-01

    Past decades have seen an accelerating increase in computing efficiency, while climate models are representing a rapidly widening set of physical processes. Yet simulations of some fundamental aspects of climate like precipitation or aerosol forcing remain highly uncertain and resistant to progress. Dust aerosol modeling of soil particles lofted by wind erosion has seen a similar conflict between increasing model sophistication and remaining uncertainty. Dust aerosols perturb the energy and water cycles by scattering radiation and acting as ice nuclei, while mediating atmospheric chemistry and marine photosynthesis (and thus the carbon cycle). These effects take place across scales from the dimensions of an ice crystal to the planetary-scale circulation that disperses dust far downwind of its parent soil. Representing this range leads to several modeling challenges. Should we limit complexity in our model, which consumes computer resources and inhibits interpretation? How do we decide if a process involving dust is worthy of inclusion within our model? Can we identify a minimal representation of a complex process that is efficient yet retains the physics relevant to climate? Answering these questions about the appropriate degree of representation is guided by model evaluation, which presents several more challenges. How do we proceed if the available observations do not directly constrain our process of interest? (This could result from competing processes that influence the observed variable and obscure the signature of our process of interest.) Examples will be presented from dust modeling, with lessons that might be more broadly applicable. The end result will either be clinical depression or there assuring promise of continued gainful employment as the community confronts these challenges.

  11. Why Is Improvement of Earth System Models So Elusive? Challenges and Strategies From Dust Aerosol Modeling

    Science.gov (United States)

    Miller, R. L.; Pérez García-Pando, C.; Perlwitz, J. P.; Ginoux, P. A.

    2015-12-01

    Past decades have seen an accelerating increase in computing efficiency,while climate models are representing a rapidly widening set ofphysical processes. Yet simulations of some fundamental aspects ofclimate like precipitation or aerosol forcing remain highly uncertainand resistent to progress. Dust aerosol modeling of soil particleslofted by wind erosion has seen a similar conflict between increasingmodel sophistication and remaining uncertainty. Dust aerosols perturbthe energy and water cycles by scattering radiation and acting as icenuclei, while mediating atmospheric chemistry and marinephotosynthesis (and thus the carbon cycle). These effects take placeacross scales from the dimensions of an ice crystal to theplanetary-scale circulation that disperses dust far downwind of itsparent soil. Representing this range leads to several modelingchallenges. Should we limit complexity in our model, which consumescomputer resources and inhibits interpretation? How do we decide if aprocess involving dust is worthy of inclusion within our model? Canwe identify a minimal representation of a complex process that isefficient yet retains the physics relevant to climate? Answeringthese questions about the appropriate degree of representation isguided by model evaluation, which presents several more challenges.How do we proceed if the available observations do not directlyconstrain our process of interest? (This could result from competingprocesses that influence the observed variable and obscure thesignature of our process of interest.) Examples will be presentedfrom dust modeling, with lessons that might be more broadlyapplicable. The end result will either be clinical depression or thereassuring promise of continued gainful employment as the communityconfronts these challenges.

  12. Practical Strategies for School Counsellor Leadership: The Leadership Challenge Model

    Science.gov (United States)

    Shillingford, Margaret

    2013-01-01

    It is crucial to the progression of the school counselling profession that counsellors-in-training receive the training, knowledge, and practice in leadership that they need to counter systemic challenges that they may face. Effective leadership practices have been shown in research to be instrumental in promoting program delivery success in the…

  13. Using animal models to overcome temporal, spatial and combinatorial challenges in HIV persistence research

    DEFF Research Database (Denmark)

    Denton, Paul W.; Søgaard, Ole Schmeltz; Tolstrup, Martin

    2016-01-01

    Research challenges associated with understanding HIV persistence during antiretroviral therapy can be categorized as temporal, spatial and combinatorial. Temporal research challenges relate to the timing of events during establishment and maintenance of HIV persistence. Spatial research challeng...... for directly addressing these research challenges. The aim of this manuscript is to provide a comprehensive review of these recent translational advances made in animal models of HIV persistence....... will improve our understanding of HIV persistence and move the field closer to achieving eradication of persistent HIV. Given that humanized mice and non-human primate HIV models permit rigorous control of experimental conditions, these models have been used extensively as in vivo research platforms...

  14. Modelling water use in global hydrological models: review, challenges and directions

    Science.gov (United States)

    Bierkens, M. F.; de Graaf, I.; Wada, Y.; Wanders, N.; Van Beek, L. P.

    2017-12-01

    During the late 1980s and early 1990s, awareness of the shortage of global water resources lead to the first detailed global water resources assessments using regional statistics of water use and observations of meteorological and hydrological variables. Shortly thereafter, the first macroscale hydrological models (MHM) appeared. In these models, blue water (i.e., surface water and renewable groundwater) availability was calculated by accumulating runoff over a stream network and comparing it with population densities or with estimated water demand for agriculture, industry and households. In this talk we review the evolution of human impact modelling in global land models with a focus on global water resources, touching upon developments of the last 15 years: i.e. calculating human water scarcity; estimating groundwater depletion; adding dams and reservoirs; fully integrating water use (demand, withdrawal, consumption, return flow) in the hydrology; simulating the effects of land use change. We show example studies for each of these steps. We identify We identify major challenges that hamper the further development of integrated water resources modelling. Examples of these are: 1) simulating reservoir operations; 2) including local infrastructure and redistribution; 3) using the correct allocations rules; 4) projecting future water demand and water use. For each of these challenges we signify promising directions for further research.

  15. Analysis of Challenges for Management Education in India Using Total Interpretive Structural Modelling

    Science.gov (United States)

    Mahajan, Ritika; Agrawal, Rajat; Sharma, Vinay; Nangia, Vinay

    2016-01-01

    Purpose: The purpose of this paper is to identify challenges for management education in India and explain their nature, significance and interrelations using total interpretive structural modelling (TISM), an innovative version of Warfield's interpretive structural modelling (ISM). Design/methodology/approach: The challenges have been drawn from…

  16. Key Challenges and Potential Urban Modelling Opportunities in ...

    African Journals Online (AJOL)

    Chris Wray

    There is a risk within .... Giere (2004) models are generally considered as simple representations of reality ..... morphology, connectivity, bid rent and virtual model room – were developed to ... term integrated planning of education and health.

  17. Modeling urban landscape: New paradigms and challenges in territorial representation

    Directory of Open Access Journals (Sweden)

    Sheyla Aguilar de Santana

    2013-05-01

    Full Text Available This paper aims to give a brief background on the production of urban space considering the social functions of the city, the needs of contemporary urban reforms and the need for tools that assist in decision making. This state of the art about the production space justifies the current studies on the development of geoprocessing tools, techniques and methodologies that attempt the needs of creating interpretive portraits of urban landscapes to facilitate dialogue between urban technical, administrators and community. In this sense, it is presented how GIS has been working within the context of urban planning and appointed the new challenges and paradigms of territorial representation.

  18. Usability and Information access challenges in complex simulation models

    CSIR Research Space (South Africa)

    Naidoo, S

    2008-07-01

    Full Text Available -sensitive help and meaningful feedback when errors occur Legibility Ease with which visual content can be understood Task Completion Whether a user can complete a task within appropriate task time when performing. Minimal action Capability of the software... by the user interface may result in some operations not being visible to the user although available in the simulation tool. The challenge has been to develop simulation tools that can be used by the users with minimal effort required both to operate...

  19. Concepts, challenges, and successes in modeling thermodynamics of metabolism.

    Science.gov (United States)

    Cannon, William R

    2014-01-01

    The modeling of the chemical reactions involved in metabolism is a daunting task. Ideally, the modeling of metabolism would use kinetic simulations, but these simulations require knowledge of the thousands of rate constants involved in the reactions. The measurement of rate constants is very labor intensive, and hence rate constants for most enzymatic reactions are not available. Consequently, constraint-based flux modeling has been the method of choice because it does not require the use of the rate constants of the law of mass action. However, this convenience also limits the predictive power of constraint-based approaches in that the law of mass action is used only as a constraint, making it difficult to predict metabolite levels or energy requirements of pathways. An alternative to both of these approaches is to model metabolism using simulations of states rather than simulations of reactions, in which the state is defined as the set of all metabolite counts or concentrations. While kinetic simulations model reactions based on the likelihood of the reaction derived from the law of mass action, states are modeled based on likelihood ratios of mass action. Both approaches provide information on the energy requirements of metabolic reactions and pathways. However, modeling states rather than reactions has the advantage that the parameters needed to model states (chemical potentials) are much easier to determine than the parameters needed to model reactions (rate constants). Herein, we discuss recent results, assumptions, and issues in using simulations of state to model metabolism.

  20. Progress and challenges in coupled hydrodynamic-ecological estuarine modeling

    Science.gov (United States)

    Ganju, Neil K.; Brush, Mark J.; Rashleigh, Brenda; Aretxabaleta, Alfredo L.; del Barrio, Pilar; Grear, Jason S.; Harris, Lora A.; Lake, Samuel J.; McCardell, Grant; O'Donnell, James; Ralston, David K.; Signell, Richard P.; Testa, Jeremy; Vaudrey, Jamie M. P.

    2016-01-01

    Numerical modeling has emerged over the last several decades as a widely accepted tool for investigations in environmental sciences. In estuarine research, hydrodynamic and ecological models have moved along parallel tracks with regard to complexity, refinement, computational power, and incorporation of uncertainty. Coupled hydrodynamic-ecological models have been used to assess ecosystem processes and interactions, simulate future scenarios, and evaluate remedial actions in response to eutrophication, habitat loss, and freshwater diversion. The need to couple hydrodynamic and ecological models to address research and management questions is clear because dynamic feedbacks between biotic and physical processes are critical interactions within ecosystems. In this review, we present historical and modern perspectives on estuarine hydrodynamic and ecological modeling, consider model limitations, and address aspects of model linkage, skill assessment, and complexity. We discuss the balance between spatial and temporal resolution and present examples using different spatiotemporal scales. Finally, we recommend future lines of inquiry, approaches to balance complexity and uncertainty, and model transparency and utility. It is idealistic to think we can pursue a “theory of everything” for estuarine models, but recent advances suggest that models for both scientific investigations and management applications will continue to improve in terms of realism, precision, and accuracy.

  1. Bioenergy crop models: Descriptions, data requirements and future challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nair, S. Surendran [University of Tennessee, Knoxville (UTK); Kang, Shujiang [ORNL; Zhang, Xuesong [Pacific Northwest National Laboratory (PNNL); Miguez, Fernando [Iowa State University; Izaurralde, Dr. R. Cesar [Pacific Northwest National Laboratory (PNNL); Post, Wilfred M [ORNL; Dietze, Michael [University of Illinois, Urbana-Champaign; Lynd, L. [Dartmouth College; Wullschleger, Stan D [ORNL

    2012-01-01

    Field studies that address the production of lignocellulosic biomass as a source of renewable energy provide critical data for the development of bioenergy crop models. A literature survey revealed that 14 models have been used for simulating bioenergy crops including herbaceous and woody bioenergy crops, and for crassulacean acid metabolism (CAM) crops. These models simulate field-scale production of biomass for switchgrass (ALMANAC, EPIC, and Agro-BGC), miscanthus (MISCANFOR, MISCANMOD, and WIMOVAC), sugarcane (APSIM, AUSCANE, and CANEGRO), and poplar and willow (SECRETS and 3PG). Two models are adaptations of dynamic global vegetation models and simulate biomass yields of miscanthus and sugarcane at regional scales (Agro-IBIS and LPJmL). Although it lacks the complexity of other bioenergy crop models, the environmental productivity index (EPI) is the only model used to estimate biomass production of CAM (Agave and Opuntia) plants. Except for the EPI model, all models include representations of leaf area dynamics, phenology, radiation interception and utilization, biomass production, and partitioning of biomass to roots and shoots. A few models simulate soil water, nutrient, and carbon cycle dynamics, making them especially useful for assessing the environmental consequences (e.g., erosion and nutrient losses) associated with the large-scale deployment of bioenergy crops. The rapid increase in use of models for energy crop simulation is encouraging; however, detailed information on the influence of climate, soils, and crop management practices on biomass production is scarce. Thus considerable work remains regarding the parameterization and validation of process-based models for bioenergy crops; generation and distribution of high-quality field data for model development and validation; and implementation of an integrated framework for efficient, high-resolution simulations of biomass production for use in planning sustainable bioenergy systems.

  2. Challenges in the development of analytical soil compaction models

    DEFF Research Database (Denmark)

    Keller, Thomas; Lamandé, Mathieu

    2010-01-01

    and recommendations for the prevention of soil compaction often rely on simulation models. This paper highlights some issues that need further consideration in order to improve soil compaction modelling, with the focus on analytical models. We discuss the different issues based on comparisons between experimental......Soil compaction can cause a number of environmental and agronomic problems (e.g. flooding, erosion, leaching of agrochemicals to recipient waters, emission of greenhouse gases to the atmosphere, crop yield losses), resulting in significant economic damage to society and agriculture. Strategies...... data and model simulations. The upper model boundary condition (i.e. contact area and stresses at the tyre-soil interface) is highly influential in stress propagation, but knowledge on the effects of loading and soil conditions on the upper model boundary condition is inadequate. The accuracy of stress...

  3. Rapid de novo shape encoding: a challenge to connectionist modeling

    OpenAIRE

    Greene, Ernest

    2018-01-01

    Neural network (connectionist) models are designed to encode image features and provide the building blocks for object and shape recognition. These models generally call for: a) initial diffuse connections from one neuron population to another, and b) training to bring about a functional change in those connections so that one or more high-tier neurons will selectively respond to a specific shape stimulus. Advanced models provide for translation, size, and rotation invariance. The present dis...

  4. Challenges of transferring models of fish abundance between coral reefs.

    Science.gov (United States)

    Sequeira, Ana M M; Mellin, Camille; Lozano-Montes, Hector M; Meeuwig, Jessica J; Vanderklift, Mathew A; Haywood, Michael D E; Babcock, Russell C; Caley, M Julian

    2018-01-01

    Reliable abundance estimates for species are fundamental in ecology, fisheries, and conservation. Consequently, predictive models able to provide reliable estimates for un- or poorly-surveyed locations would prove a valuable tool for management. Based on commonly used environmental and physical predictors, we developed predictive models of total fish abundance and of abundance by fish family for ten representative taxonomic families for the Great Barrier Reef (GBR) using multiple temporal scenarios. We then tested if models developed for the GBR (reference system) could predict fish abundances at Ningaloo Reef (NR; target system), i.e., if these GBR models could be successfully transferred to NR. Models of abundance by fish family resulted in improved performance (e.g., 44.1% fish abundance (9% fish species richness from the GBR to NR, transferability for these fish abundance models was poor. When compared with observations of fish abundance collected in NR, our transferability results had low validation scores ( R 2   0.05). High spatio-temporal variability of patterns in fish abundance at the family and population levels in both reef systems likely affected the transferability of these models. Inclusion of additional predictors with potential direct effects on abundance, such as local fishing effort or topographic complexity, may improve transferability of fish abundance models. However, observations of these local-scale predictors are often not available, and might thereby hinder studies on model transferability and its usefulness for conservation planning and management.

  5. Five challenges for stochastic epidemic models involving global transmission

    Directory of Open Access Journals (Sweden)

    Tom Britton

    2015-03-01

    Full Text Available The most basic stochastic epidemic models are those involving global transmission, meaning that infection rates depend only on the type and state of the individuals involved, and not on their location in the population. Simple as they are, there are still several open problems for such models. For example, when will such an epidemic go extinct and with what probability (questions depending on the population being fixed, changing or growing? How can a model be defined explaining the sometimes observed scenario of frequent mid-sized epidemic outbreaks? How can evolution of the infectious agent transmission rates be modelled and fitted to data in a robust way?

  6. Prediction Models and Decision Support: Chances and Challenges

    NARCIS (Netherlands)

    Kappen, T.H.

    2015-01-01

    A clinical prediction model can assist doctors in arriving at the most likely diagnosis or estimating the prognosis. By utilizing various patient- and disease-related properties, such models can yield objective estimations of the risk of a disease or the probability of a certain disease course for

  7. Five (or so) challenges for species distribution modelling

    DEFF Research Database (Denmark)

    Bastos Araujo, Miguel; Guisan, Antoine

    2006-01-01

    Species distribution modelling is central to both fundamental and applied research in biogeography. Despite widespread use of models, there are still important conceptual ambiguities as well as biotic and algorithmic uncertainties that need to be investigated in order to increase confidence in mo...

  8. The Job Demands?Resources model: Challenges for future research

    NARCIS (Netherlands)

    E. Demerouti (Eva); A.B. Bakke (Arnold B.)

    2011-01-01

    textabstractMotivation: The motivation of this overview is to present the state of the art of Job Demands-Resources (JD-R) model whilst integrating the various contributions to the special issue. Research purpose: To provide an overview of the JD-R model, which incorporates many possible working

  9. The Job Demands-Resources model: challenges for future research

    NARCIS (Netherlands)

    Demerouti, E.; Bakker, A.B.

    2011-01-01

    Motivation: The motivation of this overview is to present the state of the art of Job Demands–Resources (JD–R) model whilst integrating the various contributions to the special issue. Research purpose: To provide an overview of the JD–R model, which incorporates many possible working conditions and

  10. The Job Demands–Resources model: Challenges for future research

    Directory of Open Access Journals (Sweden)

    Evangelia Demerouti

    2011-05-01

    Research purpose: To provide an overview of the JD–R model, which incorporates many possible working conditions and focuses on both negative and positive indicators of employee well-being. Moreover, the studies of the special issue were introduced. Research design: Qualitative and quantitative studies on the JD–R model were reviewed to enlighten the health and motivational processes suggested by the model. Main findings: Next to the confirmation of the two suggested processes of the JD–R model, the studies of the special issue showed that the model can be used to predict work-place bullying, incidences of upper respiratory track infection, work-based identity, and early retirement intentions. Moreover, whilst psychological safety climate could be considered as a hypothetical precursor of job demands and resources, compassion satisfaction moderated the health process of the model. Contribution/value-add: The findings of previous studies and the studies of the special issue were integrated in the JD–R model that can be used to predict well-being and performance at work. New avenues for future research were suggested. Practical/managerial implications: The JD–R model is a framework that can be used for organisations to improve employee health and motivation, whilst simultaneously improving various organisational outcomes.

  11. Challenges in mechanical modeling of SFR fuel rod transient behavior

    Energy Technology Data Exchange (ETDEWEB)

    Feria, F.; Herranz, L. E.

    2013-07-01

    Modeling of SFR fuel rod mechanical behavior under transient conditions entails the development of a creep law to predict cladding viscoplastic strain. In this regard, this work is focused on defining a proper clad creep law structure as the basis to set a suitable model under SFR off-normal conditions as transient overpower and loss of fluid. To do so, a review of in-codes clad creep models has been done by using SAS-SFR, SCANAIR and ASTEC. The proposed creep model has been structured in two parts: viscoplastic behaviour before the failure (primary and secondary creep) and the failure due to viscoplastic collapse (tertiary creep). In order to model the first part, Norton creep law has been proposed as a conservative option. An irradiation hardening factor should be included for best estimate calculations. The recommendation for the second part is to apply a failure criterion based on strain limit or rupture time, which allows achieving conservative results.

  12. Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Stoiber, Heribert; Nchinda, Godwin; Floto, Anja; Franz, Monika; Sauermann, Ulrike; Bredl, Simon; Deml, Ludwig; Ignatius, Ralf; Norley, Steve; Racz, Paul; Tenner-Racz, Klara; Steinman, Ralph M.; Wagner, Ralf; Uberla, Klaus

    2006-01-01

    Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus

  13. Modelling nutritional mutualisms: challenges and opportunities for data integration.

    Science.gov (United States)

    Clark, Teresa J; Friel, Colleen A; Grman, Emily; Shachar-Hill, Yair; Friesen, Maren L

    2017-09-01

    Nutritional mutualisms are ancient, widespread, and profoundly influential in biological communities and ecosystems. Although much is known about these interactions, comprehensive answers to fundamental questions, such as how resource availability and structured interactions influence mutualism persistence, are still lacking. Mathematical modelling of nutritional mutualisms has great potential to facilitate the search for comprehensive answers to these and other fundamental questions by connecting the physiological and genomic underpinnings of mutualisms with ecological and evolutionary processes. In particular, when integrated with empirical data, models enable understanding of underlying mechanisms and generalisation of principles beyond the particulars of a given system. Here, we demonstrate how mathematical models can be integrated with data to address questions of mutualism persistence at four biological scales: cell, individual, population, and community. We highlight select studies where data has been or could be integrated with models to either inform model structure or test model predictions. We also point out opportunities to increase model rigour through tighter integration with data, and describe areas in which data is urgently needed. We focus on plant-microbe systems, for which a wealth of empirical data is available, but the principles and approaches can be generally applied to any nutritional mutualism. © 2017 John Wiley & Sons Ltd/CNRS.

  14. Modeling bladder cancer in mice: opportunities and challenges

    Science.gov (United States)

    Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

    2015-01-01

    The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

  15. Rising to the challenge : A model of contest performance

    OpenAIRE

    DesAutels, Philip; Berthon, Pierre; Salehi-Sangari, Esmail

    2011-01-01

    Contests are a ubiquitous form of promotion widely adopted by financial services advertisers, yet, paradoxically, academic research on them is conspicuous in its absence. This work addresses this gap by developing a model of contest engagement and performance. Using motivation theory, factors that drive participant engagement are modeled, and engagement's effect on experience and marketing success of the contest specified. Measures of contest performance, in-contest engagement and post-contes...

  16. The Job Demands?Resources model: Challenges for future research

    OpenAIRE

    Demerouti, Eva; Bakke, Arnold B.

    2011-01-01

    textabstractMotivation: The motivation of this overview is to present the state of the art of Job Demands-Resources (JD-R) model whilst integrating the various contributions to the special issue. Research purpose: To provide an overview of the JD-R model, which incorporates many possible working conditions and focuses on both negative and positive indicators of employee well-being. Moreover, the studies of the special issue were introduced. Research design: Qualitative and quantitative studie...

  17. Empirical agent-based modelling challenges and solutions

    CERN Document Server

    Barreteau, Olivier

    2014-01-01

    This instructional book showcases techniques to parameterise human agents in empirical agent-based models (ABM). In doing so, it provides a timely overview of key ABM methodologies and the most innovative approaches through a variety of empirical applications.  It features cutting-edge research from leading academics and practitioners, and will provide a guide for characterising and parameterising human agents in empirical ABM.  In order to facilitate learning, this text shares the valuable experiences of other modellers in particular modelling situations. Very little has been published in the area of empirical ABM, and this contributed volume will appeal to graduate-level students and researchers studying simulation modeling in economics, sociology, ecology, and trans-disciplinary studies, such as topics related to sustainability. In a similar vein to the instruction found in a cookbook, this text provides the empirical modeller with a set of 'recipes'  ready to be implemented. Agent-based modeling (AB...

  18. Numerical modelling of river morphodynamics: Latest developments and remaining challenges

    Science.gov (United States)

    Siviglia, Annunziato; Crosato, Alessandra

    2016-07-01

    Numerical morphodynamic models provide scientific frameworks for advancing our understanding of river systems. The research on involved topics is an important and socially relevant undertaking regarding our environment. Nowadays numerical models are used for different purposes, from answering questions about basic morphodynamic research to managing complex river engineering problems. Due to increasing computer power and the development of advanced numerical techniques, morphodynamic models are now more and more used to predict the bed patterns evolution to a broad spectrum of spatial and temporal scales. The development and the success of application of such models are based upon a wide range of disciplines from applied mathematics for the numerical solution of the equations to geomorphology for the physical interpretation of the results. In this light we organized this special issue (SI) soliciting multidisciplinary contributions which encompass any aspect needed for the development and applications of such models. Most of the papers in the SI stem from contributions to session HS9.5/GM7.11 on numerical modelling and experiments in river morphodynamics at the European Geosciences Union (EGU) General Assembly held in Vienna, April 27th to May 2nd 2014.

  19. Informing soil models using pedotransfer functions: challenges and perspectives

    Science.gov (United States)

    Pachepsky, Yakov; Romano, Nunzio

    2015-04-01

    Pedotransfer functions (PTFs) are empirical relationships between parameters of soil models and more easily obtainable data on soil properties. PTFs have become an indispensable tool in modeling soil processes. As alternative methods to direct measurements, they bridge the data we have and data we need by using soil survey and monitoring data to enable modeling for real-world applications. Pedotransfer is extensively used in soil models addressing the most pressing environmental issues. The following is an attempt to provoke a discussion by listing current issues that are faced by PTF development. 1. As more intricate biogeochemical processes are being modeled, development of PTFs for parameters of those processes becomes essential. 2. Since the equations to express PTF relationships are essentially unknown, there has been a trend to employ highly nonlinear equations, e.g. neural networks, which in theory are flexible enough to simulate any dependence. This, however, comes with the penalty of large number of coefficients that are difficult to estimate reliably. A preliminary classification applied to PTF inputs and PTF development for each of the resulting groups may provide simple, transparent, and more reliable pedotransfer equations. 3. The multiplicity of models, i.e. presence of several models producing the same output variables, is commonly found in soil modeling, and is a typical feature in the PTF research field. However, PTF intercomparisons are lagging behind PTF development. This is aggravated by the fact that coefficients of PTF based on machine-learning methods are usually not reported. 4. The existence of PTFs is the result of some soil processes. Using models of those processes to generate PTFs, and more general, developing physics-based PTFs remains to be explored. 5. Estimating the variability of soil model parameters becomes increasingly important, as the newer modeling technologies such as data assimilation, ensemble modeling, and model

  20. Challenges in Modeling the Sun-Earth System

    Science.gov (United States)

    Spann, James

    2004-01-01

    The transfer of mass, energy and momentum through the coupled Sun-Earth system spans a wide range of scales in time and space. While profound advances have been made in modeling isolated regions of the Sun-Earth system, minimal progress has been achieved in modeling the end-to-end system. Currently, end-to-end modeling of the Sun-Earth system is a major goal of the National Space Weather and NASA Living With a Star (LWS) programs. The uncertainty in the underlying physics responsible for coupling contiguous regions of the Sun-Earth system is recognized as a significant barrier to progress. Our limited understanding of the underlying coupling physics is illustrated by the following example questions: how does the propagation of a typical CME/solar flare influence the measured properties of the solar wind at 1 AU? How does the solar wind compel the dynamic response of the Earth's magnetosphere? How is variability in the ionosphere-thermosphere system coupled to magnetospheric variations? Why do these and related important questions remain unanswered? What are the primary problems that need to be resolved to enable significant progress in comprehensive modeling of the Sun-Earth system? Which model/technique improvements are required and what new data coverage is required to enable full model advances? This poster opens the discussion for how these and other important questions can be addressed. A workshop scheduled for October 8-22, 2004 in Huntsville, Alabama, will be a forum for identifying ana exploring promising new directions and approaches for characterizing and understanding the system. To focus the discussion, the workshop will emphasize the genesis, evolution, propagation and interaction of high-speed solar wind streamers or CME/flares with geospace and the subsequent response of geospace from its outer reaches in the magnetosphere to the lower edge of the ionosphere-mesosphere-thermosphere. Particular emphasis will be placed on modeling the coupling aspects

  1. Computational brain models: Advances from system biology and future challenges

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-02-01

    Full Text Available Computational brain models focused on the interactions between neurons and astrocytes, modeled via metabolic reconstructions, are reviewed. The large source of experimental data provided by the -omics techniques and the advance/application of computational and data-management tools are being fundamental. For instance, in the understanding of the crosstalk between these cells, the key neuroprotective mechanisms mediated by astrocytes in specific metabolic scenarios (1 and the identification of biomarkers for neurodegenerative diseases (2,3. However, the modeling of these interactions demands a clear view of the metabolic and signaling pathways implicated, but most of them are controversial and are still under evaluation (4. Hence, to gain insight into the complexity of these interactions a current view of the main pathways implicated in the neuron-astrocyte communication processes have been made from recent experimental reports and reviews. Furthermore, target problems, limitations and main conclusions have been identified from metabolic models of the brain reported from 2010. Finally, key aspects to take into account into the development of a computational model of the brain and topics that could be approached from a systems biology perspective in future research are highlighted.

  2. Master Data Management Model in Company: Challenges and Opportunity

    Directory of Open Access Journals (Sweden)

    Indrajani Indrajani

    2015-12-01

    Full Text Available The purpose of this research is to analyze, design, and implement Master Data Management (MDM model for company, which include database processing that will be used in the quality of data customer and produce single view of customer. The research method used is literature study from a variety of journals, books, e-books, and articles on the internet. Also, fact finding techniques are done, such as by analyze, collect, and examine the documents, interviews, and observations. Then, other research methods used to analyze and design MDM model are using cleansing and matching technique. The result obtained from this research is animplementation MDM model for the company, where if implemented, will improve the quality of data significantly. The conclusion which can be obtained from this research is that MDM is one of the factors thatcan improve the quality of customer data.

  3. Simple model systems: a challenge for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Di Carlo Marta

    2012-04-01

    Full Text Available Abstract The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD, one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds.

  4. Extending the Challenge-Hindrance Model of Occupational Stress: The Role of Appraisal

    Science.gov (United States)

    Webster, Jennica R.; Beehr, Terry A.; Love, Kevin

    2011-01-01

    Interest regarding the challenge-hindrance occupational stress model has increased in recent years, however its theoretical foundation has not been tested. Drawing from the transactional theory of stress, this study tests the assumptions made in past research (1) that workload and responsibility are appraised as challenges and role ambiguity and…

  5. Models meet data: Challenges and opportunities in implementing land management in Earth system models.

    Science.gov (United States)

    Pongratz, Julia; Dolman, Han; Don, Axel; Erb, Karl-Heinz; Fuchs, Richard; Herold, Martin; Jones, Chris; Kuemmerle, Tobias; Luyssaert, Sebastiaan; Meyfroidt, Patrick; Naudts, Kim

    2018-04-01

    As the applications of Earth system models (ESMs) move from general climate projections toward questions of mitigation and adaptation, the inclusion of land management practices in these models becomes crucial. We carried out a survey among modeling groups to show an evolution from models able only to deal with land-cover change to more sophisticated approaches that allow also for the partial integration of land management changes. For the longer term a comprehensive land management representation can be anticipated for all major models. To guide the prioritization of implementation, we evaluate ten land management practices-forestry harvest, tree species selection, grazing and mowing harvest, crop harvest, crop species selection, irrigation, wetland drainage, fertilization, tillage, and fire-for (1) their importance on the Earth system, (2) the possibility of implementing them in state-of-the-art ESMs, and (3) availability of required input data. Matching these criteria, we identify "low-hanging fruits" for the inclusion in ESMs, such as basic implementations of crop and forestry harvest and fertilization. We also identify research requirements for specific communities to address the remaining land management practices. Data availability severely hampers modeling the most extensive land management practice, grazing and mowing harvest, and is a limiting factor for a comprehensive implementation of most other practices. Inadequate process understanding hampers even a basic assessment of crop species selection and tillage effects. The need for multiple advanced model structures will be the challenge for a comprehensive implementation of most practices but considerable synergy can be gained using the same structures for different practices. A continuous and closer collaboration of the modeling, Earth observation, and land system science communities is thus required to achieve the inclusion of land management in ESMs. © 2017 John Wiley & Sons Ltd.

  6. Challenging the Standard Model with the muon g − 2

    Indian Academy of Sciences (India)

    The discrepancy between experiment and the Standard Model prediction of ... The measurement of the anomalous magnetic moment of the muon aµ = (g−2)/2 ( ... to evaluate the leading-order hadronic term (see [3,4] for recent reviews). .... update of their previous analysis and a new preliminary one based on data collected.

  7. Mathematical Modeling: Challenging the Figured Worlds of Elementary Mathematics

    Science.gov (United States)

    Wickstrom, Megan H.

    2017-01-01

    This article is a report on a teacher study group that focused on three elementary teachers' perceptions of mathematical modeling in contrast to typical mathematics instruction. Through the theoretical lens of figured worlds, I discuss how mathematics instruction was conceptualized across the classrooms in terms of artifacts, discourse, and…

  8. Schoolwide Enrichment Model: Challenging All Children to Excel

    Science.gov (United States)

    Beecher, Margaret

    2010-01-01

    This article summarizes how the components of the Schoolwide Enrichment Model were used to dramatically reduce the achievement gap in a school with a high at-risk student population. The theories of enrichment and instructional differentiation replaced an existing remedial paradigm and a strength-based methodology was embraced by the school…

  9. Challenges in soil erosion research and prediction model development

    Science.gov (United States)

    Quantification of soil erosion has been traditionally considered as a surface hydrologic process with equations for soil detachment and sediment transport derived from the mechanics and hydraulics of the rainfall and surface flow. Under the current erosion modeling framework, the soil has a constant...

  10. Leadership Identity Development: Challenges in Applying a Developmental Model

    Science.gov (United States)

    Komives, Susan R.; Longerbeam, Susan D.; Mainella, Felicia; Osteen, Laura; Owen, Julie E.; Wagner, Wendy

    2009-01-01

    The leadership identity development (LID) grounded theory (Komives, Owen, Longerbeam, Mainella, & Osteen, 2005) and related LID model (Komives, Longerbeam, Owen, Mainella, & Osteen, 2006) present a framework for understanding how individual college students develop the social identity of being collaborative, relational leaders…

  11. Challenges in Modeling the Degradation of Ceramic Waste Forms

    Energy Technology Data Exchange (ETDEWEB)

    Devanathan, Ramaswami; Gao, Fei; Sun, Xin

    2011-09-01

    We identify the state of the art, gaps in current understanding, and key research needs in the area of modeling the long-term degradation of ceramic waste forms for nuclear waste disposition. The directed purpose of this report is to define a roadmap for Waste IPSC needs to extend capabilities of waste degradation to ceramic waste forms, which overlaps with the needs of the subconsinuum scale of FMM interests. The key knowledge gaps are in the areas of (i) methodology for developing reliable interatomic potentials to model the complex atomic-level interactions in waste forms; (ii) characterization of water interactions at ceramic surfaces and interfaces; and (iii) extension of atomic-level insights to the long time and distance scales relevant to the problem of actinide and fission product immobilization.

  12. Interest rate modeling post-crisis challenges and approaches

    CERN Document Server

    Grbac, Zorana

    2015-01-01

    Filling a gap in the literature caused by the recent financial crisis, this book provides a treatment of the techniques needed to model and evaluate interest rate derivatives according to the new paradigm for fixed income markets. Concerning this new development, there presently exist only research articles and two books, one of them an edited volume, both being written by researchers working mainly in practice. The aim of this book is to concentrate primarily on the methodological side, thereby providing an overview of the state-of-the-art and also clarifying the link between the new models and the classical literature. The book is intended to serve as a guide for graduate students and researchers as well as practitioners interested in the paradigm change for fixed income markets. A basic knowledge of fixed income markets and related stochastic methodology is assumed as a prerequisite.

  13. Atmospheric dispersion modeling: Challenges of the Fukushima Daiichi response

    Energy Technology Data Exchange (ETDEWEB)

    Sugiyama, Gayle [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Nasstrom, John [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pobanz, Brenda [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Foster, Kevin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Simpson, Matthew [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vogt, Phil [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Aluzzi, Fernando [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Homann, Steve [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2012-05-01

    In this research, the U.S. Department of Energy’s (DOE) National Atmospheric Release Advisory Center (NARAC) provided a wide range of predictions and analyses as part of the response to the Fukushima Daiichi Nuclear Power Plant accident including: daily Japanese weather forecasts and atmospheric transport predictions to inform planning for field monitoring operations and to provide U.S. government agencies with ongoing situational awareness of meteorological conditions; estimates of possible dose in Japan based on hypothetical U.S. Nuclear Regulatory Commission scenarios of potential radionuclide releases to support protective action planning for U.S. citizens; predictions of possible plume arrival times and dose levels at U.S. locations; and source estimation and plume model refinement based on atmospheric dispersion modeling and available monitoring data.

  14. Challenges in the modeling of tidal disruption events lightcurves

    Directory of Open Access Journals (Sweden)

    Lodato G.

    2012-12-01

    Full Text Available In this contribution, I review the recent developments on the modeling of the lightcurve of tidal disruption events. Our understanding has evolved significantly from the earlier seminal results that imply a simple power-law decay of the bolometric light curve as t−5/3. We now know that the details of the rise to the peak of the lightcurve is determined mainly by the internal structure of the disrupted star. We also have improved models for the disc thermal emission, showing that in this case the decline of the luminosity with time should be much flatter than the standard t−5/3 law, especially in optical and UV wavelengths, while the X-ray lightcurve is generally best suited to track the bolometric one. Finally, we are just starting to explore the interesting general relativistic effects that might arise for such events, for which the tidal radius lies very close to the black hole event horizon.

  15. Challenges in Modeling the Degradation of Ceramic Waste Forms

    International Nuclear Information System (INIS)

    Devanathan, Ramaswami; Gao, Fei; Sun, Xin

    2011-01-01

    We identify the state of the art, gaps in current understanding, and key research needs in the area of modeling the long-term degradation of ceramic waste forms for nuclear waste disposition. The directed purpose of this report is to define a roadmap for Waste IPSC needs to extend capabilities of waste degradation to ceramic waste forms, which overlaps with the needs of the subconsinuum scale of FMM interests. The key knowledge gaps are in the areas of (i) methodology for developing reliable interatomic potentials to model the complex atomic-level interactions in waste forms; (ii) characterization of water interactions at ceramic surfaces and interfaces; and (iii) extension of atomic-level insights to the long time and distance scales relevant to the problem of actinide and fission product immobilization.

  16. Understanding rare disease pathogenesis: a grand challenge for model organisms.

    Science.gov (United States)

    Hieter, Philip; Boycott, Kym M

    2014-10-01

    In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS. Copyright © 2014 by the Genetics Society of America.

  17. The new challenges of multiplex networks: Measures and models

    Science.gov (United States)

    Battiston, Federico; Nicosia, Vincenzo; Latora, Vito

    2017-02-01

    What do societies, the Internet, and the human brain have in common? They are all examples of complex relational systems, whose emerging behaviours are largely determined by the non-trivial networks of interactions among their constituents, namely individuals, computers, or neurons, rather than only by the properties of the units themselves. In the last two decades, network scientists have proposed models of increasing complexity to better understand real-world systems. Only recently we have realised that multiplexity, i.e. the coexistence of several types of interactions among the constituents of a complex system, is responsible for substantial qualitative and quantitative differences in the type and variety of behaviours that a complex system can exhibit. As a consequence, multilayer and multiplex networks have become a hot topic in complexity science. Here we provide an overview of some of the measures proposed so far to characterise the structure of multiplex networks, and a selection of models aiming at reproducing those structural properties and quantifying their statistical significance. Focusing on a subset of relevant topics, this brief review is a quite comprehensive introduction to the most basic tools for the analysis of multiplex networks observed in the real-world. The wide applicability of multiplex networks as a framework to model complex systems in different fields, from biology to social sciences, and the colloquial tone of the paper will make it an interesting read for researchers working on both theoretical and experimental analysis of networked systems.

  18. Educational Modelling Language and Learning Design: new challenges for instructional re-usability and personalized learning

    NARCIS (Netherlands)

    Hummel, Hans; Manderveld, Jocelyn; Tattersall, Colin; Koper, Rob

    2003-01-01

    Published: Hummel, H. G. K., Manderveld, J. M., Tattersall, C.,& Koper, E. J. R. (2004). Educational Modelling Language: new challenges for instructional re-usability and personalized learning. International Journal of Learning Technology, 1, 1, 110-111.

  19. An anti-nicotinic cognitive challenge model using mecamylamine in comparison with the anti-muscarinic cognitive challenge using scopolamine.

    Science.gov (United States)

    Baakman, Anne Catrien; Alvarez-Jimenez, Ricardo; Rissmann, Robert; Klaassen, Erica S; Stevens, Jasper; Goulooze, Sebastiaan C; den Burger, Jeroen C G; Swart, Eleonora L; van Gerven, Joop M A; Groeneveld, Geert Jan

    2017-08-01

    The muscarinic acetylcholine receptor antagonist scopolamine is often used for proof-of-pharmacology studies with pro-cognitive compounds. From a pharmacological point of view, it would seem more rational to use a nicotinic rather than a muscarinic anticholinergic challenge to prove pharmacology of a nicotinic acetylcholine receptor agonist. This study aims to characterize a nicotinic anticholinergic challenge model using mecamylamine and to compare it to the scopolamine model. In this double-blind, placebo-controlled, four-way cross-over trial, 12 healthy male subjects received oral mecamylamine 10 and 20 mg, intravenous scopolamine 0.5 mg and placebo. Pharmacokinetics were analysed using non-compartmental analysis. Pharmacodynamic effects were measured with a multidimensional test battery that includes neurophysiological, subjective, (visuo)motor and cognitive measurements. All treatments were safe and well tolerated. Mecamylamine had a t max of 2.5 h and a C max of 64.5 ng ml -1 for the 20 mg dose. Mecamylamine had a dose-dependent effect decreasing the adaptive tracking performance and VAS alertness, and increasing the finger tapping and visual verbal learning task performance time and errors. Scopolamine significantly affected almost all pharmacodynamic tests. This study demonstrated that mecamylamine causes nicotinic receptor specific temporary decline in cognitive functioning. Compared with the scopolamine model, pharmacodynamic effects were less pronounced at the dose levels tested; however, mecamylamine caused less sedation. The cognitive effects of scopolamine might at least partly be caused by sedation. Whether the mecamylamine model can be used for proof-of-pharmacology of nicotinic acetylcholine receptor agonists remains to be established. © 2017 The British Pharmacological Society.

  20. Business Models and Producer-Owned Ventures: Choices, Challenges, and Changes

    OpenAIRE

    Kenkel, Philip L.; Park, John L.

    2007-01-01

    Producer-owned business models are rapidly evolving. Producer-owned, value-added ventures face a number of organizational challenges, including capital acquisition, security exchange registration, antitrust exemption, borrowing eligibility, and operational flexibility. This paper examines the success of evolving producer-owned business models in addressing these challenges. The need for uniform criteria to distinguish producer-owned business from other business forms throughout the complex st...

  1. Assessing dengue vaccination impact: Model challenges and future directions.

    Science.gov (United States)

    Recker, Mario; Vannice, Kirsten; Hombach, Joachim; Jit, Mark; Simmons, Cameron P

    2016-08-31

    In response to the sharp rise in the global burden caused by dengue virus (DENV) over the last few decades, the WHO has set out three specific key objectives in its disease control strategy: (i) to estimate the true burden of dengue by 2015; (ii) a reduction in dengue mortality by at least 50% by 2020 (used as a baseline); and (iii) a reduction in dengue morbidity by at least 25% by 2020. Although various elements will all play crucial parts in achieving this goal, from diagnosis and case management to integrated surveillance and outbreak response, sustainable vector control, vaccine implementation and finally operational and implementation research, it seems clear that new tools (e.g. a safe and effective vaccine and/or effective vector control) are key to success. The first dengue vaccine was licensed in December 2015, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur. The WHO has provided guidance on the use of CYD-TDV in endemic countries, for which there are a variety of considerations beyond the risk-benefit evaluation done by regulatory authorities, including public health impact and cost-effectiveness. Population-level vaccine impact and economic and financial aspects are two issues that can potentially be considered by means of mathematical modelling, especially for new products for which empirical data are still lacking. In December 2014 a meeting was convened by the WHO in order to revisit the current status of dengue transmission models and their utility for public health decision-making. Here, we report on the main points of discussion and the conclusions of this meeting, as well as next steps for maximising the use of mathematical models for vaccine decision-making. Copyright © 2016.

  2. Exploring the oxygen challenge test as a microcirculation evaluation model

    Directory of Open Access Journals (Sweden)

    Hugo Ferreira

    2013-12-01

    Full Text Available Cutaneous microcirculation has emerged in recent years as a practical accessible subject for the study of peripheral circulation. Non-invasive techniques such as Laser Doppler Flowmetry (LDF, skin Evaporimetry and Transcutaneous Gasimetry in association with provocation tests, render cutaneous circulation a very attractive research model. This study was applied to a group of healthy young female volunteers, (n = 8, (21,6 ± 2,6 years old breathing a 100 % oxygen atmosphere for 10 minutes. This test allowed us to evaluate the circulatory response in the lower limb microcirculation. Measurement techniques included local blood flow by LDF, Transcutaneous (tc pO2 partial pressure and Transepidermal Water Loss (TEWL by Evaporimetry. Data analysis revels that tc-pO2 and LDF changed significantly during the test. A reciprocal evolution profile was registered in LDF and TEWL, which seems to support previous data that changes in local blood flow may influence the epidermal “barrier” function. This model seems suitable to characterize the lower limb microcirculation.

  3. Modeling food matrix effects on chemical reactivity: Challenges and perspectives.

    Science.gov (United States)

    Capuano, Edoardo; Oliviero, Teresa; van Boekel, Martinus A J S

    2017-06-29

    The same chemical reaction may be different in terms of its position of the equilibrium (i.e., thermodynamics) and its kinetics when studied in different foods. The diversity in the chemical composition of food and in its structural organization at macro-, meso-, and microscopic levels, that is, the food matrix, is responsible for this difference. In this viewpoint paper, the multiple, and interconnected ways the food matrix can affect chemical reactivity are summarized. Moreover, mechanistic and empirical approaches to explain and predict the effect of food matrix on chemical reactivity are described. Mechanistic models aim to quantify the effect of food matrix based on a detailed understanding of the chemical and physical phenomena occurring in food. Their applicability is limited at the moment to very simple food systems. Empirical modeling based on machine learning combined with data-mining techniques may represent an alternative, useful option to predict the effect of the food matrix on chemical reactivity and to identify chemical and physical properties to be further tested. In such a way the mechanistic understanding of the effect of the food matrix on chemical reactions can be improved.

  4. Challenges for the kinetic unified dark matter model

    International Nuclear Information System (INIS)

    Giannakis, Dimitrios; Hu, Wayne

    2005-01-01

    Given that the dark matter and dark energy in the Universe affect cosmological observables only gravitationally, their phenomenology may be described by a single stress-energy tensor. True unification however requires a theory that reproduces the successful phenomenology of ΛCDM and that requirement places specific constraints on the stress structure of the matter. We show that a recently proposed unification through an offset quadratic kinetic term for a scalar field is exactly equivalent to a fluid with a closed-form barotropic equation of state plus cosmological constant. The finite pressure at high densities introduces a cutoff in the linear power spectrum, which may alleviate the dark matter substructure problem; we provide a convenient fitting function for such studies. Given that sufficient power must remain to reionize the Universe, the equation of state today is nonrelativistic with p∝ρ 2 and a Jeans scale in the parsec regime for all relevant densities. Structure may then be evolved into the nonlinear regime with standard hydrodynamic techniques. In fact, the model is equivalent to the well-studied collisional dark matter with negligible mean free path. If recent observations of the triaxiality of dark matter halos and ram pressure stripping in galaxy clusters are confirmed, this model will be ruled out

  5. Stratified flows with variable density: mathematical modelling and numerical challenges.

    Science.gov (United States)

    Murillo, Javier; Navas-Montilla, Adrian

    2017-04-01

    Stratified flows appear in a wide variety of fundamental problems in hydrological and geophysical sciences. They may involve from hyperconcentrated floods carrying sediment causing collapse, landslides and debris flows, to suspended material in turbidity currents where turbulence is a key process. Also, in stratified flows variable horizontal density is present. Depending on the case, density varies according to the volumetric concentration of different components or species that can represent transported or suspended materials or soluble substances. Multilayer approaches based on the shallow water equations provide suitable models but are not free from difficulties when moving to the numerical resolution of the governing equations. Considering the variety of temporal and spatial scales, transfer of mass and energy among layers may strongly differ from one case to another. As a consequence, in order to provide accurate solutions, very high order methods of proved quality are demanded. Under these complex scenarios it is necessary to observe that the numerical solution provides the expected order of accuracy but also converges to the physically based solution, which is not an easy task. To this purpose, this work will focus in the use of Energy balanced augmented solvers, in particular, the Augmented Roe Flux ADER scheme. References: J. Murillo , P. García-Navarro, Wave Riemann description of friction terms in unsteady shallow flows: Application to water and mud/debris floods. J. Comput. Phys. 231 (2012) 1963-2001. J. Murillo B. Latorre, P. García-Navarro. A Riemann solver for unsteady computation of 2D shallow flows with variable density. J. Comput. Phys.231 (2012) 4775-4807. A. Navas-Montilla, J. Murillo, Energy balanced numerical schemes with very high order. The Augmented Roe Flux ADER scheme. Application to the shallow water equations, J. Comput. Phys. 290 (2015) 188-218. A. Navas-Montilla, J. Murillo, Asymptotically and exactly energy balanced augmented flux

  6. Facing up to 'challenging behaviour': a model for training in staff-client interaction.

    Science.gov (United States)

    Farrell, Gerald A; Shafiei, Touran; Salmon, Peter

    2010-07-01

    This paper draws on theory and evidence to develop a conceptual staff training model for the management of 'challenging behaviour'. Staff working with clients who are experienced as challenging commonly report negative feelings such as anxiety, anger, guilt, fear, self-blame and powerlessness, as well as dissatisfaction with their jobs. Current training programmes in challenging behaviour offer a 'smorgasbord' of content, without a clearly defined conceptual framework. Medline and PsychInfo were searched for papers in English from 1998 to 2008, linking 'nurs*' to 'challenging behavio*' and its related terms. Additional hand-searching identified informative papers from disciplines outside nursing older than the search period. We developed an applied model for training educators in respect of challenging behaviours. The model directs educators to consider: the influence of the nurse, including their values, emotional processes and behavioural skills; features of the client; and features of the situation in which the behaviour occurs, including its culture and working practices and physical environment. The most striking implication of the model is that it explicitly recognizes the importance of domains of learning other than skill. This enables educators to find educationally appropriate responses to resource limitations that inevitably constrain training. Challenging behaviour should be considered as a product of several intertwined factors: the actors involved - nurses, clients and others - and the situation in which the behaviour occurs, including its culture and working practices and physical environment.

  7. Epithelium-innate immune cell axis in mucosal responses to SIV.

    Science.gov (United States)

    Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

    2017-03-01

    In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

  8. BIG DATA-Related Challenges and Opportunities in Earth System Modeling

    Science.gov (United States)

    Bamzai, A. S.

    2012-12-01

    Knowledge of the Earth's climate has increased immensely in recent decades, both through observational analysis and modeling. BIG DATA-related challenges emerge in our quest for understanding the variability and predictability of the climate and earth system on a range of time scales, as well as in our endeavor to improve predictive capability using state-of-the-science models. To enable further scientific discovery, bottlenecks in current paradigms need to be addressed. An overview of current NSF activities in Earth System Modeling with a focus on associated data-related challenges and opportunities, will be presented.

  9. Energy efficiency and renewable energy modeling with ETSAP TIAM - challenges, opportunities, and solutions

    DEFF Research Database (Denmark)

    Gregg, Jay Sterling; Balyk, Olexandr; Pérez, Cristian Hernán Cabrera

    over pre-industrial times. To accomplish this, pathways are constructed for each objective, which then form the basis for a scenario analysis using the Energy Technology System Analysis Program TIMES Integrated Assessment Model (ETSAP-TIAM). This presentation focuses on the modeling challenges...

  10. Spatial agent-based models for socio-ecological systems: challenges and prospects

    NARCIS (Netherlands)

    de Filatova, T.; Verburg, P.H.; Parker, D.C.; Stannard, S.R.

    2013-01-01

    Departing from the comprehensive reviews carried out in the field, we identify the key challenges that agent-based methodology faces when modeling coupled socio-ecological systems. Focusing primarily on the papers presented in this thematic issue, we review progress in spatial agent-based models

  11. Grand challenge problems in environmental modeling and remediation: groundwater contaminant transport

    Energy Technology Data Exchange (ETDEWEB)

    Todd Arbogast; Steve Bryant; Clint N. Dawson; Mary F. Wheeler

    1998-08-31

    This report describes briefly the work of the Center for Subsurface Modeling (CSM) of the University of Texas at Austin (and Rice University prior to September 1995) on the Partnership in Computational Sciences Consortium (PICS) project entitled Grand Challenge Problems in Environmental Modeling and Remediation: Groundwater Contaminant Transport.

  12. Ahead of the Curve: Implementation Challenges in Personalized Learning School Models

    Science.gov (United States)

    Bingham, Andrea J.; Pane, John F.; Steiner, Elizabeth D.; Hamilton, Laura S.

    2018-01-01

    In the current educational context, school models that leverage technology to personalize instruction have proliferated, as has student enrollment in, and funding of, such school models. However, even the best laid plans are subject to challenges in design and practice, particularly in the dynamic context of a school. In this collective case…

  13. Challenges and priorities for modelling livestock health and pathogens in the context of climate change

    Energy Technology Data Exchange (ETDEWEB)

    Özkan, Şeyda [Department of Animal and Aquacultural Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), Post Box 5003, Ås 1430 (Norway); Vitali, Andrea; Lacetera, Nicola [University of Tuscia, Department of Agriculture and Forestry Science (DAFNE), Via San Camillo De Lellis, snc, Viterbo 01100 (Italy); Amon, Barbara [Leibniz Institute for Agricultural Engineering Potsdam-Bornim (ATB), Max-Eyth-Allee 100, Potsdam 14469 (Germany); Bannink, André [Wageningen UR Livestock Research, P.O. Box 338, Wageningen 6700 AH (Netherlands); Bartley, Dave J. [Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ (United Kingdom); Blanco-Penedo, Isabel [Animal Welfare Subprogram, IRTA, Veinat de Sies s/n, Monells, Girona 17121 (Spain); Haas, Yvette de [Wageningen UR Livestock Research, P.O. Box 338, Wageningen 6700 AH (Netherlands); Dufrasne, Isabelle [Nutrition Unit, Animal Production Department, Veterinary Faculty, University of Liège, Boulevard de Colonster 20, Bât. B43, Liège 4000 (Belgium); Elliott, John [ADAS UK Ltd, 4205 Park Approach, Thorpe Park, Leeds LS15 8GB (United Kingdom); Eory, Vera [Scotland' s Rural College (SRUC), Peter Wilson Building, Kings Buildings, West Mains Road, Edinburgh EH9 3JG (United Kingdom); Fox, Naomi J. [Scotland' s Rural College (SRUC), Animal and Veterinary Sciences, Roslin Institute Building, Easter Bush, Midlothian EH25 9RG (United Kingdom); Garnsworthy, Phil C. [University of Nottingham, School of Biosciences, Sutton Bonington Campus, Loughborough LE12 5RD (United Kingdom); and others

    2016-11-15

    Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can

  14. Challenges and priorities for modelling livestock health and pathogens in the context of climate change

    International Nuclear Information System (INIS)

    Özkan, Şeyda; Vitali, Andrea; Lacetera, Nicola; Amon, Barbara; Bannink, André; Bartley, Dave J.; Blanco-Penedo, Isabel; Haas, Yvette de; Dufrasne, Isabelle; Elliott, John; Eory, Vera; Fox, Naomi J.; Garnsworthy, Phil C.

    2016-01-01

    Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can

  15. The Electric Vehicles Ecosystem Model: Construct, Analysis and Identification of Key Challenges

    Directory of Open Access Journals (Sweden)

    Zulkarnain

    2014-09-01

    Full Text Available This paper builds a conceptual model of electric vehicles’ (EV ecosystem and value chain build-up. Based on the literature, the research distinguishes the most critical challenges that are on the way of mobility systems’ electrification. Consumers still have some questions that call for answers before they are ready to adopt evs.With regard to technical aspects, some challenges are coming from vehicles, charging infrastructure, battery technology, and standardization. The use of battery in EVs will bring in additional environmental challenges, coming from the battery life cycle for used battery, the manufacturing, and from some materials used and treated in the manufacturing process. The policy aspects include mostly taxation strategies. For most part, established market conditions are still lacking and there are a number of unresolved challenges on both supply and demand side of the EV market.

  16. Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models.

    Directory of Open Access Journals (Sweden)

    Jonathan R Karr

    2015-05-01

    Full Text Available Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model's structure and in silico "experimental" data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation.

  17. Seven challenges for modelling indirect transmission: Vector-borne diseases, macroparasites and neglected tropical diseases

    Directory of Open Access Journals (Sweden)

    T. Déirdre Hollingsworth

    2015-03-01

    Full Text Available Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission – whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of “evolution-proof” interventions against vector-borne disease.

  18. Seven challenges for modelling indirect transmission: vector-borne diseases, macroparasites and neglected tropical diseases.

    Science.gov (United States)

    Hollingsworth, T Déirdre; Pulliam, Juliet R C; Funk, Sebastian; Truscott, James E; Isham, Valerie; Lloyd, Alun L

    2015-03-01

    Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission--whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of "evolution-proof" interventions against vector-borne disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Industrial Adoption of Model-Based Systems Engineering: Challenges and Strategies

    Science.gov (United States)

    Maheshwari, Apoorv

    As design teams are becoming more globally integrated, one of the biggest challenges is to efficiently communicate across the team. The increasing complexity and multi-disciplinary nature of the products are also making it difficult to keep track of all the information generated during the design process by these global team members. System engineers have identified Model-based Systems Engineering (MBSE) as a possible solution where the emphasis is placed on the application of visual modeling methods and best practices to systems engineering (SE) activities right from the beginning of the conceptual design phases through to the end of the product lifecycle. Despite several advantages, there are multiple challenges restricting the adoption of MBSE by industry. We mainly consider the following two challenges: a) Industry perceives MBSE just as a diagramming tool and does not see too much value in MBSE; b) Industrial adopters are skeptical if the products developed using MBSE approach will be accepted by the regulatory bodies. To provide counter evidence to the former challenge, we developed a generic framework for translation from an MBSE tool (Systems Modeling Language, SysML) to an analysis tool (Agent-Based Modeling, ABM). The translation is demonstrated using a simplified air traffic management problem and provides an example of a potential quite significant value: the ability to use MBSE representations directly in an analysis setting. For the latter challenge, we are developing a reference model that uses SysML to represent a generic infusion pump and SE process for planning, developing, and obtaining regulatory approval of a medical device. This reference model demonstrates how regulatory requirements can be captured effectively through model-based representations. We will present another case study at the end where we will apply the knowledge gained from both case studies to a UAV design problem.

  20. Physics-based distributed snow models in the operational arena: Current and future challenges

    Science.gov (United States)

    Winstral, A. H.; Jonas, T.; Schirmer, M.; Helbig, N.

    2017-12-01

    The demand for modeling tools robust to climate change and weather extremes along with coincident increases in computational capabilities have led to an increase in the use of physics-based snow models in operational applications. Current operational applications include the WSL-SLF's across Switzerland, ASO's in California, and USDA-ARS's in Idaho. While the physics-based approaches offer many advantages there remain limitations and modeling challenges. The most evident limitation remains computation times that often limit forecasters to a single, deterministic model run. Other limitations however remain less conspicuous amidst the assumptions that these models require little to no calibration based on their foundation on physical principles. Yet all energy balance snow models seemingly contain parameterizations or simplifications of processes where validation data are scarce or present understanding is limited. At the research-basin scale where many of these models were developed these modeling elements may prove adequate. However when applied over large areas, spatially invariable parameterizations of snow albedo, roughness lengths and atmospheric exchange coefficients - all vital to determining the snowcover energy balance - become problematic. Moreover as we apply models over larger grid cells, the representation of sub-grid variability such as the snow-covered fraction adds to the challenges. Here, we will demonstrate some of the major sensitivities of distributed energy balance snow models to particular model constructs, the need for advanced and spatially flexible methods and parameterizations, and prompt the community for open dialogue and future collaborations to further modeling capabilities.

  1. Participation and occupation in occupational therapy models of practice: A discussion of possibilities and challenges.

    Science.gov (United States)

    Larsson-Lund, Maria; Nyman, Anneli

    2017-11-01

    Occupation has been the focus in occupational therapy practice to greater or lesser degrees from a historical viewpoint. This evokes a need to discuss whether concepts that are added to our field will enhance or blur our focus on occupation. To explore how the concept of participation in the International Classification of Functioning, Disability and Health (ICF) is related to the concept of occupation by reviewing and comparing its use in three models of practice within occupational therapy. The aim was also to generate discussion on possibilities and challenges concerning the relationship of participation and occupation. The models reviewed were The Model of Human Occupation (MOHO), the Canadian Model of Occupational Performance and Engagement (CMOP-E) and the Occupational Therapy Intervention Process Model (OTIPM). The concept of participation was related to occupation in different ways in these models. Based on the review some challenges and considerations for occupational therapy were generated. Relating the concept of participation from the ICF to the concept of occupation in models of practice can be challenging. At the same time, relating the concepts can be a resource to develop occupational therapy and the understanding of occupational issues in society.

  2. Challenges of forest landscape modeling - simulating large landscapes and validating results

    Science.gov (United States)

    Hong S. He; Jian Yang; Stephen R. Shifley; Frank R. Thompson

    2011-01-01

    Over the last 20 years, we have seen a rapid development in the field of forest landscape modeling, fueled by both technological and theoretical advances. Two fundamental challenges have persisted since the inception of FLMs: (1) balancing realistic simulation of ecological processes at broad spatial and temporal scales with computing capacity, and (2) validating...

  3. Challenges of assessing fire and burn severity using field measures, remote sensing and modelling

    Science.gov (United States)

    Penelope Morgan; Robert E. Keane; Gregory K. Dillon; Theresa B. Jain; Andrew T. Hudak; Eva C. Karau; Pamela G. Sikkink; Zachery A. Holden; Eva K. Strand

    2014-01-01

    Comprehensive assessment of ecological change after fires have burned forests and rangelands is important if we are to understand, predict and measure fire effects. We highlight the challenges in effective assessment of fire and burn severity in the field and using both remote sensing and simulation models. We draw on diverse recent research for guidance on assessing...

  4. The Challenge of Forecasting the Onset and Development of Radiation Fog Using Mesoscale Atmospheric Models

    NARCIS (Netherlands)

    Steeneveld, G.J.; Ronda, R.J.; Holtslag, A.A.M.

    2015-01-01

    The numerical weather prediction of radiation fog is challenging, as many models typically show large biases for the timing of the onset and dispersal of the fog, as well as for its depth and liquid water content. To understand the role of physical processes, i.e. turbulence, radiation, land-surface

  5. Special Section: The third provenance challenge on using the open provenance model for interoperability

    NARCIS (Netherlands)

    Simmhan, Y; Groth, P.T.; Moreau, L

    2011-01-01

    The third provenance challenge was organized to evaluate the efficacy of the Open Provenance Model (OPM) in representing and sharing provenance with the goal of improving the specification. A data loading scientific workflow that ingests data files into a relational database for the Pan-STARRS sky

  6. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    NARCIS (Netherlands)

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment.

  7. From the Building to the Grid: An Energy Revolution and Modeling Challenge; Workshop Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Kroposki, B.; Komomua, C.; O' Malley, M.

    2013-01-01

    This report summarizes the workshop entitled: From the Building to the Grid: An Energy Revolution and Modeling Challenge. The first workshop was held May 1-2, 2012 on NREL's campus in Golden, Colorado. The second was held June 6-7, 2012 at the University College Dublin, in Dublin, Ireland.

  8. Modelling of vector hysteresis at macromagnetic scale: Open questions and challenges

    International Nuclear Information System (INIS)

    Cardelli, E.; Faba, A.

    2016-01-01

    After a short review of some experimental evidences the motivations that lead to the practical need of phenomenological modelling for the analysis of magnetic materials at macro-scale, and some challenging formulations are presented and discussed. Examples of practical applications are reported.

  9. Decision-Making in Agent-Based Models of Migration: State of the Art and Challenges.

    Science.gov (United States)

    Klabunde, Anna; Willekens, Frans

    We review agent-based models (ABM) of human migration with respect to their decision-making rules. The most prominent behavioural theories used as decision rules are the random utility theory, as implemented in the discrete choice model, and the theory of planned behaviour. We identify the critical choices that must be made in developing an ABM, namely the modelling of decision processes and social networks. We also discuss two challenges that hamper the widespread use of ABM in the study of migration and, more broadly, demography and the social sciences: (a) the choice and the operationalisation of a behavioural theory (decision-making and social interaction) and (b) the selection of empirical evidence to validate the model. We offer advice on how these challenges might be overcome.

  10. Challenges and priorities for modelling livestock health and pathogens in the context of climate change.

    Science.gov (United States)

    Özkan, Şeyda; Vitali, Andrea; Lacetera, Nicola; Amon, Barbara; Bannink, André; Bartley, Dave J; Blanco-Penedo, Isabel; de Haas, Yvette; Dufrasne, Isabelle; Elliott, John; Eory, Vera; Fox, Naomi J; Garnsworthy, Phil C; Gengler, Nicolas; Hammami, Hedi; Kyriazakis, Ilias; Leclère, David; Lessire, Françoise; Macleod, Michael; Robinson, Timothy P; Ruete, Alejandro; Sandars, Daniel L; Shrestha, Shailesh; Stott, Alistair W; Twardy, Stanislaw; Vanrobays, Marie-Laure; Ahmadi, Bouda Vosough; Weindl, Isabelle; Wheelhouse, Nick; Williams, Adrian G; Williams, Hefin W; Wilson, Anthony J; Østergaard, Søren; Kipling, Richard P

    2016-11-01

    Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can

  11. Challenges of current hydraulic modeling with three examples; Herausforderungen des heutigen wasserbaulichen Versuchswesens mit drei Beispielen

    Energy Technology Data Exchange (ETDEWEB)

    De Cesare, Giovanni; Pfister, Michael; Daneshvari, Milad; Bieri, Martin [Ecole Polytechnique Federale de Lausanne (Switzerland). Lab. de Constructions Hydrauliques (EPFL-LCH)

    2012-07-01

    Most technical universities offering courses in civil engineering operate for meanwhile 100 years hydraulic laboratories. They investigate and optimize hydraulic structures related to dams, power plants and flood protection measures using physical modelling. These laboratories are usually fully booked today although this classical engineering approach was often predicted to disappear. The authors describe their experience and the new challenges in physical modelling, illustrated with three examples. (orig.)

  12. Asset transformation and the challenges to servitize a utility business model

    International Nuclear Information System (INIS)

    Helms, Thorsten

    2016-01-01

    The traditional energy utility business model is under pressure, and energy services are expected to play an important role for the energy transition. Experts and scholars argue that utilities need to innovate their business models, and transform from commodity suppliers to service providers. The transition from a product-oriented, capital-intensive business model based on tangible assets, towards a service-oriented, expense-intensive business model based on intangible assets may present great managerial and organizational challenges. Little research exists about such transitions for capital-intensive commodity providers, and particularly energy utilities, where the challenges to servitize are expected to be greatest. This qualitative paper explores the barriers to servitization within selected Swiss and German utility companies through a series of interviews with utility managers. One of them is ‘asset transformation’, the shift from tangible to intangible assets as major input factor for the value proposition, which is proposed as a driver for the complexity of business model transitions. Managers need to carefully manage those challenges, and find ways to operate both new service and established utility business models aside. Policy makers can support the transition of utilities through more favorable regulatory frameworks for energy services, and by supporting the exchange of knowledge in the industry. - Highlights: •The paper analyses the expected transformation of utilities into service-providers. •Service and utility business models possess very different attributes. •The former is based on intangible, the latter on tangible assets. •The transformation into a service-provider is related with great challenges. •Asset transformation is proposed as a barrier for business model innovation.

  13. Data Mining and Pattern Recognition Models for Identifying Inherited Diseases: Challenges and Implications

    OpenAIRE

    Iddamalgoda, Lahiru; Das, Partha S.; Aponso, Achala; Sundararajan, Vijayaraghava S.; Suravajhala, Prashanth; Valadi, Jayaraman K.

    2016-01-01

    Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited ...

  14. Challenges for Knowledge Management in the Context of IT Global Sourcing Models Implementation

    OpenAIRE

    Perechuda , Kazimierz; Sobińska , Małgorzata

    2014-01-01

    Part 2: Models and Functioning of Knowledge Management; International audience; The article gives a literature overview of the current challenges connected with the implementation of the newest IT sourcing models. In the dynamic environment, organizations are required to build their competitive advantage not only on their own resources, but also on resources commissioned from external providers, accessed through various forms of sourcing, including the sourcing of IT services. This paper pres...

  15. Challenges of the Modeling Methods for Investigating the Interaction between the CNT and the Surrounding Polymer

    Directory of Open Access Journals (Sweden)

    Roham Rafiee

    2013-01-01

    Full Text Available The interaction between the carbon nanotubes (CNT and the polymer is a key factor for determining the mechanical, thermal, and electrical properties of the CNT/polymer nanocomposite. However, it is difficult to measure experimentally the interfacial bonding properties between the CNT and the surrounding polymer. Therefore, computational modeling is used to predict the interaction properties. Different scale models, from atomistic to continuum, are critically reviewed addressing the advantages, the disadvantages, and the future challenges. Various methods of improvement for measuring the interaction properties are described. Finally, it is concluded that the semicontinuum modeling may be the best candidate for modeling the interaction between the CNT and the polymer.

  16. Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors

    DEFF Research Database (Denmark)

    Nguyen, E.D.; Meiler, J.; Norn, C.

    2013-01-01

    screening and to design and optimize drug candidates. However, low sequence identity between receptors, conformational flexibility, and chemical diversity of ligands present an enormous challenge to molecular modeling approaches. It is our hypothesis that rapid Monte-Carlo sampling of protein backbone...... extracellular loop. Furthermore, these models are consistently correlated with low Rosetta energy score. To predict their binding modes, ligand conformers of the 14 ligands co-crystalized with the GPCRs were docked against the top ranked comparative models. In contrast to the comparative models themselves...

  17. Modeling Acute Traumatic Hemorrhagic Shock Injury: Challenges and Guidelines for Preclinical Studies.

    Science.gov (United States)

    Tremoleda, Jordi L; Watts, Sarah A; Reynolds, Penny S; Thiemermann, Christoph; Brohi, Karim

    2017-12-01

    Trauma is responsible for a large proportion of the world's burden of disease, and is by far the biggest killer of young adults. Hemorrhage is the leading cause of preventable death and its effects are directly correlated with the incidence multi-organ failure in survivors. Trauma research is challenging due to patient heterogeneity, limited randomized controlled trials, and in vitro studies that fail to mimic the systemic injury response. Preclinical research remains essential for mechanistic and therapeutic discovery. Yet modeling the multifaceted nature of traumatic injury poses important experimental and welfare challenges associated with the onset of injury and prehospital and intra-operative care, the limited inter-species validation of coagulation profiles, the use of anesthesia/analgesia, and its impact on the systemic response to trauma; and the challenge of sustaining intensive care in recovery models. Proper model selection depends on the purpose of a given model and the criteria by which the experimental readouts will be clinically relevant. Such complexity warrants further refinement of experimental methodology and outcome measures to improve its clinical efficacy, while ensuring animal well-being. We review the experimental methodologies currently used for modeling traumatic hemorrhagic shock and addressing their impact on clinical translation. The aim of the review is to improve transparency and form a consensus when reporting methodology in trauma modeling.

  18. Current challenges in health economic modeling of cancer therapies: a research inquiry.

    Science.gov (United States)

    Miller, Jeffrey D; Foley, Kathleen A; Russell, Mason W

    2014-05-01

    The demand for economic models that evaluate cancer treatments is increasing, as healthcare decision makers struggle for ways to manage their budgets while providing the best care possible to patients with cancer. Yet, after nearly 2 decades of cultivating and refining techniques for modeling the cost-effectiveness and budget impact of cancer therapies, serious methodologic and policy challenges have emerged that question the adequacy of economic modeling as a sound decision-making tool in oncology. We sought to explore some of the contentious issues associated with the development and use of oncology economic models as informative tools in current healthcare decision-making. Our objective was to draw attention to these complex pharmacoeconomic concerns and to promote discussion within the oncology and health economics research communities. Using our combined expertise in health economics research and economic modeling, we structured our inquiry around the following 4 questions: (1) Are economic models adequately addressing questions relevant to oncology decision makers; (2) What are the methodologic limitations of oncology economic models; (3) What guidelines are followed for developing oncology economic models; and (4) Is the evolution of oncology economic modeling keeping pace with treatment innovation? Within the context of each of these questions, we discuss issues related to the technical limitations of oncology modeling, the availability of adequate data for developing models, and the problems with how modeling analyses and results are presented and interpreted. There is general acceptance that economic models are good, essential tools for decision-making, but the practice of oncology and its rapidly evolving technologies present unique challenges that make assessing and demonstrating value especially complex. There is wide latitude for improvement in oncology modeling methodologies and how model results are presented and interpreted. Complex technical and

  19. Next-Generation Climate Modeling Science Challenges for Simulation, Workflow and Analysis Systems

    Science.gov (United States)

    Koch, D. M.; Anantharaj, V. G.; Bader, D. C.; Krishnan, H.; Leung, L. R.; Ringler, T.; Taylor, M.; Wehner, M. F.; Williams, D. N.

    2016-12-01

    We will present two examples of current and future high-resolution climate-modeling research that are challenging existing simulation run-time I/O, model-data movement, storage and publishing, and analysis. In each case, we will consider lessons learned as current workflow systems are broken by these large-data science challenges, as well as strategies to repair or rebuild the systems. First we consider the science and workflow challenges to be posed by the CMIP6 multi-model HighResMIP, involving around a dozen modeling groups performing quarter-degree simulations, in 3-member ensembles for 100 years, with high-frequency (1-6 hourly) diagnostics, which is expected to generate over 4PB of data. An example of science derived from these experiments will be to study how resolution affects the ability of models to capture extreme-events such as hurricanes or atmospheric rivers. Expected methods to transfer (using parallel Globus) and analyze (using parallel "TECA" software tools) HighResMIP data for such feature-tracking by the DOE CASCADE project will be presented. A second example will be from the Accelerated Climate Modeling for Energy (ACME) project, which is currently addressing challenges involving multiple century-scale coupled high resolution (quarter-degree) climate simulations on DOE Leadership Class computers. ACME is anticipating production of over 5PB of data during the next 2 years of simulations, in order to investigate the drivers of water cycle changes, sea-level-rise, and carbon cycle evolution. The ACME workflow, from simulation to data transfer, storage, analysis and publication will be presented. Current and planned methods to accelerate the workflow, including implementing run-time diagnostics, and implementing server-side analysis to avoid moving large datasets will be presented.

  20. Challenges in land model representation of heat transfer in snow and frozen soils

    Science.gov (United States)

    Musselman, K. N.; Clark, M. P.; Nijssen, B.; Arnold, J.

    2017-12-01

    Accurate model simulations of soil thermal and moisture states are critical for realistic estimates of exchanges of energy, water, and biogeochemical fluxes at the land-atmosphere interface. In cold regions, seasonal snow-cover and organic soils form insulating barriers, modifying the heat and moisture exchange that would otherwise occur between mineral soils and the atmosphere. The thermal properties of these media are highly dynamic functions of mass, water and ice content. Land surface models vary in their representation of snow and soil processes, and thus in the treatment of insulation and heat exchange. For some models, recent development efforts have improved representation of heat transfer in cold regions, such as with multi-layer snow treatment, inclusion of soil freezing and organic soil properties, yet model deficiencies remain prevalent. We evaluate models that participated in the Protocol for the Analysis of Land Surface Models (PALS) Land Surface Model Benchmarking Evaluation Project (PLUMBER) experiment for proficiency in simulating heat transfer between the soil through the snowpack to the atmosphere. Using soil observations from cold region sites and a controlled experiment with Structure for Unifying Multiple Modeling Alternatives (SUMMA), we explore the impact of snow and soil model decisions and parameter values on heat transfer model skill. Specifically, we use SUMMA to mimic the spread of behaviors exhibited by the models that participated in PLUMBER. The experiment allows us to isolate relationships between model skill and process representation. The results are aimed to better understand existing model challenges and identify potential advances for cold region models.

  1. Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

    Science.gov (United States)

    Konstorum, Anna; Vella, Anthony T; Adler, Adam J; Laubenbacher, Reinhard C

    2017-06-01

    The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development. © 2017 The Author(s).

  2. Fate of challenge schistosomula in the murine anti-schistosome vaccine model

    International Nuclear Information System (INIS)

    Von Lichtenberg, F.; Correa-Oliveira, R.; Sher, A.

    1985-01-01

    Mice exposed to irradiated cercariae of Schistosoma mansoni develop a partial resistance to subsequent parasite challenge. In this study the authors utilized histopathologic methods to investigate the fate of both the immunizing and challenge cercariae in C57BL/6J mice. After immunization by percutaneous infection, a large number of the 50 Kr irradiated organisms could be detected in tissue sections of lung. However, as early as 2 weeks after immunization, the majority of these schistosomula apparently had died, leaving residual inflammatory foci. The numbers of these foci then gradually declined during the next 4 weeks of examination. Cercarial challenge of mice vaccinated 4 weeks previously provoked an intense eosinophil-enriched inflammatory response in percutaneously exposed ear pinnae. Despite these pronounced tissue reactions, no evidence of significant parasite damage or attrition was detected in this migration site. In contrast, schistosomula arriving in the lungs of vaccinated mice produced a greater number of residual inflammatory foci than did larvae appearing in the lungs of normal mice. In addition, challenge schistosomula were cleared from the lungs of vaccinated mice at a slower rate than they were from the lungs of control mice. These observations suggest that the lung is a major site of parasite attrition for both immunizing and challenge infections in the mouse irradiated vaccine model

  3. Development of patient specific cardiovascular models predicting dynamics in response to orthostatic stress challenges

    DEFF Research Database (Denmark)

    Ottesen, Johnny T.

    2013-01-01

    Physiological realistic models of the controlled cardiovascular system are constructed and validated against clinical data. Special attention is paid to the control of blood pressure, cerebral blood flow velocity, and heart rate during postural challenges, including sit-to-stand and head-up tilt....... This study describes development of patient specific models, and how sensitivity analysis and nonlinear optimization methods can be used to predict patient specific characteristics when analyzed using experimental data. Finally, we discuss how a given model can be used to understand physiological changes...

  4. Addressing challenges in single species assessments via a simple state-space assessment model

    DEFF Research Database (Denmark)

    Nielsen, Anders

    Single-species and age-structured fish stock assessments still remains the main tool for managing fish stocks. A simple state-space assessment model is presented as an alternative to (semi) deterministic procedures and the full parametric statistical catch at age models. It offers a solution...... to some of the key challenges of these models. Compared to the deterministic procedures it solves a list of problems originating from falsely assuming that age classified catches are known without errors and allows quantification of uncertainties of estimated quantities of interest. Compared to full...

  5. Challenges in Modeling Disturbance Regimes and Their Impacts in Arctic and Boreal Ecosystems (Invited)

    Science.gov (United States)

    McGuire, A. D.; Rupp, T. S.; Kurz, W.

    2013-12-01

    Disturbances in arctic and boreal terrestrial ecosystems influence services provided by these ecosystems to society. In particular, changes in disturbance regimes in northern latitudes have uncertain consequences for the climate system. A major challenge for the scientific community is to develop the capability to predict how the frequency, severity and resultant impacts of disturbance regimes will change in response to future changes in climate projected for northern high latitudes. Here we compare what is known about drivers and impacts of wildfire, phytophagous insect pests, and thermokarst disturbance to illustrate the complexities in predicting future changes in disturbance regimes and their impacts in arctic and boreal regions. Much of the research on predicting fire has relied on the use of drivers related to fire weather. However, changes in vegetation, such as increases in broadleaf species, associated with intensified fire regimes have the potential to influence future fire regimes through negative feedbacks associated with reduced flammability. Phytophagous insect outbreaks have affected substantial portions of the boreal region in the past, but frequently the range of the tree host is larger than the range of the insect. There is evidence that a number of insect species are expanding their range in response to climate change. Major challenges to predicting outbreaks of phytophagous insects include modeling the effects of climate change on insect growth and maturation, winter mortality, plant host health, the synchrony of insect life stages and plant host phenology, and changes in the ranges of insect pests. Moreover, Earth System Models often simplify the representation of vegetation characteristics, e.g. the use of plant functional types, providing insufficient detail to link to insect population models. Thermokarst disturbance occurs when the thawing of ice-rich permafrost results in substantial ground subsidence. In the boreal forest, thermokarst can

  6. An Anti-Nicotinic Cognitive Challenge Model using Mecamylamine in Comparison with the Anti-Muscarinic Cognitive Challenge using Scopolamine

    NARCIS (Netherlands)

    Baakman, A. C.; Alvarez-jimenez, R.; Rissmann, R.; Klaassen, E. S.; Stevens, J.; Goulooze, S. C.; Burger, J.; Swart, E. L.; Van Gerven, J. M. A.; Groeneveld, G. J.

    Aims The muscarinic acetylcholine receptor antagonist scopolamine is often used for proof-of-pharmacology studies with pro-cognitive compounds. From a pharmacological point of view, it would seem more rational to use a nicotinic rather than a muscarinic anticholinergic challenge to prove

  7. Challenges of the expansive use of Building Information Modeling (BIM in construction projects

    Directory of Open Access Journals (Sweden)

    Hannele Kerosuo

    2015-06-01

    Full Text Available Building information modeling (BIM is an emerging modeling technology which challenges existing work procedures and practices in the construction industry. In this article we study the challenges, problems and potential expansions of BIM as a tool in the design, construction and operation of buildings. For this purpose the interfaces between different parties are examined in Finnish construction projects. The methodological approach of the study is cultural-historical activity theory, according to which a new artifact becomes a mediating instrument when the participatory subjects reconfigure the entire activity. The implementation of BIM is now spreading from the design activity to other phases of the construction projects, but its use is still limited in the projects' other three interfaces. BIM is an evolving set of software developed for various purposes which is locally 'combined' to fit the circumstances and capabilities of the stakeholders of the construction process.

  8. Seven challenges in modeling pathogen dynamics within-host and across scales

    OpenAIRE

    Julia R. Gog; Lorenzo Pellis; James L.N. Wood; Angela R. McLean; Nimalan Arinaminpathy; James O. Lloyd-Smith

    2015-01-01

    © 2014 The Authors. The population dynamics of infectious disease is a mature field in terms of theory and to some extent, application. However for microparasites, the theory and application of models of the dynamics within a single infected host is still an open field. Further, connecting across the scales - from cellular to host level, to population level - has potential to vastly improve our understanding of pathogen dynamics and evolution. Here, we highlight seven challenges in the follow...

  9. BARRIERS AND CHALLENGES OF BUILDING INFORMATION MODELLING IMPLEMENTATION IN JORDANIAN CONSTRUCTION INDUSTRY

    OpenAIRE

    Mohammed A.KA. AL-Btoush*, Ahmad Tarmizi Haron

    2017-01-01

    Construction companies are faced with the need to innovatively integrate the construction process and address project development challenges. One way of doing that is the integration of building information modelling (BIM) in the building design and development cycles. However, due to the lack of clear understanding and the absence of a holistic implementation guideline, many companies are unable to fully achieve BIM potentials or implement BIM in their project and building lifecycle. BIM imp...

  10. Data mining and Pattern Recognizing Models for Identifying Inherited Diseases: Challenges and Implications

    OpenAIRE

    Lahiru Iddamalgoda; Partha Sarathi Das; Partha Sarathi Das; Achala Aponso; Vijayaraghava Seshadri Sundararajan; Prashanth Suravajhala; Prashanth Suravajhala; Prashanth Suravajhala; Jayaraman K Valadi

    2016-01-01

    Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately determining the responsible genetic factors for prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern r...

  11. Implementing novel models of posttreatment care for cancer survivors: Enablers, challenges and recommendations.

    Science.gov (United States)

    Jefford, Michael; Kinnane, Nicole; Howell, Paula; Nolte, Linda; Galetakis, Spiridoula; Bruce Mann, Gregory; Naccarella, Lucio; Lai-Kwon, Julia; Simons, Katherine; Avery, Sharon; Thompson, Kate; Ashley, David; Haskett, Martin; Davies, Elise; Whitfield, Kathryn

    2015-12-01

    The American Society of Clinical Oncology and US Institute of Medicine emphasize the need to trial novel models of posttreatment care, and disseminate findings. In 2011, the Victorian State Government (Australia) established the Victorian Cancer Survivorship Program (VCSP), funding six 2-year demonstration projects, targeting end of initial cancer treatment. Projects considered various models, enrolling people of differing cancer types, age and residential areas. We sought to determine common enablers of success, as well as challenges/barriers. Throughout the duration of the projects, a formal "community of practice" met regularly to share experiences. Projects provided regular formal progress reports. An analysis framework was developed to synthesize key themes and identify critical enablers and challenges. Two external reviewers examined final project reports. Discussion with project teams clarified content. Survivors reported interventions to be acceptable, appropriate and effective. Strong clinical leadership was identified as a critical success factor. Workforce education was recognized as important. Partnerships with consumers, primary care and community organizations; risk stratified pathways with rapid re-access to specialist care; and early preparation for survivorship, self-management and shared care models supported positive project outcomes. Tailoring care to individual needs and predicted risks was supported. Challenges included: lack of valid assessment and prediction tools; limited evidence to support novel care models; workforce redesign; and effective engagement with community-based care and issues around survivorship terminology. The VCSP project outcomes have added to growing evidence around posttreatment care. Future projects should consider the identified enablers and challenges when designing and implementing survivorship care. © 2015 Wiley Publishing Asia Pty Ltd.

  12. Testing the Sarcocystis neurona vaccine using an equine protozoal myeloencephalitis challenge model.

    Science.gov (United States)

    Saville, William J A; Dubey, Jitender P; Marsh, Antoinette E; Reed, Stephen M; Keene, Robert O; Howe, Daniel K; Morrow, Jennifer; Workman, Jeffrey D

    2017-11-30

    Equine protozoal myeloencephalitis (EPM) is an important equine neurologic disorder, and treatments for the disease are often unrewarding. Prevention of the disease is the most important aspect for EPM, and a killed vaccine was previously developed for just that purpose. Evaluation of the vaccine had been hampered by lack of post vaccination challenge. The purpose of this study was to determine if the vaccine could prevent development of clinical signs after challenge with Sarcocystis neurona sporocysts in an equine challenge model. Seventy horses that were negative for antibodies to S. neurona and were neurologically normal were randomly assigned to vaccine or placebo groups and divided into short-term duration of immunity (study #1) and long-term duration of immunity (study #2) studies. S. neurona sporocysts used for the challenge were generated in the opossum/raccoon cycle isolate SN 37-R. Study #1 horses received an initial vaccination and a booster, and were challenged 34days post second vaccination. Study #2 horses received a vaccination and two boosters and were challenged 139days post third vaccination. All horses in study #1 developed neurologic signs (n=30) and there was no difference between the vaccinates and controls (P=0.7683). All but four horses in study #2 developed detectable neurologic deficits. The neurologic signs, although not statistically significant, were worse in the vaccinated horses (P=0.1559). In these two studies, vaccination with the S. neurona vaccine failed to prevent development of clinical neurologic deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Models of user involvement in the mental health context: intentions and implementation challenges.

    Science.gov (United States)

    Storm, Marianne; Edwards, Adrian

    2013-09-01

    Patient-centered care, shared decision-making, patient participation and the recovery model are models of care which incorporate user involvement and patients' perspectives on their treatment and care. The aims of this paper are to examine these different care models and their association with user involvement in the mental health context and discuss some of the challenges associated with their implementation. The sources used are health policy documents and published literature and research on patient-centered care, shared decision-making, patient participation and recovery. The policy documents advocate that mental health services should be oriented towards patients' or users' needs, participation and involvement. These policies also emphasize recovery and integration of people with mental disorders in the community. However, these collaborative care models have generally been subject to limited empirical research about effectiveness. There are also challenges to implementation of the models in inpatient care. What evidence there is indicates tensions between patients' and providers' perspectives on treatment and care. There are issues related to risk and the person's capacity for user involvement, and concerns about what role patients themselves wish to play in decision-making. Lack of competence and awareness among providers are further issues. Further work on training, evaluation and implementation is needed to ensure that inpatient mental health services are adapting user oriented care models at all levels of services.

  14. Challenges in Soft Computing: Case Study with Louisville MSD CSO Modeling

    Science.gov (United States)

    Ormsbee, L.; Tufail, M.

    2005-12-01

    The principal constituents of soft computing include fuzzy logic, neural computing, evolutionary computation, machine learning, and probabilistic reasoning. There are numerous applications of these constituents (both individually and combination of two or more) in the area of water resources and environmental systems. These range from development of data driven models to optimal control strategies to assist in more informed and intelligent decision making process. Availability of data is critical to such applications and having scarce data may lead to models that do not represent the response function over the entire domain. At the same time, too much data has a tendency to lead to over-constraining of the problem. This paper will describe the application of a subset of these soft computing techniques (neural computing and genetic algorithms) to the Beargrass Creek watershed in Louisville, Kentucky. The application include development of inductive models as substitutes for more complex process-based models to predict water quality of key constituents (such as dissolved oxygen) and use them in an optimization framework for optimal load reductions. Such a process will facilitate the development of total maximum daily loads for the impaired water bodies in the watershed. Some of the challenges faced in this application include 1) uncertainty in data sets, 2) model application, and 3) development of cause-and-effect relationships between water quality constituents and watershed parameters through use of inductive models. The paper will discuss these challenges and how they affect the desired goals of the project.

  15. Numerical Modeling of Climate-Chemistry Connections: Recent Developments and Future Challenges

    Directory of Open Access Journals (Sweden)

    Patrick Jöckel

    2013-05-01

    Full Text Available This paper reviews the current state and development of different numerical model classes that are used to simulate the global atmospheric system, particularly Earth’s climate and climate-chemistry connections. The focus is on Chemistry-Climate Models. In general, these serve to examine dynamical and chemical processes in the Earth atmosphere, their feedback, and interaction with climate. Such models have been established as helpful tools in addition to analyses of observational data. Definitions of the global model classes are given and their capabilities as well as weaknesses are discussed. Examples of scientific studies indicate how numerical exercises contribute to an improved understanding of atmospheric behavior. There, the focus is on synergistic investigations combining observations and model results. The possible future developments and challenges are presented, not only from the scientific point of view but also regarding the computer technology and respective consequences for numerical modeling of atmospheric processes. In the future, a stronger cross-linkage of subject-specific scientists is necessary, to tackle the looming challenges. It should link the specialist discipline and applied computer science.

  16. The evolution of process-based hydrologic models: historical challenges and the collective quest for physical realism

    Science.gov (United States)

    Clark, M. P.; Nijssen, B.; Wood, A.; Mizukami, N.; Newman, A. J.

    2017-12-01

    The diversity in hydrologic models has historically led to great controversy on the "correct" approach to process-based hydrologic modeling, with debates centered on the adequacy of process parameterizations, data limitations and uncertainty, and computational constraints on model analysis. In this paper, we revisit key modeling challenges on requirements to (1) define suitable model equations, (2) define adequate model parameters, and (3) cope with limitations in computing power. We outline the historical modeling challenges, provide examples of modeling advances that address these challenges, and define outstanding research needs. We illustrate how modeling advances have been made by groups using models of different type and complexity, and we argue for the need to more effectively use our diversity of modeling approaches in order to advance our collective quest for physically realistic hydrologic models.

  17. Rescheduling nursing shifts: scoping the challenge and examining the potential of mathematical model based tools.

    Science.gov (United States)

    Clark, Alistair; Moule, Pam; Topping, Annie; Serpell, Martin

    2015-05-01

    To review research in the literature on nursing shift scheduling / rescheduling, and to report key issues identified in a consultation exercise with managers in four English National Health Service trusts to inform the development of mathematical tools for rescheduling decision-making. Shift rescheduling is unrecognised as an everyday time-consuming management task with different imperatives from scheduling. Poor rescheduling decisions can have quality, cost and morale implications. A systematic critical literature review identified rescheduling issues and existing mathematic modelling tools. A consultation exercise with nursing managers examined the complex challenges associated with rescheduling. Minimal research exists on rescheduling compared with scheduling. Poor rescheduling can result in greater disruption to planned nursing shifts and may impact negatively on the quality and cost of patient care, and nurse morale and retention. Very little research examines management challenges or mathematical modelling for rescheduling. Shift rescheduling is a complex and frequent management activity that is more challenging than scheduling. Mathematical modelling may have potential as a tool to support managers to minimise rescheduling disruption. The lack of specific methodological support for rescheduling that takes into account its complexity, increases the likelihood of harm for patients and stress for nursing staff and managers. © 2013 John Wiley & Sons Ltd.

  18. Model-based nonlinear control of hydraulic servo systems: Challenges, developments and perspectives

    Science.gov (United States)

    Yao, Jianyong

    2018-06-01

    Hydraulic servo system plays a significant role in industries, and usually acts as a core point in control and power transmission. Although linear theory-based control methods have been well established, advanced controller design methods for hydraulic servo system to achieve high performance is still an unending pursuit along with the development of modern industry. Essential nonlinearity is a unique feature and makes model-based nonlinear control more attractive, due to benefit from prior knowledge of the servo valve controlled hydraulic system. In this paper, a discussion for challenges in model-based nonlinear control, latest developments and brief perspectives of hydraulic servo systems are presented: Modelling uncertainty in hydraulic system is a major challenge, which includes parametric uncertainty and time-varying disturbance; some specific requirements also arise ad hoc difficulties such as nonlinear friction during low velocity tracking, severe disturbance, periodic disturbance, etc.; to handle various challenges, nonlinear solutions including parameter adaptation, nonlinear robust control, state and disturbance observation, backstepping design and so on, are proposed and integrated, theoretical analysis and lots of applications reveal their powerful capability to solve pertinent problems; and at the end, some perspectives and associated research topics (measurement noise, constraints, inner valve dynamics, input nonlinearity, etc.) in nonlinear hydraulic servo control are briefly explored and discussed.

  19. A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa.

    Science.gov (United States)

    Li Bassi, Gianluigi; Rigol, Montserrat; Marti, Joan-Daniel; Saucedo, Lina; Ranzani, Otavio T; Roca, Ignasi; Cabanas, Maria; Muñoz, Laura; Giunta, Valeria; Luque, Nestor; Rinaudo, Mariano; Esperatti, Mariano; Fernandez-Barat, Laia; Ferrer, Miquel; Vila, Jordi; Ramirez, Jose; Torres, Antoni

    2014-05-01

    Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa. Ten healthy pigs were intubated, positioned in anti-Trendelenburg, and mechanically ventilated for 72 h. Three animals did not receive bacterial challenge, whereas in seven animals, a P. aeruginosa suspension was instilled into the oropharynx. Tracheal aspirates were cultured and respiratory mechanics were recorded. On autopsy, lobar samples were obtained to corroborate VAP through microbiological and histological studies. In animals not challenged, diverse bacterial colonization of the airways was found and monolobar VAP rarely developed. In animals with P. aeruginosa challenge, colonization of tracheal secretion increased up to 6.39 ± 0.34 log colony-forming unit (cfu)/ml (P VAP was confirmed in six of seven pigs, in 78% of the cases developed in the dependent lung segments (right medium and lower lobes, P = 0.032). The static respiratory system elastance worsened to 41.5 ± 5.8 cm H2O/l (P = 0.001). The authors devised a VAP model caused by aspiration of oropharyngeal P. aeruginosa, a frequent causative pathogen of human VAP. The model also overcomes the practical and legislative limitations associated with the use of primates. The authors' model could be employed to study pathophysiologic mechanisms, as well as novel diagnostic/preventive strategies.

  20. Challenges Handling Magnetospheric and Ionospheric Signals in Internal Geomagnetic Field Modelling

    DEFF Research Database (Denmark)

    Finlay, Chris; Lesur, V.; Thébault, E.

    2017-01-01

    systems in the ionosphere and magnetosphere. In order to fully exploit magnetic data to probe the physical properties and dynamics of the Earth’s interior, field models with suitable treatments of external sources, and their associated induced signals, are essential. Here we review the methods presently......-by-track analysis to characterize magnetospheric field fluctuations, differences in internal field models that result from alternative treatments of the quiet-time ionospheric field, and challenges associated with rapidly changing, but spatially correlated, magnetic signatures of polar cap current systems. Possible...

  1. The big challenges in modeling human and environmental well-being.

    Science.gov (United States)

    Tuljapurkar, Shripad

    2016-01-01

    This article is a selective review of quantitative research, historical and prospective, that is needed to inform sustainable development policy. I start with a simple framework to highlight how demography and productivity shape human well-being. I use that to discuss three sets of issues and corresponding challenges to modeling: first, population prehistory and early human development and their implications for the future; second, the multiple distinct dimensions of human and environmental well-being and the meaning of sustainability; and, third, inequality as a phenomenon triggered by development and models to examine changing inequality and its consequences. I conclude with a few words about other important factors: political, institutional, and cultural.

  2. Redesigning models of patient care delivery and organisation: building collegial generosity in response to workplace challenges.

    Science.gov (United States)

    Chiarella, E Mary

    2007-04-01

    This case study describes the New South Wales Nursing and Midwifery Office (NaMO) Models of Care Project, a project designed to identify, encourage and disseminate innovations in nursing care organisation and delivery. The project is a 4-year action research project, using a range of interactive engagements including workshops, seminars, questionnaires and websites to achieve the goals. This case study briefly describes the main stimuli for review and redesign of models of care identified through analysis of the clinicians' presentations, and explores the range of responses to the workplace challenges.

  3. Modelling Marine Sediment Biogeochemistry: Current Knowledge Gaps, Challenges, and Some Methodological Advice for Advancement

    Directory of Open Access Journals (Sweden)

    Gennadi Lessin

    2018-02-01

    Full Text Available The benthic environment is a crucial component of marine systems in the provision of ecosystem services, sustaining biodiversity and in climate regulation, and therefore important to human society. With the contemporary increase in computational power, model resolution and technological improvements in quality and quantity of benthic data, it is necessary to ensure that benthic systems are appropriately represented in coupled benthic-pelagic biogeochemical and ecological modelling studies. In this paper we focus on five topical challenges related to various aspects of modelling benthic environments: organic matter reactivity, dynamics of benthic-pelagic boundary layer, microphytobenthos, biological transport and small-scale heterogeneity, and impacts of episodic events. We discuss current gaps in their understanding and indicate plausible ways ahead. Further, we propose a three-pronged approach for the advancement of benthic and benthic-pelagic modelling, essential for improved understanding, management and prediction of the marine environment. This includes: (A development of a traceable and hierarchical framework for benthic-pelagic models, which will facilitate integration among models, reduce risk of bias, and clarify model limitations; (B extended cross-disciplinary approach to promote effective collaboration between modelling and empirical scientists of various backgrounds and better involvement of stakeholders and end-users; (C a common vocabulary for terminology used in benthic modelling, to promote model development and integration, and also to enhance mutual understanding.

  4. Biosignature for airway inflammation in a house dust mite-challenged murine model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Hadeesha Piyadasa

    2016-02-01

    Full Text Available House dust mite (HDM challenge is commonly used in murine models of allergic asthma for preclinical pathophysiological studies. However, few studies define objective readouts or biomarkers in this model. In this study we characterized immune responses and defined molecular markers that are specifically altered after HDM challenge. In this murine model, we used repeated HDM challenge for two weeks which induced hallmarks of allergic asthma seen in humans, including airway hyper-responsiveness (AHR and elevated levels of circulating total and HDM-specific IgE and IgG1. Kinetic studies showed that at least 24 h after last HDM challenge results in significant AHR along with eosinophil infiltration in the lungs. Histologic assessment of lung revealed increased epithelial thickness and goblet cell hyperplasia, in the absence of airway wall collagen deposition, suggesting ongoing tissue repair concomitant with acute allergic lung inflammation. Thus, this model may be suitable to delineate airway inflammation processes that precede airway remodeling and development of fixed airway obstruction. We observed that a panel of cytokines e.g. IFN-γ, IL-1β, IL-4, IL-5, IL-6, KC, TNF-α, IL-13, IL-33, MDC and TARC were elevated in lung tissue and bronchoalveolar fluid, indicating local lung inflammation. However, levels of these cytokines remained unchanged in serum, reflecting lack of systemic inflammation in this model. Based on these findings, we further monitored the expression of 84 selected genes in lung tissues by quantitative real-time PCR array, and identified 31 mRNAs that were significantly up-regulated in lung tissue from HDM-challenged mice. These included genes associated with human asthma (e.g. clca3, ear11, il-13, il-13ra2, il-10, il-21, arg1 and chia1 and leukocyte recruitment in the lungs (e.g. ccl11, ccl12 and ccl24. This study describes a biosignature to enable broad and systematic interrogation of molecular mechanisms and intervention

  5. Model Based Reasoning by Introductory Students When Analyzing Earth Systems and Societal Challenges

    Science.gov (United States)

    Holder, L. N.; Herbert, B. E.

    2014-12-01

    Understanding how students use their conceptual models to reason about societal challenges involving societal issues such as natural hazard risk assessment, environmental policy and management, and energy resources can improve instructional activity design that directly impacts student motivation and literacy. To address this question, we created four laboratory exercises for an introductory physical geology course at Texas A&M University that engages students in authentic scientific practices by using real world problems and issues that affect societies based on the theory of situated cognition. Our case-study design allows us to investigate the various ways that students utilize model based reasoning to identify and propose solutions to societally relevant issues. In each of the four interventions, approximately 60 students in three sections of introductory physical geology were expected to represent and evaluate scientific data, make evidence-based claims about the data trends, use those claims to express conceptual models, and use their models to analyze societal challenges. Throughout each step of the laboratory exercise students were asked to justify their claims, models, and data representations using evidence and through the use of argumentation with peers. Cognitive apprenticeship was the foundation for instruction used to scaffold students so that in the first exercise they are given a partially completed model and in the last exercise students are asked to generate a conceptual model on their own. Student artifacts, including representation of earth systems, representation of scientific data, verbal and written explanations of models and scientific arguments, and written solutions to specific societal issues or environmental problems surrounding earth systems, were analyzed through the use of a rubric that modeled authentic expertise and students were sorted into three categories. Written artifacts were examined to identify student argumentation and

  6. Using natural selection and optimization for smarter vegetation models - challenges and opportunities

    Science.gov (United States)

    Franklin, Oskar; Han, Wang; Dieckmann, Ulf; Cramer, Wolfgang; Brännström, Åke; Pietsch, Stephan; Rovenskaya, Elena; Prentice, Iain Colin

    2017-04-01

    Dynamic global vegetation models (DGVMs) are now indispensable for understanding the biosphere and for estimating the capacity of ecosystems to provide services. The models are continuously developed to include an increasing number of processes and to utilize the growing amounts of observed data becoming available. However, while the versatility of the models is increasing as new processes and variables are added, their accuracy suffers from the accumulation of uncertainty, especially in the absence of overarching principles controlling their concerted behaviour. We have initiated a collaborative working group to address this problem based on a 'missing law' - adaptation and optimization principles rooted in natural selection. Even though this 'missing law' constrains relationships between traits, and therefore can vastly reduce the number of uncertain parameters in ecosystem models, it has rarely been applied to DGVMs. Our recent research have shown that optimization- and trait-based models of gross primary production can be both much simpler and more accurate than current models based on fixed functional types, and that observed plant carbon allocations and distributions of plant functional traits are predictable with eco-evolutionary models. While there are also many other examples of the usefulness of these and other theoretical principles, it is not always straight-forward to make them operational in predictive models. In particular on longer time scales, the representation of functional diversity and the dynamical interactions among individuals and species presents a formidable challenge. Here we will present recent ideas on the use of adaptation and optimization principles in vegetation models, including examples of promising developments, but also limitations of the principles and some key challenges.

  7. Scale effect challenges in urban hydrology highlighted with a distributed hydrological model

    Science.gov (United States)

    Ichiba, Abdellah; Gires, Auguste; Tchiguirinskaia, Ioulia; Schertzer, Daniel; Bompard, Philippe; Ten Veldhuis, Marie-Claire

    2018-01-01

    Hydrological models are extensively used in urban water management, development and evaluation of future scenarios and research activities. There is a growing interest in the development of fully distributed and grid-based models. However, some complex questions related to scale effects are not yet fully understood and still remain open issues in urban hydrology. In this paper we propose a two-step investigation framework to illustrate the extent of scale effects in urban hydrology. First, fractal tools are used to highlight the scale dependence observed within distributed data input into urban hydrological models. Then an intensive multi-scale modelling work is carried out to understand scale effects on hydrological model performance. Investigations are conducted using a fully distributed and physically based model, Multi-Hydro, developed at Ecole des Ponts ParisTech. The model is implemented at 17 spatial resolutions ranging from 100 to 5 m. Results clearly exhibit scale effect challenges in urban hydrology modelling. The applicability of fractal concepts highlights the scale dependence observed within distributed data. Patterns of geophysical data change when the size of the observation pixel changes. The multi-scale modelling investigation confirms scale effects on hydrological model performance. Results are analysed over three ranges of scales identified in the fractal analysis and confirmed through modelling. This work also discusses some remaining issues in urban hydrology modelling related to the availability of high-quality data at high resolutions, and model numerical instabilities as well as the computation time requirements. The main findings of this paper enable a replacement of traditional methods of model calibration by innovative methods of model resolution alteration based on the spatial data variability and scaling of flows in urban hydrology.

  8. Experiences in applying Bayesian integrative models in interdisciplinary modeling: the computational and human challenges

    DEFF Research Database (Denmark)

    Kuikka, Sakari; Haapasaari, Päivi Elisabet; Helle, Inari

    2011-01-01

    We review the experience obtained in using integrative Bayesian models in interdisciplinary analysis focusing on sustainable use of marine resources and environmental management tasks. We have applied Bayesian models to both fisheries and environmental risk analysis problems. Bayesian belief...... be time consuming and research projects can be difficult to manage due to unpredictable technical problems related to parameter estimation. Biology, sociology and environmental economics have their own scientific traditions. Bayesian models are becoming traditional tools in fisheries biology, where...

  9. Seven challenges for model-driven data collection in experimental and observational studies

    Directory of Open Access Journals (Sweden)

    J. Lessler

    2015-03-01

    Full Text Available Infectious disease models are both concise statements of hypotheses and powerful techniques for creating tools from hypotheses and theories. As such, they have tremendous potential for guiding data collection in experimental and observational studies, leading to more efficient testing of hypotheses and more robust study designs. In numerous instances, infectious disease models have played a key role in informing data collection, including the Garki project studying malaria, the response to the 2009 pandemic of H1N1 influenza in the United Kingdom and studies of T-cell immunodynamics in mammals. However, such synergies remain the exception rather than the rule; and a close marriage of dynamic modeling and empirical data collection is far from the norm in infectious disease research. Overcoming the challenges to using models to inform data collection has the potential to accelerate innovation and to improve practice in how we deal with infectious disease threats.

  10. Advantages and challenges of using physics curricula as a model for reforming an undergraduate biology course.

    Science.gov (United States)

    Donovan, D A; Atkins, L J; Salter, I Y; Gallagher, D J; Kratz, R F; Rousseau, J V; Nelson, G D

    2013-06-01

    We report on the development of a life sciences curriculum, targeted to undergraduate students, which was modeled after a commercially available physics curriculum and based on aspects of how people learn. Our paper describes the collaborative development process and necessary modifications required to apply a physics pedagogical model in a life sciences context. While some approaches were easily adapted, others provided significant challenges. Among these challenges were: representations of energy, introducing definitions, the placement of Scientists' Ideas, and the replicability of data. In modifying the curriculum to address these challenges, we have come to see them as speaking to deeper differences between the disciplines, namely that introductory physics--for example, Newton's laws, magnetism, light--is a science of pairwise interaction, while introductory biology--for example, photosynthesis, evolution, cycling of matter in ecosystems--is a science of linked processes, and we suggest that this is how the two disciplines are presented in introductory classes. We illustrate this tension through an analysis of our adaptations of the physics curriculum for instruction on the cycling of matter and energy; we show that modifications of the physics curriculum to address the biological framework promotes strong gains in student understanding of these topics, as evidenced by analysis of student work.

  11. Cloud service performance evaluation: status, challenges, and opportunities – a survey from the system modeling perspective

    Directory of Open Access Journals (Sweden)

    Qiang Duan

    2017-05-01

    Full Text Available With rapid advancement of Cloud computing and networking technologies, a wide spectrum of Cloud services have been developed by various providers and utilized by numerous organizations as indispensable ingredients of their information systems. Cloud service performance has a significant impact on performance of the future information infrastructure. Thorough evaluation on Cloud service performance is crucial and beneficial to both service providers and consumers; thus forming an active research area. Some key technologies for Cloud computing, such as virtualization and the Service-Oriented Architecture (SOA, bring in special challenges to service performance evaluation. A tremendous amount of effort has been put by the research community to address these challenges and exciting progress has been made. Among the work on Cloud performance analysis, evaluation approaches developed with a system modeling perspective play an important role. However, related works have been reported in different sections of the literature; thus lacking a big picture that shows the latest status of this area. The objectives of this article is to present a survey that reflects the state of the art of Cloud service performance evaluation from the system modeling perspective. This articles also examines open issues and challenges to the surveyed evaluation approaches and identifies possible opportunities for future research in this important field.

  12. GEM-CEDAR Challenge: Poynting Flux at DMSP and Modeled Joule Heat

    Science.gov (United States)

    Rastaetter, Lutz; Shim, Ja Soon; Kuznetsova, Maria M.; Kilcommons, Liam M.; Knipp, Delores J.; Codrescu, Mihail; Fuller-Rowell, Tim; Emery, Barbara; Weimer, Daniel R.; Cosgrove, Russell; hide

    2016-01-01

    Poynting flux into the ionosphere measures the electromagnetic energy coming from the magnetosphere. This energy flux can vary greatly between quiet times and geomagnetic active times. As part of the Geospace Environment Modeling-coupling energetics and dynamics of atmospheric regions modeling challenge, physics-based models of the 3-D ionosphere and ionospheric electrodynamics solvers of magnetosphere models that specify Joule heat and empirical models specifying Poynting flux were run for six geomagnetic storm events of varying intensity. We compared model results with Poynting flux values along the DMSP-15 satellite track computed from ion drift meter and magnetic field observations. Although being a different quantity, Joule heat can in practice be correlated to incoming Poynting flux because the energy is dissipated primarily in high latitudes where Poynting flux is being deposited. Within the physics-based model group, we find mixed results with some models overestimating Joule heat and some models agreeing better with observed Poynting flux rates as integrated over auroral passes. In contrast, empirical models tend to underestimate integrated Poynting flux values. Modeled Joule heat or Poynting flux patterns often resemble the observed Poynting flux patterns on a large scale, but amplitudes can differ by a factor of 2 or larger due to the highly localized nature of observed Poynting flux deposition that is not captured by the models. In addition, the positioning of modeled patterns appear to be randomly shifted against the observed Poynting flux energy input. This study is the first to compare Poynting flux and Joule heat in a large variety of models of the ionosphere.

  13. The big data-big model (BDBM) challenges in ecological research

    Science.gov (United States)

    Luo, Y.

    2015-12-01

    The field of ecology has become a big-data science in the past decades due to development of new sensors used in numerous studies in the ecological community. Many sensor networks have been established to collect data. For example, satellites, such as Terra and OCO-2 among others, have collected data relevant on global carbon cycle. Thousands of field manipulative experiments have been conducted to examine feedback of terrestrial carbon cycle to global changes. Networks of observations, such as FLUXNET, have measured land processes. In particular, the implementation of the National Ecological Observatory Network (NEON), which is designed to network different kinds of sensors at many locations over the nation, will generate large volumes of ecological data every day. The raw data from sensors from those networks offer an unprecedented opportunity for accelerating advances in our knowledge of ecological processes, educating teachers and students, supporting decision-making, testing ecological theory, and forecasting changes in ecosystem services. Currently, ecologists do not have the infrastructure in place to synthesize massive yet heterogeneous data into resources for decision support. It is urgent to develop an ecological forecasting system that can make the best use of multiple sources of data to assess long-term biosphere change and anticipate future states of ecosystem services at regional and continental scales. Forecasting relies on big models that describe major processes that underlie complex system dynamics. Ecological system models, despite great simplification of the real systems, are still complex in order to address real-world problems. For example, Community Land Model (CLM) incorporates thousands of processes related to energy balance, hydrology, and biogeochemistry. Integration of massive data from multiple big data sources with complex models has to tackle Big Data-Big Model (BDBM) challenges. Those challenges include interoperability of multiple

  14. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    International Nuclear Information System (INIS)

    Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-01-01

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  15. Challenges in Slug Modeling and Control for Offshore Oil and Gas Productions

    DEFF Research Database (Denmark)

    Pedersen, Simon; Løhndorf, Petar Durdevic; Yang, Zhenyu

    2017-01-01

    The upstream offshore multi-phase well-pipeline-riser installations are facing huge challenges related to slugging flow: An unstable flow regime where the flow rates, pressures and temperatures oscillate in the multi-phase pipelines. One typical severe slug is induced by vertical wells or risers...... most models require specific facility and operating data which, unfortunately, often is not available from most offshore installations. Anti-slug control have been investigated for several decades in oil & gas industry, but many of these existing methods suffer the consequent risk of simultaneously...... reducing the oil & gas production. This paper concludes that slug is a well defined phenomenon, but even though it has been investigated for several decades the current anti-slug control methods still have problems related to robustness. It is predicted that slug-induced challenges will be even more severe...

  16. Challenges in Modelling and Control of Offshore De-oiling Hydrocyclone Systems

    DEFF Research Database (Denmark)

    Løhndorf, Petar Durdevic; Pedersen, Simon; Yang, Zhenyu

    2017-01-01

    , and alternatively this task imposes a number of key control challenges. Specifically, there is much research to be performed in the direction of dynamic modelling and control of de-oiling hydrocyclone systems. The current solutions rely heavily on empirical trial-and-error approaches. This paper gives a brief......Offshore de-oiling installations are facing an increasing challenge with regards to removing oil residuals from produced water prior to discharge into the ocean. The de-oiling of produced water is initially achieved in the primary separation processes using gravity-based multi-phase separators...... in the produced water before it can be discharged into the ocean. The popularity of hydrocyclone technology in the offshore oil and gas industry is mainly due to its rugged design and low maintenance requirements. However, to operate and control this type of system in an efficient way is far less simple...

  17. Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge.

    Directory of Open Access Journals (Sweden)

    Dianelys Gonzalez-Pena

    Full Text Available Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3 and cell adhesion molecule 3 (Cadm3 were over-expressed and coiled-coil domain containing 162 (Ccdc162 and titin-cap (Tcap were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9, interleukin 1 beta (Il1b and kynurenine 3-monooxygenase (Kmo were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1 and microtubule-actin crosslinking factor 1(Macf1. Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness

  18. Development of a prediction model of severe reaction in boiled egg challenges.

    Science.gov (United States)

    Sugiura, Shiro; Matsui, Teruaki; Nakagawa, Tomoko; Sasaki, Kemal; Nakata, Joon; Kando, Naoyuki; Ito, Komei

    2016-07-01

    We have proposed a new scoring system (Anaphylaxis SCoring Aichi: ASCA) for a quantitative evaluation of the anaphylactic reaction that is observed in an oral food challenge (OFC). Furthermore, the TS/Pro (Total Score of ASCA/cumulative protein dose) can be a marker to represent the overall severity of a food allergy. We aimed to develop a prediction model for a severe allergic reaction that is provoked in a boiled egg white challenge. We used two separate datasets to develop and validate the prediction model, respectively. The development dataset included 198 OFCs, that tested positive. The validation dataset prospectively included 140 consecutive OFCs, irrespective of the result. A 'severe reaction' was defined as a TS/Pro higher than 31 (the median score of the development dataset). A multivariate logistic regression analysis was performed to identify the factors associated with a severe reaction and develop the prediction model. The following four factors were independently associated with a severe reaction: ovomucoid specific IgE class (OM-sIgE: 0-6), aged 5 years or over, a complete avoidance of egg, and a total IgE prediction model. The model showed good discrimination in a receiver operating characteristic analysis; area under the curve (AUC) = 0.84 in development dataset, AUC = 0.85 in validation dataset. The prediction model significantly improved the AUC in both datasets compared to OM-sIgE alone. This simple scoring prediction model was useful for avoiding risky OFC. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  19. Challenges to Applying a Metamodel for Groundwater Flow Beyond Underlying Numerical Model Boundaries

    Science.gov (United States)

    Reeves, H. W.; Fienen, M. N.; Feinstein, D.

    2015-12-01

    Metamodels of environmental behavior offer opportunities for decision support, adaptive management, and increased stakeholder engagement through participatory modeling and model exploration. Metamodels are derived from calibrated, computationally demanding, numerical models. They may potentially be applied to non-modeled areas to provide screening or preliminary analysis tools for areas that do not yet have the benefit of more comprehensive study. In this decision-support mode, they may be fulfilling a role often accomplished by application of analytical solutions. The major challenge to transferring a metamodel to a non-modeled area is how to quantify the spatial data in the new area of interest in such a way that it is consistent with the data used to derive the metamodel. Tests based on transferring a metamodel derived from a numerical groundwater-flow model of the Lake Michigan Basin to other glacial settings across the northern U.S. show that the spatial scale of the numerical model must be appropriately scaled to adequately represent different settings. Careful GIS analysis of the numerical model, metamodel, and new area of interest is required for successful transfer of results.

  20. The Challenge of Forecasting Metropolitan Growth: Urban Characteristics Based Models versus Regional Dummy Based Models

    OpenAIRE

    NA

    2005-01-01

    This paper presents a study of errors in forecasting the population of Metropolitan Statistical Areas and the Primary MSAs of Consolidated Metropolitan Statistical Areas and New England MAs. The forecasts are for the year 2000 and are based on a semi-structural model estimated by Mills and Lubelle using 1970 to 1990 census data on population, employment and relative real wages. This model allows the testing of regional effects on population and employment growth. The year 2000 forecasts are f...

  1. Modelling noninvasively measured cerebral signals during a hypoxemia challenge: steps towards individualised modelling.

    Directory of Open Access Journals (Sweden)

    Beth Jelfs

    Full Text Available Noninvasive approaches to measuring cerebral circulation and metabolism are crucial to furthering our understanding of brain function. These approaches also have considerable potential for clinical use "at the bedside". However, a highly nontrivial task and precondition if such methods are to be used routinely is the robust physiological interpretation of the data. In this paper, we explore the ability of a previously developed model of brain circulation and metabolism to explain and predict quantitatively the responses of physiological signals. The five signals all noninvasively-measured during hypoxemia in healthy volunteers include four signals measured using near-infrared spectroscopy along with middle cerebral artery blood flow measured using transcranial Doppler flowmetry. We show that optimising the model using partial data from an individual can increase its predictive power thus aiding the interpretation of NIRS signals in individuals. At the same time such optimisation can also help refine model parametrisation and provide confidence intervals on model parameters. Discrepancies between model and data which persist despite model optimisation are used to flag up important questions concerning the underlying physiology, and the reliability and physiological meaning of the signals.

  2. Challenges and opportunities of modeling plasma–surface interactions in tungsten using high-performance computing

    Energy Technology Data Exchange (ETDEWEB)

    Wirth, Brian D., E-mail: bdwirth@utk.edu [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Nuclear Science and Engineering Directorate, Oak Ridge National Laboratory, Oak Ridge, TN (United States); Hammond, K.D. [Department of Nuclear Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Krasheninnikov, S.I. [University of California, San Diego, La Jolla, CA (United States); Maroudas, D. [University of Massachusetts, Amherst, Amherst, MA 01003 (United States)

    2015-08-15

    The performance of plasma facing components (PFCs) is critical for ITER and future magnetic fusion reactors. The ITER divertor will be tungsten, which is the primary candidate material for future reactors. Recent experiments involving tungsten exposure to low-energy helium plasmas reveal significant surface modification, including the growth of nanometer-scale tendrils of “fuzz” and formation of nanometer-sized bubbles in the near-surface region. The large span of spatial and temporal scales governing plasma surface interactions are among the challenges to modeling divertor performance. Fortunately, recent innovations in computational modeling, increasingly powerful high-performance computers, and improved experimental characterization tools provide a path toward self-consistent, experimentally validated models of PFC and divertor performance. Recent advances in understanding tungsten–helium interactions are reviewed, including such processes as helium clustering, which serve as nuclei for gas bubbles; and trap mutation, dislocation loop punching and bubble bursting; which together initiate surface morphological modification.

  3. Geant4 Hadronic Cascade Models and CMS Data Analysis : Computational Challenges in the LHC era

    CERN Document Server

    Heikkinen, Aatos

    This work belongs to the field of computational high-energy physics (HEP). The key methods used in this thesis work to meet the challenges raised by the Large Hadron Collider (LHC) era experiments are object-orientation with software engineering, Monte Carlo simulation, the computer technology of clusters, and artificial neural networks. The first aspect discussed is the development of hadronic cascade models, used for the accurate simulation of medium-energy hadron-nucleus reactions, up to 10 GeV. These models are typically needed in hadronic calorimeter studies and in the estimation of radiation backgrounds. Various applications outside HEP include the medical field (such as hadron treatment simulations), space science (satellite shielding), and nuclear physics (spallation studies). Validation results are presented for several significant improvements released in Geant4 simulation tool, and the significance of the new models for computing in the Large Hadron Collider era is estimated. In particular, we es...

  4. Recent progress and modern challenges in applied mathematics, modeling and computational science

    CERN Document Server

    Makarov, Roman; Belair, Jacques

    2017-01-01

    This volume is an excellent resource for professionals in various areas of applications of mathematics, modeling, and computational science. It focuses on recent progress and modern challenges in these areas. The volume provides a balance between fundamental theoretical and applied developments, emphasizing the interdisciplinary nature of modern trends and detailing state-of-the-art achievements in Applied Mathematics, Modeling, and Computational Science.  The chapters have been authored by international experts in their respective fields, making this book ideal for researchers in academia, practitioners, and graduate students. It can also serve as a reference in the diverse selected areas of applied mathematics, modelling, and computational sciences, and is ideal for interdisciplinary collaborations.

  5. Animal models of binge drinking, current challenges to improve face validity.

    Science.gov (United States)

    Jeanblanc, Jérôme; Rolland, Benjamin; Gierski, Fabien; Martinetti, Margaret P; Naassila, Mickael

    2018-05-05

    Binge drinking (BD), i.e., consuming a large amount of alcohol in a short period of time, is an increasing public health issue. Though no clear definition has been adopted worldwide the speed of drinking seems to be a keystone of this behavior. Developing relevant animal models of BD is a priority for gaining a better characterization of the neurobiological and psychobiological mechanisms underlying this dangerous and harmful behavior. Until recently, preclinical research on BD has been conducted mostly using forced administration of alcohol, but more recent studies used scheduled access to alcohol, to model more voluntary excessive intakes, and to achieve signs of intoxications that mimic the human behavior. The main challenges for future research are discussed regarding the need of good face validity, construct validity and predictive validity of animal models of BD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Challenges and opportunities of modeling plasma–surface interactions in tungsten using high-performance computing

    International Nuclear Information System (INIS)

    Wirth, Brian D.; Hammond, K.D.; Krasheninnikov, S.I.; Maroudas, D.

    2015-01-01

    The performance of plasma facing components (PFCs) is critical for ITER and future magnetic fusion reactors. The ITER divertor will be tungsten, which is the primary candidate material for future reactors. Recent experiments involving tungsten exposure to low-energy helium plasmas reveal significant surface modification, including the growth of nanometer-scale tendrils of “fuzz” and formation of nanometer-sized bubbles in the near-surface region. The large span of spatial and temporal scales governing plasma surface interactions are among the challenges to modeling divertor performance. Fortunately, recent innovations in computational modeling, increasingly powerful high-performance computers, and improved experimental characterization tools provide a path toward self-consistent, experimentally validated models of PFC and divertor performance. Recent advances in understanding tungsten–helium interactions are reviewed, including such processes as helium clustering, which serve as nuclei for gas bubbles; and trap mutation, dislocation loop punching and bubble bursting; which together initiate surface morphological modification

  7. Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission.

    Science.gov (United States)

    Barnett, Tony; Fournié, Guillaume; Gupta, Sunetra; Seeley, Janet

    2015-01-01

    Incorporation of 'social' variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection - a highly social process in human populations - may be considered with little reference to the social. The French sociologist Émile Durkheim proposed that the scientific study of society required identification and study of 'social currents'. Such 'currents' are what we might today describe as 'emergent properties', specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to represent complex social and economic processes bearing on infectious disease transmission.

  8. Chondronecrosis with osteomyelitis in broilers: Further defining a bacterial challenge model using the wire flooring model.

    Science.gov (United States)

    Al-Rubaye, Adnan A K; Ekesi, Nnamdi S; Zaki, Sura; Emami, Nima K; Wideman, Robert F; Rhoads, Douglas D

    2017-02-01

    Lameness in broiler chickens is a significant animal welfare and financial issue. Bacterial chondronecrosis with osteomyelitis (BCO) leading to lameness can be enhanced by rearing young broilers on wire flooring. Using the wire floor system, we identified Staphylococcus agnetis as the predominant isolate in BCO of the proximal tibiae and femora, and blood of lame broilers. Administration of S. agnetis isolates in water can induce lameness. We now report that the wire floor system increases bacterial translocation into the blood stream. We have also determined that approximately 10 5 CFU/mL is the minimum effective dose in the drinking water and that challenge at 10, 20, or 30 days of age produces similar incidences of lameness. BCO isolates of S. agnetis are much more effective than other Staphylococcus species and can overwhelm the protective effects of some commercial probiotics. Finally, we also demonstrated that the BCO lameness induced by administration of S. agnetis in the drinking water is transmissible to unchallenged broilers in the same pen. © 2016 Poultry Science Association Inc.

  9. The Nordic Model in a Global Company Situated in Norway. Challenging Institutional Orders?

    Directory of Open Access Journals (Sweden)

    Elin Kvande

    2012-11-01

    Full Text Available In this article, we explore the impact of internationalization as organizational processes where institutional actors meet in local contexts and negotiate the institutional order. The internationalization of working life implies that different traditions and practices meet and challenge each other. The focus is on how important elements of the Nordic micro model like cooperation between employees and employers and regulation of working hours are implemented in a global company situated in Norway. In general, it seems that employees and employers cooperate in line with this tradition in the Nordic micro model. Norwegian manager’s practices are described to be in accordance with Scandinavian management traditions, while managers from the United States appear to practice management consistent with the liberal working life model. The findings show a tension-filled clash between two different management practices, which indicates that the Nordic micro model in this field might be under pressure. Manager’s recommendation to the employees was not to become members of the trade union. The absence of trade unions in the organization implies that employees and employers are not cooperating on a collective level. This means that only parts of the regulatory arrangement related to participation and cooperation are implemented. Findings concerning working time and the relation to the institutional order represented by the Norwegian Work Environment Act indicate a clear tension between different institutional traditions in the organization. The company does not respect the Norwegian in working time regulations. These regulations are seen as counterproductive for a company that competes in the international market. This devaluation of the regulations in the Nordic model implies that the institutional order represented in the Nordic micro model is challenged.

  10. Advanced Modeling and Uncertainty Quantification for Flight Dynamics; Interim Results and Challenges

    Science.gov (United States)

    Hyde, David C.; Shweyk, Kamal M.; Brown, Frank; Shah, Gautam

    2014-01-01

    As part of the NASA Vehicle Systems Safety Technologies (VSST), Assuring Safe and Effective Aircraft Control Under Hazardous Conditions (Technical Challenge #3), an effort is underway within Boeing Research and Technology (BR&T) to address Advanced Modeling and Uncertainty Quantification for Flight Dynamics (VSST1-7). The scope of the effort is to develop and evaluate advanced multidisciplinary flight dynamics modeling techniques, including integrated uncertainties, to facilitate higher fidelity response characterization of current and future aircraft configurations approaching and during loss-of-control conditions. This approach is to incorporate multiple flight dynamics modeling methods for aerodynamics, structures, and propulsion, including experimental, computational, and analytical. Also to be included are techniques for data integration and uncertainty characterization and quantification. This research shall introduce new and updated multidisciplinary modeling and simulation technologies designed to improve the ability to characterize airplane response in off-nominal flight conditions. The research shall also introduce new techniques for uncertainty modeling that will provide a unified database model comprised of multiple sources, as well as an uncertainty bounds database for each data source such that a full vehicle uncertainty analysis is possible even when approaching or beyond Loss of Control boundaries. Methodologies developed as part of this research shall be instrumental in predicting and mitigating loss of control precursors and events directly linked to causal and contributing factors, such as stall, failures, damage, or icing. The tasks will include utilizing the BR&T Water Tunnel to collect static and dynamic data to be compared to the GTM extended WT database, characterizing flight dynamics in off-nominal conditions, developing tools for structural load estimation under dynamic conditions, devising methods for integrating various modeling elements

  11. Fundamental Challenges for Modeling Electrochemical Energy Storage Systems at the Atomic Scale.

    Science.gov (United States)

    Groß, Axel

    2018-04-23

    There is a strong need to improve the efficiency of electrochemical energy storage, but progress is hampered by significant technological and scientific challenges. This review describes the potential contribution of atomic-scale modeling to the development of more efficient batteries, with a particular focus on first-principles electronic structure calculations. Numerical and theoretical obstacles are discussed, along with ways to overcome them, and some recent examples are presented illustrating the insights into electrochemical energy storage that can be gained from quantum chemical studies.

  12. Advances and Challenges in Space-time Modelling of Natural Events

    CERN Document Server

    Porcu, Emilio; Schlather, Martin

    2012-01-01

    This book arises as the natural continuation of the International Spring School "Advances and Challenges in Space-Time modelling of Natural Events," which took place in Toledo (Spain) in March 2010. This Spring School above all focused on young researchers (Master students, PhD students and post-doctoral researchers) in academics, extra-university research and the industry who are interested in learning about recent developments, new methods and applications in spatial statistics and related areas, and in exchanging ideas and findings with colleagues.

  13. Challenges and Changes in University Organization: Towards a New Model of Teaching and Learning

    Directory of Open Access Journals (Sweden)

    Carlos Gómez Bahillo

    2015-01-01

    Full Text Available Globalization is producing a new world order that is affecting political, economic, social, cultural and educational institutions. Universities need to be the engine of this social change and to provide a dynamic, flexible and stable educational model which can generate a skilled workforce ready to face the new challenges of the information and knowledge society. The university must provide not only basic and specific knowledge that prepares students to embark upon a given profession but should develop students’ social and technical skills to facilitate their subsequent employment in a competitive and innovative production system that demands a skilled workforce.

  14. Challenges of implementing economic model predictive control strategy for buildings interacting with smart energy systems

    DEFF Research Database (Denmark)

    Zong, Yi; Böning, Georg Martin; Santos, Rui Mirra

    2016-01-01

    ) strategy for energy management in smart buildings, which can act as active users interacting with smart energy systems. The challenges encountered during the implementation of EMPC for active demand side management are investigated in detail in this paper. A pilot testing study shows energy savings......When there is a high penetration of renewables in the energy system, it requires proactive control of large numbers of distributed demand response resources to maintain the system’s reliability and improve its operational economics. This paper presents the Economic Model Predictive Control (EMPC...

  15. Circular Business Model Challenges and Lessons Learned—An Industrial Perspective

    Directory of Open Access Journals (Sweden)

    Pejvak Oghazi

    2018-03-01

    Full Text Available Both practitioners and researchers are concerned about resource deficiencies on the planet earth and agree that circular business models (CBMs represent solutions to move towards zero waste, improving environmental impacts and increasing economic profit. Despite all of the benefits of CBMs, the implications are not widely available, and failure rates are high. Thus, there is a need to identify the obstacles that stand in the way of CBM transition. This paper aims to identify the primary challenges of CBMs. Multiple case studies are employed, incorporating six companies and data gleaned from 17 in-depth interviews. Theoretical and managerial implications are described at the end of the study.

  16. Challenges in modeling unstable two-phase flow experiments in porous micromodels

    Science.gov (United States)

    Meheust, Y.; Ferrari, A.; Jimenez-Martinez, J.; Le Borgne, T.; Lunati, I.

    2014-12-01

    The simulation of unstable invasion patterns in porous media flow is challenging since small perturbations tend to grow in time, so that slight differences in geometry or initial conditions potentially give rise to significantly different solutions. Here we present a detailed comparison of pore scale simulations and experiments of unstable primary drainage in porous micromodels. The porous medium consists of a Hele-Shaw cell containing cylindrical obstacles. Two experimental flow cells have been constructed by soft lithography, with different degrees of heterogeneity in the grain size distribution. To model two-phase flow at the pore scale, we solve Navier-Stokes equations for mass and momentum conservation in the discretized pore space and employ the Volume of Fluid (VOF) method to track the evolution of the interface. During drainage, if the defending fluid is the most viscous, viscous forces destabilize the interface, giving rise to the formation of preferential flow paths, in the form of a branched fingering structure. We test different numerical models (a 2D vertical integrated model and a full 3D model) and different initial conditions, studying their impact on the simulated spatial distributions of the fluid phases. Although due to the unstable nature of the invasion, small discrepancies between the experimental setup and the numerical model can result in different fluids patterns (see figure), simulations show a satisfactory agreement with the structures observed experimentally. To estimate the ability of the numerical approach to reproduce unstable displacement, we compare several quantities in both the statistical and deterministic sense. We demonstrate the impact of three main sources of uncertainty : i) the uncertainty on the pore space geometry, ii) the interface initialization and ii) three dimensional effects [1]. Simulations in weakly heterogeneous geometries are found to be more challenging because uncertainties on pore neck widths are on the same

  17. Adapting a regularized canopy reflectance model (REGFLEC) for the retrieval challenges of dryland agricultural systems

    KAUST Repository

    Houborg, Rasmus

    2016-08-20

    A regularized canopy reflectance model (REGFLEC) is applied over a dryland irrigated agricultural system in Saudi Arabia for the purpose of retrieving leaf area index (LAI) and leaf chlorophyll content (Chll). To improve the robustness of the retrieved properties, REGFLEC was modified to 1) correct for aerosol and adjacency effects, 2) consider foliar dust effects on modeled canopy reflectances, 3) include spectral information in the red-edge wavelength region, and 4) exploit empirical LAI estimates in the model inversion. Using multi-spectral RapidEye imagery allowed Chll to be retrieved with a Mean Absolute Deviation (MAD) of 7.9 μg cm− 2 (16%), based upon in-situ measurements conducted in fields of alfalfa, Rhodes grass and maize over the course of a growing season. LAI and Chll compensation effects on canopy reflectance were largely avoided by informing the inversion process with ancillary LAI inputs established empirically on the basis of a statistical machine learning technique. As a result, LAI was reproduced with good accuracy, with an overall MAD of 0.42 m2 m− 2 (12.5%). Results highlighted the considerable challenges associated with the translation of at-sensor radiance observations to surface bidirectional reflectances in dryland environments, where issues such as high aerosol loadings and large spatial gradients in surface reflectance from bright desert soils to dark vegetated fields are often present. Indeed, surface reflectances in the visible bands were reduced by up to 60% after correction for such adjacency effects. In addition, dust deposition on leaves required explicit modification of the reflectance sub-model to account for its influence. By implementing these model refinements, REGFLEC demonstrated its utility for within-field characterization of vegetation conditions over the challenging landscapes typical of dryland agricultural regions, offering a means through which improvements can be made in the management of these globally

  18. Crises and Collective Socio-Economic Phenomena: Simple Models and Challenges

    Science.gov (United States)

    Bouchaud, Jean-Philippe

    2013-05-01

    Financial and economic history is strewn with bubbles and crashes, booms and busts, crises and upheavals of all sorts. Understanding the origin of these events is arguably one of the most important problems in economic theory. In this paper, we review recent efforts to include heterogeneities and interactions in models of decision. We argue that the so-called Random Field Ising model ( rfim) provides a unifying framework to account for many collective socio-economic phenomena that lead to sudden ruptures and crises. We discuss different models that can capture potentially destabilizing self-referential feedback loops, induced either by herding, i.e. reference to peers, or trending, i.e. reference to the past, and that account for some of the phenomenology missing in the standard models. We discuss some empirically testable predictions of these models, for example robust signatures of rfim-like herding effects, or the logarithmic decay of spatial correlations of voting patterns. One of the most striking result, inspired by statistical physics methods, is that Adam Smith's invisible hand can fail badly at solving simple coordination problems. We also insist on the issue of time-scales, that can be extremely long in some cases, and prevent socially optimal equilibria from being reached. As a theoretical challenge, the study of so-called "detailed-balance" violating decision rules is needed to decide whether conclusions based on current models (that all assume detailed-balance) are indeed robust and generic.

  19. Sixth Grade Students' Content-Specific Competencies and Challenges in Learning the Seasons Through Modeling

    Science.gov (United States)

    Sung, Ji Young; Oh, Phil Seok

    2017-06-01

    Recent science education reform initiatives suggest that learning in science should be organized on the basis of scientists' actual practices including the development and use of models. In line with this, the current study adapted three types of modeling practices to teach two Korean 6th grade science classes the causes of the Earth's seasons. Specifically, the study aimed to identify the students' content-specific competencies and challenges based on fine-grained descriptions and analyses of two target groups' cases. Data included digital recordings of modeling-based science lessons in the two classes, the teacher's and students' artifacts, and interviews with the students. These multiple types of data were analyzed complementarily and qualitatively. It was revealed that the students had a competency in constructing models to generate the desired phenomenon (i.e., seasons). They had difficulty, however, in considering the tilt of the Earth's rotation axis as a cause of the seasons and in finding a proper way of representing the Sun's meridian altitude on a globe. But, when the students were helped and guided by the teacher and peers' interventions, they were able to revise their models in alignment with the scientific understanding of the seasons. Based on these findings, the teacher's pedagogical roles, which include using student competencies as resources, asking physical questions, and explicit guidance on experimentation skills, were recommended to support successful incorporations of modeling practices in the science classroom.

  20. Environmental fate and exposure models: advances and challenges in 21st century chemical risk assessment.

    Science.gov (United States)

    Di Guardo, Antonio; Gouin, Todd; MacLeod, Matthew; Scheringer, Martin

    2018-01-24

    Environmental fate and exposure models are a powerful means to integrate information on chemicals, their partitioning and degradation behaviour, the environmental scenario and the emissions in order to compile a picture of chemical distribution and fluxes in the multimedia environment. A 1995 pioneering book, resulting from a series of workshops among model developers and users, reported the main advantages and identified needs for research in the field of multimedia fate models. Considerable efforts were devoted to their improvement in the past 25 years and many aspects were refined; notably the inclusion of nanomaterials among the modelled substances, the development of models at different spatial and temporal scales, the estimation of chemical properties and emission data, the incorporation of additional environmental media and processes, the integration of sensitivity and uncertainty analysis in the simulations. However, some challenging issues remain and require research efforts and attention: the need of methods to estimate partition coefficients for polar and ionizable chemical in the environment, a better description of bioavailability in different environments as well as the requirement of injecting more ecological realism in exposure predictions to account for the diversity of ecosystem structures and functions in risk assessment. Finally, to transfer new scientific developments into the realm of regulatory risk assessment, we propose the formation of expert groups that compare, discuss and recommend model modifications and updates and help develop practical tools for risk assessment.

  1. Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

    Science.gov (United States)

    Wilczynski, Bartek; Furlong, Eileen E M

    2010-04-15

    Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  2. Practice models and challenges in teledermatology: a study of collective experiences from teledermatologists.

    Directory of Open Access Journals (Sweden)

    April W Armstrong

    Full Text Available BACKGROUND: Despite increasing practice of teledermatology in the U.S., teledermatology practice models and real-world challenges are rarely studied. METHODS: The primary objective was to examine teledermatology practice models and shared challenges among teledermatologists in California, focusing on practice operations, reimbursement considerations, barriers to sustainability, and incentives. We conducted in-depth interviews with teledermatologists that practiced store-and-forward or live-interactive teledermatology from January 1, 2007 through March 30, 2011 in California. RESULTS: Seventeen teledermatologists from academia, private practice, health maintenance organizations, and county settings participated in the study. Among them, 76% practiced store-and-forward only, 6% practiced live-interactive only, and 18% practiced both modalities. Only 29% received structured training in teledermatology. The average number of years practicing teledermatology was 4.29 years (SD±2.81. Approximately 47% of teledermatologists served at least one Federally Qualified Health Center. Over 75% of patients seen via teledermatology were at or below 200% federal poverty level and usually lived in rural regions without dermatologist access. Practice challenges were identified in the following areas. Teledermatologists faced delays in reimbursements and non-reimbursement of teledermatology services. The primary reason for operational inefficiency was poor image quality and/or inadequate history. Costly and inefficient software platforms and lack of communication with referring providers also presented barriers. CONCLUSION: Teledermatology enables underserved populations to access specialty care. Improvements in reimbursement mechanisms, efficient technology platforms, communication with referring providers, and teledermatology training are necessary to support sustainable practices.

  3. Findings and Challenges in Fine-Resolution Large-Scale Hydrological Modeling

    Science.gov (United States)

    Her, Y. G.

    2017-12-01

    Fine-resolution large-scale (FL) modeling can provide the overall picture of the hydrological cycle and transport while taking into account unique local conditions in the simulation. It can also help develop water resources management plans consistent across spatial scales by describing the spatial consequences of decisions and hydrological events extensively. FL modeling is expected to be common in the near future as global-scale remotely sensed data are emerging, and computing resources have been advanced rapidly. There are several spatially distributed models available for hydrological analyses. Some of them rely on numerical methods such as finite difference/element methods (FDM/FEM), which require excessive computing resources (implicit scheme) to manipulate large matrices or small simulation time intervals (explicit scheme) to maintain the stability of the solution, to describe two-dimensional overland processes. Others make unrealistic assumptions such as constant overland flow velocity to reduce the computational loads of the simulation. Thus, simulation efficiency often comes at the expense of precision and reliability in FL modeling. Here, we introduce a new FL continuous hydrological model and its application to four watersheds in different landscapes and sizes from 3.5 km2 to 2,800 km2 at the spatial resolution of 30 m on an hourly basis. The model provided acceptable accuracy statistics in reproducing hydrological observations made in the watersheds. The modeling outputs including the maps of simulated travel time, runoff depth, soil water content, and groundwater recharge, were animated, visualizing the dynamics of hydrological processes occurring in the watersheds during and between storm events. Findings and challenges were discussed in the context of modeling efficiency, accuracy, and reproducibility, which we found can be improved by employing advanced computing techniques and hydrological understandings, by using remotely sensed hydrological

  4. The multiple time scales of sleep dynamics as a challenge for modelling the sleeping brain.

    Science.gov (United States)

    Olbrich, Eckehard; Claussen, Jens Christian; Achermann, Peter

    2011-10-13

    A particular property of the sleeping brain is that it exhibits dynamics on very different time scales ranging from the typical sleep oscillations such as sleep spindles and slow waves that can be observed in electroencephalogram (EEG) segments of several seconds duration over the transitions between the different sleep stages on a time scale of minutes to the dynamical processes involved in sleep regulation with typical time constants in the range of hours. There is an increasing body of work on mathematical and computational models addressing these different dynamics, however, usually considering only processes on a single time scale. In this paper, we review and present a new analysis of the dynamics of human sleep EEG at the different time scales and relate the findings to recent modelling efforts pointing out both the achievements and remaining challenges.

  5. Data Mining and Pattern Recognition Models for Identifying Inherited Diseases: Challenges and Implications.

    Science.gov (United States)

    Iddamalgoda, Lahiru; Das, Partha S; Aponso, Achala; Sundararajan, Vijayaraghava S; Suravajhala, Prashanth; Valadi, Jayaraman K

    2016-01-01

    Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification- and scoring-based prioritization methods in determining causal variants. While we discuss the pros and cons associated with these methods known, we argue that the gene prioritization methods and the protein interaction (PPI) methods in conjunction with the K nearest neighbors' could be used in accurately categorizing the genetic factors in disease causation.

  6. Data mining and Pattern Recognizing Models for Identifying Inherited Diseases: Challenges and Implications

    Directory of Open Access Journals (Sweden)

    Lahiru Iddamalgoda

    2016-08-01

    Full Text Available Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately determining the responsible genetic factors for prioritizing the single nucleotide polymorphisms (SNP associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification and scoring based prioritization methods for determining causal variants. While we discuss the pros and cons associated with these methods known, we argue that the gene prioritization methods and the protein interaction (PPI methods in conjunction with the K nearest neighbors’ could be used in accurately categorizing the genetic factors in disease causation

  7. From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

    Science.gov (United States)

    Dietz, Volker; Schwab, Martin E

    2017-05-01

    Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

  8. State and transition models: Theory, applications, and challenges. In: Briske, D.D. Rangeland Systems: Processes, Management and Challenges

    Science.gov (United States)

    State and transition models (STMs) are used for communicating about ecosystem change in rangelands and other ecosystems, especially the implications for management. The fundamental premise that rangelands can exhibit multiple states is now widely accepted. The current application of STMs for managem...

  9. Outreach training model for accredited colorectal specialists in laparoscopic colorectal surgery: feasibility and evaluation of challenges.

    Science.gov (United States)

    Hamdan, M F; Day, A; Millar, J; Carter, F J C; Coleman, M G; Francis, N K

    2015-07-01

    The aim of this study was to explore the feasibility and safety of an outreach model of laparoscopic colorectal training of accredited specialists in advanced laparoscopic techniques and to explore the challenges of this model from the perspective of a National Training Programme (NTP) trainer. Prospective data were collected for unselected laparoscopic colorectal training procedures performed by five laparoscopic colorectal NTP trainees supervised by a single NTP trainer with an outreach model between 2009 and 2012. The operative and postoperative outcomes were compared with standard laparoscopic colorectal training procedures performed by six senior colorectal trainees under the supervision of the same NTP trainer within the same study period. The primary outcome was 30-day mortality. The Mann-Whitney test was used to compare continuous variables and the Chi squared or Fisher's exact tests were applied for the analysis of categorical variables. The level of statistical significance was set at P groups. Seventy-eight per cent of the patients operated on by the NTP trainees had had no previous abdominal surgery, compared with 50% in the supervised trainees' group (P = 0.0005). There were no significant differences in 30-day mortality or the operative and postoperative outcome between both groups. There were, however, difficulties in training an already established consultant in his or her own hospital and these were overcome by certain adjustments to the programme. Outreach laparoscopic training of colorectal surgeons is a feasible and safe model of training accredited specialists and does not compromise patient care. The challenges encountered can be overcome with optimum training and preparation. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

  10. Business model generation a handbook for visionaries, game changers, and challengers

    CERN Document Server

    Osterwalder, Alexander

    2010-01-01

    Business Model Generation is a handbook for visionaries, game changers, and challengers striving to defy outmoded business models and design tomorrow′s enterprises. If your organization needs to adapt to harsh new realities, but you don′t yet have a strategy that will get you out in front of your competitors, you need Business Model Generation. Co–created by 470 "Business Model Canvas" practitioners from 45 countries, the book features a beautiful, highly visual, 4–color design that takes powerful strategic ideas and tools, and makes them easy to implement in your organization. It explains the most common Business Model patterns, based on concepts from leading business thinkers, and helps you reinterpret them for your own context. You will learn how to systematically understand, design, and implement a game–changing business model––or analyze and renovate an old one. Along the way, you′ll understand at a much deeper level your customers, distribution channels, partners, revenue streams, costs...

  11. Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

    Science.gov (United States)

    Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

    2015-12-10

    Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Modeling of biomass-to-energy supply chain operations: Applications, challenges and research directions

    International Nuclear Information System (INIS)

    Mafakheri, Fereshteh; Nasiri, Fuzhan

    2014-01-01

    Reducing dependency on fossil fuels and mitigating their environmental impacts are among the most promising aspects of utilizing renewable energy sources. The availability of various biomass resources has made it an appealing source of renewable energy. Given the variability of supply and sources of biomass, supply chains play an important role in the efficient provisioning of biomass resources for energy production. This paper provides a comprehensive review and classification of the excising literature in modeling of biomass supply chain operations while linking them to the wider strategic challenges and issues with the design, planning and management of biomass supply chains. On that basis, we will present an analysis of the existing gaps and the potential future directions for research in modeling of biomass supply chain operations. - Highlights: • An extensive review of biomass supply chain operations management models presented in the literature is provided. • The models are classified in line with biomass supply chain activities from harvesting to conversion. • The issues surrounding biomass supply chains are investigated manifesting the need to novel modeling approaches. • Our gap analysis has identified a number of existing shortcomings and opportunities for future research

  13. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity

    Directory of Open Access Journals (Sweden)

    Robert Nunan

    2014-11-01

    Full Text Available The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.

  14. Challenges to modeling the Sun-Earth System: A Workshop Summary

    Science.gov (United States)

    Spann, James F.

    2006-01-01

    This special issue of the Journal of' Atmospheric and Solar-Terrestrial Physics is a compilation of 23 papers presented at The 2004 Huntsville Modeling Workshop: Challenges to Modeling thc San-Earth System held in Huntsville, AB on October 18-22, 2004. The title of the workshop appropriately captures the theme of what was presented and discussed by the 120 participants. Currently, end-to-end modeling of the Sun-Earth system is a major goal of the National Space Weather and NASA living with a star (LWS) programs. While profound advances have been made in modeling isolated regions of the Sun-Earth system, minimal progress has been achieved in modeling the end-to-end system. The transfer of mass, energy and momentum through the coupled Sun-Earth system spans a wide range of scales inn time and space. The uncertainty in the underlying physics responsible for coupling contiguous regions of the Sun-Earth system is recognized as a significant barrier to progress

  15. Cloud ice: A climate model challenge with signs and expectations of progress

    Science.gov (United States)

    Waliser, Duane E.; Li, Jui-Lin F.; Woods, Christopher P.; Austin, Richard T.; Bacmeister, Julio; Chern, Jiundar; Del Genio, Anthony; Jiang, Jonathan H.; Kuang, Zhiming; Meng, Huan; Minnis, Patrick; Platnick, Steve; Rossow, William B.; Stephens, Graeme L.; Sun-Mack, Szedung; Tao, Wei-Kuo; Tompkins, Adrian M.; Vane, Deborah G.; Walker, Christopher; Wu, Dong

    2009-04-01

    Present-day shortcomings in the representation of upper tropospheric ice clouds in general circulation models (GCMs) lead to errors in weather and climate forecasts as well as account for a source of uncertainty in climate change projections. An ongoing challenge in rectifying these shortcomings has been the availability of adequate, high-quality, global observations targeting ice clouds and related precipitating hydrometeors. In addition, the inadequacy of the modeled physics and the often disjointed nature between model representation and the characteristics of the retrieved/observed values have hampered GCM development and validation efforts from making effective use of the measurements that have been available. Thus, even though parameterizations in GCMs accounting for cloud ice processes have, in some cases, become more sophisticated in recent years, this development has largely occurred independently of the global-scale measurements. With the relatively recent addition of satellite-derived products from Aura/Microwave Limb Sounder (MLS) and CloudSat, there are now considerably more resources with new and unique capabilities to evaluate GCMs. In this article, we illustrate the shortcomings evident in model representations of cloud ice through a comparison of the simulations assessed in the Intergovernmental Panel on Climate Change Fourth Assessment Report, briefly discuss the range of global observational resources that are available, and describe the essential components of the model parameterizations that characterize their "cloud" ice and related fields. Using this information as background, we (1) discuss some of the main considerations and cautions that must be taken into account in making model-data comparisons related to cloud ice, (2) illustrate present progress and uncertainties in applying satellite cloud ice (namely from MLS and CloudSat) to model diagnosis, (3) show some indications of model improvements, and finally (4) discuss a number of

  16. Prediction of lake surface temperature using the air2water model: guidelines, challenges, and future perspectives

    Directory of Open Access Journals (Sweden)

    Sebastiano Piccolroaz

    2016-04-01

    leading to the risk of overfitting. The final aim of the work is to facilitate the use of the model also by scientists that do not necessarily have a solid background on modelling or physics. However, this work should not be considered simply as a collection of best practices, but also as the attempt to foster the communication and interaction among colleagues of a branch of science, limnology, that suffer of significant fragmentation. This is summarized in the future perspectives and challenges concerning potential improvements of the air2water, with a particular emphasis on possible cross-sectoral applications.

  17. Modeling and simulation challenges pursued by the Consortium for Advanced Simulation of Light Water Reactors (CASL)

    Energy Technology Data Exchange (ETDEWEB)

    Turinsky, Paul J., E-mail: turinsky@ncsu.edu [North Carolina State University, PO Box 7926, Raleigh, NC 27695-7926 (United States); Kothe, Douglas B., E-mail: kothe@ornl.gov [Oak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831-6164 (United States)

    2016-05-15

    The Consortium for the Advanced Simulation of Light Water Reactors (CASL), the first Energy Innovation Hub of the Department of Energy, was established in 2010 with the goal of providing modeling and simulation (M&S) capabilities that support and accelerate the improvement of nuclear energy's economic competitiveness and the reduction of spent nuclear fuel volume per unit energy, and all while assuring nuclear safety. To accomplish this requires advances in M&S capabilities in radiation transport, thermal-hydraulics, fuel performance and corrosion chemistry. To focus CASL's R&D, industry challenge problems have been defined, which equate with long standing issues of the nuclear power industry that M&S can assist in addressing. To date CASL has developed a multi-physics “core simulator” based upon pin-resolved radiation transport and subchannel (within fuel assembly) thermal-hydraulics, capitalizing on the capabilities of high performance computing. CASL's fuel performance M&S capability can also be optionally integrated into the core simulator, yielding a coupled multi-physics capability with untapped predictive potential. Material models have been developed to enhance predictive capabilities of fuel clad creep and growth, along with deeper understanding of zirconium alloy clad oxidation and hydrogen pickup. Understanding of corrosion chemistry (e.g., CRUD formation) has evolved at all scales: micro, meso and macro. CFD R&D has focused on improvement in closure models for subcooled boiling and bubbly flow, and the formulation of robust numerical solution algorithms. For multiphysics integration, several iterative acceleration methods have been assessed, illuminating areas where further research is needed. Finally, uncertainty quantification and data assimilation techniques, based upon sampling approaches, have been made more feasible for practicing nuclear engineers via R&D on dimensional reduction and biased sampling. Industry adoption of CASL

  18. The Grand Challenge of Basin-Scale Groundwater Quality Management Modelling

    Science.gov (United States)

    Fogg, G. E.

    2017-12-01

    The last 50+ years of agricultural, urban and industrial land and water use practices have accelerated the degradation of groundwater quality in the upper portions of many major aquifer systems upon which much of the world relies for water supply. In the deepest and most extensive systems (e.g., sedimentary basins) that typically have the largest groundwater production rates and hold fresh groundwaters on decadal to millennial time scales, most of the groundwater is not yet contaminated. Predicting the long-term future groundwater quality in such basins is a grand scientific challenge. Moreover, determining what changes in land and water use practices would avert future, irreversible degradation of these massive freshwater stores is a grand challenge both scientifically and societally. It is naïve to think that the problem can be solved by eliminating or reducing enough of the contaminant sources, for human exploitation of land and water resources will likely always result in some contamination. The key lies in both reducing the contaminant sources and more proactively managing recharge in terms of both quantity and quality, such that the net influx of contaminants is sufficiently moderate and appropriately distributed in space and time to reverse ongoing groundwater quality degradation. Just as sustainable groundwater quantity management is greatly facilitated with groundwater flow management models, sustainable groundwater quality management will require the use of groundwater quality management models. This is a new genre of hydrologic models do not yet exist, partly because of the lack of modeling tools and the supporting research to model non-reactive as well as reactive transport on large space and time scales. It is essential that the contaminant hydrogeology community, which has heretofore focused almost entirely on point-source plume-scale problems, direct it's efforts toward the development of process-based transport modeling tools and analyses capable

  19. Statistical challenges in modelling the health consequences of social mobility: the need for diagonal reference models.

    Science.gov (United States)

    van der Waal, Jeroen; Daenekindt, Stijn; de Koster, Willem

    2017-12-01

    Various studies on the health consequences of socio-economic position address social mobility. They aim to uncover whether health outcomes are affected by: (1) social mobility, besides, (2) social origin, and (3) social destination. Conventional methods do not, however, estimate these three effects separately, which may produce invalid conclusions. We highlight that diagonal reference models (DRMs) overcome this problem, which we illustrate by focusing on overweight/obesity (OWOB). Using conventional methods (logistic-regression analyses with dummy variables) and DRMs, we examine the effects of intergenerational educational mobility on OWOB (BMI ≥ 25 kg/m 2 ) using survey data representative of the Dutch population aged 18-45 (1569 males, 1771 females). Conventional methods suggest that mobility effects on OWOB are present. Analyses with DRMs, however, indicate that no such effects exist. Conventional analyses of the health consequences of social mobility may produce invalid results. We, therefore, recommend the use of DRMs. DRMs also validly estimate the health consequences of other types of social mobility (e.g. intra- and intergenerational occupational and income mobility) and status inconsistency (e.g. in educational or occupational attainment between partners).

  20. Mathematical models for lymphatic filariasis transmission and control: Challenges and prospects

    Directory of Open Access Journals (Sweden)

    Kaliannagounder Krishnamoorthy

    2008-02-01

    Full Text Available Abstract Background Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics. Discussion EPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease. Summary The two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is

  1. GIS-Based Planning and Modeling for Renewable Energy: Challenges and Future Research Avenues

    Directory of Open Access Journals (Sweden)

    Bernd Resch

    2014-05-01

    Full Text Available In the face of the broad political call for an “energy turnaround”, we are currently witnessing three essential trends with regard to energy infrastructure planning, energy generation and storage: from planned production towards fluctuating production on the basis of renewable energy sources, from centralized generation towards decentralized generation and from expensive energy carriers towards cost-free energy carriers. These changes necessitate considerable modifications of the energy infrastructure. Even though most of these modifications are inherently motivated by geospatial questions and challenges, the integration of energy system models and Geographic Information Systems (GIS is still in its infancy. This paper analyzes the shortcomings of previous approaches in using GIS in renewable energy-related projects, extracts distinct challenges from these previous efforts and, finally, defines a set of core future research avenues for GIS-based energy infrastructure planning with a focus on the use of renewable energy. These future research avenues comprise the availability base data and their “geospatial awareness”, the development of a generic and unified data model, the usage of volunteered geographic information (VGI and crowdsourced data in analysis processes, the integration of 3D building models and 3D data analysis, the incorporation of network topologies into GIS, the harmonization of the heterogeneous views on aggregation issues in the fields of energy and GIS, fine-grained energy demand estimation from freely-available data sources, decentralized storage facility planning, the investigation of GIS-based public participation mechanisms, the transition from purely structural to operational planning, data privacy aspects and, finally, the development of a new dynamic power market design.

  2. Hyperresolution global land surface modeling: Meeting a grand challenge for monitoring Earth's terrestrial water

    Science.gov (United States)

    Wood, Eric F.; Roundy, Joshua K.; Troy, Tara J.; van Beek, L. P. H.; Bierkens, Marc F. P.; Blyth, Eleanor; de Roo, Ad; DöLl, Petra; Ek, Mike; Famiglietti, James; Gochis, David; van de Giesen, Nick; Houser, Paul; Jaffé, Peter R.; Kollet, Stefan; Lehner, Bernhard; Lettenmaier, Dennis P.; Peters-Lidard, Christa; Sivapalan, Murugesu; Sheffield, Justin; Wade, Andrew; Whitehead, Paul

    2011-05-01

    Monitoring Earth's terrestrial water conditions is critically important to many hydrological applications such as global food production; assessing water resources sustainability; and flood, drought, and climate change prediction. These needs have motivated the development of pilot monitoring and prediction systems for terrestrial hydrologic and vegetative states, but to date only at the rather coarse spatial resolutions (˜10-100 km) over continental to global domains. Adequately addressing critical water cycle science questions and applications requires systems that are implemented globally at much higher resolutions, on the order of 1 km, resolutions referred to as hyperresolution in the context of global land surface models. This opinion paper sets forth the needs and benefits for a system that would monitor and predict the Earth's terrestrial water, energy, and biogeochemical cycles. We discuss six major challenges in developing a system: improved representation of surface-subsurface interactions due to fine-scale topography and vegetation; improved representation of land-atmospheric interactions and resulting spatial information on soil moisture and evapotranspiration; inclusion of water quality as part of the biogeochemical cycle; representation of human impacts from water management; utilizing massively parallel computer systems and recent computational advances in solving hyperresolution models that will have up to 109 unknowns; and developing the required in situ and remote sensing global data sets. We deem the development of a global hyperresolution model for monitoring the terrestrial water, energy, and biogeochemical cycles a "grand challenge" to the community, and we call upon the international hydrologic community and the hydrological science support infrastructure to endorse the effort.

  3. Molecular genetic models related to schizophrenia and psychotic illness: heuristics and challenges.

    Science.gov (United States)

    O'Tuathaigh, Colm M P; Desbonnet, Lieve; Moran, Paula M; Kirby, Brian P; Waddington, John L

    2011-01-01

    Schizophrenia is a heritable disorder that may involve several common genes of small effect and/or rare copy number variation, with phenotypic heterogeneity across patients. Furthermore, any boundaries vis-à-vis other psychotic disorders are far from clear. Consequently, identification of informative animal models for this disorder, which typically relate to pharmacological and putative pathophysiological processes of uncertain validity, faces considerable challenges. In juxtaposition, the majority of mutant models for schizophrenia relate to the functional roles of a diverse set of genes associated with risk for the disorder or with such putative pathophysiological processes. This chapter seeks to outline the evidence from phenotypic studies in mutant models related to schizophrenia. These have commonly assessed the degree to which mutation of a schizophrenia-related gene is associated with the expression of several aspects of the schizophrenia phenotype or more circumscribed, schizophrenia-related endophenotypes; typically, they place specific emphasis on positive and negative symptoms and cognitive deficits, and extend to structural and other pathological features. We first consider the primary technological approaches to the generation of such mutants, to include their relative merits and demerits, and then highlight the diverse phenotypic approaches that have been developed for their assessment. The chapter then considers the application of mutant phenotypes to study pathobiological and pharmacological mechanisms thought to be relevant for schizophrenia, particularly in terms of dopaminergic and glutamatergic dysfunction, and to an increasing range of candidate susceptibility genes and copy number variants. Finally, we discuss several pertinent issues and challenges within the field which relate to both phenotypic evaluation and a growing appreciation of the functional genomics of schizophrenia and the involvement of gene × environment interactions.

  4. Modeling and simulation challenges pursued by the Consortium for Advanced Simulation of Light Water Reactors (CASL)

    Science.gov (United States)

    Turinsky, Paul J.; Kothe, Douglas B.

    2016-05-01

    The Consortium for the Advanced Simulation of Light Water Reactors (CASL), the first Energy Innovation Hub of the Department of Energy, was established in 2010 with the goal of providing modeling and simulation (M&S) capabilities that support and accelerate the improvement of nuclear energy's economic competitiveness and the reduction of spent nuclear fuel volume per unit energy, and all while assuring nuclear safety. To accomplish this requires advances in M&S capabilities in radiation transport, thermal-hydraulics, fuel performance and corrosion chemistry. To focus CASL's R&D, industry challenge problems have been defined, which equate with long standing issues of the nuclear power industry that M&S can assist in addressing. To date CASL has developed a multi-physics ;core simulator; based upon pin-resolved radiation transport and subchannel (within fuel assembly) thermal-hydraulics, capitalizing on the capabilities of high performance computing. CASL's fuel performance M&S capability can also be optionally integrated into the core simulator, yielding a coupled multi-physics capability with untapped predictive potential. Material models have been developed to enhance predictive capabilities of fuel clad creep and growth, along with deeper understanding of zirconium alloy clad oxidation and hydrogen pickup. Understanding of corrosion chemistry (e.g., CRUD formation) has evolved at all scales: micro, meso and macro. CFD R&D has focused on improvement in closure models for subcooled boiling and bubbly flow, and the formulation of robust numerical solution algorithms. For multiphysics integration, several iterative acceleration methods have been assessed, illuminating areas where further research is needed. Finally, uncertainty quantification and data assimilation techniques, based upon sampling approaches, have been made more feasible for practicing nuclear engineers via R&D on dimensional reduction and biased sampling. Industry adoption of CASL's evolving M

  5. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  6. Hyperresolution Global Land Surface Modeling: Meeting a Grand Challenge for Monitoring Earth's Terrestrial Water

    Science.gov (United States)

    Wood, Eric F.; Roundy, Joshua K.; Troy, Tara J.; van Beek, L. P. H.; Bierkens, Marc F. P.; 4 Blyth, Eleanor; de Roo, Ad; Doell. Petra; Ek, Mike; Famiglietti, James; hide

    2011-01-01

    Monitoring Earth's terrestrial water conditions is critically important to many hydrological applications such as global food production; assessing water resources sustainability; and flood, drought, and climate change prediction. These needs have motivated the development of pilot monitoring and prediction systems for terrestrial hydrologic and vegetative states, but to date only at the rather coarse spatial resolutions (approx.10-100 km) over continental to global domains. Adequately addressing critical water cycle science questions and applications requires systems that are implemented globally at much higher resolutions, on the order of 1 km, resolutions referred to as hyperresolution in the context of global land surface models. This opinion paper sets forth the needs and benefits for a system that would monitor and predict the Earth's terrestrial water, energy, and biogeochemical cycles. We discuss six major challenges in developing a system: improved representation of surface-subsurface interactions due to fine-scale topography and vegetation; improved representation of land-atmospheric interactions and resulting spatial information on soil moisture and evapotranspiration; inclusion of water quality as part of the biogeochemical cycle; representation of human impacts from water management; utilizing massively parallel computer systems and recent computational advances in solving hyperresolution models that will have up to 10(exp 9) unknowns; and developing the required in situ and remote sensing global data sets. We deem the development of a global hyperresolution model for monitoring the terrestrial water, energy, and biogeochemical cycles a grand challenge to the community, and we call upon the international hydrologic community and the hydrological science support infrastructure to endorse the effort.

  7. Modelling marine sediment biogeochemistry: Current knowledge gaps, challenges, and some methodological advice for advancement

    DEFF Research Database (Denmark)

    Lessin, Gennadi; Artioli, Yuri; Almroth-Rosell, Elin

    2018-01-01

    The benthic environment is a crucial component of marine systems in the provision of ecosystem services, sustaining biodiversity and in climate regulation, and therefore important to human society. With the contemporary increase in computational power, model resolution and technological improveme......The benthic environment is a crucial component of marine systems in the provision of ecosystem services, sustaining biodiversity and in climate regulation, and therefore important to human society. With the contemporary increase in computational power, model resolution and technological...... improvements in quality and quantity of benthic data, it is necessary to ensure that benthic systems are appropriately represented in coupled benthic-pelagic biogeochemical and ecological modelling studies. In this paper we focus on five topical challenges related to various aspects of modelling benthic...... environments: organic matter reactivity, dynamics of benthic-pelagic boundary layer, microphytobenthos, biological transport and small-scale heterogeneity, and impacts of episodic events. We discuss current gaps in their understanding and indicate plausible ways ahead. Further, we propose a three...

  8. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

    Science.gov (United States)

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

    2012-01-01

    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

  9. Integrated Payment And Delivery Models Offer Opportunities And Challenges For Residential Care Facilities.

    Science.gov (United States)

    Grabowski, David C; Caudry, Daryl J; Dean, Katie M; Stevenson, David G

    2015-10-01

    Under health care reform, new financing and delivery models are being piloted to integrate health and long-term care services for older adults. Programs using these models generally have not included residential care facilities. Instead, most of them have focused on long-term care recipients in the community or the nursing home. Our analyses indicate that individuals living in residential care facilities have similarly high rates of chronic illness and Medicare utilization when compared with matched individuals in the community and nursing home, and rates of functional dependency that fall between those of their counterparts in the other two settings. These results suggest that the residential care facility population could benefit greatly from models that coordinated health and long-term care services. However, few providers have invested in the infrastructure needed to support integrated delivery models. Challenges to greater care integration include the private-pay basis for residential care facility services, which precludes shared savings from reduced Medicare costs, and residents' preference for living in a home-like, noninstitutional environment. Project HOPE—The People-to-People Health Foundation, Inc.

  10. Challenges of Representing Sub-Grid Physics in an Adaptive Mesh Refinement Atmospheric Model

    Science.gov (United States)

    O'Brien, T. A.; Johansen, H.; Johnson, J. N.; Rosa, D.; Benedict, J. J.; Keen, N. D.; Collins, W.; Goodfriend, E.

    2015-12-01

    Some of the greatest potential impacts from future climate change are tied to extreme atmospheric phenomena that are inherently multiscale, including tropical cyclones and atmospheric rivers. Extremes are challenging to simulate in conventional climate models due to existing models' coarse resolutions relative to the native length-scales of these phenomena. Studying the weather systems of interest requires an atmospheric model with sufficient local resolution, and sufficient performance for long-duration climate-change simulations. To this end, we have developed a new global climate code with adaptive spatial and temporal resolution. The dynamics are formulated using a block-structured conservative finite volume approach suitable for moist non-hydrostatic atmospheric dynamics. By using both space- and time-adaptive mesh refinement, the solver focuses computational resources only where greater accuracy is needed to resolve critical phenomena. We explore different methods for parameterizing sub-grid physics, such as microphysics, macrophysics, turbulence, and radiative transfer. In particular, we contrast the simplified physics representation of Reed and Jablonowski (2012) with the more complex physics representation used in the System for Atmospheric Modeling of Khairoutdinov and Randall (2003). We also explore the use of a novel macrophysics parameterization that is designed to be explicitly scale-aware.

  11. Challenges to achieving sustainable community health development within a donor aid business model.

    Science.gov (United States)

    Ashwell, Helen; Barclay, Lesley

    2010-06-01

    This paper explores the paradox of donor aid being delivered through a business model through a case study in Papua New Guinea. A retrospective review of project implementation and an outcome evaluation provided an opportunity to examine the long-term results and sustainability of a large project. Analysis was informed by data collected from 175 interviews (national, provincial, district and village), 93 community discussions and observations across 10 provinces. Problems with the business model of delivering aid were evident from implementation data and in an evaluation conducted two years after project completion (2006). Compounding the business model effect were challenges of over-ambitious project goals with limited flexibility to adapt to changing circumstances, a donor payment system requiring short-term productivity and excessive reporting requirements. An overly ambitious project design, donor dominance within the business model and limited local counterpart capacity created problems in the community initiatives component of the project. Contractual pressures can negatively influence long-term outcomes that require development of local leadership and capacity. Future planning for donor project designs needs to be flexible, smaller in scope and have a longer timeframe of seven to 10 years. Donor-funded projects need to be sufficiently flexible to apply proven principles of community development, build local ownership and allow adequate time to build counterpart knowledge and skills.

  12. Review article: Hydrological modeling in glacierized catchments of central Asia - status and challenges

    Science.gov (United States)

    Chen, Yaning; Li, Weihong; Fang, Gonghuan; Li, Zhi

    2017-02-01

    Meltwater from glacierized catchments is one of the most important water supplies in central Asia. Therefore, the effects of climate change on glaciers and snow cover will have increasingly significant consequences for runoff. Hydrological modeling has become an indispensable research approach to water resources management in large glacierized river basins, but there is a lack of focus in the modeling of glacial discharge. This paper reviews the status of hydrological modeling in glacierized catchments of central Asia, discussing the limitations of the available models and extrapolating these to future challenges and directions. After reviewing recent efforts, we conclude that the main sources of uncertainty in assessing the regional hydrological impacts of climate change are the unreliable and incomplete data sets and the lack of understanding of the hydrological regimes of glacierized catchments of central Asia. Runoff trends indicate a complex response to changes in climate. For future variation of water resources, it is essential to quantify the responses of hydrologic processes to both climate change and shrinking glaciers in glacierized catchments, and scientific focus should be on reducing uncertainties linked to these processes.

  13. The challenge of modeling fuel–coolant interaction: Part II – Steam explosion

    Energy Technology Data Exchange (ETDEWEB)

    Meignen, Renaud, E-mail: renaud.meignen@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PSN-RES/SAG, BP 3, 13115 Saint-Paul-Lez-Durance Cedex (France); Raverdy, Bruno [Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PSN-RES/SAG, BP 3, 13115 Saint-Paul-Lez-Durance Cedex (France); Picchi, Stephane; Lamome, Julien [Communication and Systèmes, 22 avenue Galilée, 92350 Le Plessis Robinson (France)

    2014-12-15

    Highlights: • We present the status modeling of steam explosion in the computer code MC3D (a first paper is devoted to premixing stage of FCI). • We also propose a general state of the art, highlighting recent improvements in understanding and modeling, remaining difficulties, controversies and needs. • We highlight the need for improving the understanding of the melt fragmentation and oxidation. • The verification basis is presented. - Abstract: In the course of a severe accident in a nuclear power plant cooled or moderated by water, the core might melt and flow down into the water. Under certain circumstances, a steam explosion might develop during the mixing of the melt and the water. Such an explosion, if occurring in the reactor pit of a PWR or BWR, might challenge the containment integrity and is thus an important issue for nuclear safety. This paper aims at presenting both a status of research and understanding of the phenomenon and the main characteristics of the models developed in the 3-dimensional computer code MC3D. We make a particular emphasis on the underlying difficulties, uncertainties and needs for further improvements. We discuss more particularly the two major phenomena that are the fine fragmentation and the pressurization process. We also give insights on the impact of melt solidification on the fragmentation and on the issue of oxidation. The verification basis of the models is discussed and finally, an example of 3D calculation is presented to highlight the current code capabilities.

  14. High resolution weather data for urban hydrological modelling and impact assessment, ICT requirements and future challenges

    Science.gov (United States)

    ten Veldhuis, Marie-claire; van Riemsdijk, Birna

    2013-04-01

    presentation will highlight ICT-related requirements and limitations in high resolution urban hydrological modelling and analysis. Further ICT challenges arise in provision of high resolution radar data for diverging information needs as well as in combination with other data sources in the urban environment. Different types of information are required for such diverse activities as operational flood protection, traffic management, large event organisation, business planning in shopping districts and restaurants, timing of family activities. These different information needs may require different configurations and data processing for radars and other data sources. An ICT challenge is to develop techniques for deciding how to automatically respond to these diverging information needs (e.g., through (semi-)automated negotiation). Diverse activities also provide a wide variety of information resources that can supplement traditional networks of weather sensors, such as rain sensors on cars and social media. Another ICT challenge is how to combine data from these different sources for answering a particular information need. Examples will be presented of solutions are currently being explored.

  15. Coupled Atmosphere-Wave-Ocean Modeling of Tropical Cyclones: Progress, Challenges, and Ways Forward

    Science.gov (United States)

    Chen, Shuyi

    2015-04-01

    /s. It is found that the air-sea fluxes are quite asymmetric around a storm with complex features representing various air-sea interaction processes in TCs. A unique observation in Typhoon Fanapi is the development of a stable boundary layer in the near-storm cold wake region, which has a direct impact on TC inner core structure and intensity. Despite of the progress, challenges remain. Air-sea momentum exchange in wind speed greater than 30-40 m/s is largely unresolved. Directional wind-wave stress and wave-current stress are difficult to determine from observations. Effects of sea spray on the air-sea fluxes are still not well understood. This talk will provide an overview on progress made in recent years, challenges we are facing, and ways forward. An integrated coupled observational and atmosphere-wave-ocean modeling system is urgently needed, in which coupled model development and targeted observations from field campaign and lab measurements together form the core of the research and prediction system. Another important aspect is that fully coupled models provide explicit, integrated impact forecasts of wind, rain, waves, ocean currents and surges in TCs and winter storms, which are missing in most current NWP models. It requires a new strategy for model development, evaluation, and verification. Ensemble forecasts using high-resolution coupled atmosphere-wave-ocean models can provide probabilistic forecasts and quantitative uncertainty estimates, which also allow us to explore new methodologies to verify probabilistic impact forecasts and evaluate model physics using a stochastic approach. Examples of such approach in TCs including Superstorm Sandy will be presented.

  16. Building Information Modelling: Challenges and Barriers in Implement of BIM for Interior Design Industry in Malaysia

    Science.gov (United States)

    Hamid, A. B. Abd; Taib, M. Z. Mohd; Razak, A. H. N. Abdul; Embi, M. R.

    2018-04-01

    Building Information Modelling (BIM) is an innovative approach that has developed crossways the global in architecture, engineering and construction (AEC) industry. The construction industry of Malaysia has undergone a rapid development and dynamic technology adoption in advance and methods between the players industry and stakeholders. Consequently, limited technologies and devices have not been successful as it should have been. This study will be emphasizing scenarios of challenges and barriers in adopting BIM in interior design industry in Malaysia. The study was emphasizing the challenges and barriers in BIM usage from the designer’s perspective. The data are collected through the questionnaires as to identifying the barriers, knowledge, readiness and awareness and distributed to interior design firms were selected randomly. The finding of this research is to examine the barriers and causes of variables BIM usage for interior design industry in Malaysia. The outcome of this study is to identify the constraint of adoption BIM in interior design industry compare to others players in same industry.

  17. Multi -omics and metabolic modelling pipelines: challenges and tools for systems microbiology.

    Science.gov (United States)

    Fondi, Marco; Liò, Pietro

    2015-02-01

    Integrated -omics approaches are quickly spreading across microbiology research labs, leading to (i) the possibility of detecting previously hidden features of microbial cells like multi-scale spatial organization and (ii) tracing molecular components across multiple cellular functional states. This promises to reduce the knowledge gap between genotype and phenotype and poses new challenges for computational microbiologists. We underline how the capability to unravel the complexity of microbial life will strongly depend on the integration of the huge and diverse amount of information that can be derived today from -omics experiments. In this work, we present opportunities and challenges of multi -omics data integration in current systems biology pipelines. We here discuss which layers of biological information are important for biotechnological and clinical purposes, with a special focus on bacterial metabolism and modelling procedures. A general review of the most recent computational tools for performing large-scale datasets integration is also presented, together with a possible framework to guide the design of systems biology experiments by microbiologists. Copyright © 2015. Published by Elsevier GmbH.

  18. A Comprehensive Study on the Internet of Underwater Things: Applications, Challenges, and Channel Models

    Directory of Open Access Journals (Sweden)

    Chien-Chi Kao

    2017-06-01

    Full Text Available The Internet of Underwater Things (IoUT is a novel class of Internet of Things (IoT, and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs, and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1 we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2 we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3 we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.

  19. A Comprehensive Study on the Internet of Underwater Things: Applications, Challenges, and Channel Models.

    Science.gov (United States)

    Kao, Chien-Chi; Lin, Yi-Shan; Wu, Geng-De; Huang, Chun-Ju

    2017-06-22

    The Internet of Underwater Things (IoUT) is a novel class of Internet of Things (IoT), and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs) have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs), and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1) we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2) we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3) we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.

  20. Methodological challenges and analytic opportunities for modeling and interpreting Big Healthcare Data.

    Science.gov (United States)

    Dinov, Ivo D

    2016-01-01

    Managing, processing and understanding big healthcare data is challenging, costly and demanding. Without a robust fundamental theory for representation, analysis and inference, a roadmap for uniform handling and analyzing of such complex data remains elusive. In this article, we outline various big data challenges, opportunities, modeling methods and software techniques for blending complex healthcare data, advanced analytic tools, and distributed scientific computing. Using imaging, genetic and healthcare data we provide examples of processing heterogeneous datasets using distributed cloud services, automated and semi-automated classification techniques, and open-science protocols. Despite substantial advances, new innovative technologies need to be developed that enhance, scale and optimize the management and processing of large, complex and heterogeneous data. Stakeholder investments in data acquisition, research and development, computational infrastructure and education will be critical to realize the huge potential of big data, to reap the expected information benefits and to build lasting knowledge assets. Multi-faceted proprietary, open-source, and community developments will be essential to enable broad, reliable, sustainable and efficient data-driven discovery and analytics. Big data will affect every sector of the economy and their hallmark will be 'team science'.

  1. Challenges in modeling spatiotemporally varying phytoplankton blooms in the Northwestern Arabian Sea and Gulf of Oman

    Science.gov (United States)

    Sedigh Marvasti, S.; Gnanadesikan, A.; Bidokhti, A. A.; Dunne, J. P.; Ghader, S.

    2016-02-01

    Recent years have shown an increase in harmful algal blooms in the Northwest Arabian Sea and Gulf of Oman, raising the question of whether climate change will accelerate this trend. This has led us to examine whether the Earth System Models used to simulate phytoplankton productivity accurately capture bloom dynamics in this region - both in terms of the annual cycle and interannual variability. Satellite data (SeaWIFS ocean color) show two climatological blooms in this region, a wintertime bloom peaking in February and a summertime bloom peaking in September. On a regional scale, interannual variability of the wintertime bloom is dominated by cyclonic eddies which vary in location from one year to another. Two coarse (1°) models with the relatively complex biogeochemistry (TOPAZ) capture the annual cycle but neither eddies nor the interannual variability. An eddy-resolving model (GFDL CM2.6) with a simpler biogeochemistry (miniBLING) displays larger interannual variability, but overestimates the wintertime bloom and captures eddy-bloom coupling in the south but not in the north. The models fail to capture both the magnitude of the wintertime bloom and its modulation by eddies in part because of their failure to capture the observed sharp thermocline and/or nutricline in this region. When CM2.6 is able to capture such features in the Southern part of the basin, eddies modulate diffusive nutrient supply to the surface (a mechanism not previously emphasized in the literature). For the model to simulate the observed wintertime blooms within cyclones, it will be necessary to represent this relatively unusual nutrient structure as well as the cyclonic eddies. This is a challenge in the Northern Arabian Sea as it requires capturing the details of the outflow from the Persian Gulf - something that is poorly done in global models.

  2. Challenges and Conundrums in Modeling Global Methane Emissions from Wetlands: An Empiricist's Viewpoint

    Science.gov (United States)

    Bridgham, S. D.

    2015-12-01

    Wetlands emit a third to half of the global CH4 flux and have the largest uncertainty of any emission source. Moreover, wetlands have provided an important radiative feedback to climate in the geologic and recent past. A number of largescale wetland CH4 models have been developed recently, but intermodel comparisons show wide discrepancies in their predictions. I present an empiricist's overview of the current limitations and challenges of more accurately modeling wetland CH4 emissions. One of the largest limitations is simply the poor knowledge of wetland area, with estimated global values varying by a more than a factor of three. The areas of seasonal and tropical wetlands are particularly poorly constrained. There are also few wetlands with complete, multi-year datasets for all of the input variables for many models, and this lack of data is particularly alarming in tropical wetlands given that they are arguably the single largest natural or anthropogenic global CH4 source. Almost all largescale CH4 models have little biogeochemical mechanistic detail and treat anaerobic carbon cycling in a highly simplified manner. The CH4:CO2 ratio in anaerobic carbon mineralization is a central parameter in many models, but is at most set at a few values with no mechanistic underpinning. However, empirical data show that this ratio varies by five orders of magnitude in different wetlands, and tropical wetlands appear to be particularly methanogenic, all for reasons that are very poorly understood. The predominance of the acetoclastic pathway of methanogenesis appears to be related to total CH4 production, but different methanogenesis pathways are generally not incorporated into models. Other important anaerobic processes such as humic substances acting as terminal electron acceptors, fermentation, homoacetogenesis, and anaerobic CH4 oxidation are also not included in most models despite evidence of their importance in empirical studies. Moreover, there has been an explosion

  3. Operational use of distributed hydrological models. Experiences and challenges at a Norwegian hydropower company (Agder Energi).

    Science.gov (United States)

    Viggo Matheussen, Bernt; Andresen, Arne; Weisser, Claudia

    2014-05-01

    combined into a robust and fast data cleansing and interpolation system. One experience from this work is that advanced interpolation techniques (kriging), do not outperform calibrated inverse distance methods when also computational speed is used as a criteria for model selection. The paper also discusses several challenges related to uncertainty in simulated snow reservoir, regionalization of parameters, choice of spatial resolution, techniques for reducing computational needs without compromising information needs, amongst others.

  4. New Sustainable Model of Biorefineries: Biofactories and Challenges of Integrating Bio- and Solar Refineries.

    Science.gov (United States)

    Abate, Salvatore; Lanzafame, Paola; Perathoner, Siglinda; Centi, Gabriele

    2015-09-07

    The new scenario for sustainable (low-carbon) chemical and energy production drives the development of new biorefinery concepts (indicated as biofactories) with chemical production at the core, but flexible and small-scale production. An important element is also the integration of solar energy and CO2 use within biobased production. This concept paper, after shortly introducing the motivation and recent trends in this area, particularly at the industrial scale, and some of the possible models (olefin and intermediate/high-added-value chemicals production), discusses the opportunities and needs for research to address the challenge of integrating bio- and solar refineries. Aspects discussed regard the use of microalgae and CO2 valorization in biorefineries/biofactories by chemo- or biocatalysis, including possibilities for their synergetic cooperation and symbiosis, as well as integration within the agroenergy value chain. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Challenges of electricity production scenarios modelling for life cycle assessment of environmental impacts

    Energy Technology Data Exchange (ETDEWEB)

    Blanc, Isabelle; Beloin-Saint-Pierre, Didier [MINES ParisTech, Sophia Antipolis (France). Observation, Impacts, Energy Center

    2013-07-01

    This communication presents a first attempt at making a life cycle assessment of prospective electricity production scenarios which were designed in the EnerGEO project. We start by a basic review of system (in this case, scenario) modelling expectations in today's LCA study. We then review some of the challenges of implementation due to the lack of detailed description of present and future electricity production systems. The importance of a detailed description is then shown with an evaluation of uncertainty of life cycle impact assessment results for three scenarios of German electricity production in 2030. The significant uncertainties we found, prevent us from detecting a relevant trend or making any comparison between the three chosen scenarios. We finally come to the conclusion that the LCA methodology will become relevant for the environmental assessment of electricity production scenarios when many more detailed information are accounted to describe future technologies, structures and sources of energy. (orig.)

  6. Modern challenges for flow investigations in model hydraulic turbines on classical test rig

    International Nuclear Information System (INIS)

    Deschênes, C; Houde, S; Aeschlimann, V; Fraser, R; Ciocan, G D

    2014-01-01

    The BulbT project involved several investigations of flow phenomena in different parts of a model bulb turbine installed on the test rig of Laval University Laboratory. The aim is to create a comprehensive data base in order to increase the knowledge of the flow phenomena in this type of turbines and to validate or improve numerical flow simulation strategies. This validation being based on a kinematic comparison between experimental and numerical data, the project had to overcome challenges to facilitate the use of the experimental data for that purpose. Many parameters were checked, such as the test bench repeatability, the intrusiveness of a priori non-intrusive methods, the geometry of the runner and draft tube. This paper illustrates how some of those problematic were solved

  7. Police Training in El Salvador: Challenges and Opportunities in Promoting the Community Police Model

    Directory of Open Access Journals (Sweden)

    Luisa Carolina Arévalo Herrera

    2014-05-01

    Full Text Available The Peace Accords emphasized creating a new police force that would be diametrically opposite to previous security forces. This change would have to be expressed symbolically, and from the onset it would have to underscore the fact that the main weapon of the police would be intelligence. From its foundation to June 2011, a total of 30,344 people have graduated from the Academy. Currently, in the process of training new police with greater quality, and modernizing the entire police force, it faces the difficult challenge of adopting the Community Police philosophy to empower this model for action, promoting a new relationship between community and law enforcement, and between managers and operational personnel in the agency. Nevertheless,police training is not enough if there are no significantchanges in the organizational climate and culture within the law enforcement agency.DOI: http://dx.doi.org/10.5377/rpsp.v1i1.1390

  8. Challenges of electricity production scenarios modelling for life cycle assessment of environmental impacts

    International Nuclear Information System (INIS)

    Blanc, Isabelle; Beloin-Saint-Pierre, Didier

    2013-01-01

    This communication presents a first attempt at making a life cycle assessment of prospective electricity production scenarios which were designed in the EnerGEO project. We start by a basic review of system (in this case, scenario) modelling expectations in today's LCA study. We then review some of the challenges of implementation due to the lack of detailed description of present and future electricity production systems. The importance of a detailed description is then shown with an evaluation of uncertainty of life cycle impact assessment results for three scenarios of German electricity production in 2030. The significant uncertainties we found, prevent us from detecting a relevant trend or making any comparison between the three chosen scenarios. We finally come to the conclusion that the LCA methodology will become relevant for the environmental assessment of electricity production scenarios when many more detailed information are accounted to describe future technologies, structures and sources of energy. (orig.)

  9. Industrial-Strength Model-Based Testing - State of the Art and Current Challenges

    Directory of Open Access Journals (Sweden)

    Jan Peleska

    2013-03-01

    Full Text Available As of today, model-based testing (MBT is considered as leading-edge technology in industry. We sketch the different MBT variants that - according to our experience - are currently applied in practice, with special emphasis on the avionic, railway and automotive domains. The key factors for successful industrial-scale application of MBT are described, both from a scientific and a managerial point of view. With respect to the former view, we describe the techniques for automated test case, test data and test procedure generation for concurrent reactive real-time systems which are considered as the most important enablers for MBT in practice. With respect to the latter view, our experience with introducing MBT approaches in testing teams are sketched. Finally, the most challenging open scientific problems whose solutions are bound to improve the acceptance and effectiveness of MBT in industry are discussed.

  10. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    Science.gov (United States)

    Seah, Yu Fen Samantha; EL Farran, Chadi A.; Warrier, Tushar; Xu, Jian; Loh, Yuin-Han

    2015-01-01

    Embryonic stem cells (ESCs) are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs) via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases. PMID:26633382

  11. Current Challenges in the First Principle Quantitative Modelling of the Lower Hybrid Current Drive in Tokamaks

    Science.gov (United States)

    Peysson, Y.; Bonoli, P. T.; Chen, J.; Garofalo, A.; Hillairet, J.; Li, M.; Qian, J.; Shiraiwa, S.; Decker, J.; Ding, B. J.; Ekedahl, A.; Goniche, M.; Zhai, X.

    2017-10-01

    The Lower Hybrid (LH) wave is widely used in existing tokamaks for tailoring current density profile or extending pulse duration to steady-state regimes. Its high efficiency makes it particularly attractive for a fusion reactor, leading to consider it for this purpose in ITER tokamak. Nevertheless, if basics of the LH wave in tokamak plasma are well known, quantitative modeling of experimental observations based on first principles remains a highly challenging exercise, despite considerable numerical efforts achieved so far. In this context, a rigorous methodology must be carried out in the simulations to identify the minimum number of physical mechanisms that must be considered to reproduce experimental shot to shot observations and also scalings (density, power spectrum). Based on recent simulations carried out for EAST, Alcator C-Mod and Tore Supra tokamaks, the state of the art in LH modeling is reviewed. The capability of fast electron bremsstrahlung, internal inductance li and LH driven current at zero loop voltage to constrain all together LH simulations is discussed, as well as the needs of further improvements (diagnostics, codes, LH model), for robust interpretative and predictive simulations.

  12. Interoperability challenges in river discharge modelling: A cross domain application scenario

    Science.gov (United States)

    Santoro, Mattia; Andres, Volker; Jirka, Simon; Koike, Toshio; Looser, Ulrich; Nativi, Stefano; Pappenberger, Florian; Schlummer, Manuela; Strauch, Adrian; Utech, Michael; Zsoter, Ervin

    2018-06-01

    River discharge is a critical water cycle variable, as it integrates all the processes (e.g. runoff and evapotranspiration) occurring within a river basin and provides a hydrological output variable that can be readily measured. Its prediction is of invaluable help for many water-related tasks including water resources assessment and management, flood protection, and disaster mitigation. Observations of river discharge are important to calibrate and validate hydrological or coupled land, atmosphere and ocean models. This requires using datasets from different scientific domains (Water, Weather, etc.). Typically, such datasets are provided using different technological solutions. This complicates the integration of new hydrological data sources into application systems. Therefore, a considerable effort is often spent on data access issues instead of the actual scientific question. This paper describes the work performed to address multidisciplinary interoperability challenges related to river discharge modeling and validation. This includes definition and standardization of domain specific interoperability standards for hydrological data sharing and their support in global frameworks such as the Global Earth Observation System of Systems (GEOSS). The research was developed in the context of the EU FP7-funded project GEOWOW (GEOSS Interoperability for Weather, Ocean and Water), which implemented a "River Discharge" application scenario. This scenario demonstrates the combination of river discharge observations data from the Global Runoff Data Centre (GRDC) database and model outputs produced by the European Centre for Medium-Range Weather Forecasts (ECMWF) predicting river discharge based on weather forecast information in the context of the GEOSS.

  13. Challenges and models in supporting logistics system design for dedicated-biomass-based bioenergy industry.

    Science.gov (United States)

    Zhu, Xiaoyan; Li, Xueping; Yao, Qingzhu; Chen, Yuerong

    2011-01-01

    This paper analyzed the uniqueness and challenges in designing the logistics system for dedicated biomass-to-bioenergy industry, which differs from the other industries, due to the unique features of dedicated biomass (e.g., switchgrass) including its low bulk density, restrictions on harvesting season and frequency, content variation with time and circumambient conditions, weather effects, scattered distribution over a wide geographical area, and so on. To design it, this paper proposed a mixed integer linear programming model. It covered from planting and harvesting switchgrass to delivering to a biorefinery and included the residue handling, concentrating on integrating strategic decisions on the supply chain design and tactical decisions on the annual operation schedules. The present numerical examples verified the model and demonstrated its use in practice. This paper showed that the operations of the logistics system were significantly different for harvesting and non-harvesting seasons, and that under the well-designed biomass logistics system, the mass production with a steady and sufficient supply of biomass can increase the unit profit of bioenergy. The analytical model and practical methodology proposed in this paper will help realize the commercial production in biomass-to-bioenergy industry. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Yu Fen Samantha Seah

    2015-12-01

    Full Text Available Embryonic stem cells (ESCs are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases.

  15. A systematic review and checklist presenting the main challenges for health economic modeling in personalized medicine: towards implementing patient-level models.

    Science.gov (United States)

    Degeling, Koen; Koffijberg, Hendrik; IJzerman, Maarten J

    2017-02-01

    The ongoing development of genomic medicine and the use of molecular and imaging markers in personalized medicine (PM) has arguably challenged the field of health economic modeling (HEM). This study aims to provide detailed insights into the current status of HEM in PM, in order to identify if and how modeling methods are used to address the challenges described in literature. Areas covered: A review was performed on studies that simulate health economic outcomes for personalized clinical pathways. Decision tree modeling and Markov modeling were the most observed methods. Not all identified challenges were frequently found, challenges regarding companion diagnostics, diagnostic performance, and evidence gaps were most often found. However, the extent to which challenges were addressed varied considerably between studies. Expert commentary: Challenges for HEM in PM are not yet routinely addressed which may indicate that either (1) their impact is less severe than expected, (2) they are hard to address and therefore not managed appropriately, or (3) HEM in PM is still in an early stage. As evidence on the impact of these challenges is still lacking, we believe that more concrete examples are needed to illustrate the identified challenges and to demonstrate methods to handle them.

  16. Longitudinal Omics Modelling and Integration in Clinical Metabonomics Research: challenges in childhood metabolic health research

    Directory of Open Access Journals (Sweden)

    Peter eSperisen

    2015-08-01

    Full Text Available Systems biology is an important approach for deciphering the complex processes in health maintenance and the etiology of metabolic diseases. Such integrative methodologies will help better understand the molecular mechanisms involved in growth and development throughout childhood, and consequently will result in new insights about metabolic and nutritional requirements of infants, children and adults. To achieve this, a better understanding of the physiological processes at anthropometric, cellular and molecular level for any given individual is needed. In this respect, novel omics technologies in combination with sophisticated data modelling techniques are key. Due to the highly complex network of influential factors determining individual trajectories, it becomes imperative to develop proper tools and solutions that will comprehensively model biological information related to growth and maturation of our body functions. The aim of this review and perspective is to evaluate, succinctly, promising data analysis approaches to enable data integration for clinical research, with an emphasis on the longitudinal component. Approaches based on empirical and mechanistic modelling of omics data are essential to leverage findings from high dimensional omics datasets and enable biological interpretation and clinical translation. On the one hand, empirical methods, which provide quantitative descriptions of patterns in the data, are mostly used for exploring and mining datasets. On the other hand, mechanistic models are based on an understanding of the behavior of a system’s components and condense information about the known functions, allowing robust and reliable analyses to be performed by bioinformatics pipelines and similar tools. Herein, we will illustrate current examples, challenges and perspectives in the applications of empirical and mechanistic modelling in the context of childhood metabolic health research.

  17. The challenge of modeling fuel–coolant interaction: Part I – Premixing

    Energy Technology Data Exchange (ETDEWEB)

    Meignen, Renaud, E-mail: renaud.meignen@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PSN-RES/SAG, BP 3, 13115 Saint-Paul-Lez-Durance Cedex (France); Picchi, Stephane; Lamome, Julien [Communication and Systèmes, 22 avenue Galilée, 92350 Le Plessis Robinson (France); Raverdy, Bruno [IRSN/PSN-RES/SAG, BP3, 92362 Fontenay aux Roses Cedex (France); Escobar, Sebastian Castrillon [Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PSN-RES/SAG, BP 3, 13115 Saint-Paul-Lez-Durance Cedex (France); Nicaise, Gregory [IRSN/PSN-RES/SAG, BP3, 92362 Fontenay aux Roses Cedex (France)

    2014-12-15

    Highlights: • We present the status modeling of the fuel–coolant interaction premixing stage in the computer code MC3D. • We also propose a general state of the art, highlighting recent improvements in understanding and modeling, remaining difficulties, controversies and needs. • We highlight the need for improving the understanding of the melt fragmentation and oxidation. • The verification basis is presented. - Abstract: Fuel–coolant interaction is a complex mixing process that can occur during the course of a severe accident in a nuclear power plant involving core melting and relocation. Under certain circumstances, a steam explosion might develop during the mixing of the melt and the water and induce a loss of integrity of the containment. Even in the absence of an explosion, studying the mixing phenomenon is also of high interest due to its strong impact on the progression of the accident (debris bed formation, hydrogen production). This article is the first of two aiming at presenting both a status of research and understanding of fuel–coolant interaction and the main characteristics of the model developed in the 3-dimensional computer code MC3D. It is devoted to the premixing phase whereas the second is related to the explosion phase. A special attention is given to major difficulties, uncertainties and needs for further improvements in knowledge and modeling. We discuss more particularly the major phenomena that are melt fragmentation and film boiling heat transfer and the challenges related to modeling melt solidification and oxidation. Some highlights related to the code verification are finally given.

  18. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  19. Digital Model-Based Engineering: Expectations, Prerequisites, and Challenges of Infusion

    Science.gov (United States)

    Hale, J. P.; Zimmerman, P.; Kukkala, G.; Guerrero, J.; Kobryn, P.; Puchek, B.; Bisconti, M.; Baldwin, C.; Mulpuri, M.

    2017-01-01

    Digital model-based engineering (DMbE) is the use of digital artifacts, digital environments, and digital tools in the performance of engineering functions. DMbE is intended to allow an organization to progress from documentation-based engineering methods to digital methods that may provide greater flexibility, agility, and efficiency. The term 'DMbE' was developed as part of an effort by the Model-Based Systems Engineering (MBSE) Infusion Task team to identify what government organizations might expect in the course of moving to or infusing MBSE into their organizations. The Task team was established by the Interagency Working Group on Engineering Complex Systems, an informal collaboration among government systems engineering organizations. This Technical Memorandum (TM) discusses the work of the MBSE Infusion Task team to date. The Task team identified prerequisites, expectations, initial challenges, and recommendations for areas of study to pursue, as well as examples of efforts already in progress. The team identified the following five expectations associated with DMbE infusion, discussed further in this TM: (1) Informed decision making through increased transparency, and greater insight. (2) Enhanced communication. (3) Increased understanding for greater flexibility/adaptability in design. (4) Increased confidence that the capability will perform as expected. (5) Increased efficiency. The team identified the following seven challenges an organization might encounter when looking to infuse DMbE: (1) Assessing value added to the organization. Not all DMbE practices will be applicable to every situation in every organization, and not all implementations will have positive results. (2) Overcoming organizational and cultural hurdles. (3) Adopting contractual practices and technical data management. (4) Redefining configuration management. The DMbE environment changes the range of configuration information to be managed to include performance and design models

  20. Design Challenges of an Episode-Based Payment Model in Oncology: The Centers for Medicare & Medicaid Services Oncology Care Model.

    Science.gov (United States)

    Kline, Ronald M; Muldoon, L Daniel; Schumacher, Heidi K; Strawbridge, Larisa M; York, Andrew W; Mortimer, Laura K; Falb, Alison F; Cox, Katherine J; Bazell, Carol; Lukens, Ellen W; Kapp, Mary C; Rajkumar, Rahul; Bassano, Amy; Conway, Patrick H

    2017-07-01

    The Centers for Medicare & Medicaid Services developed the Oncology Care Model as an episode-based payment model to encourage participating practitioners to provide higher-quality, better-coordinated care at a lower cost to the nearly three-quarter million fee-for-service Medicare beneficiaries with cancer who receive chemotherapy each year. Episode payment models can be complex. They combine into a single benchmark price all payments for services during an episode of illness, many of which may be delivered at different times by different providers in different locations. Policy and technical decisions include the definition of the episode, including its initiation, duration, and included services; the identification of beneficiaries included in the model; and beneficiary attribution to practitioners with overall responsibility for managing their care. In addition, the calculation and risk adjustment of benchmark episode prices for the bundle of services must reflect geographic cost variations and diverse patient populations, including varying disease subtypes, medical comorbidities, changes in standards of care over time, the adoption of expensive new drugs (especially in oncology), as well as diverse practice patterns. Other steps include timely monitoring and intervention as needed to avoid shifting the attribution of beneficiaries on the basis of their expected episode expenditures as well as to ensure the provision of necessary medical services and the development of a meaningful link to quality measurement and improvement through the episode-based payment methodology. The complex and diverse nature of oncology business relationships and the specific rules and requirements of Medicare payment systems for different types of providers intensify these issues. The Centers for Medicare & Medicaid Services believes that by sharing its approach to addressing these decisions and challenges, it may facilitate greater understanding of the model within the oncology

  1. Challenges for modelling spatio-temporal variations of malaria risk in Malawi

    Science.gov (United States)

    Lowe, R.; Chirombo, J.; Tompkins, A. M.

    2012-04-01

    Malaria is the leading cause of morbidity and mortality in Malawi with more than 6 million episodes reported each year. Malaria poses a huge economic burden to Malawi in terms of the direct cost of treating malaria patients and also indirect costs resulting from workdays lost in agriculture and industry and absenteeism from school. Malawi implements malaria control activities within the Roll Back Malaria framework, with the objective to provide those most at risk (i.e. children under five years, pregnant woman and individuals with suppressed immune systems) access to personal and community protective measures. However, at present there is no mechanism by which to target the most 'at risk' populations ahead of an impending epidemic. Malaria transmission is influenced by variations in meteorological conditions, which impact the biology of the mosquito and the availability of breeding sites, but also socio-economic conditions such as levels of urbanisation, poverty and education, which influence human vulnerability and vector habitat. The many potential drivers of malaria, both extrinsic, such as climate, and intrinsic, such as population immunity are often difficult to disentangle. This presents a challenge for modelling of malaria risk in space and time. Using an age-stratified spatio-temporal dataset of malaria cases at the district level from July 2004 - June 2011, we use a spatio-temporal modelling framework to model variations in malaria risk in Malawi. Climatic and topographic variations are accounted for using an interpolation method to relate gridded products to administrative districts. District level data is tested in the model to account for confounding factors, including the proportion of the population living in urban areas; residing in traditional housing; with no toilet facilities; who do not attend school, etc, the number of health facilities per population and yearly estimates of insecticide-treated mosquito net distribution. In order to account for

  2. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

    Directory of Open Access Journals (Sweden)

    Joel Bozue

    Full Text Available Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  3. Challenges in modelling spatiotemporally varying phytoplankton blooms in the Northwestern Arabian Sea and Gulf of Oman

    Science.gov (United States)

    Sedigh Marvasti, S.; Gnanadesikan, A.; Bidokhti, A. A.; Dunne, J. P.; Ghader, S.

    2015-07-01

    We examine interannual variability of phytoplankton blooms in northwestern Arabian Sea and Gulf of Oman. Satellite data (SeaWIFS ocean color) shows two climatological blooms in this region, a wintertime bloom peaking in February and a summertime bloom peaking in September. A pronounced anti-correlation between the AVISO sea surface height anomaly (SSHA) and chlorophyll is found during the wintertime bloom. On a regional scale, interannual variability of the wintertime bloom is thus dominated by cyclonic eddies which vary in location from one year to another. These results were compared against the outputs from three different 3-D Earth System models. We show that two coarse (1°) models with the relatively complex biogeochemistry (TOPAZ) capture the annual cycle but neither eddies nor the interannual variability. An eddy-resolving model (GFDL CM2.6) with a simpler biogeochemistry (miniBLING) displays larger interannual variability, but overestimates the wintertime bloom and captures eddy-bloom coupling in the south but not in the north. The southern part of the domain is a region with a much sharper thermocline and nutricline relatively close to the surface, in which eddies modulate diffusive nutrient supply to the surface (a mechanism not previously emphasized in the literature). We suggest that for the model to simulate the observed wintertime blooms within cyclones, it will be necessary to represent this relatively unusual nutrient structure as well as the cyclonic eddies. This is a challenge in the Northern Arabian Sea as it requires capturing the details of the outflow from the Persian Gulf.

  4. Nuclear Power Plant Life Management - Challenges and Proposal for a Unified Model Integrating Safety and Economics

    International Nuclear Information System (INIS)

    Contri, Paolo; Elsing, Bernhard

    2011-01-01

    In recent years many electric utilities and nuclear power plants adopted policies for improved coordination of both safety and non-safety programs, called plant life management (PLIM), also in view on plant life extension programs, but mainly for an optimisation of operating costs. The implementation of PLIM programs has followed many different approaches, being intrinsically dependent on the national regulatory framework and technical traditions. In Countries with some experience, the PLIM program proved very convenient, especially when coupled with Maintenance, Surveillance an Inspection (MS and I) optimization: average savings are reported in the range of 20-30% of total (maintenance) costs. A unified European model for PLIM was developed at the JRC-Institute for Energy with the support of a network of stakeholders (SENUF), and validated at some EU nuclear plants. This paper provides a summary of the model features, the result of its validation at some plants and summarises the perceived scientific/technological challenges on which JRC proposes to focus, based upon its competencies and skills, having in mind both the European and world-wide context and its potential evolution. (author)

  5. Challenges and gaps for energy planning models in the developing-world context

    Science.gov (United States)

    Debnath, Kumar Biswajit; Mourshed, Monjur

    2018-03-01

    Energy planning models (EPMs) support multi-criteria assessments of the impact of energy policies on the economy and environment. Most EPMs originated in developed countries and are primarily aimed at reducing greenhouse gas emissions while enhancing energy security. In contrast, most, if not all, developing countries are predominantly concerned with increasing energy access. Here, we review thirty-four widely used EPMs to investigate their applicability to developing countries and find an absence of consideration of the objectives, challenges, and nuances of the developing context. Key deficiencies arise from the lack of deliberation of the low energy demand resulting from lack of access and availability of supply. Other inadequacies include the lack of consideration of socio-economic nuances such as the prevalence of corruption and resulting cost inflation, the methods for adequately addressing the shortcomings in data quality, availability and adequacy, and the effects of climate change. We argue for further research on characterization and modelling of suppressed demand, climate change impacts, and socio-political feedback in developing countries, and the development of contextual EPMs.

  6. W(h)ither the Oracle? Cognitive biases and other human challenges of integrated environmental modeling

    Science.gov (United States)

    Glynn, Pierre D.; Ames, D.P.; Quinn, N. W. T.; Rizzoli, A.E.

    2014-01-01

    Integrated environmental modeling (IEM) can organize and increase our knowledge of the complex, dynamic ecosystems that house our natural resources and control the quality of our environments. Human behavior, however, must be taken into account. Human biases/heuristics reflect adaptation over our evolutionary past to frequently experienced situations that affected our survival and that provided sharply distinguished feedbacks at the level of the individual. Unfortunately, human behavior is not adapted to the more diffusely experienced, less frequently encountered, problems and issues that IEM typically seeks to address in the simulation of natural resources and environments. While seeking inspiration from the prophetic traditions of the Oracle of Delphi, several human biases are identified that may affect how the science base of IEM is assembled, and how IEM results are interpreted and used. These biases are supported by personal observations, and by the findings of behavioral scientists. A process for critical analysis is proposed that solicits explicit accounting and cognizance of potential human biases. A number of suggestions are made to address the human challenges of IEM, in addition to maintaining attitudes of watchful humility, open-mindedness, honesty, and transparent accountability. These include creating a new area of study in the behavioral biogeosciences, using structured processes for engaging the modeling and stakeholder community in IEM, and using “red teams” to increase resilience of IEM constructs and use.

  7. Challenges in modelling the random structure correctly in growth mixture models and the impact this has on model mixtures.

    Science.gov (United States)

    Gilthorpe, M S; Dahly, D L; Tu, Y K; Kubzansky, L D; Goodman, E

    2014-06-01

    Lifecourse trajectories of clinical or anthropological attributes are useful for identifying how our early-life experiences influence later-life morbidity and mortality. Researchers often use growth mixture models (GMMs) to estimate such phenomena. It is common to place constrains on the random part of the GMM to improve parsimony or to aid convergence, but this can lead to an autoregressive structure that distorts the nature of the mixtures and subsequent model interpretation. This is especially true if changes in the outcome within individuals are gradual compared with the magnitude of differences between individuals. This is not widely appreciated, nor is its impact well understood. Using repeat measures of body mass index (BMI) for 1528 US adolescents, we estimated GMMs that required variance-covariance constraints to attain convergence. We contrasted constrained models with and without an autocorrelation structure to assess the impact this had on the ideal number of latent classes, their size and composition. We also contrasted model options using simulations. When the GMM variance-covariance structure was constrained, a within-class autocorrelation structure emerged. When not modelled explicitly, this led to poorer model fit and models that differed substantially in the ideal number of latent classes, as well as class size and composition. Failure to carefully consider the random structure of data within a GMM framework may lead to erroneous model inferences, especially for outcomes with greater within-person than between-person homogeneity, such as BMI. It is crucial to reflect on the underlying data generation processes when building such models.

  8. Meeting the challenges of bringing a new base facility operation model to Gemini Observatory

    Science.gov (United States)

    Nitta, Atsuko; Arriagada, Gustavo; Adamson, A. J.; Cordova, Martin; Nunez, Arturo; Serio, Andrew; Kleinman, Scot

    2016-08-01

    The aim of the Gemini Observatory's Base Facilities Project is to provide the capabilities to perform routine night time operations with both telescopes and their instruments from their respective base facilities without anyone present at the summit. Tightening budget constraints prompted this project as both a means to save money and an opportunity to move toward increasing remote operations in the future. We successfully moved Gemini North nighttime operation to our base facility in Hawaii in Nov., 2015. This is the first 8mclass telescope to completely move night time operations to base facility. We are currently working on implementing BFO to Gemini South. Key challenges for this project include: (1) This is a schedule driven project. We have to implement the new capabilities by the end of 2015 for Gemini North and end of 2016 for Gemini South. (2) The resources are limited and shared with operations which has the higher priority than our project. (3) Managing parallel work within the project. (4) Testing, commissioning and introducing new tools to operational systems without adding significant disruptions to nightly operations. (5) Staff buying to the new operational model. (6) The staff involved in the project are spread on two locations separated by 10,000km, seven time zones away from each other. To overcome these challenges, we applied two principles: "Bare Minimum" and "Gradual Descent". As a result, we successfully completed the project ahead of schedule at Gemini North Telescope. I will discuss how we managed the cultural and human aspects of the project through these concepts. The other management aspects will be presented by Gustavo Arriagada [2], the Project Manager of this project. For technical details, please see presentations from Andrew Serio [3] and Martin Cordova [4].

  9. 2008 GEM Modeling Challenge: Metrics Study of the Dst Index in Physics-Based Magnetosphere and Ring Current Models and in Statistical and Analytic Specifications

    Science.gov (United States)

    Rastaetter, L.; Kuznetsova, M.; Hesse, M.; Pulkkinen, A.; Glocer, A.; Yu, Y.; Meng, X.; Raeder, J.; Wiltberger, M.; Welling, D.; hide

    2011-01-01

    In this paper the metrics-based results of the Dst part of the 2008-2009 GEM Metrics Challenge are reported. The Metrics Challenge asked modelers to submit results for 4 geomagnetic storm events and 5 different types of observations that can be modeled by statistical or climatological or physics-based (e.g. MHD) models of the magnetosphere-ionosphere system. We present the results of over 25 model settings that were run at the Community Coordinated Modeling Center (CCMC) and at the institutions of various modelers for these events. To measure the performance of each of the models against the observations we use comparisons of one-hour averaged model data with the Dst index issued by the World Data Center for Geomagnetism, Kyoto, Japan, and direct comparison of one-minute model data with the one-minute Dst index calculated by the United States Geologic Survey (USGS).

  10. Infectious disease in cervids of North America: data, models, and management challenges.

    Science.gov (United States)

    Conner, Mary Margaret; Ebinger, Michael Ryan; Blanchong, Julie Anne; Cross, Paul Chafee

    2008-01-01

    Over the past two decades there has been a steady increase in the study and management of wildlife diseases. This trend has been driven by the perception of an increase in emerging zoonotic diseases and the recognition that wildlife can be a critical factor for controlling infectious diseases in domestic animals. Cervids are of recent concern because, as a group, they present a number of unique challenges. Their close ecological and phylogenetic relationship to livestock species places them at risk for receiving infections from, and reinfecting livestock. In addition, cervids are an important resource; revenue from hunting and viewing contribute substantially to agency budgets and local economies. A comprehensive coverage of infectious diseases in cervids is well beyond the scope of this chapter. In North America alone there are a number of infectious diseases that can potentially impact cervid populations, but for most of these, management is not feasible or the diseases are only a potential or future concern. We focus this chapter on three diseases that are of major management concern and the center of most disease research for cervids in North America: bovine tuberculosis, chronic wasting disease, and brucellosis. We discuss the available data and recent advances in modeling and management of these diseases.

  11. Antipsychotic activity of aqueous ethanolic extract of Tinospora Cordifolia in amphetamine challenged mice model

    Directory of Open Access Journals (Sweden)

    Bindu nee Giri Jain

    2010-01-01

    Full Text Available Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p. was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO. The in vivo receptor binding studies were carried out to correlate the antipsychotic activity of the extract with its capacity to bind to the DAD2 receptor. The results in SLA showed that the hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250 mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamine induced hyperactivity in mice when compared to standard. Extract alone treated group at a dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity when compared to the control. The plant extract increased the DAD2 receptor binding in a dose dependent manner in treated mice compared to the control group.

  12. Integration of treatment innovation planning and implementation: strategic process models and organizational challenges.

    Science.gov (United States)

    Lehman, Wayne E K; Simpson, D Dwayne; Knight, Danica K; Flynn, Patrick M

    2011-06-01

    Sustained and effective use of evidence-based practices in substance abuse treatment services faces both clinical and contextual challenges. Implementation approaches are reviewed that rely on variations of plan-do-study-act (PDSA) cycles, but most emphasize conceptual identification of core components for system change strategies. A two-phase procedural approach is therefore presented based on the integration of Texas Christian University (TCU) models and related resources for improving treatment process and program change. Phase 1 focuses on the dynamics of clinical services, including stages of client recovery (cross-linked with targeted assessments and interventions), as the foundations for identifying and planning appropriate innovations to improve efficiency and effectiveness. Phase 2 shifts to the operational and organizational dynamics involved in implementing and sustaining innovations (including the stages of training, adoption, implementation, and practice). A comprehensive system of TCU assessments and interventions for client and program-level needs and functioning are summarized as well, with descriptions and guidelines for applications in practical settings. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  13. Modeling of Materials for Energy Storage: A Challenge for Density Functional Theory

    Science.gov (United States)

    Kaltak, Merzuk; Fernandez-Serra, Marivi; Hybertsen, Mark S.

    Hollandite α-MnO2 is a promising material for rechargeable batteries and is studied extensively in the community because of its interesting tunnel structure and the corresponding large capacity for lithium as well as sodium ions. However, the presence of partially reduced Mn ions due to doping with Ag or during lithiation makes hollandite a challenging system for density functional theory and the conventionally employed PBE+U method. A naive attempt to model the ternary system LixAgyMnO2 with density functionals, similar to those employed for the case y = 0 , fails and predicts a strong monoclinic distortion of the experimentally observed tetragonal unit cell for Ag2Mn8O16. Structure and binding energies are compared with experimental data and show the importance of van der Waals interactions as well as the necessity for an accurate description of the cooperative Jan-Teller effects for silver hollandite AgyMnO2. Based on these observations a ternary phase diagram is calculated allowing to predict the physical and chemical properties of LixAgyMnO2, such as stable stoichiometries, open circuit voltages, the formation of Ag metal and the structural change during lithiation. Department of Energy (DOE) under award #DE-SC0012673.

  14. Satellites and Steep Slopes - the challenge of topography in the Himalaya - Karakorum for cryosphere models

    Science.gov (United States)

    Steiner, J. F.; Buri, P.; Miles, E. S.; Immerzeel, W.

    2016-12-01

    The topography in glaciated catchments in the Himalaya - Karakoram range are extreme in a number of aspects that proof to be a challenge for distributed modelling. High altitude regions, where accumulation areas of glaciers are generally located, can at times be very steep, covered in hanging ice and seasonal snow. On the other hand, lower areas, where ablation zones on glacier tongues are located, tend to be very shallow. This has consequences for obtaining glacier areas from satellite derived glacier inventories (e.g. RGI, ICIMOD). As they are taken perpendicular to the center of the earth, these inventories will underestimate the area of steep regions, sometimes quite considerably (Figure 1). This can have consequences for a number of statistics in glaciological modeling, especially when it comes to the relative comparison of accumulation and ablation and hence overall melt from a glacier. Additionally, these steep head walls cause topographic shading. Depending on the exposition of the valley this can result in very divergent amounts of direct solar radiation reaching the glacier surface from valley to valley. Comparisons of melt between different regions and even glaciers have to be taken with considerable caution. Finally, these shallow glacier tongues are increasingly covered in debris. Such glacier surfaces with a debris cover ranging in grain size from sand to boulders several meters in diameter are very hummocky rather than flat bare ice glacier surfaces. This in turn increases local shading but also increases the overall glacier surface. Using high resolution satellite imagery and DEMs ( 5m) from our field site we investigate the effects of areal misrepresentations on the local scale. Decreasing resolution we then take this analysis to the mountain range scale and can identify to what degree these factors are significant and considering literature values determine the quantitative impact for energy and mass balance studies. Figure 1: A schematic

  15. From California dreaming to California data: Challenging historic models for landfill CH4 emissions

    Directory of Open Access Journals (Sweden)

    Kurt Spokas

    2015-06-01

    Full Text Available Abstract Improved quantification of diverse CH4 sources at the urban scale is needed to guide local GHG mitigation strategies in the Anthropocene. Herein, we focus on landfill CH4 emissions in California, challenging the current IPCC methodology which focuses on a climate dependency for landfill CH4 generation (methanogenesis, but does not explicitly consider climate or soil dependencies for emissions. Relying on a comprehensive California landfill database, a field-validated process-based model for landfill CH4 emissions (CALMIM, and select field measurements at 10 California sites with a variety of methods, we support the contrary position: Limited climate dependency for methanogenesis, but strong climate dependency for landfill CH4 emissions. Contrary to the historic IPCC empirical model for methanogenesis with kinetic constants related to climate, we demonstrate a simpler and more robust linear empirical relationship (r2 = 0.85; n=128 between waste mass and landfill biogas recovery [126 × 10-6 Nm3 CH4 hr-1 Mgwaste-1]. More interestingly, there are no statistically significant relationships with climate, site age, or status (open/closed for landfill biogas recovery. The current IPCC methodology does not consider soil or climate drivers for gaseous transport or seasonal methanotrophy in different cover soils. On the other hand, we illustrate strong climate and soil dependencies for landfill emissions—e.g., average intermediate cover emissions below 20 g CH4 m-2 d-1 when the site’s mean annual precipitation is >500 mm y-1. Thereby, for the California landfill CH4 inventory, the highest-emitting sites shift from landfills containing the largest mass of waste to sites dominated by intermediate cover types having a reduced rate of soil CH4 oxidation during the annual cycle. These differences have profound implications for developing more realistic, science-based urban and regional scale GHG inventories for landfill CH4 while reducing

  16. Opportunity by Design: New High School Models for Student Success. Carnegie Challenge

    Science.gov (United States)

    Hamilton, Leah; Mackinnon, Anne

    2013-01-01

    The goal of Carnegie "Challenge" papers is to lift up ideas and issues in a way that elevates them to the nation's agenda. This paper is a "Challenge" paper, and serves as a call to realize the full power of the Common Core by redesigning and reshaping schools to support teachers and maximize key resources, rather than…

  17. Photons, photosynthesis, and high-performance computing: challenges, progress, and promise of modeling metabolism in green algae

    International Nuclear Information System (INIS)

    Chang, C H; Graf, P; Alber, D M; Kim, K; Murray, G; Posewitz, M; Seibert, M

    2008-01-01

    The complexity associated with biological metabolism considered at a kinetic level presents a challenge to quantitative modeling. In particular, the relatively sparse knowledge of parameters for enzymes with known kinetic responses is problematic. The possible space of these parameters is of high-dimension, and sampling of such a space typifies a combinatorial explosion of possible dynamic states. However, with sufficient quantitative transcriptomics, proteomics, and metabolomics data at hand, these challenges could be met by high-performance software with sampling, fitting, and optimization capabilities. With this in mind, we present the High-Performance Systems Biology Toolkit HiPer SBTK, an evolving software package to simulate, fit, and optimize metabolite concentrations and fluxes within the space of rate and binding parameters associated with detailed enzyme kinetic models. We present our chosen modeling paradigm for the formulation of metabolic pathway models, the means to address the challenge of representing such models in a precise and persistent fashion using the standardized Systems Biology Markup Language, and our second-generation model of H2-associated Chlamydomonas metabolism. Processing of such models for hierarchically parallelized simulation and optimization, job specification by the user through a GUI interface, software capabilities and initial scaling data, and the mapping of the computation to biological questions is also discussed. Moreover, we present near-term future software and model development goals

  18. Methodological challenges to bridge the gap between regional climate and hydrology models

    Science.gov (United States)

    Bozhinova, Denica; José Gómez-Navarro, Juan; Raible, Christoph; Felder, Guido

    2017-04-01

    The frequency and severity of floods worldwide, together with their impacts, are expected to increase under climate change scenarios. It is therefore very important to gain insight into the physical mechanisms responsible for such events in order to constrain the associated uncertainties. Model simulations of the climate and hydrological processes are important tools that can provide insight in the underlying physical processes and thus enable an accurate assessment of the risks. Coupled together, they can provide a physically consistent picture that allows to assess the phenomenon in a comprehensive way. However, climate and hydrological models work at different temporal and spatial scales, so there are a number of methodological challenges that need to be carefully addressed. An important issue pertains the presence of biases in the simulation of precipitation. Climate models in general, and Regional Climate models (RCMs) in particular, are affected by a number of systematic biases that limit their reliability. In many studies, prominently the assessment of changes due to climate change, such biases are minimised by applying the so-called delta approach, which focuses on changes disregarding absolute values that are more affected by biases. However, this approach is not suitable in this scenario, as the absolute value of precipitation, rather than the change, is fed into the hydrological model. Therefore, bias has to be previously removed, being this a complex matter where various methodologies have been proposed. In this study, we apply and discuss the advantages and caveats of two different methodologies that correct the simulated precipitation to minimise differences with respect an observational dataset: a linear fit (FIT) of the accumulated distributions and Quantile Mapping (QM). The target region is Switzerland, and therefore the observational dataset is provided by MeteoSwiss. The RCM is the Weather Research and Forecasting model (WRF), driven at the

  19. An Integrated Recovery-oriented Model (IRM) for mental health services: evolution and challenges.

    Science.gov (United States)

    Frost, Barry G; Tirupati, Srinivasan; Johnston, Suzanne; Turrell, Megan; Lewin, Terry J; Sly, Ketrina A; Conrad, Agatha M

    2017-01-17

    Over past decades, improvements in longer-term clinical and personal outcomes for individuals experiencing serious mental illness (SMI) have been moderate, although recovery has clearly been shown to be possible. Recovery experiences are inherently personal, and recovery can be complex and non-linear; however, there are a broad range of potential recovery contexts and contributors, both non-professional and professional. Ongoing refinement of recovery-oriented models for mental health (MH) services needs to be fostered. This descriptive paper outlines a service-wide Integrated Recovery-oriented Model (IRM) for MH services, designed to enhance personally valued health, wellbeing and social inclusion outcomes by increasing access to evidenced-based psychosocial interventions (EBIs) within a service context that supports recovery as both a process and an outcome. Evolution of the IRM is characterised as a series of five broad challenges, which draw together: relevant recovery perspectives; overall service delivery frameworks; psychiatric and psychosocial rehabilitation approaches and literature; our own clinical and service delivery experience; and implementation, evaluation and review strategies. The model revolves around the person's changing recovery needs, focusing on underlying processes and the service frameworks to support and reinforce hope as a primary catalyst for symptomatic and functional recovery. Within the IRM, clinical rehabilitation (CR) practices, processes and partnerships facilitate access to psychosocial EBIs to promote hope, recovery, self-agency and social inclusion. Core IRM components are detailed (remediation of functioning; collaborative restoration of skills and competencies; and active community reconnection), together with associated phases, processes, evaluation strategies, and an illustrative IRM scenario. The achievement of these goals requires ongoing collaboration with community organisations. Improved outcomes are achievable for

  20. Grand challenge problems in environmental modeling and remediation: Groundwater contaminant transport. Final project report 1998

    International Nuclear Information System (INIS)

    1998-04-01

    The over-reaching goal of the Groundwater Grand Challenge component of the Partnership in Computational Science (PICS) was to develop and establish the massively parallel approach for the description of groundwater flow and transport and to address the problem of uncertainties in the data and its interpretation. This necessitated the development of innovative algorithms and the implementation of massively parallel computational tools to provide a suite of simulators for groundwater flow and transport in heterogeneous media. This report summarizes the activities and deliverables of the Groundwater Grand Challenge project funded through the High Performance Computing grand challenge program of the Department of Energy from 1995 through 1997

  1. Simulating the impacts of disturbances on forest carbon cycling in North America: processes, data, models, and challenges

    Science.gov (United States)

    Shuguang Liu; Ben Bond-Lamberty; Jeffrey A. Hicke; Rodrigo Vargas; Shuqing Zhao; Jing Chen; Steven L. Edburg; Yueming Hu; Jinxun Liu; A. David McGuire; Jingfeng Xiao; Robert Keane; Wenping Yuan; Jianwu Tang; Yiqi Luo; Christopher Potter; Jennifer Oeding

    2011-01-01

    Forest disturbances greatly alter the carbon cycle at various spatial and temporal scales. It is critical to understand disturbance regimes and their impacts to better quantify regional and global carbon dynamics. This review of the status and major challenges in representing the impacts of disturbances in modeling the carbon dynamics across North America revealed some...

  2. Challenges in Mentoring Software Development Projects in the High School: Analysis According to Shulman's Teacher Knowledge Base Model

    Science.gov (United States)

    Meerbaum-Salant, Orni; Hazzan, Orit

    2009-01-01

    This paper focuses on challenges in mentoring software development projects in the high school and analyzes difficulties encountered by Computer Science teachers in the mentoring process according to Shulman's Teacher Knowledge Base Model. The main difficulties that emerged from the data analysis belong to the following knowledge sources of…

  3. A Meta-Analysis of Video-Modeling Based Interventions for Reduction of Challenging Behaviors for Students with EBD

    Science.gov (United States)

    Losinski, Mickey; Wiseman, Nicole; White, Sherry A.; Balluch, Felicity

    2016-01-01

    The current study examined the use of video modeling (VM)-based interventions to reduce the challenging behaviors of students with emotional or behavioral disorders. Each study was evaluated using Council for Exceptional Children's (CEC's) quality indicators for evidence-based practices. In addition, study effects were calculated along the three…

  4. Challenges in understanding, modelling, and mitigating Lake Outburst Flood Hazard: experiences from Central Asia

    Science.gov (United States)

    Mergili, Martin; Schneider, Demian; Andres, Norina; Worni, Raphael; Gruber, Fabian; Schneider, Jean F.

    2010-05-01

    Lake Outburst Floods can evolve from complex process chains like avalanches of rock or ice that produce flood waves in a lake which may overtop and eventually breach glacial, morainic, landslide, or artificial dams. Rising lake levels can lead to progressive incision and destabilization of a dam, to enhanced ground water flow (piping), or even to hydrostatic failure of ice dams which can cause sudden outflow of accumulated water. These events often have a highly destructive potential because a large amount of water is released in a short time, with a high capacity to erode loose debris, leading to a powerful debris flow with a long travel distance. The best-known example of a lake outburst flood is the Vajont event (Northern Italy, 1963), where a landslide rushed into an artificial lake which spilled over and caused a flood leading to almost 2000 fatalities. Hazards from the failure of landslide dams are often (not always) fairly manageable: most breaches occur in the first few days or weeks after the landslide event and the rapid construction of a spillway - though problematic - has solved some hazardous situations (e.g. in the case of Hattian landslide in 2005 in Pakistan). Older dams, like Usoi dam (Lake Sarez) in Tajikistan, are usually fairly stable, though landsildes into the lakes may create floodwaves overtopping and eventually weakening the dams. The analysis and the mitigation of glacial lake outburst flood (GLOF) hazard remains a challenge. A number of GLOFs resulting in fatalities and severe damage have occurred during the previous decades, particularly in the Himalayas and in the mountains of Central Asia (Pamir, Tien Shan). The source area is usually far away from the area of impact and events occur at very long intervals or as singularities, so that the population at risk is usually not prepared. Even though potentially hazardous lakes can be identified relatively easily with remote sensing and field work, modeling and predicting of GLOFs (and also

  5. List context effects in languages with opaque and transparent orthographies: A challenge for models of reading

    Directory of Open Access Journals (Sweden)

    Daniela eTraficante

    2014-09-01

    Full Text Available This paper offers a review of data which show that reading is a flexible and dynamic process and that readers can exert strategic control over it. Two main hypotheses on the control of reading processes have been suggested: the route de-emphasis hypothesis and the time-criterion hypothesis. According to the former, the presence of irregular words in the list might lead to an attenuation of the non-lexical process, while the presence of non-words could trigger a de-emphasis of the lexical route. An alternative account is proposed by the time-criterion hypothesis whereby the reader sets a flexible deadline to initiate the response. According to the latter view, it is the average pronunciation difficulty of the items in the block that modulates the time-criterion for response. However, it is worth noting that the list composition has been shown to exert different effects in transparent compared to opaque orthographies, as the consistency of spelling-sound correspondences can influence the processing costs of the non-lexical pathway. In transparent orthographies, the non-lexical route is not resource demanding and can successfully contribute to the pronunciation of regular words, thus its de-emphasis could not be as useful/necessary as in opaque orthographies. The complex patterns of results from the literature on list context effects are a challenge for computational models of reading which face the problem of simulating strategic control over reading processes. Different proposals suggest a modification of parameter setting in the non-lexical route or the implementation of a new module aimed at focusing attention on the output of the more convenient pathway. Simulation data and an assessment of the models’ fit to the behavioral results are presented and discussed to shed light on the role of the cognitive system when reading aloud.

  6. Transferring knowledge from observations and models to decision makers: an overview and challenges

    Science.gov (United States)

    Habib, Shahid; Nokra, Nada A.

    2004-02-01

    Over the last 25 years, a tremendous progress has been made in the Earth science space-based remote sensing observations, technologies and algorithms. Such advancements have improved the predictability by providing lead-time and accuracy of forecast in weather, climate, natural hazards, and natural resources. It has further reduced or bounded the overall uncertainties by partially improving our understanding of planet Earth as an integrated system that is governed by non-linear and chaotic behavior. Many countries such US, European Community, Japan, China and others have invested billions of dollars in developing and launching space-based assets in the low earth (LEO) and geostationary (GEO) orbits. However, the wealth of this scientific knowledge that has potential of extracting monumental socio-economic benefits from such large investments have been slow in reaching the public and decision makers. For instance, there are a number of areas such as energy forecasting, aviation safety, agricultural competitiveness, disaster management, homeland security, air quality and public health, which can directly take advantage. Nevertheless, we all live in a global economy that depends on access to the best available Earth Science information for all inhabitants of this planet. This paper surveys and examines a number such applications in terms of their architecture, maturity and economic applicability as they apply to the societal needs. A detailed analysis is also presented of various challenges and issues that pertain to a number of areas such as: (1) difficulties in making a speedy transition of data and information from observations and models to relevant Decision Support Systems (DSS) or tools, (2) data and models inter-operability issues, (3) limitations of spatial, spectral and temporal resolution,(4) communication limitations as dictated by the availability of image processing and data compression techniques. Additionally, the most critical element amongst all is

  7. Transferring Knowledge from Observations and Models to Decision Makers: An Overview and Challenges

    Science.gov (United States)

    Habib, Shahid; Nokra, Nada Abu

    2003-01-01

    Over the last 25 years, a tremendous progress has been made in the Earth science space-based remote sensing observations, technologies and algorithms. Such advancements have improved the predictability by providing lead-time and accuracy of forecast in weather, climate, natural hazards, and natural resources. It has further reduced or bounded the overall uncertainties by partially improving our understanding of planet Earth as an integrated system that is governed by non-linear and chaotic behavior. Many countries such US, European Community, Japan, China and others have invested billions of dollars in developing and launching space-based assets in the low earth (LEO) and geostationary (GEO) orbits. However, the wealth of this scientific knowledge that has potential of extracting monumental socio-economic benefits from such large investments have been slow in reaching to public and decision makers. For instance, there are a number of areas such as energy forecasting, aviation safety, agricultural competitiveness, disaster management, security, air quality and public health can directly take advantage. Nevertheless, we all live in a global economy that depends on access to the best available Earth Science information for all inhabitants of this planet. This paper surveys and examines a number such applications in terms of their architecture, maturity and economic applicability as they apply to the societal needs. A detailed analysis is also presented of various challenges and issues that pertain to a number of areas such as: (1) difficulties in making a speedy transition of data and information from observations and models to relevant Decision Support Systems (DSS) or tools, (2) data and models inter-operability issues, (3) limitations of spatial, spectral and temporal resolution, (4) communication limitations as dictated by the availability of image processing and data compression techniques. Additionally, the most critical element amongst all is the organizational

  8. Wind vs Water in Hurricanes: The Challenge of Multi-peril Hazard Modeling

    Science.gov (United States)

    Powell, M. D.

    2017-12-01

    operational solution to collect wind and water level measurements, and to conduct observation based modeling of wind and water impacts. My presentation will discuss some of the challenges to wind and water hazard monitoring and modeling.

  9. Why employees with higher challenging appraisals style are more affectively engaged at work? The role of challenging stressors: a moderated mediation model.

    Science.gov (United States)

    Lin, Shin-Huei; Wu, Chia-Huei; Chen, Mei-Yen; Chen, Lung Hung

    2014-10-01

    Challenging stressors have been positively linked to various work outcomes. However, the role of individual differences in stress appraisal in shaping the function of challenging stressors and work outcomes has been rarely discussed. Drawing on the individual differences perspective, the authors propose that employees higher in challenge appraisal are more likely to have challenging stressors and are more responsive to such stressors to have a higher positive affect at work. Results obtained from 117 employees supported the hypotheses. The results indicated that challenge appraisal is positively related to challenging stressors. In addition, challenging stressors has a positive association with positive affect at work when challenge appraisal is high but has a null association when challenge appraisal is low. The findings suggest that challenging stressors does not necessarily bring positive work outcomes as suggested in past studies and highlight the importance of considering dispositional tendency in stress appraisal when looking into the function of challenging stressors and work outcomes. © 2014 International Union of Psychological Science.

  10. Challenge problem and milestones for : Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC).

    Energy Technology Data Exchange (ETDEWEB)

    Freeze, Geoffrey A.; Wang, Yifeng; Howard, Robert; McNeish, Jerry A.; Schultz, Peter Andrew; Arguello, Jose Guadalupe, Jr.

    2010-09-01

    This report describes the specification of a challenge problem and associated challenge milestones for the Waste Integrated Performance and Safety Codes (IPSC) supporting the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The NEAMS challenge problems are designed to demonstrate proof of concept and progress towards IPSC goals. The goal of the Waste IPSC is to develop an integrated suite of modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. To demonstrate proof of concept and progress towards these goals and requirements, a Waste IPSC challenge problem is specified that includes coupled thermal-hydrologic-chemical-mechanical (THCM) processes that describe (1) the degradation of a borosilicate glass waste form and the corresponding mobilization of radionuclides (i.e., the processes that produce the radionuclide source term), (2) the associated near-field physical and chemical environment for waste emplacement within a salt formation, and (3) radionuclide transport in the near field (i.e., through the engineered components - waste form, waste package, and backfill - and the immediately adjacent salt). The initial details of a set of challenge milestones that collectively comprise the full challenge problem are also specified.

  11. Challenge problem and milestones for: Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC)

    International Nuclear Information System (INIS)

    Freeze, Geoffrey A.; Wang, Yifeng; Howard, Robert; McNeish, Jerry A.; Schultz, Peter Andrew; Arguello, Jose Guadalupe Jr.

    2010-01-01

    This report describes the specification of a challenge problem and associated challenge milestones for the Waste Integrated Performance and Safety Codes (IPSC) supporting the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The NEAMS challenge problems are designed to demonstrate proof of concept and progress towards IPSC goals. The goal of the Waste IPSC is to develop an integrated suite of modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. To demonstrate proof of concept and progress towards these goals and requirements, a Waste IPSC challenge problem is specified that includes coupled thermal-hydrologic-chemical-mechanical (THCM) processes that describe (1) the degradation of a borosilicate glass waste form and the corresponding mobilization of radionuclides (i.e., the processes that produce the radionuclide source term), (2) the associated near-field physical and chemical environment for waste emplacement within a salt formation, and (3) radionuclide transport in the near field (i.e., through the engineered components - waste form, waste package, and backfill - and the immediately adjacent salt). The initial details of a set of challenge milestones that collectively comprise the full challenge problem are also specified.

  12. Simulating the impacts of disturbances on forest carbon cycling in North America: Processes, data, models, and challenges

    Science.gov (United States)

    Liu, Shuguang; Bond-Lamberty, Ben; Hicke, Jeffrey A.; Vargas, Rodrigo; Zhao, Shuqing; Chen, Jing; Edburg, Steven L.; Hu, Yueming; Liu, Jinxun; McGuire, A. David; Xiao, Jingfeng; Keane, Robert; Yuan, Wenping; Tang, Jianwu; Luo, Yiqi; Potter, Christopher; Oeding, Jennifer

    2011-01-01

    Forest disturbances greatly alter the carbon cycle at various spatial and temporal scales. It is critical to understand disturbance regimes and their impacts to better quantify regional and global carbon dynamics. This review of the status and major challenges in representing the impacts of disturbances in modeling the carbon dynamics across North America revealed some major advances and challenges. First, significant advances have been made in representation, scaling, and characterization of disturbances that should be included in regional modeling efforts. Second, there is a need to develop effective and comprehensive process‐based procedures and algorithms to quantify the immediate and long‐term impacts of disturbances on ecosystem succession, soils, microclimate, and cycles of carbon, water, and nutrients. Third, our capability to simulate the occurrences and severity of disturbances is very limited. Fourth, scaling issues have rarely been addressed in continental scale model applications. It is not fully understood which finer scale processes and properties need to be scaled to coarser spatial and temporal scales. Fifth, there are inadequate databases on disturbances at the continental scale to support the quantification of their effects on the carbon balance in North America. Finally, procedures are needed to quantify the uncertainty of model inputs, model parameters, and model structures, and thus to estimate their impacts on overall model uncertainty. Working together, the scientific community interested in disturbance and its impacts can identify the most uncertain issues surrounding the role of disturbance in the North American carbon budget and develop working hypotheses to reduce the uncertainty

  13. Challenges Pre-Service Teachers Face When Implementing a 5E Inquiry Model of Instruction

    Science.gov (United States)

    Enugu, Ramya; Hokayem, Hayat

    2017-01-01

    This study examined the challenges that pre-service teachers faced when implementing inquiry and their perspective on how to overcome them. The data sample was 55 pre-service teachers (PSTs) enrolled into two sections of a science methods course in a private university in North Texas. The data sources consisted of inquiry-based lesson plans, PST…

  14. The South African Engineering Education Model with a European Perspective: History, Analogies, Transformations and Challenges

    Science.gov (United States)

    Kloot, Bruce; Rouvrais, Siegfried

    2017-01-01

    South Africa, with its national cultural diversity and post-apartheid challenges and commitments, finds echoes in the European context, especially considering the imperatives of openness and non-discrimination in higher education. With an historical tradition of excellence in engineering education, the emphasis on supporting educationally…

  15. Motivation, Challenges, Support (MCS) Cycle Model for the Development of PBL Tutors

    Science.gov (United States)

    Constantinou, Costas S.; Nicolaou, Stella A.

    2018-01-01

    Problem-Based Learning (PBL) is well known for enhancing students' problem solving skills and teamwork, while the role of PBL tutors is to facilitate discussion rather than teach. This study used four focus groups to explore PBL tutors' motivation, challenges and support mechanisms, and the relationship between these. The study found that there…

  16. From California dreaming to California data: Challenging historic models for landfill CH4 emissions

    Science.gov (United States)

    Improved quantification of diverse CH4 sources at the urban scale is needed to guide local greenhouse gas (GHG) mitigation strategies in the Anthropocene. Herein, we focus on landfill CH4 emissions in California, challenging the current IPCC methodology which focuses on a climate dependency for land...

  17. From Teacher to Manager: Expectations and Challenge in the Further Education Sector. A Relationship Model

    Science.gov (United States)

    Corbett, Stephen

    2017-01-01

    In a turbulent working environment with varying expectations and challenges is it fair to expect further education teachers and managers to maintain and improve standards? This article highlights that with the incorporation of colleges began a series of initiatives to professionalise the FE sector. This coupled with pressures for those who work…

  18. Modeling and analysis for big data challenges in nano-imaging

    NARCIS (Netherlands)

    Grollios, T.

    2012-01-01

    Very large data sets, often being referred as Big Data, that are hard to collect, store, process and visualize using traditional computational methods are bringing challenges in various domains of the technology world. The resent advances in electron microscopy that enable the collection of large

  19. Confronting the STEM Challenge: A New Modeling Tool for U.S. Education Policymakers

    Science.gov (United States)

    Business-Higher Education Forum (NJ1), 2010

    2010-01-01

    The Business-Higher Education Forum (BHEF) is an organization of Fortune 500 chief executive officers (CEOs,) prominent college and university presidents, and foundation leaders working to advance innovative solutions to the nation's education challenges in order to enhance U.S. competitiveness. This paper presents questions and answers about the…

  20. A systematic review and checklist presenting the main challenges for health economic modeling in personalized medicine : towards implementing patient-level models

    NARCIS (Netherlands)

    Degeling, Koen; Koffijberg, Hendrik; IJzerman, Maarten Joost

    2017-01-01

    Introduction: The ongoing development of genomic medicine and the use of molecular and imaging markers in personalized medicine (PM) has arguably challenged the field of health economic modeling (HEM). This study aims to provide detailed insights into the current status of HEM in PM, in order to

  1. Immunogenicity in pig-tailed macaques of poliovirus replicons expressing HIV-1 and SIV antigens and protection against SHIV-89.6P disease

    International Nuclear Information System (INIS)

    Fultz, Patricia N.; Stallworth, Jackie; Porter, Donna; Novak, Miroslav; Anderson, Marie J.; Morrow, Casey D.

    2003-01-01

    In the search for an effective vaccine against the human immunodeficiency virus (HIV), novel ways to deliver viral antigens are being evaluated. One such approach is the use of nonreplicating viral vectors encoding HIV and/or SIV genes that are expressed after infection of host cells. Nonreplicating poliovirus vectors, termed replicons, that expressed HIV-1/HXB2 and SIVmac239 gag and various HIV-1 env genes from different clades were tested for immunogenicity and protective efficacy against intravenous challenge of pig-tailed macaques with SHIV-89.6P. To maximize both cellular and humoral immune responses, a prime-boost regimen was used. Initially, macaques were immunized four times over 35 weeks by either the intranasal and intrarectal or the intramuscular (im) route with mixtures of poliovirus replicons expressing HIV-1 gag and multiple env genes. Immunization with replicons alone induced both serum antibodies and lymphocyte proliferative responses. After boosting with purified Env protein, neutralizing antibodies to SHIV-89.6P were induced in four of five immunized animals. In a second experiment, four macaques were immunized im three times over 27 weeks with replicons expressing the SIVmac239 gag and HIV-1/HXB2 env genes. All immunized animals were then boosted twice with purified HIV-1-89.6 rgp140-Env and SIVmac239 p55-Gag proteins. Four control animals received only the two protein inoculations. Immunized and control animals were then challenged intravenously with the pathogenic SHIV-89.6P. After challenge the animals were monitored for virus isolation from peripheral blood mononuclear cells and plasma viremia and for changes in virus-specific antibody titers. Naieve pig-tailed macaques experienced rapid loss of CD4 + T cells and died between 38 and 62 weeks after infection. In contrast, macaques immunized with replicons and proteins rapidly cleared plasma virus and did not experience sustained loss of CD4 + lymphocytes. Furthermore, two of the four macaques

  2. Development of a vaccine-challenge model for avian metapneumovirus subtype C in turkeys.

    Science.gov (United States)

    Velayudhan, Binu T; Noll, Sally L; Thachil, Anil J; Shaw, Daniel P; Goyal, Sagar M; Halvorson, David A; Nagaraja, Kakambi V

    2007-02-26

    The objective of this study was to evaluate different preparations of avian metapneumovirus (aMPV) subtype C as vaccine challenge in turkeys. Two aMPV isolates and their respective nasal turbinate homogenates after propagation in turkeys were used in the study. Significantly higher clinical sign scores were recorded in birds inoculated with 20 or 2% turbinate homogenate of recent isolate. Birds in the above groups showed more pronounced histopathological lesions, and a higher percentage of birds showed viral RNA and antigen in tissues. The data demonstrated that nasal turbinate homogenate of recent isolate produced severe clinical signs and lesions in turkeys and could be an ideal candidate for vaccine-challenge studies.

  3. SaaS Model, Virtualization and Information Safety - Challenge for Online Business

    OpenAIRE

    Ioana Lupasc; Gabriela Gheorghe

    2016-01-01

    The advantages of new information technologies are present in all fields, while disadvantages, weaknesses represent a relatively recent topic of study. Security issues currently facing online business is new concerns for European legislative environment and new challenges of finding methods of securing technology solution providers offered information. As for Schengen terrorist threats represent a threat to the proper functioning of the European Economic Area also the online business cyber ...

  4. SaaS Model, Virtualization and Information Safety - Challenge for Online Business

    Directory of Open Access Journals (Sweden)

    Ioana Lupasc

    2016-07-01

    Full Text Available The advantages of new information technologies are present in all fields, while disadvantages, weaknesses represent a relatively recent topic of study. Security issues currently facing online business is new concerns for European legislative environment and new challenges of finding methods of securing technology solution providers offered information. As for Schengen terrorist threats represent a threat to the proper functioning of the European Economic Area also the online business cyber threats have the effect of impeding and even huge losses.

  5. From California dreaming to California data: Challenging historic models for landfill CH4 emissions

    OpenAIRE

    Spokas, Kurt; Bogner, Jean; Corcoran, Meg; Walker, Scott

    2015-01-01

    Abstract Improved quantification of diverse CH4 sources at the urban scale is needed to guide local GHG mitigation strategies in the Anthropocene. Herein, we focus on landfill CH4 emissions in California, challenging the current IPCC methodology which focuses on a climate dependency for landfill CH4 generation (methanogenesis), but does not explicitly consider climate or soil dependencies for emissions. Relying on a comprehensive California landfill database, a field-validated process-based m...

  6. Lost in Translation: The Challenge of Exporting Models of Civil Military Relations

    Science.gov (United States)

    2012-03-01

    society.”27 As Williams has noted, traditional mili- tary culture is confronted by a number of challenges such as cultural relativism and the...imposition of nonmilitary, social, ethical , and political criteria of evaluation on the mili- tary.28 It is these postmodern militaries, and the...members see themselves and what constitutes good governance, ethical behaviour and funda- mental courage.”45 In a study of leadership mythol- ogy in

  7. Modeling and optimization for proton exchange membrane fuel cell stack using aging and challenging P systems based optimization algorithm

    International Nuclear Information System (INIS)

    Yang, Shipin; Chellali, Ryad; Lu, Xiaohua; Li, Lijuan; Bo, Cuimei

    2016-01-01

    Accurate models of PEM (proton exchange membrane) fuel cells are of great significance for the analysis and the control for power generation. We present a new semi-empirical model to predict the voltage outputs of PEM fuel cell stacks. We also introduce a new estimation method, called AC-POA (aging and challenging P systems based optimization algorithm) allowing deriving the parameters of the semi-empirical model. In our model, the cathode inlet pressure is selected as an additional factor to modify the expression of concentration over-voltage V con for traditional Amphlett's PEM fuel cell model. In AC-POA, the aging-mechanism inspired object updating rule is merged in existing P system. We validate through experiments the effectiveness of AC-POA and the fitting accuracy of our model. Modeling comparison results show that the predictions of our model are the best in terms of fitting to actual sample data. - Highlights: • Presented a p c -based modificatory semi-empirical model for PEMFC stack. • Introduced a new aging inspired improved parameter estimation algorithm, AC-POA. • Validated the effectiveness of the AC-POA and the new model. • Remodeled the practical PEM fuel cell system.

  8. Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

    Directory of Open Access Journals (Sweden)

    Strasak Alexander

    2009-06-01

    Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

  9. A New Modeling Approach for Future Challenges in Process and Product Design

    DEFF Research Database (Denmark)

    Eden, Mario Richard; Jørgensen, Sten Bay; Gani, Rafiqul

    2003-01-01

    In this paper, a new technique for model reduction that is based on rearranging a part of the model representing the constitutive equations is presented. The rearrangement of the constitutive equations leads to the definition of a new set of pseudo-intensive variables, where the component...... compositions are replaced by reduction parameters in the process model. Since the number of components dominates the size of the traditional model equations, a significant reduction of the model size is obtained through this new technique. Some interesting properties of this new technique is that the model...... reduction does not introduce any approximations to the model, it does not change the physical location of the process variables and it provides a, visualization of the process and operation that otherwise would not be possible. Furthermore by employing the recently introduced principle of reverse problem...

  10. A New Modeling Approach for Future Challenges in Process and Product Design

    DEFF Research Database (Denmark)

    In this paper, a new technique for model reduction that is based on rearranging a part of the model representing the constitutive equations is presented. The rearrangement of the constitutive equations leads to the definition of a new set of pseudo-intensive variables, where the component...... compositions are replaced by reduction parameters in the process model. Since the number of components dominates the size of the traditional model equations, a significant reduction of the model size is obtained through this new technique. Some interesting properties of this new technique is that the model...... reduction does not introduce any approximations to the model, it does not change the physical location of the process variables and it provides a visualization of the process and operation that otherwise would not be possible. Furthermore by employing the recently introduced principle of reverse problem...

  11. Towards Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis.

    Science.gov (United States)

    Francipane, Maria Giovanna; Lagasse, Eric

    2016-09-01

    In recent years, functional three-dimensional (3D) tissue generation in vitro has been significantly advanced by tissue-engineering methods, achieving better reproduction of complex native organs compared to conventional culture systems. This review will discuss traditional 3D cell culture techniques as well as newly developed technology platforms. These recent techniques provide new possibilities in the creation of human body parts and provide more accurate predictions of tissue response to drug and chemical challenges. Given the rapid advancement in the human induced pluripotent stem cell (iPSC) field, these platforms also hold great promise in the development of patient-specific, transplantable tissues and organs on demand.

  12. Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

    Directory of Open Access Journals (Sweden)

    D.S. Macêdo

    2012-03-01

    Full Text Available Prenatal immune challenge (PIC in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C, to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge for original studies published in the last 10 years (May 2001 to October 2011 concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

  13. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    Science.gov (United States)

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  14. A Simple Model for Complex Fabrication of MEMS based Pressure Sensor: A Challenging Approach

    Directory of Open Access Journals (Sweden)

    Himani SHARMA

    2010-08-01

    Full Text Available In this paper we have presented the simple model for complex fabrication of MEMS based absolute micro pressure sensor. This kind of modeling is extremely useful for determining its complexity in fabrication steps and provides complete information about process sequence to be followed during manufacturing. Therefore, the need for test iteration decreases and cost, time can be reduced significantly. By using DevEdit tool (part of SILVACO tool, a behavioral model of pressure sensor have been presented and implemented.

  15. Nucleic acid reactivity : challenges for next-generation semiempirical quantum models

    OpenAIRE

    Huang, Ming; Giese, Timothy J.; York, Darrin M.

    2015-01-01

    Semiempirical quantum models are routinely used to study mechanisms of RNA catalysis and phosphoryl transfer reactions using combined quantum mechanical/molecular mechanical methods. Herein, we provide a broad assessment of the performance of existing semiempirical quantum models to describe nucleic acid structure and reactivity in order to quantify their limitations and guide the development of next-generation quantum models with improved accuracy. Neglect of diatomic diffierential overlap (...

  16. New Economy And Global Challenge: Winning Model Of Successful Small Business Organizations

    OpenAIRE

    Mirjana Radovic Markovic

    2007-01-01

    The old principles no longer work in the age of Globalization. Businesses have reached the old model's limits with respect to complexity and speed. The real problem is a ruinously dysfunctional mismatch between today's business environment and the classic business model. Namely, the wrong model may transform a company into the vehicle of its own death. Great shifts - genuine and radical transformation- have been shaping the economy and business environment in recent decades. Technology, espec...

  17. Contemporary challenges in applying of the modified model CAPM with country risk premium in emerging economies

    OpenAIRE

    Petrović Dragana

    2017-01-01

    Modern approach in determining the expected return of foreign investors' investments is based on the evaluation investment in capital asset-CAPM (Capital Asset Pricing Model). In order to use the CAPM model for calculating the expected return of foreign investors in growing economies, it is developed the extended model CAPM with the risk premium in the country. This variant of the CAPM model has been used for estimating the cost of capital. This is the expected return on a portfolio of the co...

  18. Nucleic acid reactivity: challenges for next-generation semiempirical quantum models.

    Science.gov (United States)

    Huang, Ming; Giese, Timothy J; York, Darrin M

    2015-07-05

    Semiempirical quantum models are routinely used to study mechanisms of RNA catalysis and phosphoryl transfer reactions using combined quantum mechanical (QM)/molecular mechanical methods. Herein, we provide a broad assessment of the performance of existing semiempirical quantum models to describe nucleic acid structure and reactivity to quantify their limitations and guide the development of next-generation quantum models with improved accuracy. Neglect of diatomic differential overlap and self-consistent density-functional tight-binding semiempirical models are evaluated against high-level QM benchmark calculations for seven biologically important datasets. The datasets include: proton affinities, polarizabilities, nucleobase dimer interactions, dimethyl phosphate anion, nucleoside sugar and glycosidic torsion conformations, and RNA phosphoryl transfer model reactions. As an additional baseline, comparisons are made with several commonly used density-functional models, including M062X and B3LYP (in some cases with dispersion corrections). The results show that, among the semiempirical models examined, the AM1/d-PhoT model is the most robust at predicting proton affinities. AM1/d-PhoT and DFTB3-3ob/OPhyd reproduce the MP2 potential energy surfaces of 6 associative RNA phosphoryl transfer model reactions reasonably well. Further, a recently developed linear-scaling "modified divide-and-conquer" model exhibits the most accurate results for binding energies of both hydrogen bonded and stacked nucleobase dimers. The semiempirical models considered here are shown to underestimate the isotropic polarizabilities of neutral molecules by approximately 30%. The semiempirical models also fail to adequately describe torsion profiles for the dimethyl phosphate anion, the nucleoside sugar ring puckers, and the rotations about the nucleoside glycosidic bond. The modeling of pentavalent phosphorus, particularly with thio substitutions often used experimentally as mechanistic

  19. Evolution and challenges of dynamic global vegetation models for some aspects of plant physiology and elevated atmospheric CO2.

    Science.gov (United States)

    Rezende, L F C; Arenque, B C; Aidar, S T; Moura, M S B; Von Randow, C; Tourigny, E; Menezes, R S C; Ometto, J P H B

    2016-07-01

    Dynamic global vegetation models (DGVMs) simulate surface processes such as the transfer of energy, water, CO2, and momentum between the terrestrial surface and the atmosphere, biogeochemical cycles, carbon assimilation by vegetation, phenology, and land use change in scenarios of varying atmospheric CO2 concentrations. DGVMs increase the complexity and the Earth system representation when they are coupled with atmospheric global circulation models (AGCMs) or climate models. However, plant physiological processes are still a major source of uncertainty in DGVMs. The maximum velocity of carboxylation (Vcmax), for example, has a direct impact over productivity in the models. This parameter is often underestimated or imprecisely defined for the various plant functional types (PFTs) and ecosystems. Vcmax is directly related to photosynthesis acclimation (loss of response to elevated CO2), a widely known phenomenon that usually occurs when plants are subjected to elevated atmospheric CO2 and might affect productivity estimation in DGVMs. Despite this, current models have improved substantially, compared to earlier models which had a rudimentary and very simple representation of vegetation-atmosphere interactions. In this paper, we describe this evolution through generations of models and the main events that contributed to their improvements until the current state-of-the-art class of models. Also, we describe some main challenges for further improvements to DGVMs.

  20. Developing an inter-enterprise alignment maturity model: research challenges and solutions

    NARCIS (Netherlands)

    Santana Tapia, R.G.; Daneva, Maia; van Eck, Pascal

    Business-IT alignment is pervasive today, as organizations strive to achieve competitive advantage. Like in other areas, e.g., software development, maintenance and IT services, there are maturity models to assess such alignment. Those models, however, do not specifically address the aspects needed

  1. Modelling micro-pollutant fate in wastewater collection and treatment systems: status and challenges

    DEFF Research Database (Denmark)

    Plósz, Benedek G.; Benedetti, L.; Daigger, G. T.

    2013-01-01

    of such models. In brief, we conclude that, in order to predict the contaminant removal in centralised treatment works, considering the dramatic improvement in monitoring and detecting MPs in wastewater, more mechanistic approaches should be used to complement conventional, heuristic and other fate models...

  2. Assessing healthcare process maturity: challenges of using a business process maturity model

    NARCIS (Netherlands)

    Tarhan, A.; Turetken, O.; van den Biggelaar, F.J.H.M.

    2015-01-01

    Doi: 10.4108/icst.pervasivehealth.2015.259105 The quality of healthcare services is influenced by the maturity of healthcare processes used to develop it. A maturity model is an instrument to assess and continually improve organizational processes. In the last decade, a number of maturity models

  3. Advantages and Challenges of Using Physics Curricula as a Model for Reforming an Undergraduate Biology Course

    Science.gov (United States)

    Donovan, D. A.; Atkins, L. J.; Salter, I. Y.; Gallagher, D. J.; Kratz, R. F.; Rousseau, J. V.; Nelson, G. D.

    2013-01-01

    We report on the development of a life sciences curriculum, targeted to undergraduate students, which was modeled after a commercially available physics curriculum and based on aspects of how people learn. Our paper describes the collaborative development process and necessary modifications required to apply a physics pedagogical model in a life…

  4. Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making

    Science.gov (United States)

    The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology have grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has t...

  5. Modeling neurodegenerative diseases with patient-derived induced pluripotent cells: Possibilities and challenges.

    Science.gov (United States)

    Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya; Phanthong, Phetcharat; Schmid, Benjamin; Nielsen, Troels T; Freude, Kristine K

    2017-10-25

    The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing. The iPSCs are self-renewable and capable of being differentiated into the cell types affected by the diseases. These in vitro models based on patient-derived iPSCs provide the opportunity to model disease development, uncover novel mechanisms and test potential therapeutics. Here we review findings from iPSC-based modeling of selected neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and spinocerebellar ataxia. Furthermore, we discuss the possibilities of generating three-dimensional (3D) models using the iPSCs-derived cells and compare their advantages and disadvantages to conventional two-dimensional (2D) models. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. The Demand Side in Economic Models of Energy Markets: The Challenge of Representing Consumer Behavior

    International Nuclear Information System (INIS)

    Krysiak, Frank C.; Weigt, Hannes

    2015-01-01

    Energy models play an increasing role in the ongoing energy transition processes either as tools for forecasting potential developments or for assessments of policy and market design options. In recent years, these models have increased in scope and scale and provide a reasonable representation of the energy supply side, technological aspects and general macroeconomic interactions. However, the representation of the demand side and consumer behavior has remained rather simplistic. The objective of this paper is twofold. First, we review existing large-scale energy model approaches, namely bottom-up and top-down models, with respect to their demand-side representation. Second, we identify gaps in existing approaches and draft potential pathways to account for a more detailed demand-side and behavior representation in energy modeling.

  7. The Demand Side in Economic Models of Energy Markets: The Challenge of Representing Consumer Behavior

    Energy Technology Data Exchange (ETDEWEB)

    Krysiak, Frank C., E-mail: frank.krysiak@unibas.ch; Weigt, Hannes [Department of Business and Economics, University of Basel, Basel (Switzerland)

    2015-05-19

    Energy models play an increasing role in the ongoing energy transition processes either as tools for forecasting potential developments or for assessments of policy and market design options. In recent years, these models have increased in scope and scale and provide a reasonable representation of the energy supply side, technological aspects and general macroeconomic interactions. However, the representation of the demand side and consumer behavior has remained rather simplistic. The objective of this paper is twofold. First, we review existing large-scale energy model approaches, namely bottom-up and top-down models, with respect to their demand-side representation. Second, we identify gaps in existing approaches and draft potential pathways to account for a more detailed demand-side and behavior representation in energy modeling.

  8. The Demand Side in Economic Models of Energy Markets: The Challenge of Representing Consumer Behavior

    Directory of Open Access Journals (Sweden)

    Frank eKrysiak

    2015-05-01

    Full Text Available Energy models play an increasing role in the ongoing energy transition processes either as tools for forecasting potential developments or for assessments of policy and market design options. In recent years these models have increased in scope and scale and provide a reasonable representation of the energy supply side, technological aspects and general macroeconomic interactions. However, the representation of the demand side and consumer behavior has remained rather simplistic. The objective of this paper is twofold. First, we review existing large scale energy model approaches, namely bottom-up and top-down models, with respect to their demand side representation. Second, we identify gaps in existing approaches and draft potential pathways to account for a more detailed demand side and behavior representation in energy modeling.

  9. Cluster models of light nuclei and the method of hyperspherical harmonics: Successes and challenges

    International Nuclear Information System (INIS)

    Danilin, B. V.; Shul'gina, N. B.; Ershov, S. N.; Vaagen, J. S.

    2009-01-01

    Hyperspherical-harmonics method to investigate the lightest nuclei having three-cluster structure is discussed together with recent experiments. Properties of bound states and methods to explore three-body continuum are presented. The challenges created by large neutron excess and halo phenomena are highlighted. Astrophysical aspects of the 7 Li + n → 8 Li + γ reaction and the solar-boron-neutrinos problem are analyzed. Three-cluster structure of highly excited states in 8 Be is shown to be responsible for extreme isospin mixing. Progress in studies of 6 He- and 11 Li-induced inclusive and exclusive nuclear reactions is demonstrated, providing information on the nature of continuum structures of Borromean nuclei.

  10. Current status of deepwater oil spill modelling in the Faroe-Shetland Channel, Northeast Atlantic, and future challenges.

    Science.gov (United States)

    Gallego, Alejandro; O'Hara Murray, Rory; Berx, Barbara; Turrell, William R; Beegle-Krause, C J; Inall, Mark; Sherwin, Toby; Siddorn, John; Wakelin, Sarah; Vlasenko, Vasyl; Hole, Lars R; Dagestad, Knut Frode; Rees, John; Short, Lucy; Rønningen, Petter; Main, Charlotte E; Legrand, Sebastien; Gutierrez, Tony; Witte, Ursula; Mulanaphy, Nicole

    2018-02-01

    As oil reserves in established basins become depleted, exploration and production moves towards relatively unexploited areas, such as deep waters off the continental shelf. The Faroe-Shetland Channel (FSC, NE Atlantic) and adjacent areas have been subject to increased focus by the oil industry. In addition to extreme depths, metocean conditions in this region characterise an environment with high waves and strong winds, strong currents, complex circulation patterns, sharp density gradients, and large small- and mesoscale variability. These conditions pose operational challenges to oil spill response and question the suitability of current oil spill modelling frameworks (oil spill models and their forcing data) to adequately simulate the behaviour of a potential oil spill in the area. This article reviews the state of knowledge relevant to deepwater oil spill modelling for the FSC area and identifies knowledge gaps and research priorities. Our analysis should be relevant to other areas of complex oceanography. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  11. Research advances and challenges in one-dimensional modeling of secondary settling tanks--a critical review.

    Science.gov (United States)

    Li, Ben; Stenstrom, M K

    2014-11-15

    Sedimentation is one of the most important processes that determine the performance of the activated sludge process (ASP), and secondary settling tanks (SSTs) have been frequently investigated with the mathematical models for design and operation optimization. Nevertheless their performance is often far from satisfactory. The starting point of this paper is a review of the development of settling theory, focusing on batch settling and the development of flux theory, since they played an important role in the early stage of SST investigation. The second part is an explicit review of the established 1-D SST models, including the relevant physical law, various settling behaviors (hindered, transient, and compression settling), the constitutive functions, and their advantages and disadvantages. The third part is a discussion of numerical techniques required to solve the governing equation, which is usually a partial differential equation. Finally, the most important modeling challenges, such as settleability description, settling behavior understanding, are presented. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Contemporary challenges in applying of the modified model CAPM with country risk premium in emerging economies

    Directory of Open Access Journals (Sweden)

    Petrović Dragana

    2017-01-01

    Full Text Available Modern approach in determining the expected return of foreign investors' investments is based on the evaluation investment in capital asset-CAPM (Capital Asset Pricing Model. In order to use the CAPM model for calculating the expected return of foreign investors in growing economies, it is developed the extended model CAPM with the risk premium in the country. This variant of the CAPM model has been used for estimating the cost of capital. This is the expected return on a portfolio of the company's stocks in less developed countries. Those countries have certain problems and factors of risk investment. This research examines the limitations and shortcomings in the application of the extended model with country risk premium, during the calculation of the cost of capital in the less developed economies. We present possible models to overcome those problems and also a need for upgrading of modified CAPM model with a risk premium of the country which, beside risk of the country (CR must have a discount for the 'advantage of the country'.

  13. Modeling time-series count data: the unique challenges facing political communication studies.

    Science.gov (United States)

    Fogarty, Brian J; Monogan, James E

    2014-05-01

    This paper demonstrates the importance of proper model specification when analyzing time-series count data in political communication studies. It is common for scholars of media and politics to investigate counts of coverage of an issue as it evolves over time. Many scholars rightly consider the issues of time dependence and dynamic causality to be the most important when crafting a model. However, to ignore the count features of the outcome variable overlooks an important feature of the data. This is particularly the case when modeling data with a low number of counts. In this paper, we argue that the Poisson autoregressive model (Brandt and Williams, 2001) accurately meets the needs of many media studies. We replicate the analyses of Flemming et al. (1997), Peake and Eshbaugh-Soha (2008), and Ura (2009) and demonstrate that models missing some of the assumptions of the Poisson autoregressive model often yield invalid inferences. We also demonstrate that the effect of any of these models can be illustrated dynamically with estimates of uncertainty through a simulation procedure. The paper concludes with implications of these findings for the practical researcher. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Challenges to Rainfall-Runoff and Transit Time Distribution Modeling Within the Southeastern Coastal Plain, USA

    Science.gov (United States)

    Decker, P.; Cohen, M. J.; Jawitz, J. W.

    2017-12-01

    Previous hydrologic studies primarily focus on processes related to montane catchments with significant runoff ratios, low evapotranspiration rates, and reasonably short travel times. There is a significant lack of research for hydrologic processes occurring within the United States Southeastern Coastal Plain landscape where low-relief and high rates of evapotranspiration impact water fluxes. Hydrologic modeling efforts within this region may elucidate possible interactions and timescales of solute travel where much of the landscape is managed for agricultural crops, namely plantation forestry. A long-term paired watershed study carried out in northern Florida monitored two second-order blackwater streams for five years. Rainfall-runoff models for both catchments were created using daily discharge, precipitation, and modeled evapotranspiration as input parameters. Best fit occurred (NSE = 0.8) when the catchments were modeled as two-storage (shallow and deep) reservoirs in parallel and overland flow was allowed to contribute to streamflow in periods were shallow groundwater storage was at capacity. In addition, streamflow and rainfall chloride concentrations were used to model in-variable transit time distributions using spectral methods. In both catchments this transit time was unresolvable because output spectral power exceeded input spectral power, a result assumed to be driven by the evaporative demand of the region. A modeled chloride time series from random input concentration and modeled output through the rainfall-runoff model was used to alter the evaporation ratio. Once evaporation rates equaled known rates found in cool, high-relief catchments, spectral analysis illustrated higher input spectral power and therefore resolvable transit times. Findings from this study illustrate significant effects from evaporation within the catchment - often exceeding the signal from the background catchment process itself. Calculations illustrate a proposed mean transit

  15. Transforming SWAT for continental-scale high-resolution modeling of floodplain dynamics: opportunities and challenges

    Science.gov (United States)

    Rajib, A.; Merwade, V.; Liu, Z.; Lane, C.; Golden, H. E.; Tavakoly, A. A.; Follum, M. L.

    2017-12-01

    There have been many initiatives to develop frameworks for continental-scale modeling and mapping floodplain dynamics. The choice of a model for such needs should be governed by its suitability to be executed in high performance cyber platforms, ability to integrate supporting hydraulic/hydrodynamic tools, and ability to assimilate earth observations. Furthermore, disseminating large volume of outputs for public use and interoperability with similar frameworks should be considered. Considering these factors, we have conducted a series of modeling experiments and developed a suite of cyber-enabled platforms that have transformed Soil and Water Assessment Tool (SWAT) into an appropriate model for use in a continental-scale, high resolution, near real-time flood information framework. Our first experiment uses a medium size watershed in Indiana, USA and attempts burning-in a high resolution, National Hydrography Dataset Plus(NHDPlus) into the SWAT model. This is crucial with a view to make the outputs comparable with other global/national initiatives. The second experiment is built upon the first attempt to add a modified landscape representation in the model which differentiates between the upland and floodplain processes. Our third experiment involves two separate efforts: coupling SWAT with a hydrodynamic model LISFLOOD-FP and a new generation, low complexity hydraulic model AutoRoute. We have executed the prototype "loosely-coupled" models for the Upper Mississippi-Ohio River Basin in the USA, encompassing 1 million square km drainage area and nearly 0.2 million NHDPlus river reaches. The preliminary results suggest reasonable accuracy for both streamflow and flood inundation. In this presentation, we will also showcase three cyber-enabled platforms, including SWATShare to run and calibrate large scale SWAT models online using high performance computational resources, HydroGlobe to automatically extract and assimilate multiple remotely sensed earth observations in

  16. Challenges encountered when expanding activated sludge models: a case study based on N2O production

    DEFF Research Database (Denmark)

    Snip, Laura; Boiocchi, Riccardo; Flores Alsina, Xavier

    2014-01-01

    (WWTPs). As a consequence, these experiments might not be representative for full-scale performance, and unexpected behaviour may be observed when simulating WWTP models using the derived process equations. In this paper we want to highlight problems encountered using a simplified case study: a modified......: problems related to the overall mathematical model structure and problems related to the published set of parameter values. The paper describes the model implementation incompatibilities, the variability in parameter values and the difficulties of reaching similar conditions when simulating a full...

  17. Do Over or Make Do? Climate Models as a Software Development Challenge (Invited)

    Science.gov (United States)

    Easterbrook, S. M.

    2010-12-01

    We present the results of a comparative study of the software engineering culture and practices at four different earth system modeling centers: the UK Met Office Hadley Centre, the National Center for Atmospheric Research (NCAR), The Max-Planck-Institut für Meteorologie (MPI-M), and the Institut Pierre Simon Laplace (IPSL). The study investigated the software tools and techniques used at each center to assess their effectiveness. We also investigated how differences in the organizational structures, collaborative relationships, and technical infrastructures constrain the software development and affect software quality. Specific questions for the study included 1) Verification and Validation - What techniques are used to ensure that the code matches the scientists’ understanding of what it should do? How effective are these are at eliminating errors of correctness and errors of understanding? 2) Coordination - How are the contributions from across the modeling community coordinated? For coupled models, how are the differences in the priorities of different, overlapping communities of users addressed? 3) Division of responsibility - How are the responsibilities for coding, verification, and coordination distributed between different roles (scientific, engineering, support) in the organization? 4) Planning and release processes - How do modelers decide on priorities for model development, how do they decide which changes to tackle in a particular release of the model? 5) Debugging - How do scientists debug the models, what types of bugs do they find in their code, and how they find them? The results show that each center has evolved a set of model development practices that are tailored to their needs and organizational constraints. These practices emphasize scientific validity, but tend to neglect other software qualities, and all the centers struggle frequently with software problems. The testing processes are effective at removing software errors prior to

  18. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; van Bilsen, Jolanda; Głogowski, Robert

    2016-01-01

    of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally...... validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant...

  19. The challenge of staying happier: testing the Hedonic Adaptation Prevention model.

    Science.gov (United States)

    Sheldon, Kennon M; Lyubomirsky, Sonja

    2012-05-01

    The happiness that comes from a particular success or change in fortune abates with time. The Hedonic Adaptation Prevention (HAP) model specifies two routes by which the well-being gains derived from a positive life change are eroded--the first involving bottom-up processes (i.e., declining positive emotions generated by the positive change) and the second involving top-down processes (i.e., increased aspirations for even more positivity). The model also specifies two moderators that can forestall these processes--continued appreciation of the original life change and continued variety in change-related experiences. The authors formally tested the predictions of the HAP model in a 3-month three-wave longitudinal study of 481 students. Temporal path analyses and moderated regression analyses provided good support for the model. Implications for the stability of well-being, the feasibility of "the pursuit of happiness," and the appeal of overconsumption are discussed.

  20. Modeling European ruminant production systems: facing the challenges of climate change

    DEFF Research Database (Denmark)

    Kipling, Richard Philip; Bannink, Andre; Bellocchi, Gianni

    2016-01-01

    Ruminant production systems are important producers of food, support rural communities and culture, and help to maintain a range of ecosystem services including the sequestering of carbon in grassland soils. However, these systems also contribute significantly to climate change through greenhouse...... gas (GHG) emissions, while intensification of production has driven biodiversity and nutrient loss, and soil degradation. Modeling can offer insights into the complexity underlying the relationships between climate change, management and policy choices, food production, and the maintenance...... of ecosystem services. This paper 1) provides an overview of how ruminant systems modeling supports the efforts of stakeholders and policymakers to predict, mitigate and adapt to climate change and 2) provides ideas for enhancing modeling to fulfil this role. Many grassland models can predict plant growth...

  1. Safety Management and Risk Modelling in Aviation : The challenge of quantifying management influences

    NARCIS (Netherlands)

    Lin, P.H.

    2011-01-01

    Aviation accidents result from a combination of many different causal factors ( human errors, technical failures, environmental and organisational influences). Increasing interest over the past two decades in causal modelling of organisational factors has been motivated by the desire to understand

  2. New Challenges for the Management of the Development of Information Systems Based on Complex Mathematical Models

    DEFF Research Database (Denmark)

    Carugati, Andrea

    2002-01-01

    has been initiated with the scope of investigating the questions that mathematical modelling technology poses to traditional information systems development projects. Based on the past body of research, this study proposes a framework to guide decision making for managing projects of information......The advancements in complexity and sophistication of mathematical models for manufacturing scheduling and control and the increase of the ratio power/cost of computers are beginning to provide the manufacturing industry with new software tools to improve production. A Danish action research project...... systems development. In a presented case the indications of the model are compared with the decisions taken during the development. The results highlight discrepancies between the structure and predictions of the model and the case observations, especially with regard to the importance given to the users...

  3. Projecting hydropower production under future climates: a review of modelling challenges and open questions

    Science.gov (United States)

    Schaefli, Bettina

    2015-04-01

    Hydropower is a pillar for renewable electricity production in almost all world regions. The planning horizon of major hydropower infrastructure projects stretches over several decades and consideration of evolving climatic conditions plays an ever increasing role. This review of model-based climate change impact assessments provides a synthesis of the wealth of underlying modelling assumptions, highlights the importance of local factors and attempts to identify the most urgent open questions. Based on existing case studies, it critically discusses whether current hydro-climatic modelling frameworks are likely to provide narrow enough water scenario ranges to be included into economic analyses for end-to-end climate change impact assessments including electricity market models. This will be completed with an overview of not or indirectly climate-related boundary conditions, such as economic growth, legal constraints, national subsidy frameworks or growing competition for water, which might locally largely outweigh any climate change impacts.

  4. German model. Challenge on the way to the 21st century. Das Deutschland-Modell. Herausforderungen auf dem Weg ins 21. Jahrhundert

    Energy Technology Data Exchange (ETDEWEB)

    Pestel, E.; Bauerschmidt, R.; Gottwaldt, M.; Huebl, L.; Moeller, K.P.; Oest, W.; Stroebele, W.

    1980-06-01

    The German model is a consequent continuation of the work which has already lead to the Mesarovic-Pestel world-model and the 2nd report to the Club of Rome: The authors, members of the Institut fuer angewandte Systemforschung und Prognose (ISP) at Hanover, founded in 1975 by Professor Pestel, show the problems and challenges on the way to the 21st century on the basis of numerous model calculations. The German model consists of a number of coupled sub-models investigating the developments in the fields of population, education, economics, energy and labour market. Germany's role in the international network and its contribution to the North-South dialogue is taken into consideration. In the much-discussed energy sector, the calculations show that future requirements will probably be much lower than expected. Until the turn of the century, there will be no serious problems in energy and raw materials supply and consequently no structural changes.

  5. The Opportunities and Challenges of Persuasive Technology in Creating Sustainable Innovation and Business Model Innovation

    DEFF Research Database (Denmark)

    Aagaard, Annabeth; Lindgren, Peter

    2015-01-01

    The opportunities of persuasive technology in facilitating sustainable innovation and business model innovation have been witnessed continuously during the last decade. The unique ability of persuasive technology in interacting and mediating across users, customers, decisions makers and other...... stakeholders provides access to core knowledge about behavior and opportunities to influence and even change their behavior in a positive and more sustainable manner. Sustainable innovation and business model innovation is gaining more and more competitive leverage due to customer requirements, the growing...

  6. Review article: Hydrological modeling in glacierized catchments of central Asia – status and challenges

    OpenAIRE

    Y. Chen; W. Li; G. Fang; Z. Li

    2017-01-01

    Meltwater from glacierized catchments is one of the most important water supplies in central Asia. Therefore, the effects of climate change on glaciers and snow cover will have increasingly significant consequences for runoff. Hydrological modeling has become an indispensable research approach to water resources management in large glacierized river basins, but there is a lack of focus in the modeling of glacial discharge. This paper reviews the status of hydrological modeli...

  7. Technical challenges and limitations of current mouse models of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Garson Kenneth

    2012-11-01

    Full Text Available Abstract The development of genetically engineered models (GEM of epithelial ovarian cancer (EOC has been very successful, with well validated models representing high grade and low grade serous adenocarcinomas and endometrioid carcinoma (EC. Most of these models were developed using technologies intended to target the ovarian surface epithelium (OSE, the cell type long believed to be the origin of EOC. More recent evidence has highlighted what is likely a more prevalent role of the secretory cell of the fallopian tube in the ontogeny of EOC, however none of the GEM of EOC have demonstrated successful targeting of this important cell type. The precise technologies exploited to develop the existing GEM of EOC are varied and carry with them advantages and disadvantages. The use of tissue specific promoters to model disease has been very successful, but the lack of any truly specific OSE or oviductal secretory cell promoters makes the outcomes of these models quite unpredictable. Effecting genetic change by the administration of adenoviral vectors expressing Cre recombinase may alleviate the perceived need for tissue specific promoters, however the efficiencies of infection of different cell types is subject to numerous biological parameters that may lead to preferential targeting of certain cell populations. One important future avenue of GEM of EOC is the evaluation of the role of genetic modifiers. We have found that genetic background can lead to contrasting phenotypes in one model of ovarian cancer, and data from other laboratories have also hinted that the exact genetic background of the model may influence the resulting phenotype. The different genetic backgrounds may modify the biology of the tumors in a manner that will be relevant to human disease, but they may also be modifying parameters which impact the response of the host to the technologies employed to develop the model.

  8. Mathematical models of blast induced TBI: current status, challenges and prospects

    Directory of Open Access Journals (Sweden)

    Raj K Gupta

    2013-05-01

    Full Text Available Blast induced traumatic brain injury (TBI has become a signature wound of recent military activities and is the leading cause of death and long-term disability among U.S. soldiers. The current limited understanding of brain injury mechanisms impedes the development of protection, diagnostic and treatment strategies. We believe mathematical models of blast wave brain injury biomechanics and neurobiology, complemented with in vitro and in vivo experimental studies, will enable a better understanding of injury mechanisms and accelerate the development of both protective and treatment strategies. The goal of this paper is to review the current state of the art in mathematical and computational modeling of blast induced TBI, identify research gaps and recommend future developments. A brief overview of blast wave physics, injury biomechanics and the neurobiology of brain injury is used as a foundation for a more detailed discussion of multiscale mathematical models of primary biomechanics and secondary injury and repair mechanisms. The paper also presents a discussion of model development strategies, experimental approaches to generate benchmark data for model validation and potential applications of the model for prevention and protection against blast wave TBI.

  9. An exploratory study on the building information modeling adoption in United Arab Emirates municipal projects- current status and challenges

    Directory of Open Access Journals (Sweden)

    Venkatachalam Senthilkumar

    2017-01-01

    Full Text Available Many modern complex building projects in the public and private sectors are characterized by its poor information management which is manifested by time and cost overruns around the world. Building Information Modelling (BIM is currently being adopted around the world with various countries mandated its implementation. In specific, the implementation of BIM is rapidly growing in developed countries such as USA, UK, Singapore and Australia, with government mandate through devising strategies and initiatives to increase the adoption. The implementation of BIM in United Arab Emirates (UAE and other developing countries lags behind due to the existence of numerous implementation barriers. This study explores the current status of BIM implementation in the UAE municipalities, further explores the people, process and technology readiness towards BIM adoption in the UAE building projects. Further the study also explores the current challenges against the BIM adoption. The study adopts a positivists approach by collecting data through questionnaires, a sample of sixty participants across the UAE municipalities from different states were selected randomly to acquire the data. The collected data is statistically analyzed to obtain the findings. The analysis results showed that there are inadequate people and process related readiness towards BIM adoption whereas the technology readiness does exist. The same also was reflected in further analysis on BIM adoption barriers as the challenges. Further the paper also discusses the possible strategies adopted around the world through literature to address the explored challenges in the study

  10. Challenges in integrative approaches to modelling the marine ecosystems of the North Atlantic: Physics to fish and coasts to ocean

    DEFF Research Database (Denmark)

    Holt, Jason; Icarus Allen, J.; Anderson, Thomas R.

    2014-01-01

    It has long been recognised that there are strong interactions and feedbacks between climate, upper ocean biogeochemistry and marine food webs, and also that food web structure and phytoplankton community distribution are important determinants of variability in carbon production and export from...... for quantitative tools to support ecosystem-based management initiatives. The purpose of this paper is to review approaches to the modelling of marine ecosystems with a focus on the North Atlantic Ocean and its adjacent shelf seas, and to highlight the challenges they face and suggest ways forward. We consider...

  11. Data Logging and Data Modelling: Using seismology and seismic data to create challenge in the academic classroom.

    Science.gov (United States)

    Neighbour, Gordon

    2013-04-01

    In 2012 Computing and Information Technology was disapplied from the English National Curriculum and therefore no longer has a compulsory programme of study. Data logging and data modelling are still essential components of the curriculum in the Computing and Information Technology classroom. Once the students have mastered the basics of both spreadsheet and information handling software they need to be further challenged. All too often the data used with relation to data-logging and data-handling is not realistic enough to really challenge very able students. However, using data from seismology allows students to manipulate "real" data and enhances their experience of geo-science, developing their skills and then allowing them to build on this work in both the science and geography classroom. This new scheme of work "Seismology at School" has allowed the students to work and develop skills beyond those normally expected for their age group and has allowed them to better appreciate their learning experience of "Natural Hazards" in the science and geography classroom in later years. The students undertake research to help them develop their understanding of earthquakes. This includes using materials from other nations within the European Economic Area, to also develop and challenge their use of Modern Foreign Languages. They are then challenged to create their own seismometers using simple kits and 'free' software - this "problem-solving" approach to their work is designed to enhance team-work and to extend the challenge they experience in the classroom. The students are then are asked to manipulate a "real" set of data using international earthquake data from the most recent whole year. This allows the students to make use of many of the analytical and statistical functions of both spreadsheet software and information handling software in a meaningful way. The students will need to have developed a hypothesis which their work should have provided either validation

  12. Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications

    Science.gov (United States)

    Physiologically based kinetic (PBK) models are used widely throughout a number of working sectors, including academia and industry, to provide insight into the dosimetry related to observed adverse health effects in humans and other species. Use of these models has increased over...

  13. Understanding the limits of animal models as predictors of human biology: lessons learned from the sbv IMPROVER Species Translation Challenge.

    Science.gov (United States)

    Rhrissorrakrai, Kahn; Belcastro, Vincenzo; Bilal, Erhan; Norel, Raquel; Poussin, Carine; Mathis, Carole; Dulize, Rémi H J; Ivanov, Nikolai V; Alexopoulos, Leonidas; Rice, J Jeremy; Peitsch, Manuel C; Stolovitzky, Gustavo; Meyer, Pablo; Hoeng, Julia

    2015-02-15

    Inferring how humans respond to external cues such as drugs, chemicals, viruses or hormones is an essential question in biomedicine. Very often, however, this question cannot be addressed because it is not possible to perform experiments in humans. A reasonable alternative consists of generating responses in animal models and 'translating' those results to humans. The limitations of such translation, however, are far from clear, and systematic assessments of its actual potential are urgently needed. sbv IMPROVER (systems biology verification for Industrial Methodology for PROcess VErification in Research) was designed as a series of challenges to address translatability between humans and rodents. This collaborative crowd-sourcing initiative invited scientists from around the world to apply their own computational methodologies on a multilayer systems biology dataset composed of phosphoproteomics, transcriptomics and cytokine data derived from normal human and rat bronchial epithelial cells exposed in parallel to 52 different stimuli under identical conditions. Our aim was to understand the limits of species-to-species translatability at different levels of biological organization: signaling, transcriptional and release of secreted factors (such as cytokines). Participating teams submitted 49 different solutions across the sub-challenges, two-thirds of which were statistically significantly better than random. Additionally, similar computational methods were found to range widely in their performance within the same challenge, and no single method emerged as a clear winner across all sub-challenges. Finally, computational methods were able to effectively translate some specific stimuli and biological processes in the lung epithelial system, such as DNA synthesis, cytoskeleton and extracellular matrix, translation, immune/inflammation and growth factor/proliferation pathways, better than the expected response similarity between species. pmeyerr@us.ibm.com or Julia

  14. Challenges for Cloud Modeling in the Context of Aerosol–Cloud–Precipitation Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Lebo, Zachary J. [Department of Atmospheric Science, University of Wyoming, Laramie, Wyoming; Shipway, Ben J. [Met Office, Exeter, United Kingdom; Fan, Jiwen [Pacific Northwest National Laboratory, Richland, Washington; Geresdi, Istvan [Faculty of Science, University of Pécs, Pécs, Hungary; Hill, Adrian [Met Office, Exeter, United Kingdom; Miltenberger, Annette [School of Earth and Environment, University of Leeds, Leeds, United Kingdom; Morrison, Hugh [Mesoscale and Microscale Meteorology Laboratory, National Center for Atmospheric Research, Boulder, Colorado; Rosenberg, Phil [School of Earth and Environment, University of Leeds, Leeds, United Kingdom; Varble, Adam [Department of Atmospheric Sciences, University of Utah, Salt Lake City, Utah; Xue, Lulin [Research Applications Laboratory, National Center for Atmospheric Research, Boulder, Colorado

    2017-08-01

    The International Cloud Modeling Workshop (CMW) has been a longstanding tradition in the cloud microphysics modeling community and is typically held the week prior to the International Conference on Clouds and Precipitation (ICCP). For the Ninth CMW, more than 40 participants from 10 countries convened at the Met Office in Exeter, United Kingdom. The workshop included 4 detailed case studies (described in more detail below) rooted in recent field campaigns. The overarching objective of these cases was to utilize new observations to better understand inter-model differences and model deficiencies, explore new modeling techniques, and gain physical insight into the behavior of clouds. As was the case at the Eighth CMW, there was a general theme of understanding the role of aerosol impacts in the context of cloud-precipitation interactions. However, an additional objective was the focal point of several cases at the most recent workshop: microphysical-dynamical interactions. Many of the cases focused less on idealized small-domain simulations (as was the general focus of previous workshops) and more on large-scale nested configurations examining effects at various scales.

  15. Experimental models in predicting topical antifungal efficacy: practical aspects and challenges.

    Science.gov (United States)

    Lai, J; Maibach, H I

    2009-01-01

    What are efficient screening models for improved topical antifungals? The use of minimum inhibitory concentrations (MICs) as one such parameter is discussed; we focus on the use of animal membranes for in vitro testing while highlighting the pros and cons of each model, exploring alternatives and discussing the importance of data transferability to humans and the influence of penetration kinetics in topical antifungal efficacy. Ultimately, the gold standard of testing is in vivo in humans; however, initiating with human testing, especially for novel topical antifungal agents, may be impractical, which is why we seek the ideal experimental model that most closely mimics human skin. We conclude that the pig may be an appropriate model membrane for topical antifungal testing based on its similarities in anatomical structure, physiology and permeation to human skin. Most importantly, pig and human skins appear equally permeable to several antifungals in prior in vitro and in vivo work. We do not discuss all prior work but highlight important issues in designing the protocol and parameters of the ideal experimental model for topical antifungals. Copyright 2009 S. Karger AG, Basel.

  16. Scale effect challenges in urban hydrology highlighted with a Fully Distributed Model and High-resolution rainfall data

    Science.gov (United States)

    Ichiba, Abdellah; Gires, Auguste; Tchiguirinskaia, Ioulia; Schertzer, Daniel; Bompard, Philippe; Ten Veldhuis, Marie-Claire

    2017-04-01

    Nowadays, there is a growing interest on small-scale rainfall information, provided by weather radars, to be used in urban water management and decision-making. Therefore, an increasing interest is in parallel devoted to the development of fully distributed and grid-based models following the increase of computation capabilities, the availability of high-resolution GIS information needed for such models implementation. However, the choice of an appropriate implementation scale to integrate the catchment heterogeneity and the whole measured rainfall variability provided by High-resolution radar technologies still issues. This work proposes a two steps investigation of scale effects in urban hydrology and its effects on modeling works. In the first step fractal tools are used to highlight the scale dependency observed within distributed data used to describe the catchment heterogeneity, both the structure of the sewer network and the distribution of impervious areas are analyzed. Then an intensive multi-scale modeling work is carried out to understand scaling effects on hydrological model performance. Investigations were conducted using a fully distributed and physically based model, Multi-Hydro, developed at Ecole des Ponts ParisTech. The model was implemented at 17 spatial resolutions ranging from 100 m to 5 m and modeling investigations were performed using both rain gauge rainfall information as well as high resolution X band radar data in order to assess the sensitivity of the model to small scale rainfall variability. Results coming out from this work demonstrate scale effect challenges in urban hydrology modeling. In fact, fractal concept highlights the scale dependency observed within distributed data used to implement hydrological models. Patterns of geophysical data change when we change the observation pixel size. The multi-scale modeling investigation performed with Multi-Hydro model at 17 spatial resolutions confirms scaling effect on hydrological model

  17. Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model.

    Science.gov (United States)

    Ermler, Megan E; Kirkpatrick, Ericka; Sun, Weina; Hai, Rong; Amanat, Fatima; Chromikova, Veronika; Palese, Peter; Krammer, Florian

    2017-06-15

    Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed. Copyright © 2017 American Society for Microbiology.

  18. Cardiovascular performance with E. coli challenges in a canine model of human sepsis

    International Nuclear Information System (INIS)

    Natanson, C.; Danner, R.L.; Fink, M.P.; MacVittie, T.J.; Walker, R.I.; Conklin, J.J.; Parrillo, J.E.

    1988-01-01

    The authors investigated cardiovascular dysfunction by injecting lethal and nonlethal bacterial challenges into conscious dogs. E coli bacteria of varying numbers were placed in a peritoneal clot. Cardiovascular function was studied with simultaneous radionuclide scans and thermodilution cardiac outputs. In surviving animals, the number of bacteria in the clot increased as the corresponding systolic cardiac function decreased. Cardiac function was measured by left ventricular (LV) ejection fraction (EF) and LV function curves. Furthermore, the diastolic volume-pressure relationship of survivors shifted progressively to the right. This increase in LV size was associated with maintenance of measures of cardiac performance at similar levels. Death occurred only in the group with the highest bacterial dose. Compared with survivors receiving the same number of bacterial, nonsurvivors had a decrease in LV size, a leftward shift in LV diastolic volume-pressure relationship, and a decrease in both LVSWI and SVI. Data from survivors suggest that increasing the number of bacteria produces changes in myocardial compliance and contractility. These changes increase LV size (preload), a major determinant of cardiac performance that possibility enhances survival

  19. Computational Modeling of Cobalt-based Water Oxidation: Current Status and Future Challenges

    Science.gov (United States)

    Schilling, Mauro; Luber, Sandra

    2018-04-01

    A lot of effort is nowadays put into the development of novel water oxidation catalysts. In this context mechanistic studies are crucial in order to elucidate the reaction mechanisms governing this complex process, new design paradigms and strategies how to improve the stability and efficiency of those catalysis. This review is focused on recent theoretical mechanistic studies in the field of homogeneous cobalt-based water oxidation catalysts. In the first part, computational methodologies and protocols are summarized and evaluated on the basis of their applicability towards real catalytic or smaller model systems, whereby special emphasis is laid on the choice of an appropriate model system. In the second part, an overview of mechanistic studies is presented, from which conceptual guidelines are drawn on how to approach novel studies of catalysts and how to further develop the field of computational modeling of water oxidation reactions.

  20. Computational Modeling of Cobalt-Based Water Oxidation: Current Status and Future Challenges

    Directory of Open Access Journals (Sweden)

    Mauro Schilling

    2018-04-01

    Full Text Available A lot of effort is nowadays put into the development of novel water oxidation catalysts. In this context, mechanistic studies are crucial in order to elucidate the reaction mechanisms governing this complex process, new design paradigms and strategies how to improve the stability and efficiency of those catalysts. This review is focused on recent theoretical mechanistic studies in the field of homogeneous cobalt-based water oxidation catalysts. In the first part, computational methodologies and protocols are summarized and evaluated on the basis of their applicability toward real catalytic or smaller model systems, whereby special emphasis is laid on the choice of an appropriate model system. In the second part, an overview of mechanistic studies is presented, from which conceptual guidelines are drawn on how to approach novel studies of catalysts and how to further develop the field of computational modeling of water oxidation reactions.

  1. Spectroscopic Challenges in the Modelling and Diagnostics of High Temperature Air Plasma Radiation for Aerospace Applications

    International Nuclear Information System (INIS)

    Laux, Christophe O.

    2007-01-01

    State-of-the-art spectroscopic models of the radiative transitions of interest for Earth re-entry and ground-based diagnostic facilities for aerospace applications are reviewed. The spectral range considered extends from the vacuum ultraviolet to the mid-infrared range (80 nm to 5.5 μm). The modeling results are compared with absolute intensity measurements of the ultraviolet-visible-infrared emission of a well-characterized high-temperature air plasma produced with a 50 kW inductively coupled radio-frequency plasma torch, and with high-resolution absorption spectra from the Center for Astrophysics in the vacuum ultraviolet. The Spectroscopic data required to better model the spectral features of interest for aerospace applications are discussed

  2. Challenges in modelling isoprene and monoterpene emission dynamics of Arctic plants

    DEFF Research Database (Denmark)

    Tang, Jing; Schurgers, Guy; Valolahti, Hanna Maritta

    2016-01-01

    test. The model showed reasonable agreement to the observed vegetation CO2 fluxes in the main growing season as well as day-to-day variability of isoprene and monoterpene emissions. The observed relatively high WRs were better captured by the adjusted T response curve than by the common one. During...... 1999-2012, the modelled annual mean isoprene and monoterpene emissions were 20 and 8 mg C mg-2 yrg-1, with an increase by 55 and 57 % for 2 °C summertime warming, respectively. Warming by 4 and 8 °C for the same period further elevated isoprene emission for all years, but the impacts on monoterpene...

  3. The difficult challenge of a two-phase CFD modelling for all flow regimes

    International Nuclear Information System (INIS)

    Bestion, D.

    2014-01-01

    Highlights: • The theoretical difficulties for modelling all flow regimes at CFD scale are identified. • The choice of the number of fields and of the time and space averaging or filtering are discussed and clarified. • Closure issues related to an all flow regime CFD model are listed and the main difficulties are identified. - Abstract: System thermalhydraulic codes model all two-phase flow regimes but they are limited to a macroscopic description. Two-phase CFD tools predict two-phase flow with a much finer space resolution but the current modelling capabilities are limited to dispersed bubbly or droplet flow and separate-phase flow. Much less experience exists on more complex flow regimes which combine the existence of dispersed fields with the presence of large interfaces such as a free surface or a film surface. A list of possible reactor issues which might benefit from an “all flow regime CFD model” is given. The first difficulty is to identify the various types of local flow configuration. It is shown that a 4-field model has much better capabilities than a two-fluid approach to identify most complex regimes. Then the choice between time averaging, space averaging, or even ensemble averaging is discussed. It is shown that only the RANS-2-fluid and a space-filtered 4-field model may be reasonably envisaged. The latter has the capabilities to identify all types of interfaces and should be privileged if a good accuracy is expected or if time fluctuations in intermittent flow have to be predicted while the former may be used when a high accuracy is not necessary and if time fluctuations in intermittent flow are not of interest. Finally the closure issue is presented including wall transfers, interfacial transfers, mass transfers between dispersed and continuous fields, and turbulent transfers. An important effort is required to model all interactions between sub-filter phenomena and the transfers from the sub-filter domain to the simulated domain. The

  4. In vitro models to evaluate the permeability of poorly soluble drug entities: Challenges and perspectives

    DEFF Research Database (Denmark)

    Buckley, S. T.; Fischer, S. M.; Fricker, G.

    2012-01-01

    The application of in vitro models in drug permeability studies represents a useful screening tool for assessing the biopharmaceutical appropriateness of new chemical entities (NCEs). Of note, there remains an ever-increasing number of NCEs which exhibit poor aqueous solubility. However, in their......The application of in vitro models in drug permeability studies represents a useful screening tool for assessing the biopharmaceutical appropriateness of new chemical entities (NCEs). Of note, there remains an ever-increasing number of NCEs which exhibit poor aqueous solubility. However...

  5. Modelling floods in the Ammer catchment: limitations and challenges with a coupled meteo-hydrological model approach

    Directory of Open Access Journals (Sweden)

    R. Ludwig

    2003-01-01

    Full Text Available Numerous applications of hydrological models have shown their capability to simulate hydrological processes with a reasonable degree of certainty. For flood modelling, the quality of precipitation data — the key input parameter — is very important but often remains questionable. This paper presents a critical review of experience in the EU-funded RAPHAEL project. Different meteorological data sources were evaluated to assess their applicability for flood modelling and forecasting in the Bavarian pre-alpine catchment of the Ammer river (709 km2, for which the hydrological aspects of runoff production are described as well as the complex nature of floods. Apart from conventional rain gauge data, forecasts from several Numerical Weather Prediction Models (NWP as well as rain radar data are examined, scaled and applied within the framework of a GIS-structured and physically based hydrological model. Multi-scenario results are compared and analysed. The synergetic approach leads to promising results under certain meteorological conditions but emphasises various drawbacks. At present, NWPs are the only source of rainfall forecasts (up to 96 hours with large spatial coverage and high temporal resolution. On the other hand, the coarse spatial resolution of NWP grids cannot yet address, adequately, the heterogeneous structures of orographic rainfields in complex convective situations; hence, a major downscaling problem for mountain catchment applications is introduced. As shown for two selected Ammer flood events, a high variability in prediction accuracy has still to be accepted at present. Sensitivity analysis of both meteo-data input and hydrological model performance in terms of process description are discussed and positive conclusions have been drawn for future applications of an advanced meteo-hydro model synergy. Keywords: RAPHAEL, modelling, forecasting, model coupling, PROMET-D, TOPMODEL

  6. D Modelling and Visualization Based on the Unity Game Engine - Advantages and Challenges

    Science.gov (United States)

    Buyuksalih, I.; Bayburt, S.; Buyuksalih, G.; Baskaraca, A. P.; Karim, H.; Rahman, A. A.

    2017-11-01

    3D City modelling is increasingly popular and becoming valuable tools in managing big cities. Urban and energy planning, landscape, noise-sewage modelling, underground mapping and navigation are among the applications/fields which really depend on 3D modelling for their effectiveness operations. Several research areas and implementation projects had been carried out to provide the most reliable 3D data format for sharing and functionalities as well as visualization platform and analysis. For instance, BIMTAS company has recently completed a project to estimate potential solar energy on 3D buildings for the whole Istanbul and now focussing on 3D utility underground mapping for a pilot case study. The research and implementation standard on 3D City Model domain (3D data sharing and visualization schema) is based on CityGML schema version 2.0. However, there are some limitations and issues in implementation phase for large dataset. Most of the limitations were due to the visualization, database integration and analysis platform (Unity3D game engine) as highlighted in this paper.

  7. Adapting a regularized canopy reflectance model (REGFLEC) for the retrieval challenges of dryland agricultural systems

    KAUST Repository

    Houborg, Rasmus; McCabe, Matthew

    2016-01-01

    estimates in the model inversion. Using multi-spectral RapidEye imagery allowed Chll to be retrieved with a Mean Absolute Deviation (MAD) of 7.9 μg cm− 2 (16%), based upon in-situ measurements conducted in fields of alfalfa, Rhodes grass and maize over

  8. From Point Cloud to Bim: a Modelling Challenge in the Cultural Heritage Field

    Science.gov (United States)

    Tommasi, C.; Achille, C.; Fassi, F.

    2016-06-01

    Speaking about modelling the Cultural Heritage, nowadays it is no longer enough to build the mute model of a monument, but it has to contain plenty of information inside it, especially when we refer to existing construction. For this reason, the aim of the research is to insert an historical building inside a BIM process, proposing in this way a working method that can build a reality based model and preserve the unicity of the elements. The question is: "What is the more useful mean in term of survey data management, level of detail, information and time savings?" To test the potentialities and the limits of this process we employed the most used software in the international market, taking as example some composed elements, made by regular and complex, but also modular parts. Once a final model is obtained, it is necessary to provide a test phase on the interoperability between the used software modules, in order to give a general picture of the state of art and to contribute to further studies on this subject.

  9. National Models for Continuing Professional Development: The Challenges of Twenty-First-Century Knowledge Management

    Science.gov (United States)

    Leask, Marilyn; Younie, Sarah

    2013-01-01

    If teacher quality is the most critical factor in improving educational outcomes, then why is so little attention drawn to the knowledge and evidence base available to support teachers in improving the quality of their professional knowledge? This paper draws together findings from a range of sources to propose national models for continuing…

  10. The autism puzzle : Challenging a mechanistic model on conceptual and historical grounds

    NARCIS (Netherlands)

    Verhoeff, Berend

    2013-01-01

    Although clinicians and researchers working in the field of autism are generally not concerned with philosophical categories of kinds, a model for understanding the nature of autism is important for guiding research and clinical practice. Contemporary research in the field of autism is guided by the

  11. Future challenges for clinical care of an ageing population infected with HIV: a modelling study

    NARCIS (Netherlands)

    Smit, Mikaela; Brinkman, Kees; Geerlings, Suzanne; Smit, Colette; Thyagarajan, Kalyani; Sighem, Ard van; de Wolf, Frank; Hallett, Timothy B.

    2015-01-01

    The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. We constructed an individual-based model of the

  12. Challenges and priorities for modelling livestock health and pathogens in the context of climate change

    NARCIS (Netherlands)

    Özkan, Şeyda; Vitali, Andrea; Lacetera, Nicola; Amon, Barbara; Bannink, André; Bartley, Dave J.; Blanco-penedo, Isabel; Haas, De Yvette; Dufrasne, Isabelle; Elliott, John; Eory, Vera; Fox, Naomi J.; Garnsworthy, Phil C.; Gengler, Nicolas; Hammami, Hedi; Kyriazakis, Ilias; Leclère, David; Lessire, Françoise; Macleod, Michael; Robinson, Timothy P.; Ruete, Alejandro; Sandars, Daniel L.; Shrestha, Shailesh; Stott, Alistair W.; Twardy, Stanislaw; Vanrobays, Marie-Laure; Ahmadi, Bouda Vosough; Weindl, Isabelle; Wheelhouse, Nick; Williams, Adrian G.; Williams, Hefin W.; Wilson, Anthony J.; Østergaard, Søren; Kipling, Richard P.

    2016-01-01

    Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential

  13. From the Protein's Perspective: The Benefits and Challenges of Protein Structure-Based Pharmacophore Modeling

    NARCIS (Netherlands)

    Sanders, M.P.A.; McGuire, R; Roumen, L.; de Esch, I.J.P.; de Vlieg, J; Klomp, J.P.G; de Graaf, C.

    2011-01-01

    A pharmacophore describes the arrangement of molecular features a ligand must contain to efficaciously bind a receptor. Pharmacophore models are developed to improve molecular understanding of ligand-protein interactions, and can be used as a tool to identify novel compounds that fulfil the

  14. New challenges in municipal broadband network management : from vertical integration to wholesale-retail model

    NARCIS (Netherlands)

    Sadowski, B.M.; Nucciarelli, A.

    2008-01-01

    Over the past years, municipal networks deploying Fiber-to-the-Home (FttH) technologies have increasingly been implemented in Europe. In order to achieve compatibility with the European Union (EU) legal and regulatory framework, a variety of public and private partnership (PPP) models have been

  15. Predictive models for the assessment of occupational exposure to chemicals: A new challenge for employers

    Directory of Open Access Journals (Sweden)

    Jan Piotr Gromiec

    2013-10-01

    Full Text Available Employers are obliged to carry out and document the risk associated with the use of chemical substances. The best but the most expensive method is to measure workplace concentrations of chemicals. At present no "measureless" method for risk assessment is available in Poland, but predictive models for such assessments have been developed in some countries. The purpose of this work is to review and evaluate the applicability of selected predictive methods for assessing occupational inhalation exposure and related risk to check the compliance with Occupational Exposure Limits (OELs, as well as the compliance with REACH obligations. Based on the literature data HSE COSHH Essentials, EASE, ECETOC TRA, Stoffenmanager, and EMKG-Expo-Tool were evaluated. The data on validation of predictive models were also examined. It seems that predictive models may be used as a useful method for Tier 1 assessment of occupational exposure by inhalation. Since the levels of exposure are frequently overestimated, they should be considered as "rational worst cases" for selection of proper control measures. Bearing in mind that the number of available exposure scenarios and PROC categories is limited, further validation by field surveys is highly recommended. Predictive models may serve as a good tool for preliminary risk assessment and selection of the most appropriate risk control measures in Polish small and medium size enterprises (SMEs providing that they are available in the Polish language. This also requires an extensive training of their future users. Med Pr 2013;64(5:699–716

  16. 3D MODELLING AND VISUALIZATION BASED ON THE UNITY GAME ENGINE – ADVANTAGES AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    I. Buyuksalih

    2017-11-01

    Full Text Available 3D City modelling is increasingly popular and becoming valuable tools in managing big cities. Urban and energy planning, landscape, noise-sewage modelling, underground mapping and navigation are among the applications/fields which really depend on 3D modelling for their effectiveness operations. Several research areas and implementation projects had been carried out to provide the most reliable 3D data format for sharing and functionalities as well as visualization platform and analysis. For instance, BIMTAS company has recently completed a project to estimate potential solar energy on 3D buildings for the whole Istanbul and now focussing on 3D utility underground mapping for a pilot case study. The research and implementation standard on 3D City Model domain (3D data sharing and visualization schema is based on CityGML schema version 2.0. However, there are some limitations and issues in implementation phase for large dataset. Most of the limitations were due to the visualization, database integration and analysis platform (Unity3D game engine as highlighted in this paper.

  17. Addressing challenges in obtaining high coverage when model checking android applications

    CSIR Research Space (South Africa)

    Botha, Heila-Marie

    2017-07-01

    Full Text Available -state-comparator and can be excluded from the state using JPF’s @FilterField annotation or other con€guration options discussed in [5]. JPF-Android further optimizes state-matching by pre-loading all application classes and application speci€c models. It also rede...

  18. Challenges of Analysing Gene-Environment Interactions in Mouse Models of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Peter L. Oliver

    2011-01-01

    Full Text Available The modelling of neuropsychiatric disease using the mouse has provided a wealth of information regarding the relationship between specific genetic lesions and behavioural endophenotypes. However, it is becoming increasingly apparent that synergy between genetic and nongenetic factors is a key feature of these disorders that must also be taken into account. With the inherent limitations of retrospective human studies, experiments in mice have begun to tackle this complex association, combining well-established behavioural paradigms and quantitative neuropathology with a range of environmental insults. The conclusions from this work have been varied, due in part to a lack of standardised methodology, although most have illustrated that phenotypes related to disorders such as schizophrenia are consistently modified. Far fewer studies, however, have attempted to generate a “two-hit” model, whereby the consequences of a pathogenic mutation are analysed in combination with environmental manipulation such as prenatal stress. This significant, yet relatively new, approach is beginning to produce valuable new models of neuropsychiatric disease. Focussing on prenatal and perinatal stress models of schizophrenia, this review discusses the current progress in this field, and highlights important issues regarding the interpretation and comparative analysis of such complex behavioural data.

  19. Digital Dividend Aware Business Models for the Creative Industries: Challenges and Opportunities in EU Markets

    Science.gov (United States)

    Cossiavelou, Vassiliki

    EU counties have a historically unique opportunity to enable their creative industries to promote the knowledge societies, applying new business models to their media content and networks markets, that are digital dividend (DD) aware. This new extra-media gatekeeping factor could shape new alliances and co operations among the member states and the global media markets, as well.

  20. A Model for Considering the Financial Sustainability of Learning and Teaching Programs: Concepts and Challenges

    Science.gov (United States)

    De Bellis, David

    2012-01-01

    The expansion of tertiary education, an intensity of focus on accountability and performance, and the emergence of new governance and management structures drives an economic fiscal perspective of the value of learning and teaching. Accurate and meaningful models defining financial sustainability are therefore proposed as an imperative for…

  1. Manufacturing models permitting roll out/scale out of clinically led autologous cell therapies: regulatory and scientific challenges for comparability.

    Science.gov (United States)

    Hourd, Paul; Ginty, Patrick; Chandra, Amit; Williams, David J

    2014-08-01

    Manufacturing of more-than-minimally manipulated autologous cell therapies presents a number of unique challenges driven by complex supply logistics and the need to scale out production to multiple manufacturing sites or near the patient within hospital settings. The existing regulatory structure in Europe and the United States imposes a requirement to establish and maintain comparability between sites. Under a single market authorization, this is likely to become an unsurmountable burden beyond two or three sites. Unless alternative manufacturing approaches can be found to bridge the regulatory challenge of comparability, realizing a sustainable and investable business model for affordable autologous cell therapy supply is likely to be extremely demanding. Without a proactive approach by the regulators to close this "translational gap," these products may not progress down the development pipeline, threatening patient accessibility to an increasing number of clinician-led autologous cellular therapies that are already demonstrating patient benefits. We propose three prospective manufacturing models for the scale out/roll out of more-than-minimally manipulated clinically led autologous cell therapy products and test their prospects for addressing the challenge of product comparability with a selected expert reference panel of US and UK thought leaders. This paper presents the perspectives and insights of the panel and identifies where operational, technological and scientific improvements should be prioritized. The main purpose of this report is to solicit feedback and seek input from key stakeholders active in the field of autologous cell therapy in establishing a consensus-based manufacturing approach that may permit the roll out of clinically led autologous cell therapies. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  2. Implementation of the zooplankton functional response in plankton models: State of the art, recent challenges and future directions

    Science.gov (United States)

    Morozov, Andrew; Poggiale, Jean-Christophe; Cordoleani, Flora

    2012-09-01

    The conventional way of describing grazing in plankton models is based on a zooplankton functional response framework, according to which the consumption rate is computed as the product of a certain function of food (the functional response) and the density/biomass of herbivorous zooplankton. A large amount of literature on experimental feeding reports the existence of a zooplankton functional response in microcosms and small mesocosms, which goes a long way towards explaining the popularity of this framework both in mean-field (e.g. NPZD models) and spatially resolved models. On the other hand, the complex foraging behaviour of zooplankton (feeding cycles) as well as spatial heterogeneity of food and grazer distributions (plankton patchiness) across time and space scales raise questions as to the existence of a functional response of herbivores in vivo. In the current review, we discuss limitations of the ‘classical’ zooplankton functional response and consider possible ways to amend this framework to cope with the complexity of real planktonic ecosystems. Our general conclusion is that although the functional response of herbivores often does not exist in real ecosystems (especially in the form observed in the laboratory), this framework can be rather useful in modelling - but it does need some amendment which can be made based on various techniques of model reduction. We also show that the shape of the functional response depends on the spatial resolution (‘frame’) of the model. We argue that incorporating foraging behaviour and spatial heterogeneity in plankton models would not necessarily require the use of individual based modelling - an approach which is now becoming dominant in the literature. Finally, we list concrete future directions and challenges and emphasize the importance of a closer collaboration between plankton biologists and modellers in order to make further progress towards better descriptions of zooplankton grazing.

  3. REGIONAL DEVELOPMENT THEORIES AND MODELS, A COMPARATIVE ANALYSE.CHALLENGE OF REGIONAL DEVELOPMENT IN ALBANIA

    Directory of Open Access Journals (Sweden)

    Eva\tDHIMITRI

    2015-12-01

    Full Text Available Local governance is a broad concept and is defined as the formulation and execution of collective action at the local level. The purpose of local government is to ensure effective and efficient use of public resources and service delivery at the level closest to citizens. Regional development is a new concept that aims to stimulate and diversify the economic activity of a country (region, to encourage investment in the private sector, to create a new jobs vacancy and improves living standards of the country. Regional development policies are a number of measures designed and promoted by the central and local administration, but the cooperation undertaken at the actors are in a different one, which included the private sector and civil society. At the center of these regional policies or practices is the use of efficient potential of each region, being particularly focused on business, means promoting the development of the new enterprises, promoting labor market and investment, improve the quality of environment, health , education and culture. Traditional objective of regional development policies is the reduction of territorial disparities for achieving a relative balance between economic and social levels of development in different areas in the national territory. Regional development is the actual task of local government units in Albania, and is one of the tasks and challenges of the future. Currently it takes a special importance in the context of European Union integration. Reforms have begun to change the system in 1990 in order to implement local democracy and decentralization principles that are present today. Inequalities that exist within the region and between them indicate that in some regions the economic potential is not being fully utilized, and that it reduces the overall performance in national level.

  4. Methodological challenges of optical tweezers-based X-ray fluorescence imaging of biological model organisms at synchrotron facilities.

    Science.gov (United States)

    Vergucht, Eva; Brans, Toon; Beunis, Filip; Garrevoet, Jan; Bauters, Stephen; De Rijcke, Maarten; Deruytter, David; Janssen, Colin; Riekel, Christian; Burghammer, Manfred; Vincze, Laszlo

    2015-07-01

    Recently, a radically new synchrotron radiation-based elemental imaging approach for the analysis of biological model organisms and single cells in their natural in vivo state was introduced. The methodology combines optical tweezers (OT) technology for non-contact laser-based sample manipulation with synchrotron radiation confocal X-ray fluorescence (XRF) microimaging for the first time at ESRF-ID13. The optical manipulation possibilities and limitations of biological model organisms, the OT setup developments for XRF imaging and the confocal XRF-related challenges are reported. In general, the applicability of the OT-based setup is extended with the aim of introducing the OT XRF methodology in all research fields where highly sensitive in vivo multi-elemental analysis is of relevance at the (sub)micrometre spatial resolution level.

  5. Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description.

    Science.gov (United States)

    Spyrakis, Francesca; Cavasotto, Claudio N

    2015-10-01

    Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    Science.gov (United States)

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  7. Education for sustainability: A new challenge for the current university model

    Directory of Open Access Journals (Sweden)

    Ana Fernández Pérez

    2018-01-01

    Full Text Available Education for Sustainable Development aims to disseminate and promote a set of principles and values within the university model through management, teaching, research and university extension. It does not focus on a specific area but covers many areas such as equality, peace, health, sustainable urbanization, the environment. The objective of this study is to make an appeal in all these areas so that universities incorporate the dimension of sustainability in their curricula, through teaching, research and university management. For this, the different international and regional initiatives that have emphasized the need for Universities to be committed to the culture of sustainability and their inclusion in the current university model have been analyzed. The work will conclude with the idea that a sustainable development is perhaps one of the key pieces in the conception of the University of the 21st century.

  8. Integrated ecological-economic fisheries models - evaluation, review and challenges for implementation

    DEFF Research Database (Denmark)

    Nielsen, J. Rasmus; Thunberg, Eric; Holland, Daniel S.

    2018-01-01

    and comparative evaluation of 35 IESFM´s applied to marine fisheries and marine ecosystem resources to identify the characteristics that determine their usefulness, effectiveness and implementation. The focus is on fully integrated models that allow for feedbacks between ecological and human processes though......Marine ecosystems evolve under many interconnected and area-specific pressures. In order to fulfill society's intensifying and diversifying needs whilst ensuring ecologically sustainable development, more effective marine spatial planning and broader-scope management of marine resources...... is necessary. Integrated ecological–socioeconomic fisheries models (IESFM) of marine systems are nee¬ded to evaluate impacts and sustainability of potential management actions and understand, and anti¬ci¬pate ecological, economic, and social dynamics at a range of scales from local to national and regional...

  9. New expected loss impairment model – a challenge for the banks in Bulgaria

    Directory of Open Access Journals (Sweden)

    Nadezhda Popova-Yosifova

    2017-05-01

    Full Text Available This article introduces some of the leading works on loan impairment published by supervisory authorities, auditing companies and researchers. It makes analysis of the impairment model on the basis of the expected credit losses introduced with the requirements of International Financial Reporting Standard (IFRS 9 Financial Instruments effective for periods beginning on or after 1 January 2018. There are a number of research works which show that the senior bankers may in some ways manage the financial result through the impairment, where it is assumed that the new impairment model will bring higher recognized losses. It also makes a comparative analysis of the announced information on the loan impairment and the preparation for the introduction of the IFRS 9 Financial Instruments requirements into the annual financial statements of the public banks in Bulgaria for the period 2013 – 2016.

  10. Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas

    OpenAIRE

    de Polo, A; Scrimshaw, MD

    2012-01-01

    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 SETAC. An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by ...

  11. Transfer and Multi-task Learning in QSAR Modeling: Advances and Challenges

    OpenAIRE

    Rodolfo S. Simões; Vinicius G. Maltarollo; Patricia R. Oliveira; Kathia M. Honorio; Kathia M. Honorio

    2018-01-01

    Medicinal chemistry projects involve some steps aiming to develop a new drug, such as the analysis of biological targets related to a given disease, the discovery and the development of drug candidates for these targets, performing parallel biological tests to validate the drug effectiveness and side effects. Approaches as quantitative study of activity-structure relationships (QSAR) involve the construction of predictive models that relate a set of descriptors of a chemical compound series a...

  12. hiPSC Disease Modeling of Rare Hereditary Cerebellar Ataxias: Opportunities and Future Challenges

    Czech Academy of Sciences Publication Activity Database

    Lukovic, D.; Moreno-Manzano, V.; Rodriquez; Jimenez, F.J.; Vilches, A.; Syková, Eva; Jendelová, Pavla; Stojkovic, M.; Erceg, Slaven

    2017-01-01

    Roč. 23, č. 5 (2017), s. 554-566 ISSN 1073-8584 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LO1309; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : 3D organoids * ataxia * disease modelling Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 7.391, year: 2016

  13. Challenges in Computational Social Modeling and Simulation for National Security Decision Making

    Science.gov (United States)

    2011-06-01

    34 Sociological Theory 25:268-291. Mead , George Herbert . 1913. "The social self." Journal of Philosophy, Psychology and Scientific Methods 10:374-380...Coastal Science and Policy, and University Distinguished Research Professor in the Department of Sociology with adjunct appointments in Biology...Hopkins Applied Physics Laboratory and formerly of the U.S. Defense Modeling and Simulation Office (DMSO) to discuss the history and importance of

  14. Integrated Payment and Delivery Models Offer Opportunities and Challenges for Residential Care Facilities

    OpenAIRE

    Grabowski, David C.; Caudry, Daryl J.; Dean, Katie M.; Stevenson, David G.

    2015-01-01

    Under health care reform, a series of new financing and delivery models are being piloted to integrate health and long-term care services for older adults. To date, these programs have not encompassed residential care facilities, with most programs focusing on long-term care recipients in the community or the nursing home. Our analyses indicate that individuals living in residential care facilities have similarly high rates of chronic illness and Medicare utilization when compared with simila...

  15. Challenges in integrative approaches to modelling the marine ecosystems of the North Atlantic: Physics to fish and coasts to ocean

    Science.gov (United States)

    Holt, Jason; Icarus Allen, J.; Anderson, Thomas R.; Brewin, Robert; Butenschön, Momme; Harle, James; Huse, Geir; Lehodey, Patrick; Lindemann, Christian; Memery, Laurent; Salihoglu, Baris; Senina, Inna; Yool, Andrew

    2014-12-01

    It has long been recognised that there are strong interactions and feedbacks between climate, upper ocean biogeochemistry and marine food webs, and also that food web structure and phytoplankton community distribution are important determinants of variability in carbon production and export from the euphotic zone. Numerical models provide a vital tool to explore these interactions, given their capability to investigate multiple connected components of the system and the sensitivity to multiple drivers, including potential future conditions. A major driver for ecosystem model development is the demand for quantitative tools to support ecosystem-based management initiatives. The purpose of this paper is to review approaches to the modelling of marine ecosystems with a focus on the North Atlantic Ocean and its adjacent shelf seas, and to highlight the challenges they face and suggest ways forward. We consider the state of the art in simulating oceans and shelf sea physics, planktonic and higher trophic level ecosystems, and look towards building an integrative approach with these existing tools. We note how the different approaches have evolved historically and that many of the previous obstacles to harmonisation may no longer be present. We illustrate this with examples from the on-going and planned modelling effort in the Integrative Modelling Work Package of the EURO-BASIN programme.

  16. Overcoming Challenges in Kinetic Modeling of Magnetized Plasmas and Vacuum Electronic Devices

    Science.gov (United States)

    Omelchenko, Yuri; Na, Dong-Yeop; Teixeira, Fernando

    2017-10-01

    We transform the state-of-the art of plasma modeling by taking advantage of novel computational techniques for fast and robust integration of multiscale hybrid (full particle ions, fluid electrons, no displacement current) and full-PIC models. These models are implemented in 3D HYPERS and axisymmetric full-PIC CONPIC codes. HYPERS is a massively parallel, asynchronous code. The HYPERS solver does not step fields and particles synchronously in time but instead executes local variable updates (events) at their self-adaptive rates while preserving fundamental conservation laws. The charge-conserving CONPIC code has a matrix-free explicit finite-element (FE) solver based on a sparse-approximate inverse (SPAI) algorithm. This explicit solver approximates the inverse FE system matrix (``mass'' matrix) using successive sparsity pattern orders of the original matrix. It does not reduce the set of Maxwell's equations to a vector-wave (curl-curl) equation of second order but instead utilizes the standard coupled first-order Maxwell's system. We discuss the ability of our codes to accurately and efficiently account for multiscale physical phenomena in 3D magnetized space and laboratory plasmas and axisymmetric vacuum electronic devices.

  17. Moving Beyond Misconceptions: A New Model for Learning Challenges in Cognition

    Science.gov (United States)

    Slater, T. F.; Slater, S. J.

    2011-12-01

    For over 40 years, the science education community has given its attention to cataloging the substantial body of "misconceptions" in individual's thinking about science, and to addressing the consequences of those misconceptions in the science classroom. Despite the tremendous amount of effort given to researching and disseminating information related to misconceptions, and the development of a theory of conceptual change to mitigate misconceptions, progress continues to be less than satisfying. An analysis of the literature and our own research has persuaded the CAPER Center for Astronomy and Physics Education Research to put forth model that will allow us to operate on students' learning difficulties in a more fruitful manner. Previously, much of the field's work binned erroneous student thinking into a single construct, and from that basis, curriculum developers and instructors addressed student misconceptions with a single instructional strategy. In contrast this model suggests that "misconceptions" are a mixture of at least four learning barriers: incorrect factual information, inappropriately applied mental algorithms (phenomenological primitives), insufficient cognitive structures (e.g. spatial reasoning), and affective/emotional difficulties. Each of these types of barriers should be addressed with an appropriately designed instructional strategy. Initial applications of this model to learning problems in the Earth & Space Sciences have been fruitful, suggesting that an effort towards categorizing persistent learning difficulties in the geosciences beyond the level of "misconceptions" may allow our community to craft tailored and more effective learning experiences for our students and the general public.

  18. Transfer and Multi-task Learning in QSAR Modeling: Advances and Challenges

    Directory of Open Access Journals (Sweden)

    Rodolfo S. Simões

    2018-02-01

    Full Text Available Medicinal chemistry projects involve some steps aiming to develop a new drug, such as the analysis of biological targets related to a given disease, the discovery and the development of drug candidates for these targets, performing parallel biological tests to validate the drug effectiveness and side effects. Approaches as quantitative study of activity-structure relationships (QSAR involve the construction of predictive models that relate a set of descriptors of a chemical compound series and its biological activities with respect to one or more targets in the human body. Datasets used to perform QSAR analyses are generally characterized by a small number of samples and this makes them more complex to build accurate predictive models. In this context, transfer and multi-task learning techniques are very suitable since they take information from other QSAR models to the same biological target, reducing efforts and costs for generating new chemical compounds. Therefore, this review will present the main features of transfer and multi-task learning studies, as well as some applications and its potentiality in drug design projects.

  19. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models.

    Science.gov (United States)

    Bøgh, Katrine Lindholm; van Bilsen, Jolanda; Głogowski, Robert; López-Expósito, Iván; Bouchaud, Grégory; Blanchard, Carine; Bodinier, Marie; Smit, Joost; Pieters, Raymond; Bastiaan-Net, Shanna; de Wit, Nicole; Untersmayr, Eva; Adel-Patient, Karine; Knippels, Leon; Epstein, Michelle M; Noti, Mario; Nygaard, Unni Cecilie; Kimber, Ian; Verhoeckx, Kitty; O'Mahony, Liam

    2016-01-01

    Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured.

  20. A review on regional convection-permitting climate modeling: Demonstrations, prospects, and challenges.

    Science.gov (United States)

    Prein, Andreas F; Langhans, Wolfgang; Fosser, Giorgia; Ferrone, Andrew; Ban, Nikolina; Goergen, Klaus; Keller, Michael; Tölle, Merja; Gutjahr, Oliver; Feser, Frauke; Brisson, Erwan; Kollet, Stefan; Schmidli, Juerg; van Lipzig, Nicole P M; Leung, Ruby

    2015-06-01

    Regional climate modeling using convection-permitting models (CPMs; horizontal grid spacing 10 km). CPMs no longer rely on convection parameterization schemes, which had been identified as a major source of errors and uncertainties in LSMs. Moreover, CPMs allow for a more accurate representation of surface and orography fields. The drawback of CPMs is the high demand on computational resources. For this reason, first CPM climate simulations only appeared a decade ago. In this study, we aim to provide a common basis for CPM climate simulations by giving a holistic review of the topic. The most important components in CPMs such as physical parameterizations and dynamical formulations are discussed critically. An overview of weaknesses and an outlook on required future developments is provided. Most importantly, this review presents the consolidated outcome of studies that addressed the added value of CPM climate simulations compared to LSMs. Improvements are evident mostly for climate statistics related to deep convection, mountainous regions, or extreme events. The climate change signals of CPM simulations suggest an increase in flash floods, changes in hail storm characteristics, and reductions in the snowpack over mountains. In conclusion, CPMs are a very promising tool for future climate research. However, coordinated modeling programs are crucially needed to advance parameterizations of unresolved physics and to assess the full potential of CPMs.

  1. Leadership in Force XXI: Is the Army's Current Leadership Model and Leader Development Doctrine Properly Addressing the Challenges Brought About by the Transition to Force XXI

    National Research Council Canada - National Science Library

    Johnson, Carl

    1999-01-01

    .... The purpose of this research paper is to answer the question, Is the Army's current leadership model and leader development doctrine properly addressing the challenges brought about by the transition to Force XXI...

  2. Evaluation of a Salmonella vectored vaccine expressing Mycobacterium avium subsp. paratuberculosis antigens against challenge in a goat model.

    Directory of Open Access Journals (Sweden)

    Syed M Faisal

    Full Text Available Johnes disease (JD, caused by Mycobacterium avium subsp paratuberculosis (MAP, occurs worldwide as chronic granulomatous enteritis of domestic and wild ruminants. To develop a cost effective vaccine, in a previous study we constructed an attenuated Salmonella strain that expressed a fusion product made up of partial fragments of MAP antigens (Ag85A, Ag85B and SOD that imparted protection against challenge in a mouse model. In the current study we evaluated the differential immune response and protective efficacy of the Sal-Ag vaccine against challenge in a goat model as compared to the live attenuated vaccine MAP316F. PBMCs from goats vaccinated with Sal-Ag and challenged with MAP generated significantly lower levels of IFN-γ, following in vitro stimulation with either Antigen-mix or PPD jhonin, than PBMC from MAP316F vaccinated animals. Flow cytometric analysis showed the increase in IFN-γ correlated with a significantly higher level of proliferation of CD4, CD8 and γδT cells and an increased expression of CD25 and CD45R0 in MAP316F vaccinated animals as compared to control animals. Evaluation of a range of cytokines involved in Th1, Th2, Treg, and Th17 immune responses by quantitative PCR showed low levels of expression of Th1 (IFN-γ, IL-2, IL-12 and proinflammatory cytokines (IL-6, IL-8, IL-18, TNF-α in the Sal-Ag immunized group. Significant levels of Th2 and anti-inflammatory cytokines transcripts (IL-4, IL-10, IL-13, TGF-β were expressed but their level was low and with a pattern similar to the control group. Over all, Sal-Ag vaccine imparted partial protection that limited colonization in tissues of some animals upon challenge with wild type MAP but not to the level achieved with MAP316F. In conclusion, the data indicates that Sal-Ag vaccine induced only a low level of protective immunity that failed to limit the colonization of MAP in infected animals. Hence the Sal-Ag vaccine needs further refinement to increase its efficacy.

  3. Challenges in modelling dissolved organic matter dynamics in agricultural soil using DAISY

    DEFF Research Database (Denmark)

    Gjettermann, Birgitte; Styczen, Merete; Hansen, Hans Christian Bruun

    2008-01-01

    pedotransfer functions taking into account the soil content of organic matter, Al and Fe oxides. The turnover of several organic matter pools including one DOM pool are described by first-order kinetics. The DOM module was tested at field scale for three soil treatments applied after cultivating grass....... In the subsoil, the observed concentrations of DOC were steadier and the best simulations were obtained using a high k. The model shows that DOC and DON concentrations are levelled out in the subsoils due to soil buffering. The steady concentration levels were based on the Ceq for each horizon and the kinetic...

  4. bantib-production on the Z resonance: a challenge to the standard model

    International Nuclear Information System (INIS)

    Djouadi, A.; Renard, F.M.; Girardi, G.; Verzegnassi, C.

    1990-04-01

    We study the potentialities for exposing physics beyond the standard model that are offered by accurate measurements of the process Z → bantib in a high luminosity phase at LEP. In particular we propose a strategy by defining observables in such a way that they are separately sensitive to different kinds of New Physics. This approach enables us to show that with 10 7 - 10 8 produced bantib pairs one may either obtain very stringent bounds on the extra neutral gauge bosons sector, or identify it unambiguously. Also, it appears that Z → bantib provides under those circumstances a privileged tool to reveal clean virtual effects of supersymmetry

  5. Fragile X--a challenge to models of the mind and to best clinical practice.

    Science.gov (United States)

    Hay, David A

    2008-06-01

    Cornish et al. (2008, this issue) provide an excellent review of Fragile X a common but very complex cause of intellectual disability. They report on a cohort of such males of normal intelligence quotient (IQ) and socioeconomic status (SES), but who have deficits in selective attention and growing impairment in response inhibition. This paper has theoretical views for our models of the mind and clinical implications for families where Fragile X may never have been considered as a possible cause of some of the problems in male and female family members and possibly as well for other disorders such as attention deficit hyperactivity disorder (ADHD) and autism.

  6. The continuing challenge of understanding and modeling hemodynamic variation in fMRI

    OpenAIRE

    Handwerker, Daniel A.; Gonzalez-Castillo, Javier; D’Esposito, Mark; Bandettini, Peter A.

    2012-01-01

    Interpretation of fMRI data depends on our ability to understand or model the shape of the hemodynamic response (HR) to a neural event. Although the HR has been studied almost since the beginning of fMRI, we are still far from having robust methods to account for the full range of known HR variation in typical fMRI analyses. This paper reviews how the authors and others contributed to our understanding of HR variation. We present an overview of studies that describe HR variation across voxels...

  7. Bridging Numerical and Analytical Models of Transient Travel Time Distributions: Challenges and Opportunities

    Science.gov (United States)

    Danesh Yazdi, M.; Klaus, J.; Condon, L. E.; Maxwell, R. M.

    2017-12-01

    Recent advancements in analytical solutions to quantify water and solute time-variant travel time distributions (TTDs) and the related StorAge Selection (SAS) functions synthesize catchment complexity into a simplified, lumped representation. While these analytical approaches are easy and efficient in application, they require high frequency hydrochemical data for parameter estimation. Alternatively, integrated hydrologic models coupled to Lagrangian particle-tracking approaches can directly simulate age under different catchment geometries and complexity at a greater computational expense. Here, we compare and contrast the two approaches by exploring the influence of the spatial distribution of subsurface heterogeneity, interactions between distinct flow domains, diversity of flow pathways, and recharge rate on the shape of TTDs and the relating SAS functions. To this end, we use a parallel three-dimensional variably saturated groundwater model, ParFlow, to solve for the velocity fields in the subsurface. A particle-tracking model, SLIM, is then implemented to determine the age distributions at every real time and domain location, facilitating a direct characterization of the SAS functions as opposed to analytical approaches requiring calibration of such functions. Steady-state results reveal that the assumption of random age sampling scheme might only hold in the saturated region of homogeneous catchments resulting in an exponential TTD. This assumption is however violated when the vadose zone is included as the underlying SAS function gives a higher preference to older ages. The dynamical variability of the true SAS functions is also shown to be largely masked by the smooth analytical SAS functions. As the variability of subsurface spatial heterogeneity increases, the shape of TTD approaches a power-law distribution function, including a broader distribution of shorter and longer travel times. We further found that larger (smaller) magnitude of effective

  8. THE PROPAGATION OF UNCERTAINTIES IN STELLAR POPULATION SYNTHESIS MODELING. II. THE CHALLENGE OF COMPARING GALAXY EVOLUTION MODELS TO OBSERVATIONS

    International Nuclear Information System (INIS)

    Conroy, Charlie; Gunn, James E.; White, Martin

    2010-01-01

    Models for the formation and evolution of galaxies readily predict physical properties such as star formation rates, metal-enrichment histories, and, increasingly, gas and dust content of synthetic galaxies. Such predictions are frequently compared to the spectral energy distributions of observed galaxies via the stellar population synthesis (SPS) technique. Substantial uncertainties in SPS exist, and yet their relevance to the task of comparing galaxy evolution models to observations has received little attention. In the present work, we begin to address this issue by investigating the importance of uncertainties in stellar evolution, the initial stellar mass function (IMF), and dust and interstellar medium (ISM) properties on the translation from models to observations. We demonstrate that these uncertainties translate into substantial uncertainties in the ultraviolet, optical, and near-infrared colors of synthetic galaxies. Aspects that carry significant uncertainties include the logarithmic slope of the IMF above 1 M sun , dust attenuation law, molecular cloud disruption timescale, clumpiness of the ISM, fraction of unobscured starlight, and treatment of advanced stages of stellar evolution including blue stragglers, the horizontal branch, and the thermally pulsating asymptotic giant branch. The interpretation of the resulting uncertainties in the derived colors is highly non-trivial because many of the uncertainties are likely systematic, and possibly correlated with the physical properties of galaxies. We therefore urge caution when comparing models to observations.

  9. Moving forward in circles: Challenges and opportunities in modeling population cycles

    Science.gov (United States)

    Barraquand, Frederic; Louca, Stilianos; Abbott, Karen C; Cobbold, Christina A; Cordoleani, Flora; DeAngelis, Donald L.; Elderd, Bret D; Fox, Jeremy W; Greenwood, Priscilla; Hilker, Frank M; Murray, Dennis; Stieha, Christopher R; Taylor, Rachel A; Vitense, Kelsey; Wolkowicz, Gail; Tyson, Rebecca C

    2017-01-01

    Population cycling is a widespread phenomenon, observed across a multitude of taxa in both laboratory and natural conditions. Historically, the theory associated with population cycles was tightly linked to pairwise consumer–resource interactions and studied via deterministic models, but current empirical and theoretical research reveals a much richer basis for ecological cycles. Stochasticity and seasonality can modulate or create cyclic behaviour in non-intuitive ways, the high-dimensionality in ecological systems can profoundly influence cycling, and so can demographic structure and eco-evolutionary dynamics. An inclusive theory for population cycles, ranging from ecosystem-level to demographic modelling, grounded in observational or experimental data, is therefore necessary to better understand observed cyclical patterns. In turn, by gaining better insight into the drivers of population cycles, we can begin to understand the causes of cycle gain and loss, how biodiversity interacts with population cycling, and how to effectively manage wildly fluctuating populations, all of which are growing domains of ecological research.

  10. Measurement of filtration efficiency of Nuclepore filters challenged with polystyrene latex nanoparticles: experiments and modeling

    International Nuclear Information System (INIS)

    Ling, Tsz Yan; Wang Jing; Pui, David Y. H.

    2011-01-01

    Membrane filtration has been demonstrated to be effective for the removal of liquid-borne nanoparticles (NPs). Such technique can be applied to purify and disinfect drinking water as well as remove NPs in highly pure chemicals used in the industries. This study aims to study the filtration process of a model membrane filter, the Nuclepore filter. Experiments were carried out using standard filtration tools and the nanoparticle tracking analysis (NTA) technique was used to measure particle (50–500 nm) concentration upstream and downstream of the filter to determine the filtration efficiency. The NTA technique has been calibrated using 150-nm polystyrene latex particles to determine its accuracy of particle concentration measurement. Measurements were found reliable within a certain concentration limit (about 10 8 –10 10 particles/cm 3 ), which is dependent on the camera settings during the measurement. Experimental results are comparable with previously published data obtained using the aerosolization method, validating the capability of the NTA technique. The capillary tube model modified from that developed for aerosol filtration was found to be useful to represent the experimental results, when a sticking coefficient of 0.15 is incorporated. This suggests that only 15% of the particle collisions with the filter results in successful attachment. The small sticking coefficient found can be explained by the unfavorable surface interactions between the particles and the filter medium.

  11. Prevention approaches in a preclinical canine model of Alzheimer’s disease: Benefits and challenges

    Directory of Open Access Journals (Sweden)

    Paulina R. Davis

    2014-03-01

    Full Text Available Aged dogs spontaneously develop many features of human aging and Alzheimer’s disease (AD including cognitive decline and neuropathology. In this review, we discuss age-dependent learning tasks, memory tasks, and functional measures that can be used in aged dogs for sensitive treatment outcome measures. Neuropathology that is linked to cognitive decline is described along with examples of treatment studies that show reduced neuropathology in aging dogs (dietary manipulations, behavioral enrichment, immunotherapy, and statins. Studies in canine show that multi-targeted approaches may be more beneficial than single pathway manipulations (e.g. antioxidants combined with behavioral enrichment. Aging canine studies show good predictive validity for human clinical trials outcomes (e.g. immunotherapy and several interventions tested in dogs strongly support a prevention approach (e.g. immunotherapy and statins. Further, dogs are ideally suited for prevention studies as they the age because onset of cognitive decline and neuropathology strongly support longitudinal interventions that can be completed within a 3-5 year period. Disadvantages to using the canine model are that they lengthy, use labor-intensive comprehensive cognitive testing, and involve costly housing (almost as high as that of nonhuman primates. However overall, using the dog as a preclinical model for testing preventive approaches for AD may complement work in rodents and nonhuman primates.

  12. Challenges of including nitrogen effects on decomposition in earth system models

    Science.gov (United States)

    Hobbie, S. E.

    2011-12-01

    Despite the importance of litter decomposition for ecosystem fertility and carbon balance, key uncertainties remain about how this fundamental process is affected by nitrogen (N) availability. Nevertheless, resolving such uncertainties is critical for mechanistic inclusion of such processes in earth system models, towards predicting the ecosystem consequences of increased anthropogenic reactive N. Towards that end, we have conducted a series of experiments examining nitrogen effects on litter decomposition. We found that both substrate N and externally supplied N (regardless of form) accelerated the initial decomposition rate. Faster initial decomposition rates were linked to the higher activity of carbohydrate-degrading enzymes associated with externally supplied N and the greater relative abundances of Gram negative and Gram positive bacteria associated with green leaves and externally supplied organic N (assessed using phospholipid fatty acid analysis, PLFA). By contrast, later in decomposition, externally supplied N slowed decomposition, increasing the fraction of slowly decomposing litter and reducing lignin-degrading enzyme activity and relative abundances of Gram negative and Gram positive bacteria. Our results suggest that elevated atmospheric N deposition may have contrasting effects on the dynamics of different soil carbon pools, decreasing mean residence times of active fractions comprising very fresh litter, while increasing those of more slowly decomposing fractions including more processed litter. Incorporating these contrasting effects of N on decomposition processes into models is complicated by lingering uncertainties about how these effects generalize across ecosystems and substrates.

  13. Waterfowl populations of conservation concern: learning from diverse challenges, models, and conservation strategies

    Science.gov (United States)

    Austin, Jane E.; Slattery, Stuart; Clark, Robert G.

    2014-01-01

    There are 30 threatened or endangered species of waterfowl worldwide, and several sub-populations are also threatened. Some of these species occur in North America, and others there are also of conservation concern due to declining population trends and their importance to hunters. Here we review conservation initiatives being undertaken for several of these latter species, along with conservation measures in place in Europe, to seek common themes and approaches that could be useful in developing broad conservation guidelines. While focal species may vary in their life histories, population threats and geopolitical context, most conservation efforts have used a systematic approach to understand factors limiting populations and o identify possible management or policy actions. This approach generally includes a priori identification of plausible hypotheses about population declines or status, incorporation of hypotheses into conceptual or quantitative planning models, and the use of some form of structured decision making and adaptive management to develop and implement conservation actions in the face of many uncertainties. A climate of collaboration among jurisdictions sharing these birds is important to the success of a conservation or management programme. The structured conservation approach exemplified herein provides an opportunity to involve stakeholders at all planning stages, allows for all views to be examined and incorporated into model structures, and yields a format for improved communication, cooperation and learning, which may ultimately be one of the greatest benefits of this strategy.

  14. Recent successes and emerging challenges for coordinated satellite/ground-based magnetospheric exploration and modeling.

    Science.gov (United States)

    Angelopoulos, Vassilis

    With the availability of a distributed constellation of spacecraft (THEMIS, Geotail, Cluster) and increased capability ground based arrays (SuperDARN, THEMIS/GBOs), it is now pos-sible to infer simply from timing significant information regarding mapping of magnetospheric phenomena. Optical, magnetometer and radar data can pinpoint the location and nature of onset signatures. On the other hand, magnetic field modeling constrained by physical bound-aries (such as the isotropy boundary) the measured magnetic field and total pressure values at a distibuted network of satellites has proven to do a much better job at correlating ionospheric precipitation and diffuse auroral boundaries to magnetospheric phenomena, such as the inward boundary of the dipolarization fronts. It is now possible to routinely compare in-situ measured phase space densities of ion and electron distributions during ionosphere -magnetosphere con-junctions, in the absense of potential drops. It is also possible to not only infer equivalent current systems from the ground, but use reconstruction of the ionospheric current system from space to determine the full electrodynamics evolution of the ionosphere and compare with radars. Assimilation of this emerging ground based and global magnetospheric panoply into a self consistent magnetospheric model will likely be one of the most fruitful endeavors in magnetospheric exploration during the next few years.

  15. Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.

    Science.gov (United States)

    Deslauriers, Jessica; Toth, Mate; Der-Avakian, Andre; Risbrough, Victoria B

    2018-05-15

    Increasing predictability of animal models of posttraumatic stress disorder (PTSD) has required active collaboration between clinical and preclinical scientists. Modeling PTSD is challenging, as it is a heterogeneous disorder with ≥20 symptoms. Clinical research increasingly utilizes objective biological measures (e.g., imaging, peripheral biomarkers) or nonverbal behaviors and/or physiological responses to complement verbally reported symptoms. This shift toward more-objectively measurable phenotypes enables refinement of current animal models of PTSD, and it supports the incorporation of homologous measures across species. We reviewed >600 articles to examine the ability of current rodent models to probe biological phenotypes of PTSD (e.g., sleep disturbances, hippocampal and fear-circuit dysfunction, inflammation, glucocorticoid receptor hypersensitivity) in addition to behavioral phenotypes. Most models reliably produced enduring generalized anxiety-like or depression-like behaviors, as well as hyperactive fear circuits, glucocorticoid receptor hypersensitivity, and response to long-term selective serotonin reuptake inhibitors. Although a few paradigms probed fear conditioning/extinction or utilized peripheral immune, sleep, and noninvasive imaging measures, we argue that these should be incorporated more to enhance translation. Data on female subjects, on subjects at different ages across the life span, or on temporal trajectories of phenotypes after stress that can inform model validity and treatment study design are needed. Overall, preclinical (and clinical) PTSD researchers are increasingly incorporating homologous biological measures to assess markers of risk, response, and treatment outcome. This shift is exciting, as we and many others hope it not only will support translation of drug efficacy from animal models to clinical trials but also will potentially improve predictability of stage II for stage III clinical trials. Published by Elsevier Inc.

  16. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

    2003-01-01

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  17. Modelling the impacts of challenging 2020 non-ETS GHG emissions reduction targets on Ireland′s energy system

    International Nuclear Information System (INIS)

    Chiodi, Alessandro; Gargiulo, Maurizio; Deane, J.P.; Lavigne, Denis; Rout, Ullash K.; Ó Gallachóir, Brian P.

    2013-01-01

    This paper focuses on Ireland's ambitious target for 2020 to reduce greenhouse gas (GHG) emissions by 20% below 2005 levels for sectors not covered by ETS (Non-ETS). Ireland is an interesting case study due to the role of agriculture (a particularly challenging sector with regard to GHG emissions reduction), that represents 29% of Ireland's GHG emissions compared with less than 10% for the EU. The analysis is carried out with the Irish TIMES model, a bottom-up energy systems modelling tool with detailed characterization of Ireland's energy system. The paper uses scenario analysis to provide pathways that demonstrate how Ireland can meet the non-ETS target at least cost. The paper considers the impacts (in terms of different technology choices and higher marginal abatement costs) arising from higher targets for the energy system to compensate for growth in agriculture activity and low mitigation potential in that sector. The results point to a need to reconsider Ireland's renewable energy focus, with a need for increased effort in renewable transport and renewable heat in particular. The results also point to significant electrification of residential heating. The results also point to a high marginal abatement cost (€213/tCO 2 ), which challenges the analysis carried out at EU level to establish Ireland's non-ETS target. - Highlights: • Techno-economic energy model to deliver EU GHG mitigation target by 2020 in Ireland. • Agriculture represents nearly half of Non-ETS emissions in Ireland. • The target set for Non-ETS GHG for Ireland is far from a cost optimal target. • The results point to a need to reconsider Ireland's renewable energy focus. • Key pathways: electrification of heating in buildings and biofuels in transport

  18. Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS.

    Science.gov (United States)

    Asante, Emmanuel A; Grimshaw, Andrew; Smidak, Michelle; Jakubcova, Tatiana; Tomlinson, Andrew; Jeelani, Asif; Hamdan, Shyma; Powell, Caroline; Joiner, Susan; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

    2015-07-01

    Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann-Sträussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease.

  19. Software Engineering Support of the Third Round of Scientific Grand Challenge Investigations: Earth System Modeling Software Framework Survey

    Science.gov (United States)

    Talbot, Bryan; Zhou, Shu-Jia; Higgins, Glenn; Zukor, Dorothy (Technical Monitor)

    2002-01-01

    One of the most significant challenges in large-scale climate modeling, as well as in high-performance computing in other scientific fields, is that of effectively integrating many software models from multiple contributors. A software framework facilitates the integration task, both in the development and runtime stages of the simulation. Effective software frameworks reduce the programming burden for the investigators, freeing them to focus more on the science and less on the parallel communication implementation. while maintaining high performance across numerous supercomputer and workstation architectures. This document surveys numerous software frameworks for potential use in Earth science modeling. Several frameworks are evaluated in depth, including Parallel Object-Oriented Methods and Applications (POOMA), Cactus (from (he relativistic physics community), Overture, Goddard Earth Modeling System (GEMS), the National Center for Atmospheric Research Flux Coupler, and UCLA/UCB Distributed Data Broker (DDB). Frameworks evaluated in less detail include ROOT, Parallel Application Workspace (PAWS), and Advanced Large-Scale Integrated Computational Environment (ALICE). A host of other frameworks and related tools are referenced in this context. The frameworks are evaluated individually and also compared with each other.

  20. Cognitive models of executive functions development: methodological limitations and theoretical challenges

    Directory of Open Access Journals (Sweden)

    Florencia Stelzer

    2014-01-01

    Full Text Available Executive functions (EF have been defined as a series of higher-order cognitive processes which allow the control of thought, behavior and affection according to the achievement of a goal. Such processes present a lengthy postnatal development which matures completely by the end of adolescence. In this article we make a review of some of the main models of EF development during childhood. The aim of this work is to describe the state of the art related to the topic, identifying the main theoretical difficulties and methodological limitations associated with the different proposed paradigms. Finally, some suggestions are given to cope with such difficulties, emphasizing that the development of an ontology of EF could be a viable alternative to counter them. We believe that futture researches should guide their efforts toward the development of that ontology.

  1. Using Science Data and Models for Space Weather Forecasting - Challenges and Opportunities

    Science.gov (United States)

    Hesse, Michael; Pulkkinen, Antti; Zheng, Yihua; Maddox, Marlo; Berrios, David; Taktakishvili, Sandro; Kuznetsova, Masha; Chulaki, Anna; Lee, Hyesook; Mullinix, Rick; hide

    2012-01-01

    Space research, and, consequently, space weather forecasting are immature disciplines. Scientific knowledge is accumulated frequently, which changes our understanding or how solar eruptions occur, and of how they impact targets near or on the Earth, or targets throughout the heliosphere. Along with continuous progress in understanding, space research and forecasting models are advancing rapidly in capability, often providing substantially increases in space weather value over time scales of less than a year. Furthermore, the majority of space environment information available today is, particularly in the solar and heliospheric domains, derived from research missions. An optimal forecasting environment needs to be flexible enough to benefit from this rapid development, and flexible enough to adapt to evolving data sources, many of which may also stem from non-US entities. This presentation will analyze the experiences obtained by developing and operating both a forecasting service for NASA, and an experimental forecasting system for Geomagnetically Induced Currents.

  2. Continuous Measurements and Quantitative Constraints: Challenge Problems for Discrete Modeling Techniques

    Science.gov (United States)

    Goodrich, Charles H.; Kurien, James; Clancy, Daniel (Technical Monitor)

    2001-01-01

    We present some diagnosis and control problems that are difficult to solve with discrete or purely qualitative techniques. We analyze the nature of the problems, classify them and explain why they are frequently encountered in systems with closed loop control. This paper illustrates the problem with several examples drawn from industrial and aerospace applications and presents detailed information on one important application: In-Situ Resource Utilization (ISRU) on Mars. The model for an ISRU plant is analyzed showing where qualitative techniques are inadequate to identify certain failure modes and to maintain control of the system in degraded environments. We show why the solution to the problem will result in significantly more robust and reliable control systems. Finally, we illustrate requirements for a solution to the problem by means of examples.

  3. Operational benefits and challenges of the use of fingerprint statistical models: a field study.

    Science.gov (United States)

    Neumann, Cedric; Mateos-Garcia, Ismael; Langenburg, Glenn; Kostroski, Jennifer; Skerrett, James E; Koolen, Martin

    2011-10-10

    Research projects aimed at proposing fingerprint statistical models based on the likelihood ratio framework have shown that low quality finger impressions left on crime scenes may have significant evidential value. These impressions are currently either not recovered, considered to be of no value when first analyzed by fingerprint examiners, or lead to inconclusive results when compared to control prints. There are growing concerns within the fingerprint community that recovering and examining these low quality impressions will result in a significant increase of the workload of fingerprint units and ultimately of the number of backlogged cases. This study was designed to measure the number of impressions currently not recovered or not considered for examination, and to assess the usefulness of these impressions in terms of the number of additional detections that would result from their examination. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Climate, ecosystems, and planetary futures: The challenge to predict life in Earth system models.

    Science.gov (United States)

    Bonan, Gordon B; Doney, Scott C

    2018-02-02

    Many global change stresses on terrestrial and marine ecosystems affect not only ecosystem services that are essential to humankind, but also the trajectory of future climate by altering energy and mass exchanges with the atmosphere. Earth system models, which simulate terrestrial and marine ecosystems and biogeochemical cycles, offer a common framework for ecological research related to climate processes; analyses of vulnerability, impacts, and adaptation; and climate change mitigation. They provide an opportunity to move beyond physical descriptors of atmospheric and oceanic states to societally relevant quantities such as wildfire risk, habitat loss, water availability, and crop, fishery, and timber yields. To achieve this, the science of climate prediction must be extended to a more multifaceted Earth system prediction that includes the biosphere and its resources. Copyright © 2018, American Association for the Advancement of Science.

  5. Challenges of implementing collaborative models of decision making with trans-identified patients.

    Science.gov (United States)

    Dewey, Jodie M

    2015-10-01

    Factors health providers face during the doctor-patient encounter both impede and assist the development of collaborative models of treatment. I investigated decision making among medical and therapeutic professionals who work with trans-identified patients to understand factors that might impede or facilitate the adoption of the collaborative decision-making model in their clinical work. Following a grounded theory approach, I collected and analysed data from semi-structured interviews with 10 U.S. physicians and 10 U.S. mental health professionals. Doctors and therapists often desire collaboration with their patients but experience dilemmas in treating the trans-identified patients. Dilemmas include lack of formal education, little to no institutional support and inconsistent understanding and application of the main documents used by professionals treating trans-patients. Providers face considerable risk in providing unconventional treatments due to the lack of institutional and academic support relating to the treatment for trans-people, and the varied interpretation and application of the diagnostic and treatment documents used in treating trans-people. To address this risk, the relationship with the patient becomes crucial. However, trust, a component required for collaboration, is thwarted when the patients feel obliged to present in ways aligned with these documents in order to receive desired treatments. When trust cannot be established, medical and mental health providers can and do delay or deny treatments, resulting in the imbalance of power between patient and provider. The documents created to assist in treatment actually thwart professional desire to work collaboratively with patients. © 2013 John Wiley & Sons Ltd.

  6. Modelling the impacts of challenging 2050 European climate mitigation targets on Ireland’s energy system

    International Nuclear Information System (INIS)

    Chiodi, Alessandro; Gargiulo, Maurizio; Rogan, Fionn; Deane, J.P.; Lavigne, Denis; Rout, Ullash K.; Ó Gallachóir, Brian P.

    2013-01-01

    The Copenhagen Accord established political consensus on the 2 °C limit (in global temperature increase) and for deep cuts in greenhouse gas (GHG) emissions levels to achieve this goal. The European Union has set ambitious GHG targets for the year 2050 (80–95% below 1990 levels), with each Member State developing strategies to contribute to these targets. This paper focuses on mitigation targets for one Member State, Ireland, an interesting case study due to the growth in GHG emissions (24% increase between 1990 and 2005) and the high share of emissions from agriculture (30% of total GHG emissions). We use the Irish TIMES energy systems modelling tool to build a number of scenarios delivering an 80% emissions reduction target by 2050, including accounting for the limited options for agriculture GHG abatement by increasing the emissions reduction target for the energy system. We then compare the scenario results in terms of changes in energy technology, the role of energy efficiency and renewable energy. We also quantify the economic impacts of the mitigation scenarios in terms of marginal CO 2 abatement costs and energy system costs. The paper also sheds light on the impacts of short term targets and policies on long term mitigation pathways. - Highlights: ► We developed a techno-economic energy model of Ireland to the year 2050. ► Reductions between 80% and 95% of GHG emissions can be technically achieved. ► A 50% emissions cut in agriculture requires a 95% reductions from the energy system. ► Extending current policies implies greater electrification and efficiency measures. ► The additional cost to achieve mitigation remain less than 2% of GDP levels in 2050.

  7. A 'joint venture' model of recontacting in clinical genomics: challenges for responsible implementation.

    Science.gov (United States)

    Dheensa, Sandi; Carrieri, Daniele; Kelly, Susan; Clarke, Angus; Doheny, Shane; Turnpenny, Peter; Lucassen, Anneke

    2017-07-01

    Advances in genomics often lead healthcare professionals (HCPs) to learn new information, e.g., about reinterpreted variants that could have clinical significance for patients seen previously. A question arises of whether HCPs should recontact these former patients. We present some findings interrogating the views of patients (or parents of patients) with a rare or undiagnosed condition about how such recontacting might be organised ethically and practically. Forty-one interviews were analysed thematically. Participants suggested a 'joint venture' model in which efforts to recontact are shared with HCPs. Some proposed an ICT-approach involving an electronic health record that automatically alerts them to potentially relevant updates. The need for rigorous privacy controls and transparency about who could access their data was emphasised. Importantly, these findings highlight that the lack of clarity about recontacting is a symptom of a wider problem: the lack of necessary infrastructure to pool genomic data responsibly, to aggregate it with other health data, and to enable patients/parents to receive updates. We hope that our findings will instigate a debate about the way responsibilities for recontacting under any joint venture model could be allocated, as well as the limitations and normative implications of using ICT as a solution to this intractable problem. As a first step to delineating responsibilities in the clinical setting, we suggest HCPs should routinely discuss recontacting with patients/parents, including the new information that should trigger a HCP to initiate recontact, as part of the consent process for genetic testing. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  8. High-speed photometry of Gaia14aae: an eclipsing AM CVn that challenges formation models

    Science.gov (United States)

    Green, M. J.; Marsh, T. R.; Steeghs, D. T. H.; Kupfer, T.; Ashley, R. P.; Bloemen, S.; Breedt, E.; Campbell, H. C.; Chakpor, A.; Copperwheat, C. M.; Dhillon, V. S.; Hallinan, G.; Hardy, L. K.; Hermes, J. J.; Kerry, P.; Littlefair, S. P.; Milburn, J.; Parsons, S. G.; Prasert, N.; van Roestel, J.; Sahman, D. I.; Singh, N.

    2018-05-01

    AM CVn-type systems are ultracompact, hydrogen-deficient accreting binaries with degenerate or semidegenerate donors. The evolutionary history of these systems can be explored by constraining the properties of their donor stars. We present high-speed photometry of Gaia14aae, an AM CVn with a binary period of 49. 7 min and the first AM CVn in which the central white dwarf is fully eclipsed by the donor star. Modelling of the light curves of this system allows for the most precise measurement to date of the donor mass of an AM CVn, and relies only on geometric and well-tested physical assumptions. We find a mass ratio q = M2/M1 = 0.0287 ± 0.0020 and masses M1 = 0.87 ± 0.02 M⊙ and M2 = 0.0250 ± 0.0013 M⊙. We compare these properties to the three proposed channels for AM CVn formation. Our measured donor mass and radius do not fit with the contraction that is predicted for AM CVn donors descended from white dwarfs or helium stars at long orbital periods. The donor properties we measure fall in a region of parameter space in which systems evolved from hydrogen-dominated cataclysmic variables are expected, but such systems should show spectroscopic hydrogen, which is not seen in Gaia14aae. The evolutionary history of this system is therefore not clear. We consider a helium-burning star or an evolved cataclysmic variable to be the most likely progenitors, but both models require additional processes and/or fine-tuning to fit the data. Additionally, we calculate an updated ephemeris which corrects for an anomalous time measurement in the previously published ephemeris.

  9. On beyond the standard model for high explosives: challenges & obstacles to surmount

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph Ds [Los Alamos National Laboratory

    2009-01-01

    Plastic-bonded explosives (PBX) are heterogeneous materials. Nevertheless, current explosive models treat them as homogeneous materials. To compensate, an empirically determined effective burn rate is used in place of a chemical reaction rate. A significant limitation of these models is that different burn parameters are needed for applications in different regimes; for example, shock initiation of a PBX at different initial temperatures or different initial densities. This is due to temperature fluctuations generated when a heterogeneous material is shock compressed. Localized regions of high temperatures are called hot spots. They dominate the reaction for shock initiation. The understanding of hot spot generation and their subsequent evolution has been limited by the inability to measure transients on small spatial ({approx} 1 {micro}m) and small temporal ({approx} 1 ns) scales in the harsh environment of a detonation. With the advances in computing power, it is natural to try and gain an understanding of hot-spot initiation with numerical experiments based on meso-scale simulations that resolve material heterogeneities and utilize realistic chemical reaction rates. However, to capture the underlying physics correctly, such high resolution simulations will require more than fast computers with a large amount of memory. Here we discuss some of the issues that need to be addressed. These include dissipative mechanisms that generate hot spots, accurate thermal propceties for the equations of state of the reactants and products, and controlling numerical entropy error from shock impedance mismatches at material interfaces. The later can generate artificial hot spots and lead to premature reaction. Eliminating numerical hot spots is critical for shock initiation simulations due to the positive feedback between the energy release from reaction and the hydrodynamic flow.

  10. The Pediatric Home Care/Expenditure Classification Model (P/ECM): A Home Care Case-Mix Model for Children Facing Special Health Care Challenges.

    Science.gov (United States)

    Phillips, Charles D

    2015-01-01

    Case-mix classification and payment systems help assure that persons with similar needs receive similar amounts of care resources, which is a major equity concern for consumers, providers, and programs. Although health service programs for adults regularly use case-mix payment systems, programs providing health services to children and youth rarely use such models. This research utilized Medicaid home care expenditures and assessment data on 2,578 children receiving home care in one large state in the USA. Using classification and regression tree analyses, a case-mix model for long-term pediatric home care was developed. The Pediatric Home Care/Expenditure Classification Model (P/ECM) grouped children and youth in the study sample into 24 groups, explaining 41% of the variance in annual home care expenditures. The P/ECM creates the possibility of a more equitable, and potentially more effective, allocation of home care resources among children and youth facing serious health care challenges.

  11. Challenges in modelling isoprene and monoterpene emission dynamics of Arctic plants: a case study from a subarctic tundra heath

    Science.gov (United States)

    Tang, Jing; Schurgers, Guy; Valolahti, Hanna; Faubert, Patrick; Tiiva, Päivi; Michelsen, Anders; Rinnan, Riikka

    2016-12-01

    The Arctic is warming at twice the global average speed, and the warming-induced increases in biogenic volatile organic compounds (BVOCs) emissions from Arctic plants are expected to be drastic. The current global models' estimations of minimal BVOC emissions from the Arctic are based on very few observations and have been challenged increasingly by field data. This study applied a dynamic ecosystem model, LPJ-GUESS, as a platform to investigate short-term and long-term BVOC emission responses to Arctic climate warming. Field observations in a subarctic tundra heath with long-term (13-year) warming treatments were extensively used for parameterizing and evaluating BVOC-related processes (photosynthesis, emission responses to temperature and vegetation composition). We propose an adjusted temperature (T) response curve for Arctic plants with much stronger T sensitivity than the commonly used algorithms for large-scale modelling. The simulated emission responses to 2 °C warming between the adjusted and original T response curves were evaluated against the observed warming responses (WRs) at short-term scales. Moreover, the model responses to warming by 4 and 8 °C were also investigated as a sensitivity test. The model showed reasonable agreement to the observed vegetation CO2 fluxes in the main growing season as well as day-to-day variability of isoprene and monoterpene emissions. The observed relatively high WRs were better captured by the adjusted T response curve than by the common one. During 1999-2012, the modelled annual mean isoprene and monoterpene emissions were 20 and 8 mg C m-2 yr-1, with an increase by 55 and 57 % for 2 °C summertime warming, respectively. Warming by 4 and 8 °C for the same period further elevated isoprene emission for all years, but the impacts on monoterpene emissions levelled off during the last few years. At hour-day scale, the WRs seem to be strongly impacted by canopy air T, while at the day-year scale, the WRs are a combined

  12. LigB subunit vaccine confers sterile immunity against challenge in the hamster model of leptospirosis.

    Directory of Open Access Journals (Sweden)

    Neida L Conrad

    2017-03-01

    Full Text Available Neglected tropical diseases, including zoonoses such as leptospirosis, have a major impact on rural and poor urban communities, particularly in developing countries. This has led to major investment in antipoverty vaccines that focus on diseases that influence public health and thereby productivity. While the true, global, impact of leptospirosis is unknown due to the lack of adequate laboratory diagnosis, the WHO estimates that incidence has doubled over the last 15 years to over 1 million cases that require hospitalization every year. Leptospirosis is caused by pathogenic Leptospira spp. and is spread through direct contact with infected animals, their urine or contaminated water and soil. Inactivated leptospirosis vaccines, or bacterins, are approved in only a handful of countries due to the lack of heterologous protection (there are > 250 pathogenic Leptospira serovars and the serious side-effects associated with vaccination. Currently, research has focused on recombinant vaccines, a possible solution to these problems. However, due to a lack of standardised animal models, rigorous statistical analysis and poor reproducibility, this approach has met with limited success. We evaluated a subunit vaccine preparation, based on a conserved region of the leptospiral immunoglobulin-like B protein (LigB(131-645 and aluminium hydroxide (AH, in the hamster model of leptospirosis. The vaccine conferred significant protection (80.0-100%, P < 0.05 against mortality in vaccinated animals in seven independent experiments. The efficacy of the LigB(131-645/AH vaccine ranged from 87.5-100% and we observed sterile immunity (87.5-100% among the vaccinated survivors. Significant levels of IgM and IgG were induced among vaccinated animals, although they did not correlate with immunity. A mixed IgG1/IgG2 subclass profile was associated with the subunit vaccine, compared to the predominant IgG2 profile seen in bacterin vaccinated hamsters. These findings suggest

  13. An overview of challenges in modeling heat and mass transfer for living on Mars.

    Science.gov (United States)

    Yamashita, Masamichi; Ishikawa, Yoji; Kitaya, Yoshiaki; Goto, Eiji; Arai, Mayumi; Hashimoto, Hirofumi; Tomita-Yokotani, Kaori; Hirafuji, Masayuki; Omori, Katsunori; Shiraishi, Atsushi; Tani, Akira; Toki, Kyoichiro; Yokota, Hiroki; Fujita, Osamu

    2006-09-01

    Engineering a life-support system for living on Mars requires the modeling of heat and mass transfer. This report describes the analysis of heat and mass transfer phenomena in a greenhouse dome, which is being designed as a pressurized life-support system for agricultural production on Mars. In this Martian greenhouse, solar energy will be converted into chemical energy in plant biomass. Agricultural products will be harvested for food and plant cultivation, and waste materials will be processed in a composting microbial ecosystem. Transpired water from plants will be condensed and recycled. In our thermal design and analysis for the Martian greenhouse, we addressed the question of whether temperature and pressure would be maintained in the appropriate range for humans as well as plants. Energy flow and material circulation should be controlled to provide an artificial ecological system on Mars. In our analysis, we assumed that the greenhouse would be maintained at a subatmospheric pressure under 1/3-G gravitational force with 1/2 solar light intensity on Earth. Convection of atmospheric gases will be induced inside the greenhouse, primarily by heating from sunlight. Microclimate (thermal and gas species structure) could be generated locally around plant bodies, which would affect gas transport. Potential effects of those environmental factors are discussed on the phenomena including plant growth and plant physiology and focusing on transport processes. Fire safety is a crucial issue and we evaluate its impact on the total gas pressure in the greenhouse dome.

  14. Pencilbeam irradiation technique for whole brain radiotherapy: technical and biological challenges in a small animal model.

    Science.gov (United States)

    Schültke, Elisabeth; Trippel, Michael; Bräuer-Krisch, Elke; Renier, Michel; Bartzsch, Stefan; Requardt, Herwig; Döbrössy, Máté D; Nikkhah, Guido

    2013-01-01

    We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.

  15. High-resolution digital 3D models of Algar do Penico Chamber: limitations, challenges, and potential

    Directory of Open Access Journals (Sweden)

    Ivo Silvestre M.Sc.

    2015-01-01

    Full Text Available The study of karst and its geomorphological structures is important for understanding the relationships between hydrology and climate over geological time. In that context, we conducted a terrestrial laser-scan survey to map geomorphological structures in the karst cave of Algar do Penico in southern Portugal. The point cloud data set obtained was used to generate 3D meshes with different levels of detail, allowing the limitations of mapping capabilities to be explored. In addition to cave mapping, the study focuses on 3D-mesh analysis, including the development of two algorithms for determination of stalactite extremities and contour lines, and on the interactive visualization of 3D meshes on the Web. Data processing and analysis were performed using freely available open-source software. For interactive visualization, we adopted a framework based on Web standards X3D, WebGL, and X3DOM. This solution gives both the general public and researchers access to 3D models and to additional data produced from map tools analyses through a web browser, without the need for plug-ins.

  16. Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas.

    Science.gov (United States)

    de Polo, Anna; Scrimshaw, Mark D

    2012-02-01

    An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by controlling its speciation, but also by affecting the osmoregulatory physiology of the organism, which varies according to salinity. In an attempt to understand the mechanisms of Cu toxicity and predict its impacts, we explore the hypothesis that the common factor linking the main toxic effects of Cu is the enzyme carbonic anhydrase (CA), because it is a Cu target with multiple functions and salinity-dependent expression and activity. According to this hypothesis, the site of action of Cu in marine fish may be not only the gill, but also the intestine, because in this tissue CA plays an important role in ion transport and water adsorption. Therefore, the BLM of Cu toxicity to marine fish should also consider the intestine as a biotic ligand. Finally, we underline the need to incorporate the osmotic gradient into the BLM calculations to account for the influence of physiology on Cu toxicity. Copyright © 2011 SETAC.

  17. The developing cancer stem-cell model: clinical challenges and opportunities.

    Science.gov (United States)

    Vermeulen, Louis; de Sousa e Melo, Felipe; Richel, Dick J; Medema, Jan Paul

    2012-02-01

    During the past decade, a stem-cell-like subset of cancer cells has been identified in many malignancies. These cells, referred to as cancer stem cells (CSCs), are of particular interest because they are believed to be the clonogenic core of the tumour and therefore represent the cell population that drives growth and progression. Many efforts have been made to design therapies that specifically target the CSC population, since this was predicted to be the crucial population to eliminate. However, recent insights have complicated the initial elegant model, by showing a dominant role for the tumour microenvironment in determining CSC characteristics within a malignancy. This is particularly important since dedifferentiation of non-tumorigenic tumour cells towards CSCs can occur, and therefore the CSC population in a neoplasm is expected to vary over time. Moreover, evidence suggests that not all tumours are driven by rare CSCs, but might instead contain a large population of tumorigenic cells. Even though these results suggest that specific targeting of the CSC population might not be a useful therapeutic strategy, research into the hierarchical cellular organisation of malignancies has provided many important new insights in the biology of tumours. In this Personal View, we highlight how the CSC concept is developing and influences our thinking on future treatment for solid tumours, and recommend ways to design clinical trials to assess drugs that target malignant disease in a rational fashion. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Current Understanding and Remaining Challenges in Modeling Long-Term Degradation of Borosilicate Nuclear Waste Glasses

    International Nuclear Information System (INIS)

    Vienna, John D.; Ryan, Joseph V.; Gin, Stephane; Inagaki, Yaohiro

    2013-01-01

    Chemical durability is not a single material property that can be uniquely measured. Instead it is the response to a host of coupled material and environmental processes whose rates are estimated by a combination of theory, experiment, and modeling. High-level nuclear waste (HLW) glass is perhaps the most studied of any material yet there remain significant technical gaps regarding their chemical durability. The phenomena affecting the long-term performance of HLW glasses in their disposal environment include surface reactions, transport properties to and from the reacting glass surface, and ion exchange between the solid glass and the surrounding solution and alteration products. The rates of these processes are strongly influenced and are coupled through the solution chemistry, which is in turn influenced by the reacting glass and also by reaction with the near-field materials and precipitation of alteration products. Therefore, those processes must be understood sufficiently well to estimate or bound the performance of HLW glass in its disposal environment over geologic time-scales. This article summarizes the current state of understanding of surface reactions, transport properties, and ion exchange along with the near-field materials and alteration products influences on solution chemistry and glass reaction rates. Also summarized are the remaining technical gaps along with recommended approaches to fill those technical gaps

  19. Co-production and modeling landscape change - successes and challenges in developing useful climate science

    Science.gov (United States)

    Timm, K.; Reynolds, J.; Littell, J. S.; Murphy, K.; Euskirchen, E. S.; Breen, A. L.; Gray, S. T.; McGuire, A. D.; Rupp, S. T.

    2017-12-01

    Responding to the impacts of climate change and generating information that helps inform resource management requires exceptional communication and collaboration among researchers, managers, and other stakeholders. However, there is relatively little guidance on how to practically develop, facilitate, and evaluate this process given the highly specific and localized nature of many co-production efforts in terms of information needs, research questions, partners, and associated institutions. The Integrated Ecosystem Model (IEM) for Alaska and Northwest Canada was developed to understand how climate change influences interactions among disturbance (e.g. wildfire, thermokarst), permafrost, hydrology, and vegetation and identify how these changes affect valuable ecosystem services. The IEM was a unique co-production effort in that it was driven by broad management interests (rather than one research question), and because of the landscape-scale outputs, much broader engagement was warranted. Communication between the research team and the broader community of resource managers was facilitated by the Alaska Landscape Conservation Cooperatives and the Alaska Climate Science Center. Team members' reflections on the project confirm the importance of deliberate approaches to collaboration, where everyone has frequent opportunities to discuss goals, assumptions, and presumed outcomes of the project itself, as well as the elements of the process (i.e. meetings, reports, etc.). However, managing these activities requires significant time, resources, and perhaps more dedicated personnel. The lessons learned from the design and application of the IEM are highly relevant to researchers and land managers in other regions that are considering the development of a similar tool or an undertaking of similar magnitude, scale, and complexity.

  20. A personality trait model for the Diagnostic and Statistical Manual of Mental Disorders (DSM): the challenges ahead.

    Science.gov (United States)

    Krueger, Robert F; Eaton, Nicholas R

    2010-04-01

    We were sincerely flattered to discover that John Gunderson, Michael First, Paul Costa, Robert McCrae, Michael Hallquist, and Paul Pilkonis provided commentaries on our target article. In this brief response, we cannot hope to discuss the myriad points raised by this august group. Such a task would be particularly daunting given the diversity of the commentaries. Indeed, the diversity of the commentaries provides a kind of "metacommentary" on the state of personality and psychopathology research. That is, the intellectual diversity contained in the commentaries underlines the substantial challenges that lie ahead of us, in terms of articulating a model of personality and psychopathology with both scientific validity and clinical applicability. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  1. Interconnection between nitric oxide formation and hypersensitivity parameters under guinea pig model of acute asthma with multiple challenges

    Directory of Open Access Journals (Sweden)

    O. O. Parilova

    2015-10-01

    Full Text Available An immunoregulatory role of nitric oxide (NO in the development of adaptive immune responses associated with allergic diseases is very important. The present study extended these observations by the examination of the reciprocal changes in characteristic immunologic parameters of the disease and NO level of bronchoalveolar lavage (BAL cells under guinea pig model of acute asthma with multiple challenges. Development of guinea pig Th2 mediated asthma was accompanied by increasing the level of allergic markers: ovalbumin (OVA specific IgG and IL-4. We demonstrated that the infiltrate of airway cells contributes to NO synthesis in the respiratory tract during allergic inflammation. The level of intracellular NO formation significantly correlated with plasma allergen specific IgG value in OVA-induced asthma. The presented data evidence that the elevated intracellular NO level in BAL fluid may reflect a nitrosative stress in respiratory tract in general, when allergic asthma exacerbation is present.

  2. Gut Health of Pigs: Challenge Models and Response Criteria with a Critical Analysis of the Effectiveness of Selected Feed Additives - A Review.

    Science.gov (United States)

    Adewole, D I; Kim, I H; Nyachoti, C M

    2016-07-01

    The gut is the largest organ that helps with the immune function. Gut health, especially in young pigs has a significant benefit to health and performance. In an attempt to maintain and enhance intestinal health in pigs and improve productivity in the absence of in-feed antibiotics, researchers have evaluated a wide range of feed additives. Some of these additives such as zinc oxide, copper sulphate, egg yolk antibodies, mannan-oligosaccharides and spray dried porcine plasma and their effectiveness are discussed in this review. One approach to evaluate the effectiveness of these additives in vivo is to use an appropriate disease challenge model. Over the years, researchers have used a number of challenge models which include the use of specific strains of enterotoxigenic Escherichia coli, bacteria lipopolysaccharide challenge, oral challenge with Salmonella enteric serotype Typhimurium, sanitation challenge, and Lawsonia intercellularis challenge. These challenge models together with the criteria used to evaluate the responses of the animals to them are also discussed in this review.

  3. Gut Health of Pigs: Challenge Models and Response Criteria with a Critical Analysis of the Effectiveness of Selected Feed Additives — A Review

    Science.gov (United States)

    Adewole, D. I.; Kim, I. H.; Nyachoti, C. M.

    2016-01-01

    The gut is the largest organ that helps with the immune function. Gut health, especially in young pigs has a significant benefit to health and performance. In an attempt to maintain and enhance intestinal health in pigs and improve productivity in the absence of in-feed antibiotics, researchers have evaluated a wide range of feed additives. Some of these additives such as zinc oxide, copper sulphate, egg yolk antibodies, mannan-oligosaccharides and spray dried porcine plasma and their effectiveness are discussed in this review. One approach to evaluate the effectiveness of these additives in vivo is to use an appropriate disease challenge model. Over the years, researchers have used a number of challenge models which include the use of specific strains of enterotoxigenic Escherichia coli, bacteria lipopolysaccharide challenge, oral challenge with Salmonella enteric serotype Typhimurium, sanitation challenge, and Lawsonia intercellularis challenge. These challenge models together with the criteria used to evaluate the responses of the animals to them are also discussed in this review. PMID:26954144

  4. Cognitive Challenges

    Science.gov (United States)

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Cognitive Challenges Approximately 45% to 60% of individuals with TSC develop cognitive challenges (intellectual disabilities), although the degree of intellectual ...

  5. Incorporating Ecosystem Experiments and Observations into Process Models of Forest Carbon and Water Cycles: Challenges and Solutions

    Science.gov (United States)

    Ward, E. J.; Thomas, R. Q.; Sun, G.; McNulty, S. G.; Domec, J. C.; Noormets, A.; King, J. S.

    2015-12-01

    Numerous studies, both experimental and observational, have been conducted over the past two decades in an attempt to understand how water and carbon cycling in terrestrial ecosystems may respond to changes in climatic conditions. These studies have produced a wealth of detailed data on key processes driving these cycles. In parallel, sophisticated models of these processes have been formulated to answer a variety of questions relevant to natural resource management. Recent advances in data assimilation techniques offer exciting new possibilities to combine this wealth of ecosystem data with process models of ecosystem function to improve prediction and quantify associated uncertainty. Using forests of the southeastern United States as our focus, we will specify how fine-scale physiological (e.g. half-hourly sap flux) can be scaled up with quantified error for use in models of stand growth and hydrology. This approach represents an opportunity to leverage current and past research from experiments including throughfall displacement × fertilization (PINEMAP), irrigation × fertilization (SETRES), elevated CO­2­ (Duke and ORNL FACE) and a variety of observational studies in both conifer and hardwood forests throughout the region, using a common platform for data assimilation and prediction. As part of this discussion, we will address variation in dominant species, stand structure, site age, management practices, soils and climate that represent both challenges to the development of a common analytical approach and opportunities to address questions of interest to policy makers and natural resource managers.

  6. Synthetic biology between challenges and risks: suggestions for a model of governance and a regulatory framework, based on fundamental rights.

    Science.gov (United States)

    Colussi, Ilaria Anna

    2013-01-01

    This paper deals with the emerging synthetic biology, its challenges and risks, and tries to design a model for the governance and regulation of the field. The model is called of "prudent vigilance" (inspired by the report about synthetic biology, drafted by the U.S. Presidential Commission on Bioethics, 2010), and it entails (a) an ongoing and periodically revised process of assessment and management of all the risks and concerns, and (b) the adoption of policies - taken through "hard law" and "soft law" sources - that are based on the principle of proportionality (among benefits and risks), on a reasonable balancing between different interests and rights at stake, and are oriented by a constitutional frame, which is represented by the protection of fundamental human rights emerging in the field of synthetic biology (right to life, right to health, dignity, freedom of scientific research, right to environment). After the theoretical explanation of the model, its operability is "checked", by considering its application with reference to only one specific risk brought up by synthetic biology - biosecurity risk, i.e. the risk of bioterrorism.

  7. Progress Towards Achieving the Challenge of Indian Summer Monsoon Climate Simulation in a Coupled Ocean-Atmosphere Model

    Science.gov (United States)

    Hazra, Anupam; Chaudhari, Hemantkumar S.; Saha, Subodh Kumar; Pokhrel, Samir; Goswami, B. N.

    2017-10-01

    Simulation of the spatial and temporal structure of the monsoon intraseasonal oscillations (MISOs), which have effects on the seasonal mean and annual cycle of Indian summer monsoon (ISM) rainfall, remains a grand challenge for the state-of-the-art global coupled models. Biases in simulation of the amplitude and northward propagation of MISOs and related dry rainfall bias over ISM region in climate models are limiting the current skill of monsoon prediction. Recent observations indicate that the convective microphysics of clouds may be critical in simulating the observed MISOs. The hypothesis is strongly supported by high fidelity in simulation of the amplitude and space-time spectra of MISO by a coupled climate model, when our physically based modified cloud microphysics scheme is implemented in conjunction with a modified new Simple Arakawa Schubert (nSAS) convective parameterization scheme. Improved simulation of MISOs appears to have been aided by much improved simulation of the observed high cloud fraction and convective to stratiform rain fractions and resulted into a much improved simulation of the ISM rainfall, monsoon onset, and the annual cycle.

  8. PENERAPAN MODEL CHALLENGE BASED LEARNING DENGAN METODE EKSPERIMEN DAN PROYEK DITINJAU DARI KEINGINTAHUAN DAN SIKAP ILMIAH TERHADAP PRESTASI BELAJAR SISWA

    Directory of Open Access Journals (Sweden)

    Sodikin .

    2014-09-01

    Full Text Available The purposes of the research were to know the effect of challenge based learning (CBL model by experiments method and project, learning of inquiring and scientific attitude and their interaction towards students’  achievement in cognitive, affective and psychomotoric. Data was collected using test technique for cognitive, non test technique for affective, psikomotoric, learning motivation, learning activity, and obsevation sheet is used for affective and psychomotoric. The data were analyzed by using anova test through software PASW 18.  Based on the analysis of the data concluded: 1 there was effect of CBL model by experiments method and project toward cognitive, affective and psychomotoric towards students’ achievement; 2 there was an effect of learning inquiring towards cognitive and affective students’ achievement, but there was no effect towards psychomotoric students’ achievement; 3 there was an effect of scientific attitude toward cognitive students’ achievement, but there was no effect toward affective and psychomotoric students’ achievement; 4 there was no an interaction between CBL model by experiments method and project method with learning inquiring toward cognitive, affective and psikomotoric student’ achievement; 5 there was no an interaction between CBL model by experiments method and project method with scientific attitude toward cognitive, affective and psychomotoric students’ achievement; 6 there was no an interaction between learning inquiring with scientific attitude toward cognitive, affective and psychomotoric students’ achievement;  7 there was no an interaction between CBL  model by experiments method and project with learning inquiring and scientific attitude toward cognitive, affective and psychomotoric students’ achievement.

  9. Estimating parametric phenotypes that determine anthesis date in Zea mays: Challenges in combining ecophysiological models with genetics

    Science.gov (United States)

    Welch, Stephen M.; White, Jeffrey W.; Thorp, Kelly R.; Bello, Nora M.

    2018-01-01

    Ecophysiological crop models encode intra-species behaviors using parameters that are presumed to summarize genotypic properties of individual lines or cultivars. These genotype-specific parameters (GSP’s) can be interpreted as quantitative traits that can be mapped or otherwise analyzed, as are more conventional traits. The goal of this study was to investigate the estimation of parameters controlling maize anthesis date with the CERES-Maize model, based on 5,266 maize lines from 11 plantings at locations across the eastern United States. High performance computing was used to develop a database of 356 million simulated anthesis dates in response to four CERES-Maize model parameters. Although the resulting estimates showed high predictive value (R2 = 0.94), three issues presented serious challenges for use of GSP’s as traits. First (expressivity), the model was unable to express the observed data for 168 to 3,339 lines (depending on the combination of site-years), many of which ended up sharing the same parameter value irrespective of genetics. Second, for 2,254 lines, the model reproduced the data, but multiple parameter sets were equally effective (equifinality). Third, parameter values were highly dependent (p<10−6919) on the sets of environments used to estimate them (instability), calling in to question the assumption that they represent fundamental genetic traits. The issues of expressivity, equifinality and instability must be addressed before the genetic mapping of GSP’s becomes a robust means to help solve the genotype-to-phenotype problem in crops. PMID:29672629

  10. [Manpower migrations and Arab unity: the challenges of the Iraqi model].

    Science.gov (United States)

    Roussillon, A

    1985-01-01

    the presence of large numbers of foreign workers not only to the countries employing them but to the Arab nation as a whole allows Iraq to criticize the migration policies of the Gulf oil exporters, which are increasingly favoring more productive labor from Asian countries and which cede much of the authority to select and admit workers to private concerns. The evolution of Iraq's policy demonstrates the concern of its governing party with reconciling its Arab identity and its analysis of international power relations with consolidation of its own position internally and in the Arab world as a whole. The labor policy of the oil exporters exposes their countries and thus the Arab world to the possibility of sabotage and to demographic overpowering of ethnic and cultural identity. Interpretations differ as to whether the Iraqi model has led to a better deployment of labor and as to its theoretical contribution to pan-Arab unity, given the diverging interests of the individual states concerned.

  11. Looking under Kachru's (1982, 1985 three circles model of World Englishes: the hidden reality and current challenges

    Directory of Open Access Journals (Sweden)

    John Robert Schmitz

    2014-03-01

    Full Text Available This paper examines the pioneering model of World Englishes formulated by Kachru in the early 1980s that allocates the presence of English into three concentric circles: first of all, the inner circle (Great Britain, the USA where the language functions as an L1 (or native language; secondly, the outer circle (India, Nigeria where the language was forced upon the subjugated people by Britain; thirdly, the expanding circle (China, Brazil where English is studied as a foreign language. Researchers in the area of language studies tend to put too much store in Kachru's model expecting it to expose the different circles: (i the proficiency level of the speakers, (ii the variation that exists in the different dialects of the language, and (iii how the many users appropriate the language to perform their daily routine. Pung (2009 suggests "going beyond" the three circle model with his proposal of a Conical Model of English (CME, while Park and Wee (2009, p.402 state that models have no "magical efficacy in challenging dominant ideologies of English" and that change in the world is not brought about by models but my people. Based on Park and Lee's caution with regard to models, and in lieu of Pung's "going beyond" the well-known Kachruvian model, the thrust of this article is to look specifically under the inner circle, that is, the supposed "native speaker domain". It will be argued in this paper that the circles function as a palimpsest erasing and ignoring what happened in the past linguistically, historically and culturally before the appearance of English in the spaces that the language occupies at the present time in the inner, outer, and expanding circles. An examination of days gone-by, with a focus on Kachru's inner circle, can present a mirror to examine: (i bilingual (multilingual biases, (ii migration of peoples and treatment of immigrants, (iii respect (or lack of for the linguistic and cultural rights of minorities, and (iv the hegemony of

  12. The challenges of modelling phosphorus in a headwater catchment: Applying a 'limits of acceptability' uncertainty framework to a water quality model

    Science.gov (United States)

    Hollaway, M. J.; Beven, K. J.; Benskin, C. McW. H.; Collins, A. L.; Evans, R.; Falloon, P. D.; Forber, K. J.; Hiscock, K. M.; Kahana, R.; Macleod, C. J. A.; Ockenden, M. C.; Villamizar, M. L.; Wearing, C.; Withers, P. J. A.; Zhou, J. G.; Barber, N. J.; Haygarth, P. M.

    2018-03-01

    There is a need to model and predict the transfer of phosphorus (P) from land to water, but this is challenging because of the large number of complex physical and biogeochemical processes involved. This study presents, for the first time, a 'limits of acceptability' approach of the Generalized Likelihood Uncertainty Estimation (GLUE) framework to the Soil and Water Assessment Tool (SWAT), in an application to a water quality problem in the Newby Beck catchment (12.5 km2), Cumbria, United Kingdom (UK). Using high frequency outlet data (discharge and P), individual evaluation criteria (limits of acceptability) were assigned to observed discharge and P loads for all evaluation time steps, identifying where the model was performing well/poorly and to infer which processes required improvement in the model structure. Initial limits of acceptability were required to be relaxed by a substantial amount (by factors of between 5.3 and 6.7 on a normalized scale depending on the evaluation criteria used) in order to gain a set of behavioral simulations (1001 and 1016, respectively out of 5,000,000)