WorldWideScience

Sample records for modeling significant progress

  1. Modeling Progress in AI

    OpenAIRE

    Brundage, Miles

    2015-01-01

    Participants in recent discussions of AI-related issues ranging from intelligence explosion to technological unemployment have made diverse claims about the nature, pace, and drivers of progress in AI. However, these theories are rarely specified in enough detail to enable systematic evaluation of their assumptions or to extrapolate progress quantitatively, as is often done with some success in other technological domains. After reviewing relevant literatures and justifying the need for more ...

  2. Differential action of glycoprotein hormones: significance in cancer progression.

    Science.gov (United States)

    Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

    2014-02-01

    Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

  3. Scalar Potential Model progress

    Science.gov (United States)

    Hodge, John

    2007-04-01

    Because observations of galaxies and clusters have been found inconsistent with General Relativity (GR), the focus of effort in developing a Scalar Potential Model (SPM) has been on the examination of galaxies and clusters. The SPM has been found to be consistent with cluster cellular structure, the flow of IGM from spiral galaxies to elliptical galaxies, intergalactic redshift without an expanding universe, discrete redshift, rotation curve (RC) data without dark matter, asymmetric RCs, galaxy central mass, galaxy central velocity dispersion, and the Pioneer Anomaly. In addition, the SPM suggests a model of past expansion, past contraction, and current expansion of the universe. GR corresponds to the SPM in the limit in which a flat and static scalar potential field replaces the Sources and Sinks such as between clusters and on the solar system scale which is small relative to the distance to a Source. The papers may be viewed at http://web.infoave.net/˜scjh/ .

  4. On the significance of magnetospheric research for progress in astrophysics

    International Nuclear Information System (INIS)

    Faelthammar, C-G.; Akasofu, S-I.; Alfen, H.

    1978-04-01

    Recent discoveries by means of in situ measurements have led to a substantial revision of our picture of the magnetosphere and parts of the heliosphere. This concerns such essential aspects as the character and distribution of electric fields and currents, the ways in which charged particles are energized, and the chemical composition of the magnetospheric plasma. This revision reflects the fact that even in fundamental respects, real cosmical plasmas behave in different ways than predicted by the idealized models that have traditionally been used in magnetospheric physics as well as in astrophysics. The new understanding of the general properties of cosmical plasma that has been, and continues to be, provided by in situ measurements gives us a much improved basis on which to interpret astrophysical observations

  5. Progress in modeling and simulation.

    Science.gov (United States)

    Kindler, E

    1998-01-01

    For the modeling of systems, the computers are more and more used while the other "media" (including the human intellect) carrying the models are abandoned. For the modeling of knowledges, i.e. of more or less general concepts (possibly used to model systems composed of instances of such concepts), the object-oriented programming is nowadays widely used. For the modeling of processes existing and developing in the time, computer simulation is used, the results of which are often presented by means of animation (graphical pictures moving and changing in time). Unfortunately, the object-oriented programming tools are commonly not designed to be of a great use for simulation while the programming tools for simulation do not enable their users to apply the advantages of the object-oriented programming. Nevertheless, there are exclusions enabling to use general concepts represented at a computer, for constructing simulation models and for their easy modification. They are described in the present paper, together with true definitions of modeling, simulation and object-oriented programming (including cases that do not satisfy the definitions but are dangerous to introduce misunderstanding), an outline of their applications and of their further development. In relation to the fact that computing systems are being introduced to be control components into a large spectrum of (technological, social and biological) systems, the attention is oriented to models of systems containing modeling components.

  6. On an orthotropic model for progressive degradation

    DEFF Research Database (Denmark)

    Hammer, Velaja B.; Pedersen, Pauli

    1999-01-01

    Progressive degradation in orthotropic materials is modelled from a smear-out point of view, and physical measurable quantities are used as the describing parameters. Evolution of stiffness and evolution of strength are kept uncoupled. For plane problems the stiffness evolution is modelled...

  7. Does significant renal ablation truly and invariably lead to hyperfiltration and progressive chronic kidney disease?

    Science.gov (United States)

    Wang, Andrew; Sam, Ramin

    2017-06-01

    It is generally believed that significant renal ablation leads to hyperfiltration and eventually progressively worsening chronic kidney disease. The data behind this belief have not been scrutinized intensively. More importantly, the above belief leads many physicians to manage patients differently than they otherwise would manage. Here, we examine the data behind whether hyperfiltration occurs when patients lose kidney mass (by excision or by disease) and whether the hyperfiltration is uniformly injurious.

  8. Modelling vocal anatomy's significant effect on speech

    NARCIS (Netherlands)

    de Boer, B.

    2010-01-01

    This paper investigates the effect of larynx position on the articulatory abilities of a humanlike vocal tract. Previous work has investigated models that were built to resemble the anatomy of existing species or fossil ancestors. This has led to conflicting conclusions about the relation between

  9. Progress in modeling hypersonic turbulent boundary layers

    Science.gov (United States)

    Zeman, Otto

    1993-01-01

    A good knowledge of the turbulence structure, wall heat transfer, and friction in turbulent boundary layers (TBL) at high speeds is required for the design of hypersonic air breathing airplanes and reentry space vehicles. This work reports on recent progress in the modeling of high speed TBL flows. The specific research goal described here is the development of a second order closure model for zero pressure gradient TBL's for the range of Mach numbers up to hypersonic speeds with arbitrary wall cooling requirements.

  10. Sepsis progression and outcome: a dynamical model

    Directory of Open Access Journals (Sweden)

    Gessler Damian DG

    2006-02-01

    Full Text Available Abstract Background Sepsis (bloodstream infection is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis progression, based upon basic physiologic principles, which could eventually guide hourly treatment decisions. Results We present an initial mathematical model of sepsis, based on metabolic rate theory that links basic vascular and immunological dynamics. The model includes the rate of vascular circulation, a surrogate for the metabolic rate that is mechanistically associated with disease progression. We use the mass-specific rate of blood circulation (SRBC, a correlate of the body mass index, to build a differential equation model of circulation, infection, organ damage, and recovery. This introduces a vascular component into an infectious disease model that describes the interaction between a pathogen and the adaptive immune system. Conclusion The model predicts that deviations from normal SRBC correlate with disease progression and adverse outcome. We compare the predictions with population mortality data from cardiovascular disease and cancer and show that deviations from normal SRBC correlate with higher mortality rates.

  11. Electric power and its significance as the energy for innovation and progress

    International Nuclear Information System (INIS)

    Klinger, H.; Boehmer, T.

    1999-01-01

    The significance of electric power as the essential form of energy to support innovation and progress well into the future is explained with respect to four major domains of application: 1. Innovative activities in microelectronics and semiconductor technology, for applications such as automation and computer technology, instrumentation and control technology, facility and systems management and control. 2. Energy efficiency programmes and schemes for increasing the penetration of energiy from renewable sources in the market. Example: Heat pump technology. 3. Electric power as an energy boosting innovation in industrial production processes. Examples are given from the transportation sector. (orig./CB) [de

  12. IAEA Mission Sees Significant Progress in Georgia’s Regulatory Framework, Challenges Ahead

    International Nuclear Information System (INIS)

    2018-01-01

    An International Atomic Energy Agency (IAEA) team of experts said Georgia has made significant progress in strengthening its regulatory framework for nuclear and radiation safety. The team also pointed to challenges ahead as Georgia seeks to achieve further progress. The Integrated Regulatory Review Service (IRRS) team concluded a 10-day mission on 28 February to assess the regulatory safety framework in Georgia. The mission was conducted at the request of the Government and hosted by the Agency of Nuclear and Radiation Safety (ANRS), which is responsible for regulatory oversight in the country. IRRS missions are designed to strengthen the effectiveness of the national safety regulatory infrastructure, while recognizing the responsibility of each State to ensure nuclear and radiation safety. Georgia uses radioactive sources in medicine and industry and operates radioactive waste management facilities. It has decommissioned its only research reactor and has no nuclear power plants. In recent years, the Government and ANRS, with assistance from the IAEA, introduced new safety regulations and increased the number of regulatory inspections.

  13. Demonstrating the benefits of fuel cells: further significant progress towards commercialisation

    Energy Technology Data Exchange (ETDEWEB)

    Anon,

    1995-01-01

    The fourteenth Fuel Cell Seminar held in San Diego, California in 1994 is reported. The phosphoric acid fuel cell (PAFC) is the closest to widespread commercialization. PAFC cogeneration plants have to be shown to compare favourable in reliability with current mature natural gas-fuelled engine and turbine technologies. Although highly efficient, further development is necessary to produce cost effective generators. Progress is being made on proton exchange membrane fuel cell (PEMFC) stationary power plants, too, which may prove to be cost effective. In view of its lower operating temperature, at below 100[sup o]C compared with about 200[sup o]C for the PAFC, the principal use of the PEMFC has been identified as powering vehicles. Fuel cells have significant environmental advantages but further capital cost reductions are necessary if they are to compete with established technologies. (UK)

  14. Progression of Diabetic Capillary Occlusion: A Model.

    Directory of Open Access Journals (Sweden)

    Xiao Fu

    2016-06-01

    Full Text Available An explanatory computational model is developed of the contiguous areas of retinal capillary loss which play a large role in diabetic maculapathy and diabetic retinal neovascularization. Strictly random leukocyte mediated capillary occlusion cannot explain the occurrence of large contiguous areas of retinal ischemia. Therefore occlusion of an individual capillary must increase the probability of occlusion of surrounding capillaries. A retinal perifoveal vascular sector as well as a peripheral retinal capillary network and a deleted hexagonal capillary network are modelled using Compucell3D. The perifoveal modelling produces a pattern of spreading capillary loss with associated macular edema. In the peripheral network, spreading ischemia results from the progressive loss of the ladder capillaries which connect peripheral arterioles and venules. System blood flow was elevated in the macular model before a later reduction in flow in cases with progression of capillary occlusions. Simulations differing only in initial vascular network structures but with identical dynamics for oxygen, growth factors and vascular occlusions, replicate key clinical observations of ischemia and macular edema in the posterior pole and ischemia in the retinal periphery. The simulation results also seem consistent with quantitative data on macular blood flow and qualitative data on venous oxygenation. One computational model applied to distinct capillary networks in different retinal regions yielded results comparable to clinical observations in those regions.

  15. Progressive significance map and its application to error-resilient image transmission.

    Science.gov (United States)

    Hu, Yang; Pearlman, William A; Li, Xin

    2012-07-01

    Set partition coding (SPC) has shown tremendous success in image compression. Despite its popularity, the lack of error resilience remains a significant challenge to the transmission of images in error-prone environments. In this paper, we propose a novel data representation called the progressive significance map (prog-sig-map) for error-resilient SPC. It structures the significance map (sig-map) into two parts: a high-level summation sig-map and a low-level complementary sig-map (comp-sig-map). Such a structured representation of the sig-map allows us to improve its error-resilient property at the price of only a slight sacrifice in compression efficiency. For example, we have found that a fixed-length coding of the comp-sig-map in the prog-sig-map renders 64% of the coded bitstream insensitive to bit errors, compared with 40% with that of the conventional sig-map. Simulation results have shown that the prog-sig-map can achieve highly competitive rate-distortion performance for binary symmetric channels while maintaining low computational complexity. Moreover, we note that prog-sig-map is complementary to existing independent packetization and channel-coding-based error-resilient approaches and readily lends itself to other source coding applications such as distributed video coding.

  16. Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition.

    Science.gov (United States)

    Mukherjee, Pinku; Basu, Gargi D; Tinder, Teresa L; Subramani, Durai B; Bradley, Judy M; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

    2009-01-01

    With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRAS(G12D) mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E(2) and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer.

  17. Significant progress towards development of the low-level radioactive waste disposal facility in Illinois

    International Nuclear Information System (INIS)

    Klebe, M.; Henry, T.L.; Corpstein, P.

    1996-01-01

    Development of disposal sites for low-level radioactive waste is a complicated legal, regulatory and public sector process. Development of the low-level radioactive waste disposal facility to support generators in Illinois and Kentucky is well under way. Significant progress has been made to re-engineer the siting development process capitalizing on prior lessons learned and a recommitment from Illinois state leadership assuring the future success of the program. Comparisons of why this new process will succeed are the major focus of this paper. Specific changes in approach from the previous process including changes in the Illinois Management Act (Management Act), creation of the Illinois Low-Level Radioactive Waste Siting Task Group (Task Group), new roles for the Illinois State Geologic Survey and Illinois State Water Survey (Scientific Surveys) and the Illinois Department of Nuclear Safety (IDNS), a new contractor reliance approach and increased confidence on the open-quote science close-quote are the major contrasts between the previous process and the new process currently underway

  18. Progress in D-brane model building

    International Nuclear Information System (INIS)

    Marchesano, F.

    2007-01-01

    The state of the art in D-brane model building is briefly reviewed, focusing on recent achievements in the construction of D=4 N=1 type II string vacua with semi-realistic gauge sectors. Such progress relies on a better understanding of the spectrum of BPS D-branes, the effective field theory obtained from them and the explicit construction of vacua. We first consider D-branes in standard Calabi-Yau compactifications, and then the more involved case of compactifications with fluxes. We discuss how the non-trivial interplay between D-branes and fluxes modifies the previous model-building rules, as well as provides new possibilities to connect string theory to particle physics. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

  19. Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Fanming Meng

    2018-01-01

    Full Text Available Background Long non-coding RNAs (lncRNAs have been reported to modulate cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream were proposed to be potential biomarkers for clinical diagnosis. However, few cardiovascular diseases-related circulating lncRNAs were identified and their prediction power has not been investigated in depth. Here we report a new circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript (APPAT, and evaluated its role and predicting ability in atherosclerotic development. Methods APPAT was analyzed and screened by high-throughput sequencing, and then detected in vitro and in vivo. Immunofluorescence-fluorescence in situ hybridization (IF-FISH was utilized to explore distribution and subcellular location of APPAT. The expressing alteration of APPAT in samples of healthy and pathological coronary artery was explored further. We also assessed the level of circulating APPAT in blood samples from healthy individuals, and patients with angina pectoris (AP or myocardial infarction (MI. Additionally, we predicted and validated microRNA targets of APPAT, then showed the expression level of a candidate target which was primarily measured in human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined the potential indicating ability of APPAT for the risk of AP or MI. Results APPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It enriched in contractile VSMCs of artery tunica media and mainly existed in cytoplasm. Significant down-regulation of APPAT was found in coronary artery samples with severe stenosis. More importantly, we observed decreased expression of APPAT in blood samples accompanying disease progression. ROC and correlation analyses further verified the relatively high predicting ability of APPAT. We also observed the predicted miRNA exhibited opposite expression direction to that of APPAT. Conclusions This study revealed that

  20. Discovery of CDH23 as a Significant Contributor to Progressive Postlingual Sensorineural Hearing Loss in Koreans.

    Directory of Open Access Journals (Sweden)

    Bong Jik Kim

    Full Text Available CDH23 mutations have mostly been associated with prelingual severe-to-profound sensorineural hearing loss (SNHL in either syndromic or nonsyndromic SNHL (DFNB12. Herein, we demonstrate the contribution of CDH23 mutations to postlingual nonsyndromic SNHL (NS-SNHL. We screened 32 Korean adult probands with postlingual NS-SNHL sporadically or in autosomal recessive fashion using targeted panel or whole exome sequencing. We identified four (12.5%, 4/32 potential postlingual DFNB12 families that segregated the recessive CDH23 variants, qualifying for our criteria along with rapidly progressive SNHL. Three of the four families carried one definite pathogenic CDH23 variant previously known as the prelingual DFNB12 variant in a trans configuration with rare CDH23 variants. To determine the contribution of rare CDH23 variants to the postlingual NS-SNHL, we checked the minor allele frequency (MAF of CDH23 variants detected from our postlingual NS-SNHL cohort and prelingual NS-SNHL cohort, among the 2040 normal control chromosomes. The allele frequency of these CDH23 variants in our postlingual cohort was 12.5%, which was significantly higher than that of the 2040 control chromosomes (5.53%, confirming the contribution of these rare CDH23 variants to postlingual NS-SNHL. Furthermore, MAF of rare CDH23 variants from the postlingual NS-SNHL group was significantly higher than that from the prelingual NS-SNHL group. This study demonstrates an important contribution of CDH23 mutations to poslingual NS-SNHL and shows that the phenotypic spectrum of DFNB12 can be broadened even into the presbycusis, depending on the pathogenic potential of variants. We also propose that pathogenic potential of CDH23 variants and the clinical fate of DFNB12 may be predicted by MAF.

  1. Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response.

    Science.gov (United States)

    Mori, Tetsuya; Nakamura, Tatsuro; Okazaki, Naoto; Furukohri, Asako; Maki, Hisaji; Akiyama, Masahiro Tatsumi

    2012-01-01

    The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

  2. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

    Science.gov (United States)

    Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

    2016-09-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

  3. Recent progress in sorption mechanisms and models

    International Nuclear Information System (INIS)

    Fedoroff, M.; Lefevre, G.

    2005-01-01

    reactivity of the different faces. Finally, we know more about the sorption processes and are able to model them with a better agreement with the real sorption mechanisms. However, this progress concerns a few simple systems and a further task will be the application of this knowledge to more complex systems. (authors)

  4. Significant uncertainty in global scale hydrological modeling from precipitation data erros

    NARCIS (Netherlands)

    Sperna Weiland, F.; Vrugt, J.A.; Beek, van P.H.; Weerts, A.H.; Bierkens, M.F.P.

    2015-01-01

    In the past decades significant progress has been made in the fitting of hydrologic models to data. Most of this work has focused on simple, CPU-efficient, lumped hydrologic models using discharge, water table depth, soil moisture, or tracer data from relatively small river basins. In this paper, we

  5. Significant uncertainty in global scale hydrological modeling from precipitation data errors

    NARCIS (Netherlands)

    Weiland, Frederiek C. Sperna; Vrugt, Jasper A.; van Beek, Rens (L. ) P. H.; Weerts, Albrecht H.; Bierkens, Marc F. P.

    2015-01-01

    In the past decades significant progress has been made in the fitting of hydrologic models to data. Most of this work has focused on simple, CPU-efficient, lumped hydrologic models using discharge, water table depth, soil moisture, or tracer data from relatively small river basins. In this paper, we

  6. Progress towards Continental River Dynamics modeling

    Science.gov (United States)

    Yu, Cheng-Wei; Zheng, Xing; Liu, Frank; Maidment, Daivd; Hodges, Ben

    2017-04-01

    The high-resolution National Water Model (NWM), launched by U.S. National Oceanic and Atmospheric Administration (NOAA) in August 2016, has shown it is possible to provide real-time flow prediction in rivers and streams across the entire continental United States. The next step for continental-scale modeling is moving from reduced physics (e.g. Muskingum-Cunge) to full dynamic modeling with the Saint-Venant equations. The Simulation Program for River Networks (SPRNT) provides a computational approach for the Saint-Venant equations, but obtaining sufficient channel bathymetric data and hydraulic roughness is seen as a critical challenge. However, recent work has shown the Height Above Nearest Drainage (HAND) method can be applied with the National Elevation Dataset (NED) to provide automated estimation of effective channel bathymetry suitable for large-scale hydraulic simulations. The present work examines the use of SPRNT with the National Hydrography Dataset (NHD) and HAND-derived bathymetry for automated generation of rating curves that can be compared to existing data. The approach can, in theory, be applied to every stream reach in the NHD and thus provide flood guidance where none is available. To test this idea we generated 2000+ rating curves in two catchments in Texas and Alabama (USA). Field data from the USGS and flood records from an Austin, Texas flood in May 2015 were used as validation. Large-scale implementation of this idea requires addressing several critical difficulties associated with numerical instabilities, including ill-posed boundary conditions generated in automated model linkages and inconsistencies in the river geometry. A key to future progress is identifying efficient approaches to isolate numerical instability contributors in a large time-space varying solution. This research was supported in part by the National Science Foundation under grant number CCF-1331610.

  7. The Significance of Trust in the Political System and Motivation for Pupils' Learning Progress in Politics Lessons

    Science.gov (United States)

    Landwehr, Barbara; Weisseno, Georg

    2016-01-01

    Very little research has been conducted on the contribution of political education to learning progress in Germany. Hence, there is a need for intervention studies measuring performance against the theoretical background of a political competence model. This model comprises three constructs: subject knowledge, motivation and attitudes. According…

  8. Coupled Immunological and Biomechanical Model of Emphysema Progression

    Directory of Open Access Journals (Sweden)

    Mario Ceresa

    2018-04-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a disabling respiratory pathology, with a high prevalence and a significant economic and social cost. It is characterized by different clinical phenotypes with different risk profiles. Detecting the correct phenotype, especially for the emphysema subtype, and predicting the risk of major exacerbations are key elements in order to deliver more effective treatments. However, emphysema onset and progression are influenced by a complex interaction between the immune system and the mechanical properties of biological tissue. The former causes chronic inflammation and tissue remodeling. The latter influences the effective resistance or appropriate mechanical response of the lung tissue to repeated breathing cycles. In this work we present a multi-scale model of both aspects, coupling Finite Element (FE and Agent Based (AB techniques that we would like to use to predict the onset and progression of emphysema in patients. The AB part is based on existing biological models of inflammation and immunological response as a set of coupled non-linear differential equations. The FE part simulates the biomechanical effects of repeated strain on the biological tissue. We devise a strategy to couple the discrete biological model at the molecular /cellular level and the biomechanical finite element simulations at the tissue level. We tested our implementation on a public emphysema image database and found that it can indeed simulate the evolution of clinical image biomarkers during disease progression.

  9. Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2013-01-01

    Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

  10. Progressive degradation of alloy 690 and the development of a significant improvement in alloy 800CR

    International Nuclear Information System (INIS)

    Staehle, Roger W.; Arioka, Koji; Tapping, Robert

    2015-01-01

    The present most widely used alloys for tubing in steam generators and structural materials in water cooled reactors are Alloy 690 and Alloy 800. However, both alloys, while improved over Alloy 600 may not meet the needs of longer range applications in the range of 80-100 years. Alloy 690 sustains damage resulting from the formation of cavities at grain boundaries which eventually cover about 50% of the area of the grain boundaries with the remainder covering being covered with carbides. The cavities seem to nucleate on the carbides leaving the grain boundaries a structure of cavities and carbides. Such a structure will lead the Alloy 690 to fail completely. Normal Alloy 800 does not produce such cavities and probably retains a large amount of its corrosion resistance but does sustain progressive SCC at low rate. A new alloy, 800CR, has been developed in a collaboration among Arioka, Tapping, and Staehle. This alloy is based on a Cr composition of 23.5-27% with the remainder retaining the previous Alloy 800 composition. 800CR sustains a crack velocity about 100 times less than Alloy 690 and a negligible rate of initiation. The 800CR, alloy is now seeking a patent. (authors)

  11. Determining significant endpoints for ecological risk analyses. 1997 annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, T.G.; Congdon, J.; Rowe, C.; Scott, D. [Univ. of Georgia, Aiken, SC (US). Savannah River Ecology Lab.; Bedford, J.; Whicker, F.W. [Colorado State Univ., Fort Collins, CO (US)

    1997-11-01

    'This report summarizes the first year''s progress of research funded under the Department of Energy''s Environmental Management Science Program. The research was initiated to better determine ecological risks from toxic and radioactive contaminants. More precisely, the research is designed to determine the relevancy of sublethal cellular damage to the performance of individuals and to identify characteristics of non-human populations exposed to chronic, low-level radiation, as is typically found on many DOE sites. The authors propose to establish a protocol to assess risks to non-human species at higher levels of biological organization by relating molecular damage to more relevant responses that reflect population health. They think that they can achieve this by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables, and by using novel biological dosimeters in controlled, manipulative dose/effects experiments. They believe that a scientifically defensible endpoint for measuring ecological risks can only be determined once its understood the extent to which molecular damage from contaminant exposure is detrimental at the individual and population levels of biological organization.'

  12. Developing and Validating a Predictive Model for Stroke Progression

    Directory of Open Access Journals (Sweden)

    L.E. Craig

    2011-12-01

    Full Text Available Background: Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Methods: Two patient cohorts were used for this study – the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863 was used to develop the model. Variables that were statistically significant (p 0.1 in turn. The second cohort (n = 216 was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Results: Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72–0.73] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50–0.92]. Conclusion: The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the

  13. Developing and validating a predictive model for stroke progression.

    Science.gov (United States)

    Craig, L E; Wu, O; Gilmour, H; Barber, M; Langhorne, P

    2011-01-01

    Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Two patient cohorts were used for this study - the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72-0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50-0.92)]. The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear

  14. Developing and Validating a Predictive Model for Stroke Progression

    Science.gov (United States)

    Craig, L.E.; Wu, O.; Gilmour, H.; Barber, M.; Langhorne, P.

    2011-01-01

    Background Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Methods Two patient cohorts were used for this study – the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Results Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72–0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50–0.92)]. Conclusion The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and

  15. Enforcement actions: significant actions resolved. Quarterly progress report, July-September 1982

    International Nuclear Information System (INIS)

    1982-10-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July to September 1982) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to the licensee with respect to the enforcement action. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, in the interest of promoting public health and safety as well as common defense and security. This publication is issued on a quarterly basis to include significant enforcement actions resolved during the preceding quarter

  16. Enforcement actions: significant actions resolved. Quarterly progress report, January-June 1982

    International Nuclear Information System (INIS)

    1982-09-01

    This compilation summarizes significant enforcement actions that have been resolved during two quarterly periods (January to June 1982) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to the licensee with respect to the enforcement action. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, in the interest of promoting public health and safety as well as common defense and security. The intention is that this publication will be issued on a quarterly basis to include significant enforcement actions resolved during the preceding quarter

  17. Enforcement actions: Significant actions resolved individual actions. Semiannual progress report, January 1996--June 1996

    International Nuclear Information System (INIS)

    1996-08-01

    This document summarizes significant enforcement actions that have been resolved during the period of January-June 1996. The report includes copies of Orders and Notices of Violations sent by the Nuclear Regulatory Commission to individuals with respect to the enforcement actions

  18. Enforcement actions: Significant actions resolved individual actions. Semiannual progress report, January 1996--June 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-08-01

    This document summarizes significant enforcement actions that have been resolved during the period of January-June 1996. The report includes copies of Orders and Notices of Violations sent by the Nuclear Regulatory Commission to individuals with respect to the enforcement actions.

  19. Enforcement actions: significant actions resolved. Quarterly progress report, October-December 1985. Volume 4, No. 4

    International Nuclear Information System (INIS)

    1986-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1985) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory commission to licensees with respects to these enforcement actions, and the licensees' responses

  20. Future health care applications resulting from progress in the neurosciences: The significance of neural plasticity research

    NARCIS (Netherlands)

    Gelijns, A.C.; Graaff, P.J.; Lopes da Silva, F.A.; Gispen, W.H.

    1987-01-01

    Neurological, communicative and behavioral disorders afflict a significant part of the population in industrialized countries, and these disorders can be expected to gain in importance in the coming decades. In a considerable number of these dis-orders impairments in plasticity, i.e. deficiencies in

  1. Enforcement actions: Significant actions resolved individuals actions. Semiannual progress report, July--December 1996

    International Nuclear Information System (INIS)

    1997-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July - December 1996) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to-these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions

  2. Enforcement actions: Significant actions resolved; Quarterly progress report, October--December 1993: Volume 12, No. 4

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  3. Enforcement actions: Significant actions resolved material licensees. Semiannual progress report, July--December 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  4. Enforcement actions: Significant actions resolved individual actions. Semiannual progress report, January 1997--June 1997

    International Nuclear Information System (INIS)

    1997-09-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (January - June 1997) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions

  5. Enforcement actions: Significant actions resolved material licensees. Semiannual progress report, July--December 1996

    International Nuclear Information System (INIS)

    1997-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  6. Enforcement actions: Significant actions resolved individual actions. Semiannual progress report, January 1997--June 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (January - June 1997) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions.

  7. Enforcement actions: Significant actions resolved individuals actions. Semiannual progress report, July--December 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July - December 1996) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to-these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions.

  8. Evaluating significance in linear mixed-effects models in R.

    Science.gov (United States)

    Luke, Steven G

    2017-08-01

    Mixed-effects models are being used ever more frequently in the analysis of experimental data. However, in the lme4 package in R the standards for evaluating significance of fixed effects in these models (i.e., obtaining p-values) are somewhat vague. There are good reasons for this, but as researchers who are using these models are required in many cases to report p-values, some method for evaluating the significance of the model output is needed. This paper reports the results of simulations showing that the two most common methods for evaluating significance, using likelihood ratio tests and applying the z distribution to the Wald t values from the model output (t-as-z), are somewhat anti-conservative, especially for smaller sample sizes. Other methods for evaluating significance, including parametric bootstrapping and the Kenward-Roger and Satterthwaite approximations for degrees of freedom, were also evaluated. The results of these simulations suggest that Type 1 error rates are closest to .05 when models are fitted using REML and p-values are derived using the Kenward-Roger or Satterthwaite approximations, as these approximations both produced acceptable Type 1 error rates even for smaller samples.

  9. Enforcement actions: Significant actions resolved: Quarterly progress report, October--December 1988

    International Nuclear Information System (INIS)

    1989-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1988) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  10. Enforcement actions: Significant actions resolved: Quarterly progress report, April-June 1987

    International Nuclear Information System (INIS)

    1987-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1987) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  11. Enforcement actions: Significant actions resolved reactor licensees. Semiannual progress report, July 1996--December 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July-December 1996) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  12. Enforcement actions: significant actions resolved. Quarterly progress report, January-March 1986. Volume 5, No. 1

    International Nuclear Information System (INIS)

    1986-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January-March 1986) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions, and the licensees' responses. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, in the interest of promoting public health and safety as well as common defense and security

  13. Enforcement actions: Significant actions resolved industrial licensees. Quarterly progress report, April 1994--June 1994

    International Nuclear Information System (INIS)

    1994-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April - June 1994) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to industrial licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  14. Enforcement actions: Significant actions resolved: Quarterly progress report, July--September 1988

    International Nuclear Information System (INIS)

    1988-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1988) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  15. Enforcement actions: significant actions resolved. Quarterly progress report, April-June 1986. Volume 5, No. 2

    International Nuclear Information System (INIS)

    1986-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1986) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions and the licensees' responses. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, in the interest of promoting public health and safety as well as common defense and security

  16. Enforcement actions: significant actions resolved. Quarterly progress report, July-September 1985. Volume 4, No. 3

    International Nuclear Information System (INIS)

    1985-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July-September 1985) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions, and the licensees' responses. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, in the interest of promoting public health and safety as well as common defense and security

  17. Enforcement actions: significant actions resolved. Quarterly progress report, July-September 1984. Volume 3, No. 3

    International Nuclear Information System (INIS)

    1984-10-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July-September 1984 and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions and the licensees' responses. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, in the interest of promoting public health and safety as well as common defense and security

  18. Enforcement actions: Significant actions resolved material licensees. Quarterly progress report, April 1995--June 1995

    International Nuclear Information System (INIS)

    1995-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Enforcement actions: Significant actions resolved: Quarterly progress report, April--June 1988

    International Nuclear Information System (INIS)

    1988-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1988) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Enforcement actions: Significant actions resolved: Quarterly progress report, July-September 1987

    International Nuclear Information System (INIS)

    1987-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July-September 1987) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  1. Enforcement actions: significant actions resolved. Quarterly progress report, July-September 1983. Volume 2, No.3

    International Nuclear Information System (INIS)

    1983-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July-September 1983) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions ad licensees' responses. This and future issues will include cases involving Severity Level III violations for which no civil penalty was assessed. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, in the interest of promoting public health and safety as well as common defense and security

  2. Enforcement actions: Significant actions resolved. Quarterly progress report, April--June 1993: Volume 12, No. 2

    Energy Technology Data Exchange (ETDEWEB)

    1993-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  3. Enforcement actions: Significant actions resolved reactor licensees. Semiannual progress report, July 1996--December 1996

    International Nuclear Information System (INIS)

    1997-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July-December 1996) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  4. Enforcement actions: Significant actions resolved: Quarterly progress report, January-March 1988

    International Nuclear Information System (INIS)

    1988-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January-March 1988) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  5. Retention Esophagitis as a Significant Clinical Predictor of Progression to Esophageal Cancer in Achalasia

    Directory of Open Access Journals (Sweden)

    Haewon Kim

    2018-03-01

    Full Text Available Background/Aims Chronic liquid and/or food stasis caused by retention esophagitis (RE in achalasia is a notable endoscopic finding because of the presence of a thickened or whitish esophageal mucosa and histologically altered squamous hyperplasia. We aimed to identify the clinical features of RE associated with achalasia and to clarify the clinical definition of RE in achalasia as a precancerous lesion identified by analyzing biomarker expressions. Methods From 2006 to 2015, we retrospectively reviewed 37 patients with achalasia without previous treatment. Among them, 21 patients had diagnostic findings of RE (RE+ and 16 patients had no diagnostic findings of RE (RE–. Immunohistochemical staining of p53, p16, and Ki-67 was performed on the endoscopic biopsy tissues from the patients with achalasia and 10 control patients with non-obstructive dysphagia. Results The symptom duration and transit delay were significantly longer in the RE+ group than in the RE– group. We found particularly high p53 positivity rates in the RE+ group (p<0.001. The rate of p16 expression was also significantly higher in the RE+ group than in the other two groups (p=0.003. Conclusions A high p53 expression rate was more frequently found in the RE+ group than in the other two groups. RE could be a meaningful clinical feature of achalasia for predicting esophageal carcinogenesis.

  6. Tumor heterogeneity and progression: conceptual foundations for modeling.

    Science.gov (United States)

    Greller, L D; Tobin, F L; Poste, G

    1996-01-01

    A conceptual foundation for modeling tumor progression, growth, and heterogeneity is presented. The purpose of such models is to aid understanding, test ideas, formulate experiments, and to model cancer 'in machina' to address the dynamic features of tumor cell heterogeneity, progression, and growth. The descriptive capabilities of such an approach provides a consistent language for qualitatively reasoning about tumor behavior. This approach provides a schema for building conceptual models that combine three key phenomenological driving elements: growth, progression, and genetic instability. The growth element encompasses processes contributing to changes in tumor bulk and is distinct from progression per se. The progression element subsumes a broad collection of processes underlying phenotypic progression. The genetics elements represents heritable changes which potentially affect tumor character and behavior. Models, conceptual and mathematical, can be built for different tumor situations by drawing upon the interaction of these three distinct driving elements. These models can be used as tools to explore a diversity of hypotheses concerning dynamic changes in cellular populations during tumor progression, including the generation of intratumor heterogeneity. Such models can also serve to guide experimentation and to gain insight into dynamic aspects of complex tumor behavior.

  7. Oxide behaviour modelling progress in COMETHE

    International Nuclear Information System (INIS)

    Vliet, J. van; Hoppe, N.

    1983-01-01

    An attempt has been made to develop a global model which simultaneously describes many important aspects of uranium oxide under irradiation. The individual models describing fuel structural changes, swelling and gas release, which were earlier separate from one another, are now part of a more realistic integral fuel model. Fission gas release depends now on an explicitely calculated open porosity, which is generated by fuel swelling; the latter is in turn connected to fission gas release. The paper describes the individual oxide models and how they are linked together. (author)

  8. In silico ADME-Tox modeling: progress and prospects.

    Science.gov (United States)

    Alqahtani, Saeed

    2017-11-01

    Although significant progress has been made in high-throughput screening of absorption, distribution, metabolism and excretion, and toxicity (ADME-Tox) properties in drug discovery and development, in silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials. Areas covered: This review provides an overview of the available in silico models that have been used to predict the ADME-Tox properties of compounds. It also provides a comprehensive overview and summarization of the latest modeling methods and algorithms available for the prediction of physicochemical characteristics, ADME properties, and drug toxicity issues. Expert opinion: The in silico models currently available have greatly contributed to the knowledge of screening approaches in the early stages of drug discovery and the development process. As the definitive goal of in silico molding is to predict the pharmacokinetics and disposition of compounds in vivo by assembling all kinetic processes within one global model, PBPK models can serve this purpose. However, much work remains to be done in this area to generate more data and input parameters to build more reliable and accurate prediction models.

  9. Progress in Global Multicompartmental Modelling of DDT

    Science.gov (United States)

    Stemmler, I.; Lammel, G.

    2009-04-01

    Dichlorophenyltrichloroethane, DDT, and its major metabolite dichlorophenyldichloroethylene, DDE, are long-lived in the environment (persistent) and circulate since the 1950s. They accumulate along food chains, cause detrimental effects in marine and terrestrial wild life, and pose a hazard for human health. DDT was widely used as an insecticide in the past and is still in use in a number of tropical countries to combat vector borne diseases like malaria and typhus. It is a multicompartmental substance with only a small mass fraction residing in air. A global multicompartment chemistry transport model (MPI-MCTM; Semeena et al., 2006) is used to study the environmental distribution and fate of dichlorodiphenyltrichloroethane (DDT). For the first time a horizontally and vertically resolved global model was used to perform a long-term simulation of DDT and DDE. The model is based on general circulation models for the ocean (MPIOM; Marsland et al., 2003) and atmosphere (ECHAM5). In addition, an oceanic biogeochemistry model (HAMOCC5.1; Maier-Reimer et al., 2005 ) and a microphysical aerosol model (HAM; Stier et al., 2005 ) are included. Multicompartmental substances are cycling in atmosphere (3 phases), ocean (3 phases), top soil (3 phases), and vegetation surfaces. The model was run for 40 years forced with historical agricultural application data of 1950-1990. The model results show that the global environmental contamination started to decrease in air, soil and vegetation after the applications peaked in 1965-70. In some regions, however, the DDT mass had not yet reached a maximum in 1990 and was still accumulating mass until the end of the simulation. Modelled DDT and DDE concentrations in atmosphere, ocean and soil are evaluated by comparison with observational data. The evaluation of the model results indicate that degradation of DDE in air was underestimated. Also for DDT, the discrepancies between model results and observations are related to uncertainties of

  10. The Peierls model: Progress and limitations

    International Nuclear Information System (INIS)

    Schoeck, Gunther

    2005-01-01

    The basic features of the Peierls model are reviewed. The original model is based on the concept of balance of stresses in 1D and has serious limitations. These limitations can be overcome by a treatment as a variational problem on the energy level in 2D. The fundamental equations are given and applications to determine displacement profiles for dislocations and their dissociations are discussed. When the core misfit has a planar extension and the misfit energy in the glide plane - the γ-surface - is determined from ab initio methods, very reliable core configurations can be determined. For dislocations along close-packed lattice directions the misfit energy can be obtained by a summing procedure using Euler coordinates. When these dislocations are dissociated multiple equilibrium configurations with different splitting widths can exist, but the values of energy difference in between - the Peierls energy - are too small to be determined reliably, considering the simplifying assumptions of the model

  11. Flood Progression Modelling and Impact Analysis

    DEFF Research Database (Denmark)

    Mioc, Darka; Anton, François; Nickerson, B.

    People living in the lower valley of the St. John River, New Brunswick, Canada, frequently experience flooding when the river overflows its banks during spring ice melt and rain. To better prepare the population of New Brunswick for extreme flooding, we developed a new flood prediction model...

  12. Progress and Overview on Neutronics Modelling Development in RTP

    International Nuclear Information System (INIS)

    Mohamad Hairie Rabir; Muhammad Rawi Mohamed Zin; Julia Abdul Karim

    2016-01-01

    Reactor calculation and simulation are significantly important to ensure safety and better utilization of a research reactor. The Malaysian PUSPATI TRIGA Reactor (RTP) achieved initial criticality on June 28, 1982. The reactor is designed to effectively implement the various fields of basic nuclear research, manpower training, and production of radioisotopes. Since early 90s, neutronics modelling were used as part of its routine in-core fuel management activities. The are several computer codes have been used in RTP since then, based on 1D neutron diffusion, 2D neutron diffusion and 3D Monte Carlo neutron transport method. This paper describes current progress and overview on neutronics modelling development in RTP. Several important parameters were analysed such as k_e_f_f, reactivity, neutron flux, power distribution, B_e_f_f, and fission product build-up for the latest core configuration. The developed core neutronics model was validated by means of comparison with experimental and measurement data. Along with the RTP core model, the calculation procedure also developed to establish better prediction capability of RTP behaviour. (author)

  13. A keyword spotting model using perceptually significant energy features

    Science.gov (United States)

    Umakanthan, Padmalochini

    The task of a keyword recognition system is to detect the presence of certain words in a conversation based on the linguistic information present in human speech. Such keyword spotting systems have applications in homeland security, telephone surveillance and human-computer interfacing. General procedure of a keyword spotting system involves feature generation and matching. In this work, new set of features that are based on the psycho-acoustic masking nature of human speech are proposed. After developing these features a time aligned pattern matching process was implemented to locate the words in a set of unknown words. A word boundary detection technique based on frame classification using the nonlinear characteristics of speech is also addressed in this work. Validation of this keyword spotting model was done using widely acclaimed Cepstral features. The experimental results indicate the viability of using these perceptually significant features as an augmented feature set in keyword spotting.

  14. Teaching physical activities to students with significant disabilities using video modeling.

    Science.gov (United States)

    Cannella-Malone, Helen I; Mizrachi, Sharona V; Sabielny, Linsey M; Jimenez, Eliseo D

    2013-06-01

    The objective of this study was to examine the effectiveness of video modeling on teaching physical activities to three adolescents with significant disabilities. The study implemented a multiple baseline across six physical activities (three per student): jumping rope, scooter board with cones, ladder drill (i.e., feet going in and out), ladder design (i.e., multiple steps), shuttle run, and disc ride. Additional prompt procedures (i.e., verbal, gestural, visual cues, and modeling) were implemented within the study. After the students mastered the physical activities, we tested to see if they would link the skills together (i.e., complete an obstacle course). All three students made progress learning the physical activities, but only one learned them with video modeling alone (i.e., without error correction). Video modeling can be an effective tool for teaching students with significant disabilities various physical activities, though additional prompting procedures may be needed.

  15. Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

    Directory of Open Access Journals (Sweden)

    Xin Qiao

    2017-09-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

  16. Progressive IRP Models for Power Resources Including EPP

    Directory of Open Access Journals (Sweden)

    Yiping Zhu

    2017-01-01

    Full Text Available In the view of optimizing regional power supply and demand, the paper makes effective planning scheduling of supply and demand side resources including energy efficiency power plant (EPP, to achieve the target of benefit, cost, and environmental constraints. In order to highlight the characteristics of different supply and demand resources in economic, environmental, and carbon constraints, three planning models with progressive constraints are constructed. Results of three models by the same example show that the best solutions to different models are different. The planning model including EPP has obvious advantages considering pollutant and carbon emission constraints, which confirms the advantages of low cost and emissions of EPP. The construction of progressive IRP models for power resources considering EPP has a certain reference value for guiding the planning and layout of EPP within other power resources and achieving cost and environmental objectives.

  17. Progress in wall turbulence 2 understanding and modelling

    CERN Document Server

    Jimenez, Javier; Marusic, Ivan

    2016-01-01

    This is the proceedings of the ERCOFTAC Workshop on Progress in Wall Turbulence: Understanding and Modelling, that was held in Lille, France from June 18 to 20, 2014. The workshop brought together world specialists of near wall turbulence and stimulated exchanges between them around up-to-date theories, experiments, simulations and numerical models. This book contains a coherent collection of recent results on near wall turbulence including theory, new experiments, DNS, and modeling with RANS, LES.The fact that both physical understanding and modeling by different approaches are addressed by the best specialists in a single workshop is original.

  18. Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer

    DEFF Research Database (Denmark)

    See, W; Iversen, P; Wirth, M

    2003-01-01

    To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer.......To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer....

  19. Progression of Pancreatic Adenocarcinoma Is Significantly Impeded with a Combination of Vaccine and COX-2 Inhibition1

    Science.gov (United States)

    Mukherjee, Pinku; Basu, Gargi D.; Tinder, Teresa L.; Subramani, Durai B.; Bradley, Judy M.; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

    2013-01-01

    With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRASG12D mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E2 and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer. PMID:19109152

  20. Modeling of environmentally significant interfaces: Two case studies

    International Nuclear Information System (INIS)

    Williford, R.E.

    2006-01-01

    When some parameters cannot be easily measured experimentally, mathematical models can often be used to deconvolute or interpret data collected on complex systems, such as those characteristic of many environmental problems. These models can help quantify the contributions of various physical or chemical phenomena that contribute to the overall behavior, thereby enabling the scientist to control and manipulate these phenomena, and thus to optimize the performance of the material or device. In the first case study presented here, a model is used to test the hypothesis that oxygen interactions with hydrogen on the catalyst particles of solid oxide fuel cell anodes can sometimes occur a finite distance away from the triple phase boundary (TPB), so that such reactions are not restricted to the TPB as normally assumed. The model may help explain a discrepancy between the observed structure of SOFCs and their performance. The second case study develops a simple physical model that allows engineers to design and control the sizes and shapes of mesopores in silica thin films. Such pore design can be useful for enhancing the selectivity and reactivity of environmental sensors and catalysts. This paper demonstrates the mutually beneficial interactions between experiment and modeling in the solution of a wide range of problems

  1. Multiresolution wavelet-ANN model for significant wave height forecasting.

    Digital Repository Service at National Institute of Oceanography (India)

    Deka, P.C.; Mandal, S.; Prahlada, R.

    Hybrid wavelet artificial neural network (WLNN) has been applied in the present study to forecast significant wave heights (Hs). Here Discrete Wavelet Transformation is used to preprocess the time series data (Hs) prior to Artificial Neural Network...

  2. SIGNIFICANT PROGRESS IN THE DEPLOYMENT OF NEW TECHNOLOGIES FOR THE RETRIEVAL OF HANFORD RADIOACTIVE WASTE STORAGE TANKS

    International Nuclear Information System (INIS)

    RAYMOND RE; DODD RA; CARPENTER KE; STURGES MH

    2008-01-01

    Significant enhancements in the development and deployment of new technologies for removing waste from storage tanks at the Hanford Site have resulted in accelerated progress and reduced costs for tank cleanup. CH2M HILL Hanford Group, Inc. is the U.S. Department of Energy, Office of River Protection's prime contractor responsible for safely storing and retrieving approximately 53 million gallons of highly-radioactive and hazardous waste stored in 177 underground tanks. The waste is stored in 149 older single-shell tanks (SST) and 28 newer double-shell tanks (DST) that are grouped in 18 so-called farms near the center of the Hanford Site, located in southeastern Washington State. Tank contents include materials from years of World-War II and post-war weapons production, which account for 60 percent by volume of the nation's high-level radioactive waste. A key strategy for improved cleanup is the development and deployment of innovative technologies, which enhance worker safety, resolve technical challenges, streamline retrieval processes, and cut project costs and durations. During the past seven years of tank cleanout projects we have encountered conditions and waste chemistry that defy conventional approaches, requiring a variety of new tools and techniques. Through the deployment of advanced technology and the creative application of resources, we are finding ways to accomplish the retrieval process safely, swiftly, and economically. To date, retrieval operations have been completed in seven tanks, including a record six tanks in a two-year period. Retrieval operations are in progress for another three tanks. This paper describes the following tank cleanup technologies deployed at Hanford in the past few years: Modified waste sluicing, High pressure water lance, Mobile retrieval tools, Saltcake dissolution, Vacuum retrieval, Sparging of wastes, Selective dissolution for waste treatment, Oxalic acid dissolution, High-pressure water mixers, Variable height pumps

  3. A Segmented Signal Progression Model for the Modern Streetcar System

    Directory of Open Access Journals (Sweden)

    Baojie Wang

    2015-01-01

    Full Text Available This paper is on the purpose of developing a segmented signal progression model for modern streetcar system. The new method is presented with the following features: (1 the control concept is based on the assumption of only one streetcar line operating along an arterial under a constant headway and no bandwidth demand for streetcar system signal progression; (2 the control unit is defined as a coordinated intersection group associated with several streetcar stations, and the control joints must be streetcar stations; (3 the objective function is built to ensure the two-way streetcar arrival times distributing within the available time of streetcar phase; (4 the available time of streetcar phase is determined by timing schemes, intersection structures, track locations, streetcar speeds, and vehicular accelerations; (5 the streetcar running speed is constant separately whether it is in upstream or downstream route; (6 the streetcar dwell time is preset according to historical data distribution or charging demand. The proposed method is experimentally examined in Hexi New City Streetcar Project in Nanjing, China. In the experimental results, the streetcar system operation and the progression impacts are shown to affect transit and vehicular traffic. The proposed model presents promising outcomes through the design of streetcar system segmented signal progression, in terms of ensuring high streetcar system efficiency and minimizing negative impacts on transit and vehicular traffic.

  4. Model-based setup assistant for progressive tools

    Science.gov (United States)

    Springer, Robert; Gräler, Manuel; Homberg, Werner; Henke, Christian; Trächtler, Ansgar

    2018-05-01

    In the field of production systems, globalization and technological progress lead to increasing requirements regarding part quality, delivery time and costs. Hence, today's production is challenged much more than a few years ago: it has to be very flexible and produce economically small batch sizes to satisfy consumer's demands and avoid unnecessary stock. Furthermore, a trend towards increasing functional integration continues to lead to an ongoing miniaturization of sheet metal components. In the industry of electric connectivity for example, the miniaturized connectors are manufactured by progressive tools, which are usually used for very large batches. These tools are installed in mechanical presses and then set up by a technician, who has to manually adjust a wide range of punch-bending operations. Disturbances like material thickness, temperatures, lubrication or tool wear complicate the setup procedure. In prospect of the increasing demand of production flexibility, this time-consuming process has to be handled more and more often. In this paper, a new approach for a model-based setup assistant is proposed as a solution, which is exemplarily applied in combination with a progressive tool. First, progressive tools, more specifically, their setup process is described and based on that, the challenges are pointed out. As a result, a systematic process to set up the machines is introduced. Following, the process is investigated with an FE-Analysis regarding the effects of the disturbances. In the next step, design of experiments is used to systematically develop a regression model of the system's behaviour. This model is integrated within an optimization in order to calculate optimal machine parameters and the following necessary adjustment of the progressive tool due to the disturbances. Finally, the assistant is tested in a production environment and the results are discussed.

  5. Tumour model with intrusive morphology, progressive phenotypical heterogeneity and memory

    Science.gov (United States)

    Atangana, Abdon; Alqahtani, Rubayyi T.

    2018-03-01

    The model of a tumour, taking into account invasive morphology, progressive phenotypical heterogeneity and also memory, is developed and analyzed in this paper. Three models are investigated: first we consider the model describing the proliferation concentrates in proximity of tumour boundaries, in which the oxygen levels are pronounced. Then we consider the model where the oxygen around the tumour is considered to be unchanged by the vascular system. Finally, we investigate the model of growth of tumours using the concept of non-local operators with the Mittag-Leffler kernel. We provide the numerical solution using the extended 3/8 Simpson method for the new trends of fractional integration for the proliferation concentrates in the proximity of the tumour model. Then we provide the exact solutions of the Gompertz model with three different fractional differentiations involving power law, exponential decay law and the Mittag-Leffler law.

  6. Significance of matrix diagonalization in modelling inelastic electron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Z. [University of Ulm, Ulm 89081 (Germany); Hambach, R. [University of Ulm, Ulm 89081 (Germany); University of Jena, Jena 07743 (Germany); Kaiser, U.; Rose, H. [University of Ulm, Ulm 89081 (Germany)

    2017-04-15

    Electron scattering is always applied as one of the routines to investigate nanostructures. Nowadays the development of hardware offers more and more prospect for this technique. For example imaging nanostructures with inelastic scattered electrons may allow to produce component-sensitive images with atomic resolution. Modelling inelastic electron scattering is therefore essential for interpreting these images. The main obstacle to study inelastic scattering problem is its complexity. During inelastic scattering, incident electrons entangle with objects, and the description of this process involves a multidimensional array. Since the simulation usually involves fourdimensional Fourier transforms, the computation is highly inefficient. In this work we have offered one solution to handle the multidimensional problem. By transforming a high dimensional array into twodimensional array, we are able to perform matrix diagonalization and approximate the original multidimensional array with its twodimensional eigenvectors. Our procedure reduces the complicated multidimensional problem to a twodimensional problem. In addition, it minimizes the number of twodimensional problems. This method is very useful for studying multiple inelastic scattering. - Highlights: • 4D problems are involved in modelling inelastic electron scattering. • By means of matrix diagonalization, the 4D problems can be simplified as 2D problems. • The number of 2D problems is minimized by using this approach.

  7. Progress in integrated energy-economy-environment model system development

    International Nuclear Information System (INIS)

    Yasukawa, Shigeru; Mankin, Shuichi; Sato, Osamu; Tadokoro, Yoshihiro; Nakano, Yasuyuki; Nagano, Takao

    1987-11-01

    The Integrated Energy-Economy-Environment Model System has been developed for providing analytical tools for the system analysis and technology assessments in the field of nuclear research and development. This model system consists of the following four model groups. The first model block installs 5 models and can serve to analyze and generate long-term scenarios on economy-energy-environment evolution. The second model block installs 2 models and can serve to analyze the structural transition phenomena in energy-economy-environment interactions. The third model block installs 2 models and can handle power reactor installation strategy problem and long-term fuel cycle analysis. The fourth model block installs 5 models and codes and can treats cost-benefit-risk analysis and assessments. This report describes mainly the progress and the outlines of application of the model system in these years after the first report on the research and development of the model system (JAERI-M 84 - 139). (author)

  8. Progressive Damage Modeling of Durable Bonded Joint Technology

    Science.gov (United States)

    Leone, Frank A.; Davila, Carlos G.; Lin, Shih-Yung; Smeltzer, Stan; Girolamo, Donato; Ghose, Sayata; Guzman, Juan C.; McCarville, Duglas A.

    2013-01-01

    The development of durable bonded joint technology for assembling composite structures for launch vehicles is being pursued for the U.S. Space Launch System. The present work is related to the development and application of progressive damage modeling techniques to bonded joint technology applicable to a wide range of sandwich structures for a Heavy Lift Launch Vehicle. The joint designs studied in this work include a conventional composite splice joint and a NASA-patented Durable Redundant Joint. Both designs involve a honeycomb sandwich with carbon/epoxy facesheets joined with adhesively bonded doublers. Progressive damage modeling allows for the prediction of the initiation and evolution of damage. For structures that include multiple materials, the number of potential failure mechanisms that must be considered increases the complexity of the analyses. Potential failure mechanisms include fiber fracture, matrix cracking, delamination, core crushing, adhesive failure, and their interactions. The joints were modeled using Abaqus parametric finite element models, in which damage was modeled with user-written subroutines. Each ply was meshed discretely, and layers of cohesive elements were used to account for delaminations and to model the adhesive layers. Good correlation with experimental results was achieved both in terms of load-displacement history and predicted failure mechanisms.

  9. Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study.

    Science.gov (United States)

    Chang, Su-Hsin; Luo, Suhong; O'Brian, Katiuscia K; Thomas, Theodore S; Colditz, Graham A; Carlsson, Nils P; Carson, Kenneth R

    2015-01-01

    Multiple myeloma is one of the most common haematological malignancies in the USA and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). We aimed to assess the association between metformin use and progression of MGUS to multiple myeloma. We did a retrospective cohort study of patients registered in the US Veterans Health Administration database and diagnosed with MGUS between Oct 1, 1999, and Dec 31, 2009. We included patients (aged >18 years) with at least one International Classification of Diseases (9th revision) code for diabetes mellitus and one treatment for their diabetes before MGUS diagnosis. We reviewed patient-level clinical data to verify diagnoses and extract any available data for size of baseline M-protein and type of MGUS. We defined metformin users as patients with diabetes who were given metformin consistently for 4 years after their diabetes diagnosis and before multiple myeloma development, death, or censorship. Our primary outcome was time from MGUS diagnosis to multiple myeloma diagnosis. We used Kaplan-Meier curves and Cox models to analyse the association between metformin use and MGUS progression. We obtained data for 3287 patients, of whom 2003 (61%) were included in the final analytical cohort. Median follow-up was 69 months (IQR 49–96). 463 (23%) participants were metformin users and 1540 (77%) participants were non-users. 13 (3%) metformin users progressed to multiple myeloma compared with 74 (5%) non-users. After adjustment, metformin use was associated with a reduced risk of progression to multiple myeloma (hazard ratio 0·47, 95% CI 0·25–0·87). For patients with diabetes diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of progression of MGUS to multiple myeloma. Prospective studies are needed to establish whether this association is causal and whether these results can be extrapolated to non-diabetic individuals. Barnes-Jewish Hospital Foundation

  10. Computational algebraic geometry for statistical modeling FY09Q2 progress.

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, David C.; Rojas, Joseph Maurice; Pebay, Philippe Pierre

    2009-03-01

    This is a progress report on polynomial system solving for statistical modeling. This is a progress report on polynomial system solving for statistical modeling. This quarter we have developed our first model of shock response data and an algorithm for identifying the chamber cone containing a polynomial system in n variables with n+k terms within polynomial time - a significant improvement over previous algorithms, all having exponential worst-case complexity. We have implemented and verified the chamber cone algorithm for n+3 and are working to extend the implementation to handle arbitrary k. Later sections of this report explain chamber cones in more detail; the next section provides an overview of the project and how the current progress fits into it.

  11. Progress towards localization in the attractive Hubbard model

    Science.gov (United States)

    Morong, W.; Xu, W.; Demarco, B.

    2017-04-01

    The interplay between fermionic superfluidity and disorder is a topic of long-standing interest that has recently come within reach of ultracold gas experiments. Outstanding questions include the fate of Cooper pairs in a localized superfluid and the effect of disorder on the superfluid transition temperature. We report progress on tackling this problem using a realization of the Hubbard model with attractive interactions. Our system consists of two spin states of fermionic potassium-40 trapped in a cubic optical lattice. Disorder is introduced using an optical speckle potential, and interactions are controlled via a Feshbach resonance. We study the binding and unbinding of Cooper pairs in this system using rf spectroscopy, changes in Tc by measuring the condensate fraction, and transport properties by observing the response to an applied impulse. We will discuss progress towards these measurements.

  12. Progress in tritium retention and release modeling for ceramic breeders

    International Nuclear Information System (INIS)

    Raffray, A.R.; Federici, G.; Billone, M.C.; Tanaka, S.

    1994-01-01

    Tritium behavior in ceramic breeder blankets is a key design issue for this class of blanket because of its impact on safety and fuel self-sufficiency. Over the past 10-15 years, substantial theoretical and experimental efforts have been dedicated world-wide to develop a better understanding of tritium transport in ceramic breeders. Models that are available today seem to cover reasonably well all the key physical transport and trapping mechanisms. They have allowed for reasonable interpretation and reproduction of experimental data and have helped in pointing out deficiencies in material property data base, in providing guidance for future experiments, and in analyzing blanket tritium behavior. This paper highlights the progress in tritium modeling over the last decade. Key tritium transport mechanisms are briefly described along with the more recent and sophisticated models developed to help understand them. Recent experimental data are highlighted and model calibration and validation discussed. Finally, example applications to blanket cases are shown as illustration of progress in the prediction of ceramic breeder blanket tritium inventory

  13. The complex model of risk and progression of AMD estimation

    Directory of Open Access Journals (Sweden)

    V. S. Akopyan

    2012-01-01

    Full Text Available Purpose: to develop a method and a statistical model to estimate individual risk of AMD and the risk for progression to advanced AMD using clinical and genetic risk factors.Methods: A statistical risk assessment model was developed using stepwise binary logistic regression analysis. to estimate the population differences in the prevalence of allelic variants of genes and for the development of models adapted to the population of Moscow region genotyping and assessment of the influence of other risk factors was performed in two groups: patients with differ- ent stages of AMD (n = 74, and control group (n = 116. Genetic risk factors included in the study: polymorphisms in the complement system genes (C3 and CFH, genes at 10q26 locus (ARMS2 and HtRA1, polymorphism in the mitochondrial gene Mt-ND2. Clinical risk factors included in the study: age, gender, high body mass index, smoking history.Results: A comprehensive analysis of genetic and clinical risk factors for AMD in the study group was performed. Compiled statis- tical model assessment of individual risk of AMD, the sensitivity of the model — 66.7%, specificity — 78.5%, AUC = 0.76. Risk factors of late AMD, compiled a statistical model describing the probability of late AMD, the sensitivity of the model — 66.7%, specificity — 78.3%, AUC = 0.73. the developed system allows determining the most likely version of the current late AMD: dry or wet.Conclusion: the developed test system and the mathematical algorhythm for determining the risk of AMD, risk of progression to advanced AMD have fair diagnostic informative and promising for use in clinical practice.

  14. A model to predict progression in brain-injured patients.

    Science.gov (United States)

    Tommasino, N; Forteza, D; Godino, M; Mizraji, R; Alvarez, I

    2014-11-01

    The study of brain death (BD) epidemiology and the acute brain injury (ABI) progression profile is important to improve public health programs, organ procurement strategies, and intensive care unit (ICU) protocols. The purpose of this study was to analyze the ABI progression profile among patients admitted to ICUs with a Glasgow Coma Score (GCS) ≤8, as well as establishing a prediction model of probability of death and BD. This was a retrospective analysis of prospective data that included all brain-injured patients with GCS ≤8 admitted to a total of four public and private ICUs in Uruguay (N = 1447). The independent predictor factors of death and BD were studied using logistic regression analysis. A hierarchical model consisting of 2 nested logit regression models was then created. With these models, the probabilities of death, BD, and death by cardiorespiratory arrest were analyzed. In the first regression, we observed that as the GCS decreased and age increased, the probability of death rose. Each additional year of age increased the probability of death by 0.014. In the second model, however, BD risk decreased with each year of age. The presence of swelling, mass effect, and/or space-occupying lesion increased BD risk for the same given GCS. In the presence of injuries compatible with intracranial hypertension, age behaved as a protective factor that reduced the probability of BD. Based on the analysis of the local epidemiology, a model to predict the probability of death and BD can be developed. The organ potential donation of a country, region, or hospital can be predicted on the basis of this model, customizing it to each specific situation.

  15. A new model of progressive pulmonary fibrosis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. (Univ. of California, Davis (United States))

    1993-08-01

    Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

  16. Modeling and Predicting AD Progression by Regression Analysis of Sequential Clinical Data

    KAUST Repository

    Xie, Qing

    2016-02-23

    Alzheimer\\'s Disease (AD) is currently attracting much attention in elders\\' care. As the increasing availability of massive clinical diagnosis data, especially the medical images of brain scan, it is highly significant to precisely identify and predict the potential AD\\'s progression based on the knowledge in the diagnosis data. In this paper, we follow a novel sequential learning framework to model the disease progression for AD patients\\' care. Different from the conventional approaches using only initial or static diagnosis data to model the disease progression for different durations, we design a score-involved approach and make use of the sequential diagnosis information in different disease stages to jointly simulate the disease progression. The actual clinical scores are utilized in progress to make the prediction more pertinent and reliable. We examined our approach by extensive experiments on the clinical data provided by the Alzheimer\\'s Disease Neuroimaging Initiative (ADNI). The results indicate that the proposed approach is more effective to simulate and predict the disease progression compared with the existing methods.

  17. Modeling and Predicting AD Progression by Regression Analysis of Sequential Clinical Data

    KAUST Repository

    Xie, Qing; Wang, Su; Zhu, Jia; Zhang, Xiangliang

    2016-01-01

    Alzheimer's Disease (AD) is currently attracting much attention in elders' care. As the increasing availability of massive clinical diagnosis data, especially the medical images of brain scan, it is highly significant to precisely identify and predict the potential AD's progression based on the knowledge in the diagnosis data. In this paper, we follow a novel sequential learning framework to model the disease progression for AD patients' care. Different from the conventional approaches using only initial or static diagnosis data to model the disease progression for different durations, we design a score-involved approach and make use of the sequential diagnosis information in different disease stages to jointly simulate the disease progression. The actual clinical scores are utilized in progress to make the prediction more pertinent and reliable. We examined our approach by extensive experiments on the clinical data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI). The results indicate that the proposed approach is more effective to simulate and predict the disease progression compared with the existing methods.

  18. A MATHEMATICAL MODEL OF CHP 2000 TYPE PROGRESSIVE GEAR

    Directory of Open Access Journals (Sweden)

    Paweł Lonkwic

    2016-12-01

    Full Text Available The project of CHP2000 type progressive gear has been presented in the article. The offered solution from its construction point of view differs from the existing solutions due to the application of Belleville springs packets supporting the braking roller cam and achieving a flexible range of the gear loading. The standard concept of the gear loading within a mathematical and a geometrical model has been presented in the article. The proposed solution can be used in the friction lifts with the loading capacity from 8500 up to 20000 N.

  19. 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.

  20. 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

  1. 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.

  2. Significant uncertainty in global scale hydrological modeling from precipitation data errors

    Science.gov (United States)

    Sperna Weiland, Frederiek C.; Vrugt, Jasper A.; van Beek, Rens (L.) P. H.; Weerts, Albrecht H.; Bierkens, Marc F. P.

    2015-10-01

    In the past decades significant progress has been made in the fitting of hydrologic models to data. Most of this work has focused on simple, CPU-efficient, lumped hydrologic models using discharge, water table depth, soil moisture, or tracer data from relatively small river basins. In this paper, we focus on large-scale hydrologic modeling and analyze the effect of parameter and rainfall data uncertainty on simulated discharge dynamics with the global hydrologic model PCR-GLOBWB. We use three rainfall data products; the CFSR reanalysis, the ERA-Interim reanalysis, and a combined ERA-40 reanalysis and CRU dataset. Parameter uncertainty is derived from Latin Hypercube Sampling (LHS) using monthly discharge data from five of the largest river systems in the world. Our results demonstrate that the default parameterization of PCR-GLOBWB, derived from global datasets, can be improved by calibrating the model against monthly discharge observations. Yet, it is difficult to find a single parameterization of PCR-GLOBWB that works well for all of the five river basins considered herein and shows consistent performance during both the calibration and evaluation period. Still there may be possibilities for regionalization based on catchment similarities. Our simulations illustrate that parameter uncertainty constitutes only a minor part of predictive uncertainty. Thus, the apparent dichotomy between simulations of global-scale hydrologic behavior and actual data cannot be resolved by simply increasing the model complexity of PCR-GLOBWB and resolving sub-grid processes. Instead, it would be more productive to improve the characterization of global rainfall amounts at spatial resolutions of 0.5° and smaller.

  3. A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Mao Yu

    2009-07-01

    Full Text Available Abstract Background The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. Results In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method. This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS and Progression Score (PS in progression analysis, True Positive Rate (TPR in gene pair analysis, and Pathway Enrichment Score (PES in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From

  4. Is organizational progress in the EFQM model related to employee satisfaction?

    Science.gov (United States)

    Matthies-Baraibar, Carmen; Arcelay-Salazar, Andoni; Cantero-González, David; Colina-Alonso, Alberto; García-Urbaneja, Marbella; González-Llinares, Rosa María; Letona-Aranburu, Jon; Martínez-Carazo, Catalina; Mateos-Del Pino, Maider; Nuño-Solinís, Roberto; Olaetxea-Urizar, Esther; de la Rica-Giménez, José Antonio; Rodríguez-González, María Angeles; Dabouza-Acebal, Silvia

    2014-10-24

    To determine whether there is greater employee satisfaction in organisations that have made more progress in implementation of the European Foundation for Quality Management (EFQM) model. A series of cross-sectional studies (one for each assessment cycle) comparing staff satisfaction survey results between groups of healthcare organisations by degree of implementation of the EFQM model (assessed in terms of external recognition of management quality in each organisation). 30 healthcare organisations including hospitals, primary care and mental health providers in Osakidetza, the Basque public health service. Employees of 30 Osakidetza organisations. Progress in implementation of EFQM model. Scores in 9 dimensions of employee satisfaction from questionnaires administered in healthcare organisations in 4 assessment cycles between 2001 and 2010. Comparing satisfaction results in organisations granted Gold or Silver Q Awards and those without this type of external recognition, we found statistically significant differences in the dimensions of training and internal communication. Then, comparing recipients of Gold Q Awards with those with no Q Certification, differences in leadership style and in policy and strategy also emerged as significant. Progress of healthcare organisations in the implementation of the EFQM Excellence Model is associated with increases in their employee satisfaction in dimensions that can be managed at the level of each organisation, while dimensions in which no statistically significant differences were found represent common organisational elements with little scope for self-management.

  5. Models and correlations of the DEBRIS Late-Phase Melt Progression Model

    International Nuclear Information System (INIS)

    Schmidt, R.C.; Gasser, R.D.

    1997-09-01

    The DEBRIS Late Phase Melt Progression Model is an assembly of models, embodied in a computer code, which is designed to treat late-phase melt progression in dry rubble (or debris) regions that can form as a consequence of a severe core uncover accident in a commercial light water nuclear reactor. The approach is fully two-dimensional, and incorporates a porous medium modeling framework together with conservation and constitutive relationships to simulate the time-dependent evolution of such regions as various physical processes act upon the materials. The objective of the code is to accurately model these processes so that the late-phase melt progression that would occur in different hypothetical severe nuclear reactor accidents can be better understood and characterized. In this report the models and correlations incorporated and used within the current version of DEBRIS are described. These include the global conservation equations solved, heat transfer and fission heating models, melting and refreezing models (including material interactions), liquid and solid relocation models, gas flow and pressure field models, and the temperature and compositionally dependent material properties employed. The specific models described here have been used in the experiment design analysis of the Phebus FPT-4 debris-bed fission-product release experiment. An earlier DEBRIS code version was used to analyze the MP-1 and MP-2 late-phase melt progression experiments conducted at Sandia National Laboratories for the US Nuclear Regulatory Commission

  6. 2D model for melt progression through rods and debris

    International Nuclear Information System (INIS)

    Fichot, F.

    2001-01-01

    During the degradation of a nuclear core in a severe accident scenario, the high temperatures reached lead to the melting of materials. The formation of liquid mixtures at various elevations is followed by the flow of molten materials through the core. Liquid mixture may flow under several configurations: axial relocation along the rods, horizontal motion over a plane surface such as the core support plate or a blockage of material, 2D relocation through a debris bed, etc.. The two-dimensional relocation of molten material through a porous debris bed, implemented for the simulation of late degradation phases, has opened a new way to the elaboration of the relocation model for the flow of liquid mixture along the rods. It is based on a volume averaging method, where wall friction and capillary effects are taken into account by introducing effective coefficients to characterize the solid matrix (rods, grids, debris, etc.). A local description of the liquid flow is necessary to derive the effective coefficients. Heat transfers are modelled in a similar way. The derivation of the conservation equations for the liquid mixture falling flow (momentum) in two directions (axial and radial-horizontal) and for the heat exchanges (energy) are the main points of this new model for simulating melt progression. In this presentation, the full model for the relocation and solidification of liquid materials through a rod bundle or a debris bed is described. It is implemented in the ICARE/CATHARE code, developed by IPSN in Cadarache. The main improvements and advantages of the new model are: A single formulation for liquid mixture relocation, in 2D, either through a rod bundle or a porous debris bed, Extensions to complex structures (grids, by-pass, etc..), The modeling of relocation of a liquid mixture over plane surfaces. (author)

  7. PET studies of brain energy metabolism in a model of subcortical dementia: progressive supranuclear Palsy

    International Nuclear Information System (INIS)

    Blin, J.; Baron, J.C.; Cambon, H.

    1988-01-01

    In 41 patients with clinically determined Progressive Supranuclear Palsy, a model of degenerative subcortical dementia, alterations in regional brain energy metabolism with respect to control subjects have been investigated using positron computed tomography and correlated to clinical and neuropsychological scores. A generalized significant reduction in brain metabolism was found, which predominated in the prefrontal cortex in accordance with, and statistically correlated to, the frontal neuropsychological score

  8. Maximum standard uptake value on pre-chemotherapeutic FDG-PET is a significant parameter for disease progression of newly diagnosed lymphoma

    International Nuclear Information System (INIS)

    Eo, Jae Seon; Lee, Won Woo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

    2005-01-01

    F-18 FDG-PET is useful for detection and staging of lymphoma. We investigated the prognostic significance of maximum standard uptake (maxSUV) value of FDG-PET for newly diagnosed lymphoma patients before chemotherapy. Twenty-seven patients (male: female = 17: 10: age: 49±19 years) with newly diagnosed lymphoma were enrolled. Nine-teen patients suffered from B cell lymphoma, 6 Hodgkins disease and 2 T cell lymphoma. One patient was stage I, 9 stage II, 3 stage III, 1 stage IV and 13 others. All patients underwent FDG-PET before initiation of chemotherapy. MaxSUV values using lean body weight were obtained for main and largest lesion to represent maxSUV of the patients. The disease progression was defined as total change of the chemotherapeutic regimen or addition of new chemotherapeutic agent during follow up period. The observed period was 389±224 days. The value of maxSUV ranged from 3 to 18 (mean±SD = 10.6±4.4). The disease progressions occurred in 6 patients. Using Cox proportional-hazard regression analysis, maxSUV was identified as a significant parameter for the disease progression free survival (p=0.044). Kaplan-Meier survival curve analysis revealed that the group with higher maxSUV (=10.6, n=5) suffered from shorter disease progression free survival (median 299 days) than the group with lower maxSUV (<10.6, n = 22) (median 378 days, p=0.0146). We found that maxSUV on pre-chemotherapeutic F-18 FDG-PET for newly diagnosed lymphoma patients is a significant parameter for disease progression. Lymphoma patients can be stratified before initiation of chemotherapy in terms of disease progression by the value of maxSUV 10.6

  9. Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

    Directory of Open Access Journals (Sweden)

    Flavia Mattioli

    Full Text Available Previous studies reported that Multiple Sclerosis (MS patients treated with natalizumab for one or two years exhibit a significant reduction in relapse rate and in cognitive impairment, but the long term effects on cognitive performance are unknown. This study aimed to evaluate the effects of natalizumab on cognitive impairment in a cohort of 24 consecutive patients with relapsing remitting MS treated for 3 years. The neuropsychological tests, as well as relapse number and EDSS, were assessed at baseline and yearly for three years. The impact on cortical atrophy was also considered in a subgroup of them, and are thus to be considered as preliminary. Results showed a significant reduction in the number of impaired neuropsychological tests after three years, a significant decrease in annualized relapse rate at each time points compared to baseline and a stable EDSS. In the neuropsychological assessment, a significant improvement in memory, attention and executive function test scores was detected. Preliminary MRI data show that, while GM volume did not change at 3 years, a significantly greater parahippocampal and prefrontal gray matter density was noticed, the former correlating with neuropsychological improvement in a memory test. This study showed that therapy with Natalizumab is helpful in improving cognitive performance, and is likely to have a protective role on grey matter, over a three years follow-up.

  10. Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Tsung-Yi Huang

    2015-06-01

    Full Text Available It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2 and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene

  11. Significance of Selective Predation and Development of Prey Protection Measures for Juvenile Salmonids in the Columbia and Snake River Reservoirs: Annual Progress Report, February 1991-February 1992.

    Energy Technology Data Exchange (ETDEWEB)

    Poe, Thomas P.

    1992-12-31

    This document is the 1991 annual report of progress for the Bonneville Power Administration (BPA) research Project conducted by the US Fish and Wildlife Service (FWS). Our approach was to present the progress achieved during 1991 in a series of separate reports for each major project task. Each report is prepared in the format of a scientific paper and is able to stand alone, whatever the state of progress or completion. This project has two major goals. One is to understand the significance of selective predation and prey vulnerability by determining if substandard juvenile salmonids (dead, injured, stressed, diseased, or naive) are more vulnerable to predation by northern squawfish, than standard or normal juvenile salmonids. The second goal is to develop and test prey protection measures to control predation on juvenile salmonids by reducing predator-smolt encounters or predator capture efficiency.

  12. Enforcement actions: Significant actions resolved -- individual actions. Semiannual progress report, July--December 1997; Volume 16, Number 2, Part 1

    International Nuclear Information System (INIS)

    1998-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1997) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions

  13. Significance of coagulase negative Staphylococcus from blood cultures: persisting problems and partial progress in resource constrained settings.

    Science.gov (United States)

    Sidhu, Shailpreet K; Malhotra, Sita; Devi, Pushpa; Tuli, Arpandeep K

    2016-12-01

    Coagulase negative Staphylococcus (CoNS) is frequently isolated from blood cultures but their significance is difficult to interpret. CoNS bacteria which are often previously dismissed as culture contaminants are attracting greater importance as true pathogens in the past decades. Clinical evaluation of these isolates suggests that although there is a relative increase of CoNS associated bloodstream infections in recent years, the microorganisms still remain the most common contaminants in blood cultures. The objective of this study was to determine the significance of CoNS isolated from blood cultures. A retrospective study was conducted to evaluate the rate of contamination in blood cultures in a tertiary care hospital. The paired specimens of blood were cultured using conventional culture methods and the isolates of coagulase negative staphylococci were identified by standard methodology. Clinical data, laboratory indices, microbiological parameters and patient characteristics were analyzed. Of 3503 blood samples, CoNS were isolated from blood culture of 307 patients (8.76%). The isolates were reported as true pathogens of bloodstream infections in only 74 out of 307 cases (24.1%). In the vast majority, 212 of 307 (69.0%), they were mere blood culture contaminants and reported as insignificant/contaminant. Determining whether a growth in the blood culture is a pathogen or a contaminant is a critical issue and multiple parameters have to be considered before arriving at a conclusion. Ideally, the molecular approach is for the most part a consistent method in determining the significant isolates of CoNS. However, in countries with inadequate resources, species identification and antibiogram tests are recommended when determining significance of these isolates.

  14. Enforcement actions: Significant actions resolved. Volume 14, No. 2, Part 1: Individual actions. Quarterly progress report, April--June 1995

    International Nuclear Information System (INIS)

    1995-01-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1995) and includes copies of Orders sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions

  15. Enforcement actions: Significant actions resolved. Volume 14, No. 2, Part 1: Individual actions. Quarterly progress report, April--June 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1995) and includes copies of Orders sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions.

  16. Enforcement actions: Significant actions resolved -- individual actions. Semiannual progress report, July--December 1997; Volume 16, Number 2, Part 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1997) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions.

  17. Enforcement actions: Significant actions resolved medical licensees. Quarterly progress report, January 1995--March 1995. Volume 14, No. 1, Part 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January-March 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to medical licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  18. Enforcement actions: Significant actions resolved material licensees (non-medical). Quarterly progress report, October 1994--December 1994

    International Nuclear Information System (INIS)

    1995-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1994) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees (non-medical) with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Enforcement actions: Significant actions resolved reactor licensees. Quarterly progress report, October--December 1994, Volume 13, No. 4, Part 1

    International Nuclear Information System (INIS)

    1995-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1994) and includes copies of letters Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Enforcement actions: Significant actions resolved, reactor licensees. Quarterly progress report, July--September 1994; Volume 13, Number 3, Part 1

    International Nuclear Information System (INIS)

    1994-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1994) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  1. Enforcement actions: Significant actions resolved. Reactor licensees: Volume 14, No. 1, Part 1, Quarterly progress report January--March 1995

    International Nuclear Information System (INIS)

    1995-01-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  2. Enforcement actions: Significant actions resolved, medical licensees. Quarterly progress report, July--September 1994: Volume 13, Number 3, Part 2

    International Nuclear Information System (INIS)

    1994-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1994) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to medical licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  3. Enforcement actions: Significant actions resolved medical licensees. Quarterly progress report, January 1995--March 1995. Volume 14, No. 1, Part 2

    International Nuclear Information System (INIS)

    1995-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January-March 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to medical licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  4. Enforcement actions: Significant actions resolved, reactor licensees. Semiannual progress report, July--December 1997; Volume 16, Number 2, Part 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1997) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  5. Enforcement actions: Significant actions resolved, material licensees. Semiannual progress report, July--December 1997; Volume 16, Number 2, Part 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1997) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  6. Enforcement actions: Significant actions resolved material licensees (non-medical). Quarterly progress report, October 1994--December 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1994) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees (non-medical) with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  7. Enforcement actions: Significant actions resolved reactor licensees. Volume 14, No. 2, Part 2, Quarterly progress report, April--June 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  8. Enforcement actions: Significant actions resolved reactor licensees. Quarterly progress report, October--December 1994, Volume 13, No. 4, Part 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1994) and includes copies of letters Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  9. Enforcement actions: Significant actions resolved reactor licensees. Volume 14, No. 2, Part 2, Quarterly progress report, April--June 1995

    International Nuclear Information System (INIS)

    1995-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  10. Enforcement actions: Significant actions resolved, material licensees. Semiannual progress report, July--December 1997; Volume 16, Number 2, Part 3

    International Nuclear Information System (INIS)

    1998-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1997) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  11. Enforcement actions: Significant actions resolved reactor licensees. Volume 13, No. 1, Part 1: Quarterly progress report, January--March 1994

    International Nuclear Information System (INIS)

    1994-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1994) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to these described in this publication

  12. Enforcement actions: Significant actions resolved, reactor licensees. Semiannual progress report, January--June 1997; Volume 16, Number 1, Part 2

    International Nuclear Information System (INIS)

    1997-09-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (January--June 1997) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  13. Enforcement actions: Significant actions resolved, reactor licensees. Semiannual progress report, July--December 1997; Volume 16, Number 2, Part 2

    International Nuclear Information System (INIS)

    1998-04-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1997) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  14. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    International Nuclear Information System (INIS)

    Hillman, Gilda G; Wang, Yu; Che, Mingxin; Raffoul, Julian J; Yudelev, Mark; Kucuk, Omer; Sarkar, Fazlul H

    2007-01-01

    We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more

  15. The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

    Directory of Open Access Journals (Sweden)

    Jackalina M Van Kampen

    Full Text Available The development of effective neuroprotective therapies for Parkinson's disease (PD has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the

  16. Atypical squamous cells of undetermined significance in patients with HPV positive DNA testing and correlation with disease progression by age group: an institutional experience.

    Science.gov (United States)

    Rodriguez, Erika F; Reynolds, Jordan P; Jenkins, Sarah M; Winter, Stephanie M; Henry, Michael R; Nassar, Aziza

    2012-01-01

    Atypical squamous cells of undetermined significance (ASC-US) is a broad diagnostic category that could be attributed to human papillomavirus infection (HPV), malignant neoplasia and reactive conditions. We evaluated our institutional experience with ASC-US in women who are positive for high risk HPV (HRHPV+) by the Digene hybrid capture method from 2005-2009 to identify the risk of progression to squamous intraepithelial lesion (SIL) and cervical intraepithelial neoplasia (CIN) in association with age. We reviewed cytologic and follow-up surgical pathology reports for all specimens available. Progression was defined as a diagnosis of at least CINI on follow-up biopsy or resection or SIL on cytology. We identified 2613 cases and follow-up was available in 1839 (70.4%). Of these 74.2% had just one follow-up, 16.2% had a total of 2 follow-ups, 5.3% had a total of 3 follow-ups, and the remaining had as many as 6 follow-ups. Among the 1839 patients, 69.4% were age 30 or younger, 16.0% were between 31 to 40, 9.0% were between 41 to 50, and 5.6% were 51 or older. Among these, 25-30% progressed to dysplasia. The risk of progression varied by age (p=0.04) and was lowest among women between the ages of 41-50. Our findings highlight the importance of continued cytologic follow-up in women with HRHPV+ ASC-US in order to detect progression of disease, although the risk of progression is age dependent.

  17. Changes in gene expression and cellular architecture in an ovarian cancer progression model.

    Directory of Open Access Journals (Sweden)

    Amy L Creekmore

    Full Text Available BACKGROUND: Ovarian cancer is the fifth leading cause of cancer deaths among women. Early stage disease often remains undetected due the lack of symptoms and reliable biomarkers. The identification of early genetic changes could provide insights into novel signaling pathways that may be exploited for early detection and treatment. METHODOLOGY/PRINCIPAL FINDINGS: Mouse ovarian surface epithelial (MOSE cells were used to identify stage-dependent changes in gene expression levels and signal transduction pathways by mouse whole genome microarray analyses and gene ontology. These cells have undergone spontaneous transformation in cell culture and transitioned from non-tumorigenic to intermediate and aggressive, malignant phenotypes. Significantly changed genes were overrepresented in a number of pathways, most notably the cytoskeleton functional category. Concurrent with gene expression changes, the cytoskeletal architecture became progressively disorganized, resulting in aberrant expression or subcellular distribution of key cytoskeletal regulatory proteins (focal adhesion kinase, α-actinin, and vinculin. The cytoskeletal disorganization was accompanied by altered patterns of serine and tyrosine phosphorylation as well as changed expression and subcellular localization of integral signaling intermediates APC and PKCβII. CONCLUSIONS/SIGNIFICANCE: Our studies have identified genes that are aberrantly expressed during MOSE cell neoplastic progression. We show that early stage dysregulation of actin microfilaments is followed by progressive disorganization of microtubules and intermediate filaments at later stages. These stage-specific, step-wise changes provide further insights into the time and spatial sequence of events that lead to the fully transformed state since these changes are also observed in aggressive human ovarian cancer cell lines independent of their histological type. Moreover, our studies support a link between aberrant cytoskeleton

  18. Direct modeling of regression effects for transition probabilities in the progressive illness-death model

    DEFF Research Database (Denmark)

    Azarang, Leyla; Scheike, Thomas; de Uña-Álvarez, Jacobo

    2017-01-01

    In this work, we present direct regression analysis for the transition probabilities in the possibly non-Markov progressive illness–death model. The method is based on binomial regression, where the response is the indicator of the occupancy for the given state along time. Randomly weighted score...

  19. Malignant progressive tumor cell clone exhibits significant up-regulation of cofilin-2 and 27-kDa modified form of cofilin-1 compared to regressive clone.

    Science.gov (United States)

    Kuramitsu, Yasuhiro; Wang, Yufeng; Okada, Futoshi; Baron, Byron; Tokuda, Kazuhiro; Kitagawa, Takao; Akada, Junko; Nakamura, Kazuyuki

    2013-09-01

    QR-32 is a regressive murine fibrosarcoma cell clone which cannot grow when they are transplanted in mice; QRsP-11 is a progressive malignant tumor cell clone derived from QR-32 which shows strong tumorigenicity. A recent study showed there to be differentially expressed up-regulated and down-regulated proteins in these cells, which were identified by proteomic differential display analyses by using two-dimensional gel electrophoresis and mass spectrometry. Cofilins are small proteins of less than 20 kDa. Their function is the regulation of actin assembly. Cofilin-1 is a small ubiquitous protein, and regulates actin dynamics by means of binding to actin filaments. Cofilin-1 plays roles in cell migration, proliferation and phagocytosis. Cofilin-2 is also a small protein, but it is mainly expressed in skeletal and cardiac muscles. There are many reports showing the positive correlation between the level of cofilin-1 and cancer progression. We have also reported an increased expression of cofilin-1 in pancreatic cancer tissues compared to adjacent paired normal tissues. On the other hand, cofilin-2 was significantly less expressed in pancreatic cancer tissues. Therefore, the present study investigated the comparison of the levels of cofilin-1 and cofilin-2 in regressive QR-32 and progressive QRsP-11cells by western blotting. Cofilin-2 was significantly up-regulated in QRsP-11 compared to QR-32 cells (p<0.001). On the other hand, the difference of the intensities of the bands of cofilin-1 (18 kDa) in QR-32 and QRsP-11 was not significant. However, bands of 27 kDa showed a quite different intensity between QR-32 and QRsP-11, with much higher intensities in QRsP-11 compared to QR-32 (p<0.001). These results suggested that the 27-kDa protein recognized by the antibody against cofilin-1 is a possible biomarker for progressive tumor cells.

  20. Developing and validating a predictive model for stroke progression

    OpenAIRE

    Craig, L.E.; Wu, Olivia; Gilmour, H.; Barber, M.; Langhorne, P.

    2011-01-01

    Background: Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. \\ud \\ud Methods: Two patient cohorts were used for this study – the first cohort formed the trainin...

  1. Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression.

    Science.gov (United States)

    Green, Colin; Shearer, James; Ritchie, Craig W; Zajicek, John P

    2011-01-01

    To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD. A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review. The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD. Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  2. Chronic Progressive Neurodegeneration in a transgenic mouse model of Prion disease

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2016-11-01

    Full Text Available Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic protein without accompanying neurodegeneration pattern. The lack of a comprehensive model hinders the efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice, mimicking for genetic Creutzfeldt-Jacob disease as compared to age matched wild type mice. Mice exhibited a neurodegenerative process indicated by progressive reduction in cortical neurons and synapses, starting at age of 4-6 months, in accordance with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with progressive neurological disease, indicating these mice can serve as a model for neurodegenerative diseases.

  3. Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion Disease.

    Science.gov (United States)

    Fainstein, Nina; Dori, Dvir; Frid, Kati; Fritz, Alexa T; Shapiro, Ilona; Gabizon, Ruth; Ben-Hur, Tamir

    2016-01-01

    Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic proteins without an accompanying neurodegeneration pattern. The lack of a comprehensive model hinders efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice mimicking for genetic Creutzfeldt-Jacob disease as compared to age-matched wild-type mice. Mice exhibited a neurodegenerative process of progressive reduction in cortical neurons and synapses starting at age of 4-6 months, in accord with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with neurological disease progression, indicating these mice can serve as a model for neurodegenerative diseases.

  4. Dietary folate deficiency blocks prostate cancer progression in the TRAMP model.

    Science.gov (United States)

    Bistulfi, Gaia; Foster, Barbara A; Karasik, Ellen; Gillard, Bryan; Miecznikowski, Jeff; Dhiman, Vineet K; Smiraglia, Dominic J

    2011-11-01

    Dietary folate is essential in all tissues to maintain several metabolite pools and cellular proliferation. Prostate cells, due to specific metabolic characteristics, have increased folate demand to support proliferation and prevent genetic and epigenetic damage. Although several studies have found that dietary folate interventions can affect colon cancer biology in rodent models, its impact on prostate is unknown. The purpose of this study was to determine whether dietary folate manipulation, possibly being of primary importance for prostate epithelial cell metabolism, could significantly affect prostate cancer progression. Strikingly, mild dietary folate depletion arrested prostate cancer progression in 25 of 26 transgenic adenoma of the mouse prostate (TRAMP) mice, in which tumorigenesis is prostate-specific and characteristically aggressive. The significant effect on prostate cancer growth was characterized by size, grade, proliferation, and apoptosis analyses. Folate supplementation had a mild, nonsignificant, beneficial effect on grade. In addition, characterization of folate pools (correlated with serum), metabolite pools (polyamines and nucleotides), genetic and epigenetic damage, and expression of key biosynthetic enzymes in prostate tissue revealed interesting correlations with tumor progression. These findings indicate that prostate cancer is highly sensitive to folate manipulation and suggest that antifolates, paired with current therapeutic strategies, might significantly improve treatment of prostate cancer, the most commonly diagnosed cancer in American men.

  5. Progress in Developing Finite Element Models Replicating Flexural Graphite Testing

    International Nuclear Information System (INIS)

    Bratton, Robert

    2010-01-01

    This report documents the status of flexural strength evaluations from current ASTM procedures and of developing finite element models predicting the probability of failure. This work is covered under QLD REC-00030. Flexural testing procedures of the American Society for Testing and Materials (ASTM) assume a linear elastic material that has the same moduli for tension and compression. Contrary to this assumption, graphite is known to have different moduli for tension and compression. A finite element model was developed and demonstrated that accounts for the difference in moduli tension and compression. Brittle materials such as graphite exhibit significant scatter in tensile strength, so probabilistic design approaches must be used when designing components fabricated from brittle materials. ASTM procedures predicting probability of failure in ceramics were compared to methods from the current version of the ASME graphite core components rules predicting probability of failure. Using the ASTM procedures yields failure curves at lower applied forces than the ASME rules. A journal paper was published in the Journal of Nuclear Engineering and Design exploring the statistical models of fracture in graphite.

  6. Progress in inertial fusion energy modelling at DENIM

    International Nuclear Information System (INIS)

    Velarde, G.; Cabellos, O.; Caturla, M.J.

    2005-01-01

    New results of the jet driven ignition target are presented, both with direct and indirect drive. This target is based on the conical guided target used in fast ignition, but use only one laser pulse. The ignition of the target is started by the impact of a jet produced in the guiding cone, instead of using charged particles generated by a other high power laser. We have shown that a laser or X-ray pulse could be used to produce a high velocity jet of several hundred of km/s by an accumulative effect, and we use these ideas to design this new kind of targets. In order to increase the efficiency of the process, we scan in the simulations different materials, cone profiles and laser intensities. ANALOP is a code developed to calculate opacities for hot plasmas, using analytical potentials including density and temperature effects. It has been recently updated to include the radiative transport into the rate equations by mean of the escape factors, and in parallel a line transport code which solve self-consistently the rate equation and radiative transfer equation in 1D planar geometry has been also developed. We have developed a comprehensive methodology to compute uncertainties on activation calculations. First we developed a sensitivity-uncertainty analysis method, providing the uncertainties of the different inventory responses functions due to the uncertainty of each of the reaction cross sections separately. Lately, we have developed and proved the excellent behaviour of a Monte Carlo-based methodology in assessing the synergetic/global effect of the complete set of cross-sections uncertainties on calculated radiological quantities. The methods have been applied to the activation analysis of the National Ignition Facility (NIF) and different IFE concepts (HYLIFE and Sombrero). Research on multiscale modelling of radiation damage in metals will be presented in comparison with 'ad hoc' experiments. Research on SiC composite is being pursued at macroscopic level

  7. Interleukin-1 may link helplessness-hopelessness with cancer progression: A proposed model

    OpenAIRE

    Argaman, M; Gidron, Y; Ariad, S

    2005-01-01

    A model of the relations between psychological factors and cancer progression should include brain and systemic components and their link with critical cellular stages in cancer progression. We present a psychoneuroimmunological (PNI) model that links helplessness-hopelessness (HH) with cancer progression via interleukin-1β (IL-1β). IL-1β was elevated in the brain following exposure to inescapable shock, and HH was minimized by antagonizing cerebral IL-1β. Elevated cerebral IL-1β increased ca...

  8. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia.

    Science.gov (United States)

    Ueki, Yumi; Ramirez, Grisela; Salcedo, Ernesto; Stabio, Maureen E; Lefcort, Frances

    2016-01-01

    Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein ( IKBKAP ). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre ( Tα1-Cre ). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients.

  9. Prediction of autoignition in a lifted methane/air flame using an unsteady flamelet/progress variable model

    Energy Technology Data Exchange (ETDEWEB)

    Ihme, Matthias; See, Yee Chee [Department of Aerospace Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2010-10-15

    An unsteady flamelet/progress variable (UFPV) model has been developed for the prediction of autoignition in turbulent lifted flames. The model is a consistent extension to the steady flamelet/progress variable (SFPV) approach, and employs an unsteady flamelet formulation to describe the transient evolution of all thermochemical quantities during the flame ignition process. In this UFPV model, all thermochemical quantities are parameterized by mixture fraction, reaction progress parameter, and stoichiometric scalar dissipation rate, eliminating the explicit dependence on a flamelet time scale. An a priori study is performed to analyze critical modeling assumptions that are associated with the population of the flamelet state space. For application to LES, the UFPV model is combined with a presumed PDF closure to account for subgrid contributions of mixture fraction and reaction progress variable. The model was applied in LES of a lifted methane/air flame. Additional calculations were performed to quantify the interaction between turbulence and chemistry a posteriori. Simulation results obtained from these calculations are compared with experimental data. Compared to the SFPV results, the unsteady flamelet/progress variable model captures the autoignition process, and good agreement with measurements is obtained for mixture fraction, temperature, and species mass fractions. From the analysis of scatter data and mixture fraction-conditional results it is shown that the turbulence/chemistry interaction delays the ignition process towards lower values of scalar dissipation rate, and a significantly larger region in the flamelet state space is occupied during the ignition process. (author)

  10. Modelling T4 cell count as a marker of HIV progression in the ...

    African Journals Online (AJOL)

    Modelling T4 cell count as a marker of HIV progression in the absence of any defense mechanism. VSM Yadavalli, MMO Labeodan, S Udayabaskaran, N Forche. Abstract. The T4 cell count, which is considered one of the markers of disease progression in an HIV infected individual, is modelled in this paper. The World ...

  11. Technical progress in INPRO activities on modelling and innovation

    International Nuclear Information System (INIS)

    Villalibre, P.; Haas, E.; Khartabil, H.; Kim, S.; Korinny, A.; Usanov, V. and others

    2010-01-01

    Among the 31 Members of the 'International Project on Innovative Nuclear Reactors and Fuel Cycles' (INPRO) in April 2010, more than 20 are cooperating in the implementation of Collaborative Projects (CPs) related to the four substantive Programme Areas of the INPRO Action Plan. The purpose of the CPs is to contribute to the achievement of goals established in the programmatic areas. This paper presents progress status of several CPs dealing with Modelling and Innovation: - CP on Environmental Impact Benchmarking applicable to Nuclear Energy Systems under Normal Operation (ENV): A benchmark of codes and methods for determining radiation released during normal operation of nuclear facilities is performed by using established source term, release scenario, and target group (humans). - CP on Proliferation Resistance: Acquisition/Diversion Pathway Analysis (PRADA): 'PRADA' addresses the identification and analyses of high level pathways for the acquisition of weapons usable material, and makes recommendations for evaluating the multiplicity and robustness of barriers against proliferation. PRADA develops a case study based on DUPIC fuel cycle. The outcome from the project will support the assessment methodologies developed at GIF and INPRO. - CP on Global Architecture of Nuclear Energy Systems based on Thermal and Fast Reactors including Closed Fuel Cycle (GAINS): GAINS objective is to develop a methodological platform for assessing future nuclear energy systems taking into account the sustainable development, and to validate the results through sample analyses. High and moderate scenarios of nuclear energy demand and supply during the Century (5000 and 2500 GWe respectively in the year 2100) are being analysed using homogeneous and heterogeneous considerations. A non-geographic approach grouping the countries according to their planned use of nuclear energy has being established. - CP on Investigations of the 233 U/Th Fuel Cycle (ThFC): ThFC objective is to explore FC

  12. A genetic model of progressively partial melting for uranium-bearing granites in south China

    International Nuclear Information System (INIS)

    Zhai Jianping.

    1989-01-01

    A genetic model of progressively partial and enrichment mechanism of uranium during partial melting of the sources of material studied and the significance of the genetic model in search of uranium deposits is elaborated. This model accounts better for some geological and geochemical features of uranium-bearing granties and suspects the traditional idea that igneous uranium-bearing granites were formed by fusion of U-rich strata surrounding these granites. Finally this paper points out that the infuence of U-rich strata of wall rocks of granites over uranium-bearing granites depends on variation of water solubility in the magma and assimilation of magma to wall rocks during its ascending and crystallization

  13. Progress in transport modelling of internal transport barrier plasmas in JET

    International Nuclear Information System (INIS)

    Tala, T.; Bourdelle, C.; Imbeaux, F.; Moreau, D.; Garbet, X.; Joffrin, E.; Laborde, L.; Litaudon, X.; Mazon, D.; Parail, V.; Corrigan, G.; Heading, D.; Crisanti, F.; Mantica, P.; Salmi, A.; Strand, P.; Weiland, J.

    2005-01-01

    This paper will report on the recent progress in transport modelling of Internal Transport Barrier (ITB) plasmas. Two separate issues will be covered, fully predictive transport modelling of ITBs in the multi-tokamak database, including micro-stability analyses of ITBs, and predictive closed-loop (i.e. real-time control) transport simulations of the q-profile and ITBs. For the first time, the predictive capabilities of the mixed Bohm/GyroBohm and Weiland transport models are investigated with discharges from the ITPA ITB database by fully predictive transport simulations. The predictive transport simulations with the Bohm/GyroBohm model agree very well with experimental results from JET and JT-60U. In order to achieve a good agreement in DIII-D, the stabilisation had to be included into the model, showing the significant role played by the stabilisation in governing the physics of the ITBs. The significant role of the stabilisation is also emphasised by the gyrokinetic analysis. The Weiland transport model shows only limited agreement between the model predictions and experimental results with respect to the formation and location of the ITB. The fully predictive closed-loop simulations with real-time control of the q-profile and ITB show that it is possible to reach various set-point profiles for q and ITB and control them for longer than a current diffusion time in JET using the same real-time control technique as in the experiments. (author)

  14. How Often Is the Misfit of Item Response Theory Models Practically Significant?

    Science.gov (United States)

    Sinharay, Sandip; Haberman, Shelby J.

    2014-01-01

    Standard 3.9 of the Standards for Educational and Psychological Testing ([, 1999]) demands evidence of model fit when item response theory (IRT) models are employed to data from tests. Hambleton and Han ([Hambleton, R. K., 2005]) and Sinharay ([Sinharay, S., 2005]) recommended the assessment of practical significance of misfit of IRT models, but…

  15. Development and Validation of a Model to Determine Risk of Progression of Barrett's Esophagus to Neoplasia.

    Science.gov (United States)

    Parasa, Sravanthi; Vennalaganti, Sreekar; Gaddam, Srinivas; Vennalaganti, Prashanth; Young, Patrick; Gupta, Neil; Thota, Prashanthi; Cash, Brooks; Mathur, Sharad; Sampliner, Richard; Moawad, Fouad; Lieberman, David; Bansal, Ajay; Kennedy, Kevin F; Vargo, John; Falk, Gary; Spaander, Manon; Bruno, Marco; Sharma, Prateek

    2018-04-01

    A system is needed to determine the risk of patients with Barrett's esophagus for progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). We developed and validated a model to determine of progression to HGD or EAC in patients with BE, based on demographic data and endoscopic and histologic findings at the time of index endoscopy. We performed a longitudinal study of patients with BE at 5 centers in United States and 1 center in Netherlands enrolled in the Barrett's Esophagus Study database from 1985 through 2014. Patients were excluded from the analysis if they had less than 1 year of follow-up, were diagnosed with HGD or EAC within the past year, were missing baseline histologic data, or had no intestinal metaplasia. Seventy percent of the patients were used to derive the model and 30% were used for the validation study. The primary outcome was development of HGD or EAC during the follow-up period (median, 5.9 years). Survival analysis was performed using the Kaplan-Meier method. We assigned a specific number of points to each BE risk factor, and point totals (scores) were used to create categories of low, intermediate, and high risk. We used Cox regression to compute hazard ratios and 95% confidence intervals to determine associations between risk of progression and scores. Of 4584 patients in the database, 2697 were included in our analysis (84.1% men; 87.6% Caucasian; mean age, 55.4 ± 20.1 years; mean body mass index, 27.9 ± 5.5 kg/m 2 ; mean length of BE, 3.7 ± 3.2 cm). During the follow-up period, 154 patients (5.7%) developed HGD or EAC, with an annual rate of progression of 0.95%. Male sex, smoking, length of BE, and baseline-confirmed low-grade dysplasia were significantly associated with progression. Scores assigned identified patients with BE that progressed to HGD or EAC with a c-statistic of 0.76 (95% confidence interval, 0.72-0.80; P Esophagus score) based on male sex, smoking, length of BE, and baseline low-grade dysplasia

  16. Model-based Prognostics with Concurrent Damage Progression Processes

    Data.gov (United States)

    National Aeronautics and Space Administration — Model-based prognostics approaches rely on physics-based models that describe the behavior of systems and their components. These models must account for the several...

  17. Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.

    Science.gov (United States)

    Imamura, Naoko; Horikoshi, Yosuke; Matsuzaki, Tomohiko; Toriumi, Kentaro; Kitatani, Kanae; Ogura, Go; Masuda, Ryota; Nakamura, Naoya; Takekoshi, Susumu; Iwazaki, Masayuki

    2013-12-20

    Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.

  18. Reduced estimated glomerular filtration rate (eGFR 73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

    Science.gov (United States)

    Blute, Michael L; Kucherov, Victor; Rushmer, Timothy J; Damodaran, Shivashankar; Shi, Fangfang; Abel, E Jason; Jarrard, David F; Richards, Kyle A; Messing, Edward M; Downs, Tracy M

    2017-09-01

    To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) 73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of 73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of 73 m 2 (P 73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of 73 m 2 (P = 0.01). Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  19. The significance of MMP-9 examination in serum from embryo of gastric cancer model

    International Nuclear Information System (INIS)

    Liu Zhan; Zhao Xuejian; Wang Lu; Li Yulin; Zhang Lihong; Zhang Hong

    2003-01-01

    Objective: To investigate the changes matrix metalloproteinase-9 (MMP-9) content from sera of chick embryos during the progression of transformed models of gastric cancer cells on chorioallantoic membrane (CAM). Methods: Morphometric investigation method was used to study the tumor generation on CAM; Enzyme-linked immunosorbent assay (ELISA) method was used to test MMP-9 concentrations in chick embryos'sera transferred by cancer cells at different points of time; the relationship between MMP-9 and cancer biological characteristics was analyzed. Results: In the group of 1 x 10 6 ·ml -1 gastric cancer cells, a single clot which could be seen by naked eyes appeared at 72 hours after inoculation. With the time going on, the volumes of the clot became larger and larger, and the neovessels on CAM accumulated to the clot. In the group of 1 x 10 6 ·ml -1 gastric cancer cells, the MMP-9 content in sera extremely increased at 72 hours after inoculation and increased continuously till the maxim at 7 days after inoculation. Conclusion: The whole progression of cancer development is accompanied with the increase of MMP-9 concentration. This model is feasible to study the characteristics of gastric cancer

  20. Using Rasch models to develop and validate an environmental thinking learning progression

    Science.gov (United States)

    Hashimoto-Martell, Erin A.

    Environmental understanding is highly relevant in today's global society. Social, economic, and political structures are connected to the state of environmental degradation and exploitation, and disproportionately affect those in poor or urban communities (Brulle & Pellow, 2006; Executive Order No. 12898, 1994). Environmental education must challenge the way we live, and our social and ecological quality of life, with the goal of responsible action. The development of a learning progression in environmental thinking, along with a corresponding assessment, could provide a tool that could be used across environmental education programs to help evaluate and guide programmatic decisions. This study sought to determine if a scale could be constructed that allowed individuals to be ordered along a continuum of environmental thinking. First, I developed the Environmental Thinking Learning Progression, a scale of environmental thinking from novice to advanced, based on the current available research and literature. The scale consisted of four subscales, each measuring a different aspect of environmental thinking: place consciousness, human connection, agency, and science concepts. Second, a measurement instrument was developed, so that the data appropriately fit the model using Rasch analysis. A Rasch analysis of the data placed respondents along a continuum, given the range of item difficulty for each subscale. Across three iterations of instrument revision and data collection, findings indicated that the items were ordered in a hierarchical way that corresponded to the construct of environmental thinking. Comparisons between groups showed that the average score of respondents who had participated in environmental education programs was significantly higher than those who had not. A comparison between males and females showed no significant difference in average measure, however, there were varied significant differences between how racial/ethnic groups performed. Overall

  1. Effect of fluoxetine on disease progression in a mouse model of ALS

    Science.gov (United States)

    Koschnitzky, J. E.; Quinlan, K. A.; Lukas, T. J.; Kajtaz, E.; Kocevar, E. J.; Mayers, W. F.; Siddique, T.

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are often prescribed to amyotrophic lateral sclerosis (ALS) patients; however, the impact of these prescriptions on ALS disease progression has not been systematically tested. To determine whether SSRIs impact disease progression, fluoxetine (Prozac, 5 or 10 mg/kg) was administered to mutant superoxide dismutase 1 (SOD1) mice during one of three age ranges: neonatal [postnatal day (P)5–11], adult presymptomatic (P30 to end stage), and adult symptomatic (P70 to end stage). Long-term adult fluoxetine treatment (started at either P30 or P70 and continuing until end stage) had no significant effect on disease progression. In contrast, neonatal fluoxetine treatment (P5-11) had two effects. First, all animals (mutant SOD1G93A and control: nontransgenic and SOD1WT) receiving the highest dose (10 mg/kg) had a sustained decrease in weight from P30 onward. Second, the high-dose SOD1G93A mice reached end stage ∼8 days (∼6% decrease in life span) sooner than vehicle and low-dose animals because of an increased rate of motor impairment. Fluoxetine increases synaptic serotonin (5-HT) levels, which is known to increase spinal motoneuron excitability. We confirmed that 5-HT increases spinal motoneuron excitability during this neonatal time period and therefore hypothesized that antagonizing 5-HT receptors during the same time period would improve disease outcome. However, cyproheptadine (1 or 5 mg/kg), a 5-HT receptor antagonist, had no effect on disease progression. These results show that a brief period of antidepressant treatment during a critical time window (the transition from neonatal to juvenile states) can be detrimental in ALS mouse models. PMID:24598527

  2. Basic fibroblast growth factor in an animal model of spontaneous mammary tumor progression.

    Science.gov (United States)

    Kao, Steven; Mo, Jeffrey; Baird, Andrew; Eliceiri, Brian P

    2012-06-01

    Although basic fibroblast growth factor (FGF2) was the first pro-angiogenic molecule discovered, it has numerous activities on the growth and differentiation of non-vascular cell types. FGF2 is both stimulatory and inhibitory, depending on the cell type evaluated, the experimental design used and the context in which it is tested. Here, we investigated the effects of manipulating endogenous FGF2 on the development of mammary cancer to determine whether its endogenous contribution in vivo is pro- or anti-tumorigenic. Specifically, we examined the effects of FGF2 gene dosing in a cross between a spontaneous breast tumor model (PyVT+ mice) and FGF2-/- (FGF KO) mice. Using these mice, the onset and progression of mammary tumors was determined. As predicted, female FGF2 WT mice developed mammary tumors starting around 60 days after birth and by 80 days, 100% of FGF2 WT female mice had mammary tumors. In contrast, 80% of FGF2 KO female mice had no palpable tumors until nearly three weeks later (85 days) at times when 100% of the WT cohort was tumor positive. All FGF KO mice were tumor-bearing by 115 days. When we compared the onset of mammary tumor development and the tumor progression curves between FGF het and FGF KO mice, we observed a difference, which suggested a gene dosing effect. Analysis of the tumors demonstrated that there were significant differences in tumor size depending on FGF2 status. The delay in tumor onset supports a functional role for FGF2 in mammary tumor progression, but argues against an essential role for FGF2 in overall mammary tumor progression.

  3. Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis

    Science.gov (United States)

    Kim, Yee Suk; Lee, Sungin; Zong, Nansu; Kahng, Jimin

    2017-01-01

    The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (Paged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; Page and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status. PMID:28587376

  4. Further modelling work: progress report April 1983 to March 1984

    International Nuclear Information System (INIS)

    Rae, J.; Hodgkinson, D.P.; Robinson, P.C.; Herbert, A.W.

    1984-06-01

    The aim of the work described here is to develop a set of related mathematical models for the transport of radionuclides in flowing groundwater. These models have an important role to play in making safety assessments of geological disposal options, and in the planning and interpretation of experiments in both laboratories and the field. Since the announcement of NIREX preferred sites the priority is to have models which apply to real situations and are properly validated. The particular features of the programme are as follows: First, we are developing very general multidimensional models for flow and transport which can include many of the complications found in real rock masses, such as the presence of large fracture zones. Secondly, we are developing simpler but more efficient models forming approximate scoping calculations and sensitivity analysis. Finally, we are attempting to validate these models in all possible ways - by comparing with other models and testing against field and laboratory experiments. (author)

  5. The Significance of the Bystander Effect: Modeling, Experiments, and More Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, David J.

    2009-07-22

    Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assumed the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions were implemented by a mathematical formalism and computational algorithms. The model adequately described data on bystander responses in the 3D system using a small number of adjustable parameters. Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long

  6. Progress in Chemical Kinetic Modeling for Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Westbrook, C K; Herbinet, O; Silke, E J

    2008-06-06

    Gasoline, diesel, and other alternative transportation fuels contain hundreds to thousands of compounds. It is currently not possible to represent all these compounds in detailed chemical kinetic models. Instead, these fuels are represented by surrogate fuel models which contain a limited number of representative compounds. We have been extending the list of compounds for detailed chemical models that are available for use in fuel surrogate models. Detailed models for components with larger and more complicated fuel molecular structures are now available. These advancements are allowing a more accurate representation of practical and alternative fuels. We have developed detailed chemical kinetic models for fuels with higher molecular weight fuel molecules such as n-hexadecane (C16). Also, we can consider more complicated fuel molecular structures like cyclic alkanes and aromatics that are found in practical fuels. For alternative fuels, the capability to model large biodiesel fuels that have ester structures is becoming available. These newly addressed cyclic and ester structures in fuels profoundly affect the reaction rate of the fuel predicted by the model. Finally, these surrogate fuel models contain large numbers of species and reactions and must be reduced for use in multi-dimensional models for spark-ignition, HCCI and diesel engines.

  7. 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.

  8. Mapping the Most Significant Computer Hacking Events to a Temporal Computer Attack Model

    OpenAIRE

    Heerden , Renier ,; Pieterse , Heloise; Irwin , Barry

    2012-01-01

    Part 4: Section 3: ICT for Peace and War; International audience; This paper presents eight of the most significant computer hacking events (also known as computer attacks). These events were selected because of their unique impact, methodology, or other properties. A temporal computer attack model is presented that can be used to model computer based attacks. This model consists of the following stages: Target Identification, Reconnaissance, Attack, and Post-Attack Reconnaissance stages. The...

  9. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  10. Progress with modeling activity landscapes in drug discovery.

    Science.gov (United States)

    Vogt, Martin

    2018-04-19

    Activity landscapes (ALs) are representations and models of compound data sets annotated with a target-specific activity. In contrast to quantitative structure-activity relationship (QSAR) models, ALs aim at characterizing structure-activity relationships (SARs) on a large-scale level encompassing all active compounds for specific targets. The popularity of AL modeling has grown substantially with the public availability of large activity-annotated compound data sets. AL modeling crucially depends on molecular representations and similarity metrics used to assess structural similarity. Areas covered: The concepts of AL modeling are introduced and its basis in quantitatively assessing molecular similarity is discussed. The different types of AL modeling approaches are introduced. AL designs can broadly be divided into three categories: compound-pair based, dimensionality reduction, and network approaches. Recent developments for each of these categories are discussed focusing on the application of mathematical, statistical, and machine learning tools for AL modeling. AL modeling using chemical space networks is covered in more detail. Expert opinion: AL modeling has remained a largely descriptive approach for the analysis of SARs. Beyond mere visualization, the application of analytical tools from statistics, machine learning and network theory has aided in the sophistication of AL designs and provides a step forward in transforming ALs from descriptive to predictive tools. To this end, optimizing representations that encode activity relevant features of molecules might prove to be a crucial step.

  11. Significance of apparent diffusion coefficient measurement for the differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and Parkinson's disease: evaluation by 3.0-T MR imaging

    International Nuclear Information System (INIS)

    Tsukamoto, Kazumichi; Kanasaki, Yoshiko; Kakite, Suguru; Fujii, Shinya; Kaminou, Toshio; Ogawa, Toshihide; Matsusue, Eiji

    2012-01-01

    The clinical differentiation of Parkinson's disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) may be challenging, especially in their early stages. The aim of this study was to evaluate the utility of apparent diffusion coefficient (ADC) measurement to distinguish among these degenerative disorders. Twenty-five MSA, 20 PSP, and 17 PD patients and 18 healthy controls were retrospectively studied. Axial diffusion-weighted and T2-weighted images were obtained using a 3-T MR system. Regions of interest (ROIs) were precisely placed in the midbrain, pons, putamen, globus pallidus, caudate nucleus, thalamus, superior cerebellar peduncle, middle cerebellar peduncle, cerebellar white matter, and cerebellar dentate nucleus, and the regional ADC (rADC) value was calculated in each ROI. In MSA, rADC values in the pons, middle cerebellar peduncle, cerebellar white matter, and cerebellar dentate nucleus were significantly higher than in PSP, PD, and controls. Furthermore, rADC values in the posterior putamen were significantly higher in MSA than in PSP and controls. In PSP, rADC values were significantly higher in the globus pallidus and midbrain than in MSA, PD, and controls. Furthermore, rADC values in the caudate nucleus and superior cerebellar peduncle were significantly higher in PSP than in MSA and controls. In PD, there were no significant differences in the rADC values compared to in MSA, PSP, and controls in all regions. Evaluation of rADC values in characteristic lesions in MSA, PSP, and PD by placing ROIs using 3-T systems can provide useful additional information for differentiating these disorders. (orig.)

  12. Progressive sampling-based Bayesian optimization for efficient and automatic machine learning model selection.

    Science.gov (United States)

    Zeng, Xueqiang; Luo, Gang

    2017-12-01

    Machine learning is broadly used for clinical data analysis. Before training a model, a machine learning algorithm must be selected. Also, the values of one or more model parameters termed hyper-parameters must be set. Selecting algorithms and hyper-parameter values requires advanced machine learning knowledge and many labor-intensive manual iterations. To lower the bar to machine learning, miscellaneous automatic selection methods for algorithms and/or hyper-parameter values have been proposed. Existing automatic selection methods are inefficient on large data sets. This poses a challenge for using machine learning in the clinical big data era. To address the challenge, this paper presents progressive sampling-based Bayesian optimization, an efficient and automatic selection method for both algorithms and hyper-parameter values. We report an implementation of the method. We show that compared to a state of the art automatic selection method, our method can significantly reduce search time, classification error rate, and standard deviation of error rate due to randomization. This is major progress towards enabling fast turnaround in identifying high-quality solutions required by many machine learning-based clinical data analysis tasks.

  13. The quest for significance model of radicalization: implications for the management of terrorist detainees.

    Science.gov (United States)

    Dugas, Michelle; Kruglanski, Arie W

    2014-01-01

    Radicalization and its culmination in terrorism represent a grave threat to the security and stability of the world. A related challenge is effective management of extremists who are detained in prison facilities. The major aim of this article is to review the significance quest model of radicalization and its implications for management of terrorist detainees. First, we review the significance quest model, which elaborates on the roles of motivation, ideology, and social processes in radicalization. Secondly, we explore the implications of the model in relation to the risks of prison radicalization. Finally, we analyze the model's implications for deradicalization strategies and review preliminary evidence for the effectiveness of a rehabilitation program targeting components of the significance quest. Based on this evidence, we argue that the psychology of radicalization provides compelling reason for the inclusion of deradicalization efforts as an essential component of the management of terrorist detainees. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Pile group program for full material modeling and progressive failure.

    Science.gov (United States)

    2008-12-01

    Strain wedge (SW) model formulation has been used, in previous work, to evaluate the response of a single pile or a group of piles (including its : pile cap) in layered soils to lateral loading. The SW model approach provides appropriate prediction f...

  15. Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma.

    Science.gov (United States)

    Robl, Bernhard; Botter, Sander Martijn; Boro, Aleksandar; Meier, Daniela; Neri, Dario; Fuchs, Bruno

    2017-06-01

    The targeted delivery of tumor necrosis factor-α (TNF-α) with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA) domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2-derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs) as well as metastases. In mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was evaluated. Intratibial PT growth was not affected by F8-TNF, yet early micrometastases were reduced possibly due to an F8-TNF-dependent attraction of pulmonary CD4 + , CD8 + , and natural killer cells. Furthermore, immunofluorescence revealed stronger expression of EDA in early pulmonary metastases compared with PT tissue. To study progressing pulmonary metastases, a hind limb amputation model was established, and the efficacy of F8-TNF, alone or combined with doxorubicin, was investigated. Despite the presence of EDA in metastases, no inhibition of progressive metastatic growth was detected. No significant differences in numbers of CD4 + or CD8 + cells or F4/80 + and Ly6G + myeloid-derived cells were observed, although a strong association between metastatic growth and presence of pulmonary Ly6G + myeloid-derived cells was detected. In summary, these findings demonstrate the potential of F8-TNF in activating the immune system and reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone or combined with doxorubicin against progressing osteosarcoma metastases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Bernhard Robl

    2017-06-01

    Full Text Available The targeted delivery of tumor necrosis factor-α (TNF-α with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2–derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs as well as metastases. In mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was evaluated. Intratibial PT growth was not affected by F8-TNF, yet early micrometastases were reduced possibly due to an F8-TNF–dependent attraction of pulmonary CD4+, CD8+, and natural killer cells. Furthermore, immunofluorescence revealed stronger expression of EDA in early pulmonary metastases compared with PT tissue. To study progressing pulmonary metastases, a hind limb amputation model was established, and the efficacy of F8-TNF, alone or combined with doxorubicin, was investigated. Despite the presence of EDA in metastases, no inhibition of progressive metastatic growth was detected. No significant differences in numbers of CD4+ or CD8+ cells or F4/80+ and Ly6G+ myeloid-derived cells were observed, although a strong association between metastatic growth and presence of pulmonary Ly6G+ myeloid-derived cells was detected. In summary, these findings demonstrate the potential of F8-TNF in activating the immune system and reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone or combined with doxorubicin against progressing osteosarcoma metastases.

  17. Global gene expression profile progression in Gaucher disease mouse models

    Directory of Open Access Journals (Sweden)

    Zhang Wujuan

    2011-01-01

    Full Text Available Abstract Background Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells in visceral organs and their abnormal functions are obscure. Results To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null. About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change, representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk of INFγ-regulated pro-inflammatory (13 and IL-4-regulated anti-inflammatory (11 cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation. Conclusions Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.

  18. Progressive Learning of Topic Modeling Parameters: A Visual Analytics Framework.

    Science.gov (United States)

    El-Assady, Mennatallah; Sevastjanova, Rita; Sperrle, Fabian; Keim, Daniel; Collins, Christopher

    2018-01-01

    Topic modeling algorithms are widely used to analyze the thematic composition of text corpora but remain difficult to interpret and adjust. Addressing these limitations, we present a modular visual analytics framework, tackling the understandability and adaptability of topic models through a user-driven reinforcement learning process which does not require a deep understanding of the underlying topic modeling algorithms. Given a document corpus, our approach initializes two algorithm configurations based on a parameter space analysis that enhances document separability. We abstract the model complexity in an interactive visual workspace for exploring the automatic matching results of two models, investigating topic summaries, analyzing parameter distributions, and reviewing documents. The main contribution of our work is an iterative decision-making technique in which users provide a document-based relevance feedback that allows the framework to converge to a user-endorsed topic distribution. We also report feedback from a two-stage study which shows that our technique results in topic model quality improvements on two independent measures.

  19. Explicit modeling the progressive interface damage in fibrous composite: Analytical vs. numerical approach

    DEFF Research Database (Denmark)

    Kushch, V.I.; Shmegera, S.V.; Mishnaevsky, Leon

    2011-01-01

    of the multiple inclusion problem by means of complex potentials. The second, finite element model of FRC is based on the cohesive zone model of interface. Simulation of progressive debonding in FRC using the many-fiber models of composite has been performed. The advantageous features and applicability areas...... of both models are discussed. It has been shown that the developed models provide detailed analysis of the progressive debonding phenomena including the interface crack cluster formation, overall stiffness reduction and induced anisotropy of the effective elastic moduli of composite....

  20. Modelling gas migration in fractured rock. A contribution to the EU's PROGRESS project

    International Nuclear Information System (INIS)

    Humm, J.; Robinson, P.; Clark, K.

    2001-01-01

    make comparison of results uninformative. Despite this disagreement, the developed approach of using a time-step approach to move fluid mass, with a steady-state pressure calculation at each step, appears to be capable of producing realistic behaviour. The dynamic model also produces behaviours, such as intermittence, which would not be expected of simpler models. The calculation time for the model allows a single fracture calculation to be undertaken in tens of minutes to hours, depending on the problem size and the chosen time-step. Clearly, scaling this to a fracture network would be impractical. Moreover, the data requirements cannot be met in any precise way. The limited modelling work carried out here supports the existing understanding that gas will find its way through heterogeneous systems by the easiest route. As far as gas migration through the geosphere in general is concerned, it may be considered conservative to assume that there is no significant delay and that gas will tend to reach the surface quickly. A comparison with the FRAC model is also made. The uncertainties in the measurements of aperture and gas fractions within the fracture that was modelled make it impossible to determine which model is most appropriate for such systems. Both models support the existing understanding that gas will find its way through heterogeneous systems by the easiest route available, i.e. through fractures with the greatest apertures. Finally, a summary is given of the key results from the PROGRESS Project (Research into Gas Generation and Migration in Radioactive Waste Repository Systems, carried out as part of the European Commission's IV th framework R and D programme)

  1. Progress in microscopic direct reaction modeling of nucleon induced reactions

    Energy Technology Data Exchange (ETDEWEB)

    Dupuis, M.; Bauge, E.; Hilaire, S.; Lechaftois, F.; Peru, S.; Pillet, N.; Robin, C. [CEA, DAM, DIF, Arpajon (France)

    2015-12-15

    A microscopic nuclear reaction model is applied to neutron elastic and direct inelastic scatterings, and pre-equilibrium reaction. The JLM folding model is used with nuclear structure information calculated within the quasi-particle random phase approximation implemented with the Gogny D1S interaction. The folding model for direct inelastic scattering is extended to include rearrangement corrections stemming from both isoscalar and isovector density variations occurring during a transition. The quality of the predicted (n,n), (n,n{sup '}), (n,xn) and (n,n{sup '}γ) cross sections, as well as the generality of the present microscopic approach, shows that it is a powerful tool that can help improving nuclear reactions data quality. Short- and long-term perspectives are drawn to extend the present approach to more systems, to include missing reactions mechanisms, and to consistently treat both structure and reaction problems. (orig.)

  2. Progress in sensor performance testing, modeling and range prediction using the TOD method: an overview

    Science.gov (United States)

    Bijl, Piet; Hogervorst, Maarten A.; Toet, Alexander

    2017-05-01

    The Triangle Orientation Discrimination (TOD) methodology includes i) a widely applicable, accurate end-to-end EO/IR sensor test, ii) an image-based sensor system model and iii) a Target Acquisition (TA) range model. The method has been extensively validated against TA field performance for a wide variety of well- and under-sampled imagers, systems with advanced image processing techniques such as dynamic super resolution and local adaptive contrast enhancement, and sensors showing smear or noise drift, for both static and dynamic test stimuli and as a function of target contrast. Recently, significant progress has been made in various directions. Dedicated visual and NIR test charts for lab and field testing are available and thermal test benches are on the market. Automated sensor testing using an objective synthetic human observer is within reach. Both an analytical and an image-based TOD model have recently been developed and are being implemented in the European Target Acquisition model ECOMOS and in the EOSTAR TDA. Further, the methodology is being applied for design optimization of high-end security camera systems. Finally, results from a recent perception study suggest that DRI ranges for real targets can be predicted by replacing the relevant distinctive target features by TOD test patterns of the same characteristic size and contrast, enabling a new TA modeling approach. This paper provides an overview.

  3. The Naval Ocean Vertical Aerosol Model : Progress Report

    NARCIS (Netherlands)

    Leeuw, G. de; Gathman, S.G.; Davidson, K.L.; Jensen, D.R.

    1990-01-01

    The Naval Oceanic Vertical Aerosol Model (NOVAM) has been formulated to estimate the vertical structure of the optical and infrared extinction coefficients in the marine atmospheric boundary layer (MABL). NOVAM was designed to predict the non-uniform and non-logarithmic extinction profiles which are

  4. Modeling sheet-flow sand transport under progressive surface waves

    NARCIS (Netherlands)

    Kranenburg, Wouter

    2013-01-01

    In the near-shore zone, energetic sea waves generate sheet-flow sand transport. In present day coastal models, wave-induced sheet-flow sand transport rates are usually predicted with semi-empirical transport formulas, based on extensive research on this phenomenon in oscillatory flow tunnels.

  5. Progress towards a lightning ignition model for the Northern Rockies

    Science.gov (United States)

    Paul Sopko; Don Latham

    2010-01-01

    We are in the process of constructing a lightning ignition model specific to the Northern Rockies using fire occurrence, lightning strike, ecoregion, and historical weather, NFDRS (National Fire Danger Rating System), lightning efficiency and lightning "possibility" data. Daily grids for each of these categories were reconstructed for the 2003 fire season (...

  6. Recent progress in the modelling of thermal plasma systems

    International Nuclear Information System (INIS)

    Xi Chen

    2002-01-01

    Plasma flow and heat transfer in thermal plasma systems are often of three-dimensional (3-D) features and cannot be well studied by use of a two-dimensional modelling approach. 3-D modelling studies are recently performed in our group. It is found that appreciable 3-D effects exist within non-transferred DC arc plasma torches even for the case with axisymmetrical external conditions. The key for the successful 3-D modelling of the non-transferred arc plasma torch is that the anode-nozzle wall is included in the computational domain. The predicted results are favorably compared with experimental observation. 3-D modelling of the plasma jets with lateral injection of particulate matter and its carrier gas also reveals distinct 3-D effects with the injection velocity and the distance between the carrier-gas injection-tube tip and the jet edge as critical parameters. The 3-D effects appreciably influence the trajectories and heating histories of particles injected into the plasma jet. (author)

  7. Significance of categorization and the modeling of age related factors for radiation protection

    International Nuclear Information System (INIS)

    Matsuoka, Osamu

    1987-01-01

    It is proposed that the categorization and modelling are necessary with regard to age related factors of radionuclide metabolism for the radiation protection of the public. In order to utilize the age related information as a model for life time risk estimate of public, it is necessary to generalize and simplify it according to the categorized model patterns. Since the patterns of age related changes in various parameters of radionuclide metabolism seem to be rather simple, it is possible to categorize them into eleven types of model patterns. Among these models, five are selected as positively significant models to be considered. Examples are shown as to the fitting of representative parameters of both physiological and metabolic parameter of radionuclides into the proposed model. The range of deviation from adult standard value is also analyzed for each model. The fitting of each parameter to categorized models, and its comparative consideration provide the effective information as to the physiological basis of radionuclide metabolism. Discussions are made on the problems encountered in the application of available age related information to radiation protection of the public, i.e. distribution of categorized parameter, period of life covered, range of deviation from adult value, implication to other dosimetric and pathological models and to the final estimation. 5 refs.; 3 figs.; 4 tabs

  8. Measurements and models for hazardous chemical and mixed wastes. 1998 annual progress report

    International Nuclear Information System (INIS)

    Holcomb, C.; Louie, B.; Mullins, M.E.; Outcalt, S.L.; Rogers, T.N.; Watts, L.

    1998-01-01

    'Aqueous waste of various chemical compositions constitutes a significant fraction of the total waste produced by industry in the US. A large quantity of the waste generated by the US chemical process industry is waste water. In addition, the majority of the waste inventory at DoE sites previously used for nuclear weapons production is aqueous waste. Large quantities of additional aqueous waste are expected to be generated during the clean-up of those sites. In order to effectively treat, safely handle, and properly dispose of these wastes, accurate and comprehensive knowledge of basic thermophysical property information is paramount. This knowledge will lead to huge savings by aiding in the design and optimization of treatment and disposal processes. The main objectives of this project are: Develop and validate models that accurately predict the phase equilibria and thermodynamic properties of hazardous aqueous systems necessary for the safe handling and successful design of separation and treatment processes for hazardous chemical and mixed wastes. Accurately measure the phase equilibria and thermodynamic properties of a representative system (water + acetone + isopropyl alcohol + sodium nitrate) over the applicable ranges of temperature, pressure, and composition to provide the pure component, binary, ternary, and quaternary experimental data required for model development. As of May, 1998, nine months into the first year of a three year project, the authors have made significant progress in the database development, have begun testing the models, and have been performance testing the apparatus on the pure components.'

  9. Progress in fuel pin modelling in the USA

    Energy Technology Data Exchange (ETDEWEB)

    Stephen, J D; Biancheria, A; Leibnitz, D; O' Reilly, B D; Liu, Y Y; Labar, M P; Gneiting, B C [General Electric Company, Sunnyvale, CA (United States)

    1979-12-01

    In the USA, the focus for theoretical fuel pin modeling is the LIFE system. This system of codes, algorithms, criteria and analysis guidelines is intended to provide a common basis for communication amongst the development groups, a reference set of analysis guidelines for design, and eventually a consensus on the state-of-the-art for licensing. The technical objective is to predict the effect of design options on fuel pin performance limits, which include fuel temperature, pin deformation and cladding breach during normal operation and design basis transients. The mechanistic approach to modeling is taken in LIFE to the extent possible. That is, the approach is to describe the key phenomena in sufficient detail to provide a fundamental understanding of their synergistic effect on the fuel pin performance limits.

  10. Progress in Geant4 Electromagnetic Physics Modelling and Validation

    International Nuclear Information System (INIS)

    Apostolakis, J; Burkhardt, H; Ivanchenko, V N; Asai, M; Bagulya, A; Grichine, V; Brown, J M C; Chikuma, N; Cortes-Giraldo, M A; Elles, S; Jacquemier, J; Guatelli, S; Incerti, S; Kadri, O; Maire, M; Urban, L; Pandola, L; Sawkey, D; Toshito, T; Yamashita, T

    2015-01-01

    In this work we report on recent improvements in the electromagnetic (EM) physics models of Geant4 and new validations of EM physics. Improvements have been made in models of the photoelectric effect, Compton scattering, gamma conversion to electron and muon pairs, fluctuations of energy loss, multiple scattering, synchrotron radiation, and high energy positron annihilation. The results of these developments are included in the new Geant4 version 10.1 and in patches to previous versions 9.6 and 10.0 that are planned to be used for production for run-2 at LHC. The Geant4 validation suite for EM physics has been extended and new validation results are shown in this work. In particular, the effect of gamma-nuclear interactions on EM shower shape at LHC energies is discussed. (paper)

  11. ARMA modeling of stochastic processes in nuclear reactor with significant detection noise

    International Nuclear Information System (INIS)

    Zavaljevski, N.

    1992-01-01

    The theoretical basis of ARMA modelling of stochastic processes in nuclear reactor was presented in a previous paper, neglecting observational noise. The identification of real reactor data indicated that in some experiments the detection noise is significant. Thus a more rigorous theoretical modelling of stochastic processes in nuclear reactor is performed. Starting from the fundamental stochastic differential equations of the Langevin type for the interaction of the detector with neutron field, a new theoretical ARMA model is developed. preliminary identification results confirm the theoretical expectations. (author)

  12. Preface: International Reference Ionosphere - Progress in Ionospheric Modelling

    Science.gov (United States)

    Bilitza Dieter; Reinisch, Bodo

    2010-01-01

    The international reference ionosphere (lRI) is the internationally recommended empirical model for the specification of ionospheric parameters supported by the Committee on Space Research (COSPAR) and the International Union of Radio Science (URSI) and recognized by the International Standardization Organization (ISO). IRI is being continually improved by a team of international experts as new data become available and better models are being developed. This issue chronicles the latest phase of model updates as reported during two IRI-related meetings. The first was a special session during the Scientific Assembly of the Committee of Space Research (COSPAR) in Montreal, Canada in July 2008 and the second was an IRI Task Force Activity at the US Air Force Academy in Colorado Springs in May 2009. This work led to several improvements and additions of the model which will be included in the next version, IRI-201O. The issue is divided into three sections focusing on the improvements made in the topside ionosphere, the F-peak, and the lower ionosphere, respectively. This issue would not have been possible without the reviewing efforts of many individuals. Each paper was reviewed by two referees. We thankfully acknowledge the contribution to this issue made by the following reviewers: Jacob Adeniyi, David Altadill, Eduardo Araujo, Feza Arikan, Dieter Bilitza, Jilijana Cander, Bela Fejer, Tamara Gulyaeva, Manuel Hermindez-Pajares, Ivan Kutiev, John MacDougal, Leo McNamara, Bruno Nava, Olivier Obrou, Elijah Oyeyemi, Vadym Paznukhov, Bodo Reinisch, John Retterer, Phil Richards, Gary Sales, J.H. Sastri, Ludger Scherliess, Iwona Stanislavska, Stamir Stankov, Shin-Yi Su, Manlian Zhang, Y ongliang Zhang, and Irina Zakharenkova. We are grateful to Peggy Ann Shea for her final review and guidance as the editor-in-chief for special issues of Advances in Space Research. We thank the authors for their timely submission and their quick response to the reviewer comments and humbly

  13. Progress and problems in modelling HTR core dynamics

    International Nuclear Information System (INIS)

    Scherer, W.; Gerwin, H.

    1991-01-01

    In recent years greater effort has been made to establish theoretical models for HTR core dynamics. At KFA Juelich the TINTE (TIme dependent Neutronics and TEmperatures) code system has been developed, which is able to model the primary circuit of an HTR plant using modern numerical techniques and taking into account the mutual interference of the relevant physical variables. The HTR core is treated in 2-D R-Z geometry for both nucleonics and thermo-fluid-dynamics. 2-energy-group diffusion theory is used in the nuclear part including 6 groups of delayed neutron precursors and 14 groups of decay heat producers. Local and non-local heat sources are incorporated, thus simulating gamma ray transport. The thermo-fluid-dynamics module accounts for heterogeneity effects due to the pebble bed structure. Pipes and other components of the primary loop are modelled in 1-D geometry. Forced convection may be treated as well as natural convection in case of blower breakdown accidents. Validation of TINTE has started using the results of a comprehensive experimental program that has been performed at the Arbeitsgemeinschaft Versuchsreaktor GmbH (AVR) high temperature pebble bed reactor at Juelich. In the frame of this program power transients were initiated by varying the helium blower rotational speed or by moving the control rods. In most cases a good accordance between experiment and calculation was found. Problems in modelling the special AVR reactor geometry in two dimensions are described and suggestions for overcoming the uncertainties of experimentally determined control rod reactivities are given. The influence of different polynomial expansions of xenon cross sections to long term transients is discussed together with effects of burnup during that time. Up to now the TINTE code has proven its general applicability to operational core transients of HTR. The effects of water ingress on reactivity, fuel element corrosion and cooling gas properties are now being

  14. Progress Towards an LES Wall Model Including Unresolved Roughness

    Science.gov (United States)

    Craft, Kyle; Redman, Andrew; Aikens, Kurt

    2015-11-01

    Wall models used in large eddy simulations (LES) are often based on theories for hydraulically smooth walls. While this is reasonable for many applications, there are also many where the impact of surface roughness is important. A previously developed wall model has been used primarily for jet engine aeroacoustics. However, jet simulations have not accurately captured thick initial shear layers found in some experimental data. This may partly be due to nozzle wall roughness used in the experiments to promote turbulent boundary layers. As a result, the wall model is extended to include the effects of unresolved wall roughness through appropriate alterations to the log-law. The methodology is tested for incompressible flat plate boundary layers with different surface roughness. Correct trends are noted for the impact of surface roughness on the velocity profile. However, velocity deficit profiles and the Reynolds stresses do not collapse as well as expected. Possible reasons for the discrepancies as well as future work will be presented. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1053575. Computational resources on TACC Stampede were provided under XSEDE allocation ENG150001.

  15. Theory, Modeling and Simulation: Research progress report 1994--1995

    Energy Technology Data Exchange (ETDEWEB)

    Garrett, B.C.; Dixon, D.A.; Dunning, T.H.

    1997-01-01

    The Pacific Northwest National Laboratory (PNNL) has established the Environmental Molecular Sciences Laboratory (EMSL). In April 1994, construction began on the new EMSL, a collaborative research facility devoted to advancing the understanding of environmental molecular science. Research in the Theory, Modeling, and Simulation (TM and S) program will play a critical role in understanding molecular processes important in restoring DOE`s research, development, and production sites, including understanding the migration and reactions of contaminants in soils and ground water, developing processes for isolation and processing of pollutants, developing improved materials for waste storage, understanding the enzymatic reactions involved in the biodegradation of contaminants, and understanding the interaction of hazardous chemicals with living organisms. The research objectives of the TM and S program are fivefold: to apply available electronic structure and dynamics techniques to study fundamental molecular processes involved in the chemistry of natural and contaminated systems; to extend current electronic structure and dynamics techniques to treat molecular systems of future importance and to develop new techniques for addressing problems that are computationally intractable at present; to apply available molecular modeling techniques to simulate molecular processes occurring in the multi-species, multi-phase systems characteristic of natural and polluted environments; to extend current molecular modeling techniques to treat ever more complex molecular systems and to improve the reliability and accuracy of such simulations; and to develop technologies for advanced parallel architectural computer systems. Research highlights of 82 projects are given.

  16. A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

    Directory of Open Access Journals (Sweden)

    Cigudosa Juan C

    2011-05-01

    Full Text Available Abstract Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs, will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents. With the extension of this analysis to an Array-CGH dataset (glioblastomas from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.

  17. Workshop on defining the significance of progressive brain change in schizophrenia: December 12, 2008 American College of Neuropsychopharmacology (ACNP) all-day satellite, Scottsdale, Arizona. The rapporteurs' report.

    Science.gov (United States)

    Borgwardt, Stefan J; Dickey, Chandlee; Hulshoff Pol, Hilleke; Whitford, Thomas J; DeLisi, Lynn E

    2009-07-01

    In 1990 a satellite session of the American College of Neuropsychopharmacology (ACNP) Annual Meeting was held that focused on the question of whether progressive changes in brain structure occur in schizophrenia and this session raised considerable controversy. Eighteen years later, on December 12, 2008, after much data have since accumulated on this topic, a group of approximately 45 researchers gathered after the annual ACNP meeting to participate in a similar workshop on several unresolved questions still remaining: (1) How strong and consistent is the evidence? (2) Is there anatomic specificity to changes and is it disease specific or subject specific? (3) What is the time course? (4) What is the underlying pathophysiology (i.e. is it central to the disease process or is it due to neuroleptic treatment or other epiphenomena? (5) What is its clinical significance? and (6) Are there treatment implications? The day was chaired by Lynn E. DeLisi and co-chaired by Stephen J. Wood. Christos Pantelis and Jeffrey A. Lieberman extensively helped with its planning. The ACNP assisted in its organization as an official satellite of its annual meeting and several pharmaceutical companies provided support with unrestricted educational grants. The following is a summary of the sessions as recounted by rapporteurs whose job was to record as closely as possible the outcome of discussions on the above outlined questions.

  18. Recent progress in modelling 3D lithospheric deformation

    Science.gov (United States)

    Kaus, B. J. P.; Popov, A.; May, D. A.

    2012-04-01

    Modelling 3D lithospheric deformation remains a challenging task, predominantly because the variations in rock types, as well as nonlinearities due to for example plastic deformation result in sharp and very large jumps in effective viscosity contrast. As a result, there are only a limited number of 3D codes available, most of which are using direct solvers which are computationally and memory-wise very demanding. As a result, the resolutions for typical model runs are quite modest, despite the use of hundreds of processors (and using much larger computers is unlikely to bring much improvement in this situation). For this reason we recently developed a new 3D deformation code,called LaMEM: Lithosphere and Mantle Evolution Model. LaMEM is written on top of PETSc, and as a result it runs on massive parallel machines and we have a large number of iterative solvers available (including geometric and algebraic multigrid methods). As it remains unclear which solver combinations work best under which conditions, we have implemented most currently suggested methods (such as schur complement reduction or Fully coupled iterations). In addition, we can use either a finite element discretization (with Q1P0, stabilized Q1Q1 or Q2P-1 elements) or a staggered finite difference discretization for the same input geometry, which is based on a marker and cell technique). This gives us he flexibility to test various solver methodologies on the same model setup, in terms of accuracy, speed, memory usage etc. Here, we will report on some features of LaMEM, on recent code additions, as well as on some lessons we learned which are important for modelling 3D lithospheric deformation. Specifically we will discuss: 1) How we combine a particle-and-cell method to make it work with both a finite difference and a (lagrangian, eulerian or ALE) finite element formulation, with only minor code modifications code 2) How finite difference and finite element discretizations compare in terms of

  19. Androgen receptor levels during progression of prostate cancer in the transgenic adenocarcinoma of mouse prostate model

    Directory of Open Access Journals (Sweden)

    Krisna Murti

    2010-02-01

    Full Text Available Aim To construct tissue microarrays (TMAs that consisted of prostate tumours from the transgenic adenocarcinoma of mouse prostate (TRAMP mice and non-transgenic murine prostates and to assess androgen receptor (AR levels during progression of prostate cancer in TRAMP mice by immunohistochemistry.Methods Haematoxylin and eosin (H&E sections from the ventral and dorso-lateral prostate lobes of non-transgenic, intact TRAMP and castrated TRAMP were used to demarcate regions of interest for TMAs construction. The samples on TMAs were used to evaluate AR expression using video image analysis (VIA.Results AR was expressed during cancer progression, but AR levels were reduced or absent in late stage disease. Furthermore, when AR levels were compared in tumours from intact and castrate animals, a significant increase in AR levels was observed following androgen ablation.Conclusion Similar to clinical prostate cancer, in the TRAMP model, prostate tumours evolve mechanisms to maintain AR expression and AR responsive gene pathways following castration to facilitate continued tumour growth. (Med J Indones 2010; 19:5-13Keywords : androgen ablation therapy, tissue microarrays, haematoxylin and eosin, video image analysis

  20. On the selection of significant variables in a model for the deteriorating process of facades

    Science.gov (United States)

    Serrat, C.; Gibert, V.; Casas, J. R.; Rapinski, J.

    2017-10-01

    In previous works the authors of this paper have introduced a predictive system that uses survival analysis techniques for the study of time-to-failure in the facades of a building stock. The approach is population based, in order to obtain information on the evolution of the stock across time, and to help the manager in the decision making process on global maintenance strategies. For the decision making it is crutial to determine those covariates -like materials, morphology and characteristics of the facade, orientation or environmental conditions- that play a significative role in the progression of different failures. The proposed platform also incorporates an open source GIS plugin that includes survival and test moduli that allow the investigator to model the time until a lesion taking into account the variables collected during the inspection process. The aim of this paper is double: a) to shortly introduce the predictive system, as well as the inspection and the analysis methodologies and b) to introduce and illustrate the modeling strategy for the deteriorating process of an urban front. The illustration will be focused on the city of L’Hospitalet de Llobregat (Barcelona, Spain) in which more than 14,000 facades have been inspected and analyzed.

  1. Strategies for Testing Statistical and Practical Significance in Detecting DIF with Logistic Regression Models

    Science.gov (United States)

    Fidalgo, Angel M.; Alavi, Seyed Mohammad; Amirian, Seyed Mohammad Reza

    2014-01-01

    This study examines three controversial aspects in differential item functioning (DIF) detection by logistic regression (LR) models: first, the relative effectiveness of different analytical strategies for detecting DIF; second, the suitability of the Wald statistic for determining the statistical significance of the parameters of interest; and…

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

    Science.gov (United States)

    Chen, Shuyi

    2015-04-01

    It has long been recognized that air-sea interaction plays an important role in tropical cyclones (TC) intensity change. However, most current numerical weather prediction (NWP) models are deficient in predicting TC intensity. The extreme high winds, intense rainfall, large ocean waves, and copious sea spray in TCs push the surface-exchange parameters for temperature, water vapor, and momentum into untested regimes. Parameterizations of air-sea fluxes in NWP models are often crude and create "manmade" energy source/sink that does not exist, especially in the absence of a fully interactive ocean in the model. The erroneous surface heat, moisture, and momentum fluxes can cause compounding errors in the model (e.g., precipitation, water vapor, boundary layer properties). The energy source (heat and moisture fluxes from the ocean) and sink (surface friction and wind-induced upper ocean cooling) are critical to TC intensity. However, observations of air-sea fluxes in TCs are very limited, especially in extreme high wind conditions underneath of the eyewall region. The Coupled Boundary Layer Air-Sea Transfer (CBLAST) program was designed to better understand the air-sea interaction, especially in high wind conditions, which included laboratory and coupled model experiments and field campaign in 2003-04 hurricane seasons. Significant progress has been made in better understanding of air-sea exchange coefficients up to 30 m/s, i.e., a leveling off in drag coefficient and relatively invariant exchange coefficient of enthalpy with wind speed. More recently, the Impact of Typhoon on the Ocean in the Pacific (ITOP) field campaign in 2010 has provided an unprecedented data set to study the air-sea fluxes in TCs and their impact on TC structure and intensity. More than 800 GPS dropsondes and 900 AXBTs/AXCTs as well as drifters, floats, and moorings were deployed in TCs, including Typhoons Fanapi and Malakas, and Supertyphoon Megi with a record peak wind speed of more than 80 m

  3. Progress in lung modelling by the ICRP Task Group

    International Nuclear Information System (INIS)

    James, A.C.; Birchall, A.

    1989-01-01

    The Task Group has reviewed the data on: (a) morphology and physiology of the human respiratory tract; (b) inspirability of aerosols and their deposition in anatomical regions as functions of respiratory parameters; (c) clearance of particles within and from the respiratory tract; (d) absorption of different materials into the blood in humans and in animals. The Task Group proposes a new model which predicts the deposition, retention and systemic uptake of materials, enabling doses absorbed by different respiratory tissues and other body organs to be evaluated. In the proposed model, clearance is described in terms of competition between the processes moving particles to the oropharynx or to lymph nodes and that of absorption into the blood. From studies with human subjects, characteristic rates and pathways are defined to represent mechanical clearance of particles from each region, which do not depend on the material. Conversely, the absorption rate is determined solely by the material: it is assumed to be the same in all parts of the respiratory tract and in other animal species. For several of the radiologically important forms of actinides, absorption rates can be derived from animal experiments, or, in some cases, directly from human data. Otherwise, default values are used, based on the current D, W and Y classification system. (author)

  4. Recent progress in plasma modelling at INFN-LNS

    Science.gov (United States)

    Neri, L.; Castro, G.; Torrisi, G.; Galatà, A.; Mascali, D.; Celona, L.; Gammino, S.

    2016-02-01

    At Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS), the development of intense ion and proton sources has been supported by a great deal of work on the modelling of microwave generated plasmas for many years. First, a stationary version of the particle-in-cell code was developed for plasma modelling starting from an iterative strategy adopted for the space charge dominated beam transport simulations. Electromagnetic properties of the plasma and full-waves simulations are now affordable for non-homogenous and non-isotropic magnetized plasma via "cold" approximation. The effects of Coulomb collisions on plasma particles dynamics was implemented with the Langevin formalism, instead of simply applying the Spitzer 90° collisions through a Monte Carlo technique. A wide database of different cross sections related to reactions occurring in a hydrogen plasma was implemented. The next step consists of merging such a variety of approaches for retrieving an "as-a-whole" picture of plasma dynamics in ion sources. The preliminary results will be summarized in the paper for a microwave discharge ion source designed for intense and high quality proton beams production, proton source for European Spallation Source project. Even if the realization of a predictive software including the complete processes involved in plasma formation is still rather far, a better comprehension of the source behavior is possible and so the simulations may support the optimization phase.

  5. Recent progress in plasma modelling at INFN-LNS

    Energy Technology Data Exchange (ETDEWEB)

    Neri, L., E-mail: neri@lns.infn.it; Castro, G.; Mascali, D.; Celona, L.; Gammino, S. [INFN-Laboratori Nazionali del Sud, Via S. Sofia 62, 95125 Catania (Italy); Torrisi, G. [INFN-Laboratori Nazionali del Sud, Via S. Sofia 62, 95125 Catania (Italy); Università Mediterranea di Reggio Calabria, Via Graziella, 89100 Reggio Calabria (Italy); Galatà, A. [INFN-Laboratori Nazionali di Legnaro, Viale dell’Università 2, 35020 Legnaro, Padova (Italy)

    2016-02-15

    At Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS), the development of intense ion and proton sources has been supported by a great deal of work on the modelling of microwave generated plasmas for many years. First, a stationary version of the particle-in-cell code was developed for plasma modelling starting from an iterative strategy adopted for the space charge dominated beam transport simulations. Electromagnetic properties of the plasma and full-waves simulations are now affordable for non-homogenous and non-isotropic magnetized plasma via “cold” approximation. The effects of Coulomb collisions on plasma particles dynamics was implemented with the Langevin formalism, instead of simply applying the Spitzer 90° collisions through a Monte Carlo technique. A wide database of different cross sections related to reactions occurring in a hydrogen plasma was implemented. The next step consists of merging such a variety of approaches for retrieving an “as-a-whole” picture of plasma dynamics in ion sources. The preliminary results will be summarized in the paper for a microwave discharge ion source designed for intense and high quality proton beams production, proton source for European Spallation Source project. Even if the realization of a predictive software including the complete processes involved in plasma formation is still rather far, a better comprehension of the source behavior is possible and so the simulations may support the optimization phase.

  6. Recent progress in biomass burning research: a perspective from analyses of satellite data and model studies. (Invited)

    Science.gov (United States)

    Logan, J. A.

    2010-12-01

    Significant progress has been made in using satellite data to provide bottom-up constraints on biomass burning (BB) emissions. However, inverse studies with CO satellite data imply that tropical emissions are underestimated by current inventories, while model simulations of the ARCTAS period imply that the FLAMBE estimates of extratropical emissions are significantly overestimated. Injection heights of emissions from BB have been quantified recently using MISR data, and these data provide some constraints on 1-d plume models. I will discuss recent results in these areas, highlighting future research needs.

  7. Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model.

    Science.gov (United States)

    Li, Xiaoxia; Wu, Miaoqin; Zhang, Luyi; Liu, Hui; Zhang, Lan; He, Jinjing

    2017-12-01

    In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. 3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A.

    2016-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

  9. On the computational assessment of white matter hyperintensity progression: difficulties in method selection and bias field correction performance on images with significant white matter pathology

    Energy Technology Data Exchange (ETDEWEB)

    Valdes Hernandez, Maria del C.; Gonzalez-Castro, Victor; Wang, Xin; Doubal, Fergus; Munoz Maniega, Susana; Wardlaw, Joanna M. [Centre for Clinical Brian Sciences, Department of Neuroimaging Sciences, Edinburgh (United Kingdom); Ghandour, Dina T. [University of Edinburgh, College of Medicine and Veterinary Medicine, Edinburgh (United Kingdom); Armitage, Paul A. [University of Sheffield, Department of Cardiovascular Sciences, Sheffield (United Kingdom)

    2016-05-15

    Subtle inhomogeneities in the scanner's magnetic fields (B{sub 0} and B{sub 1}) alter the intensity levels of the structural magnetic resonance imaging (MRI) affecting the volumetric assessment of WMH changes. Here, we investigate the influence that (1) correcting the images for the B{sub 1} inhomogeneities (i.e. bias field correction (BFC)) and (2) selection of the WMH change assessment method can have on longitudinal analyses of WMH progression and discuss possible solutions. We used brain structural MRI from 46 mild stroke patients scanned at stroke onset and 3 years later. We tested three BFC approaches: FSL-FAST, N4 and exponentially entropy-driven homomorphic unsharp masking (E{sup 2}D-HUM) and analysed their effect on the measured WMH change. Separately, we tested two methods to assess WMH changes: measuring WMH volumes independently at both time points semi-automatically (MCMxxxVI) and subtracting intensity-normalised FLAIR images at both time points following image gamma correction. We then combined the BFC with the computational method that performed best across the whole sample to assess WMH changes. Analysis of the difference in the variance-to-mean intensity ratio in normal tissue between BFC and uncorrected images and visual inspection showed that all BFC methods altered the WMH appearance and distribution, but FSL-FAST in general performed more consistently across the sample and MRI modalities. The WMH volume change over 3 years obtained with MCMxxxVI with vs. without FSL-FAST BFC did not significantly differ (medians(IQR)(with BFC) = 3.2(6.3) vs. 2.9(7.4)ml (without BFC), p = 0.5), but both differed significantly from the WMH volume change obtained from subtracting post-processed FLAIR images (without BFC)(7.6(8.2)ml, p < 0.001). This latter method considerably inflated the WMH volume change as subtle WMH at baseline that became more intense at follow-up were counted as increase in the volumetric change. Measurement of WMH volume change remains

  10. Vision deficits precede structural losses in a mouse model of mitochondrial dysfunction and progressive retinal degeneration.

    Science.gov (United States)

    Laliberté, Alex M; MacPherson, Thomas C; Micks, Taft; Yan, Alex; Hill, Kathleen A

    2011-12-01

    Current animal models of retinal disease often involve the rapid development of a retinal disease phenotype; however, this is at odds with age-related diseases that take many years to manifest clinical symptoms. The present study was performed to examine an apoptosis-inducing factor (Aif)-deficient model, the harlequin carrier mouse (X(hq)X), and determine how mitochondrial dysfunction and subsequent accelerated aging affect the function and structure of the mouse retina. Vision and eye structure for cohorts of 6 X(hq)X and 6 wild type mice at 3, 11, and 15 months of age were studied using in vivo electroretinography (ERG), and optical coherence tomography (OCT). Retinal superoxide levels were determined in situ using dihydroethidium (DHE) histochemistry. Retinal cell counts were quantified post mortem using hematoxylin and eosin (H&E) staining. ERG analysis of X(hq)X retinal function indicated a reduction in b-wave amplitude significant at 3 months of age (p retina (p retina may account for the early and significant reduction in retinal function. This remodeling of retinal neurochemistry in response to stress may be a relevant mechanism in the progression of normal retinal aging and early stages of some retinal degenerative diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Modeling carbon dioxide sequestration in saline aquifers: Significance of elevated pressures and salinities

    International Nuclear Information System (INIS)

    Allen, D.E.; Strazisar, B.R.; Soong, Y.; Hedges, S.W.

    2005-01-01

    The ultimate capacity of saline formations to sequester carbon dioxide by solubility and mineral trapping must be determined by simulating sequestration with geochemical models. These models, however, are only as reliable as the data and reaction scheme on which they are based. Several models have been used to make estimates of carbon dioxide solubility and mineral formation as a function of pressure and fluid composition. Intercomparison of modeling results indicates that failure to adjust all equilibrium constants to account for elevated carbon dioxide pressures results in significant errors in both solubility and mineral formation estimates. Absence of experimental data at high carbon dioxide pressures and high salinities make verification of model results difficult. Results indicate standalone solubility models that do not take mineral reactions into account will underestimate the total capacity of aquifers to sequester carbon dioxide in the long term through enhanced solubility and mineral trapping mechanisms. Overall, it is difficult to confidently predict the ultimate sequestration capacity of deep saline aquifers using geochemical models. (author)

  12. Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Izumi Masashi

    2012-08-01

    Full Text Available Abstract Background Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3 on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA which is considered a degenerative rather than an inflammatory disease. Methods We induced OA via intra-articular mono-iodoacetate (MIA injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2 on pain behavior, disease progression, and ASIC3 expression in knee joint afferents. Results OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia. ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase. Conclusions Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.

  13. Field significance of performance measures in the context of regional climate model evaluation. Part 2: precipitation

    Science.gov (United States)

    Ivanov, Martin; Warrach-Sagi, Kirsten; Wulfmeyer, Volker

    2018-04-01

    A new approach for rigorous spatial analysis of the downscaling performance of regional climate model (RCM) simulations is introduced. It is based on a multiple comparison of the local tests at the grid cells and is also known as `field' or `global' significance. The block length for the local resampling tests is precisely determined to adequately account for the time series structure. New performance measures for estimating the added value of downscaled data relative to the large-scale forcing fields are developed. The methodology is exemplarily applied to a standard EURO-CORDEX hindcast simulation with the Weather Research and Forecasting (WRF) model coupled with the land surface model NOAH at 0.11 ∘ grid resolution. Daily precipitation climatology for the 1990-2009 period is analysed for Germany for winter and summer in comparison with high-resolution gridded observations from the German Weather Service. The field significance test controls the proportion of falsely rejected local tests in a meaningful way and is robust to spatial dependence. Hence, the spatial patterns of the statistically significant local tests are also meaningful. We interpret them from a process-oriented perspective. While the downscaled precipitation distributions are statistically indistinguishable from the observed ones in most regions in summer, the biases of some distribution characteristics are significant over large areas in winter. WRF-NOAH generates appropriate stationary fine-scale climate features in the daily precipitation field over regions of complex topography in both seasons and appropriate transient fine-scale features almost everywhere in summer. As the added value of global climate model (GCM)-driven simulations cannot be smaller than this perfect-boundary estimate, this work demonstrates in a rigorous manner the clear additional value of dynamical downscaling over global climate simulations. The evaluation methodology has a broad spectrum of applicability as it is

  14. Scoping review identifies significant number of knowledge translation theories, models and frameworks with limited use.

    Science.gov (United States)

    Strifler, Lisa; Cardoso, Roberta; McGowan, Jessie; Cogo, Elise; Nincic, Vera; Khan, Paul A; Scott, Alistair; Ghassemi, Marco; MacDonald, Heather; Lai, Yonda; Treister, Victoria; Tricco, Andrea C; Straus, Sharon E

    2018-04-13

    To conduct a scoping review of knowledge translation (KT) theories, models and frameworks that have been used to guide dissemination or implementation of evidence-based interventions targeted to prevention and/or management of cancer or other chronic diseases. We used a comprehensive multistage search process from 2000-2016, which included traditional bibliographic database searching, searching using names of theories, models and frameworks, and cited reference searching. Two reviewers independently screened the literature and abstracted data. We found 596 studies reporting on the use of 159 KT theories, models or frameworks. A majority (87%) of the identified theories, models or frameworks were used in five or fewer studies, with 60% used once. The theories, models and frameworks were most commonly used to inform planning/design, implementation and evaluation activities, and least commonly used to inform dissemination and sustainability/scalability activities. Twenty-six were used across the full implementation spectrum (from planning/design to sustainability/scalability) either within or across studies. All were used for at least individual-level behavior change, while 48% were used for organization-level, 33% for community-level and 17% for system-level change. We found a significant number of KT theories, models and frameworks with a limited evidence base describing their use. Copyright © 2018. Published by Elsevier Inc.

  15. Computation of spatial significance of mountain objects extracted from multiscale digital elevation models

    International Nuclear Information System (INIS)

    Sathyamoorthy, Dinesh

    2014-01-01

    The derivation of spatial significance is an important aspect of geospatial analysis and hence, various methods have been proposed to compute the spatial significance of entities based on spatial distances with other entities within the cluster. This paper is aimed at studying the spatial significance of mountain objects extracted from multiscale digital elevation models (DEMs). At each scale, the value of spatial significance index SSI of a mountain object is the minimum number of morphological dilation iterations required to occupy all the other mountain objects in the terrain. The mountain object with the lowest value of SSI is the spatially most significant mountain object, indicating that it has the shortest distance to the other mountain objects. It is observed that as the area of the mountain objects reduce with increasing scale, the distances between the mountain objects increase, resulting in increasing values of SSI. The results obtained indicate that the strategic location of a mountain object at the centre of the terrain is more important than its size in determining its reach to other mountain objects and thus, its spatial significance

  16. Constrained parameterisation of photosynthetic capacity causes significant increase of modelled tropical vegetation surface temperature

    Science.gov (United States)

    Kattge, J.; Knorr, W.; Raddatz, T.; Wirth, C.

    2009-04-01

    Photosynthetic capacity is one of the most sensitive parameters of terrestrial biosphere models whose representation in global scale simulations has been severely hampered by a lack of systematic analyses using a sufficiently broad database. Due to its coupling to stomatal conductance changes in the parameterisation of photosynthetic capacity may potentially influence transpiration rates and vegetation surface temperature. Here, we provide a constrained parameterisation of photosynthetic capacity for different plant functional types in the context of the photosynthesis model proposed by Farquhar et al. (1980), based on a comprehensive compilation of leaf photosynthesis rates and leaf nitrogen content. Mean values of photosynthetic capacity were implemented into the coupled climate-vegetation model ECHAM5/JSBACH and modelled gross primary production (GPP) is compared to a compilation of independent observations on stand scale. Compared to the current standard parameterisation the root-mean-squared difference between modelled and observed GPP is substantially reduced for almost all PFTs by the new parameterisation of photosynthetic capacity. We find a systematic depression of NUE (photosynthetic capacity divided by leaf nitrogen content) on certain tropical soils that are known to be deficient in phosphorus. Photosynthetic capacity of tropical trees derived by this study is substantially lower than standard estimates currently used in terrestrial biosphere models. This causes a decrease of modelled GPP while it significantly increases modelled tropical vegetation surface temperatures, up to 0.8°C. These results emphasise the importance of a constrained parameterisation of photosynthetic capacity not only for the carbon cycle, but also for the climate system.

  17. Development of a Conceptual Model of Disease Progression for Use in Economic Modeling of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Tabberer, Maggie; Gonzalez-McQuire, Sebastian; Muellerova, Hana; Briggs, Andrew H; Rutten-van Mölken, Maureen P M H; Chambers, Mike; Lomas, David A

    2017-05-01

    To develop and validate a new conceptual model (CM) of chronic obstructive pulmonary disease (COPD) for use in disease progression and economic modeling. The CM identifies and describes qualitative associations between disease attributes, progression and outcomes. A literature review was performed to identify any published CMs or literature reporting the impact and association of COPD disease attributes with outcomes. After critical analysis of the literature, a Steering Group of experts from the disciplines of health economics, epidemiology and clinical medicine was convened to develop a draft CM, which was refined using a Delphi process. The refined CM was validated by testing for associations between attributes using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). Disease progression attributes included in the final CM were history and occurrence of exacerbations, lung function, exercise capacity, signs and symptoms (cough, sputum, dyspnea), cardiovascular disease comorbidities, 'other' comorbidities (including depression), body composition (body mass index), fibrinogen as a biomarker, smoking and demographic characteristics (age, gender). Mortality and health-related quality of life were determined to be the most relevant final outcome measures for this model, intended to be the foundation of an economic model of COPD. The CM is being used as the foundation for developing a new COPD model of disease progression and to provide a framework for the analysis of patient-level data. The CM is available as a reference for the implementation of further disease progression and economic models.

  18. The Chronic Kidney Disease Model: A General Purpose Model of Disease Progression and Treatment

    Directory of Open Access Journals (Sweden)

    Patel Uptal D

    2011-06-01

    Full Text Available Abstract Background Chronic kidney disease (CKD is the focus of recent national policy efforts; however, decision makers must account for multiple therapeutic options, comorbidities and complications. The objective of the Chronic Kidney Disease model is to provide guidance to decision makers. We describe this model and give an example of how it can inform clinical and policy decisions. Methods Monte Carlo simulation of CKD natural history and treatment. Health states include myocardial infarction, stroke with and without disability, congestive heart failure, CKD stages 1-5, bone disease, dialysis, transplant and death. Each cycle is 1 month. Projections account for race, age, gender, diabetes, proteinuria, hypertension, cardiac disease, and CKD stage. Treatment strategies include hypertension control, diabetes control, use of HMG-CoA reductase inhibitors, use of angiotensin converting enzyme inhibitors, nephrology specialty care, CKD screening, and a combination of these. The model architecture is flexible permitting updates as new data become available. The primary outcome is quality adjusted life years (QALYs. Secondary outcomes include health state events and CKD progression rate. Results The model was validated for GFR change/year -3.0 ± 1.9 vs. -1.7 ± 3.4 (in the AASK trial, and annual myocardial infarction and mortality rates 3.6 ± 0.9% and 1.6 ± 0.5% vs. 4.4% and 1.6% in the Go study. To illustrate the model's utility we estimated lifetime impact of a hypothetical treatment for primary prevention of vascular disease. As vascular risk declined, QALY improved but risk of dialysis increased. At baseline, 20% and 60% reduction: QALYs = 17.6, 18.2, and 19.0 and dialysis = 7.7%, 8.1%, and 10.4%, respectively. Conclusions The CKD Model is a valid, general purpose model intended as a resource to inform clinical and policy decisions improving CKD care. Its value as a tool is illustrated in our example which projects a relationship between

  19. Significance of Bias Correction in Drought Frequency and Scenario Analysis Based on Climate Models

    Science.gov (United States)

    Aryal, Y.; Zhu, J.

    2015-12-01

    Assessment of future drought characteristics is difficult as climate models usually have bias in simulating precipitation frequency and intensity. To overcome this limitation, output from climate models need to be bias corrected based on the specific purpose of applications. In this study, we examine the significance of bias correction in the context of drought frequency and scenario analysis using output from climate models. In particular, we investigate the performance of three widely used bias correction techniques: (1) monthly bias correction (MBC), (2) nested bias correction (NBC), and (3) equidistance quantile mapping (EQM) The effect of bias correction in future scenario of drought frequency is also analyzed. The characteristics of drought are investigated in terms of frequency and severity in nine representative locations in different climatic regions across the United States using regional climate model (RCM) output from the North American Regional Climate Change Assessment Program (NARCCAP). The Standardized Precipitation Index (SPI) is used as the means to compare and forecast drought characteristics at different timescales. Systematic biases in the RCM precipitation output are corrected against the National Centers for Environmental Prediction (NCEP) North American Regional Reanalysis (NARR) data. The results demonstrate that bias correction significantly decreases the RCM errors in reproducing drought frequency derived from the NARR data. Preserving mean and standard deviation is essential for climate models in drought frequency analysis. RCM biases both have regional and timescale dependence. Different timescale of input precipitation in the bias corrections show similar results. Drought frequency obtained from the RCM future (2040-2070) scenarios is compared with that from the historical simulations. The changes in drought characteristics occur in all climatic regions. The relative changes in drought frequency in future scenario in relation to

  20. Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.

    Science.gov (United States)

    Gorden, D Lee; Ivanova, Pavlina T; Myers, David S; McIntyre, J Oliver; VanSaun, Michael N; Wright, J Kelly; Matrisian, Lynn M; Brown, H Alex

    2011-01-01

    The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD. Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts. Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts. Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD.

  1. Mapping of Students’ Learning Progression Based on Mental Model in Magnetic Induction Concepts

    Science.gov (United States)

    Hamid, R.; Pabunga, D. B.

    2017-09-01

    The progress of student learning in a learning process has not been fully optimally observed by the teacher. The concept being taught is judged only at the end of learning as a product of thinking, and does not assess the mental processes that occur in students’ thinking. Facilitating students’ thinking through new phenomena can reveal students’ variation in thinking as a mental model of a concept, so that students who are assimilative and or accommodative can be identified in achieving their equilibrium of thought as well as an indicator of progressiveness in the students’ thinking stages. This research data is obtained from the written documents and interviews of students who were learned about the concept of magnetic induction through Constructivist Teaching Sequences (CTS) models. The results of this study indicate that facilitating the students’ thinking processes on the concept of magnetic induction contributes to increasing the number of students thinking within the "progressive change" category, and it can be said that the progress of student learning is more progressive after their mental models were facilitated through a new phenomena by teacher.

  2. Impact of changes in metabolic control on progression to photocoagulation for clinically significant macular oedema:a 20 year study of type 1 diabetes

    DEFF Research Database (Denmark)

    Sander, B.; Larsen, M.; Andersen, Elisabeth Wreford

    2013-01-01

    Aims/hypothesis Although increasing hyperglycaemia, arterial hypertension and longer duration of diabetes raise the risk of progression of diabetic retinopathy, short-term benefits in terms of improved metabolic control and lowered blood pressure have not been demonstrated. We therefore examined ...

  3. Significance of settling model structures and parameter subsets in modelling WWTPs under wet-weather flow and filamentous bulking conditions.

    Science.gov (United States)

    Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen; Plósz, Benedek Gy

    2014-10-15

    Current research focuses on predicting and mitigating the impacts of high hydraulic loadings on centralized wastewater treatment plants (WWTPs) under wet-weather conditions. The maximum permissible inflow to WWTPs depends not only on the settleability of activated sludge in secondary settling tanks (SSTs) but also on the hydraulic behaviour of SSTs. The present study investigates the impacts of ideal and non-ideal flow (dry and wet weather) and settling (good settling and bulking) boundary conditions on the sensitivity of WWTP model outputs to uncertainties intrinsic to the one-dimensional (1-D) SST model structures and parameters. We identify the critical sources of uncertainty in WWTP models through global sensitivity analysis (GSA) using the Benchmark simulation model No. 1 in combination with first- and second-order 1-D SST models. The results obtained illustrate that the contribution of settling parameters to the total variance of the key WWTP process outputs significantly depends on the influent flow and settling conditions. The magnitude of the impact is found to vary, depending on which type of 1-D SST model is used. Therefore, we identify and recommend potential parameter subsets for WWTP model calibration, and propose optimal choice of 1-D SST models under different flow and settling boundary conditions. Additionally, the hydraulic parameters in the second-order SST model are found significant under dynamic wet-weather flow conditions. These results highlight the importance of developing a more mechanistic based flow-dependent hydraulic sub-model in second-order 1-D SST models in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. An observation-based progression modeling approach to spring and autumn deciduous tree phenology

    Science.gov (United States)

    Yu, Rong; Schwartz, Mark D.; Donnelly, Alison; Liang, Liang

    2016-03-01

    It is important to accurately determine the response of spring and autumn phenology to climate change in forest ecosystems, as phenological variations affect carbon balance, forest productivity, and biodiversity. We observed phenology intensively throughout spring and autumn in a temperate deciduous woodlot at Milwaukee, WI, USA, during 2007-2012. Twenty-four phenophase levels in spring and eight in autumn were recorded for 106 trees, including white ash, basswood, white oak, boxelder, red oak, and hophornbeam. Our phenological progression models revealed that accumulated degree-days and day length explained 87.9-93.4 % of the variation in spring canopy development and 75.8-89.1 % of the variation in autumn senescence. In addition, the timing of community-level spring and autumn phenophases and the length of the growing season from 1871 to 2012 were reconstructed with the models developed. All simulated spring phenophases significantly advanced at a rate from 0.24 to 0.48 days/decade ( p ≤ 0.001) during the 1871-2012 period and from 1.58 to 2.00 days/decade ( p coloration) and 0.50 (full-leaf coloration) days/decade ( p coloration and leaf fall, and suggested accelerating simulated ecosystem responses to climate warming over the last four decades in comparison to the past 142 years.

  5. Dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease.

    Directory of Open Access Journals (Sweden)

    Yumiko Nakagawa-Toyama

    Full Text Available BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/h called 'HypoE' when fed an atherogenic, 'Paigen' diet develop occlusive, atherosclerotic coronary arterial disease (CHD, myocardial infarctions (MI, and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet. Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. METHODOLOGY/PRINCIPAL FINDINGS: HypoE mice were maintained on a standard lab chow diet (control until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. CONCLUSIONS/SIGNIFICANCE: HypoE mice provide a powerful, surgery-free, diet-'titratable' small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation on a variety of features of

  6. Intriguing model significantly reduces boarding of psychiatric patients, need for inpatient hospitalization.

    Science.gov (United States)

    2015-01-01

    As new approaches to the care of psychiatric emergencies emerge, one solution is gaining particular traction. Under the Alameda model, which has been put into practice in Alameda County, CA, patients who are brought to regional EDs with emergency psychiatric issues are quickly transferred to a designated emergency psychiatric facility as soon as they are medically stabilized. This alleviates boarding problems in area EDs while also quickly connecting patients with specialized care. With data in hand on the model's effectiveness, developers believe the approach could alleviate boarding problems in other communities as well. The model is funded by through a billing code established by California's Medicaid program for crisis stabilization services. Currently, only 22% of the patients brought to the emergency psychiatric facility ultimately need to be hospitalized; the other 78% are able to go home or to an alternative situation. In a 30-day study of the model, involving five community hospitals in Alameda County, CA, researchers found that ED boarding times were as much as 80% lower than comparable ED averages, and that patients were stabilized at least 75% of the time, significantly reducing the need for inpatient hospitalization.

  7. Expression and significance of Bax protein in model of radiation injury in mouse skin

    International Nuclear Information System (INIS)

    Feng Yizhong; Mo Yahong

    2002-01-01

    Objective: The study is to find some valuable criteria for diagnosis and treatment of radiation injury in skin. Methods: The expression of Bax protein was studied by SP immunohistochemistry in 40 cases of model of radiation injury in mouse skin. Their relationship relating to radiation dose was also investigated. Results: The expression rates of Bax were 30%, 30%, 70%, 70% in 5 Gy group, 15 Gy group, 30 Gy group, 45 Gy group respectively. There was no significant correlation between the expression of Bax and radiation groups. Conclusions: The experiment shows that radiation can increase the expression of Bax protein which might be related to poor healing in radiation skin injury

  8. Field significance of performance measures in the context of regional climate model evaluation. Part 1: temperature

    Science.gov (United States)

    Ivanov, Martin; Warrach-Sagi, Kirsten; Wulfmeyer, Volker

    2018-04-01

    A new approach for rigorous spatial analysis of the downscaling performance of regional climate model (RCM) simulations is introduced. It is based on a multiple comparison of the local tests at the grid cells and is also known as "field" or "global" significance. New performance measures for estimating the added value of downscaled data relative to the large-scale forcing fields are developed. The methodology is exemplarily applied to a standard EURO-CORDEX hindcast simulation with the Weather Research and Forecasting (WRF) model coupled with the land surface model NOAH at 0.11 ∘ grid resolution. Monthly temperature climatology for the 1990-2009 period is analysed for Germany for winter and summer in comparison with high-resolution gridded observations from the German Weather Service. The field significance test controls the proportion of falsely rejected local tests in a meaningful way and is robust to spatial dependence. Hence, the spatial patterns of the statistically significant local tests are also meaningful. We interpret them from a process-oriented perspective. In winter and in most regions in summer, the downscaled distributions are statistically indistinguishable from the observed ones. A systematic cold summer bias occurs in deep river valleys due to overestimated elevations, in coastal areas due probably to enhanced sea breeze circulation, and over large lakes due to the interpolation of water temperatures. Urban areas in concave topography forms have a warm summer bias due to the strong heat islands, not reflected in the observations. WRF-NOAH generates appropriate fine-scale features in the monthly temperature field over regions of complex topography, but over spatially homogeneous areas even small biases can lead to significant deteriorations relative to the driving reanalysis. As the added value of global climate model (GCM)-driven simulations cannot be smaller than this perfect-boundary estimate, this work demonstrates in a rigorous manner the

  9. The Significant of Model School in Pluralistic Society of the Three Southern Border Provinces of Thailand

    Directory of Open Access Journals (Sweden)

    Haji-Awang Faisol

    2016-01-01

    The result of the study show that, a significant traits of the model schools in the multi-cultural society are not merely performed well in administrative procedure, teaching and learning process, but these schools also able to reveal the real social norm and religious believe into communities’ practical life as a truly “Malay-Muslim” society. It is means that, the school able to run the integrated programs under the shade of philosophy of Islamic education paralleled the National Education aims to ensure that the productivities of the programs able to serve both sides, national education on the one hand and the Malay Muslim communities’ satisfaction on the other hand.

  10. Model training across multiple breeding cycles significantly improves genomic prediction accuracy in rye (Secale cereale L.).

    Science.gov (United States)

    Auinger, Hans-Jürgen; Schönleben, Manfred; Lehermeier, Christina; Schmidt, Malthe; Korzun, Viktor; Geiger, Hartwig H; Piepho, Hans-Peter; Gordillo, Andres; Wilde, Peer; Bauer, Eva; Schön, Chris-Carolin

    2016-11-01

    Genomic prediction accuracy can be significantly increased by model calibration across multiple breeding cycles as long as selection cycles are connected by common ancestors. In hybrid rye breeding, application of genome-based prediction is expected to increase selection gain because of long selection cycles in population improvement and development of hybrid components. Essentially two prediction scenarios arise: (1) prediction of the genetic value of lines from the same breeding cycle in which model training is performed and (2) prediction of lines from subsequent cycles. It is the latter from which a reduction in cycle length and consequently the strongest impact on selection gain is expected. We empirically investigated genome-based prediction of grain yield, plant height and thousand kernel weight within and across four selection cycles of a hybrid rye breeding program. Prediction performance was assessed using genomic and pedigree-based best linear unbiased prediction (GBLUP and PBLUP). A total of 1040 S 2 lines were genotyped with 16 k SNPs and each year testcrosses of 260 S 2 lines were phenotyped in seven or eight locations. The performance gap between GBLUP and PBLUP increased significantly for all traits when model calibration was performed on aggregated data from several cycles. Prediction accuracies obtained from cross-validation were in the order of 0.70 for all traits when data from all cycles (N CS  = 832) were used for model training and exceeded within-cycle accuracies in all cases. As long as selection cycles are connected by a sufficient number of common ancestors and prediction accuracy has not reached a plateau when increasing sample size, aggregating data from several preceding cycles is recommended for predicting genetic values in subsequent cycles despite decreasing relatedness over time.

  11. A theoretical model to describe progressions and regressions for exercise rehabilitation.

    Science.gov (United States)

    Blanchard, Sam; Glasgow, Phil

    2014-08-01

    This article aims to describe a new theoretical model to simplify and aid visualisation of the clinical reasoning process involved in progressing a single exercise. Exercise prescription is a core skill for physiotherapists but is an area that is lacking in theoretical models to assist clinicians when designing exercise programs to aid rehabilitation from injury. Historical models of periodization and motor learning theories lack any visual aids to assist clinicians. The concept of the proposed model is that new stimuli can be added or exchanged with other stimuli, either intrinsic or extrinsic to the participant, in order to gradually progress an exercise whilst remaining safe and effective. The proposed model maintains the core skills of physiotherapists by assisting clinical reasoning skills, exercise prescription and goal setting. It is not limited to any one pathology or rehabilitation setting and can adapted by any level of skilled clinician. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Interleukin-1 may link helplessness-hopelessness with cancer progression: a proposed model.

    Science.gov (United States)

    Argaman, Miriam; Gidron, Yori; Ariad, Shmuel

    2005-01-01

    A model of the relations between psychological factors and cancer progression should include brain and systemic components and their link with critical cellular stages in cancer progression. We present a psychoneuroimmunological (PNI) model that links helplessness-hopelessness (HH) with cancer progression via interleukin-1beta (IL-1beta). IL-1beta was elevated in the brain following exposure to inescapable shock, and HH was minimized by antagonizing cerebral IL-1beta. Elevated cerebral IL-1beta increased cancer metastasis in animals. Inescapable shock was associated with systemic elevations of IL-1beta and peripheral IL-1beta was associated with escape from apoptosis, angiogenesis, and metastasis. Involvement of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis are discussed. Future studies need to identify the role of additional factors in this PNI pathway.

  13. Cell-based multi-parametric model of cleft progression during submandibular salivary gland branching morphogenesis.

    Directory of Open Access Journals (Sweden)

    Shayoni Ray

    Full Text Available Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft

  14. Bayesian spatial modelling and the significance of agricultural land use to scrub typhus infection in Taiwan.

    Science.gov (United States)

    Wardrop, Nicola A; Kuo, Chi-Chien; Wang, Hsi-Chieh; Clements, Archie C A; Lee, Pei-Fen; Atkinson, Peter M

    2013-11-01

    Scrub typhus is transmitted by the larval stage of trombiculid mites. Environmental factors, including land cover and land use, are known to influence breeding and survival of trombiculid mites and, thus, also the spatial heterogeneity of scrub typhus risk. Here, a spatially autoregressive modelling framework was applied to scrub typhus incidence data from Taiwan, covering the period 2003 to 2011, to provide increased understanding of the spatial pattern of scrub typhus risk and the environmental and socioeconomic factors contributing to this pattern. A clear spatial pattern in scrub typhus incidence was observed within Taiwan, and incidence was found to be significantly correlated with several land cover classes, temperature, elevation, normalized difference vegetation index, rainfall, population density, average income and the proportion of the population that work in agriculture. The final multivariate regression model included statistically significant correlations between scrub typhus incidence and average income (negatively correlated), the proportion of land that contained mosaics of cropland and vegetation (positively correlated) and elevation (positively correlated). These results highlight the importance of land cover on scrub typhus incidence: mosaics of cropland and vegetation represent a transitional land cover type which can provide favourable habitats for rodents and, therefore, trombiculid mites. In Taiwan, these transitional land cover areas tend to occur in less populated and mountainous areas, following the frontier establishment and subsequent partial abandonment of agricultural cultivation, due to demographic and socioeconomic changes. Future land use policy decision-making should ensure that potential public health outcomes, such as modified risk of scrub typhus, are considered.

  15. Optimization of electronic enclosure design for thermal and moisture management using calibrated models of progressive complexity

    DEFF Research Database (Denmark)

    Mohanty, Sankhya; Staliulionis, Zygimantas; Shojaee Nasirabadi, Parizad

    2016-01-01

    the development of rigorous calibrated CFD models as well as simple predictive numerical tools, the current paper tackles the optimization of critical features of a typical two-chamber electronic enclosure. The progressive optimization strategy begins the design parameter selection by initially using simpler...

  16. Accessing key steps of human tumor progression in vivo by using an avian embryo model

    Science.gov (United States)

    Hagedorn, Martin; Javerzat, Sophie; Gilges, Delphine; Meyre, Aurélie; de Lafarge, Benjamin; Eichmann, Anne; Bikfalvi, Andreas

    2005-02-01

    Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening. angiogenesis | animal model alternatives | glioblastoma

  17. Mental Model Progression in Learning the Electron Transport Chain: Effects of Instructional Strategies and Cognitive Flexibility

    Science.gov (United States)

    Darabi, Aubteen; Hemphill, Jennifer; Nelson, David W.; Boulware, Wilma; Liang, Xinya

    2010-01-01

    This study investigated the effect of two instructional strategies, segmented and holistic, on the progression over time of learners' mental models toward that of an expert with the moderator of cognitive flexibility. Sixty-four juniors and seniors in a college metabolism course were randomly assigned to one of the two strategies for instruction…

  18. Progress in the improved lattice calculation of direct CP-violation in the Standard Model

    Science.gov (United States)

    Kelly, Christopher

    2018-03-01

    We discuss the ongoing effort by the RBC & UKQCD collaborations to improve our lattice calculation of the measure of Standard Model direct CP violation, ɛ', with physical kinematics. We present our progress in decreasing the (dominant) statistical error and discuss other related activities aimed at reducing the systematic errors.

  19. The Significance of α-Synuclein, Amyloid-β and Tau Pathologies in Parkinson’s Disease Progression and Related Dementia

    Science.gov (United States)

    Compta, Y.; Parkkinen, L.; Kempster, P.; Selikhova, M.; Lashley, T.; Holton, J.L.; Lees, A.J.; Revesz, T.

    2014-01-01

    Background Dementia is one of the milestones of advanced Parkinson’s disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications. Objective The aim of this study was to review the relative importance of Lewy-related α-synuclein and Alzheimer’s tau and amyloid-β (Aβ) pathologies in disease progression and dementia in PD. Methods We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts. Results Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn, linked to dementia. The combination of these pathologies is the most robust neuropathological substrate of PD-related dementia, with cortical Aβ burden determining a faster progression to dementia. Conclusion The shared relevance of these pathologies in PD progression and dementia is in line with experimental data suggesting synergism between α-synuclein, tau and Aβ and with studies testing these proteins as disease biomarkers, hence favouring the eventual testing of therapeutic strategies targeting these proteins in PD. PMID:24028925

  20. VALORA: data base system for storage significant information used in the behavior modelling in the biosphere

    International Nuclear Information System (INIS)

    Valdes R, M.; Aguero P, A.; Perez S, D.; Cancio P, D.

    2006-01-01

    The nuclear and radioactive facilities can emit to the environment effluents that contain radionuclides, which are dispersed and/or its accumulate in the atmosphere, the terrestrial surface and the surface waters. As part of the evaluations of radiological impact, it requires to be carried out qualitative and quantitative analysis. In many of the cases it doesn't have the real values of the parameters that are used in the modelling, neither it is possible to carry out their measure, for that to be able to carry out the evaluation it needs to be carried out an extensive search of that published in the literature about the possible values of each parameter, under similar conditions to the object of study, this work can be extensive. In this work the characteristics of the VALORA Database System developed with the purpose of organizing and to automate significant information that it appears in different sources (scientific or technique literature) of the parameters that are used in the modelling of the behavior of the pollutants in the environment and the values assigned to these parameters that are used in the evaluation of the radiological impact potential is described; VALORA allows the consultation and selection of the characteristic parametric data of different situations and processes that are required by the calculation pattern implemented. The software VALORA it is a component of a group of tools computer that have as objective to help to the resolution of dispersion models and transfer of pollutants. (Author)

  1. Biological variability in biomechanical engineering research: Significance and meta-analysis of current modeling practices.

    Science.gov (United States)

    Cook, Douglas; Julias, Margaret; Nauman, Eric

    2014-04-11

    Biological systems are characterized by high levels of variability, which can affect the results of biomechanical analyses. As a review of this topic, we first surveyed levels of variation in materials relevant to biomechanics, and compared these values to standard engineered materials. As expected, we found significantly higher levels of variation in biological materials. A meta-analysis was then performed based on thorough reviews of 60 research studies from the field of biomechanics to assess the methods and manner in which biological variation is currently handled in our field. The results of our meta-analysis revealed interesting trends in modeling practices, and suggest a need for more biomechanical studies that fully incorporate biological variation in biomechanical models and analyses. Finally, we provide some case study example of how biological variability may provide valuable insights or lead to surprising results. The purpose of this study is to promote the advancement of biomechanics research by encouraging broader treatment of biological variability in biomechanical modeling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.

    Directory of Open Access Journals (Sweden)

    Patrick Aldrin-Kirk

    Full Text Available Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable

  3. Progress in modelling agricultural impacts of and adaptations to climate change.

    Science.gov (United States)

    Rötter, R P; Hoffmann, M P; Koch, M; Müller, C

    2018-06-01

    Modelling is a key tool to explore agricultural impacts of and adaptations to climate change. Here we report recent progress made especially referring to the large project initiatives MACSUR and AgMIP; in particular, in modelling potential crop impacts from field to global using multi-model ensembles. We identify two main fields where further progress is necessary: a more mechanistic understanding of climate impacts and management options for adaptation and mitigation; and focusing on cropping systems and integrative multi-scale assessments instead of single season and crops, especially in complex tropical and neglected but important cropping systems. Stronger linking of experimentation with statistical and eco-physiological crop modelling could facilitate the necessary methodological advances. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Phasic firing in vasopressin cells: understanding its functional significance through computational models.

    Directory of Open Access Journals (Sweden)

    Duncan J MacGregor

    Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

  5. Applications of Living Fire PRA models to Fire Protection Significance Determination Process in Taiwan

    International Nuclear Information System (INIS)

    De-Cheng, Chen; Chung-Kung, Lo; Tsu-Jen, Lin; Ching-Hui, Wu; Lin, James C.

    2004-01-01

    The living fire probabilistic risk assessment (PRA) models for all three operating nuclear power plants (NPPs) in Taiwan had been established in December 2000. In that study, a scenario-based PRA approach was adopted to systematically evaluate the fire and smoke hazards and associated risks. Using these fire PRA models developed, a risk-informed application project had also been completed in December 2002 for the evaluation of cable-tray fire-barrier wrapping exemption. This paper presents a new application of the fire PRA models to fire protection issues using the fire protection significance determination process (FP SDP). The fire protection issues studied may involve the selection of appropriate compensatory measures during the period when an automatic fire detection or suppression system in a safety-related fire zone becomes inoperable. The compensatory measure can either be a 24-hour fire watch or an hourly fire patrol. The living fire PRA models were used to estimate the increase in risk associated with the fire protection issue in terms of changes in core damage frequency (CDF) and large early release frequency (LERF). In compliance with SDP at-power and the acceptance guidelines specified in RG 1.174, the fire protection issues in question can be grouped into four categories; red, yellow, white and green, in accordance with the guidelines developed for FD SDP. A 24-hour fire watch is suggested only required for the yellow condition, while an hourly fire patrol may be adopted for the white condition. More limiting requirement is suggested for the red condition, but no special consideration is needed for the green condition. For the calculation of risk measures, risk impacts from any additional fire scenarios that may have been introduced, as well as more severe initiating events and fire damages that may accompany the fire protection issue should be considered carefully. Examples are presented in this paper to illustrate the evaluation process. (authors)

  6. MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma.

    Science.gov (United States)

    Tinder, Teresa L; Subramani, Durai B; Basu, Gargi D; Bradley, Judy M; Schettini, Jorge; Million, Arefayene; Skaar, Todd; Mukherjee, Pinku

    2008-09-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune-competent host. Significant enhancement in the development of pancreatic intraepithelial preneoplastic lesions and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and IDO compared with PDA mice lacking MUC1, especially during early stages of tumor development. The increased proinflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease, which in turn regulate the immune responses. Thus, the mouse model is ideally suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer.

  7. MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

    Science.gov (United States)

    Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

    2008-01-01

    MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

  8. Disease Progression/Clinical Outcome Model for Castration-Resistant Prostate Cancer in Patients Treated with Eribulin

    NARCIS (Netherlands)

    Van Hasselt, J. G C; Gupta, A.; Hussein, Z.; Beijnen, J. H.; Schellens, J. H M; Huitema, A. D R

    2015-01-01

    Frameworks that associate cancer dynamic disease progression models with parametric survival models for clinical outcome have recently been proposed to support decision making in early clinical development. Here we developed such a disease progression clinical outcome model for castration-resistant

  9. Knowledge-fused differential dependency network models for detecting significant rewiring in biological networks.

    Science.gov (United States)

    Tian, Ye; Zhang, Bai; Hoffman, Eric P; Clarke, Robert; Zhang, Zhen; Shih, Ie-Ming; Xuan, Jianhua; Herrington, David M; Wang, Yue

    2014-07-24

    Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context-specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. While differential networks cannot be constructed by existing knowledge alone, novel incorporation of prior knowledge into data-driven approaches can improve the robustness and biological relevance of network inference. However, the major unresolved roadblocks include: big solution space but a small sample size; highly complex networks; imperfect prior knowledge; missing significance assessment; and heuristic structural parameter learning. To address these challenges, we formulated the inference of differential dependency networks that incorporate both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to "random" knowledge. Based on that scheme, we developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results. The open-source R software package and the experimental data are freely available at http://www.cbil.ece.vt.edu/software.htm. Experiments on both synthetic and real data demonstrate the effectiveness of the knowledge-fused differential dependency network in revealing the statistically significant rewiring in biological

  10. Significance of flow clustering and sequencing on sediment transport: 1D sediment transport modelling

    Science.gov (United States)

    Hassan, Kazi; Allen, Deonie; Haynes, Heather

    2016-04-01

    . Results illustrate that clustered flood events generated sediment loads up to an order of magnitude greater than that of individual events of the same flood volume. Correlations were significant for sediment volume compared to both maximum flow discharge (R2<0.8) and number of events (R2 -0.5 to -0.7) within the cluster. The strongest correlations occurred for clusters with a greater number of flow events only slightly above-threshold. This illustrates that the numerical model can capture a degree of the non-linear morphological response to flow magnitude. Analysis of the relationship between morphological change and the skewness of flow events within each cluster was also determined, illustrating only minor sensitivity to cluster peak distribution skewness. This is surprising and discussion is presented on model limitations, including the capability of sediment transport formulae to effectively account for temporal processes of antecedent flow, hysteresis, local supply etc.

  11. A systematic experimental investigation of significant parameters affecting model tire hydroplaning

    Science.gov (United States)

    Wray, G. A.; Ehrlich, I. R.

    1973-01-01

    The results of a comprehensive parametric study of model and small pneumatic tires operating on a wet surface are presented. Hydroplaning inception (spin down) and rolling restoration (spin up) are discussed. Conclusions indicate that hydroplaning inception occurs at a speed significantly higher than the rolling restoration speed. Hydroplaning speed increases considerably with tread depth, surface roughness and tire inflation pressure of footprint pressure, and only moderately with increased load. Water film thickness affects spin down speed only slightly. Spin down speed varies inversely as approximately the one-sixth power of film thickness. Empirical equations relating tire inflation pressure, normal load, tire diameter and water film thickness have been generated for various tire tread and surface configurations.

  12. Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    Jang Hyun Koh

    2014-01-01

    Full Text Available The overexpression of vascular endothelial growth factor (VEGF is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10, OLETF rats as diabetic control group (n=10, and OLETF rats treated with taurine group (n=10. We treated taurine (200 mg/kg/day for 20 weeks and treated high glucose (HG, 30 mM with or without taurine (30 mM in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

  13. Analysis of significance of environmental factors in landslide susceptibility modeling: Case study Jemma drainage network, Ethiopia

    Directory of Open Access Journals (Sweden)

    Vít Maca

    2017-06-01

    Full Text Available Aim of the paper is to describe methodology for calculating significance of environmental factors in landslide susceptibility modeling and present result of selected one. As a study area part of a Jemma basin in Ethiopian Highland is used. This locality is highly affected by mass movement processes. In the first part all major factors and their influence are described briefly. Majority of the work focuses on research of other methodologies used in susceptibility models and design of own methodology. This method is unlike most of the methods used completely objective, therefore it is not possible to intervene in the results. In article all inputs and outputs of the method are described as well as all stages of calculations. Results are illustrated on specific examples. In study area most important factor for landslide susceptibility is slope, on the other hand least important is land cover. At the end of article landslide susceptibility map is created. Part of the article is discussion of results and possible improvements of the methodology.

  14. Significance tests to determine the direction of effects in linear regression models.

    Science.gov (United States)

    Wiedermann, Wolfgang; Hagmann, Michael; von Eye, Alexander

    2015-02-01

    Previous studies have discussed asymmetric interpretations of the Pearson correlation coefficient and have shown that higher moments can be used to decide on the direction of dependence in the bivariate linear regression setting. The current study extends this approach by illustrating that the third moment of regression residuals may also be used to derive conclusions concerning the direction of effects. Assuming non-normally distributed variables, it is shown that the distribution of residuals of the correctly specified regression model (e.g., Y is regressed on X) is more symmetric than the distribution of residuals of the competing model (i.e., X is regressed on Y). Based on this result, 4 one-sample tests are discussed which can be used to decide which variable is more likely to be the response and which one is more likely to be the explanatory variable. A fifth significance test is proposed based on the differences of skewness estimates, which leads to a more direct test of a hypothesis that is compatible with direction of dependence. A Monte Carlo simulation study was performed to examine the behaviour of the procedures under various degrees of associations, sample sizes, and distributional properties of the underlying population. An empirical example is given which illustrates the application of the tests in practice. © 2014 The British Psychological Society.

  15. Composition of fibrin glues significantly influences axial vascularization and degradation in isolation chamber model.

    Science.gov (United States)

    Arkudas, Andreas; Pryymachuk, Galyna; Hoereth, Tobias; Beier, Justus P; Polykandriotis, Elias; Bleiziffer, Oliver; Gulle, Heinz; Horch, Raymund E; Kneser, Ulrich

    2012-07-01

    In this study, different fibrin sealants with varying concentrations of the fibrin components were evaluated in terms of matrix degradation and vascularization in the arteriovenous loop (AVL) model of the rat. An AVL was placed in a Teflon isolation chamber filled with 500 μl fibrin gel. The matrix was composed of commercially available fibrin gels, namely Beriplast (Behring GmbH, Marburg, Germany) (group A), Evicel (Omrix Biopharmaceuticals S.A., Somerville, New Jersey, USA) (group B), Tisseel VH S/D (Baxter, Vienna, Austria) with a thrombin concentration of 4 IU/ml and a fibrinogen concentration of 80 mg/ml [Tisseel S F80 (Baxter), group C] and with an fibrinogen concentration of 20 mg/ml [Tisseel S F20 (Baxter), group D]. After 2 and 4 weeks, five constructs per group and time point were investigated using micro-computed tomography, and histological and morphometrical analysis techniques. The aprotinin, factor XIII and thrombin concentration did not affect the degree of clot degradation. An inverse relationship was found between fibrin matrix degradation and sprouting of blood vessels. By reducing the fibrinogen concentration in group D, a significantly decreased construct weight and an increased generation of vascularized connective tissue were detected. There was an inverse relationship between matrix degradation and vascularization detectable. Fibrinogen as the major matrix component showed a significant impact on the matrix properties. Alteration of fibrin gel properties might optimize formation of blood vessels.

  16. Multilevel linear modelling of the response-contingent learning of young children with significant developmental delays.

    Science.gov (United States)

    Raab, Melinda; Dunst, Carl J; Hamby, Deborah W

    2018-02-27

    The purpose of the study was to isolate the sources of variations in the rates of response-contingent learning among young children with multiple disabilities and significant developmental delays randomly assigned to contrasting types of early childhood intervention. Multilevel, hierarchical linear growth curve modelling was used to analyze four different measures of child response-contingent learning where repeated child learning measures were nested within individual children (Level-1), children were nested within practitioners (Level-2), and practitioners were nested within the contrasting types of intervention (Level-3). Findings showed that sources of variations in rates of child response-contingent learning were associated almost entirely with type of intervention after the variance associated with differences in practitioners nested within groups were accounted for. Rates of child learning were greater among children whose existing behaviour were used as the building blocks for promoting child competence (asset-based practices) compared to children for whom the focus of intervention was promoting child acquisition of missing skills (needs-based practices). The methods of analysis illustrate a practical approach to clustered data analysis and the presentation of results in ways that highlight sources of variations in the rates of response-contingent learning among young children with multiple developmental disabilities and significant developmental delays. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  17. Adjustment modes in the trajectory of progressive multiple sclerosis: a qualitative study and conceptual model.

    Science.gov (United States)

    Bogosian, Angeliki; Morgan, Myfanwy; Bishop, Felicity L; Day, Fern; Moss-Morris, Rona

    2017-03-01

    We examined cognitive and behavioural challenges and adaptations for people with progressive multiple sclerosis (MS) and developed a preliminary conceptual model of changes in adjustment over time. Using theoretical sampling, 34 semi-structured interviews were conducted with people with MS. Participants were between 41 and 77 years of age. Thirteen were diagnosed with primary progressive MS and 21 with secondary progressive MS. Data were analysed using a grounded theory approach. Participants described initially bracketing the illness off and carrying on their usual activities but this became problematic as the condition progressed and they employed different adjustment modes to cope with increased disabilities. Some scaled back their activities to live a more comfortable life, others identified new activities or adapted old ones, whereas at times, people disengaged from the adjustment process altogether and resigned to their condition. Relationships with partners, emotional reactions, environment and perception of the environment influenced adjustment, while people were often flexible and shifted among modes. Adjusting to a progressive condition is a fluid process. Future interventions can be tailored to address modifiable factors at different stages of the condition and may involve addressing emotional reactions concealing/revealing the condition and perceptions of the environment.

  18. Application of a prediction model for the progression of rheumatoid arthritis in patients with undifferentiated arthritis.

    Science.gov (United States)

    Arana-Guajardo, Ana; Pérez-Barbosa, Lorena; Vega-Morales, David; Riega-Torres, Janett; Esquivel-Valerio, Jorge; Garza-Elizondo, Mario

    2014-01-01

    Different prediction rules have been applied to patients with undifferentiated arthritis (UA) to identify those that progress to rheumatoid arthritis (RA). The Leiden Prediction Rule (LPR) has proven useful in different UA cohorts. To apply the LPR to a cohort of patients with UA of northeastern Mexico. We included 47 patients with UA, LPR was applied at baseline. They were evaluated and then classified after one year of follow-up into two groups: those who progressed to RA (according to ACR 1987) and those who did not. 43% of the AI patients developed RA. In the RA group, 56% of patients obtained a score ≤ 6 and only 15% ≥ 8. 70% who did not progress to RA had a score between 6 and ≤ 8. There was no difference in median score of LPR between groups, p=0.940. Most patients who progressed to RA scored less than 6 points in the LPR. Unlike what was observed in other cohorts, the model in our population did not allow us to predict the progression of the disease. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  19. EGFR inhibitor erlotinib delays disease progression but does not extend survival in the SOD1 mouse model of ALS.

    Directory of Open Access Journals (Sweden)

    Claire E Le Pichon

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease that causes progressive paralysis due to motor neuron death. Several lines of published evidence suggested that inhibition of epidermal growth factor receptor (EGFR signaling might protect neurons from degeneration. To test this hypothesis in vivo, we treated the SOD1 transgenic mouse model of ALS with erlotinib, an EGFR inhibitor clinically approved for oncology indications. Although erlotinib failed to extend ALS mouse survival it did provide a modest but significant delay in the onset of multiple behavioral measures of disease progression. However, given the lack of protection of motor neuron synapses and the lack of survival extension, the small benefits observed after erlotinib treatment appear purely symptomatic, with no modification of disease course.

  20. The Model of Optimum Economic Growth with the Induced Scientific-Technological Progress

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    Dilenko Viktor A.

    2017-07-01

    Full Text Available On the basis of the economic dynamics of the Harrod – Domar model, a model of optimum economic growth in line with the induced scientific-technological progress (STP has been built. In order to reflect the induced scientific-technological progress, with this model is proposed to further allocate the income element that is specially used for the investment of innovation activity, implementation of which reduces the capital intensity in development of the discussed economy. For the simplest way of presenting an economic mechanism for the investment of induced STP, analytical solutions of an appropriate task in optimum management have been obtained. Studying these decisions allowed to reveal the characteristics of the impact of parameters of scientific-technological progress and the analyzed economic system on choosing the best trajectory for its evolution. Possible directions for further developing the results presented can be considered the tasks in building and analyzing models of optimum economic growth that implement different investment options for the induced STP, as well as the models in which this investment mechanism is not exogenouslyed, but rather the result of the corresponding economic-mathematical research.

  1. A joint frailty-copula model between tumour progression and death for meta-analysis.

    Science.gov (United States)

    Emura, Takeshi; Nakatochi, Masahiro; Murotani, Kenta; Rondeau, Virginie

    2017-12-01

    Dependent censoring often arises in biomedical studies when time to tumour progression (e.g., relapse of cancer) is censored by an informative terminal event (e.g., death). For meta-analysis combining existing studies, a joint survival model between tumour progression and death has been considered under semicompeting risks, which induces dependence through the study-specific frailty. Our paper here utilizes copulas to generalize the joint frailty model by introducing additional source of dependence arising from intra-subject association between tumour progression and death. The practical value of the new model is particularly evident for meta-analyses in which only a few covariates are consistently measured across studies and hence there exist residual dependence. The covariate effects are formulated through the Cox proportional hazards model, and the baseline hazards are nonparametrically modeled on a basis of splines. The estimator is then obtained by maximizing a penalized log-likelihood function. We also show that the present methodologies are easily modified for the competing risks or recurrent event data, and are generalized to accommodate left-truncation. Simulations are performed to examine the performance of the proposed estimator. The method is applied to a meta-analysis for assessing a recently suggested biomarker CXCL12 for survival in ovarian cancer patients. We implement our proposed methods in R joint.Cox package.

  2. Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

    Science.gov (United States)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

    This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

  3. Modeling freedom from progression for standard-risk medulloblastoma: a mathematical tumor control model with multiple modes of failure

    DEFF Research Database (Denmark)

    Brodin, Nils Patrik; Vogelius, Ivan R.; Bjørk-Eriksson, Thomas

    2013-01-01

    As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published...

  4. Inference of type-specific HPV transmissibility, progression and clearance rates: a mathematical modelling approach.

    Directory of Open Access Journals (Sweden)

    Helen C Johnson

    Full Text Available Quantifying rates governing the clearance of Human Papillomavirus (HPV and its progression to clinical disease, together with viral transmissibility and the duration of naturally-acquired immunity, is essential in estimating the impact of vaccination programmes and screening or testing regimes. However, the complex natural history of HPV makes this difficult. We infer the viral transmissibility, rate of waning natural immunity and rates of progression and clearance of infection of 13 high-risk and 2 non-oncogenic HPV types, making use of a number of rich datasets from Sweden. Estimates of viral transmissibility, clearance of initial infection and waning immunity were derived in a Bayesian framework by fitting a susceptible-infectious-recovered-susceptible (SIRS transmission model to age- and type-specific HPV prevalence data from both a cross-sectional study and a randomised controlled trial (RCT of primary HPV screening. The models fitted well, but over-estimated the prevalence of four high-risk types with respect to the data. Three of these types (HPV-33, -35 and -58 are among the most closely related phylogenetically to the most prevalent HPV-16. The fourth (HPV-45 is the most closely related to HPV-18; the second most prevalent type. We suggest that this may be an indicator of cross-immunity. Rates of progression and clearance of clinical lesions were additionally estimated from longitudinal data gathered as part of the same RCT. Our estimates of progression and clearance rates are consistent with the findings of survival analysis studies and we extend the literature by estimating progression and clearance rates for non-16 and non-18 high-risk types. We anticipate that such type-specific estimates will be useful in the parameterisation of further models and in developing our understanding of HPV natural history.

  5. The Process-Oriented Simulation (POS) model for common cause failures: recent progress

    International Nuclear Information System (INIS)

    Berg, H.P.; Goertz, R.; Schimetschka, E.; Kesten, J.

    2006-01-01

    A common-cause failure (CCF) model based on stochastic simulation has been developed to complement the established approaches and to overcome some of their shortcomings. Reflecting the models proximity to the CCF process it was called Process Oriented Simulation (POS) Model. In recent years, some progress has been made to render the POS model fit for practical applications comprising the development of parameter estimates and a number of test applications in areas where results were already available - especially from CCF benchmarks - and comparison can provide insights in strong and weak points of the different approaches. In this paper, a detailed description of the POS model is provided together with the approach to parameter estimation and representative test applications. It is concluded, that the POS model has a number of strengths - especially the feature to provide reasonable extrapolation to CCF groups with high degrees of redundancy - and thus a considerable potential to complement the insights obtained from existing modeling. (orig.)

  6. Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Richard F Loeser

    Full Text Available Osteoarthritis (OA is the most common form of arthritis and has multiple risk factors including joint injury. The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model and to identify genes regulated during different stages of the disease, using RNA isolated from the joint "organ" and analyzed using microarrays. Histologic changes seen in OA, including articular cartilage lesions and osteophytes, were present in the medial tibial plateaus of the DMM knees beginning at the earliest (2 week time point and became progressively more severe by 16 weeks. 427 probe sets (371 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin. Immunostaining revealed the presence of these three proteins in cartilage and soft tissues including ligaments as well as in the fibrocartilage covering osteophytes. The results support a phasic development of OA with early matrix remodeling and transcriptional activity followed by a more quiescent period that is not maintained. This implies that the response to an OA intervention will depend on the timing of the intervention. The quiescent period at 8 weeks may be due to the maturation of the osteophytes which are thought to temporarily stabilize the joint.

  7. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Cyclosporin A significantly improves preeclampsia signs and suppresses inflammation in a rat model.

    Science.gov (United States)

    Hu, Bihui; Yang, Jinying; Huang, Qian; Bao, Junjie; Brennecke, Shaun Patrick; Liu, Huishu

    2016-05-01

    Preeclampsia is associated with an increased inflammatory response. Immune suppression might be an effective treatment. The aim of this study was to examine whether Cyclosporin A (CsA), an immunosuppressant, improves clinical characteristics of preeclampsia and suppresses inflammation in a lipopolysaccharide (LPS) induced preeclampsia rat model. Pregnant rats were randomly divided into 4 groups: group 1 (PE) rats each received LPS via tail vein on gestational day (GD) 14; group 2 (PE+CsA5) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (5mg/kg, ip) on GDs 16, 17 and 18; group 3 (PE+CsA10) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (10mg/kg, ip) on GDs 16, 17 and 18; group 4 (pregnant control, PC) rats were treated with the vehicle (saline) used for groups 1, 2 and 3. Systolic blood pressure, urinary albumin, biometric parameters and the levels of serum cytokines were measured on day 20. CsA treatment significantly reduced LPS-induced systolic blood pressure and the mean 24-h urinary albumin excretion. Pro-inflammatory cytokines IL-6, IL-17, IFN-γ and TNF-α were increased in the LPS treatment group but were reduced in (LPS+CsA) group (Ppreeclampsia signs and attenuated inflammatory responses in the LPS induced preeclampsia rat model which suggests that immunosuppressant might be an alternative management option for preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Kernel density surface modelling as a means to identify significant concentrations of vulnerable marine ecosystem indicators.

    Directory of Open Access Journals (Sweden)

    Ellen Kenchington

    Full Text Available The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify "significant concentrations" of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores, and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here

  10. Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

    Science.gov (United States)

    Camacho, A; Simão, M; Ea, H-K; Cohen-Solal, M; Richette, P; Branco, J; Cancela, M L

    2016-03-01

    Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

    Science.gov (United States)

    Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

    2014-11-01

    Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

  12. Significance of settling model structures and parameter subsets in modelling WWTPs under wet-weather flow and filamentous bulking conditions

    DEFF Research Database (Denmark)

    Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen

    2014-01-01

    Current research focuses on predicting and mitigating the impacts of high hydraulic loadings on centralized wastewater treatment plants (WWTPs) under wet-weather conditions. The maximum permissible inflow to WWTPs depends not only on the settleability of activated sludge in secondary settling tanks...... (SSTs) but also on the hydraulic behaviour of SSTs. The present study investigates the impacts of ideal and non-ideal flow (dry and wet weather) and settling (good settling and bulking) boundary conditions on the sensitivity of WWTP model outputs to uncertainties intrinsic to the one-dimensional (1-D...... of settling parameters to the total variance of the key WWTP process outputs significantly depends on the influent flow and settling conditions. The magnitude of the impact is found to vary, depending on which type of 1-D SST model is used. Therefore, we identify and recommend potential parameter subsets...

  13. An Innovative Academic Progression in Nursing Model in New York State.

    Science.gov (United States)

    Markowitz, Marianne; Bastable, Susan B

    2017-05-01

    The Dual Degree Partnership in Nursing (DDPN) is a unique articulation model created in 2005 between two nursing programs that provides a seamless pathway for students to earn both an associate's degree and a bachelor's degree in nursing while benefiting from the strengths of each program. Archival data has been systematically collected for a decade on admission, progression, retention, satisfaction, graduation, and NCLEX-RN pass rates to measure the reliability, validity, and integrity of this DDPN model for nursing education. The findings demonstrate consistent performance and positive outcomes on all factors measured, which have been benchmarked against available state and national results. This innovative approach to academic progression in nursing is replicable and serves as a prototype to educate more nurses at the baccalaureate level, which directly contributes to the Institute of Medicine's goal of 80% of RNs having a minimum of a bachelor's degree by 2020. [J Nurs Educ. 2017;56(5):266-273.]. Copyright 2017, SLACK Incorporated.

  14. Designing and Implementing the Model of Public Assessment of Social and Cultural Progress in Universities

    Directory of Open Access Journals (Sweden)

    Gholamreza Khaje Sarvi

    2013-03-01

    Full Text Available Implementing Investigations, analyzes and performance measurements in special and qualitative social/cultural arena in our country, needs local and special methodologies. Thus the aim of present article is investigating these issues: the concept of culture, classification of cultural organizations in Islamic Republic of Iran, the Pyramidal structure of cultural hierarchy, the process of development and mutual influences of institutions, reviewing related literature of policy making in cultural issues, compatibility of strategies to existing realities in cultural performance structure, double division in measures and analyzing and elaborating suggested measures in elaborating weighting model and assessment method and investigating progress measures by focusing on Islamic-Iranian pattern of progress and investigating the effects of implementing this pattern plus weighting method and using related measures and studying some university cases which are implemented in three phases in universities and high education centers overall the country. This research has shown a linear model by considering weighting coefficients.

  15. Quo natas, Danio?—Recent Progress in Modeling Cancer in Zebrafish

    Directory of Open Access Journals (Sweden)

    Stefanie Kirchberger

    2017-08-01

    Full Text Available Over the last decade, zebrafish has proven to be a powerful model in cancer research. Zebrafish form tumors that histologically and genetically resemble human cancers. The live imaging and cost-effective compound screening possible with zebrafish especially complement classic mouse cancer models. Here, we report recent progress in the field, including genetically engineered zebrafish cancer models, xenotransplantation of human cancer cells into zebrafish, promising approaches toward live investigation of the tumor microenvironment, and identification of therapeutic strategies by performing compound screens on zebrafish cancer models. Given the recent advances in genome editing, personalized zebrafish cancer models are now a realistic possibility. In addition, ongoing automation will soon allow high-throughput compound screening using zebrafish cancer models to be part of preclinical precision medicine approaches.

  16. [RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].

    Science.gov (United States)

    Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

    2015-12-01

    To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.

  17. MODELLING THE PROGRESSION OF COMPETITIVE PERFORMANCE OF AN ACADEMY'S SOCCER TEAMS

    Directory of Open Access Journals (Sweden)

    Rita M. Malcata

    2012-09-01

    Full Text Available Progression of a team's performance is a key issue in competitive sport, but there appears to have been no published research on team progression for periods longer than a season. In this study we report the game-score progression of three teams of a youth talent-development academy over five seasons using a novel analytic approach based on generalised mixed modelling. The teams consisted of players born in 1991, 1992 and 1993; they played totals of 115, 107 and 122 games in Asia and Europe between 2005 and 2010 against teams differing in age by up to 3 years. Game scores predicted by the mixed model were assumed to have an over-dispersed Poisson distribution. The fixed effects in the model estimated an annual linear pro-gression for Aspire and for the other teams (grouped as a single opponent with adjustment for home-ground advantage and for a linear effect of age difference between competing teams. A random effect allowed for different mean scores for Aspire and opposition teams. All effects were estimated as factors via log-transformation and presented as percent differences in scores. Inferences were based on the span of 90% confidence intervals in relation to thresholds for small factor effects of x/÷1.10 (+10%/-9%. Most effects were clear only when data for the three teams were combined. Older teams showed a small 27% increase in goals scored per year of age difference (90% confidence interval 13 to 42%. Aspire experienced a small home-ground advantage of 16% (-5 to 41%, whereas opposition teams experienced 31% (7 to 60% on their own ground. After adjustment for these effects, the Aspire teams scored on average 1.5 goals per match, with little change in the five years of their existence, whereas their opponents' scores fell from 1.4 in their first year to 1.0 in their last. The difference in progression was trivial over one year (7%, -4 to 20%, small over two years (15%, -8 to 44%, but unclear over >2 years. In conclusion, the generalized

  18. Uncertainty from the choice of microphysics scheme in convection-permitting models significantly exceeds aerosol effects

    Directory of Open Access Journals (Sweden)

    B. White

    2017-10-01

    Full Text Available This study investigates the hydrometeor development and response to cloud droplet number concentration (CDNC perturbations in convection-permitting model configurations. We present results from a real-data simulation of deep convection in the Congo basin, an idealised supercell case, and a warm-rain large-eddy simulation (LES. In each case we compare two frequently used double-moment bulk microphysics schemes and investigate the response to CDNC perturbations. We find that the variability among the two schemes, including the response to aerosol, differs widely between these cases. In all cases, differences in the simulated cloud morphology and precipitation are found to be significantly greater between the microphysics schemes than due to CDNC perturbations within each scheme. Further, we show that the response of the hydrometeors to CDNC perturbations differs strongly not only between microphysics schemes, but the inter-scheme variability also differs between cases of convection. Sensitivity tests show that the representation of autoconversion is the dominant factor that drives differences in rain production between the microphysics schemes in the idealised precipitating shallow cumulus case and in a subregion of the Congo basin simulations dominated by liquid-phase processes. In this region, rain mass is also shown to be relatively insensitive to the radiative effects of an overlying layer of ice-phase cloud. The conversion of cloud ice to snow is the process responsible for differences in cold cloud bias between the schemes in the Congo. In the idealised supercell case, thermodynamic impacts on the storm system using different microphysics parameterisations can equal those due to aerosol effects. These results highlight the large uncertainty in cloud and precipitation responses to aerosol in convection-permitting simulations and have important implications not only for process studies of aerosol–convection interaction, but also for

  19. Selective expression of long non-coding RNAs in a breast cancer cell progression model.

    Science.gov (United States)

    Tracy, Kirsten M; Tye, Coralee E; Page, Natalie A; Fritz, Andrew J; Stein, Janet L; Lian, Jane B; Stein, Gary S

    2018-02-01

    Long non-coding RNAs (lncRNAs) are acknowledged as regulators of cancer biology and pathology. Our goal was to perform a stringent profiling of breast cancer cell lines that represent disease progression. We used the MCF-10 series, which includes the normal-like MCF-10A, HRAS-transformed MCF-10AT1 (pre-malignant), and MCF-10CA1a (malignant) cells, to perform transcriptome wide sequencing. From these data, we have identified 346 lncRNAs with dysregulated expression across the progression series. By comparing lncRNAs from these datasets to those from an additional set of cell lines that represent different disease stages and subtypes, MCF-7 (early stage, luminal), and MDA-MB-231 (late stage, basal), 61 lncRNAs that are associated with breast cancer progression were identified. Querying breast cancer patient data from The Cancer Genome Atlas, we selected a lncRNA, IGF-like family member 2 antisense RNA 1 (IGFL2-AS1), of potential clinical relevance for functional characterization. Among the 61 lncRNAs, IGFL2-AS1 was the most significantly decreased. Our results indicate that this lncRNA plays a role in downregulating its nearest neighbor, IGFL1, and affects migration of breast cancer cells. Furthermore, the lncRNAs we identified provide a valuable resource to mechanistically and clinically understand the contribution of lncRNAs in breast cancer progression. © 2017 Wiley Periodicals, Inc.

  20. A CASE STUDY OF STUDENT’S PROGRESS IN PIANO PLAYING: THE ROLE OF TRAINING MODEL IN STUDENT’S EXPERTISE

    Directory of Open Access Journals (Sweden)

    Maja Marijan

    2016-02-01

    Full Text Available A case study of student’s progress in piano playing was carried out as an empirical research investigating student’s progress in piano performance. The research was outlined as a multiple process carrying out in three phases. The paper discusses the valuation of the training model through the assessment of the student’s level of attainment. The analysis included descriptive statistics for all the variables, and correlations between variables and the level of attainment. Factors that influence the student’s progress in piano playing, student’s individual characteristics (traits,and cognitive abilities, were measured objectively and were related to significant aspect of musical behavior. These items were assessed at the commencement of the student’s tuition program and at the cut-off date set for the study period. Findings confirmed that the change of training model has significant impact on the student’s progress in very short period, in this case three-week research period. Introduction of organized, and intuitive training model influenced cognitive abilities and motor skills, and personality constructs, such as anxiety, motivation, sense of contentment, self confidence, energy and effort. The difference is large enough to permit the conclusion that the proper training model leads to an important progress in student’s piano playing.

  1. A 3-D model of tumor progression based on complex automata driven by particle dynamics.

    Science.gov (United States)

    Wcisło, Rafał; Dzwinel, Witold; Yuen, David A; Dudek, Arkadiusz Z

    2009-12-01

    The dynamics of a growing tumor involving mechanical remodeling of healthy tissue and vasculature is neglected in most of the existing tumor models. This is due to the lack of efficient computational framework allowing for simulation of mechanical interactions. Meanwhile, just these interactions trigger critical changes in tumor growth dynamics and are responsible for its volumetric and directional progression. We describe here a novel 3-D model of tumor growth, which combines particle dynamics with cellular automata concept. The particles represent both tissue cells and fragments of the vascular network. They interact with their closest neighbors via semi-harmonic central forces simulating mechanical resistance of the cell walls. The particle dynamics is governed by both the Newtonian laws of motion and the cellular automata rules. These rules can represent cell life-cycle and other biological interactions involving smaller spatio-temporal scales. We show that our complex automata, particle based model can reproduce realistic 3-D dynamics of the entire system consisting of the tumor, normal tissue cells, blood vessels and blood flow. It can explain phenomena such as the inward cell motion in avascular tumor, stabilization of tumor growth by the external pressure, tumor vascularization due to the process of angiogenesis, trapping of healthy cells by invading tumor, and influence of external (boundary) conditions on the direction of tumor progression. We conclude that the particle model can serve as a general framework for designing advanced multiscale models of tumor dynamics and it is very competitive to the modeling approaches presented before.

  2. Progress report on SYVAC chemical modelling studies during 1984/85

    International Nuclear Information System (INIS)

    Cross, J.E.; Read, D.; Smith, G.L.; Williams, D.R.

    1985-05-01

    This report summarises progress made from April 1984 to May 1985 on chemical modelling within the DOE SYVAC project. Three new computer programs; the reaction path codes, PHREEQE and EQ3/6, and the chemical transport simulator CHEMTRN, have been acquired. Their applicability, overall capabilities, ease of use and database requirements are assessed. Coupled approaches to geochemical - hydrological modelling and the use of CHEMTRN is discussed. Modelling has been performed in connection with the ''Dry Run Assessment''. Speciation and solubilities of the actinides were simulated, assuming the vault to be a concrete solution and the geosphere to be represented by Harwell site groundwater analyses. Model verification and validation by collaboration with experimentalists and other modellers is discussed. (author)

  3. The significance of the choice of radiobiological (NTCP) models in treatment plan objective functions

    International Nuclear Information System (INIS)

    Miller, J.; Fuller, M.; Vinod, S.; Holloway, L.

    2009-01-01

    Full text: A Clinician's discrimination between radiation therapy treatment plans is traditionally a subjective process, based on experience and existing protocols. A more objective and quantitative approach to distinguish between treatment plans is to use radiobiological or dosimetric objective functions, based on radiobiological or dosimetric models. The efficacy of models is not well understood, nor is the correlation of the rank of plans resulting from the use of models compared to the traditional subjective approach. One such radiobiological model is the Normal Tissue Complication Probability (NTCP). Dosimetric models or indicators are more accepted in clinical practice. In this study, three radiobiological models, Lyman NTCP, critical volume NTCP and relative seriality NTCP, and three dosimetric models, Mean Lung Dose (MLD) and the Lung volumes irradiated at lOGy (V|0) and 20 G y (V20), were used to rank a series of treatment plans using, harm to normal (Lung) tissue as the objective criterion. None of the models considered in this study showed consistent correlation with the Radiation Oncologists plan ranking. If radiobiological or dosimetric models are to be used in objective functions for lung treatments, based on this study it is recommended that the Lyman NTCP model be used because it will provide most consistency with traditional clinician ranking.

  4. The third RAdiation transfer Model Intercomparison (RAMI) exercise: Documenting progress in canopy reflectance models

    NARCIS (Netherlands)

    Widlowski, J.L.; Taberner, M.; Pinty, B.; Bruniquel-Pinel, V.; Disney, M.I.; Fernandes, R.; Gastellu-Etchegorry, J.P.; Gobron, N.; Kuusk, A.; Lavergne, T.; LeBlanc, S.; Lewis, P.E.; Martin, E.; Mõttus, M.; North, P.R.J.; Qin, W.; Robustelli, M.; Rochdi, N.; Ruiloba, R.; Thompson, R.; Verhoef, W.; Verstraete, M.M.; Xie, D.

    2007-01-01

    [1] The Radiation Transfer Model Intercomparison ( RAMI) initiative benchmarks canopy reflectance models under well-controlled experimental conditions. Launched for the first time in 1999, this triennial community exercise encourages the systematic evaluation of canopy reflectance models on a

  5. Third Radiation Transfer Model Intercomparison (RAMI) exercise : Documenting progress in canopy reflectance models

    NARCIS (Netherlands)

    Widlowski, J.-L.; Taberner, M.; Pinty, B.; Bruniquel-Pinel, V.; Disney, M.; Fernandes, R.; Gastellu-Etchegorry, J.P.; Gobron, N.; Kuusk, A.; Lavergne, T.; Leblanc, S.; Lewis, P.E.; Martin, E.; Mottus, M.; North, P.R.J.; Qin, W.; Robustelli, M.; Rochdi, N.; Ruiloba, R.; Soler, C.; Thompson, R.; Verhoef, W.; Xie, D.; Thompson, R.

    2007-01-01

    The Radiation Transfer Model Intercomparison (RAMI) initiative benchmarks canopy reflectance models under well‐controlled experimental conditions. Launched for the first time in 1999, this triennial community exercise encourages the systematic evaluation of canopy reflectance models on a voluntary

  6. Biomedical Progress Rates as New Parameters for Models of Economic Growth in Developed Countries

    Directory of Open Access Journals (Sweden)

    Alex Zhavoronkov

    2013-11-01

    Full Text Available While the doubling of life expectancy in developed countries during the 20th century can be attributed mostly to decreases in child mortality, the trillions of dollars spent on biomedical research by governments, foundations and corporations over the past sixty years are also yielding longevity dividends in both working and retired population. Biomedical progress will likely increase the healthy productive lifespan and the number of years of government support in the old age. In this paper we introduce several new parameters that can be applied to established models of economic growth: the biomedical progress rate, the rate of clinical adoption and the rate of change in retirement age. The biomedical progress rate is comprised of the rejuvenation rate (extending the productive lifespan and the non-rejuvenating rate (extending the lifespan beyond the age at which the net contribution to the economy becomes negative. While staying within the neoclassical economics framework and extending the overlapping generations (OLG growth model and assumptions from the life cycle theory of saving behavior, we provide an example of the relations between these new parameters in the context of demographics, labor, households and the firm.

  7. Biomedical progress rates as new parameters for models of economic growth in developed countries.

    Science.gov (United States)

    Zhavoronkov, Alex; Litovchenko, Maria

    2013-11-08

    While the doubling of life expectancy in developed countries during the 20th century can be attributed mostly to decreases in child mortality, the trillions of dollars spent on biomedical research by governments, foundations and corporations over the past sixty years are also yielding longevity dividends in both working and retired population. Biomedical progress will likely increase the healthy productive lifespan and the number of years of government support in the old age. In this paper we introduce several new parameters that can be applied to established models of economic growth: the biomedical progress rate, the rate of clinical adoption and the rate of change in retirement age. The biomedical progress rate is comprised of the rejuvenation rate (extending the productive lifespan) and the non-rejuvenating rate (extending the lifespan beyond the age at which the net contribution to the economy becomes negative). While staying within the neoclassical economics framework and extending the overlapping generations (OLG) growth model and assumptions from the life cycle theory of saving behavior, we provide an example of the relations between these new parameters in the context of demographics, labor, households and the firm.

  8. Toward a Progress Indicator for Machine Learning Model Building and Data Mining Algorithm Execution: A Position Paper

    Science.gov (United States)

    Luo, Gang

    2017-01-01

    For user-friendliness, many software systems offer progress indicators for long-duration tasks. A typical progress indicator continuously estimates the remaining task execution time as well as the portion of the task that has been finished. Building a machine learning model often takes a long time, but no existing machine learning software supplies a non-trivial progress indicator. Similarly, running a data mining algorithm often takes a long time, but no existing data mining software provides a nontrivial progress indicator. In this article, we consider the problem of offering progress indicators for machine learning model building and data mining algorithm execution. We discuss the goals and challenges intrinsic to this problem. Then we describe an initial framework for implementing such progress indicators and two advanced, potential uses of them, with the goal of inspiring future research on this topic. PMID:29177022

  9. Enforcement actions: Significant actions resolved individual actions. Volume 14, Nos. 3 and 4, Part 1. Semiannual progress report, July--December 1995

    International Nuclear Information System (INIS)

    1996-02-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July - December 1995) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions

  10. Enforcement actions: Significant actions resolved individual actions. Volume 14, Nos. 3 and 4, Part 1. Semiannual progress report, July--December 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-02-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July - December 1995) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions.

  11. A Progress Review on Soot Experiments and Modeling in the Engine Combustion Network (ECN)

    KAUST Repository

    Skeen, Scott A.

    2016-04-05

    The 4th Workshop of the Engine Combustion Network (ECN) was held September 5-6, 2015 in Kyoto, Japan. This manuscript presents a summary of the progress in experiments and modeling among ECN contributors leading to a better understanding of soot formation under the ECN “Spray A” configuration and some parametric variants. Relevant published and unpublished work from prior ECN workshops is reviewed. Experiments measuring soot particle size and morphology, soot volume fraction (fv), and transient soot mass have been conducted at various international institutions providing target data for improvements to computational models. Multiple modeling contributions using both the Reynolds Averaged Navier-Stokes (RANS) Equations approach and the Large-Eddy Simulation (LES) approach have been submitted. Among these, various chemical mechanisms, soot models, and turbulence-chemistry interaction (TCI) methodologies have been considered.

  12. A Progress Review on Soot Experiments and Modeling in the Engine Combustion Network (ECN)

    KAUST Repository

    Skeen, Scott A.; Manin, Julien; Pickett, Lyle M.; Cenker, Emre; Bruneaux, Gilles; Kondo, Katsufumi; Aizawa, Tets; Westlye, Fredrik; Dalen, Kristine; Ivarsson, Anders; Xuan, Tiemin; Garcia-Oliver, Jose M; Pei, Yuanjiang; Som, Sibendu; Hu, Wang; Reitz, Rolf D.; Lucchini, Tommaso; D'Errico, Gianluca; Farrace, Daniele; Pandurangi, Sushant S.; Wright, Yuri M.; Chishty, Muhammad Aqib; Bolla, Michele; Hawkes, Evatt

    2016-01-01

    The 4th Workshop of the Engine Combustion Network (ECN) was held September 5-6, 2015 in Kyoto, Japan. This manuscript presents a summary of the progress in experiments and modeling among ECN contributors leading to a better understanding of soot formation under the ECN “Spray A” configuration and some parametric variants. Relevant published and unpublished work from prior ECN workshops is reviewed. Experiments measuring soot particle size and morphology, soot volume fraction (fv), and transient soot mass have been conducted at various international institutions providing target data for improvements to computational models. Multiple modeling contributions using both the Reynolds Averaged Navier-Stokes (RANS) Equations approach and the Large-Eddy Simulation (LES) approach have been submitted. Among these, various chemical mechanisms, soot models, and turbulence-chemistry interaction (TCI) methodologies have been considered.

  13. Longitudinal quantification of the gingival crevicular fluid proteome during progression from gingivitis to periodontitis in a canine model.

    Science.gov (United States)

    Davis, Ian J; Jones, Andrew W; Creese, Andrew J; Staunton, Ruth; Atwal, Jujhar; Chapple, Iain L C; Harris, Stephen; Grant, Melissa M

    2016-07-01

    Inflammatory periodontal disease is widespread in dogs. This study evaluated site-specific changes in the canine gingival crevicular fluid (GCF) proteome during longitudinal progression from very mild gingivitis to mild periodontitis. Periodontitis diagnosis in dogs requires general anaesthesia with associated risks and costs; our ultimate aim was to develop a periodontitis diagnostic for application in conscious dogs. The objective of this work was to identify potential biomarkers of periodontal disease progression in dogs. Gingival crevicular fluid was sampled from a total of 10 teeth in eight dogs at three different stages of health/disease and samples prepared for quantitative mass spectrometry (data available via ProteomeXchange; identifier PXD003337). A univariate mixed model analysis determined significantly altered proteins between health states and six were evaluated by ELISA. Four hundred and six proteins were identified with 84 present in all samples. The prevalence of 40 proteins was found to be significantly changed in periodontitis relative to gingivitis. ELISA measurements confirmed that haptoglobin was significantly increased. This study demonstrates for the first time that proteins detected by mass spectrometry have potential to identify novel biomarkers for canine periodontal disease. Further work is required to validate additional biomarkers for a periodontitis diagnostic. © 2016 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

  14. Innovations in individual feature history management - The significance of feature-based temporal model

    Science.gov (United States)

    Choi, J.; Seong, J.C.; Kim, B.; Usery, E.L.

    2008-01-01

    A feature relies on three dimensions (space, theme, and time) for its representation. Even though spatiotemporal models have been proposed, they have principally focused on the spatial changes of a feature. In this paper, a feature-based temporal model is proposed to represent the changes of both space and theme independently. The proposed model modifies the ISO's temporal schema and adds new explicit temporal relationship structure that stores temporal topological relationship with the ISO's temporal primitives of a feature in order to keep track feature history. The explicit temporal relationship can enhance query performance on feature history by removing topological comparison during query process. Further, a prototype system has been developed to test a proposed feature-based temporal model by querying land parcel history in Athens, Georgia. The result of temporal query on individual feature history shows the efficiency of the explicit temporal relationship structure. ?? Springer Science+Business Media, LLC 2007.

  15. Modelling the Progression of Competitive Performance of an Academy's Soccer Teams.

    Science.gov (United States)

    Malcata, Rita M; Hopkins, Will G; Richardson, Scott

    2012-01-01

    Progression of a team's performance is a key issue in competitive sport, but there appears to have been no published research on team progression for periods longer than a season. In this study we report the game-score progression of three teams of a youth talent-development academy over five seasons using a novel analytic approach based on generalised mixed modelling. The teams consisted of players born in 1991, 1992 and 1993; they played totals of 115, 107 and 122 games in Asia and Europe between 2005 and 2010 against teams differing in age by up to 3 years. Game scores predicted by the mixed model were assumed to have an over-dispersed Poisson distribution. The fixed effects in the model estimated an annual linear pro-gression for Aspire and for the other teams (grouped as a single opponent) with adjustment for home-ground advantage and for a linear effect of age difference between competing teams. A random effect allowed for different mean scores for Aspire and opposition teams. All effects were estimated as factors via log-transformation and presented as percent differences in scores. Inferences were based on the span of 90% confidence intervals in relation to thresholds for small factor effects of x/÷1.10 (+10%/-9%). Most effects were clear only when data for the three teams were combined. Older teams showed a small 27% increase in goals scored per year of age difference (90% confidence interval 13 to 42%). Aspire experienced a small home-ground advantage of 16% (-5 to 41%), whereas opposition teams experienced 31% (7 to 60%) on their own ground. After adjustment for these effects, the Aspire teams scored on average 1.5 goals per match, with little change in the five years of their existence, whereas their opponents' scores fell from 1.4 in their first year to 1.0 in their last. The difference in progression was trivial over one year (7%, -4 to 20%), small over two years (15%, -8 to 44%), but unclear over >2 years. In conclusion, the generalized mixed model

  16. On the significance of modeling nuclear fuel behavior with the right representation of physical phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Karahan, Aydin, E-mail: karahan@mit.ed [Center for Advanced Nuclear Energy Systems, Nuclear Science and Engineering Department, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 24-204, Cambridge, MA 02139 (United States); Kazimi, Mujid S. [Center for Advanced Nuclear Energy Systems, Nuclear Science and Engineering Department, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 24-204, Cambridge, MA 02139 (United States)

    2011-02-15

    Research highlights: Essence of more physics based modeling approaches to the fuel behavior problem is emphasized. Demonstrations on modeling of metallic and oxide fuel dimensional changes and fission gas behavior with more physics based and semi-empirical approaches are given. Essence of fuel clad chemical interaction modeling of the metallic fuel in an appropriate way and implications during short and long term transients for sodium fast reactor applications are discussed. - Abstract: This work emphasizes the relevance of representation of appropriate mechanisms for understanding the actual physical behavior of the fuel pin under irradiation. Replacing fully empirical simplified treatments with more rigorous semi-empirical models which include the important pieces of physics, would open the path to more accurately capture the sensitivity to various parameters such as operating conditions, geometry, composition, and enhance the uncertainty quantification process. Steady state and transient fuel behavior demonstration examples and implications are given for sodium fast reactor metallic fuels by using FEAST-METAL. The essence of appropriate modeling of the fuel clad mechanical interaction and fuel clad chemical interaction of the metallic fuels are emphasized. Furthermore, validation efforts for oxide fuel pellet swelling behavior at high temperature and high burnup LWR conditions and comparison with FRAPCON-EP and FRAPCON-3.4 codes will be given. The value of discriminating the oxide fuel swelling modes, instead of applying a linear line, is pointed out. Future directions on fuel performance modeling will be addressed.

  17. Enforcement actions: Significant actions resolved, material licensees. Semiannual progress report, July--December 1995: Volume 14, Numbers 3 and 4, Part 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-02-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  18. Enforcement actions: Significant actions resolved, material licensees (non-medical). Quarterly progress report, July--September 1994: Volume 13, Number 3, Part 3

    International Nuclear Information System (INIS)

    1994-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1994) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees (non-medical) with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated the managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Enforcement actions: Significant actions resolved material licensees (non-medical). Volume 14, No. 1, Part 3, Quarterly progress report, January--March 1995

    International Nuclear Information System (INIS)

    1995-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to Material Licensees (non-Medical) with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Enforcement actions: Significant actions resolved material licensees (non-medical). Volume 14, No. 1, Part 3, Quarterly progress report, January--March 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to Material Licensees (non-Medical) with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication.

  1. Enforcement actions: Significant actions resolved, reactor licensees. Semiannual progress report, July--December 1995. Volume 14, Numbers 3 and 4, Part 2

    International Nuclear Information System (INIS)

    1996-02-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to reactor licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  2. Enforcement actions: Significant actions resolved, material licensees. Semiannual progress report, July--December 1995: Volume 14, Numbers 3 and 4, Part 3

    International Nuclear Information System (INIS)

    1996-02-01

    This compilation summarizes significant enforcement actions that have been resolved during the period (July--December 1995) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to material licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  3. Modeling Freedom From Progression for Standard-Risk Medulloblastoma: A Mathematical Tumor Control Model With Multiple Modes of Failure

    International Nuclear Information System (INIS)

    Brodin, N. Patrik; Vogelius, Ivan R.; Björk-Eriksson, Thomas; Munck af Rosenschöld, Per; Bentzen, Søren M.

    2013-01-01

    Purpose: As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials: Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results: The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions: Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available

  4. An epidemic model for the future progression of the current Haiti cholera epidemic

    Science.gov (United States)

    Bertuzzo, E.; Mari, L.; Righetto, L.; Casagrandi, R.; Gatto, M.; Rodriguez-Iturbe, I.; Rinaldo, A.

    2012-04-01

    As a major cholera epidemic progresses in Haiti, and the figures of the infection, up to December 2011, climb to 522,000 cases and 7,000 deaths, the development of general models to track and predict the evolution of the outbreak, so as to guide the allocation of medical supplies and staff, is gaining notable urgency. We propose here a spatially explicit epidemic model that accounts for the dynamics of susceptible and infected individuals as well as the redistribution of Vibrio cholera, the causative agent of the disease, among different human communities. In particular, we model two spreading pathways: the advection of pathogens through hydrologic connections and the dissemination due to human mobility described by means of a gravity-like model. To this end the country has been divided into hydrologic units based on drainage directions derived from a digital terrain model. Moreover the population of each unit has been estimated from census data downscaled to 1 km x 1 km resolution via remotely sensed geomorphological information (LandScan project). The model directly accounts for the role of rainfall patterns in driving the seasonality of cholera outbreaks. The two main outbreaks in fact occurred during the rainy seasons (October and May) when extensive floodings severely worsened the sanitation conditions and, in turn, raised the risk of infection. The model capability to reproduce the spatiotemporal features of the epidemic up to date grants robustness to the foreseen future development. To this end, we generate realistic scenario of future precipitation in order to forecast possible epidemic paths up to the end of the 2013. In this context, the duration of acquired immunity, a hotly debated topic in the scientific community, emerges as a controlling factor for progression of the epidemic in the near future. The framework presented here can straightforwardly be used to evaluate the effectiveness of alternative intervention strategies like mass vaccinations

  5. A spatially explicit model for the future progression of the current Haiti cholera epidemic

    Science.gov (United States)

    Bertuzzo, E.; Mari, L.; Righetto, L.; Gatto, M.; Casagrandi, R.; Rodriguez-Iturbe, I.; Rinaldo, A.

    2011-12-01

    As a major cholera epidemic progresses in Haiti, and the figures of the infection, up to July 2011, climb to 385,000 cases and 5,800 deaths, the development of general models to track and predict the evolution of the outbreak, so as to guide the allocation of medical supplies and staff, is gaining notable urgency. We propose here a spatially explicit epidemic model that accounts for the dynamics of susceptible and infected individuals as well as the redistribution of textit{Vibrio cholera}, the causative agent of the disease, among different human communities. In particular, we model two spreading pathways: the advection of pathogens through hydrologic connections and the dissemination due to human mobility described by means of a gravity-like model. To this end the country has been divided into hydrologic units based on drainage directions derived from a digital terrain model. Moreover the population of each unit has been estimated from census data downscaled to 1 km x 1 km resolution via remotely sensed geomorphological information (LandScan texttrademark project). The model directly account for the role of rainfall patterns in driving the seasonality of cholera outbreaks. The two main outbreaks in fact occurred during the rainy seasons (October and May) when extensive floodings severely worsened the sanitation conditions and, in turn, raised the risk of infection. The model capability to reproduce the spatiotemporal features of the epidemic up to date grants robustness to the foreseen future development. In this context, the duration of acquired immunity, a hotly debated topic in the scientific community, emerges as a controlling factor for progression of the epidemic in the near future. The framework presented here can straightforwardly be used to evaluate the effectiveness of alternative intervention strategies like mass vaccinations, clean water supply and educational campaigns, thus emerging as an essential component of the control of future cholera

  6. Extended causal modeling to assess Partial Directed Coherence in multiple time series with significant instantaneous interactions.

    Science.gov (United States)

    Faes, Luca; Nollo, Giandomenico

    2010-11-01

    The Partial Directed Coherence (PDC) and its generalized formulation (gPDC) are popular tools for investigating, in the frequency domain, the concept of Granger causality among multivariate (MV) time series. PDC and gPDC are formalized in terms of the coefficients of an MV autoregressive (MVAR) model which describes only the lagged effects among the time series and forsakes instantaneous effects. However, instantaneous effects are known to affect linear parametric modeling, and are likely to occur in experimental time series. In this study, we investigate the impact on the assessment of frequency domain causality of excluding instantaneous effects from the model underlying PDC evaluation. Moreover, we propose the utilization of an extended MVAR model including both instantaneous and lagged effects. This model is used to assess PDC either in accordance with the definition of Granger causality when considering only lagged effects (iPDC), or with an extended form of causality, when we consider both instantaneous and lagged effects (ePDC). The approach is first evaluated on three theoretical examples of MVAR processes, which show that the presence of instantaneous correlations may produce misleading profiles of PDC and gPDC, while ePDC and iPDC derived from the extended model provide here a correct interpretation of extended and lagged causality. It is then applied to representative examples of cardiorespiratory and EEG MV time series. They suggest that ePDC and iPDC are better interpretable than PDC and gPDC in terms of the known cardiovascular and neural physiologies.

  7. Generalizability of the Disease State Index Prediction Model for Identifying Patients Progressing from Mild Cognitive Impairment to Alzheimer's Disease

    NARCIS (Netherlands)

    Hall, A.; Munoz-Ruiz, M.; Mattila, J.; Koikkalainen, J.; Tsolaki, M.; Mecocci, P.; Kloszewska, I.; Vellas, B.; Lovestone, S.; Visser, P.J.; Lotjonen, J.; Soininen, H.

    2015-01-01

    Background: The Disease State Index (DSI) prediction model measures the similarity of patient data to diagnosed stable and progressive mild cognitive impairment (MCI) cases to identify patients who are progressing to Alzheimer's disease. Objectives: We evaluated how well the DSI generalizes across

  8. White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

    Science.gov (United States)

    Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

    2010-01-01

    The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

  9. Significance of uncertainties derived from settling tank model structure and parameters on predicting WWTP performance - A global sensitivity analysis study

    DEFF Research Database (Denmark)

    Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen

    2011-01-01

    Uncertainty derived from one of the process models – such as one-dimensional secondary settling tank (SST) models – can impact the output of the other process models, e.g., biokinetic (ASM1), as well as the integrated wastewater treatment plant (WWTP) models. The model structure and parameter...... and from the last aerobic bioreactor upstream to the SST (Garrett/hydraulic method). For model structure uncertainty, two one-dimensional secondary settling tank (1-D SST) models are assessed, including a first-order model (the widely used Takács-model), in which the feasibility of using measured...... uncertainty of settler models can therefore propagate, and add to the uncertainties in prediction of any plant performance criteria. Here we present an assessment of the relative significance of secondary settling model performance in WWTP simulations. We perform a global sensitivity analysis (GSA) based...

  10. Progressive polyuria without vasopressin neuron loss in a mouse model for familial neurohypophysial diabetes insipidus.

    Science.gov (United States)

    Hayashi, Masayuki; Arima, Hiroshi; Ozaki, Noriyuki; Morishita, Yoshiaki; Hiroi, Maiko; Ozaki, Nobuaki; Nagasaki, Hiroshi; Kinoshita, Noriaki; Ueda, Masatsugu; Shiota, Akira; Oiso, Yutaka

    2009-05-01

    Familial neurohypophysial diabetes insipidus (FNDI), an autosomal dominant disorder, is mostly caused by mutations in the gene of neurophysin II (NPII), the carrier protein of arginine vasopressin (AVP). Previous studies suggest that loss of AVP neurons might be the cause of polyuria in FNDI. Here we analyzed knockin mice expressing mutant NPII that causes FNDI in humans. The heterozygous mice manifested progressive polyuria as do patients with FNDI. Immunohistochemical analyses revealed that inclusion bodies that were not immunostained with antibodies for mutant NPII, normal NPII, or AVP were present in the AVP cells in the supraoptic nucleus (SON), and that the size of inclusion bodies gradually increased in parallel with the increases in urine volume. Electron microscopic analyses showed that aggregates existed in the endoplasmic reticulum (ER) as well as in the nucleus of AVP neurons in 1-mo-old heterozygous mice. At 12 mo, dilated ER filled with aggregates occupied the cytoplasm of AVP cells, while few aggregates were found in the nucleus. Analyses with in situ hybridization revealed that expression of AVP mRNA was significantly decreased in the SON in the heterozygous mice compared with that in wild-type mice. Counting cells expressing AVP mRNA in the SON indicated that polyuria had progressed substantially in the absence of neuronal loss. These data suggest that cell death is not the primary cause of polyuria in FNDI, and that the aggregates accumulated in the ER might be involved in the dysfunction of AVP neurons that lead to the progressive polyuria.

  11. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  12. Developing Quantum Chemical and Polyparameter Models for Predicting Environmentally Significant Parameters for New Munition Compounds

    Science.gov (United States)

    2017-05-31

    in fish , plants, and soil invertebrates have been used to build the models. In addition the BCFs for a soil invertebrate (oligochaete Eisenia......Streit B, Nagel R. Tubifex tubifex as a link in food chain transfer of hexachlorobenzene from contaminated sediment to fish . Hydrobiologia

  13. 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.

  14. Progressive Conversion from B-rep to BSP for Streaming Geometric Modeling.

    Science.gov (United States)

    Bajaj, Chandrajit; Paoluzzi, Alberto; Scorzelli, Giorgio

    2006-01-01

    We introduce a novel progressive approach to generate a Binary Space Partition (BSP) tree and a convex cell decomposition for any input triangles boundary representation (B-rep), by utilizing a fast calculation of the surface inertia. We also generate a solid model at progressive levels of detail. This approach relies on a variation of standard BSP tree generation, allowing for labeling cells as in, out and fuzzy, and which permits a comprehensive representation of a solid as the Hasse diagram of a cell complex. Our new algorithm is embedded in a streaming computational framework, using four types of dataflow processes that continuously produce, transform, combine or consume subsets of cells depending on their number or input/output stream. A varied collection of geometric modeling techniques are integrated in this streaming framework, including polygonal, spline, solid and heterogeneous modeling with boundary and decompositive representations, Boolean set operations, Cartesian products and adaptive refinement. The real-time B-rep to BSP streaming results we report in this paper are a large step forward in the ultimate unification of rapid conceptual and detailed shape design methodologies.

  15. EGovernment Stage Model: Evaluating the Rate of Web Development Progress of Government Websites in Saudi Arabia

    OpenAIRE

    Osama Alfarraj; Steve Drew; Rayed Abdullah AlGhamdi

    2011-01-01

    This paper contributes to the issue of eGovernment implementation in Saudi Arabia by discussing the current situation of ministry websites. It evaluates the rate of web development progress of vital government websites in Saudi Arabia using the eGovernment stage model. In 2010, Saudi Arabia ranked 58th in the world and 4th in the Gulf region in eGovernment readiness according to United Nations reports. In particular, Saudi Arabia has ranked 75th worldwide for its online service index and its ...

  16. Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress

    Science.gov (United States)

    Milad, Mohammed R.; Quirk, Gregory J.

    2016-01-01

    The psychology of extinction has been studied for decades. Approximately 10 years ago, however, there began a concerted effort to understand the neural circuits of extinction of fear conditioning, in both animals and humans. Progress during this period has been facilitated by an unusual degree of coordination between rodent and human researchers examining fear extinction. This successful research program could serve as a model for translational research in other areas of behavioral neuroscience. Here we review the major advances and highlight new approaches to understanding and exploiting fear extinction. PMID:22129456

  17. MRI and morphological observation in C6 glioma model rats and significance

    International Nuclear Information System (INIS)

    Zhou Ying; Yuan Bo; Wang Hao; Lu Jin; Yuan Changji; Ma Yue; Tong Dan; Zhang Kun; Gao Feng; Wu Xiaogang

    2013-01-01

    Objective: To establish stable and reliable rat C6 glioma model, and to perform MRI dynamic observation and pathomorphological observation in model animal brain, and to provide experimental basis for pharmaceutical research on anti-glioma drugs. Methods: The C6 glioma cells were cultured and 20 μL cultural fluid containing 1×10 6 C6 cells was sterotactically implanted into the left caudate nuclei in 10 male Wistar rats, respectively. The changes in the behavior of the rats after implantation were observed and recorded. MRI dynamic scanning was performed in 10 rats 2, 3 and 4 weeks after implantation and the brain tissues were taken for general and pathological examination when the 10 rats were naturally dead. The survival period of tumor-bearing rats was calculated. Results: 2 weeks after implantation the rats showed decreased activities and food intake, fur lackluster, and conjunctival congestion and so on; 3 weeks later, some rats appeared nerve symptoms such as body twitch, body hemiplegy, body distortion, rotation and so on. All the 10 rats died in 8-30 d. The median survival period of the tumor-bearing rats was 18 d, the average survival period was (18.3±7.3) d. The pathological examination showed that the tumor cells were arranged irregularly closely and karyokinesis was easy to see; tumor vascular tissue proliferation and tumor invasive growth into surrounding normal tissues were found. The expression of glial fibrillary acidic protein (GFAP) was positive in the tumors. Conclusion: A stable animal model of intracranial glioma is successfully established by stereotactic implantation of C6 cells into the rat caudate nucleus. The results of MRI dynamic observation and pathohistological observation on the model animal brain tissue. Can provide experimental basis for selecting the appropriate time window to perform the pharmaceutical research on anti-glioma drugs. (authors)

  18. Inhibition of 5-Lipoxygenase inhibitor zileuton in high-fat diet-induced nonalcoholic fatty liver disease progression model

    Directory of Open Access Journals (Sweden)

    Kuifen Ma

    2017-11-01

    Full Text Available Objective(s: Arachidonic Acid/5-lipoxygenase (AA/5-LOX pathway connects lipid metabolism and proinflammatory cytokine, which are both related to the development and progression of nonalcoholic fatty liver disease (NAFLD. Therefore, the present study was designed to investigate the role of AA/5-LOX pathway in progression of NAFLD, and the effect of zileuton, an inhibitor of 5-LOX, in this model. Materials and Methods: Animal model for progression of NAFLD was established via feeding high saturated fat diet (HFD. Liver function, HE staining, NAFLD activity score (NAS were used to evaluate NAFLD progression. We detected the lipid metabolism substrates: free fatty acids (FFA and AA, products: cysteinyl-leukotrienes (CysLTs, and changes in gene and protein level of key enzyme in AA/5-LOX pathway including PLA2 and 5-LOX. Furthermore, we determined whether NAFLD progression pathway was delayed or reversed when zileuton (1-[1-(1-benzothiophen-2-ylethyl]-1-hydroxyurea was administrated. Results: Rat model for progression of NAFLD was well established as analyzed by liver transaminase activities, hematoxylin-eosin (HE staining and NAS. The concentrations of substrates and products in AA/5-LOX pathway were increased with the progression of NAFLD. mRNA and protein expression of PLA2 and 5-LOX were all enhanced. Moreover, administration of zileuton inhibited AA/5-LOX pathway and reversed the increased transamine activities and NAS. Conclusion: AA/5-LOX pathway promotes the progression of NAFLD, which can be reversed by zileuton.

  19. On the significance of the noise model for the performance of a linear MPC in closed-loop operation

    DEFF Research Database (Denmark)

    Hagdrup, Morten; Boiroux, Dimitri; Mahmoudi, Zeinab

    2016-01-01

    This paper discusses the significance of the noise model for the performance of a Model Predictive Controller when operating in closed-loop. The process model is parametrized as a continuous-time (CT) model and the relevant sampled-data filtering and control algorithms are developed. Using CT...... models typically means less parameters to identify. Systematic tuning of such controllers is discussed. Simulation studies are conducted for linear time-invariant systems showing that choosing a noise model of low order is beneficial for closed-loop performance. (C) 2016, IFAC (International Federation...

  20. Data-driven models of dominantly-inherited Alzheimer's disease progression.

    Science.gov (United States)

    Oxtoby, Neil P; Young, Alexandra L; Cash, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Bateman, Randall J; Fox, Nick C; Schott, Jonathan M; Alexander, Daniel C

    2018-03-22

    Dominantly-inherited Alzheimer's disease is widely hoped to hold the key to developing interventions for sporadic late onset Alzheimer's disease. We use emerging techniques in generative data-driven disease progression modelling to characterize dominantly-inherited Alzheimer's disease progression with unprecedented resolution, and without relying upon familial estimates of years until symptom onset. We retrospectively analysed biomarker data from the sixth data freeze of the Dominantly Inherited Alzheimer Network observational study, including measures of amyloid proteins and neurofibrillary tangles in the brain, regional brain volumes and cortical thicknesses, brain glucose hypometabolism, and cognitive performance from the Mini-Mental State Examination (all adjusted for age, years of education, sex, and head size, as appropriate). Data included 338 participants with known mutation status (211 mutation carriers in three subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to four visits each, 1.1 ± 1.9 years in duration; spanning 30 years before, to 21 years after, parental age of symptom onset). We used an event-based model to estimate sequences of biomarker changes from baseline data across disease subtypes (mutation groups), and a differential equation model to estimate biomarker trajectories from longitudinal data (up to 66 mutation carriers, all subtypes combined). The two models concur that biomarker abnormality proceeds as follows: amyloid deposition in cortical then subcortical regions (∼24 ± 11 years before onset); phosphorylated tau (17 ± 8 years), tau and amyloid-β changes in cerebrospinal fluid; neurodegeneration first in the putamen and nucleus accumbens (up to 6 ± 2 years); then cognitive decline (7 ± 6 years), cerebral hypometabolism (4 ± 4 years), and further regional neurodegeneration. Our models predicted symptom onset more accurately than predictions that used familial estimates: root mean squared error of 1

  1. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

    Directory of Open Access Journals (Sweden)

    Sara Marcó

    2016-09-01

    Full Text Available Mucopolysaccharidosis type IIIC (MPSIIIC is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches.

  2. Assessment of Food Chain Pathway Parameters in Biosphere Models: Annual Progress Report for Fiscal Year 2004

    Energy Technology Data Exchange (ETDEWEB)

    Napier, Bruce A.; Krupka, Kenneth M.; Fellows, Robert J.; Cataldo, Dominic A.; Valenta, Michelle M.; Gilmore, Tyler J.

    2004-12-02

    This Annual Progress Report describes the work performed and summarizes some of the key observations to date on the U.S. Nuclear Regulatory Commission’s project Assessment of Food Chain Pathway Parameters in Biosphere Models, which was established to assess and evaluate a number of key parameters used in the food-chain models used in performance assessments of radioactive waste disposal facilities. Section 2 of this report describes activities undertaken to collect samples of soils from three regions of the United States, the Southeast, Northwest, and Southwest, and perform analyses to characterize their physical and chemical properties. Section 3 summarizes information gathered regarding agricultural practices and common and unusual crops grown in each of these three areas. Section 4 describes progress in studying radionuclide uptake in several representative crops from the three soil types in controlled laboratory conditions. Section 5 describes a range of international coordination activities undertaken by Project staff in order to support the underlying data needs of the Project. Section 6 provides a very brief summary of the status of the GENII Version 2 computer program, which is a “client” of the types of data being generated by the Project, and for which the Project will be providing training to the US NRC staff in the coming Fiscal Year. Several appendices provide additional supporting information.

  3. Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

  4. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  5. Support for significant evolutions of the user data model in ROOT files

    International Nuclear Information System (INIS)

    Canal, Ph; Russo, P; Brun, R; Janyst, L; Fine, V; Lauret, J

    2010-01-01

    One of the main strengths of ROOT input and output (I/O) is its inherent support for schema evolution. Two distinct modes are supported, one manual via a hand coded streamer function and one fully automatic via the ROOT StreamerInfo. One draw back of the streamer functions is that they are not usable by TTree objects in split mode. Until now, the user could not customize the automatic schema evolution mechanism and the only mechanism to go beyond the default rules was to revert to using the streamer function. In ROOT 5.22/00, we introduced a new mechanism which allows user provided extensions of the automatic schema evolution that can be used in object-wise, member-wise and split modes. This paper will describe the many possibilities ranging from the simple assignment of transient members to the complex reorganization of the user's object model.

  6. An efficient numerical progressive diagonalization scheme for the quantum Rabi model revisited

    International Nuclear Information System (INIS)

    Pan, Feng; Bao, Lina; Dai, Lianrong; Draayer, Jerry P

    2017-01-01

    An efficient numerical progressive diagonalization scheme for the quantum Rabi model is revisited. The advantage of the scheme lies in the fact that the quantum Rabi model can be solved almost exactly by using the scheme that only involves a finite set of one variable polynomial equations. The scheme is especially efficient for a specified eigenstate of the model, for example, the ground state. Some low-lying level energies of the model for several sets of parameters are calculated, of which one set of the results is compared to that obtained from the Braak’s exact solution proposed recently. It is shown that the derivative of the entanglement measure defined in terms of the reduced von Neumann entropy with respect to the coupling parameter does reach the maximum near the critical point deduced from the classical limit of the Dicke model, which may provide a probe of the critical point of the crossover in finite quantum many-body systems, such as that in the quantum Rabi model. (paper)

  7. Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer

    Directory of Open Access Journals (Sweden)

    Engelhardt John F

    2003-11-01

    Full Text Available Abstract Mammalian cloning by nuclear transfer from somatic cells has created new opportunities to generate animal models of genetic diseases in species other than mice. Although genetic mouse models play a critical role in basic and applied research for numerous diseases, often mouse models do not adequately reproduce the human disease phenotype. Cystic fibrosis (CF is one such disease. Targeted ablation of the cystic fibrosis transmembrane conductance regulator (CFTR gene in mice does not adequately replicate spontaneous bacterial infections observed in the human CF lung. Hence, several laboratories are pursuing alternative animal models of CF in larger species such as the pig, sheep, rabbits, and ferrets. Our laboratory has focused on developing the ferret as a CF animal model. Over the past few years, we have investigated several experimental parameters required for gene targeting and nuclear transfer (NT cloning in the ferret using somatic cells. In this review, we will discuss our progress and the hurdles to NT cloning and gene-targeting that accompany efforts to generate animal models of genetic diseases in species such as the ferret.

  8. Impacts of fresh lime juice and peel on atherosclerosis progression in an animal model.

    Science.gov (United States)

    Boshtam, Maryam; Asgary, Sedigheh; Moshtaghian, Jamal; Naderi, Gholamali; Jafari-Dinani, Narges

    2013-11-01

    The main protective role of antioxidants in the progression of atherosclerosis has been shown in some studies. Therefore, this project evaluated the effects of Citrus aurantifolia (Christm) juice and peel on antioxidant activity and atherosclerosis progression in rabbits receiving a hypercholesterolemic diet. Forty white New Zealand male rabbits were randomly allocated to four groups. All groups were on hypercholesterolemic diet for two months. While the first group was considered as the hypercholesterolemic control, groups 2 and 3 (intervention groups) received 5 ml/day lime juice and 1 g/day dried lime peel powder, respectively. Group 4 was fed a normal diet (normal control). Before and after the study, weight was measured and a fasting blood specimen was taken from the rabbits. Serum lipids analyses and antioxidant activity evaluations were then performed. The rabbits' aorta and coronary arteries were separated and the presence of fatty streaks was studied. Comparing to the hypercholesterolemic control group (-25.2 ± 7.0), only the plasma total antioxidant capacity change was significantly more in rabbits supplemented with lime juice (16.3 ± 14.7) and peel (8.6 ± 7.1) (P = 0.008). The presence of fatty streaks in coronary arteries and aorta of the intervention groups [juice (0.2 ± 0.01); peel (0.0 ± 0.00)] was significantly decreased compared to the hypercholesterolemic control group (1.2 ± 0.4) (P lime peel is more effective than lime juice.

  9. Towards the Significance of Decision Aid in Building Information Modeling (BIM Software Selection Process

    Directory of Open Access Journals (Sweden)

    Omar Mohd Faizal

    2014-01-01

    Full Text Available Building Information Modeling (BIM has been considered as a solution in construction industry to numerous problems such as delays, increased lead in times and increased costs. This is due to the concept and characteristic of BIM that will reshaped the way construction project teams work together to increase productivity and improve the final project outcomes (cost, time, quality, safety, functionality, maintainability, etc.. As a result, the construction industry has witnesses numerous of BIM software available in market. Each of this software has offers different function, features. Furthermore, the adoption of BIM required high investment on software, hardware and also training expenses. Thus, there is indentified that there is a need of decision aid for appropriated BIM software selection that fulfill the project needs. However, research indicates that there is limited study attempt to guide decision in BIM software selection problem. Thus, this paper highlight the importance of decision making and support for BIM software selection as it is vital to increase productivity, construction project throughout building lifecycle.

  10. Roles and significance of water conducting features for transport models in performance assessment

    International Nuclear Information System (INIS)

    Carrera, J.; Sanchez-Vila, X.; Medina, A.

    1999-01-01

    The term water conducting features (WCF) refers to zones of high hydraulic conductivity. In the context of waste disposal, it is further implied that they are narrow so that chances of sampling them are low. Yet, they may carry significant amounts of water. Moreover, their relatively small volumetric water content causes solutes to travel fast through them. Water-conducting features are a rather common feature of natural media. The fact that they have become a source of concern in recent years, reflects more the increased level of testing and monitoring than any intrinsic property of low permeability media. Accurate simulations of solute transport require a realistic accounting for water conducting features. Methods are presented to do so and examples are shown to illustrate these methods. Since detailed accounting of WCF's will not be possible in actual performance assessments, efforts should be directed towards typification, so as to identify the essential effects of WCF's on solute transport through different types of rocks. Field evidence suggests that, although individual WCF's may be difficult to characterize, their effects are quite predictable. (author)

  11. The significance of calcified fibrocartilage on the cortical endplate of the translational sheep spine model.

    Science.gov (United States)

    Sinclair, Sarina K; Bell, Spencer; Epperson, Richard Tyler; Bloebaum, Roy D

    2013-05-01

    To gain an understanding of the vertebral cortical endplate and factors that may affect the ability to achieve skeletal attachment to intervertebral implants and fusion, this study aimed to characterize the hypermineralized tissue on the cortical endplate of the vertebral body on a commonly used animal model. Skeletally mature sheep were injected with tetracycline prior to euthanasia and the C2-C3, T5-T6, and L2-L3 spinal motion segments were excised and prepared. Vertebral tissues were imaged using backscatter electron (BSE) imaging, histology, and tetracycline labeling was used to assess bone remodeling within different tissue layers. It was determined that the hypermineralized tissue layer was calcified fibrocartilage (CFC). No tetracycline labels were identified in the CFC layer, in contrast to single and double labels that were present in the underlying bone, indicating the CFC present on the cortical endplate was not being actively remodeled. The average thickness of the CFC layer was 146.3 ± 70.53 µm in the cervical region, 98.2 ± 40.29 µm in the thoracic region, and 150.89 ± 69.25 µm in the lumbar region. This difference in thickness may be attributed to the regional biomechanical properties of the spine. Results from this investigation indicate the presence of a nonremodeling tissue on the cortical endplate of the vertebral body in sheep spines, which attaches the intervertebral disc to the vertebrae. This tissue, if not removed, would likely prevent successful bony attachment to an intervertebral device in spinal fusion studies and total disc replacement surgeries. Copyright © 2013 Wiley Periodicals, Inc.

  12. Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.

    Directory of Open Access Journals (Sweden)

    Nadja Rodrigues de Melo

    Full Text Available Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC and amphotericin B (AMPH. Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.

  13. A Progressive Damage Model for unidirectional Fibre Reinforced Composites with Application to Impact and Penetration Simulation

    Science.gov (United States)

    Kerschbaum, M.; Hopmann, C.

    2016-06-01

    The computationally efficient simulation of the progressive damage behaviour of continuous fibre reinforced plastics is still a challenging task with currently available computer aided engineering methods. This paper presents an original approach for an energy based continuum damage model which accounts for stress-/strain nonlinearities, transverse and shear stress interaction phenomena, quasi-plastic shear strain components, strain rate effects, regularised damage evolution and consideration of load reversal effects. The physically based modelling approach enables experimental determination of all parameters on ply level to avoid expensive inverse analysis procedures. The modelling strategy, implementation and verification of this model using commercially available explicit finite element software are detailed. The model is then applied to simulate the impact and penetration of carbon fibre reinforced cross-ply specimens with variation of the impact speed. The simulation results show that the presented approach enables a good representation of the force-/displacement curves and especially well agreement with the experimentally observed fracture patterns. In addition, the mesh dependency of the results were assessed for one impact case showing only very little change of the simulation results which emphasises the general applicability of the presented method.

  14. A model to calculate the progression of the centre of pressure under the foot during gait analysis.

    Science.gov (United States)

    Louey, Melissa Gar Yee; Mudge, Anita; Wojciechowski, Elizabeth; Sangeux, Morgan

    2017-09-01

    Pedobarography and the centre of pressure (COP) progression is useful to understand foot function. Pedobarography is often unavailable in gait laboratories or completed asynchronously to kinematic and kinetic data collection. This paper presents a model that allows calculation of COP progression synchronously using force plate data. The model is an adjunct to Plug-In-Gait and was applied to 49 typically developing children to create reference COP data. COP progressions were noted to spend 8% of stance behind the ankle joint centre, traverse lateral of the longitudinal axis of the foot through the midfoot for 76% of stance and finishing past the second metatarsal head on the medial side for 16% of stance. It is hoped the model will bridge the information gap for gait laboratories lacking pedobarography during foot assessments and will open up the possibility of retrospective research into COP progression based indices on kinematic data. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Metformin blocks progression of obesity-activated thyroid cancer in a mouse model.

    Science.gov (United States)

    Park, Jeongwon; Kim, Won Gu; Zhao, Li; Enomoto, Keisuke; Willingham, Mark; Cheng, Sheue-Yann

    2016-06-07

    Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/-mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/-mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/-mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/-mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/-mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer.

  16. Co-firing biomass and coal-progress in CFD modelling capabilities

    DEFF Research Database (Denmark)

    Kær, Søren Knudsen; Rosendahl, Lasse Aistrup; Yin, Chungen

    2005-01-01

    This paper discusses the development of user defined FLUENT™ sub models to improve the modelling capabilities in the area of large biomass particle motion and conversion. Focus is put on a model that includes the influence from particle size and shape on the reactivity by resolving intra-particle......This paper discusses the development of user defined FLUENT™ sub models to improve the modelling capabilities in the area of large biomass particle motion and conversion. Focus is put on a model that includes the influence from particle size and shape on the reactivity by resolving intra......-particle gradients. The advanced reaction model predicts moisture and volatiles release characteristics that differ significantly from those found from a 0-dimensional model partly due to the processes occurring in parallel rather than sequentially. This is demonstrated for a test case that illustrates single...

  17. 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

  18. Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

    Science.gov (United States)

    Luján, S; Santamaría, C; Pontones, J L; Ruiz-Cerdá, J L; Trassierra, M; Vera-Donoso, C D; Solsona, E; Jiménez-Cruz, F

    2014-12-01

    To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  19. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model.

    Science.gov (United States)

    Zhang, Zhuo; Leong, Daniel J; Xu, Lin; He, Zhiyong; Wang, Angela; Navati, Mahantesh; Kim, Sun J; Hirsh, David M; Hardin, John A; Cobelli, Neil J; Friedman, Joel M; Sun, Hui B

    2016-06-03

    Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1β. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan

  20. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech.

    Science.gov (United States)

    Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Lowe, Val J; Jack, Clifford R; Josephs, Keith A

    2016-01-01

    Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects.

  1. Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

    Science.gov (United States)

    Ishibashi, Hidetoshi; Minakawa, Eiko N.; Motohashi, Hideyuki H.; Takayama, Osamu; Popiel, H. Akiko; Puentes, Sandra; Owari, Kensuke; Nakatani, Terumi; Nogami, Naotake; Yamamoto, Kazuhiro; Yonekawa, Takahiro; Tanaka, Yoko; Fujita, Naoko; Suzuki, Hikaru; Aizawa, Shu; Nagano, Seiichi; Yamada, Daisuke; Wada, Keiji; Kohsaka, Shinichi

    2017-01-01

    Abstract Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases. PMID:28374014

  2. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech

    Directory of Open Access Journals (Sweden)

    Jennifer L. Whitwell

    2016-01-01

    Full Text Available Beta-amyloid (Aβ deposition can be observed in primary progressive aphasia (PPA and progressive apraxia of speech (PAOS. While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified and PAOS (n = 42 subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+ status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+ status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+ status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified

  3. A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy.

    Science.gov (United States)

    van Leeuwen, Pim J; Hayen, Andrew; Thompson, James E; Moses, Daniel; Shnier, Ron; Böhm, Maret; Abuodha, Magdaline; Haynes, Anne-Maree; Ting, Francis; Barentsz, Jelle; Roobol, Monique; Vass, Justin; Rasiah, Krishan; Delprado, Warick; Stricker, Phillip D

    2017-12-01

    To develop and externally validate a predictive model for detection of significant prostate cancer. Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P prostate cancer. Individualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  4. Enhanced expression of melanoma progression markers in mouse model of sleep apnea

    Directory of Open Access Journals (Sweden)

    S. Perini

    2016-07-01

    Full Text Available Introduction: Obstructive sleep apnea has been associated with higher cancer incidence and mortality. Increased melanoma aggressivity was reported in obstructive sleep apnea patients. Mice exposed to intermittent hypoxia (IH mimicking sleep apnea show enhanced melanoma growth. Markers of melanoma progression have not been investigated in this model. Objective: The present study examined whether IH affects markers of melanoma tumor progression. Methods: Mice were exposed to isocapnic IH to a nadir of 8% oxygen fraction for 14 days. One million B16F10 melanoma cells were injected subcutaneously. Immunohistochemistry staining for Ki-67, PCNA, S100-beta, HMB-45, Melan-A, TGF-beta, Caspase-1, and HIF-1alpha were quantified using Photoshop. Results: Percentage of positive area stained was higher in IH than sham IH group for Caspase-1, Ki-67, PCNA, and Melan-A. The greater expression of several markers of tumor aggressiveness, including markers of ribosomal RNA transcription (Ki-67 and of DNA synthesis (PCNA, in mice exposed to isocapnic IH than in controls provide molecular evidence for a apnea–cancer relationship. Conclusions: These findings have potential repercussions in the understanding of differences in clinical course of tumors in obstructive sleep apnea patients. Further investigation is necessary to confirm mechanisms of these descriptive results. Keywords: Apnea, Melanoma, Biological markers

  5. Blood Transcriptional Signatures for Disease Progression in a Rat Model of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Michał Korostyński

    2017-01-01

    Full Text Available Biomarkers of osteoarthritis (OA that can accurately diagnose the disease at the earliest stage would significantly support efforts to develop treatments for prevention and early intervention. We have sought to determine the time course of alterations in peripheral blood gene expression profile associated with the development of OA. Blood samples were collected from a tail vein of individual rats with monosodium iodoacetate- (MIA- induced OA (2, 14, 21, and 28 days after the treatment. We used whole-genome microarrays to reveal OA-related transcriptional alterations of 72 transcripts. Three main groups of coexpressed genes revealed diverse time-dependent profiles of up- and downregulation. Functional links that connect expression of the gradually downregulated genes to the G13 signaling pathway were indicated. The mRNA abundance levels of the identified transcripts were further analyzed in publicly available gene expression dataset obtained from a GARP study cohort of OA patients. We revealed three-gene signature differentially expressed in both rat and human blood (TNK2, KCTD2, and WDR37. The alterations in expression of the selected transcripts in peripheral blood samples of the patients indicate heterogeneity of the OA profiles potentially related to disease progress and severity of clinical symptoms. Our study identifies several potential stage-specific biomarkers of OA progression.

  6. A Progressive Damage Model for Predicting Permanent Indentation and Impact Damage in Composite Laminates

    Science.gov (United States)

    Ji, Zhaojie; Guan, Zhidong; Li, Zengshan

    2017-10-01

    In this paper, a progressive damage model was established on the basis of ABAQUS software for predicting permanent indentation and impact damage in composite laminates. Intralaminar and interlaminar damage was modelled based on the continuum damage mechanics (CDM) in the finite element model. For the verification of the model, low-velocity impact tests of quasi-isotropic laminates with material system of T300/5228A were conducted. Permanent indentation and impact damage of the laminates were simulated and the numerical results agree well with the experiments. It can be concluded that an obvious knee point can be identified on the curve of the indentation depth versus impact energy. Matrix cracking and delamination develops rapidly with the increasing impact energy, while considerable amount of fiber breakage only occurs when the impact energy exceeds the energy corresponding to the knee point. Predicted indentation depth after the knee point is very sensitive to the parameter μ which is proposed in this paper, and the acceptable value of this parameter is in range from 0.9 to 1.0.

  7. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Progress and Preliminary Results

    Science.gov (United States)

    Rosenzweig, C.

    2011-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a distributed climate-scenario simulation exercise for historical model intercomparison and future climate change conditions with participation of multiple crop and agricultural trade modeling groups around the world. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Recent progress and the current status of AgMIP will be presented, highlighting three areas of activity: preliminary results from crop pilot studies, outcomes from regional workshops, and emerging scientific challenges. AgMIP crop modeling efforts are being led by pilot studies, which have been established for wheat, maize, rice, and sugarcane. These crop-specific initiatives have proven instrumental in testing and contributing to AgMIP protocols, as well as creating preliminary results for aggregation and input to agricultural trade models. Regional workshops are being held to encourage collaborations and set research activities in motion for key agricultural areas. The first of these workshops was hosted by Embrapa and UNICAMP and held in Campinas, Brazil. Outcomes from this meeting have informed crop modeling research activities within South America, AgMIP protocols, and future regional workshops. Several scientific challenges have emerged and are currently being addressed by AgMIP researchers. Areas of particular interest include geospatial weather generation, ensemble methods for climate scenarios and crop models, spatial aggregation of field-scale yields to regional and global production, and characterization of future changes in climate variability.

  8. Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features.

    Directory of Open Access Journals (Sweden)

    Fumiaki Sato

    2008-04-01

    Full Text Available Barrett's esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett's esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett's esophagus. Moreover, high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency.We defined high-grade dysplasia as endpoint of progression, and Barrett's esophagus progressor patients as Barrett's esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barrett's esophagus tissues obtained from 35 progressor and 27 non-progressor Barrett's esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC curve: 0.8386 and 0.7910, respectively, Barrett's esophagus specimens were stratified into high-risk (HR, intermediate-risk (IR, or low-risk (LR groups. This 3-tiered stratification method retained both the high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p = 0.0022 (HR vs. IR and p<0.0001 (HR or IR vs. LR. Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy.This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.

  9. A critical review of predictive models for the onset of significant void in forced-convection subcooled boiling

    International Nuclear Information System (INIS)

    Dorra, H.; Lee, S.C.; Bankoff, S.G.

    1993-06-01

    This predictive models for the onset of significant void (OSV) in forced-convection subcooled boiling are reviewed and compared with extensive data. Three analytical models and seven empirical correlations are considered in this review. These models and correlations are put onto a common basis and are compared, again on a common basis, with a variety of data. The evaluation of their range of validity and applicability under various operating conditions are discussed. The results show that the correlations of Saha-Zuber seems to be the best model to predict OSV in vertical subcooled boiling flow

  10. Bayesian mixture modeling of significant p values: A meta-analytic method to estimate the degree of contamination from H₀.

    Science.gov (United States)

    Gronau, Quentin Frederik; Duizer, Monique; Bakker, Marjan; Wagenmakers, Eric-Jan

    2017-09-01

    Publication bias and questionable research practices have long been known to corrupt the published record. One method to assess the extent of this corruption is to examine the meta-analytic collection of significant p values, the so-called p -curve (Simonsohn, Nelson, & Simmons, 2014a). Inspired by statistical research on false-discovery rates, we propose a Bayesian mixture model analysis of the p -curve. Our mixture model assumes that significant p values arise either from the null-hypothesis H ₀ (when their distribution is uniform) or from the alternative hypothesis H1 (when their distribution is accounted for by a simple parametric model). The mixture model estimates the proportion of significant results that originate from H ₀, but it also estimates the probability that each specific p value originates from H ₀. We apply our model to 2 examples. The first concerns the set of 587 significant p values for all t tests published in the 2007 volumes of Psychonomic Bulletin & Review and the Journal of Experimental Psychology: Learning, Memory, and Cognition; the mixture model reveals that p values higher than about .005 are more likely to stem from H ₀ than from H ₁. The second example concerns 159 significant p values from studies on social priming and 130 from yoked control studies. The results from the yoked controls confirm the findings from the first example, whereas the results from the social priming studies are difficult to interpret because they are sensitive to the prior specification. To maximize accessibility, we provide a web application that allows researchers to apply the mixture model to any set of significant p values. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Effects of Vitamin D Supplementation during the Induction and Progression of Osteoarthritis in a Rat Model

    Directory of Open Access Journals (Sweden)

    E. C. Castillo

    2012-01-01

    Full Text Available Epidemiological studies correlate low levels of vitamin D with the osteoarthritis (OA progression. Cytokines and metalloproteases play a major role in OA promoting the inflammation and degradation of the cartilage and can be induced through the Toll-like receptor (TLR pathway. The aim of this study was to evaluate the protective effect of vitamin D supplementation on the development of osteoarthritis (OA through examining the genetic regulation of TLRs, cytokines, and metalloproteases in chondrocytes as well as the wideness of cartilage in rats with OA. Our results demonstrate that the signaling through TLR-4 is a proinflammatory mechanism in osteoarthritis that drives the upregulation of MMP-3, IL-1β, and TNF-α gene expression, leading to cartilage degradation and inflammation. Vitamin D supplementation had a protective effect during the onset but not during the chronic stage of OA in the rat model.

  12. Regularized finite element modeling of progressive failure in soils within nonlocal softening plasticity

    Science.gov (United States)

    Huang, Maosong; Qu, Xie; Lü, Xilin

    2017-11-01

    By solving a nonlinear complementarity problem for the consistency condition, an improved implicit stress return iterative algorithm for a generalized over-nonlocal strain softening plasticity was proposed, and the consistent tangent matrix was obtained. The proposed algorithm was embodied into existing finite element codes, and it enables the nonlocal regularization of ill-posed boundary value problem caused by the pressure independent and dependent strain softening plasticity. The algorithm was verified by the numerical modeling of strain localization in a plane strain compression test. The results showed that a fast convergence can be achieved and the mesh-dependency caused by strain softening can be effectively eliminated. The influences of hardening modulus and material characteristic length on the simulation were obtained. The proposed algorithm was further used in the simulations of the bearing capacity of a strip footing; the results are mesh-independent, and the progressive failure process of the soil was well captured.

  13. An ETP model (exclusion-tolerance-progression for multi drug resistance

    Directory of Open Access Journals (Sweden)

    Kannan Subburaj

    2005-04-01

    Full Text Available Abstract Background It is known that sensitivity or resistance of tumor cells to a given chemotherapeutic agent is an acquired characteristic(s, depending on the heterogeneity of the tumor mass subjected to the treatment. The clinical success of a chemotherapeutic regimen depends on the ratio of sensitive to resistant cell populations. Results Based on findings from clinical and experimental studies, a unifying model is proposed to delineate the potential mechanism by which tumor cells progress towards multi drug resistance, resulting in failure of chemotherapy. Conclusion It is suggested that the evolution of multi drug resistance is a developmentally orchestrated event. Identifying stage-specific time windows during this process would help to identify valid therapeutic targets for the effective elimination of malignancy.

  14. [Geothermal system temperature-depth database and model for data analysis]. 5. quarterly technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    Blackwell, D.D.

    1998-04-25

    During this first quarter of the second year of the contract activity has involved several different tasks. The author has continued to work on three tasks most intensively during this quarter: the task of implementing the data base for geothermal system temperature-depth, the maintenance of the WWW site with the heat flow and gradient data base, and finally the development of a modeling capability for analysis of the geothermal system exploration data. The author has completed the task of developing a data base template for geothermal system temperature-depth data that can be used in conjunction with the regional data base that he had already developed and is now implementing it. Progress is described.

  15. Zebrafish as a model to assess cancer heterogeneity, progression and relapse

    Science.gov (United States)

    Blackburn, Jessica S.; Langenau, David M.

    2014-01-01

    Clonal evolution is the process by which genetic and epigenetic diversity is created within malignant tumor cells. This process culminates in a heterogeneous tumor, consisting of multiple subpopulations of cancer cells that often do not contain the same underlying mutations. Continuous selective pressure permits outgrowth of clones that harbor lesions that are capable of enhancing disease progression, including those that contribute to therapy resistance, metastasis and relapse. Clonal evolution and the resulting intratumoral heterogeneity pose a substantial challenge to biomarker identification, personalized cancer therapies and the discovery of underlying driver mutations in cancer. The purpose of this Review is to highlight the unique strengths of zebrafish cancer models in assessing the roles that intratumoral heterogeneity and clonal evolution play in cancer, including transgenesis, imaging technologies, high-throughput cell transplantation approaches and in vivo single-cell functional assays. PMID:24973745

  16. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Nielsen, Lotte B; Andersen, Marie-Louise

    2016-01-01

    Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type...... 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several...

  17. Damaging role of neutrophilic infiltration in a mouse model of progressive tuberculosis.

    Science.gov (United States)

    Marzo, Elena; Vilaplana, Cristina; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanessa; Cardona, Pere-Joan

    2014-01-01

    Tuberculosis was studied using an experimental model based on the C3HeB/FeJ mouse strain, which mimics the liquefaction of caseous necrosis occurring during active disease in immunocompetent adults. Mice were intravenously infected with 2 × 10(4) Colony Forming Units of Mycobacterium tuberculosis and their histopathology, immune response, bacillary load, and survival were evaluated. The effects of the administration of drugs with anti-inflammatory activity were examined, and the C3H/HeN mouse strain was also included for comparative purposes. Massive intra-alveolar neutrophilic infiltration led to rapid granuloma growth and coalescence of lesions into superlesions. A central necrotic area appeared showing progressive cellular destruction, the alveoli cell walls being initially conserved (caseous necrosis) but finally destroyed (liquefactive necrosis). Increasing levels of pro-inflammatory mediators were detected in lungs. C3HeB/FeJ treated with anti-inflammatory drugs and C3H/HeN animals presented lower levels of pro-inflammatory mediators such as TNF-α, IL-17, IL-6 and CXCL5, a lower bacillary load, better histopathology, and increased survival compared with untreated C3HeB/FeJ. The observation of massive neutrophilic infiltration suggests that inflammation may be a key factor in progression towards active tuberculosis. On the basis of our findings, we consider that the C3HeB/FeJ mouse model would be useful for evaluating new therapeutic strategies against human tuberculosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Progress with lossy compression of data from the Community Earth System Model

    Science.gov (United States)

    Xu, H.; Baker, A.; Hammerling, D.; Li, S.; Clyne, J.

    2017-12-01

    Climate models, such as the Community Earth System Model (CESM), generate massive quantities of data, particularly when run at high spatial and temporal resolutions. The burden of storage is further exacerbated by creating large ensembles, generating large numbers of variables, outputting at high frequencies, and duplicating data archives (to protect against disk failures). Applying lossy compression methods to CESM datasets is an attractive means of reducing data storage requirements, but ensuring that the loss of information does not negatively impact science objectives is critical. In particular, test methods are needed to evaluate whether critical features (e.g., extreme values and spatial and temporal gradients) have been preserved and to boost scientists' confidence in the lossy compression process. We will provide an overview on our progress in applying lossy compression to CESM output and describe our unique suite of metric tests that evaluate the impact of information loss. Further, we will describe our processes how to choose an appropriate compression algorithm (and its associated parameters) given the diversity of CESM data (e.g., variables may be constant, smooth, change abruptly, contain missing values, or have large ranges). Traditional compression algorithms, such as those used for images, are not necessarily ideally suited for floating-point climate simulation data, and different methods may have different strengths and be more effective for certain types of variables than others. We will discuss our progress towards our ultimate goal of developing an automated multi-method parallel approach for compression of climate data that both maximizes data reduction and minimizes the impact of data loss on science results.

  19. Impacts of fresh lime juice and peel on atherosclerosis progression in an animal model

    Directory of Open Access Journals (Sweden)

    Maryam Boshtam

    2013-11-01

    Full Text Available BACKGROUND: The main protective role of antioxidants in the progression of atherosclerosis has been shown in some studies. Therefore, this project evaluated the effects of Citrus aurantifolia (Christm juice and peel on antioxidant activity and atherosclerosis progression in rabbits receiving a hypercholesterolemic diet. METHODS: Forty white New Zealand male rabbits were randomly allocated to four groups. All groups were on hypercholesterolemic diet for two months. While the first group was considered as the hypercholesterolemic control, groups 2 and 3 (intervention groups received 5 ml/day lime juice and 1 g/day dried lime peel powder, respectively. Group 4 was fed a normal diet (normal control. Before and after the study, weight was measured and a fasting blood specimen was taken from the rabbits. Serum lipids analyses and antioxidant activity evaluations were then performed. The rabbits’ aorta and coronary arteries were separated and the presence of fatty streaks was studied. RESULTS: Comparing to the hypercholesterolemic control group (-25.2 ± 7.0, only the plasma total antioxidant capacity change was significantly more in rabbits supplemented with lime juice (16.3 ± 14.7 and peel (8.6 ± 7.1 (P = 0.008. The presence of fatty streaks in coronary arteries and aorta of the intervention groups [juice (0.2 ± 0.01; peel (0.0 ± 0.00] was significantly decreased compared to the hypercholesterolemic control group (1.2 ± 0.4 (P < 0.001. CONCLUSION: Based on our findings, Citrus aurantifolia peel and juice increase plasma antioxidant capacity in rabbits, and can thus prevent or decelerate the process of atherogenesis. However, lime peel is more effective than lime juice.   Keywords: Animal, Atherosclerosis, Atherogenic Diet, Fatty Streak, Intervention, Lime    Normal 0 false false false EN-US X-NONE AR-SA

  20. Azimuth cut-off model for significant wave height investigation along coastal water of Kuala Terengganu, Malaysia

    Science.gov (United States)

    Marghany, Maged; Ibrahim, Zelina; Van Genderen, Johan

    2002-11-01

    The present work is used to operationalize the azimuth cut-off concept in the study of significant wave height. Three ERS-1 images have been used along the coastal waters of Terengganu, Malaysia. The quasi-linear transform was applied to map the SAR wave spectra into real ocean wave spectra. The azimuth cut-off was then used to model the significant wave height. The results show that azimuth cut-off varied with the different period of the ERS-1 images. This is because of the fact that the azimuth cut-off is a function of wind speed and significant wave height. It is of interest to find that the significant wave height modeled from azimuth cut-off is in good relation with ground wave conditions. It can be concluded that ERS-1 can be used as a monitoring tool in detecting the significant wave height variation. The azimuth cut-off can be used to model the significant wave height. This means that the quasi-linear transform could be a good application to significant wave height variation during different seasons.

  1. Presentation on the Modeling and Educational Demonstrations Laboratory Curriculum Materials Center (MEDL-CMC): A Working Model and Progress Report

    Science.gov (United States)

    Glesener, G. B.; Vican, L.

    2015-12-01

    Physical analog models and demonstrations can be effective educational tools for helping instructors teach abstract concepts in the Earth, planetary, and space sciences. Reducing the learning challenges for students using physical analog models and demonstrations, however, can often increase instructors' workload and budget because the cost and time needed to produce and maintain such curriculum materials is substantial. First, this presentation describes a working model for the Modeling and Educational Demonstrations Laboratory Curriculum Materials Center (MEDL-CMC) to support instructors' use of physical analog models and demonstrations in the science classroom. The working model is based on a combination of instructional resource models developed by the Association of College & Research Libraries and by the Physics Instructional Resource Association. The MEDL-CMC aims to make the curriculum materials available for all science courses and outreach programs within the institution where the MEDL-CMC resides. The sustainability and value of the MEDL-CMC comes from its ability to provide and maintain a variety of physical analog models and demonstrations in a wide range of science disciplines. Second, the presentation then reports on the development, progress, and future of the MEDL-CMC at the University of California Los Angeles (UCLA). Development of the UCLA MEDL-CMC was funded by a grant from UCLA's Office of Instructional Development and is supported by the Department of Earth, Planetary, and Space Sciences. Other UCLA science departments have recently shown interest in the UCLA MEDL-CMC services, and therefore, preparations are currently underway to increase our capacity for providing interdepartmental service. The presentation concludes with recommendations and suggestions for other institutions that wish to start their own MEDL-CMC in order to increase educational effectiveness and decrease instructor workload. We welcome an interuniversity collaboration to

  2. Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models.

    Science.gov (United States)

    Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

    2014-09-01

    To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87-97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4-5 months and sites recovered with a high probability (96-98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. © 2014 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

  3. Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models

    Science.gov (United States)

    Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

    2014-01-01

    Aim To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Material and Methods Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. Results In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87–97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4–5 months and sites recovered with a high probability (96–98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Conclusion Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. PMID:24888705

  4. Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model

    Directory of Open Access Journals (Sweden)

    Yi Lu

    2018-02-01

    Full Text Available Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD, while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo1H nuclear magnetic resonance (NMR spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI and taurine (Tau were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

  5. Microscopic and macroscopic models for the onset and progression of Alzheimer's disease

    International Nuclear Information System (INIS)

    Bertsch, Michiel; Franchi, Bruno; Tesi, Maria Carla; Tosin, Andrea

    2017-01-01

    In the first part of this paper we review a mathematical model for the onset and progression of Alzheimer’s disease (AD) that was developed in subsequent steps over several years. The model is meant to describe the evolution of AD in vivo . In Achdou et al (2013 J. Math. Biol . 67 1369–92) we treated the problem at a microscopic scale, where the typical length scale is a multiple of the size of the soma of a single neuron. Subsequently, in Bertsch et al (2017 Math. Med. Biol . 34 193–214) we concentrated on the macroscopic scale, where brain neurons are regarded as a continuous medium, structured by their degree of malfunctioning. In the second part of the paper we consider the relation between the microscopic and the macroscopic models. In particular we show under which assumptions the kinetic transport equation, which in the macroscopic model governs the evolution of the probability measure for the degree of malfunctioning of neurons, can be derived from a particle-based setting. The models are based on aggregation and diffusion equations for β -Amyloid (A β from now on), a protein fragment that healthy brains regularly produce and eliminate. In case of dementia A β monomers are no longer properly washed out and begin to coalesce forming eventually plaques. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: (i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons; (ii) neuron-to-neuron prion-like transmission. In the microscopic model we consider mechanism (i), modelling it by a system of Smoluchowski equations for the amyloid concentration (describing the agglomeration phenomenon), with the addition of a diffusion term as well as of a source term on the neuronal membrane. At the macroscopic level instead we model processes (i) and (ii) by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution

  6. Microscopic and macroscopic models for the onset and progression of Alzheimer's disease

    Science.gov (United States)

    Bertsch, Michiel; Franchi, Bruno; Carla Tesi, Maria; Tosin, Andrea

    2017-10-01

    In the first part of this paper we review a mathematical model for the onset and progression of Alzheimer’s disease (AD) that was developed in subsequent steps over several years. The model is meant to describe the evolution of AD in vivo. In Achdou et al (2013 J. Math. Biol. 67 1369-92) we treated the problem at a microscopic scale, where the typical length scale is a multiple of the size of the soma of a single neuron. Subsequently, in Bertsch et al (2017 Math. Med. Biol. 34 193-214) we concentrated on the macroscopic scale, where brain neurons are regarded as a continuous medium, structured by their degree of malfunctioning. In the second part of the paper we consider the relation between the microscopic and the macroscopic models. In particular we show under which assumptions the kinetic transport equation, which in the macroscopic model governs the evolution of the probability measure for the degree of malfunctioning of neurons, can be derived from a particle-based setting. The models are based on aggregation and diffusion equations for β-Amyloid (Aβ from now on), a protein fragment that healthy brains regularly produce and eliminate. In case of dementia Aβ monomers are no longer properly washed out and begin to coalesce forming eventually plaques. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: (i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons; (ii) neuron-to-neuron prion-like transmission. In the microscopic model we consider mechanism (i), modelling it by a system of Smoluchowski equations for the amyloid concentration (describing the agglomeration phenomenon), with the addition of a diffusion term as well as of a source term on the neuronal membrane. At the macroscopic level instead we model processes (i) and (ii) by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the

  7. Hydrothermal Fe cycling and deep ocean organic carbon scavenging: Model-based evidence for significant POC supply to seafloor sediments

    Digital Repository Service at National Institute of Oceanography (India)

    German, C.R.; Legendre, L.L.; Sander, S.G.;; Niquil, N.; Luther-III, G.W.; LokaBharathi, P.A.; Han, X.; LeBris, N.

    by more than ~10% over background values, what the model does indicate is that scavenging of carbon in association with Fe-rich hydrothermal plume particles should play a significant role in the delivery of particulate organic carbon to deep ocean...

  8. Methods for significance testing of categorical covariates in logistic regression models after multiple imputation: power and applicability analysis

    NARCIS (Netherlands)

    Eekhout, I.; Wiel, M.A. van de; Heymans, M.W.

    2017-01-01

    Background. Multiple imputation is a recommended method to handle missing data. For significance testing after multiple imputation, Rubin’s Rules (RR) are easily applied to pool parameter estimates. In a logistic regression model, to consider whether a categorical covariate with more than two levels

  9. A Multiscale Agent-Based in silico Model of Liver Fibrosis Progression

    Energy Technology Data Exchange (ETDEWEB)

    Dutta-Moscato, Joyeeta [Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, University of Pittsburgh, Pittsburgh, PA (United States); Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Solovyev, Alexey [Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Mathematics, University of Pittsburgh, Pittsburgh, PA (United States); Mi, Qi [Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA (United States); Nishikawa, Taichiro [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States); Soto-Gutierrez, Alejandro [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Pathology, University of Pittsburgh, Pittsburgh, PA (United States); Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA (United States); Fox, Ira J. [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States); Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA (United States); Vodovotz, Yoram, E-mail: vodovotzy@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA (United States); Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States)

    2014-05-30

    Chronic hepatic inflammation involves a complex interplay of inflammatory and mechanical influences, ultimately manifesting in a characteristic histopathology of liver fibrosis. We created an agent-based model (ABM) of liver tissue in order to computationally examine the consequence of liver inflammation. Our liver fibrosis ABM (LFABM) is comprised of literature-derived rules describing molecular and histopathological aspects of inflammation and fibrosis in a section of chemically injured liver. Hepatocytes are modeled as agents within hexagonal lobules. Injury triggers an inflammatory reaction, which leads to activation of local Kupffer cells and recruitment of monocytes from circulation. Portal fibroblasts and hepatic stellate cells are activated locally by the products of inflammation. The various agents in the simulation are regulated by above-threshold concentrations of pro- and anti-inflammatory cytokines and damage-associated molecular pattern molecules. The simulation progresses from chronic inflammation to collagen deposition, exhibiting periportal fibrosis followed by bridging fibrosis, and culminating in disruption of the regular lobular structure. The ABM exhibited key histopathological features observed in liver sections from rats treated with carbon tetrachloride (CCl{sub 4}). An in silico “tension test” for the hepatic lobules predicted an overall increase in tissue stiffness, in line with clinical elastography literature and published studies in CCl{sub 4}-treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing tumor necrosis factor alpha vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathological and macroscopic properties of CCl{sub 4}-injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant

  10. A Multiscale Agent-Based in silico Model of Liver Fibrosis Progression

    International Nuclear Information System (INIS)

    Dutta-Moscato, Joyeeta; Solovyev, Alexey; Mi, Qi; Nishikawa, Taichiro; Soto-Gutierrez, Alejandro; Fox, Ira J.; Vodovotz, Yoram

    2014-01-01

    Chronic hepatic inflammation involves a complex interplay of inflammatory and mechanical influences, ultimately manifesting in a characteristic histopathology of liver fibrosis. We created an agent-based model (ABM) of liver tissue in order to computationally examine the consequence of liver inflammation. Our liver fibrosis ABM (LFABM) is comprised of literature-derived rules describing molecular and histopathological aspects of inflammation and fibrosis in a section of chemically injured liver. Hepatocytes are modeled as agents within hexagonal lobules. Injury triggers an inflammatory reaction, which leads to activation of local Kupffer cells and recruitment of monocytes from circulation. Portal fibroblasts and hepatic stellate cells are activated locally by the products of inflammation. The various agents in the simulation are regulated by above-threshold concentrations of pro- and anti-inflammatory cytokines and damage-associated molecular pattern molecules. The simulation progresses from chronic inflammation to collagen deposition, exhibiting periportal fibrosis followed by bridging fibrosis, and culminating in disruption of the regular lobular structure. The ABM exhibited key histopathological features observed in liver sections from rats treated with carbon tetrachloride (CCl 4 ). An in silico “tension test” for the hepatic lobules predicted an overall increase in tissue stiffness, in line with clinical elastography literature and published studies in CCl 4 -treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing tumor necrosis factor alpha vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathological and macroscopic properties of CCl 4 -injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant insights into

  11. Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

    Directory of Open Access Journals (Sweden)

    Lunt Sarah

    2008-05-01

    Full Text Available Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG lesions in the transgenic polyomavirus middle T (PyMT breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs, demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

  12. Protective effects of long-term lithium administration in a slowly progressive SMA mouse model.

    Science.gov (United States)

    Biagioni, Francesca; Ferrucci, Michela; Ryskalin, Larisa; Fulceri, Federica; Lazzeri, Gloria; Calierno, Maria Teresa; Busceti, Carla L; Ruffoli, Riccardo; Fornai, Francesco

    2017-12-01

    In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/-; SMN1A2G+/-; SMN2+/+) of Spinal Muscle Atrophy type III (SMA-III). This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course. In addition, lithium prevents motor neuron enlargement and motor neuron heterotopy and suppresses the occurrence of radial-like glial fibrillary acidic protein immunostaining in the ventral white matter of SMA-III mice. In SMA-III mice long-term lithium administration determines a dramatic increase of survival motor neuron protein levels in the spinal cord. These data demonstrate that long-term lithium administration during a long-lasting motor neuron disorder attenuates behavioural deficit and neuropathology. Since low level of survival motor neuron protein is bound to disease severity in SMA, the robust increase in protein level produced by lithium provides solid evidence which calls for further investigations considering lithium in the long-term treatment of spinal muscle atrophy.

  13. A Review of the Progress with Statistical Models of Passive Component Reliability

    Directory of Open Access Journals (Sweden)

    Bengt O.Y. Lydell

    2017-03-01

    Full Text Available During the past 25 years, in the context of probabilistic safety assessment, efforts have been directed towards establishment of comprehensive pipe failure event databases as a foundation for exploratory research to better understand how to effectively organize a piping reliability analysis task. The focused pipe failure database development efforts have progressed well with the development of piping reliability analysis frameworks that utilize the full body of service experience data, fracture mechanics analysis insights, expert elicitation results that are rolled into an integrated and risk-informed approach to the estimation of piping reliability parameters with full recognition of the embedded uncertainties. The discussion in this paper builds on a major collection of operating experience data (more than 11,000 pipe failure records and the associated lessons learned from data analysis and data applications spanning three decades. The piping reliability analysis lessons learned have been obtained from the derivation of pipe leak and rupture frequencies for corrosion resistant piping in a raw water environment, loss-of-coolant-accident frequencies given degradation mitigation, high-energy pipe break analysis, moderate-energy pipe break analysis, and numerous plant-specific applications of a statistical piping reliability model framework. Conclusions are presented regarding the feasibility of determining and incorporating aging effects into probabilistic safety assessment models.

  14. The effect of physician staffing model on patient outcomes in a medical progressive care unit.

    Science.gov (United States)

    Yoo, E J; Damaghi, N; Shakespeare, W G; Sherman, M S

    2016-04-01

    Although evidence supports the impact of intensivist physician staffing in improving intensive care unit (ICU) outcomes, the optimal coverage for progressive care units (PCU) is unknown. We sought to determine how physician staffing models influence outcomes for intermediate care patients. We conducted a retrospective observational comparison of patients admitted to the medical PCU of an academic hospital during 12-month periods of high-intensity and low-intensity staffing. A total of 318 PCU patients were eligible for inclusion (143 high-intensity and 175 low-intensity). We found that low-intensity patients were more often stepped up from the emergency department and floor, whereas high-intensity patients were ICU transfers (61% vs 42%, P = .001). However, Mortality Probability Model scoring was similar between the 2 groups. In adjusted analysis, there was no association between intensity of staffing and hospital mortality (odds ratio, 0.84; 95% confidence interval, 0.36-1.99; P = .69) or PCU mortality (odds ratio, 0.96; 95% confidence interval, 0.38-2.45; P = .69). There was also no difference in subsequent ICU admission rates or in PCU length of stay. We found no evidence that high-intensity intensivist physician staffing improves outcomes for intermediate care patients. In a strained critical care system, our study raises questions about the role of the intensivist in the graded care options between intensive and conventional ward care. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. A review of the progress with statistical models of passive component reliability

    Energy Technology Data Exchange (ETDEWEB)

    Lydell, Bengt O. Y. [Sigma-Phase Inc., Vail (United States)

    2017-03-15

    During the past 25 years, in the context of probabilistic safety assessment, efforts have been directed towards establishment of comprehensive pipe failure event databases as a foundation for exploratory research to better understand how to effectively organize a piping reliability analysis task. The focused pipe failure database development efforts have progressed well with the development of piping reliability analysis frameworks that utilize the full body of service experience data, fracture mechanics analysis insights, expert elicitation results that are rolled into an integrated and risk-informed approach to the estimation of piping reliability parameters with full recognition of the embedded uncertainties. The discussion in this paper builds on a major collection of operating experience data (more than 11,000 pipe failure records) and the associated lessons learned from data analysis and data applications spanning three decades. The piping reliability analysis lessons learned have been obtained from the derivation of pipe leak and rupture frequencies for corrosion resistant piping in a raw water environment, loss-of-coolant-accident frequencies given degradation mitigation, high-energy pipe break analysis, moderate-energy pipe break analysis, and numerous plant-specific applications of a statistical piping reliability model framework. Conclusions are presented regarding the feasibility of determining and incorporating aging effects into probabilistic safety assessment models.

  16. Progress report on SYVAC chemical speciation modelling studies during 1983/4

    International Nuclear Information System (INIS)

    Cross, J.; Smith, G.L.; Williams, D.R.

    1984-01-01

    This report summarises progress made on the SYVAC (System Variability Analysis program) chemical speciation project during 1983-4. Chemical speciation is defined and its importance in the SYVAC approach to Radioactive Waste Management is discussed. Computer modelling of chemical equilibria is described and the two programs presently operational at UWIST - SOLMNQ and MINEQL - are compared and discussed in detail. In view of the shortcomings of the databases supplied with these programs, a new database of equilibrium constants has been compiled containing 483 aqueous species and 329 solid phases, including data for the radionuclides uranium, plutonium, americium, neptunium and thorium. The collaborative work with AERE, Harwell, is reported. A leaching experiment carried out at Harwell has been modelled using the chemical speciation programs. The results for uranium, plutonium, americium and neptunium, are presented. However, the experimental data provided by AERE is insufficient for accurate simulations. Chemical speciation studies relating to specific sites require accurate characterisation of the groundwater, i.e. chemical composition, Eh and pH. In the absence of such information, preliminary studies have been made using an average granite groundwater. The results of these studies are presented and include solubility and speciation plots for uranium, plutonium, thorium and neptunium. The future aims of the project are discussed. (author)

  17. A review of the progress with statistical models of passive component reliability

    International Nuclear Information System (INIS)

    Lydell, Bengt O. Y.

    2017-01-01

    During the past 25 years, in the context of probabilistic safety assessment, efforts have been directed towards establishment of comprehensive pipe failure event databases as a foundation for exploratory research to better understand how to effectively organize a piping reliability analysis task. The focused pipe failure database development efforts have progressed well with the development of piping reliability analysis frameworks that utilize the full body of service experience data, fracture mechanics analysis insights, expert elicitation results that are rolled into an integrated and risk-informed approach to the estimation of piping reliability parameters with full recognition of the embedded uncertainties. The discussion in this paper builds on a major collection of operating experience data (more than 11,000 pipe failure records) and the associated lessons learned from data analysis and data applications spanning three decades. The piping reliability analysis lessons learned have been obtained from the derivation of pipe leak and rupture frequencies for corrosion resistant piping in a raw water environment, loss-of-coolant-accident frequencies given degradation mitigation, high-energy pipe break analysis, moderate-energy pipe break analysis, and numerous plant-specific applications of a statistical piping reliability model framework. Conclusions are presented regarding the feasibility of determining and incorporating aging effects into probabilistic safety assessment models

  18. A simplified baseline prediction model for joint damage progression in rheumatoid arthritis: a step toward personalized medicine.

    Science.gov (United States)

    de Punder, Yvonne M R; van Riel, Piet L C M; Fransen, Jaap

    2015-03-01

    To compare the performance of an extended model and a simplified prognostic model for joint damage in rheumatoid arthritis (RA) based on 3 baseline risk factors: anticyclic citrullinated peptide antibodies (anti-CCP), erosions, and acute-phase reaction. Data were used from the Nijmegen early RA cohort. An extended model and a simplified baseline prediction model were developed to predict joint damage progression between 0 and 3 years. Joint damage progression was assessed using the Ratingen score. In the extended model, prediction factors were positivity for anti-CCP and/or rheumatoid factor, the level of erythrocyte sedimentation rate, and the quantity of erosions. The prediction score was calculated as the sum of the regression coefficients. In the simplified model, the prediction factors were dichotomized and the number of risk factors was counted. Performances of both models were compared using discrimination and calibration. The models were internally validated using bootstrapping. The extended model resulted in a prediction score between 0 and 5.6 with an area under the receiver-operation characteristic (ROC) curve of 0.77 (95% CI 0.72-0.81). The simplified model resulted in a prediction score between 0 and 3. This model had an area under the ROC curve of 0.75 (95% CI 0.70-0.80). In internal validation, the 2 models showed reasonably well the agreement between observed and predicted probabilities for joint damage progression (Hosmer-Lemeshow test p > 0.05 and calibration slope near 1.0). A simple prediction model for joint damage progression in early RA, by only counting the number of risk factors, has adequate performance. This facilitates the translation of the theoretical prognostic models to daily clinical practice.

  19. From goal motivation to goal progress: the mediating role of coping in the Self-Concordance Model.

    Science.gov (United States)

    Gaudreau, Patrick; Carraro, Natasha; Miranda, Dave

    2012-01-01

    The present studies examined the mediating role of self-regulatory mechanisms in the relationship between goal motivation and goal progress in the Self-Concordance Model. First, a systematic review, using meta-analytical path analysis, supported the mediating role of effort and action planning in the positive association between autonomous goal motivation and goal progress. Second, results from two additional empirical studies, using structural equation modeling, lent credence to the mediating role of coping in the relationship between goal motivation and goal progress of university students. Autonomous goal motivation was positively associated with task-oriented coping, which predicted greater goal progress during midterm exams (Study 1, N=702) and at the end of the semester in a different sample (Study 2, N=167). Controlled goal motivation was associated with greater disengagement-oriented coping (Study 1 and Study 2) and lesser use of task-oriented coping (Study 2), which reduced goal progress. These results held up after controlling for perceived stress (Study 2). Our findings highlight the importance of coping in the "inception-to-attainment" goal process because autonomous goal motivation indirectly rather than directly predicts goal progress of university students through their usage of task-oriented coping.

  20. Modelling Pre-eruptive Progressive Damage in Basaltic Volcanoes: Consequences for the Pre-eruptive Process

    Science.gov (United States)

    Got, J. L.; Amitrano, D.; Carrier, A.; Marsan, D.; Jouanne, F.; Vogfjord, K. S.

    2017-12-01

    At Grimsvötn volcano, high-quality earthquake and continuous GPS data were recorded by the Icelandic Meteorological Office during its 2004-2011 inter-eruptive period and exhibited remarkable patterns : acceleration of the cumulated earthquake number, and a 2-year exponential decrease in displacement rate followed by a 4-year constant inflation rate. We proposed a model with one magma reservoir in a non-linear elastic damaging edifice, with incompressible magma and a constant pressure at the base of the magma conduit. We first modelled seismicity rate and damage as a function of time, and show that Kachanov's elastic brittle damage law may be used to express the decrease of the effective shear modulus with time. We then derived simple analytical expressions for the magma reservoir overpressure and the surface displacement as a function of time. We got a very good fit of the seismicity and surface displacement data by adjusting only three phenomenological parameters and computed magma reservoir overpressure, magma flow and strain power as a function of time. Overpressure decrease is controlled by damage and shear modulus decrease. Displacement increases, although overpressure is decreasing, because shear modulus decreases more than overpressure. Normalized strain power reaches a maximum 0.25 value. This maximum is a physical limit, after which the elasticity laws are no longer valid, earthquakes cluster, cumulative number of earthquakes departs from the model. State variable extrema provide four reference times that may be used to assess the mechanical state and dynamics of the volcanic edifice. We also performed the spatial modelling of the progressive damage and strain localization around a pressurized magma reservoir. We used Kachanov's damage law and finite element modelling of an initially elastic volcanic edifice pressurized by a spherical magma reservoir, with a constant pressure in the reservoir and various external boundary conditions. At each node of the

  1. A more robust model of the biodiesel reaction, allowing identification of process conditions for significantly enhanced rate and water tolerance.

    Science.gov (United States)

    Eze, Valentine C; Phan, Anh N; Harvey, Adam P

    2014-03-01

    A more robust kinetic model of base-catalysed transesterification than the conventional reaction scheme has been developed. All the relevant reactions in the base-catalysed transesterification of rapeseed oil (RSO) to fatty acid methyl ester (FAME) were investigated experimentally, and validated numerically in a model implemented using MATLAB. It was found that including the saponification of RSO and FAME side reactions and hydroxide-methoxide equilibrium data explained various effects that are not captured by simpler conventional models. Both the experiment and modelling showed that the "biodiesel reaction" can reach the desired level of conversion (>95%) in less than 2min. Given the right set of conditions, the transesterification can reach over 95% conversion, before the saponification losses become significant. This means that the reaction must be performed in a reactor exhibiting good mixing and good control of residence time, and the reaction mixture must be quenched rapidly as it leaves the reactor. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Progression of liver cirrhosis to HCC: an application of hidden Markov model

    Directory of Open Access Journals (Sweden)

    Serio Gabriella

    2011-04-01

    Full Text Available Abstract Background Health service databases of administrative type can be a useful tool for the study of progression of a disease, but the data reported in such sources could be affected by misclassifications of some patients' real disease states at the time. Aim of this work was to estimate the transition probabilities through the different degenerative phases of liver cirrhosis using health service databases. Methods We employed a hidden Markov model to determine the transition probabilities between two states, and of misclassification. The covariates inserted in the model were sex, age, the presence of comorbidities correlated with alcohol abuse, the presence of diagnosis codes indicating hepatitis C virus infection, and the Charlson Index. The analysis was conducted in patients presumed to have suffered the onset of cirrhosis in 2000, observing the disease evolution and, if applicable, death up to the end of the year 2006. Results The incidence of hepatocellular carcinoma (HCC in cirrhotic patients was 1.5% per year. The probability of developing HCC is higher in males (OR = 2.217 and patients over 65 (OR = 1.547; over 65-year-olds have a greater probability of death both while still suffering from cirrhosis (OR = 2.379 and if they have developed HCC (OR = 1.410. A more severe casemix affects the transition from HCC to death (OR = 1.714. The probability of misclassifying subjects with HCC as exclusively affected by liver cirrhosis is 14.08%. Conclusions The hidden Markov model allowing for misclassification is well suited to analyses of health service databases, since it is able to capture bias due to the fact that the quality and accuracy of the available information are not always optimal. The probability of evolution of a cirrhotic subject to HCC depends on sex and age class, while hepatitis C virus infection and comorbidities correlated with alcohol abuse do not seem to have an influence.

  3. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  4. Modelling of electric tree progression due to space charge modified fields

    International Nuclear Information System (INIS)

    Seralathan, K E; Mahajan, A; Gupta, Nandini

    2008-01-01

    Tree initiation and growth require localized field enhancement that results in material erosion and formation of tree channels. Tree progression is linked to partial discharges within the tree tubules, characterized by recurrent periods of activity followed by quiescent states. Charge builds up across the non-conducting tree channels during the inactive regime, and discharge follows. In this work, the role of the space charge modified field during the non-discharging regime in deciding the site of subsequent discharges and thereby shaping tree structures is studied. A simple stochastic model was developed, in order to understand the respective effects of charges trapped on the walls of tree tubules, at channel tips, or in the volume of the dielectric. While some charge distributions are seen to arrest tree growth, others encourage axial growth towards the other electrode, and some aid in producing bushy trees clustered around the needle tip. The effect of carbon deposition within tree channels, making them effectively conducting, was also investigated. The insights gained from the simulations were successfully used to explain tree growth in the laboratory under high- and low-field conditions

  5. Recent progress of an integrated implosion code and modeling of element physics

    International Nuclear Information System (INIS)

    Nagatomo, H.; Takabe, H.; Mima, K.; Ohnishi, N.; Sunahara, A.; Takeda, T.; Nishihara, K.; Nishiguchu, A.; Sawada, K.

    2001-01-01

    Physics of the inertial fusion is based on a variety of elements such as compressible hydrodynamics, radiation transport, non-ideal equation of state, non-LTE atomic process, and relativistic laser plasma interaction. In addition, implosion process is not in stationary state and fluid dynamics, energy transport and instabilities should be solved simultaneously. In order to study such complex physics, an integrated implosion code including all physics important in the implosion process should be developed. The details of physics elements should be studied and the resultant numerical modeling should be installed in the integrated code so that the implosion can be simulated with available computer within realistic CPU time. Therefore, this task can be basically separated into two parts. One is to integrate all physics elements into a code, which is strongly related to the development of hydrodynamic equation solver. We have developed 2-D integrated implosion code which solves mass, momentum, electron energy, ion energy, equation of states, laser ray-trace, laser absorption radiation, surface tracing and so on. The reasonable results in simulating Rayleigh-Taylor instability and cylindrical implosion are obtained using this code. The other is code development on each element physics and verification of these codes. We had progress in developing a nonlocal electron transport code and 2 and 3 dimension radiation hydrodynamic code. (author)

  6. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

    Directory of Open Access Journals (Sweden)

    N V Bobkova

    Full Text Available The Y-box binding protein 1 (YB-1 is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42 inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.

  7. Transient Abnormalities in Masking Tuning Curve in Early Progressive Hearing Loss Mouse Model

    Directory of Open Access Journals (Sweden)

    Marion Souchal

    2018-01-01

    Full Text Available Damage to cochlear outer hair cells (OHCs usually affects frequency selectivity in proportion to hearing threshold increase. However, the current clinical heuristics that attributes poor hearing performance despite near-normal auditory sensitivity to auditory neuropathy or “hidden” synaptopathy overlooks possible underlying OHC impairment. Here, we document the part played by OHCs in influencing suprathreshold auditory performance in the presence of noise in a mouse model of progressive hair cell degeneration, the CD1 strain, at postnatal day 18–30 stages when high-frequency auditory thresholds remained near-normal. Nonetheless, total loss of high-frequency distortion product otoacoustic emissions pointed to nonfunctioning basal OHCs. This “discordant profile” came with a huge low-frequency shift of masking tuning curves that plot the level of interfering sound necessary to mask the response to a probe tone, against interfering frequency. Histology revealed intense OHC hair bundle abnormalities in the basal cochlea uncharacteristically associated with OHC survival and preserved coupling with the tectorial membrane. This pattern dismisses the superficial diagnosis of “hidden” neuropathy while underpinning a disorganization of cochlear frequency mapping with optimistic high-frequency auditory thresholds perhaps because responses to high frequencies are apically shifted. The audiometric advantage of frequency transposition is offset by enhanced masking by low-frequency sounds, a finding essential for guiding rehabilitation.

  8. A saposin deficiency model in Drosophila: Lysosomal storage, progressive neurodegeneration and sensory physiological decline.

    Science.gov (United States)

    Hindle, Samantha J; Hebbar, Sarita; Schwudke, Dominik; Elliott, Christopher J H; Sweeney, Sean T

    2017-02-01

    Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration. Our data suggests a genetic interaction with a calcium exchanger (Calx) pointing to a possible calcium homeostasis deficit in dSap-r mutants. Together these findings support the use of dSap-r mutants in advancing our understanding of the cellular pathology implicated in saposin deficiency and related LSDs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Electroacupuncture decreases the progression of ovarian hyperstimulation syndrome in a rat model.

    Science.gov (United States)

    Chen, Li; Sun, Hai-Xiang; Xia, You-Bing; Sui, Liu-Cai; Zhou, Ji; Huang, Xuan; Zhou, Jing-Wei; Shao, Yi-Dan; Shen, Tao; Sun, Qin; Liang, Yuan-Jiao; Yao, Bing

    2016-05-01

    This study aimed to elucidate the effect of electroacupuncture treatment on preventing early ovarian hyperstimulation syndrome (OHSS) and the potential mechanisms involved using an induced rat model. The ovarian response was examined by measuring ovary weight, vascular permeability, levels of inflammation (interleukin-6), tumour necrosis factor alpha, chemokine ligand 2 (also known as monocyte chemoactic protein 1), vascular endothelial growth factor and hormone concentrations (oestradiol, progesterone, testosterone and prolactin). Sprague-Dawley female rats underwent ovarian stimulation to induce OHSS. Hyperstimulated rats received consecutive electroacupuncture treatment from 3 days before the beginning of pregnant mare serum gonadotrophin treatment or the time point of pregnant mare serum gonadotrophin treatment respectively, and last until 3 days after HCG administration. Electroacupuncture treatment reduced ovary weight and vascular permeability in hyperstimulated rats. Electroacupuncture treatment also reduced the levels of serum steroid hormones (progesterone and testosterone), inflammatory cytokines (interleukin-6, tumour necrosis factor alpha and monocyte chemotactic protein 1 and vascular endothelial growth factor in hyperstimulated rats. The results indicate that electroacupuncture can modulate endocrine hormone secretion and affect the secretion of inflammatory cytokines and vascular endothelial growth factor, and thus prevent the progress of OHSS. Electroacupuncture may provide a simple and effective method for the prevention and treatment of OHSS. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. A new model using routinely available clinical parameters to predict significant liver fibrosis in chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Wai-Kay Seto

    Full Text Available OBJECTIVE: We developed a predictive model for significant fibrosis in chronic hepatitis B (CHB based on routinely available clinical parameters. METHODS: 237 treatment-naïve CHB patients [58.4% hepatitis B e antigen (HBeAg-positive] who had undergone liver biopsy were randomly divided into two cohorts: training group (n = 108 and validation group (n = 129. Liver histology was assessed for fibrosis. All common demographics, viral serology, viral load and liver biochemistry were analyzed. RESULTS: Based on 12 available clinical parameters (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP, GGT and AFP, a model to predict significant liver fibrosis (Ishak fibrosis score ≥3 was derived using the five best parameters (age, ALP, AST, AFP and platelet. Using the formula log(index+1 = 0.025+0.0031(age+0.1483 log(ALP+0.004 log(AST+0.0908 log(AFP+1-0.028 log(platelet, the PAPAS (Platelet/Age/Phosphatase/AFP/AST index predicts significant fibrosis with an area under the receiving operating characteristics (AUROC curve of 0.776 [0.797 for patients with ALT <2×upper limit of normal (ULN] The negative predictive value to exclude significant fibrosis was 88.4%. This predictive power is superior to other non-invasive models using common parameters, including the AST/platelet/GGT/AFP (APGA index, AST/platelet ratio index (APRI, and the FIB-4 index (AUROC of 0.757, 0.708 and 0.723 respectively. Using the PAPAS index, 67.5% of liver biopsies for patients being considered for treatment with ALT <2×ULN could be avoided. CONCLUSION: The PAPAS index can predict and exclude significant fibrosis, and may reduce the need for liver biopsy in CHB patients.

  11. Early life exposure to permethrin: a progressive animal model of Parkinson's disease.

    Science.gov (United States)

    Nasuti, Cinzia; Brunori, Gloria; Eusepi, Piera; Marinelli, Lisa; Ciccocioppo, Roberto; Gabbianelli, Rosita

    Oxidative stress, alpha-synuclein changes, mitochondrial complex I defects and dopamine loss, observed in the striatum of rats exposed to the pesticide permethrin in early life, could represent neuropathological hallmarks of Parkinson's disease (PD). Nevertheless, an animal model of PD should also fulfill criteria of face and predictive validities. This study was designed to: 1) verify dopaminergic status in the striatum and substantia nigra pars compacta; 2) recognize non-motor symptoms; 3) investigate the time-course development of motor disabilities; 4) assess L-Dopa effectiveness on motor symptoms in rats previously exposed to permethrin in early life. The permethrin-treated group received 34mg/kg daily of permethrin from postnatal day 6 to 21, whereas the age-matched control group was administered with the vehicle only. At adolescent age, the permethrin-treated group showed decreased levels of dopamine in the striatum, loss of dopaminergic neurons in the substantia nigra pars compacta and cognitive impairments. Motor coordination defects appeared at adult age (150days old) in permethrin-treated rats on rotarod and beam walking tasks, whereas no differences between the treated and control groups were detected on the foot print task. Predictive validity was evaluated by testing the ability of L-Dopa (5, 10 or 15mg/kg, os) to restore the postural instability in permethrin-treated rats (150days old) tested in a beam walking task. The results revealed full reversal of motor deficits starting from 10mg/kg of L-Dopa. The overall results indicate that this animal model replicates the progressive, time-dependent nature of the neurodegenerative process in Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Correction of the significance level when attempting multiple transformations of an explanatory variable in generalized linear models

    Science.gov (United States)

    2013-01-01

    Background In statistical modeling, finding the most favorable coding for an exploratory quantitative variable involves many tests. This process involves multiple testing problems and requires the correction of the significance level. Methods For each coding, a test on the nullity of the coefficient associated with the new coded variable is computed. The selected coding corresponds to that associated with the largest statistical test (or equivalently the smallest pvalue). In the context of the Generalized Linear Model, Liquet and Commenges (Stat Probability Lett,71:33–38,2005) proposed an asymptotic correction of the significance level. This procedure, based on the score test, has been developed for dichotomous and Box-Cox transformations. In this paper, we suggest the use of resampling methods to estimate the significance level for categorical transformations with more than two levels and, by definition those that involve more than one parameter in the model. The categorical transformation is a more flexible way to explore the unknown shape of the effect between an explanatory and a dependent variable. Results The simulations we ran in this study showed good performances of the proposed methods. These methods were illustrated using the data from a study of the relationship between cholesterol and dementia. Conclusion The algorithms were implemented using R, and the associated CPMCGLM R package is available on the CRAN. PMID:23758852

  13. Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

    Science.gov (United States)

    Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay

    2017-01-01

    This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

  14. Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

    Directory of Open Access Journals (Sweden)

    Shiyan Zhai

    Full Text Available This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

  15. Progression to multi-scale models and the application to food system intervention strategies.

    Science.gov (United States)

    Gröhn, Yrjö T

    2015-02-01

    The aim of this article is to discuss how the systems science approach can be used to optimize intervention strategies in food animal systems. It advocates the idea that the challenges of maintaining a safe food supply are best addressed by integrating modeling and mathematics with biological studies critical to formulation of public policy to address these challenges. Much information on the biology and epidemiology of food animal systems has been characterized through single-discipline methods, but until now this information has not been thoroughly utilized in a fully integrated manner. The examples are drawn from our current research. The first, explained in depth, uses clinical mastitis to introduce the concept of dynamic programming to optimize management decisions in dairy cows (also introducing the curse of dimensionality problem). In the second example, a compartmental epidemic model for Johne's disease with different intervention strategies is optimized. The goal of the optimization strategy depends on whether there is a relationship between Johne's and Crohn's disease. If so, optimization is based on eradication of infection; if not, it is based on the cow's performance only (i.e., economic optimization, similar to the mastitis example). The third example focuses on food safety to introduce risk assessment using Listeria monocytogenes and Salmonella Typhimurium. The last example, practical interventions to effectively manage antibiotic resistance in beef and dairy cattle systems, introduces meta-population modeling that accounts for bacterial growth not only in the host (cow), but also in the cow's feed, drinking water and the housing environment. Each example stresses the need to progress toward multi-scale modeling. The article ends with examples of multi-scale systems, from food supply systems to Johne's disease. Reducing the consequences of foodborne illnesses (i.e., minimizing disease occurrence and associated costs) can only occur through an

  16. Progress Report on SAM Reduced-Order Model Development for Thermal Stratification and Mixing during Reactor Transients

    Energy Technology Data Exchange (ETDEWEB)

    Hu, R. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-09-01

    This report documents the initial progress on the reduced-order flow model developments in SAM for thermal stratification and mixing modeling. Two different modeling approaches are pursued. The first one is based on one-dimensional fluid equations with additional terms accounting for the thermal mixing from both flow circulations and turbulent mixing. The second approach is based on three-dimensional coarse-grid CFD approach, in which the full three-dimensional fluid conservation equations are modeled with closure models to account for the effects of turbulence.

  17. DIFFERENCES IN WATER VAPOR RADIATIVE TRANSFER AMONG 1D MODELS CAN SIGNIFICANTLY AFFECT THE INNER EDGE OF THE HABITABLE ZONE

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jun; Wang, Yuwei [Department of Atmospheric and Oceanic Sciences, School of Physics, Peking University, Beijing (China); Leconte, Jérémy; Forget, François [Laboratoire de Météorologie Dynamique, Institut Pierre Simon Laplace, CNRS, Paris (France); Wolf, Eric T. [Laboratory for Atmospheric and Space Physics, University of Colorado in Boulder, CO (United States); Goldblatt, Colin [School of Earth and Ocean Sciences, University of Victoria, Victoria, BC (Canada); Feldl, Nicole [Division of Geological and Planetary Sciences, California Institute of Technology, CA (United States); Merlis, Timothy [Department of Atmospheric and Oceanic Sciences at McGill University, Montréal (Canada); Koll, Daniel D. B.; Ding, Feng; Abbot, Dorian S., E-mail: junyang@pku.edu.cn, E-mail: abbot@uchicago.edu [Department of the Geophysical Sciences, University of Chicago, Chicago, IL (United States)

    2016-08-01

    An accurate estimate of the inner edge of the habitable zone is critical for determining which exoplanets are potentially habitable and for designing future telescopes to observe them. Here, we explore differences in estimating the inner edge among seven one-dimensional radiative transfer models: two line-by-line codes (SMART and LBLRTM) as well as five band codes (CAM3, CAM4-Wolf, LMDG, SBDART, and AM2) that are currently being used in global climate models. We compare radiative fluxes and spectra in clear-sky conditions around G and M stars, with fixed moist adiabatic profiles for surface temperatures from 250 to 360 K. We find that divergences among the models arise mainly from large uncertainties in water vapor absorption in the window region (10 μ m) and in the region between 0.2 and 1.5 μ m. Differences in outgoing longwave radiation increase with surface temperature and reach 10–20 W m{sup 2}; differences in shortwave reach up to 60 W m{sup 2}, especially at the surface and in the troposphere, and are larger for an M-dwarf spectrum than a solar spectrum. Differences between the two line-by-line models are significant, although smaller than among the band models. Our results imply that the uncertainty in estimating the insolation threshold of the inner edge (the runaway greenhouse limit) due only to clear-sky radiative transfer is ≈10% of modern Earth’s solar constant (i.e., ≈34 W m{sup 2} in global mean) among band models and ≈3% between the two line-by-line models. These comparisons show that future work is needed that focuses on improving water vapor absorption coefficients in both shortwave and longwave, as well as on increasing the resolution of stellar spectra in broadband models.

  18. DIFFERENCES IN WATER VAPOR RADIATIVE TRANSFER AMONG 1D MODELS CAN SIGNIFICANTLY AFFECT THE INNER EDGE OF THE HABITABLE ZONE

    International Nuclear Information System (INIS)

    Yang, Jun; Wang, Yuwei; Leconte, Jérémy; Forget, François; Wolf, Eric T.; Goldblatt, Colin; Feldl, Nicole; Merlis, Timothy; Koll, Daniel D. B.; Ding, Feng; Abbot, Dorian S.

    2016-01-01

    An accurate estimate of the inner edge of the habitable zone is critical for determining which exoplanets are potentially habitable and for designing future telescopes to observe them. Here, we explore differences in estimating the inner edge among seven one-dimensional radiative transfer models: two line-by-line codes (SMART and LBLRTM) as well as five band codes (CAM3, CAM4-Wolf, LMDG, SBDART, and AM2) that are currently being used in global climate models. We compare radiative fluxes and spectra in clear-sky conditions around G and M stars, with fixed moist adiabatic profiles for surface temperatures from 250 to 360 K. We find that divergences among the models arise mainly from large uncertainties in water vapor absorption in the window region (10 μ m) and in the region between 0.2 and 1.5 μ m. Differences in outgoing longwave radiation increase with surface temperature and reach 10–20 W m 2 ; differences in shortwave reach up to 60 W m 2 , especially at the surface and in the troposphere, and are larger for an M-dwarf spectrum than a solar spectrum. Differences between the two line-by-line models are significant, although smaller than among the band models. Our results imply that the uncertainty in estimating the insolation threshold of the inner edge (the runaway greenhouse limit) due only to clear-sky radiative transfer is ≈10% of modern Earth’s solar constant (i.e., ≈34 W m 2 in global mean) among band models and ≈3% between the two line-by-line models. These comparisons show that future work is needed that focuses on improving water vapor absorption coefficients in both shortwave and longwave, as well as on increasing the resolution of stellar spectra in broadband models.

  19. Chronic administration of ethanol leaf extract of Moringa oleifera Lam. (Moringaceae) may compromise glycaemic efficacy of Sitagliptin with no significant effect in retinopathy in a diabetic rat model.

    Science.gov (United States)

    Olurishe, Comfort; Kwanashie, Helen; Zezi, Abdulkadiri; Danjuma, Nuhu; Mohammed, Bisalla

    2016-12-24

    Moringa oleifera Lam. (Moringaceae) has gained awareness for its antidiabetic effect, and is used as alternative therapy or concurrently with orthodox medicines such as sitagliptin in diabetes mellitus. This is without ascertaining the possibility of drug-herb interactions, which could either lead to enhanced antidiabetic efficacy, increased toxicity, or compromised glycaemic control with negative consequence in diabetic retinopathy. To investigate the effect, of sitagliptin (50mg/kg), Moringa oleifera (300mg/kg) leaf extract, and a combination of both on glycaemic control parameters, lenticular opacity and changes in retinal microvasculature in alloxan (150mg/kg i.p) induced diabetic rat model. Seven groups of eight rats per group were used, with groups I, II and VII as normal (NC), diabetic (DC) and post-prandial controls (PPC). Groups III to VI were diabetic rats on sitagliptin (III), M. oleifera (IV), sitagliptin and M. oleifera (SM) (V), for 42 days with 2 weeks delayed treatment in a post-prandial hyperglycaemic group (PPSM) (VI). Glycaemic control parameters, insulin levels, body weights, and effects of retinal microvasculature on lenticular opacity/morphology were investigated. A significant decrease in fasting blood glucose (FBG) levels was displayed in SM group from day 14(60%) (p<0.01) to day 28 (38%) (p<0.01) of treatment, compared to day 1. Thereafter, a steady increase of up to 57% on day 42 compared to day 28 was observed. A significant decrease in random blood glucose (RBG) levels, were demonstrated on day 42 (24%) (p<0.001), compared to day 1. No significant difference was seen in mean serum levels of insulin across groups. No significant changes in body weights. Evidence of mild lenticular opacity was observed, with no significant effect in pathologic lesions in the retina. The chronic co-administration of sitagliptin and M. oleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of

  20. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2

    DEFF Research Database (Denmark)

    Nielsen, Signe Marie Borch; Hasholt, Lis; Nørremølle, Anne

    2015-01-01

    of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood...

  1. Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model

    NARCIS (Netherlands)

    Lascano, Valeria; Guadagnoli, Marco; Schot, Jan G.; Luijks, Dieuwertje M.; Guikema, Jeroen E. J.; Cameron, Katherine; Hahne, Michael; Pals, Steven; Slinger, Erik; Kipps, Thomas J.; van Oers, Marinus H. J.; Eldering, Eric; Medema, Jan Paul; Kater, Arnon P.

    2013-01-01

    Although in vitro studies pointed to the tumor necrosis factor family member APRIL (a proliferation-inducing ligand) in mediating survival of chronic lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and progression in CLL is lacking. APRIL significantly prolonged in

  2. The Association of Unintentional Changes in Weight, Body Composition, and Homeostasis Model Assessment Index with Glycemic Progression in Non-Diabetic Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Eun-Jung Rhee

    2011-04-01

    Full Text Available BackgroundWe performed a retrospective longitudinal study on the effects of changes in weight, body composition, and homeostasis model assessment (HOMA indices on glycemic progression in subjects without diabetes during a four-year follow-up period in a community cohort without intentional intervention.MethodsFrom 28,440 non-diabetic subjects who participated in a medical check-up program in 2004, data on anthropometric and metabolic parameters were obtained after four years in 2008. Body composition analyses were performed with a bioelectrical impedance analyzer. Skeletal muscle index (SMI, % was calculated with lean mass/weight×100. Subjects were divided into three groups according to weight change status in four years: weight loss (≤-5.0%, stable weight (-5.0 to 5.0%, weight gain (≥5.0%. Progressors were defined as the subjects who progressed to impaired fasting glucose or diabetes.ResultsProgressors showed worse baseline metabolic profiles compared with non-progressors. In logistic regression analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR in four years presented higher odds ratios for glycemic progression compared with other changes during that period. Among the components of body composition, a change in waist-hip ratio was the strongest predictor, and SMI change in four years was a significant negative predictor for glycemic progression. Changes in HOMA β-cell function in four years was a negative predictor for glycemic progression.ConclusionIncreased interval changes in HOMA-IR, weight gain and waist-hip ratio was associated with glycemic progression during a four-year period without intentional intervention in non-diabetic Korean subjects.

  3. Progress in model development to quantify High Explosive Violent Response (HEVR) to mechanical insult

    International Nuclear Information System (INIS)

    Reaugh, J.E.

    2008-01-01

    explosive near the trajectory of the impactor. The damage is manifest as surface area through the creation of cracks and fragments, and also as porosity through the separation of crack faces and isolation of the fragments. Open porosity permits a flame to spread easily and so ignite the surface area that was created. The surface area itself leads to in increase in the mass-burning rate. As the kinetic energy and power of the insult increases, the degree of damage and the volume of damage both increase. Upon a localized ignition, the flame spreads to envelop the damaged volume, and the pressure rises at an accelerated rate until neither mechanical strength nor inertial confinement can successfully contain the pressure. The confining structure begins to expand. This reduces the pressure and may even extinguish the flame. Both the mass of explosive involved and the rate at which the gas is produced contribute to each of several different measures of violence. Such measures include damage to the confinement, the velocity and fragment size distributions from what was the confinement, and air blast. Figure 1 illustrates the interaction of the various phenomena described above. Our model comprises several interacting elements. The production of damage, the ignition criterion, the mass rate of burning (reaction rate), the equations of state and constitutive models of the solid explosive reactant (unburned) and gas products, flame propagation in damaged reactant, and the progressive failure of the confinement are all elements of the model. The model is intended for implementation in a general-purpose simulation program (hydrocode) that solves the partial differential equations for the conservation of mass, momentum, and energy in conjunction with equations of state and strength

  4. Coronary risk assessment by point-based vs. equation-based Framingham models: significant implications for clinical care.

    Science.gov (United States)

    Gordon, William J; Polansky, Jesse M; Boscardin, W John; Fung, Kathy Z; Steinman, Michael A

    2010-11-01

    US cholesterol guidelines use original and simplified versions of the Framingham model to estimate future coronary risk and thereby classify patients into risk groups with different treatment strategies. We sought to compare risk estimates and risk group classification generated by the original, complex Framingham model and the simplified, point-based version. We assessed 2,543 subjects age 20-79 from the 2001-2006 National Health and Nutrition Examination Surveys (NHANES) for whom Adult Treatment Panel III (ATP-III) guidelines recommend formal risk stratification. For each subject, we calculated the 10-year risk of major coronary events using the original and point-based Framingham models, and then compared differences in these risk estimates and whether these differences would place subjects into different ATP-III risk groups (20% risk). Using standard procedures, all analyses were adjusted for survey weights, clustering, and stratification to make our results nationally representative. Among 39 million eligible adults, the original Framingham model categorized 71% of subjects as having "moderate" risk (20%) risk. Estimates of coronary risk by the original and point-based models often differed substantially. The point-based system classified 15% of adults (5.7 million) into different risk groups than the original model, with 10% (3.9 million) misclassified into higher risk groups and 5% (1.8 million) into lower risk groups, for a net impact of classifying 2.1 million adults into higher risk groups. These risk group misclassifications would impact guideline-recommended drug treatment strategies for 25-46% of affected subjects. Patterns of misclassifications varied significantly by gender, age, and underlying CHD risk. Compared to the original Framingham model, the point-based version misclassifies millions of Americans into risk groups for which guidelines recommend different treatment strategies.

  5. Effect of self-assembled peptide–mesenchymal stem cell complex on the progression of osteoarthritis in a rat model

    Directory of Open Access Journals (Sweden)

    Kim JE

    2014-05-01

    Full Text Available Ji Eun Kim,1 Sang Mok Lee,2 Soo Hyun Kim,1 Phil Tatman,3 Albert O Gee,4 Deok-Ho Kim,3,5 Kyung Eun Lee,6 Youngmee Jung,1 Sang Jun Kim21Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, South Korea; 2Department of Physical and Rehabilitation Medicine, Samsung Medical Center, Seoul, South Korea; 3Department of Bioengineering, 4Department of Orthopaedics and Sports Medicine, 5Institute for Stem Cell and Regenerative Medicine and Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA; 6Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, South KoreaPurpose: To evaluate the efficacy of mesenchymal stem cells (MSCs encapsulated in self-assembled peptide (SAP hydrogels in a rat knee model for the prevention of osteoarthritis (OA progression.Materials and methods: Nanostructured KLD-12 SAPs were used as the injectable hydrogels. Thirty-three Sprague Dawley rats were used for the OA model. Ten rats were used for the evaluation of biotin-tagged SAP disappearance. Twenty-three rats were divided into four groups: MSC (n=6, SAP (n=6, SAP-MSC (n=6, and no treatment (n=5. MSCs, SAPs, and SAP-MSCs were injected into the knee joints 3 weeks postsurgery. Histologic examination, immunofluorescent staining, measurement of cytokine levels, and micro-computed tomography analysis were conducted 6 weeks after injections. Behavioral studies were done to establish baseline measurements before treatment, and repeated 3 and 6 weeks after treatment to measure the efficacy of SAP-MSCs.Results: Concentration of biotinylated SAP at week 1 was not significantly different from those at week 3 and week 6 (P=0.565. Bone mineral density was significantly lower in SAP-MSC groups than controls (P=0.002. Significant differences in terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining between the control group and all other groups were observed. Caspase-8, tissue inhibitor of

  6. Coal to SNG: Technical progress, modeling and system optimization through exergy analysis

    International Nuclear Information System (INIS)

    Li, Sheng; Ji, Xiaozhou; Zhang, Xiaosong; Gao, Lin; Jin, Hongguang

    2014-01-01

    Highlights: • Technical progresses of coal to SNG technologies are reported. • The entire coal to SNG system is modeled. • Coupling between SNG production and power generation is investigated. • Breakthrough points for further energy saving are determined. • System performance is optimized based on the first and second laws of thermodynamics. - Abstract: For both energy security and CO 2 emission reduction, synthetic natural gas (SNG) production from coal is an important path to implement clean coal technologies in China. In this paper, an overview of the progress of coal to SNG technologies, including the development of catalysts, reactor designs, synthesis processes, and systems integration, is provided. The coal to SNG system is modeled, the coupling between SNG production and power generation is investigated, the breakthrough points for further energy savings are determined, and the system performance is optimized based on the first and the second laws of thermodynamics. From the viewpoint of the first law of thermodynamics, the energy conversion efficiency of coal to SNG system can reach 59.8%. To reduce the plant auxiliary power, the breakthrough points are the development of low-energy-consumption oxygen production technology and gas purification technology or seeking new oxidants for coal gasification instead of oxygen. From the viewpoint of the second law of thermodynamics, the major exergy destruction in a coal to SNG system occurs in the coal gasification unit, SNG synthesis unit and the raw syngas cooling process. How to reduce the exergy destruction in these units is the key to energy savings and system performance enhancement. The conversion ratio of the first SNG synthesis reactor and the split ratio of the recycle gas are key factors that determine the performance of both the SNG synthesis process and the whole plant. A “turning point” phenomenon is observed: when the split ratio is higher than 0.90, the exergy destruction of the SNG

  7. A Unique Model System for Tumor Progression in GBM Comprising Two Developed Human Neuro-Epithelial Cell Lines with Differential Transforming Potential and Coexpressing Neuronal and Glial Markers

    Directory of Open Access Journals (Sweden)

    Anjali Shiras

    2003-11-01

    Full Text Available The molecular mechanisms involved in tumor progression from a low-grade astrocytoma to the most malignant glioblastoma multiforme (GBM have been hampered due to lack of suitable experimental models. We have established a model of tumor progression comprising of two cell lines derived from the same astrocytoma tumor with a set of features corresponding to low-grade glioma (as in HNGC-1 and high-grade GBM (as in HNGC-2. The HNGC-1 cell line is slowgrowing, contact-inhibited, nontumorigenic, and noninvasive, whereas HNGC-2 is a rapidly proliferating, anchorage-independent, highly tumorigenic, and invasive cell line. The proliferation of cell lines is independent of the addition of exogenous growth factors. Interestingly, the HNGC-2 cell line displays a near-haploid karyotype except for a disomy of chromosome 2. The two cell lines express the neuronal precursor and progenitor markers vimentin, nestin, MAP-2, and NFP160, as well as glial differentiation protein S100μ. The HNGC-1 cell line also expresses markers of mature neurons like Tuj1 and GFAP, an astrocytic differentiation marker, hence contributing toward a more morphologically differentiated phenotype with a propensity for neural differentiation in vitro. Additionally, overexpression of epidermal growth factor receptor and c-erbB2, and loss of fibronectin were observed only in the HNGC-2 cell line, implicating the significance of these pathways in tumor progression. This in vitro model system assumes importance in unraveling the cellular and molecular mechanisms in differentiation, transformation, and gliomagenesis.

  8. Caffeine alleviates progressive motor deficits in a transgenic mouse model of spinocerebellar ataxia.

    Science.gov (United States)

    Gonçalves, Nélio; Simões, Ana T; Prediger, Rui D; Hirai, Hirokazu; Cunha, Rodrigo A; Pereira de Almeida, Luís

    2017-03-01

    Machado-Joseph disease (MJD) is a neurodegenerative spinocerebellar ataxia (SCA) associated with an expanded polyglutamine tract within ataxin-3 for which there is currently no available therapy. We previously showed that caffeine, a nonselective adenosine receptor antagonist, delays the appearance of striatal damage resulting from expression of full-length mutant ataxin-3. Here we investigated the ability of caffeine to alleviate behavioral deficits and cerebellar neuropathology in transgenic mice with a severe ataxia resulting from expression of a truncated fragment of polyglutamine-expanded ataxin-3 in Purkinje cells. Control and transgenic c57Bl6 mice expressing in the mouse cerebella a truncated form of human ataxin-3 with 69 glutamine repeats were allowed to freely drink water or caffeinated water (1g/L). Treatments began at 7 weeks of age, when motor and ataxic phenotype emerges in MJD mice, and lasted up to 20 weeks. Mice were tested in a panel of locomotor behavioral paradigms, namely rotarod, beam balance and walking, pole, and water maze cued-platform version tests, and then sacrificed for cerebellar histology. Caffeine consumption attenuated the progressive loss of general and fine-tuned motor function, balance, and grip strength, in parallel with preservation of cerebellar morphology through decreasing the loss of Purkinje neurons and the thinning of the molecular layer in different folia. Caffeine also rescued the putative striatal-dependent executive and cognitive deficiencies in MJD mice. Our findings provide the first in vivo demonstration that caffeine intake alleviates behavioral disabilities in a severely impaired animal model of SCA. Ann Neurol 2017;81:407-418. © 2016 American Neurological Association.

  9. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease.

    Science.gov (United States)

    Cifuentes, Diana; Poittevin, Marine; Dere, Ekrem; Broquères-You, Dong; Bonnin, Philippe; Benessiano, Joëlle; Pocard, Marc; Mariani, Jean; Kubis, Nathalie; Merkulova-Rainon, Tatyana; Lévy, Bernard I

    2015-01-01

    Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; P<0.05). Our results indicate that hypertension accelerates the development of Alzheimer disease-related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production. © 2014 American Heart Association, Inc.

  10. Model Agreements for the granting of Associate Member Status Implementation arrangements concerning eligibility for personnel appointments and industrial participation for Associate Member States Progress report by the Management

    CERN Document Server

    2011-01-01

    Model Agreements for the granting of Associate Member Status Implementation arrangements concerning eligibility for personnel appointments and industrial participation for Associate Member States Progress report by the Management

  11. Evaluation of the implementation and impact of an integrated prevention model on the academic progress of students with disabilities.

    Science.gov (United States)

    Barlow, Alexandra; Humphrey, Neil; Lendrum, Ann; Wigelsworth, Michael; Squires, Garry

    2014-11-12

    In this paper we report on the implementation and impact of an integrated prevention model (Achievement for All - AfA) to improve the educational experiences and outcomes of students with disabilities. It comprises three inter-related strands: assessment, tracking and intervention; structured conversations with parents; and, developing provision for wider outcomes. Participants were 12,038 students with disabilities from 431 mainstream primary and secondary schools across 10 Local Authorities in England involved in the two-year AfA pilot. Pre- and post-test data on academic attainment in English and Maths were compared with national data on academic progress for students with and without disabilities over an equivalent period of time. School-level contextual and implementation data and student-level socio-demographic and psychosocial data were also collected. Four hypotheses were tested regarding the impact of AfA on academic attainment in English (H1) and Maths (H2); the influence of aspects of the implementation context and processes (H3); and individual differences between students (H4). Our findings are discussed in relation to the identification and validation of critical intervention components and standards for assessing the practical significance of attempts to improve outcomes for students. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Protective Effect of a Lipid-Based Preparation from Mycobacterium smegmatis in a Murine Model of Progressive Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Maria de los Angeles García

    2014-01-01

    Full Text Available A more effective vaccine against tuberculosis (TB is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb, the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms, could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL or nonadjuvanted (LMs showed significant reductions in bacterial load (P<0.01 compared to the negative control group (animals immunized with phosphate buffered saline (PBS. Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG. Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P<0.01 and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.

  13. Celecoxib does not significantly delay bone healing in a rat femoral osteotomy model: a bone histomorphometry study

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2011-12-01

    Full Text Available Jun Iwamoto1, Azusa Seki2, Yoshihiro Sato3, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Hamri Co, Ltd, Tokyo, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, JapanBackground and objective: The objective of the present study was to determine whether celecoxib, a cyclo-oxygenase-2 inhibitor, would delay bone healing in a rat femoral osteotomy model by examining bone histomorphometry parameters.Methods: Twenty-one 6-week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation; the rats were then divided into three groups: the vehicle administration group (control, n = 8, the vitamin K2 administration (menatetrenone 30 mg/kg orally, five times a week group (positive control, n = 5, and the celecoxib administration (4 mg/kg orally, five times a week group (n = 8. After 6 weeks of treatment, the wires were removed, and a bone histomorphometric analysis was performed on the bone tissue inside the callus. The lamellar area relative to the bone area was significantly higher and the total area and woven area relative to the bone area were significantly lower in the vitamin K2 group than in the vehicle group. However, none of the structural parameters, such as the callus and bone area relative to the total area, lamellar and woven areas relative to the bone area, or the formative and resorptive parameters such as osteoclast surface, number of osteoclasts, osteoblast surface, osteoid surface, eroded surface, and bone formation rate per bone surface differed significantly between the vehicle and celecoxib groups.Conclusion: The present study implies that celecoxib may not significantly delay bone healing in a rat femoral osteotomy model based on the results of a bone histomorphometric analysis.Keywords: femoral osteotomy, bone healing, callus, rat, celecoxib

  14. A spray flamelet/progress variable approach combined with a transported joint PDF model for turbulent spray flames

    Science.gov (United States)

    Hu, Yong; Olguin, Hernan; Gutheil, Eva

    2017-05-01

    A spray flamelet/progress variable approach is developed for use in spray combustion with partly pre-vaporised liquid fuel, where a laminar spray flamelet library accounts for evaporation within the laminar flame structures. For this purpose, the standard spray flamelet formulation for pure evaporating liquid fuel and oxidiser is extended by a chemical reaction progress variable in both the turbulent spray flame model and the laminar spray flame structures, in order to account for the effect of pre-vaporised liquid fuel for instance through use of a pilot flame. This new approach is combined with a transported joint probability density function (PDF) method for the simulation of a turbulent piloted ethanol/air spray flame, and the extension requires the formulation of a joint three-variate PDF depending on the gas phase mixture fraction, the chemical reaction progress variable, and gas enthalpy. The molecular mixing is modelled with the extended interaction-by-exchange-with-the-mean (IEM) model, where source terms account for spray evaporation and heat exchange due to evaporation as well as the chemical reaction rate for the chemical reaction progress variable. This is the first formulation using a spray flamelet model considering both evaporation and partly pre-vaporised liquid fuel within the laminar spray flamelets. Results with this new formulation show good agreement with the experimental data provided by A.R. Masri, Sydney, Australia. The analysis of the Lagrangian statistics of the gas temperature and the OH mass fraction indicates that partially premixed combustion prevails near the nozzle exit of the spray, whereas further downstream, the non-premixed flame is promoted towards the inner rich-side of the spray jet since the pilot flame heats up the premixed inner spray zone. In summary, the simulation with the new formulation considering the reaction progress variable shows good performance, greatly improving the standard formulation, and it provides new

  15. A Simple Diet- and Chemical-Induced Murine NASH Model with Rapid Progression of Steatohepatitis, Fibrosis and Liver Cancer.

    Science.gov (United States)

    Tsuchida, Takuma; Lee, Youngmin A; Fujiwara, Naoto; Ybanez, Maria; Allen, Brittany; Martins, Sebastiao; Fiel, M Isabel; Goossens, Nicolas; Chou, Hsin-I; Hoshida, Yujin; Friedman, Scott L

    2018-03-20

    Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl 4 ), which served as an accelerator. C57BL/6J mice were fed a normal chow diet (ND) ± CCl 4 or WD ± CCl 4 for 12 and 24 weeks. Addition of CCl 4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl 4 mice and immunologic features were closely similar to those of human NASH. Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing. A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  16. Genome-wide significant localization for working and spatial memory: Identifying genes for psychosis using models of cognition.

    Science.gov (United States)

    Knowles, Emma E M; Carless, Melanie A; de Almeida, Marcio A A; Curran, Joanne E; McKay, D Reese; Sprooten, Emma; Dyer, Thomas D; Göring, Harald H; Olvera, Rene; Fox, Peter; Almasy, Laura; Duggirala, Ravi; Kent, Jack W; Blangero, John; Glahn, David C

    2014-01-01

    It is well established that risk for developing psychosis is largely mediated by the influence of genes, but identifying precisely which genes underlie that risk has been problematic. Focusing on endophenotypes, rather than illness risk, is one solution to this problem. Impaired cognition is a well-established endophenotype of psychosis. Here we aimed to characterize the genetic architecture of cognition using phenotypically detailed models as opposed to relying on general IQ or individual neuropsychological measures. In so doing we hoped to identify genes that mediate cognitive ability, which might also contribute to psychosis risk. Hierarchical factor models of genetically clustered cognitive traits were subjected to linkage analysis followed by QTL region-specific association analyses in a sample of 1,269 Mexican American individuals from extended pedigrees. We identified four genome wide significant QTLs, two for working and two for spatial memory, and a number of plausible and interesting candidate genes. The creation of detailed models of cognition seemingly enhanced the power to detect genetic effects on cognition and provided a number of possible candidate genes for psychosis. © 2013 Wiley Periodicals, Inc.

  17. Progressive Neuronal Pathology and Synaptic Loss Induced by Prediabetes and Type 2 Diabetes in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Ramos-Rodriguez, Juan Jose; Spires-Jones, Tara; Pooler, Amy M; Lechuga-Sancho, Alfonso Maria; Bacskai, Brian J; Garcia-Alloza, Monica

    2017-07-01

    Age remains the main risk factor for developing Alzheimer's disease (AD) although certain metabolic alterations, including prediabetes and type 2 diabetes (T2D), may also increase this risk. In order to understand this relationship, we have studied an AD-prediabetes mouse model (APP/PS1) with severe hyperinsulinemia induced by long-term high fat diet (HFD), and an AD-T2D model, generated by crossing APP/PS1 and db/db mice (APP/PS1xdb/db). In both, prediabetic and diabetic AD mice, we have analyzed underlying neuronal pathology and synaptic loss. At 26 weeks of age, when both pathologies were clearly established, we observed severe brain atrophy in APP/PS1xdb/db animals as well as cortical thinning, accompanied by increased caspase activity. Reduced senile plaque burden and elevated soluble Aβ40 and 42 levels were observed in AD-T2D mice. Further assessment revealed a significant increase of neurite curvature in prediabetic-AD mice, and this effect was worsened in AD-T2D animals. Synaptic density loss, analyzed by array tomography, revealed a synergistic effect between T2D and AD, whereas an intermediate state was observed, once more, in prediabetic-AD mice. Altogether, our data suggest that early prediabetic hyperinsulinemia may exacerbate AD pathology, and that fully established T2D clearly worsens these effects. Therefore, it is feasible that early detection of prediabetic state and strict metabolic control could slow or delay progression of AD-associated neuropathological features.

  18. Abduction aiming at empirical progress or even at truth approximation, leading to challenge for computational modelling

    NARCIS (Netherlands)

    Kuipers, Theo A.F.

    1999-01-01

    This paper primarily deals with the conceptual prospects for generalizing the aim of abduction from the standard one of explaining surprising or anomalous observations to that of empirical progress or even truth approximation. It turns out that the main abduction task then becomes the

  19. Tumour Progression and Spontaneous Regression in the Lewis Rat Sarcoma Model

    Czech Academy of Sciences Publication Activity Database

    Kovalská, Jana; Mishra, Rajbardhan; Jebavý, L.; Makovický, P.; Janda, Jozef; Plánská, D.; Červinková, Monika; Horák, Vratislav

    2015-01-01

    Roč. 35, č. 12 (2015), s. 6539-6549 ISSN 0250-7005 R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : spontaneous regression * progression * sarcoma Subject RIV: FD - Oncology ; Hematology Impact factor: 1.895, year: 2015

  20. Modelling T4 cell count as a marker of HIV progression in the ...

    African Journals Online (AJOL)

    ∗Corresponding author: Department of Industrial and Systems Engineering, University ... T4 cell count as a marker of HIV progression in the absence of any defense ... This observation enables us to make the assumption that the population of ...

  1. Formal modeling and analysis of the hexosamine biosynthetic pathway: role of O-linked N-acetylglucosamine transferase in oncogenesis and cancer progression

    Directory of Open Access Journals (Sweden)

    Muhammad Tariq Saeed

    2016-09-01

    Full Text Available The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression. We compute delay constraints to reveal important associations between the production and degradation rates of proteins. O-linked N-acetylglucosamine transferase (OGT, an enzyme used for addition of O-GlcNAc during O-GlcNAcylation, is identified as a key regulator to promote oncogenesis in a feedback mechanism through the stabilization of c-Myc. Silencing of the OGT and c-Myc loop decreases glycolytic flux and leads to programmed cell death. Results of network analyses also identify a significant cycle that highlights the role of p53-Mdm2 circuit oscillations in cancer recovery and homeostasis. Together, our findings suggest that the OGT and c-Myc feedback loop is critical in tumor progression, and targeting these mediators may provide a mechanism-based therapeutic approach to regulate hyper-O-GlcNAcylation in human cancer.

  2. Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression

    Science.gov (United States)

    2008-02-01

    identify new and structurally diverse chemical analogs of the polyphenolic phytochemical Curcumin from the Indian herb Curcuma longa (family...AD_________________ Award Number: W81XWH-07-1-0081 TITLE: Curcumin Based Drug Screening for... Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-07-1-0081 5c

  3. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington?s Disease Mouse Model R6/2

    OpenAIRE

    Nielsen, Signe Marie Borch; Hasholt, Lis; N?rrem?lle, Anne; Josefsen, Knud

    2015-01-01

    Huntington?s disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indic...

  4. Early Prediction of Disease Progression in Small Cell Lung Cancer: Toward Model-Based Personalized Medicine in Oncology.

    Science.gov (United States)

    Buil-Bruna, Núria; Sahota, Tarjinder; López-Picazo, José-María; Moreno-Jiménez, Marta; Martín-Algarra, Salvador; Ribba, Benjamin; Trocóniz, Iñaki F

    2015-06-15

    Predictive biomarkers can play a key role in individualized disease monitoring. Unfortunately, the use of biomarkers in clinical settings has thus far been limited. We have previously shown that mechanism-based pharmacokinetic/pharmacodynamic modeling enables integration of nonvalidated biomarker data to provide predictive model-based biomarkers for response classification. The biomarker model we developed incorporates an underlying latent variable (disease) representing (unobserved) tumor size dynamics, which is assumed to drive biomarker production and to be influenced by exposure to treatment. Here, we show that by integrating CT scan data, the population model can be expanded to include patient outcome. Moreover, we show that in conjunction with routine medical monitoring data, the population model can support accurate individual predictions of outcome. Our combined model predicts that a change in disease of 29.2% (relative standard error 20%) between two consecutive CT scans (i.e., 6-8 weeks) gives a probability of disease progression of 50%. We apply this framework to an external dataset containing biomarker data from 22 small cell lung cancer patients (four patients progressing during follow-up). Using only data up until the end of treatment (a total of 137 lactate dehydrogenase and 77 neuron-specific enolase observations), the statistical framework prospectively identified 75% of the individuals as having a predictable outcome in follow-up visits. This included two of the four patients who eventually progressed. In all identified individuals, the model-predicted outcomes matched the observed outcomes. This framework allows at risk patients to be identified early and therapeutic intervention/monitoring to be adjusted individually, which may improve overall patient survival. ©2015 American Association for Cancer Research.

  5. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression.

    Science.gov (United States)

    Estrada, Marta F; Rebelo, Sofia P; Davies, Emma J; Pinto, Marta T; Pereira, Hugo; Santo, Vítor E; Smalley, Matthew J; Barry, Simon T; Gualda, Emilio J; Alves, Paula M; Anderson, Elizabeth; Brito, Catarina

    2016-02-01

    3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Recent Progress in Understanding Natural-Hazards-Generated TEC Perturbations: Measurements and Modeling Results

    Science.gov (United States)

    Komjathy, A.; Yang, Y. M.; Meng, X.; Verkhoglyadova, O. P.; Mannucci, A. J.; Langley, R. B.

    2015-12-01

    Natural hazards, including earthquakes, volcanic eruptions, and tsunamis, have been significant threats to humans throughout recorded history. The Global Positioning System satellites have become primary sensors to measure signatures associated with such natural hazards. These signatures typically include GPS-derived seismic deformation measurements, co-seismic vertical displacements, and real-time GPS-derived ocean buoy positioning estimates. Another way to use GPS observables is to compute the ionospheric total electron content (TEC) to measure and monitor post-seismic ionospheric disturbances caused by earthquakes, volcanic eruptions, and tsunamis. Research at the University of New Brunswick (UNB) laid the foundations to model the three-dimensional ionosphere at NASA's Jet Propulsion Laboratory by ingesting ground- and space-based GPS measurements into the state-of-the-art Global Assimilative Ionosphere Modeling (GAIM) software. As an outcome of the UNB and NASA research, new and innovative GPS applications have been invented including the use of ionospheric measurements to detect tiny fluctuations in the GPS signals between the spacecraft and GPS receivers caused by natural hazards occurring on or near the Earth's surface.We will show examples for early detection of natural hazards generated ionospheric signatures using ground-based and space-borne GPS receivers. We will also discuss recent results from the U.S. Real-time Earthquake Analysis for Disaster Mitigation Network (READI) exercises utilizing our algorithms. By studying the propagation properties of ionospheric perturbations generated by natural hazards along with applying sophisticated first-principles physics-based modeling, we are on track to develop new technologies that can potentially save human lives and minimize property damage. It is also expected that ionospheric monitoring of TEC perturbations might become an integral part of existing natural hazards warning systems.

  7. Progression of biopsy-measured liver fibrosis in untreated patients with hepatitis C infection: non-Markov multistate model analysis.

    Directory of Open Access Journals (Sweden)

    Peter Bacchetti

    Full Text Available BACKGROUND: Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times. METHODS: We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR quantified the estimated effects of covariates on progression risk at any given time. RESULTS: Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018, and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002. When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80. There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059. Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection. DISCUSSION: The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating

  8. Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice.

    Science.gov (United States)

    Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji

    2012-03-01

    The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS.

  9. Improved progressive morphological filter for digital terrain model generation from airborne lidar data.

    Science.gov (United States)

    Hui, Zhenyang; Wu, Beiping; Hu, Youjian; Ziggah, Yao Yevenyo

    2017-12-01

    Obtaining high-precision filtering results from airborne lidar point clouds in complex environments has always been a hot topic. Mathematical morphology was widely used for filtering, owing to its simplicity and high efficiency. However, the morphology-based algorithms are deficient in preserving terrain details. In order to obtain a better filtering effect, this paper proposed an improved progressive morphological filter based on hierarchical radial basis function interpolation (PMHR) to refine the classical progressive morphological filter. PMHR involved two main improvements, namely, automatic setting of self-adaptive thresholds and terrain details preservation, respectively. The performance of PMHR was evaluated using datasets provided by the International Society for Photogrammetry and Remote Sensing. Experimental results show that PMHR achieved good performance under variant terrain features with an average total error of 4.27% and average Kappa coefficient of 84.57%.

  10. Modelling noise propagation using Grid Resources. Progress within GDI-Grid

    Science.gov (United States)

    Kiehle, Christian; Mayer, Christian; Padberg, Alexander; Stapelfeld, Hartmut

    2010-05-01

    Modelling noise propagation using Grid Resources. Progress within GDI-Grid. GDI-Grid (english: SDI-Grid) is a research project funded by the German Ministry for Science and Education (BMBF). It aims at bridging the gaps between OGC Web Services (OWS) and Grid infrastructures and identifying the potential of utilizing the superior storage capacities and computational power of grid infrastructures for geospatial applications while keeping the well-known service interfaces specified by the OGC. The project considers all major OGC webservice interfaces for Web Mapping (WMS), Feature access (Web Feature Service), Coverage access (Web Coverage Service) and processing (Web Processing Service). The major challenge within GDI-Grid is the harmonization of diverging standards as defined by standardization bodies for Grid computing and spatial information exchange. The project started in 2007 and will continue until June 2010. The concept for the gridification of OWS developed by lat/lon GmbH and the Department of Geography of the University of Bonn is applied to three real-world scenarios in order to check its practicability: a flood simulation, a scenario for emergency routing and a noise propagation simulation. The latter scenario is addressed by the Stapelfeldt Ingenieurgesellschaft mbH located in Dortmund adapting their LimA software to utilize grid resources. Noise mapping of e.g. traffic noise in urban agglomerates and along major trunk roads is a reoccurring demand of the EU Noise Directive. Input data requires road net and traffic, terrain, buildings and noise protection screens as well as population distribution. Noise impact levels are generally calculated in 10 m grid and along relevant building facades. For each receiver position sources within a typical range of 2000 m are split down into small segments, depending on local geometry. For each of the segments propagation analysis includes diffraction effects caused by all obstacles on the path of sound propagation

  11. Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

    Directory of Open Access Journals (Sweden)

    Eline Boghaert

    2014-12-01

    Full Text Available Ductal carcinoma in situ (DCIS is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo, but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

  12. Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

    Science.gov (United States)

    Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

    2014-12-01

    Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

  13. Use of dispersion modelling for Environmental Impact Assessment of biological air pollution from composting: Progress, problems and prospects.

    Science.gov (United States)

    Douglas, P; Hayes, E T; Williams, W B; Tyrrel, S F; Kinnersley, R P; Walsh, K; O'Driscoll, M; Longhurst, P J; Pollard, S J T; Drew, G H

    2017-12-01

    With the increase in composting asa sustainable waste management option, biological air pollution (bioaerosols) from composting facilities have become a cause of increasing concern due to their potential health impacts. Estimating community exposure to bioaerosols is problematic due to limitations in current monitoring methods. Atmospheric dispersion modelling can be used to estimate exposure concentrations, however several issues arise from the lack of appropriate bioaerosol data to use as inputs into models, and the complexity of the emission sources at composting facilities. This paper analyses current progress in using dispersion models for bioaerosols, examines the remaining problems and provides recommendations for future prospects in this area. A key finding is the urgent need for guidance for model users to ensure consistent bioaerosol modelling practices. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. GeoSciML v3.0 - a significant upgrade of the CGI-IUGS geoscience data model

    Science.gov (United States)

    Raymond, O.; Duclaux, G.; Boisvert, E.; Cipolloni, C.; Cox, S.; Laxton, J.; Letourneau, F.; Richard, S.; Ritchie, A.; Sen, M.; Serrano, J.-J.; Simons, B.; Vuollo, J.

    2012-04-01

    GeoSciML version 3.0 (http://www.geosciml.org), released in late 2011, is the latest version of the CGI-IUGS* Interoperability Working Group geoscience data interchange standard. The new version is a significant upgrade and refactoring of GeoSciML v2 which was released in 2008. GeoSciML v3 has already been adopted by several major international interoperability initiatives, including OneGeology, the EU INSPIRE program, and the US Geoscience Information Network, as their standard data exchange format for geoscience data. GeoSciML v3 makes use of recently upgraded versions of several Open Geospatial Consortium (OGC) and ISO data transfer standards, including GML v3.2, SWE Common v2.0, and Observations and Measurements v2 (ISO 19156). The GeoSciML v3 data model has been refactored from a single large application schema with many packages, into a number of smaller, but related, application schema modules with individual namespaces. This refactoring allows the use and future development of modules of GeoSciML (eg; GeologicUnit, GeologicStructure, GeologicAge, Borehole) in smaller, more manageable units. As a result of this refactoring and the integration with new OGC and ISO standards, GeoSciML v3 is not backwardly compatible with previous GeoSciML versions. The scope of GeoSciML has been extended in version 3.0 to include new models for geomorphological data (a Geomorphology application schema), and for geological specimens, geochronological interpretations, and metadata for geochemical and geochronological analyses (a LaboratoryAnalysis-Specimen application schema). In addition, there is better support for borehole data, and the PhysicalProperties model now supports a wider range of petrophysical measurements. The previously used CGI_Value data type has been superseded in favour of externally governed data types provided by OGC's SWE Common v2 and GML v3.2 data standards. The GeoSciML v3 release includes worked examples of best practice in delivering geochemical

  15. Investigating the Effect of Damage Progression Model Choice on Prognostics Performance

    Data.gov (United States)

    National Aeronautics and Space Administration — The success of model-based approaches to systems health management depends largely on the quality of the underly- ing models. In model-based prognostics, it is...

  16. Significance of myoglobin as an oxygen store and oxygen transporter in the intermittently perfused human heart: a model study.

    Science.gov (United States)

    Endeward, Volker; Gros, Gerolf; Jürgens, Klaus D

    2010-07-01

    The mechanisms by which the left ventricular wall escapes anoxia during the systolic phase of low blood perfusion are investigated, especially the role of myoglobin (Mb), which can (i) store oxygen and (ii) facilitate intracellular oxygen transport. The quantitative role of these two Mb functions is studied in the maximally working human heart. Because discrimination between Mb functions has not been achieved experimentally, we use a Krogh cylinder model here. At a heart rate of 200 beats/min and a 1:1 ratio of diastole/systole, the systole lasts for 150 ms. The basic model assumption is that, with mobile Mb, the oxygen stored in the end-diastolic left ventricle wall exactly meets the demand during the 150 ms of systolic cessation of blood flow. The coronary blood flow necessary to achieve this agrees with literature data. By considering Mb immobile or setting its concentration to zero, respectively, we find that, depending on Mb concentration, Mb-facilitated O(2) transport maintains O(2) supply to the left ventricle wall during 22-34 of the 150 ms, while Mb storage function accounts for a further 12-17 ms. When Mb is completely absent, anoxia begins to develop after 116-99 ms. While Mb plays no significant role during diastole, it supplies O(2) to the left ventricular wall for < or = 50 ms of the 150 ms systole, whereas capillary haemoglobin is responsible for approximately 80 ms. Slight increases in haemoglobin concentration, blood flow, or capillary density can compensate the absence of Mb, a finding which agrees well with the observations using Mb knockout mice.

  17. Intelligent system for statistically significant expertise knowledge on the basis of the model of self-organizing nonequilibrium dissipative system

    Directory of Open Access Journals (Sweden)

    E. A. Tatokchin

    2017-01-01

    Full Text Available Development of the modern educational technologies caused by broad introduction of comput-er testing and development of distant forms of education does necessary revision of methods of an examination of pupils. In work it was shown, need transition to mathematical criteria, exami-nations of knowledge which are deprived of subjectivity. In article the review of the problems arising at realization of this task and are offered approaches for its decision. The greatest atten-tion is paid to discussion of a problem of objective transformation of rated estimates of the ex-pert on to the scale estimates of the student. In general, the discussion this question is was con-cluded that the solution to this problem lies in the creation of specialized intellectual systems. The basis for constructing intelligent system laid the mathematical model of self-organizing nonequilibrium dissipative system, which is a group of students. This article assumes that the dissipative system is provided by the constant influx of new test items of the expert and non-equilibrium – individual psychological characteristics of students in the group. As a result, the system must self-organize themselves into stable patterns. This patern will allow for, relying on large amounts of data, get a statistically significant assessment of student. To justify the pro-posed approach in the work presents the data of the statistical analysis of the results of testing a large sample of students (> 90. Conclusions from this statistical analysis allowed to develop intelligent system statistically significant examination of student performance. It is based on data clustering algorithm (k-mean for the three key parameters. It is shown that this approach allows you to create of the dynamics and objective expertise evaluation.

  18. A novel quantitative model of cell cycle progression based on cyclin-dependent kinases activity and population balances.

    Science.gov (United States)

    Pisu, Massimo; Concas, Alessandro; Cao, Giacomo

    2015-04-01

    Cell cycle regulates proliferative cell capacity under normal or pathologic conditions, and in general it governs all in vivo/in vitro cell growth and proliferation processes. Mathematical simulation by means of reliable and predictive models represents an important tool to interpret experiment results, to facilitate the definition of the optimal operating conditions for in vitro cultivation, or to predict the effect of a specific drug in normal/pathologic mammalian cells. Along these lines, a novel model of cell cycle progression is proposed in this work. Specifically, it is based on a population balance (PB) approach that allows one to quantitatively describe cell cycle progression through the different phases experienced by each cell of the entire population during its own life. The transition between two consecutive cell cycle phases is simulated by taking advantage of the biochemical kinetic model developed by Gérard and Goldbeter (2009) which involves cyclin-dependent kinases (CDKs) whose regulation is achieved through a variety of mechanisms that include association with cyclins and protein inhibitors, phosphorylation-dephosphorylation, and cyclin synthesis or degradation. This biochemical model properly describes the entire cell cycle of mammalian cells by maintaining a sufficient level of detail useful to identify check point for transition and to estimate phase duration required by PB. Specific examples are discussed to illustrate the ability of the proposed model to simulate the effect of drugs for in vitro trials of interest in oncology, regenerative medicine and tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Evaluation of an unsteady flamelet progress variable model for autoignition and flame development in compositionally stratified mixtures

    Science.gov (United States)

    Mukhopadhyay, Saumyadip; Abraham, John

    2012-07-01

    The unsteady flamelet progress variable (UFPV) model has been proposed by Pitsch and Ihme ["An unsteady/flamelet progress variable method for LES of nonpremixed turbulent combustion," AIAA Paper No. 2005-557, 2005] for modeling the averaged/filtered chemistry source terms in Reynolds averaged simulations and large eddy simulations of reacting non-premixed combustion. In the UFPV model, a look-up table of source terms is generated as a function of mixture fraction Z, scalar dissipation rate χ, and progress variable C by solving the unsteady flamelet equations. The assumption is that the unsteady flamelet represents the evolution of the reacting mixing layer in the non-premixed flame. We assess the accuracy of the model in predicting autoignition and flame development in compositionally stratified n-heptane/air mixtures using direct numerical simulations (DNS). The focus in this work is primarily on the assessment of accuracy of the probability density functions (PDFs) employed for obtaining averaged source terms. The performance of commonly employed presumed functions, such as the dirac-delta distribution function, the β distribution function, and statistically most likely distribution (SMLD) approach in approximating the shapes of the PDFs of the reactive and the conserved scalars is evaluated. For unimodal distributions, it is observed that functions that need two-moment information, e.g., the β distribution function and the SMLD approach with two-moment closure, are able to reasonably approximate the actual PDF. As the distribution becomes multimodal, higher moment information is required. Differences are observed between the ignition trends obtained from DNS and those predicted by the look-up table, especially for smaller gradients where the flamelet assumption becomes less applicable. The formulation assumes that the shape of the χ(Z) profile can be modeled by an error function which remains unchanged in the presence of heat release. We show that this

  20. Topical Loperamide-Encapsulated Liposomal Gel Increases the Severity of Inflammation and Accelerates Disease Progression in the Adjuvant-Induced Model of Experimental Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Susan Hua

    2017-08-01

    Full Text Available This study evaluates the prophylactic effect of the peripherally-selective mu-opioid receptor agonist, loperamide, administered topically in a liposomal gel formulation on pain, inflammation, and disease progression in the adjuvant-induced model of experimental rheumatoid arthritis in female Lewis rats. In a randomized, blinded and controlled animal trial, AIA rats were divided into six groups consisting of eleven rats per group based on the following treatments: loperamide liposomal gel, free loperamide gel, empty liposomal gel, diclofenac gel (Voltaren®, no treatment, and naive control. Topical formulations were applied daily for a maximum of 17 days—starting from day 0 at the same time as immunization. The time course of the effect of the treatments on antinocieption and inflammation was assessed using a paw pressure analgesiometer and plethysmometer, respectively. Arthritis progression was scored daily using an established scoring protocol. At the end of the study, hind paws were processed for histological analysis. Administration of loperamide liposomal gel daily across the duration of the study produced significant peripheral antinociception as expected; however, increased the severity of inflammation and accelerated arthritis progression. This was indicated by an increase in paw volume, behavioral and observational scoring, and histological analysis compared to the control groups. In particular, histology results showed an increase in pannus formation and synovial inflammation, as well as an upregulation of markers of inflammation and angiogenesis. These findings may have implications for the use of loperamide and other opioids in arthritis and potentially other chronic inflammatory diseases.

  1. Dose-dependent striatal changes in dopaminergic terminals and alpha-synuclein reactivity in a porcine model of progressive Parkinson’s disease

    DEFF Research Database (Denmark)

    Nielsen, Mette Slot; Glud, Andreas Nørgaard; Møller, Arne

    2011-01-01

    to discover effective compounds halting PD progression have so far failed in clinical trials, perhaps because current animal models do not imitate the neuropathological progression of PD well enough. We recently established a progressive large animal PD model in Göttingen minipigs based on chronic infusion......Parkinson disease (PD) is a common neurodegenerative disorder, resulting from a progressive dopaminergic neuron loss in the substantia nigra (SN). Alpha-synuclein positive neuronal inclusion bodies and progressive loss of dopaminergic striatal terminals is also well described in PD. Attempts...... the SN were paraffin embedded and immunohistochemically stained for tyrosine hydroxylase (TH) and alpha-synuclein. Stereological examination of the SN showed progressive nigral neuron loss with increased MPTP dosages. Occasional neuronal staining confined to the cytoplasm and cell membrane was observed...

  2. Progress in the development of the GMM-2 gravity field model for Mars

    Science.gov (United States)

    Lemoine, F. G.; Smith, D. E.; Lerch, F. J.; Zuber, M. T.; Patel, G. B.

    1994-01-01

    Last year we published the GMM-1 (Goddard Mars Model-1) gravity model for Mars. We have completely re-analyzed the Viking and Mariner 9 tracking data in the development of the new field, designated GMM-2. The model is complete to degree and order 70. Various aspects of the model are discussed.

  3. Research progress from the SCI Model Systems (SCIMS): An interactive discussion on future directions.

    Science.gov (United States)

    Boninger, Michael L; Field-Fote, Edelle C; Kirshblum, Steven C; Lammertse, Daniel P; Dyson-Hudson, Trevor A; Hudson, Lesley; Heinemann, Allen W

    2018-03-01

    To describe current and future directions in spinal cord injury (SCI) research. The SCI Model Systems (SCIMS) programs funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) during the 2011 to 2016 cycle provided abstracts describing findings from current research projects. Discussion among session participants generated ideas for research opportunities. Pre-conference workshop before the 2016 American Spinal Injury Association (ASIA) annual meeting. A steering committee selected by the SCIMS directors that included the moderators of the sessions at the ASIA pre-conference workshop, researchers presenting abstracts during the session, and the audience of over 100 attending participants in the pre-conference workshop. Group discussion followed presentations in 5 thematic areas of (1) Demographics and Measurement; (2) Functional Training; (3) Psychosocial Considerations; (4) Assistive Technology; and (5) Secondary Conditions. The steering committee reviewed and summarized discussion points on future directions for research and made recommendations for research based on the discussion in each of the five areas. Significant areas in need of research in SCI remain, the goal of which is continued improvement in the quality of life of individuals with SCI.

  4. How cold was Europe at the Last Glacial Maximum? A synthesis of the progress achieved since the first PMIP model-data comparison

    Directory of Open Access Journals (Sweden)

    G. Ramstein

    2007-06-01

    Full Text Available The Last Glacial Maximum has been one of the first foci of the Paleoclimate Modelling Intercomparison Project (PMIP. During its first phase, the results of 17 atmosphere general circulation models were compared to paleoclimate reconstructions. One of the largest discrepancies in the simulations was the systematic underestimation, by at least 10°C, of the winter cooling over Europe and the Mediterranean region observed in the pollen-based reconstructions. In this paper, we investigate the progress achieved to reduce this inconsistency through a large modelling effort and improved temperature reconstructions. We show that increased model spatial resolution does not significantly increase the simulated LGM winter cooling. Further, neither the inclusion of a vegetation cover compatible with the LGM climate, nor the interactions with the oceans simulated by the atmosphere-ocean general circulation models run in the second phase of PMIP result in a better agreement between models and data. Accounting for changes in interannual variability in the interpretation of the pollen data does not result in a reduction of the reconstructed cooling. The largest recent improvement in the model-data comparison has instead arisen from a new climate reconstruction based on inverse vegetation modelling, which explicitly accounts for the CO2 decrease at LGM and which substantially reduces the LGM winter cooling reconstructed from pollen assemblages. As a result, the simulated and observed LGM winter cooling over Western Europe and the Mediterranean area are now in much better agreement.

  5. Spectroscopy, modeling and computation of metal chelate solubility in supercritical CO2. 1998 annual progress report

    International Nuclear Information System (INIS)

    Brennecke, J.F.; Chateauneuf, J.E.; Stadtherr, M.A.

    1998-01-01

    'This report summarizes work after 1 year and 8 months (9/15/96-5/14/98) of a 3 year project. Thus far, progress has been made in: (1) the measurement of the solubility of metal chelates in SC CO 2 with and without added cosolvents, (2) the spectroscopic determination of preferential solvation of metal chelates by cosolvents in SC CO 2 solutions, and (3) the development of a totally reliable computational technique for phase equilibrium computations. An important factor in the removal of metals from solid matrices with CO 2 /chelate mixtures is the equilibrium solubility of the metal chelate complex in the CO 2 .'

  6. Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression.

    Science.gov (United States)

    Malekian, Negin; Habibi, Jafar; Zangooei, Mohammad Hossein; Aghakhani, Hojjat

    2016-11-01

    There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test. The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis. In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Using hemoglobin A1C as a predicting model for time interval from pre-diabetes progressing to diabetes.

    Directory of Open Access Journals (Sweden)

    Chen-Ling Huang

    Full Text Available The early identification of subjects at high risk for diabetes is essential, thus, random rather than fasting plasma glucose is more useful. We aim to evaluate the time interval between pre-diabetes to diabetes with anti-diabetic drugs by using HbA1C as a diagnostic tool, and predicting it using a mathematic model.We used the Taipei Medical University Affiliated Hospital Patient Profile Database (AHPPD from January-2007 to June-2011. The patients who progressed and were prescribed anti-diabetic drugs were selected from AHPPD. The mathematical model used to predict the time interval of HbA1C value ranged from 5.7% to 6.5% for diabetes progression.We predicted an average overall time interval for all participants in between 5.7% to 6.5% during a total of 907 days (standard error, 103 days. For each group found among 5.7% to 6.5% we determined 1169.3 days for the low risk group (i.e. 3.2 years, 1080.5 days (i.e. 2.96 years for the increased risk group and 729.4 days (i.e. 1.99 years for the diabetes group. This indicates the patients will take an average of 2.49 years to reach 6.5%.This prediction model is very useful to help prioritize the diagnosis at an early stage for targeting individuals with risk of diabetes. Using patients' HbA1C before anti-diabetes drugs are used we predicted the time interval from pre-diabetes progression to diabetes is 2.49 years without any influence of age and gender. Additional studies are needed to support this model for a long term prediction.

  8. History of Physics Education Research as a Model for Geoscience Education Research Community Progress

    Science.gov (United States)

    Slater, T. F.

    2011-12-01

    Discipline-based Education Research (DBER) is a research field richly combining a deep understanding of how to teach a particular discipline with an evolving understanding how people learn that discipline. At its center, DBER has an overarching goal of improving the teaching and learning of a discipline by focusing on understanding the underlying mental mechanisms learners use as they develop expertise. Geoscience Education Research, or GER, is a young but rapidly advancing field which is poised to make important contributions to the teaching and learning of earth and space science. Nascent geoscience education researchers could accelerate their community's progress by learning some of the lessons from the more mature field of Physics Education Research, PER. For the past three decades, the PER community has been on the cutting edge of DBER. PER started purely as an effort among traditionally trained physicists to overcome students' tenaciously held misconceptions about force, motion, and electricity. Over the years, PER has wrestled with the extent to which they included the faculty from the College of Education, the value placed on interpretive and qualitative research methods, the most appropriate involvement of professional societies, the nature of its PhD programs in the College of Science, and how to best disseminate the results of PER to the wider physics teaching community. Decades later, as a more fully mature field, PER still struggles with some of these aspects, but has learned important lessons in how its community progresses and evolves to be successful, valuable, and pertinent.

  9. Progress in Energy Storage Technologies: Models and Methods for Policy Analysis

    Science.gov (United States)

    Matteson, Schuyler W.

    Climate change and other sustainability challenges have led to the development of new technologies that increase energy efficiency and reduce the utilization of finite resources. To promote the adoption of technologies with social benefits, governments often enact policies that provide financial incentives at the point of purchase. In their current form, these subsidies have the potential to increase the diffusion of emerging technologies; however, accounting for technological progress can improve program success while decreasing net public investment. This research develops novel methods using experience curves for the development of more efficient subsidy policies. By providing case studies in the field of automotive energy storage technologies, this dissertation also applies the methods to show the impacts of incorporating technological progress into energy policies. Specific findings include learning-dependent tapering subsidies for electric vehicles based on the lithium-ion battery experience curve, the effects of residual learning rates in lead-acid batteries on emerging technology cost competitiveness, and a cascading diffusion assessment of plug-in hybrid electric vehicle subsidy programs. Notably, the results show that considering learning rates in policy development can save billions of dollars in public funds, while also lending insight into the decision of whether or not to subsidize a given technology.

  10. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals

    Directory of Open Access Journals (Sweden)

    Dorian S Houser

    2013-11-01

    Full Text Available Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris, which fasts from food and water for periods of up to three months. During this time, ~90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM. All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures

  11. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

    Science.gov (United States)

    Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

    2013-11-01

    Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.

  12. Solutions for Determining the Significance Region Using the Johnson-Neyman Type Procedure in Generalized Linear (Mixed) Models

    Science.gov (United States)

    Lazar, Ann A.; Zerbe, Gary O.

    2011-01-01

    Researchers often compare the relationship between an outcome and covariate for two or more groups by evaluating whether the fitted regression curves differ significantly. When they do, researchers need to determine the "significance region," or the values of the covariate where the curves significantly differ. In analysis of covariance (ANCOVA),…

  13. Multi-state Markov models for disease progression in the presence of informative examination times: an application to hepatitis C.

    Science.gov (United States)

    Sweeting, M J; Farewell, V T; De Angelis, D

    2010-05-20

    In many chronic diseases it is important to understand the rate at which patients progress from infection through a series of defined disease states to a clinical outcome, e.g. cirrhosis in hepatitis C virus (HCV)-infected individuals or AIDS in HIV-infected individuals. Typically data are obtained from longitudinal studies, which often are observational in nature, and where disease state is observed only at selected examinations throughout follow-up. Transition times between disease states are therefore interval censored. Multi-state Markov models are commonly used to analyze such data, but rely on the assumption that the examination times are non-informative, and hence the examination process is ignorable in a likelihood-based analysis. In this paper we develop a Markov model that relaxes this assumption through the premise that the examination process is ignorable only after conditioning on a more regularly observed auxiliary variable. This situation arises in a study of HCV disease progression, where liver biopsies (the examinations) are sparse, irregular, and potentially informative with respect to the transition times. We use additional information on liver function tests (LFTs), commonly collected throughout follow-up, to inform current disease state and to assume an ignorable examination process. The model developed has a similar structure to a hidden Markov model and accommodates both the series of LFT measurements and the partially latent series of disease states. We show through simulation how this model compares with the commonly used ignorable Markov model, and a Markov model that assumes the examination process is non-ignorable. Copyright 2010 John Wiley & Sons, Ltd.

  14. v-Ha-ras oncogene insertion: A model for tumor progression of human small cell lung cancer

    International Nuclear Information System (INIS)

    Mabry, M.; Nakagawa, Toshitaro; Nelkin, B.D.; McDowell, E.; Gesell, M.; Eggleston, J.C.; Casero, R.A. Jr.; Baylin, S.B.

    1988-01-01

    Small cell lung cancer (SCLC) manifests a range of phenotypes in culture that may be important in understanding its relationship to non-SCLCs and to tumor progression events in patients. Most SCLC-derived cell lines, termed classic SCLC lines, have properties similar to SCLC tumors in patients. To delineate further the relationships between these phenotypes and the molecular events involved, the authors inserted the v-Ha-ras gene in SCLC cell lines with (biochemical variant) and without (classic) an amplified c-myc gene. These two SCLC subtypes had markedly different phenotypic responses to similar levels of expression of v-Ha-ras RNA. No biochemical or morphologic changes were observed in classic SCLC cells. In contrast, in biochemical variant SCLC cells, v-Ha-ras expression induced features typical of large cell undifferentiated lung carcinoma. Expression of v-Ha-ras in biochemical variant SCLC cells directly demonstrates that important transitions can occur between phenotypes of human lung cancer cells and that these may play a critical role in tumor progression events in patients. The finding provide a model system to study molecular events involved in tumor progression steps within a series of related tumor types

  15. On the automatic generation of FEM models for complex gears - A work-in-progress report

    Science.gov (United States)

    Drago, R. J.

    1982-01-01

    A description is presented of the development and use of a preprocessor to create a NASTRAN finite element model of a complex spur, helical, or spiral bevel gear quickly, inexpensively, and accurately. The preprocessor creates a ready to run NASTRAN input deck including the executive, case control, and bulk data sections. It generates nodes and solid elements to model spur, helical, or spiral bevel gear teeth with integral shafting. Either a complete gear shafting model or a symmetric model is created. The fundamental building block of the gear model is the base layer. The base layer is the mesh configuration of one layer of one tooth segment which is in turn duplicated, translated, and rotated to create the completed model of the gear. Once the base layer is created, the construction of the finite element model is straightforward.

  16. Progress toward bridging from atomistic to continuum modeling to predict nuclear waste glass dissolution.

    Energy Technology Data Exchange (ETDEWEB)

    Zapol, Peter (Argonne National Laboratory, Argonne, IL); Bourg, Ian (Lawrence Berkeley National Laboratories, Berkeley, CA); Criscenti, Louise Jacqueline; Steefel, Carl I. (Lawrence Berkeley National Laboratories, Berkeley, CA); Schultz, Peter Andrew

    2011-10-01

    This report summarizes research performed for the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Subcontinuum and Upscaling Task. The work conducted focused on developing a roadmap to include molecular scale, mechanistic information in continuum-scale models of nuclear waste glass dissolution. This information is derived from molecular-scale modeling efforts that are validated through comparison with experimental data. In addition to developing a master plan to incorporate a subcontinuum mechanistic understanding of glass dissolution into continuum models, methods were developed to generate constitutive dissolution rate expressions from quantum calculations, force field models were selected to generate multicomponent glass structures and gel layers, classical molecular modeling was used to study diffusion through nanopores analogous to those in the interfacial gel layer, and a micro-continuum model (K{mu}C) was developed to study coupled diffusion and reaction at the glass-gel-solution interface.

  17. L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway.

    Directory of Open Access Journals (Sweden)

    Hisashi Ishikawa

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC. Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid, an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1 high-fat diet (HFD (control group; 2 HFD mixed with 0.28% L-carnitine (L-carnitine group; and 3 HFD mixed with 0.01% α-tocopherol (α-tocopherol group. After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial β-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by

  18. Nuclear structure models: Applications and development. Progress report, May 1, 1993--June 30, 1994

    International Nuclear Information System (INIS)

    Semmes, P.B.

    1994-06-01

    This report summarizes the progress made during the period May 1, 1993 through June 30, 1994 on Grant No. DE-FG05-92ER40694. Our calculations of M1 transition rates within rotational bands of superdeformed nuclei have been extended to 2-quasiparticle states (mainly for odd-odd nuclei) in the A ∼ 190 region. Several bands are predicted with large B(MI) values and suggest that the MI properties can give information on details of occupied single particle orbitals, alignment of some high-N particles and the residual two-body interactions at extreme deformation. Detailed calculations and comparison with UNISOR data for the low energy, low spin structure of 187 Au have revealed two coexisting prolate structures built on the π[h 9/2 + f 7/2 ] configuration. This result was completely unexpected and presents strong challenges to our understanding of shape coexistence

  19. Progression of suicidal ideation to suicidal behavior from a perspective of selected suicidological models.

    Science.gov (United States)

    Rodziński, Paweł; Rutkowski, Krzysztof; Ostachowska, Anna

    2017-06-18

    In clinical practice suicidal ideation (SI) is one of the most commonly encountered symptoms in patients with mental disorders. Such encounter calls for diligent evaluation of suicidal risk. Although the risk factors are widely known, accurate estimation of suicidal risk remains one of the most difficult and most important tasks that clinicians face - especially considering recently collected data showing increase in suicide prevalence in Poland. More thorough estimation of suicidal risk in patients with SI requires taking under consideration not only suicidal risk factors but also factors that are more specific for progression of SI to suicidal behaviors (SB). The review presented in this paper consists of a range of suicidological theories that allow to select a number of groups of factors and mechanisms that are most specific for progression of SI to SB. These groups include: (1) transgression of fear of causing harm and pain to oneself, as well as disintegration of other protective barriers such as (2) decline of social integration with others, feeling of being alienated or abandoned, decline of sense of belongingness, lack of social support, (3) resignation from family and social obligations, (4) dismissing cultural or religious norms, (5) rejection of life goals, values and aspirations that were appreciated earlier, (6) narrowing down in perceived alternatives for suicide, i.e., "tunnel vision", feelings of helplessness and powerlessness, (7) devising in details and accepting simple suicidal plan, especially when such plan is being consolidated through rehearsals and as if "automatized", (8) impulsiveness, (9) accumulation of aggression that may be vented out as suicide, and finally (10) accessibility of means to commit suicide.

  20. Segmentation process significantly influences the accuracy of 3D surface models derived from cone beam computed tomography

    International Nuclear Information System (INIS)

    Fourie, Zacharias; Damstra, Janalt; Schepers, Rutger H.; Gerrits, Peter O.; Ren Yijin

    2012-01-01

    Aims: To assess the accuracy of surface models derived from 3D cone beam computed tomography (CBCT) with two different segmentation protocols. Materials and methods: Seven fresh-frozen cadaver heads were used. There was no conflict of interests in this study. CBCT scans were made of the heads and 3D surface models were created of the mandible using two different segmentation protocols. The one series of 3D models was segmented by a commercial software company, while the other series was done by an experienced 3D clinician. The heads were then macerated following a standard process. A high resolution laser surface scanner was used to make a 3D model of the macerated mandibles, which acted as the reference 3D model or “gold standard”. The 3D models generated from the two rendering protocols were compared with the “gold standard” using a point-based rigid registration algorithm to superimpose the three 3D models. The linear difference at 25 anatomic and cephalometric landmarks between the laser surface scan and the 3D models generate from the two rendering protocols was measured repeatedly in two sessions with one week interval. Results: The agreement between the repeated measurement was excellent (ICC = 0.923–1.000). The mean deviation from the gold standard by the 3D models generated from the CS group was 0.330 mm ± 0.427, while the mean deviation from the Clinician's rendering was 0.763 mm ± 0.392. The surface models segmented by both CS and DS protocols tend to be larger than those of the reference models. In the DS group, the biggest mean differences with the LSS models were found at the points ConLatR (CI: 0.83–1.23), ConMedR (CI: −3.16 to 2.25), CoLatL (CI: −0.68 to 2.23), Spine (CI: 1.19–2.28), ConAntL (CI: 0.84–1.69), ConSupR (CI: −1.12 to 1.47) and RetMolR (CI: 0.84–1.80). Conclusion: The Commercially segmented models resembled the reality more closely than the Doctor's segmented models. If 3D models are needed for surgical drilling

  1. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2.

    Science.gov (United States)

    Nielsen, Signe Marie Borch; Hasholt, Lis; Nørremølle, Anne; Josefsen, Knud

    2015-04-20

    Huntington's disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood glucose levels during prolonged fasting compared to wild type animals.

  2. Progress on nuclear data work at Nankai University in 1995

    Energy Technology Data Exchange (ETDEWEB)

    Chonghai, Cai; Ziqiang, Yu; Yixin, Zuo [Nankai Univ., Tianjin (China)

    1996-06-01

    The research work on nuclear model programs and QMD theory are reported. Two nuclear models programs CCRMN and OMHF have finished in 1995. The theoretical research on quantum molecular dynamics (QMD) have made significant progress in 1995.

  3. Final Report on Models, Periodic Progress, Report No D1.3, Globeman21, ESPRIT 26509

    DEFF Research Database (Denmark)

    Pedersen, Jens Dahl; Tølle, Martin; Vesterager, Johan

    1999-01-01

    ), a collection of practical experiences, and requirements for enhanced methods and tools for modelling. First, the deliverable outlines the GM21 understanding regarding extended enterprises and virtual enterprises. This is done by extracting and synthesising the essence of key definitions and concepts...... concepts that have been defined and studied in the project. The aim of the Concept Model is to show how the different concepts are related to each other and to the GM21 pilot projects. Complementary, the Methodology Model models the life cycle based activities of the Extended Enterprise Methodology as well...

  4. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Overview and Progress

    Science.gov (United States)

    Rosenzweig, C.; Hatfield, J.; Jones, J. W.; Ruane, A. C.

    2012-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is an international effort to assess the state of global agricultural modeling and to understand climate impacts on the agricultural sector. AgMIP connects the climate science, crop modeling, and agricultural economic modeling communities to generate probabilistic projections of current and future climate impacts. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. This presentation will describe the general approach of AgMIP and highlight its findings and activities. AgMIP crop model intercomparisons have been established for wheat (27 models participating), maize (25 models), and rice (15+ models), and are being established for sugarcane, soybean, sorghum/millet, and peanut. In coordination with these pilots, methodologies to utilize weather generators and downscaled climate simulations for agricultural applications are under development. An AgMIP global agricultural economics model intercomparison with participation of 11 international groups is ongoing, and a number of global biophysical models are currently being evaluated for future climate impacts on agricultural lands both as part of the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) and for contribution to the IPCC Fifth Assessment Report (AR5). AgMIP is also organizing regional research efforts, and has already held workshops in South America, Sub-Saharan Africa, South Asia, Europe, and North America. Outcomes from these meetings have informed AgMIP activities, and 10 research teams from Sub-Saharan Africa and South Asia have been selected for project funding. Additional activities are planned for Australia and East Asia. As the AgMIP research community continues to work towards its goals, three key cross-cutting scientific challenges have emerged and are being

  5. Arginase-1 expressing microglia in close proximity to motor neurons were increased early in disease progression in canine degenerative myelopathy, a model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Toedebusch, Christine M; Snyder, John C; Jones, Maria R; Garcia, Virginia B; Johnson, Gayle C; Villalón, Eric L; Coates, Joan R; Garcia, Michael L

    2018-04-01

    Toxicity within superoxide dismutase-1 (SOD1)-associated familial amyotrophic lateral sclerosis (ALS) is non-cell autonomous with direct contribution from microglia. Microglia exhibit variable expression of neuroprotective and neurotoxic molecules throughout disease progression. The mechanisms regulating microglial phenotype within ALS are not well understood. This work presents a first study to examine the specific microglial phenotypic response in close association to motor neurons in a naturally occurring disease model of ALS, canine degenerative myelopathy (DM). Microglia closely associated with motor neurons were increased in all stages of DM progression, although only DM Late reached statistical significance. Furthermore, the number of arginase-1 expressing microglia per motor neuron were significantly increased in early stages of DM, whereas the number of inducible nitric oxide synthase (iNOS)-expressing microglia per motor neuron was indistinguishable from aged controls at all stages of disease. Fractalkine, a chemotactic molecule for microglia, was expressed in motor neurons, and the fractalkine receptor was specifically localized to microglia. However, we found no correlation between microglial response and lumbar spinal cord fractalkine levels. Taken together, these data suggest that arginase-1-expressing microglia are recruited to the motor neuron early in DM disease through a fractalkine-independent mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. AtomDB Progress Report: Atomic data and new models for X-ray spectroscopy.

    Science.gov (United States)

    Smith, Randall K.; Foster, Adam; Brickhouse, Nancy S.; Stancil, Phillip C.; Cumbee, Renata; Mullen, Patrick Dean; AtomDB Team

    2018-06-01

    The AtomDB project collects atomic data from both theoretical and observational/experimental sources, providing both a convenient interface (http://www.atomdb.org/Webguide/webguide.php) as well as providing input to spectral models for many types of astrophysical X-ray plasmas. We have released several updates to AtomDB in response to the Hitomi data, including new data for the Fe K complex, and have expanded the range of models available in AtomDB to include the Kronos charge exchange models from Mullen at al. (2016, ApJS, 224, 2). Combined with the previous AtomDB charge exchange model (http://www.atomdb.org/CX/), these data enable a velocity-dependent model for X-ray and EUV charge exchange spectra. We also present a new Kappa-distribution spectral model, enabling plasmas with non-Maxwellian electron distributions to be modeled with AtomDB. Tools are provided within pyAtomDB to explore and exploit these new plasma models. This presentation will review these enhancements and describe plans for the new few years of database and code development in preparation for XARM, Athena, and (hopefully) Arcus.

  7. Inflammation and oxidative stress are elevated in the brain, blood, and adrenal glands during the progression of post-traumatic stress disorder in a predator exposure animal model.

    Science.gov (United States)

    Wilson, C Brad; McLaughlin, Leslie D; Nair, Anand; Ebenezer, Philip J; Dange, Rahul; Francis, Joseph

    2013-01-01

    This study sought to analyze specific pathophysiological mechanisms involved in the progression of post-traumatic stress disorder (PTSD) by utilizing an animal model. To examine PTSD pathophysiology, we measured damaging reactive oxygen species and inflammatory cytokines to determine if oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation were upregulated in response to constant stress. Pre-clinical PTSD was induced in naïve, male Sprague-Dawley rats via a predator exposure/psychosocial stress regimen. PTSD group rats were secured in Plexiglas cylinders and placed in a cage with a cat for one hour on days 1 and 11 of a 31-day stress regimen. In addition, PTSD group rats were subjected to psychosocial stress whereby their cage cohort was changed daily. This model has been shown to cause heightened anxiety, exaggerated startle response, impaired cognition, and increased cardiovascular reactivity, all of which are common symptoms seen in humans with PTSD. At the conclusion of the predator exposure/psychosocial stress regimen, the rats were euthanized and their brains were dissected to remove the hippocampus, amygdala, and pre-frontal cortex (PFC), the three areas commonly associated with PTSD development. The adrenal glands and whole blood were also collected to assess systemic oxidative stress. Analysis of the whole blood, adrenal glands, and brain regions revealed oxidative stress increased during PTSD progression. In addition, examination of pro-inflammatory cytokine (PIC) mRNA and protein demonstrated neurological inflammatory molecules were significantly upregulated in the PTSD group vs. controls. These results indicate oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation may play a critical role in the development and further exacerbation of PTSD. Thus, PTSD may not be solely a neurological pathology but may progress as a systemic condition involving multiple organ systems.

  8. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation.

    Science.gov (United States)

    Afrin, Rejina; Arumugam, Somasundaram; Rahman, Azizur; Wahed, Mir Imam Ibne; Karuppagounder, Vengadeshprabhu; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Suzuki, Kenji; Yoneyama, Hiroyuki; Ueno, Kazuyuki; Watanabe, Kenichi

    2017-03-01

    Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1β and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington's Disease: A Targeted GC-MS/MS Sterol Analysis.

    Science.gov (United States)

    Kreilaus, Fabian; Spiro, Adena S; Hannan, Anthony J; Garner, Brett; Jenner, Andrew M

    2015-01-01

    Cholesterol has essential functions in neurological processes that require tight regulation of synthesis and metabolism. Perturbed cholesterol homeostasis has been demonstrated in Huntington's disease, however the exact role of these changes in disease pathogenesis is not fully understood. This study aimed to comprehensively examine changes in cholesterol biosynthetic precursors, metabolites and oxidation products in the striatum and cortex of the R6/1 transgenic mouse model of Huntington's disease. We also aimed to characterise the progression of the physical phenotype in these mice. GC-MS/MS was used to quantify a broad range of sterols in the striatum and cortex of R6/1 and wild type mice at 6, 12, 20, 24 and 28 weeks of age. Motor dysfunction was assessed over 28 weeks using the RotaRod and the hind-paw clasping tests. 24(S)-Hydroxycholesterol and 27-hydroxycholesterol were the major cholesterol metabolites that significantly changed in R6/1 mice. These changes were specifically localised to the striatum and were detected at the end stages of the disease. Cholesterol synthetic precursors (lathosterol and lanosterol) were significantly reduced in the cortex and striatum by 6 weeks of age, prior to the onset of motor dysfunction, as well as the cognitive and affective abnormalities previously reported. Elevated levels of desmosterol, a substrate of delta(24)-sterol reductase (DHCR24), were also detected in R6/1 mice at the end time-point. Female R6/1 mice exhibited a milder weight loss and hind paw clasping phenotype compared to male R6/1 mice, however, no difference in the brain sterol profile was detected between sexes. Several steps in cholesterol biosynthetic and metabolic pathways are differentially altered in the R6/1 mouse brain as the disease progresses and this is most severe in the striatum. This provides further insights into early molecular mediators of HD onset and disease progression and identifies candidate molecular targets for novel therapeutic

  10. Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model.

    Science.gov (United States)

    Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

    2016-01-01

    The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of

  11. Predicting the multi-domain progression of Parkinson's disease: a Bayesian multivariate generalized linear mixed-effect model.

    Science.gov (United States)

    Wang, Ming; Li, Zheng; Lee, Eun Young; Lewis, Mechelle M; Zhang, Lijun; Sterling, Nicholas W; Wagner, Daymond; Eslinger, Paul; Du, Guangwei; Huang, Xuemei

    2017-09-25

    It is challenging for current statistical models to predict clinical progression of Parkinson's disease (PD) because of the involvement of multi-domains and longitudinal data. Past univariate longitudinal or multivariate analyses from cross-sectional trials have limited power to predict individual outcomes or a single moment. The multivariate generalized linear mixed-effect model (GLMM) under the Bayesian framework was proposed to study multi-domain longitudinal outcomes obtained at baseline, 18-, and 36-month. The outcomes included motor, non-motor, and postural instability scores from the MDS-UPDRS, and demographic and standardized clinical data were utilized as covariates. The dynamic prediction was performed for both internal and external subjects using the samples from the posterior distributions of the parameter estimates and random effects, and also the predictive accuracy was evaluated based on the root of mean square error (RMSE), absolute bias (AB) and the area under the receiver operating characteristic (ROC) curve. First, our prediction model identified clinical data that were differentially associated with motor, non-motor, and postural stability scores. Second, the predictive accuracy of our model for the training data was assessed, and improved prediction was gained in particularly for non-motor (RMSE and AB: 2.89 and 2.20) compared to univariate analysis (RMSE and AB: 3.04 and 2.35). Third, the individual-level predictions of longitudinal trajectories for the testing data were performed, with ~80% observed values falling within the 95% credible intervals. Multivariate general mixed models hold promise to predict clinical progression of individual outcomes in PD. The data was obtained from Dr. Xuemei Huang's NIH grant R01 NS060722 , part of NINDS PD Biomarker Program (PDBP). All data was entered within 24 h of collection to the Data Management Repository (DMR), which is publically available ( https://pdbp.ninds.nih.gov/data-management ).

  12. Local inflammation, dissemination and coalescence of lesions are key for the progression towards active tuberculosis: the bubble model

    Directory of Open Access Journals (Sweden)

    Clara ePrats

    2016-02-01

    Full Text Available The evolution of a tuberculosis (TB infection towards active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions.Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i lesions grow logistically due to the inflammatory reaction; (ii new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response.The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by oscillations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed.These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection and a coalescence of lesions, are needed in order to progress towards active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the

  13. Damage-Based Time-Dependent Modeling of Paraglacial to Postglacial Progressive Failure of Large Rock Slopes

    Science.gov (United States)

    Riva, Federico; Agliardi, Federico; Amitrano, David; Crosta, Giovanni B.

    2018-01-01

    Large alpine rock slopes undergo long-term evolution in paraglacial to postglacial environments. Rock mass weakening and increased permeability associated with the progressive failure of deglaciated slopes promote the development of potentially catastrophic rockslides. We captured the entire life cycle of alpine slopes in one damage-based, time-dependent 2-D model of brittle creep, including deglaciation, damage-dependent fluid occurrence, and rock mass property upscaling. We applied the model to the Spriana rock slope (Central Alps), affected by long-term instability after Last Glacial Maximum and representing an active threat. We simulated the evolution of the slope from glaciated conditions to present day and calibrated the model using site investigation data and available temporal constraints. The model tracks the entire progressive failure path of the slope from deglaciation to rockslide development, without a priori assumptions on shear zone geometry and hydraulic conditions. Complete rockslide differentiation occurs through the transition from dilatant damage to a compacting basal shear zone, accounting for observed hydraulic barrier effects and perched aquifer formation. Our model investigates the mechanical role of deglaciation and damage-controlled fluid distribution in the development of alpine rockslides. The absolute simulated timing of rock slope instability development supports a very long "paraglacial" period of subcritical rock mass damage. After initial damage localization during the Lateglacial, rockslide nucleation initiates soon after the onset of Holocene, whereas full mechanical and hydraulic rockslide differentiation occurs during Mid-Holocene, supporting a key role of long-term damage in the reported occurrence of widespread rockslide clusters of these ages.

  14. Role of DNA Methylation in Altering Gene Expression During the Early Stages of Human Breast Cancer Progression in the MCF10AT Xenograft Model

    National Research Council Canada - National Science Library

    Christman, Judith

    2004-01-01

    ...) Collect microdissected tissue representative of each of the morphologically different stages of early breast cancer progression in the MCFlOAT model to obtain RNA and DNA for miroarray analysis...

  15. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS mouse model.

    Directory of Open Access Journals (Sweden)

    Csilla Ari

    Full Text Available Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG, the main ingredient of the DP, and the ketogenic diet (KD, would increase motor function and survival in a mouse model of ALS (SOD1-G93A. ALS mice were fed standard rodent diet (SD, KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001 and 4.2% (p = 0.006, respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which

  16. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model.

    Science.gov (United States)

    Ari, Csilla; Poff, Angela M; Held, Heather E; Landon, Carol S; Goldhagen, Craig R; Mavromates, Nicholas; D'Agostino, Dominic P

    2014-01-01

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survi