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Sample records for modeling significant progress

  1. Models and Mechanisms of Acquired Antihormone Resistance in Breast Cancer: Significant Clinical Progress Despite Limitations

    Science.gov (United States)

    Sweeney, Elizabeth E.; McDaniel, Russell E.; Maximov, Philipp Y.; Fan, Ping; Jordan, V. Craig

    2012-01-01

    Translational research for the treatment and prevention of breast cancer depends upon the four Ms: models, molecules, and mechanisms in order to create medicines. The process, to target the estrogen receptor (ER) in estrogen-dependent breast cancer, has yielded significant advances in patient survivorship and the first approved medicines (tamoxifen and raloxifene) to reduce the incidence of any cancer in high- or low-risk women. This review focuses on the critical role of the few ER-positive cell lines (MCF-7, T47D, BT474, ZR-75) that continue to advance our understanding of the estrogen-regulated biology of breast cancer. More importantly, the model cell lines have provided an opportunity to document the development and evolution of acquired antihormone resistance. The description of this evolutionary process that occurs in micrometastatic disease during up to a decade of adjuvant therapy would not be possible in the patient. The use of the MCF-7 breast cancer cell line in particular has been instrumental in discovering a vulnerability of ER-positive breast cancer exhaustively treated with antihormone therapy. Physiologic estradiol acts as an apoptotic trigger to cause tumor regression. These unanticipated findings in the laboratory have translated to clinical advances in our knowledge of the paradoxical role of estrogen in the life and death of breast cancer. PMID:23308083

  2. Glenohumeral arthritis after Latarjet procedure: Progression and it's clinical significance.

    Science.gov (United States)

    Kee, Young Moon; Kim, Hwan Jin; Kim, Jung Youn; Rhee, Yong Girl

    2017-09-01

    The risk factors of glenohumeral arthritis after the Latarjet procedure remain relatively unexplored. The purposes of this study are to evaluate the clinical significance of glenohumeral arthritis after the Latarjet procedure, and to investigate risk factors associated with arthritis progression. We evaluated 110 patients (110 shoulders) who underwent the Latarjet procedure for recurrent anterior shoulder instability. Patients had a mean age of 23.8 years (range, 14-52 years) at the time of the operation, and the mean duration of follow-up was 31 months (range, 24-111 months). At the last follow-up, the mean Visual Analog Scale (VAS), Rowe and University of California at Los Angeles (UCLA) scores significantly improved from 3.1, 36.5 and 23.6 points preoperatively to 1.6, 87.6 and 32.6 points (all P Latarjet procedure was in 20 shoulders (18.2%). At the final, overall prevalence of arthritis was 23.6% (26 shoulders). The non-arthritis group showed significantly better functional outcomes (VAS score: 0.9, Rowe Score: 89.3, UCLA score: 33.5) than the arthritis group (2.1, 84.9, 29.2; all P Latarjet procedure yielded satisfactory functional outcomes with low recurrent rate at mid-term follow-up. Development or progression of arthritis was observed in 18.2% of patients, postoperatively. Glenohumeral arthritis after the Latarjet procedure had an adverse effect on clinical outcome. Generalized laxity and lateral overhang should be considered as risk factors of progression to glenohumeral arthritis after the Latarjet procedure. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  3. 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.

  4. Progress in modeling asphaltene precipitation

    Energy Technology Data Exchange (ETDEWEB)

    Yarranton, H.W.; Satyro, M.A. [Department of Chemical and Petroleum Engineering, University of Calgary (Canada); Taylor, S.D. [DBR Technology Center, Schlumberger (Canada)

    2011-07-01

    In the oil industry, asphaltene precipitation may happen when heavy oils are in contact with a solvent, crude oils are blended or when light oils containing asphaltenes are depressurized. Asphaltene precipitation has proven challenging to predict and the aim of this paper is to evaluate 2 different approaches for asphaltene precipitation modeling: regular solution and equation of state. Two case were studied: an Athabasca bitumen diluted with n-alkane and a depressurized Gulf of Mexico crude oil and both models were applied to each case. Results showed that both thermodynamic models are, to a limited extend, suitable for asphaltene precipitation prediction but they do not offer a correct prediction at low asphaltene concentrations and the equation of state cannot predict asphaltene precipitation from depressurized crude oils. This study showed the limits of current models in predicting precipitation of asphaltene and provided a trick to overcome these deficiencies; further work should be undertaken to develop a consistent approach.

  5. Amyotrophic lateral sclerosis disease progression model.

    Science.gov (United States)

    Gomeni, Roberto; Fava, Maurizio

    2014-03-01

    Our objective was to develop: 1) a longitudinal model to describe amyotrophic lateral sclerosis (ALS) disease progression using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R); and 2) a probabilistic model to estimate the presence of clusters of trajectories in ALS progression over 12 months of treatment. Three hundred and thirty-eight patients treated with placebo from the PRO-ACT database were included in the analyses. A non-linear Weibull model best described the ALS disease progression, and a stepwise logistic regression approach was used to select the variables predicting a slow or fast disease progression. Results identified two clusters of trajectories: 1) slow disease progressors (46% of patients with a change from baseline of 13%); 2) fast disease progressors (54% of patients with a change from baseline of 49%). ROC curve analysis estimated the optimal cut-off for classifying patients as slow or fast disease progressors given ALSFRS-R measurements at 2-4 weeks. Results showed that the degree of ALS disease progression quantified by the ALSFRS-R symptomatic change on placebo is highly heterogeneous. In conclusion, this finding indicates the potential interest of disease progression models for implementing a population enrichment strategy to control the level of heterogeneity in the patients included in new trials.

  6. 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

  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. A multiscale approach for modeling atherosclerosis progression.

    Science.gov (United States)

    Exarchos, Konstantinos P; Carpegianni, Clara; Rigas, Georgios; Exarchos, Themis P; Vozzi, Federico; Sakellarios, Antonis; Marraccini, Paolo; Naka, Katerina; Michalis, Lambros; Parodi, Oberdan; Fotiadis, Dimitrios I

    2015-03-01

    Progression of atherosclerotic process constitutes a serious and quite common condition due to accumulation of fatty materials in the arterial wall, consequently posing serious cardiovascular complications. In this paper, we assemble and analyze a multitude of heterogeneous data in order to model the progression of atherosclerosis (ATS) in coronary vessels. The patient's medical record, biochemical analytes, monocyte information, adhesion molecules, and therapy-related data comprise the input for the subsequent analysis. As indicator of coronary lesion progression, two consecutive coronary computed tomography angiographies have been evaluated in the same patient. To this end, a set of 39 patients is studied using a twofold approach, namely, baseline analysis and temporal analysis. The former approach employs baseline information in order to predict the future state of the patient (in terms of progression of ATS). The latter is based on an approach encompassing dynamic Bayesian networks whereby snapshots of the patient's status over the follow-up are analyzed in order to model the evolvement of ATS, taking into account the temporal dimension of the disease. The quantitative assessment of our work has resulted in 93.3% accuracy for the case of baseline analysis, and 83% overall accuracy for the temporal analysis, in terms of modeling and predicting the evolvement of ATS. It should be noted that the application of the SMOTE algorithm for handling class imbalance and the subsequent evaluation procedure might have introduced an overestimation of the performance metrics, due to the employment of synthesized instances. The most prominent features found to play a substantial role in the progression of the disease are: diabetes, cholesterol and cholesterol/HDL. Among novel markers, the CD11b marker of leukocyte integrin complex is associated with coronary plaque progression.

  9. 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

  10. 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.

  11. 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.

  12. Modelling Progressive Failure in Rock-slopes

    Science.gov (United States)

    Pons, M. Güell I.; Jaboyedoff, M.

    2009-04-01

    Rock failures are common in Alpine mountain chains and pose a threat to life and infrastructures. In general, rock slope stability is an interplay between existing discontinuities and development of new ones in intact material. In this work, we study progressive failure by means of numerical methods at multiple scales and using distinct element methods (DEM). Distinct element methods are of advantage because they account for discontinuities and are able to simulate the development of failure in time. The use of micro-parameters instead of constitutive laws allows studying the influence of heterogeneities present in the rock mass. In the first case, the code PFC-2D is used at the slope scale to test the influence of the slope geometry, the joint sets distribution and the joint set persistence in the case of toppling failures under various triggering mechanisms. Heterogeneity properties (cohesion and friction angle) are distributed randomly to simulate natural rock variability. In the second case, a cellular automata model, which is based on concepts of progressive failure in disordered systems, is used to explain the role of heterogeneities in the fracture process at a small scale. The results provide a link to time-to-failure predictions observed in some field cases. This study aims to be a base for the development of a model which permits to understand why some rock masses accelerate until global failure while other are capable to stabilize under the same conditions.

  13. Modelling amyotrophic lateral sclerosis: progress and possibilities

    Directory of Open Access Journals (Sweden)

    Philip Van Damme

    2017-05-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder that primarily affects the motor system and presents with progressive muscle weakness. Most patients survive for only 2-5 years after disease onset, often due to failure of the respiratory muscles. ALS is a familial disease in ∼10% of patients, with the remaining 90% developing sporadic ALS. Over the past decade, major advances have been made in our understanding of the genetics and neuropathology of ALS. To date, around 20 genes are associated with ALS, with the most common causes of typical ALS associated with mutations in SOD1, TARDBP, FUS and C9orf72. Advances in our understanding of the genetic basis of ALS have led to the creation of different models of this disease. The molecular pathways that have emerged from these systems are more heterogeneous than previously anticipated, ranging from protein aggregation and defects in multiple key cellular processes in neurons, to dysfunction of surrounding non-neuronal cells. Here, we review the different model systems used to study ALS and discuss how they have contributed to our current knowledge of ALS disease mechanisms. A better understanding of emerging disease pathways, the detrimental effects of the various gene mutations and the causes underlying motor neuron denegation in sporadic ALS will accelerate progress in the development of novel treatments.

  14. 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.

  15. Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer--20 Years of Progress.

    Science.gov (United States)

    Hardingham, Jennifer E; Grover, Phulwinder; Winter, Marnie; Hewett, Peter J; Price, Timothy J; Thierry, Benjamin

    2015-10-27

    Circulating tumor cells (CTC) may be defined as tumor- or metastasis-derived cells that are present in the bloodstream. The CTC pool in colorectal cancer (CRC) patients may include not only epithelial tumor cells, but also tumor cells undergoing epithelial-mesenchymal transition (EMT) and tumor stem cells. A significant number of patients diagnosed with early stage CRC subsequently relapse with recurrent or metastatic disease despite undergoing "curative" resection of their primary tumor. This suggests that an occult metastatic disease process was already underway, with viable tumor cells being shed from the primary tumor site, at least some of which have proliferative and metastatic potential and the ability to survive in the bloodstream. Such tumor cells are considered to be responsible for disease relapse in these patients. Their detection in peripheral blood at the time of diagnosis or after resection of the primary tumor may identify those early-stage patients who are at risk of developing recurrent or metastatic disease and who would benefit from adjuvant therapy. CTC may also be a useful adjunct to radiological assessment of tumor response to therapy. Over the last 20 years many approaches have been developed for the isolation and characterization of CTC. However, none of these methods can be considered the gold standard for detection of the entire pool of CTC. Recently our group has developed novel unbiased inertial microfluidics to enrich for CTC, followed by identification of CTC by imaging flow cytometry. Here, we provide a review of progress on CTC detection and clinical significance over the last 20 years.

  16. 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.

  17. 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)

  18. 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

  19. 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.|info:eu-repo/dai/nl/14749799X; Weerts, Albrecht H.; Bierkens, Marc F. P.|info:eu-repo/dai/nl/125022794

    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

  20. Patient Age Is Significantly Related to the Progression of Papillary Microcarcinoma of the Thyroid Under Observation

    Science.gov (United States)

    Ito, Yasuhiro; Kihara, Minoru; Higashiyama, Takuya; Kobayashi, Kaoru; Miya, Akihiro

    2014-01-01

    Background: We showed previously that subclinical low-risk papillary thyroid microcarcinoma (PTMC) could be observed without immediate surgery. Patient age is an important prognostic factor of clinical papillary thyroid carcinoma (PTC). In this study, we investigated how patient age influences the observation of low-risk PTMC. Methods: Between 1993 and 2011, 1235 patients with low-risk PTMC chose observation without immediate surgery. They were followed periodically with ultrasound examinations. These patients were enrolled in this study. We divided them into three subsets based on age at the beginning of observation: young (<40 years), middle-aged (40–59 years), and old patients (≥60 years). Observation periods ranged from 18 to 227 months (average 75 months). Results: We set three parameters for the evaluation of PTMC progression: (i) size enlargement, (ii) novel appearance of lymph-node metastasis, and (iii) progression to clinical disease (tumor size reaching 12 mm or larger, or novel appearance of nodal metastasis). The proportion of patients with PTMC progression was lowest in the old patients and highest in the young patients. On multivariate analysis, young age was an independent predictor of PTMC progression. However, none of the 1235 patients showed distant metastasis or died of PTC during observation. Although only 51 patients (4%) underwent thyrotropin (TSH) suppression based on physician preference, the PTMC of all patients enrolled in this TSH suppression study, except one, were clinically stable. To date, 191 patients underwent surgery for various reasons after observation. None showed recurrence except for one in the residual thyroid, and none died of PTC after surgery. Conclusions: Old patients with subclinical low-risk PTMC may be the best candidates for observation. Although PTMC in young patients may be more progressive than in older patients, it might not be too late to perform surgery after subclinical PTMC has progressed to clinical

  1. A Progressive 5-Week Exercise Therapy Program Leads to Significant Improvement in Knee Function Early After Anterior Cruciate Ligament Injury

    Science.gov (United States)

    EITZEN, INGRID; MOKSNES, HÅVARD; SNYDER-MACKLER, LYNN; RISBERG, MAY ARNA

    2011-01-01

    STUDY DESIGN Prospective cohort study without a control group. OBJECTIVES Firstly, to present our 5-week progressive exercise therapy program in the early stage after anterior cruciate ligament (ACL) injury. Secondly, to evaluate changes in knee function after completion of the program for patients with ACL injury in general and also when classified as potential copers or noncopers, and, finally, to examine potential adverse events. BACKGROUND Few studies concerning early-stage ACL rehabilitation protocols exist. Consequently, little is known about the tolerance for, and outcomes from, short-term exercise therapy programs in the early stage after injury. METHODS One-hundred patients were included in a 5-week progressive exercise therapy program, within 3 months after injury. Knee function before and after completion of the program was evaluated from isokinetic quadriceps and hamstrings muscle strength tests, 4 single-leg hop tests, 2 different self-assessment questionnaires, and a global rating of knee function. A 2-way mixed-model analysis of variance was conducted to evaluate changes from pretest to posttest for the limb symmetry index for muscle strength and single-leg hop tests, and the change in scores for the patient-reported questionnaires. In addition, absolute values and the standardized response mean for muscle strength and single-leg hop tests were calculated at pretest and posttest for the injured and uninjured limb. Adverse events during the 5-week period were recorded. RESULTS The progressive 5-week exercise therapy program led to significant improvements (Ptherapy programs are well tolerated and should be incorporated in early-stage ACL rehabilitation, either to improve knee function before ACL reconstruction or as a first step in further nonoperative management. PMID:20710097

  2. 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…

  3. Bayesian Test of Significance for Conditional Independence: The Multinomial Model

    Directory of Open Access Journals (Sweden)

    Pablo de Morais Andrade

    2014-03-01

    Full Text Available Conditional independence tests have received special attention lately in machine learning and computational intelligence related literature as an important indicator of the relationship among the variables used by their models. In the field of probabilistic graphical models, which includes Bayesian network models, conditional independence tests are especially important for the task of learning the probabilistic graphical model structure from data. In this paper, we propose the full Bayesian significance test for tests of conditional independence for discrete datasets. The full Bayesian significance test is a powerful Bayesian test for precise hypothesis, as an alternative to the frequentist’s significance tests (characterized by the calculation of the p-value.

  4. Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology

    Science.gov (United States)

    McCarroll, Steven A.; Hyman, Steven E.

    2014-01-01

    Advances in genome analysis, accompanied by the assembly of large patient cohorts, have made possible successful genetic analyses of polygenic brain disorders. If the resulting molecular clues, previously hidden in the genomes of affected individuals, are to yield useful information about pathogenesis and inform the discovery of new treatments, neurobiology will have to rise to many difficult challenges. Here we review the underlying logic of the genetic investigations, describe in more detail progress in schizophrenia and autism, and outline the challenges for neurobiology that lie ahead. We argue that technologies at the disposal of neuroscience are adequately advanced to begin to study the biology of common and devastating polygenic disorders. PMID:24183011

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

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    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.

  6. Progress in the genetics of polygenic brain disorders: significant new challenges for neurobiology.

    Science.gov (United States)

    McCarroll, Steven A; Hyman, Steven E

    2013-10-30

    Advances in genome analysis, accompanied by the assembly of large patient cohorts, are making possible successful genetic analyses of polygenic brain disorders. If the resulting molecular clues, previously hidden in the genomes of affected individuals, are to yield useful information about pathogenesis and inform the discovery of new treatments, neurobiology will have to rise to many difficult challenges. Here we review the underlying logic of the genetic investigations, describe in more detail progress in schizophrenia and autism, and outline the challenges for neurobiology that lie ahead. We argue that technologies at the disposal of neuroscience are adequately advanced to begin to study the biology of common and devastating polygenic disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. 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.'

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Recent progress in human reliability models for nuclear power safety

    International Nuclear Information System (INIS)

    Bersini, U.; Devooght, J.; Smidts, C.

    1988-01-01

    The importance of a human factor in the safety of nuclear power plants hardly needs to be stressed after the Three Mile Island and Chernobyl accidents. Following TMI, such progress was made that Chernobyl did not reveal significant faults in the design or operation of Western nuclear power plants. Post-TMI progress concerns: design of control rooms, development of simulators for training operators, use of computer aided diagnostics, a better understanding of procedural safety, the collection of human error data, etc. We shall concentrate here on the specific point of modelling human errors for incorporation in the standard tools of reliability and safety engineering (e.g. fault trees). The Rasmussen report (WASH 1400) has already included human error in the analysis of fault and event trees and since then new models have been developed and tested. Human reliability methods, which first appeared in the early 1980s, model operator behavior during routine tasks and quantify his error probability. Here three of these methods are briefly described: THERP, SLIM and MAPPS. 17 refs

  20. 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

  1. 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

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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  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 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

  16. Studies on diversity and biogeography of island bryophytes:significances, progress and dircetion

    Directory of Open Access Journals (Sweden)

    YU Jing

    2016-02-01

    Full Text Available There are few studies on bryophytes diversity and biogeography of bryophytes in coastal islands.Our reviews on bryophyte diversity and biogeography of bryophytes on islands showed disputes existing on breeding characteristics,spreading ability of bryophytes and applicability of island biogeography theory on bryophytes.China has a large number of coastal islands,but most of them lack any bryophytes information.Therefore,studies on bryophytes in Chinese coastal islands are of theoretical and practical significances.Zhoushan archipelago of Zhejiang province is an ideal region for us to conduct bryophyte diversity and biogeographical study,especially for us to understand the influences of habitat fragmentation on the genetic diversity of bryophytes.The 4607 islands along the coast of Zhejiang and Fujiang,accounting for 62.5% of that of China,are suitable for us to study the gradient distribution of bryophyte diversity and its relationship with climate.

  17. Recent Progress in Greenland Ice Sheet Modelling

    NARCIS (Netherlands)

    Goelzer, Heiko; Robinson, Alexander; Seroussi, Helene; Van De Wal, Roderik S.w.

    2017-01-01

    Purpose of Review This paper reviews the recent literature on numerical modelling of the dynamics of the Greenland ice sheet with the goal of providing an overview of advancements and to highlight important directions of future research. In particular, the review is focused on large-scale modelling

  18. 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.

  19. 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

  20. Mouse models of metastasis: progress and prospects

    Directory of Open Access Journals (Sweden)

    Laura Gómez-Cuadrado

    2017-09-01

    Full Text Available Metastasis is the spread of cancer cells from a primary tumor to distant sites within the body to establish secondary tumors. Although this is an inefficient process, the consequences are devastating as metastatic disease accounts for >90% of cancer-related deaths. The formation of metastases is the result of a series of events that allow cancer cells to escape from the primary site, survive in the lymphatic system or blood vessels, extravasate and grow at distant sites. The metastatic capacity of a tumor is determined by genetic and epigenetic changes within the cancer cells as well as contributions from cells in the tumor microenvironment. Mouse models have proven to be an important tool for unraveling the complex interactions involved in the metastatic cascade and delineating its many stages. Here, we critically appraise the strengths and weaknesses of the current mouse models and highlight the recent advances that have been made using these models in our understanding of metastasis. We also discuss the use of these models for testing potential therapies and the challenges associated with the translation of these findings into the provision of new and effective treatments for cancer patients.

  1. Pelagic functional group modeling: Progress, challenges and prospects

    Science.gov (United States)

    Hood, Raleigh R.; Laws, Edward A.; Armstrong, Robert A.; Bates, Nicholas R.; Brown, Christopher W.; Carlson, Craig A.; Chai, Fei; Doney, Scott C.; Falkowski, Paul G.; Feely, Richard A.; Friedrichs, Marjorie A. M.; Landry, Michael R.; Keith Moore, J.; Nelson, David M.; Richardson, Tammi L.; Salihoglu, Baris; Schartau, Markus; Toole, Dierdre A.; Wiggert, Jerry D.

    2006-03-01

    In this paper, we review the state of the art and major challenges in current efforts to incorporate biogeochemical functional groups into models that can be applied on basin-wide and global scales, with an emphasis on models that might ultimately be used to predict how biogeochemical cycles in the ocean will respond to global warming. We define the term "biogeochemical functional group" to refer to groups of organisms that mediate specific chemical reactions in the ocean. Thus, according to this definition, "functional groups" have no phylogenetic meaning—these are composed of many different species with common biogeochemical functions. Substantial progress has been made in the last decade toward quantifying the rates of these various functions and understanding the factors that control them. For some of these groups, we have developed fairly sophisticated models that incorporate this understanding, e.g. for diazotrophs (e.g. Trichodesmium), silica producers (diatoms) and calcifiers (e.g. coccolithophorids and specifically Emiliania huxleyi). However, current representations of nitrogen fixation and calcification are incomplete, i.e., based primarily upon models of Trichodesmium and E. huxleyi, respectively, and many important functional groups have not yet been considered in open-ocean biogeochemical models. Progress has been made over the last decade in efforts to simulate dimethylsulfide (DMS) production and cycling (i.e., by dinoflagellates and prymnesiophytes) and denitrification, but these efforts are still in their infancy, and many significant problems remain. One obvious gap is that virtually all functional group modeling efforts have focused on autotrophic microbes, while higher trophic levels have been completely ignored. It appears that in some cases (e.g., calcification), incorporating higher trophic levels may be essential not only for representing a particular biogeochemical reaction, but also for modeling export. Another serious problem is our

  2. Significance of peak height velocity as a predictive factor for curve progression in patients with idiopathic scoliosis

    Science.gov (United States)

    2015-01-01

    progression in patients with IS. Conclusions These findings indicate that 31.5 degrees of spinal curvature when patients are at PHV is a significant predictive indicator for progression of the curve to a magnitude requiring surgery. We suggest that the curve-progression risk assessment in patients with IS should include PHV, along with measures of skeletal and non-skeletal maturities. PMID:25815057

  3. User-Defined Material Model for Progressive Failure Analysis

    Science.gov (United States)

    Knight, Norman F. Jr.; Reeder, James R. (Technical Monitor)

    2006-01-01

    An overview of different types of composite material system architectures and a brief review of progressive failure material modeling methods used for structural analysis including failure initiation and material degradation are presented. Different failure initiation criteria and material degradation models are described that define progressive failure formulations. These progressive failure formulations are implemented in a user-defined material model (or UMAT) for use with the ABAQUS/Standard1 nonlinear finite element analysis tool. The failure initiation criteria include the maximum stress criteria, maximum strain criteria, the Tsai-Wu failure polynomial, and the Hashin criteria. The material degradation model is based on the ply-discounting approach where the local material constitutive coefficients are degraded. Applications and extensions of the progressive failure analysis material model address two-dimensional plate and shell finite elements and three-dimensional solid finite elements. Implementation details and use of the UMAT subroutine are described in the present paper. Parametric studies for composite structures are discussed to illustrate the features of the progressive failure modeling methods that have been implemented.

  4. Progress in studying scintillator proportionality: Phenomenological model

    Energy Technology Data Exchange (ETDEWEB)

    Bizarri, Gregory; Cherepy, Nerine; Choong, Woon-Seng; Hull, Giulia; Moses, William; Payne, Sephen; Singh, Jai; Valentine, John; Vasilev, Andrey; Williams, Richard

    2009-04-30

    We present a model to describe the origin of non-proportional dependence of scintillator light yield on the energy of an ionizing particle. The non-proportionality is discussed in terms of energy relaxation channels and their linear and non-linear dependences on the deposited energy. In this approach, the scintillation response is described as a function of the deposited energy deposition and the kinetic rates of each relaxation channel. This mathematical framework allows both a qualitative interpretation and a quantitative fitting representation of scintillation non-proportionality response as function of kinetic rates. This method was successfully applied to thallium doped sodium iodide measured with SLYNCI, a new facility using the Compton coincidence technique. Finally, attention is given to the physical meaning of the dominant relaxation channels, and to the potential causes responsible for the scintillation non-proportionality. We find that thallium doped sodium iodide behaves as if non-proportionality is due to competition between radiative recombinations and non-radiative Auger processes.

  5. 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.

  6. College Students' Technology Arc: A Model for Understanding Progress

    Science.gov (United States)

    Langer, Arthur; Knefelkamp, L. Lee

    2008-01-01

    This article introduces the Student Technology Arc, a model that evaluates college students 'technology literacy, or how they operate within an education system influenced by new technologies. Student progress is monitored through the Arc's 5 interdependent stages, which reflect growing technological maturity through levels of increasing cognitive…

  7. 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.

  8. The MPTP/probenecid model of progressive Parkinson's disease.

    Science.gov (United States)

    Carta, Anna R; Carboni, Ezio; Spiga, Saturnino

    2013-01-01

    Parkinson's disease (PD) is characterized by a progressive degeneration of dopamine (DA) neurons and a chronic loss of motor functions. The investigation of progressive degenerative mechanisms and possible neuroprotective approaches for PD depends upon the development of an experimental animal model that reproduces the neuropathology observed in humans. This chapter describes the generation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTPp) chronic mouse model of PD. This model displays key features of PD, including impairment of motor and olfactory functions associated with partial loss of tyrosine hydroxylase-positive neurons and DA levels in the brain. The MPTPp mouse model provides an important tool for the study of mechanisms contributing to the pathological dysfunction of PD at the cellular and whole animal level.

  9. 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.

  10. 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.

    (ANN) modeling. The transformed output data are used as inputs to ANN models. Various decomposition levels have been tried for a db3 wavelet to obtain optimal results. It is found that the performance of hybrid WLNN is better than that of ANN when lead...

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

    Science.gov (United States)

    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.; Mõttus, M.; North, P. R. J.; Qin, W.; Robustelli, M.; Rochdi, N.; Ruiloba, R.; Soler, C.; Thompson, R.; Verhoef, W.; Verstraete, M. M.; Xie, D.

    2007-05-01

    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 basis. The first phase of RAMI focused on documenting the spread among radiative transfer (RT) simulations over a small set of primarily 1-D canopies. The second phase expanded the scope to include structurally complex 3-D plant architectures with and without background topography. Here sometimes significant discrepancies were noted which effectively prevented the definition of a reliable "surrogate truth," over heterogeneous vegetation canopies, against which other RT models could then be compared. The present paper documents the outcome of the third phase of RAMI, highlighting both the significant progress that has been made in terms of model agreement since RAMI-2 and the capability of/need for RT models to accurately reproduce local estimates of radiative quantities under conditions that are reminiscent of in situ measurements. Our assessment of the self-consistency and the relative and absolute performance of 3-D Monte Carlo models in RAMI-3 supports their usage in the generation of a "surrogate truth" for all RAMI test cases. This development then leads (1) to the presentation of the "RAMI Online Model Checker" (ROMC), an open-access web-based interface to evaluate RT models automatically, and (2) to a reassessment of the role, scope, and opportunities of the RAMI project in the future.

  12. 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.

  13. 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....

  14. 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

  15. 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

  16. A MATHEMATICAL MODEL OF CHP 2000 TYPE PROGRESSIVE GEAR

    OpenAIRE

    Paweł Lonkwic

    2016-01-01

    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 th...

  17. 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)

  18. 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.

  19. 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.

  20. Modelling the progression of bird migration with conditional autoregressive models applied to ringing data.

    Science.gov (United States)

    Ambrosini, Roberto; Borgoni, Riccardo; Rubolini, Diego; Sicurella, Beatrice; Fiedler, Wolfgang; Bairlein, Franz; Baillie, Stephen R; Robinson, Robert A; Clark, Jacquie A; Spina, Fernando; Saino, Nicola

    2014-01-01

    Migration is a fundamental stage in the life history of several taxa, including birds, and is under strong selective pressure. At present, the only data that may allow for both an assessment of patterns of bird migration and for retrospective analyses of changes in migration timing are the databases of ring recoveries. We used ring recoveries of the Barn Swallow Hirundo rustica collected from 1908-2008 in Europe to model the calendar date at which a given proportion of birds is expected to have reached a given geographical area ('progression of migration') and to investigate the change in timing of migration over the same areas between three time periods (1908-1969, 1970-1990, 1991-2008). The analyses were conducted using binomial conditional autoregressive (CAR) mixed models. We first concentrated on data from the British Isles and then expanded the models to western Europe and north Africa. We produced maps of the progression of migration that disclosed local patterns of migration consistent with those obtained from the analyses of the movements of ringed individuals. Timing of migration estimated from our model is consistent with data on migration phenology of the Barn Swallow available in the literature, but in some cases it is later than that estimated by data collected at ringing stations, which, however, may not be representative of migration phenology over large geographical areas. The comparison of median migration date estimated over the same geographical area among time periods showed no significant advancement of spring migration over the whole of Europe, but a significant advancement of autumn migration in southern Europe. Our modelling approach can be generalized to any records of ringing date and locality of individuals including those which have not been recovered subsequently, as well as to geo-referenced databases of sightings of migratory individuals.

  1. Significance of Various Experimental Models and Assay Techniques in Cancer Diagnosis.

    Science.gov (United States)

    Ghanghoria, Raksha; Kesharwani, Prashant; Jain, Narendra K

    2017-01-01

    The experimental models are of vital significance to provide information regarding biological as well as genetic factors that control the phenotypic characteristics of the disease and serve as the foundation for the development of rational intervention stratagem. This review highlights the importance of experimental models in the field of cancer management. The process of pathogenesis in cancer progression, invasion and metastasis can be successfully explained by employing clinically relevant laboratory models of the disease. Cancer cell lines have been used extensively to monitor the process of cancer pathogenesis process by controlling growth regulation and chemo-sensitivity for the evaluation of novel therapeutics in both in vitro and xenograft models. The experimental models have been used for the elaboration of diagnostic or therapeutic protocols, and thus employed in preclinical studies of bioactive agents relevant for cancer prevention. The outcome of this review should provide useful information in understanding and selection of various models in accordance with the stage of cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Evaluating Alzheimer's Disease Progression by Modeling Crosstalk Network Disruption

    Science.gov (United States)

    Liu, Haochen; Wei, Chunxiang; He, Hua; Liu, Xiaoquan

    2016-01-01

    Aβ, tau, and P-tau have been widely accepted as reliable markers for Alzheimer's disease (AD). The crosstalk between these markers forms a complex network. AD may induce the integral variation and disruption of the network. The aim of this study was to develop a novel mathematic model based on a simplified crosstalk network to evaluate the disease progression of AD. The integral variation of the network is measured by three integral disruption parameters. The robustness of network is evaluated by network disruption probability. Presented results show that network disruption probability has a good linear relationship with Mini Mental State Examination (MMSE). The proposed model combined with Support vector machine (SVM) achieves a relative high 10-fold cross-validated performance in classification of AD vs. normal and mild cognitive impairment (MCI) vs. normal (95% accuracy, 95% sensitivity, 95% specificity for AD vs. normal; 90% accuracy, 94% sensitivity, 83% specificity for MCI vs. normal). This research evaluates the progression of AD and facilitates AD early diagnosis. PMID:26834548

  7. Modeling Diverse Pathways to Age Progressive Volcanism in Subduction Zones.

    Science.gov (United States)

    Kincaid, C. R.; Szwaja, S.; Sylvia, R. T.; Druken, K. A.

    2015-12-01

    One of the best, and most challenging clues to unraveling mantle circulation patterns in subduction zones comes in the form of age progressive volcanic and geochemical trends. Hard fought geological data from many subduction zones, like Tonga-Lau, the Cascades and Costa-Rica/Nicaragua, reveal striking temporal patterns used in defining mantle flow directions and rates. We summarize results from laboratory subduction models showing a range in circulation and thermal-chemical transport processes. These interaction styles are capable of producing such trends, often reflecting apparent instead of actual mantle velocities. Lab experiments use a glucose working fluid to represent Earth's upper mantle and kinematically driven plates to produce a range in slab sinking and related wedge transport patterns. Kinematic forcing assumes most of the super-adiabatic temperature gradient available to drive major downwellings is in the tabular slabs. Moreover, sinking styles for fully dynamic subduction depend on many complicating factors that are only poorly understood and which can vary widely even for repeated parameter combinations. Kinematic models have the benefit of precise, repeatable control of slab motions and wedge flow responses. Results generated with these techniques show the evolution of near-surface thermal-chemical-rheological heterogeneities leads to age progressive surface expressions in a variety of ways. One set of experiments shows that rollback and back-arc extension combine to produce distinct modes of linear, age progressive melt delivery to the surface through a) erosion of the rheological boundary layer beneath the overriding plate, and deformation and redistribution of both b) mantle residuum produced from decompression melting and c) formerly active, buoyant plumes. Additional experiments consider buoyant diapirs rising in a wedge under the influence of rollback, back-arc spreading and slab-gaps. Strongly deflected diapirs, experiencing variable rise

  8. PUMA promotes apoptosis of hematopoietic progenitors driving leukemic progression in a mouse model of myelodysplasia.

    Science.gov (United States)

    Guirguis, A A; Slape, C I; Failla, L M; Saw, J; Tremblay, C S; Powell, D R; Rossello, F; Wei, A; Strasser, A; Curtis, D J

    2016-06-01

    Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis with resultant cytopenias. Increased apoptosis and aberrantly functioning progenitors are thought to contribute to this phenotype. As is the case for other malignancies, overcoming apoptosis is believed to be important in progression toward acute myeloid leukemia (AML). Using the NUP98-HOXD13 (NHD13) transgenic mouse model of MDS, we previously reported that overexpression of the anti-apoptotic protein BCL2, blocked apoptosis and improved cytopenias, paradoxically, delaying leukemic progression. To further understand this surprising result, we examined the role of p53 and its pro-apoptotic effectors, PUMA and NOXA in NHD13 mice. The absence of p53 or PUMA but not NOXA reduced apoptosis and expanded the numbers of MDS-repopulating cells. Despite a similar effect on apoptosis and cell numbers, the absence of p53 and PUMA had diametrically opposed effects on progression to AML: absence of p53 accelerated leukemic progression, while absence of PUMA significantly delayed progression. This may be explained in part by differences in cellular responses to DNA damage. The absence of p53 led to higher levels of γ-H2AX (indicative of persistent DNA lesions) while PUMA-deficient NHD13 progenitors resolved DNA lesions in a manner comparable to wild-type cells. These results suggest that targeting PUMA may improve the cytopenias of MDS without a detrimental effect on leukemic progression thus warranting further investigation.

  9. Modeling the dynamics of chromosomal alteration progression in cervical cancer: A computational model.

    Directory of Open Access Journals (Sweden)

    Augusto Cabrera-Becerril

    Full Text Available Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC is a process in which the cell acquires dynamic behavior from non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamics of deleterious and non-deleterious mutations as an outcome of tumor progression. The analysis of chromosomal alterations mediated by our model reveals that multiple deleterious mutations are more frequent in precursor lesions than in CC. Cells with lethal deleterious mutations would be eliminated, which would mitigate cancer progression; on the other hand, cells with non-deleterious mutations would become dominant, which could predispose them to cancer progression. The study of somatic alterations through computer simulations of cancer progression provides a feasible pathway for insights into the transformation of cell mechanisms in humans. During cancer progression, tumors may acquire new phenotype traits, such as the ability to invade and metastasize or to become clinically important when they develop drug resistance. Non-deleterious chromosomal alterations contribute to this progression.

  10. 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

  11. 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.

  12. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, R.C.; Gasser, R.D. [Sandia National Labs., Albuquerque, NM (United States). Reactor Safety Experiments Dept.

    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.

  14. Modelling the Progression of Male Swimmers’ Performances through Adolescence

    Directory of Open Access Journals (Sweden)

    Shilo J. Dormehl

    2016-01-01

    Full Text Available Insufficient data on adolescent athletes is contributing to the challenges facing youth athletic development and accurate talent identification. The purpose of this study was to model the progression of male sub-elite swimmers’ performances during adolescence. The performances of 446 males (12–19 year olds competing in seven individual events (50, 100, 200 m freestyle, 100 m backstroke, breaststroke, butterfly, 200 m individual medley over an eight-year period at an annual international schools swimming championship, run under FINA regulations were collected. Quadratic functions for each event were determined using mixed linear models. Thresholds of peak performance were achieved between the ages of 18.5 ± 0.1 (50 m freestyle and 200 m individual medley and 19.8 ± 0.1 (100 m butterfly years. The slowest rate of improvement was observed in the 200 m individual medley (20.7% and the highest in the 100 m butterfly (26.2%. Butterfly does however appear to be one of the last strokes in which males specialise. The models may be useful as talent identification tools, as they predict the age at which an average sub-elite swimmer could potentially peak. The expected rate of improvement could serve as a tool in which to monitor and evaluate benchmarks.

  15. 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

  16. Modeling progression risk for smoldering multiple myeloma: results from a prospective clinical study.

    Science.gov (United States)

    Cherry, Benjamin M; Korde, Neha; Kwok, Mary; Manasanch, Elisabet E; Bhutani, Manisha; Mulquin, Marcia; Zuchlinski, Diamond; Yancey, Mary Ann; Maric, Irina; Calvo, Katherine R; Braylan, Raul; Stetler-Stevenson, Maryalice; Yuan, Constance; Tembhare, Prashant; Zingone, Adriana; Costello, Rene; Roschewski, Mark J; Landgren, Ola

    2013-10-01

    The risk of progression to multiple myeloma (MM) from the precursor condition smoldering MM (SMM) varies considerably among individual patients. Reliable markers for progression to MM are vital to advance the understanding of myeloma precursor disease and for the development of intervention trials designed to delay/prevent MM. The Mayo Clinic and Spanish PETHEMA have proposed models to stratify patient risk based on clinical parameters. The aim of our study was to define the degree of concordance between these two models by comparing the distribution of patients with SMM classified as low, medium and high risk for progression. A total of 77 patients with SMM were enrolled in our prospective natural history study. Per study protocol, each patient was assigned risk scores based on both the Mayo and the Spanish models. The Mayo Clinic model identified 38, 35 and four patients as low, medium and high risk, respectively. The Spanish PETHEMA model classified 17, 22 and 38 patients as low, medium and high risk, respectively. There was significant discordance in overall patient risk classification (28.6% concordance) and in classifying patients as low versus high (p < 0.0001), low versus non-low (p = 0.0007) and high versus non-high (p < 0.0001) risk. There is a need for prospectively validated models to characterize individual patient risk of transformation to MM.

  17. Stereometric parameters change vs. Topographic Change Analysis (TCA) agreement in Heidelberg Retina Tomography III (HRT-3) early detection of clinical significant glaucoma progression.

    Science.gov (United States)

    Dascalu, A M; Cherecheanu, A P; Stana, D; Voinea, L; Ciuluvica, R; Savlovschi, C; Serban, D

    2014-01-01

    to investigate the sensitivity and specificity of the stereometric parameters change analysis vs. Topographic Change Analysis in early detection of glaucoma progression. 81 patients with POAG were monitored for 4 years (GAT monthly, SAP at every 6 months, optic disc photographs and HRT3 yearly). The exclusion criteria were other optic disc or retinal pathology; topographic standard deviation (TSD>30; inter-test variation of reference height>25 μm. The criterion for structural progression was the following: at least 20 adjacent super-pixels with a clinically significant decrease in height (>5%). 16 patients of the total 81 presented structural progression on TCA. The most useful stereometric parameters for the early detection of glaucoma progression were the following: Rim Area change (sensitivity 100%, specificity 74.2% for a "cut-off " value of -0.05), C/D Area change (sensitivity 85.7%, specificity 71.5% for a "cut off " value of 0.02), C/D linear change (sensitivity 85.7%, specificity 71.5% for a "cut-off " value of 0.02), Rim Volume change (sensitivity 71.4%, specificity 88.8% for a "cut-off " value of -0.04). RNFL Thickness change (<0) was highly sensitive (82%), but less specific for glaucoma progression (45,2%). Changes of the other stereometric parameters have a limited diagnostic value for the early detection of glaucoma progression. TCA is a valuable tool for the assessment of the structural progression in glaucoma patients and its inter-test variability is low. On long-term, the quantitative analysis according to stereometric parameters change is also very important. The most relevant parameters to detect progression are RA, C/D Area, Linear C/D and RV.

  18. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger (Nicolaus); H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is

  19. Comparisons of model simulations of climate variability with data, Task 2. [Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-31

    Significant progress has been made in our investigations aimed at diagnosing low frequency variations of climate in General Circulation Models. We have analyzed three versions of the Oregon State University General Circulation Model (OSU GCM). These are: (1) the Slab Model in which the ocean is treated as a static heat reservoir of fixed depth, (2) the coupled upper ocean-atmosphere model in which the ocean dynamics are calculated in two layers of variable depths representing the mixed layers and the thermocline; this model is referred to OSU2 in the following discussion, and (3) the coupled full ocean-atmosphere model in which the ocean is represented by six layers of variable depth; this model is referred to as OSU6 GCM in the discussion.

  20. Alzheimer's disease: a mathematical model for onset and progression.

    Science.gov (United States)

    Bertsch, Michiel; Franchi, Bruno; Marcello, Norina; Tesi, Maria Carla; Tosin, Andrea

    2017-06-01

    In this article we propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We regard brain neurons as a continuous medium and structure them by their degree of malfunctioning. 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 and ii) neuron-to-neuron prion-like transmission. We model these two processes by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The second equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. Our numerical simulations are in good qualitative agreement with clinical images of the disease distribution in the brain which vary from early to advanced stages. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Towards predictive stochastic dynamical modeling of cancer genesis and progression.

    Science.gov (United States)

    Ao, P; Galas, D; Hood, L; Yin, L; Zhu, X M

    2010-06-01

    Based on an innovative endogenous network hypothesis on cancer genesis and progression we have been working towards a quantitative cancer theory along the systems biology perspective. Here we give a brief report on our progress and illustrate that combing ideas from evolutionary and molecular biology, mathematics, engineering, and physics, such quantitative approach is feasible.

  12. 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.

  13. 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.

  14. 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

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

    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 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.

  16. 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.

  17. 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.

  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: 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  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 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

  10. Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.

    Science.gov (United States)

    Haritoglou, Christos; Kernt, Marcus; Neubauer, Aljoscha; Gerss, Joachim; Oliveira, Carlos Manta; Kampik, Anselm; Ulbig, Michael

    2014-01-01

    To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs. Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient "positive." The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated. The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up ("true positive") and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME ("true negative"). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%. Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the

  11. 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...

  12. 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.

  13. 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.

  14. Modeling, analysis and experiments for fusion nuclear technology: FNT progress report: Modeling and FINESSE

    International Nuclear Information System (INIS)

    Abdou, M.A.; Tillack, M.S.; Raffray, A.R.

    1987-01-01

    This document is a progress report on two technical studies carried out during 1986, both of which relate to the implementation phase of FNT. The first, which is a follow-up to FINESSE, focuses on specific key questions for: (1) very near-term (0 to 3 years) non-fusion experiments and facilities, and (2) FNT testing in a fusion facility. The second is the initial stage of a detailed effort to develop theory, models and computer codes for predicting the performance of nuclear components. Chapters are presented on (1) introduction and chapter summaries, (2) non-fusion experiments and facilities, (3) fusion testing issues, and (4) theory and modeling. Chapter 2 is an assessment of the relative advantages of many solid breeders, neutron multipliers and configurations. Various issues affecting design and cost of the blanket are examined in Chapter 3. Chapter 4 reports on the progress of the initial stage of an effort to develop theory and analytical and numerical models for nuclear components. A major part of the effort has focused on modeling of MHD effects for liquid metal blankets. Progress has also been made on modeling tritium transport and inventory in solid breeder blankets and the thermomechanical behavior of liquid-metal-cooled limiters

  15. Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic significance on tumor progression.

    Science.gov (United States)

    Brivio, Fernando; Fumagalli, Luca; Fumagalli, Gabriele; Pescia, Simonetta; Brivio, Rinaldo; Di Fede, Giuseppe; Rovelli, Franco; Lissoni, Paolo

    2010-01-01

    Cancer progression has been associated with neuroendocrine alterations involved in the control of the circadian rhythms, particularly those of cortisol. Moreover, the evidence of an altered cortisol rhythm may predict a poor prognosis in cancer patients. Finally, cancer progression has been proven to be associated with alterations in the pineal gland, which plays a fundamental role in the control of circadian biological rhythms. On this basis, a study was planned to evaluate the effects of a chronic treatment with the pineal hormone melatonin (MLT) in advanced cancer patients with altered cortisol circadian rhythm. The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mg/day orally, in the evening, for 3 consecutive months. a normalization of cortisol rhythm was achieved in 4/14 (29%) patients. Moreover, stable disease (SD) was obtained in 6/14 (43%) patients under MLT therapy, whereas the other 8 patients had progressive disease (PD). Finally, the percentage of cortisol rhythm normalization achieved in patients with SD was significantly higher than that observed in patients with PD. These results show that MLT may normalize cortisol rhythm in advanced cancer patients and this effect appears to be associated with SD, thus confirming the negative prognostic significance of cortisol rhythm alterations in cancer.

  16. 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

    the effect of changes in glycaemia and arterial blood pressure on the incidence of clinically significant macular oedema in a population of diabetic patients. Methods We performed a retrospective review of all patients with type 1 diabetes who attended the retinopathy screening clinic at the Steno Diabetes......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......-free interval before referral, where the median screening interval was 6 months. Results Risk of progression to photocoagulation for macular oedema increased with duration of diabetes (p 

  17. Superficial spreading and nodular melanoma are distinct biological entities: a challenge to the linear progression model.

    Science.gov (United States)

    Greenwald, Holly S; Friedman, Erica B; Osman, Iman

    2012-02-01

    The classification of melanoma subtypes into prognostically relevant and therapeutically insightful categories has been a challenge since the first description of melanoma in the 1800s. One limitation has been the assumption that the two most common histological subtypes of melanoma, superficial spreading and nodular, evolve according to a linear model of progression, as malignant melanocytes spread radially and then invade vertically. However, recent clinical, pathological, and molecular data indicate that these two histological subtypes might evolve as distinct entities. Here, we review the published data that support distinct molecular characterization of superficial spreading and nodular melanoma, the clinical significance of this distinction including prognostic relevance and the therapeutic implications.

  18. 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 ...

  19. Oxygen Transport Characterization of a Human Model of Progressive Hemorrhage

    Science.gov (United States)

    2010-01-01

    treatment of hemorrhaging patients . 2. Methods 2.1. Study design, setting, and population This was a prospective study performed at the USAISR in San...70mmHg, and/or the presence of pre- syncopal symptoms expressed by the subject such as gray-out, sweating, nausea, or dizziness. 2.3. Instrumentation...protocol was terminated.23 This approach avoids attrition of sample size as the individual absolute levels of LBNP progressed and considers the data

  20. 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...

  1. 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…

  2. Low-level laser therapy ameliorates disease progression in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Farfara, Dorit; Tuby, Hana; Trudler, Dorit; Doron-Mandel, Ella; Maltz, Lidya; Vassar, Robert J; Frenkel, Dan; Oron, Uri

    2015-02-01

    Low-level laser therapy (LLLT) has been used to treat inflammation, tissue healing, and repair processes. We recently reported that LLLT to the bone marrow (BM) led to proliferation of mesenchymal stem cells (MSCs) and their homing in the ischemic heart suggesting its role in regenerative medicine. The aim of the present study was to investigate the ability of LLLT to stimulate MSCs of autologous BM in order to affect neurological behavior and β-amyloid burden in progressive stages of Alzheimer's disease (AD) mouse model. MSCs from wild-type mice stimulated with LLLT showed to increase their ability to maturate towards a monocyte lineage and to increase phagocytosis activity towards soluble amyloid beta (Aβ). Furthermore, weekly LLLT to BM of AD mice for 2 months, starting at 4 months of age (progressive stage of AD), improved cognitive capacity and spatial learning, as compared to sham-treated AD mice. Histology revealed a significant reduction in Aβ brain burden. Our results suggest the use of LLLT as a therapeutic application in progressive stages of AD and imply its role in mediating MSC therapy in brain amyloidogenic diseases.

  3. Multiple Damage Progression Paths in Model-based Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Model-based prognostics approaches employ do- main knowledge about a system, its components, and how they fail through the use of physics-based models. Compo- nent...

  4. 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

  5. Theoretical models regarding factors influencing switching regimes and the hydrological and erosional significance of hydrophobicity

    Science.gov (United States)

    Walsh, Rory; Urbanek, Emilia; Ferreira, Carla; Shakesby, Richard; Bento, Celia; Ferreira, Antonio

    2013-04-01

    The influence which soil hydrophobicity may have on hillslope hydrology and erosion in any location will depend on the proportion of storm events in which it is spatially contiguous. This in turn is dependent upon (a) the speed and three-dimensional pattern with which it disappears in wet weather and (b) the speed, three-dimensional pattern and degree of re-establishment of hydrophobicity in dry weather following hydrophilic or partially hydrophilic episodes. This paper draws upon results of laboratory and field investigations of changes through time in hydrophobicity, as well as recent advances in knowledge of switching mechanisms, to develop theory relating to hydrophobicity, its three-dimensional temporal dynamics and controls and its influence on overland flow and slopewash. Particular attention is given to modelling temporal change following fire. Use is made of key findings from (1) a field study of changes over a 4.2-year period January 2009 to March 2013 in hydrophobicity at two 10 m x 10 m grids (270 points, surface and 5 cm depth) on heather moorland in Central Portugal, where one grid was burned by an experimental fire in February 2009 and the other was an immediately adjacent unburned control; (2) a laboratory study of three-dimensional change in hydrophobicity with wetting (by an 8 mm simulated rainfall) and at different stages in an 80-hour drying phase of three different but initially equally hydrophobic soils, each of which comprising variants with and without artificial vertical routeways (simulated roots or linear cracks) and with or without drainage impedance at 2.5 cm depth. A series of theoretical models are presented addressing 1) factors and mechanisms influencing post-fire temporal change in hydrophobicity and (2) factors and mechanisms controlling the significance and temporal dynamics of hydrophobicity influence on overland flow and erosion (i) in unburned terrain and (ii) following fire. The field evidence from Portugal suggests a three

  6. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management.

    Science.gov (United States)

    Kyle, R A; Durie, B G M; Rajkumar, S V; Landgren, O; Blade, J; Merlini, G; Kröger, N; Einsele, H; Vesole, D H; Dimopoulos, M; San Miguel, J; Avet-Loiseau, H; Hajek, R; Chen, W M; Anderson, K C; Ludwig, H; Sonneveld, P; Pavlovsky, S; Palumbo, A; Richardson, P G; Barlogie, B; Greipp, P; Vescio, R; Turesson, I; Westin, J; Boccadoro, M

    2010-06-01

    Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2-3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1-2% per year for the next 10 years. Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months.

  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 M; Vaudrey, Jamie M P

    2016-03-01

    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. 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

  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. A comparative study of two prediction models for brain tumor progression

    Science.gov (United States)

    Zhou, Deqi; Tran, Loc; Wang, Jihong; Li, Jiang

    2015-03-01

    MR diffusion tensor imaging (DTI) technique together with traditional T1 or T2 weighted MRI scans supplies rich information sources for brain cancer diagnoses. These images form large-scale, high-dimensional data sets. Due to the fact that significant correlations exist among these images, we assume low-dimensional geometry data structures (manifolds) are embedded in the high-dimensional space. Those manifolds might be hidden from radiologists because it is challenging for human experts to interpret high-dimensional data. Identification of the manifold is a critical step for successfully analyzing multimodal MR images. We have developed various manifold learning algorithms (Tran et al. 2011; Tran et al. 2013) for medical image analysis. This paper presents a comparative study of an incremental manifold learning scheme (Tran. et al. 2013) versus the deep learning model (Hinton et al. 2006) in the application of brain tumor progression prediction. The incremental manifold learning is a variant of manifold learning algorithm to handle large-scale datasets in which a representative subset of original data is sampled first to construct a manifold skeleton and remaining data points are then inserted into the skeleton by following their local geometry. The incremental manifold learning algorithm aims at mitigating the computational burden associated with traditional manifold learning methods for large-scale datasets. Deep learning is a recently developed multilayer perceptron model that has achieved start-of-the-art performances in many applications. A recent technique named "Dropout" can further boost the deep model by preventing weight coadaptation to avoid over-fitting (Hinton et al. 2012). We applied the two models on multiple MRI scans from four brain tumor patients to predict tumor progression and compared the performances of the two models in terms of average prediction accuracy, sensitivity, specificity and precision. The quantitative performance metrics were

  11. 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...

  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. Developing an animal model for infantile spasms: pathogenesis, problems and progress

    Science.gov (United States)

    Marsh, Eric D.; Golden, Jeffrey A.

    2009-01-01

    Infantile spasms (IS), the most common of the early epileptic encephalopathies, afflicts thousands of children each year and results in significant disability. Also known as West syndrome, IS is characterized by intractable stereotyped seizures, poor developmental outcome and a characteristic electroencephalogram (EEG) pattern. IS often progresses into another epileptic encephalopathy known as Lennox-Gastaut syndrome, and continues with the patient being burdened by lifelong epilepsy and varying degrees of mental retardation. Little is known about the biological basis of IS. As the etiologies of IS are diverse, the multiple causes must converge into a final common pathway that results in this specific epilepsy phenotype. Finding a model or models to test this final pathway is necessary both to understand why the greatest susceptibility to seizure development occurs during infancy and early childhood, and what underlies the decreased cognitive potential associated with IS. Furthermore, appropriate models would permit better testing of potential therapies directed specifically at IS. This review will describe the clinical features and etiologies of IS; the ideal features that IS models should contain; and the IS models that exist currently. Finally, we will discuss the limitations of these models and the potential avenues for future research on IS. PMID:19553693

  14. 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...

  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. Epigenetic changes associated with disease progression in a mouse model of childhood allergic asthma

    Directory of Open Access Journals (Sweden)

    Adam Collison

    2013-07-01

    Development of asthma in childhood is linked to viral infections of the lower respiratory tract in early life, with subsequent chronic exposure to allergens. Progression to persistent asthma is associated with a Th2-biased immunological response and structural remodelling of the airways. The underlying mechanisms are unclear, but could involve epigenetic changes. To investigate this, we employed a recently developed mouse model in which self-limited neonatal infection with a pneumovirus, followed by sensitisation to ovalbumin via the respiratory tract and low-level chronic challenge with aerosolised antigen, leads to development of an asthmatic phenotype. We assessed expression of microRNA by cells in the proximal airways, comparing changes over the period of disease progression, and used target prediction databases to identify genes likely to be up- or downregulated as a consequence of altered regulation of microRNA. In parallel, we assessed DNA methylation in pulmonary CD4+ T cells. We found that a limited number of microRNAs exhibited marked up- or downregulation following early-life infection and sensitisation, for many of which the levels of expression were further changed following chronic challenge with the sensitizing antigen. Targets of these microRNAs included genes involved in immune or inflammatory responses (e.g. Gata3, Kitl and in tissue remodelling (e.g. Igf1, Tgfbr1, as well as genes for various transcription factors and signalling proteins. In pulmonary CD4+ T cells, there was significant demethylation at promoter sites for interleukin-4 and interferon-γ, the latter increasing following chronic challenge. We conclude that, in this model, progression to an asthmatic phenotype is linked to epigenetic regulation of genes associated with inflammation and structural remodelling, and with T-cell commitment to a Th2 immunological response. Epigenetic changes associated with this pattern of gene activation might play a role in the development of childhood

  17. 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.

  18. Beethoven, a mouse model for dominant, progressive hearing loss DFNA36.

    Science.gov (United States)

    Vreugde, Sarah; Erven, Alexandra; Kros, Corné J; Marcotti, Walter; Fuchs, Helmut; Kurima, Kiyoto; Wilcox, Edward R; Friedman, Thomas B; Griffith, Andrew J; Balling, Rudi; Hrabé De Angelis, Martin; Avraham, Karen B; Steel, Karen P

    2002-03-01

    Despite recent progress in identifying genes underlying deafness, there are still relatively few mouse models of specific forms of human deafness. Here we describe the phenotype of the Beethoven (Bth) mouse mutant and a missense mutation in Tmc1 (transmembrane cochlear-expressed gene 1). Progressive hearing loss (DFNA36) and profound congenital deafness (DFNB7/B11) are caused by dominant and recessive mutations of the human ortholog, TMC1 (ref. 1), for which Bth and deafness (dn) are mouse models, respectively.

  19. A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection.

    Directory of Open Access Journals (Sweden)

    Nasheed Moqueet

    Full Text Available Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis.A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119. HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679 were eligible. A random subcohort (n = 236 was selected from those eligible. Pro-fibrogenic markers and Interferon Lambda (IFNL rs8099917 genotype were measured from first available sample in all fibrosis cases (APRI ≥ 1.5 during follow-up and the subcohort. We used Cox proportional hazards and compared Model 1 (selected clinical predictors only to Model 2 (Model 1 plus selected markers for predicting 3-year risk of liver fibrosis using weighted Harrell's C and Net Reclassification Improvement indices.113 individuals developed significant liver fibrosis over 1300 person-years (8.63 per 100 person-years 95% CI: 7.08, 10.60. Model 1 (age, sex, current alcohol use, HIV RNA, baseline APRI, HCV genotype was nested in model 2, which also included IFNL genotype and IL-8, sICAM-1, RANTES, hsCRP, and sCD14. The C indexes (95% CI for model 1 vs. model 2 were 0.720 (0.649, 0.791 and 0.756 (0.688, 0.825, respectively. Model 2 classified risk more appropriately (overall net reclassification improvement, p<0.05.Including IFNL genotype and inflammatory markers IL-8, sICAM-1, RANTES, hs-CRP, and sCD14 enabled better prediction of the 3-year risk of significant liver fibrosis over clinical predictors alone. Whether this modest improvement in prediction justifies their additional cost requires further cost-benefit analyses.

  20. 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.

  1. Progress in modeling solidification in molten salt coolants

    Science.gov (United States)

    Tano, Mauricio; Rubiolo, Pablo; Doche, Olivier

    2017-10-01

    Molten salts have been proposed as heat carrier media in the nuclear and concentrating solar power plants. Due to their high melting temperature, solidification of the salts is expected to occur during routine and accidental scenarios. Furthermore, passive safety systems based on the solidification of these salts are being studied. The following article presents new developments in the modeling of eutectic molten salts by means of a multiphase, multicomponent, phase-field model. Besides, an application of this methodology for the eutectic solidification process of the ternary system LiF-KF-NaF is presented. The model predictions are compared with a newly developed semi-analytical solution for directional eutectic solidification at stable growth rate. A good qualitative agreement is obtained between the two approaches. The results obtained with the phase-field model are then used for calculating the homogenized properties of the solid phase distribution. These properties can then be included in a mixture macroscale model, more suitable for industrial applications.

  2. Amniotic mesenchymal stem cells mitigate osteoarthritis progression in a synovial macrophage-mediated in vitro explant coculture model.

    Science.gov (United States)

    Topoluk, Natasha; Steckbeck, Kathleen; Siatkowski, Sandra; Burnikel, Brian; Tokish, John; Mercuri, Jeremy

    2017-11-13

    Osteoarthritis (OA) is a disease of the synovial joint marked by chronic, low-grade inflammation leading to cartilage destruction. Regenerative medicine strategies for mitigating OA progression and/or promoting cartilage regeneration must be assessed using models that mimic the hallmarks of OA. More specifically, these models should maintain synovial macrophage phenotype in their native micro-environment. Herein, an in vitro coculture model of patient-matched human OA cartilage and synovium was assessed for viability, macrophage phenotype, and progressive cartilage destruction in the presence of an inflammatory milieu. Additionally, the influence of synovial macrophages and their polarization within the model was defined using depletion studies. Finally, the model was used to compare the ability of human amniotic stem cells (hAMSCs) and human adipose stem cells (hADSCs) to mitigate OA progression. OA cocultures demonstrated progressive and significant reductions in chondrocyte viability and cartilage glycosaminoglycan content within a proinflammatory environment. Selective depletion of synovial macrophages resulted in significant decreases in M1:M2 percentage ratio yielding significant reductions in concentrations of interleukin-1 beta, matrix metalloproteinase-13 and attenuation of cartilage damage. Finally, hAMSCs were found to be more chondroprotective versus hADSCs as indicated by significantly improved OA chondrocyte viability (89.8 ± 2.4% vs. 58.4 ± 2.4%) and cartilage glycosaminoglycan content (499.0 ± 101.9 μg/mg dry weight vs. 155.0 ± 26.3 μg/mg dry weight) and were more effective at shifting OA synovial macrophage M1:M2 ratio (1.3:1 vs. 5:1), respectively. Taken together, the coculture model mimics salient features of OA, including macrophage-mediated cartilage destruction that was effectively abrogated by hAMSCs but not hADSCs. Copyright © 2017 John Wiley & Sons, Ltd.

  3. 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.

  4. Qualitative modelling macroeconomics indicators for prediction of progress branch

    Directory of Open Access Journals (Sweden)

    Jiří Luňáček

    2010-01-01

    Full Text Available A qualitative modelling philosophy has been developed in an effort to produce a general and reasonably unified common sense approach to the modelling of unique, complex and unsteady state systems. Economics, Ecology, Sociology and Politics are sciences, which study such systems. An integration of sub models from those sciences into supermodels is inevitable if realistic decision making tasks are analysed. Therefore conventional formal tools (e.g. statistics cannot be correctly applied because of lack of information. Qualitative variables are quantified using three values only – positive (increasing, zero (constant and negative (decreasing. Knowledge items of qualitative nature (e.g. if productivity goes up then profit does not decrease are often the only available information. The classical quantitative tools cannot deal with such information items. However, qualitative models can absorb shallow qualitative knowledge and generate all possible scenarios i.e. qualitative solutions. The complete list of scenarios guarantees that any analysis (decision making based on it does not ignore any promising solution. The case study of oil related macro economical risks is presented in details (15 variables e.g. Inflation, Corruption, 14 qualitative relations among the variables. No a priory know­ledge of qualitative analysis is required.

  5. 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)

  6. The Choice of a Progressive Bilingual Education Model

    Science.gov (United States)

    Zelin, Li

    2017-01-01

    Bilingual education has unique and complex features. In the course of language study, with the mother tongue as a foundation, acquiring a second language depends on the features of student's learning and age. Based on the construction of J. Cummins's (1984) dual iceberg theory dual-language model, students' bilingual education is founded on the…

  7. 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 (...

  8. Significance of predictive models/risk calculators for HBV-related hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    DONG Jing

    2015-06-01

    Full Text Available Hepatitis B virus (HBV-related hepatocellular carcinoma (HCC is a major public health problem in Southeast Asia. In recent years, researchers from Hong Kong and Taiwan have reported predictive models or risk calculators for HBV-associated HCC by studying its natural history, which, to some extent, predicts the possibility of HCC development. Generally, risk factors of each model involve age, sex, HBV DNA level, and liver cirrhosis. This article discusses the evolution and clinical significance of currently used predictive models for HBV-associated HCC and assesses the advantages and limits of risk calculators. Updated REACH-B model and LSM-HCC model show better negative predictive values and have better performance in predicting the outcomes of patients with chronic hepatitis B (CHB. These models can be applied to stratified screening of HCC and, meanwhile, become an assessment tool for the management of CHB patients.

  9. 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.'

  10. Progress in Geant4 Electromagnetic Physics Modelling and Validation

    CERN Document Server

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

  11. 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

  12. 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.

  13. Progress in Mathematical Modeling of Gastrointestinal Slow Wave Abnormalities.

    Science.gov (United States)

    Du, Peng; Calder, Stefan; Angeli, Timothy R; Sathar, Shameer; Paskaranandavadivel, Niranchan; O'Grady, Gregory; Cheng, Leo K

    2017-01-01

    Gastrointestinal (GI) motility is regulated in part by electrophysiological events called slow waves, which are generated by the interstitial cells of Cajal (ICC). Slow waves propagate by a process of "entrainment," which occurs over a decreasing gradient of intrinsic frequencies in the antegrade direction across much of the GI tract. Abnormal initiation and conduction of slow waves have been demonstrated in, and linked to, a number of GI motility disorders. A range of mathematical models have been developed to study abnormal slow waves and applied to propose novel methods for non-invasive detection and therapy. This review provides a general outline of GI slow wave abnormalities and their recent classification using multi-electrode (high-resolution) mapping methods, with a particular emphasis on the spatial patterns of these abnormal activities. The recently-developed mathematical models are introduced in order of their biophysical scale from cellular to whole-organ levels. The modeling techniques, main findings from the simulations, and potential future directions arising from notable studies are discussed.

  14. 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

  15. 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

  16. Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression.

    Directory of Open Access Journals (Sweden)

    Lora C Bailey-Downs

    Full Text Available Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to complete experiments with a reasonable dormancy period, which can be used to better study metastatic progression. The basis for the model is a 4T1 triple negative syngeneic breast cancer model without resection of the primary tumor. A cell titration from 500 to 15,000 GFP tagged 4T1 cells implanted into fat pad number four of immune proficient eight week female BALB/cJ mice optimized speed of the model while possessing metastatic processes including dormancy and beginning of reactivation. The frequency of primary tumors was less than 50% in animals implanted with 500-1500 cells. Although implantation with over 10,000 cells resulted in 100% primary tumor development, the tumors and macrometastases formed were highly aggressive, lacked dormancy, and offered no opportunity for treatment. Implantation of 7,500 cells resulted in >90% tumor take by 10 days; in 30-60 micrometastases in the lung (with many animals also having 2-30 brain micrometastases two weeks post-implantation, with the first small macrometastases present at five weeks; many animals displaying macrometastases at five weeks and animals becoming moribund by six weeks post-implantation. Using the optimum of 7,500 cells the efficacy of a chemotherapeutic agent for breast cancer, doxorubicin, given at its maximal tolerated dose (MTD; 1 mg/kg weekly was tested for an effect on metastasis. Doxorubicin treatment significantly reduced primary tumor growth and lung micrometastases but the number of macrometastases at experiment end was not significantly affected. This model should prove useful for development of drugs to target metastasis and to study the biology of metastasis.

  17. Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression

    Science.gov (United States)

    Rose, Amy E.; Poliseno, Laura; Wang, Jinhua; Clark, Michael; Pearlman, Alexander; Wang, Guimin; Vega y Saenz de Miera, Eleazar C.; Medicherla, Ratna; Christos, Paul J.; Shapiro, Richard; Pavlick, Anna; Darvishian, Farbod; Zavadil, Jiri; Polsky, David; Hernando, Eva; Ostrer, Harry; Osman, Iman

    2011-01-01

    Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathological and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (SNP 6.0, Affymetrix) with gene expression array (U133A 2.0, Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N=114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (Pmelanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM. PMID:21343389

  18. Exercise Does Not Attenuate Early Coronary Artery Disease Progression in a Pig Model

    Science.gov (United States)

    Arce-Esquivel, Arturo A.; Kreutzer, Kurt V.; Rush, James W. E.; Turk, James R.; Laughlin, M. Harold

    2012-01-01

    Purpose This study was designed to examine the effects of high fat (HF) diet and subsequent exercise training (Ex) on coronary arteries of an animal model of early stage coronary artery disease (CAD). We hypothesized that HF diet would induce early stage disease and promote a pro-atherogenic coronary phenotype, while Ex would blunt disease progression and induce a healthier anti-inflammatory environment reflected by increased expression of antioxidant capacity and decreased expression of inflammatory markers in both the macro and microvasculature of the coronary circulation. Methods Immunohistochemistry in left anterior descending (LAD) and right coronary arteries (RCA), and immunoblots in LAD and left ventricular (LV) arterioles were used to characterize effects of HF diet and Ex on the progression of coronary atherosclerosis. Results Our results revealed that HF diet promoted a pro-atherogenic coronary endothelial cell phenotype as evidenced by the endothelial expression of inflammatory and oxidative stress markers. Ex did not significantly alter any of these immunohistochemical markers in conduit arteries; however, Ex did increase antioxidant protein content in LV arterioles. Conclusions We conclude that, at this early stage of CAD, Ex did not seem to modify vascular cell phenotypes of conduit coronary arteries from pro- to a more favorable anti-atherogenic status; however, Ex increased antioxidant protein content in coronary arterioles. These findings also support the idea that endothelial phenotype expression follows different patterns in the macro and microvasculature of the coronary circulation. PMID:21685817

  19. 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

  20. Sexual Recruitment in Zostera marina: Progress toward a Predictive Model.

    Science.gov (United States)

    Furman, Bradley T; Peterson, Bradley J

    2015-01-01

    Ecophysiological stress and physical disturbance are capable of structuring meadows through a combination of direct biomass removal and recruitment limitation; however, predicting these effects at landscape scales has rarely been successful. To model environmental influence on sexual recruitment in perennial Zostera marina, we selected a sub-tidal, light-replete study site with seasonal extremes in temperature and wave energy. During an 8-year observation period, areal coverage increased from 4.8 to 42.7%. Gains were stepwise in pattern, attributable to annual recruitment of patches followed by centrifugal growth and coalescence. Recruitment varied from 13 to 4,894 patches per year. Using a multiple linear regression approach, we examined the association between patch appearance and relative wave energy, atmospheric condition and water temperature. Two models were developed, one appropriate for the dispersal of naked seeds, and another for rafted flowers. Results indicated that both modes of sexual recruitment varied as functions of wind, temperature, rainfall and wave energy, with a regime shift in wind-wave energy corresponding to periods of rapid colonization within our site. Temporal correlations between sexual recruitment and time-lagged climatic summaries highlighted floral induction, seed bank and small patch development as periods of vulnerability. Given global losses in seagrass coverage, regions of recovery and re-colonization will become increasingly important. Lacking landscape-scale process models for seagrass recruitment, temporally explicit statistical approaches presented here could be used to forecast colonization trajectories and to provide managers with real-time estimates of future meadow performance; i.e., when to expect a good year in terms of seagrass expansion. To facilitate use as forecasting tools, we did not use statistical composites or normalized variables as our predictors. This study, therefore, represents a first step toward linking

  1. Progress towards quantum simulating the classical O(2) Model

    Science.gov (United States)

    2014-12-01

    by L3, the third component of the angular momentum in the SU(2) Lie algebra . Pursuing the analogy, we replace e±iθ̂ by an operator proportional to the...becomes diagonal because In(0) = 0 except for n = 0 [I0(0) = 1], and by the conservation law the same index nx characterizes the interaction along the time...Understanding how the symmetries of this initial tensor affect the universality class is under study. The O(2) model has an exact conservation law

  2. 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)

  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. Reprogramming of human cancer cells to pluripotency for models of cancer progression.

    Science.gov (United States)

    Kim, Jungsun; Zaret, Kenneth S

    2015-03-12

    The ability to study live cells as they progress through the stages of cancer provides the opportunity to discover dynamic networks underlying pathology, markers of early stages, and ways to assess therapeutics. Genetically engineered animal models of cancer, where it is possible to study the consequences of temporal-specific induction of oncogenes or deletion of tumor suppressors, have yielded major insights into cancer progression. Yet differences exist between animal and human cancers, such as in markers of progression and response to therapeutics. Thus, there is a need for human cell models of cancer progression. Most human cell models of cancer are based on tumor cell lines and xenografts of primary tumor cells that resemble the advanced tumor state, from which the cells were derived, and thus do not recapitulate disease progression. Yet a subset of cancer types have been reprogrammed to pluripotency or near-pluripotency by blastocyst injection, by somatic cell nuclear transfer and by induced pluripotent stem cell (iPS) technology. The reprogrammed cancer cells show that pluripotency can transiently dominate over the cancer phenotype. Diverse studies show that reprogrammed cancer cells can, in some cases, exhibit early-stage phenotypes reflective of only partial expression of the cancer genome. In one case, reprogrammed human pancreatic cancer cells have been shown to recapitulate stages of cancer progression, from early to late stages, thus providing a model for studying pancreatic cancer development in human cells where previously such could only be discerned from mouse models. We discuss these findings, the challenges in developing such models and their current limitations, and ways that iPS reprogramming may be enhanced to develop human cell models of cancer progression. © 2015 The Authors.

  6. 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.

  7. 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…

  8. 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.

  9. 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.

  10. 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; Guelcher, Scott A

    2017-01-01

    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 vs. 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 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 that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs.

  11. A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression

    Science.gov (United States)

    Giotopoulos, George; van der Weyden, Louise; Osaki, Hikari; Rust, Alistair G.; Gallipoli, Paolo; Meduri, Eshwar; Horton, Sarah J.; Chan, Wai-In; Foster, Donna; Prinjha, Rab K.; Pimanda, John E.; Tenen, Daniel G.; Vassiliou, George S.; Koschmieder, Steffen; Adams, David J.

    2015-01-01

    The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease. PMID:26304963

  12. Applications of computer modeling to fusion research. Progress report, 1988--1989

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, J.M.

    1989-12-31

    Progress achieved during this report period is presented on the following topics: Development and application of gyrokinetic particle codes to tokamak transport, development of techniques to take advantage of parallel computers; model dynamo and bootstrap current drive; and in general maintain our broad-based program in basic plasma physics and computer modeling.

  13. 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.

  14. 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

  15. 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.

  16. Significant ecological impact on the progression of fluoroquinolone resistance in Escherichia coli with increased community use of moxifloxacin, levofloxacin and amoxicillin/clavulanic acid.

    Science.gov (United States)

    Cuevas, Oscar; Oteo, Jesús; Lázaro, Edurne; Aracil, Belén; de Abajo, Francisco; García-Cobos, Silvia; Ortega, Adriana; Campos, José

    2011-03-01

    To determine trends in ciprofloxacin resistance and co-resistance to other antibiotic classes in blood isolates of Escherichia coli, and to investigate if there is an ecological relationship to the community use of fluoroquinolones and other antibiotics. Forty-two Spanish hospitals of the European Antimicrobial Resistance Surveillance Network collected ciprofloxacin and other antibiotic susceptibility data for non-duplicate consecutive E. coli isolates from patients with bacteraemia between 2001 and 2009. The nationwide ambulatory use of antibiotics between 1997 and 2008 was determined by WHO methods, and the co-evolution of both parameters was further analysed. Of the 28 307 E. coli blood isolates, 27.9% were ciprofloxacin non-susceptible (CIPNS), increasing from 17.6% in 2001 to 32.7% in 2009. A continuous increase was observed between CIPNS and other resistances, including cephalosporin resistance due to the production of extended-spectrum β-lactamases (ESBLs) and non-susceptibility to both amoxicillin/clavulanic acid and tobramycin. Although the total use of antibiotics did not increase, community use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid increased by 307.2%, 62.6% and 70.1%, respectively. Yearly rates of CIPNS E. coli strongly correlated with the use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid (r(2 )> 0.80; P resistance to amoxicillin/clavulanic acid, production of ESBLs and resistance to aminoglycosides. Community use of fluoroquinolones (mainly moxifloxacin and levofloxacin) and of amoxicillin/clavulanic acid represents a significant driver in the progression of fluoroquinolone resistance in bacteraemic E. coli.

  17. 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

  18. 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.

  19. Three-dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model

    OpenAIRE

    Maguire, Sarah L.; Peck, Barrie; Wai, Patty T.; Campbell, James; Barker, Holly; Gulati, Aditi; Daley, Frances; Vyse, Simon; Huang, Paul; Lord, Christopher J.; Farnie, Gillian; Brennan, Keith; Natrajan, Rachael

    2016-01-01

    Abstract The initiation and progression of breast cancer from the transformation of the normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a complex process involving the acquisition of genetic alterations and changes in gene expression, alongside microenvironmental and recognized histological alterations. Here, we sought to comprehensively characterise the genomic and transcriptomic features of the MCF10 isogenic model of breast cancer progression, and to functional...

  20. Incorporating representation of agricultural ecosystems and management within a dynamic biosphere model: Approach, validation, and significance

    Science.gov (United States)

    Kucharik, C.

    2004-12-01

    At the scale of individual fields, crop models have long been used to examine the interactions between soils, vegetation, the atmosphere and human management, using varied levels of numerical sophistication. While previous efforts have contributed significantly towards the advancement of modeling tools, the models themselves are not typically applied across larger continental scales due to a lack of crucial data. Furthermore, many times crop models are used to study a single quantity, process, or cycle in isolation, limiting their value in considering the important tradeoffs between competing ecosystem services such as food production, water quality, and sequestered carbon. In response to the need for a more integrated agricultural modeling approach across the continental scale, an updated agricultural version of a dynamic biosphere model (IBIS) now integrates representations of land-surface physics and soil physics, canopy physiology, terrestrial carbon and nitrogen balance, crop phenology, solute transport, and farm management into a single framework. This version of the IBIS model (Agro-IBIS) uses a short 20 to 60-minute timestep to simulate the rapid exchange of energy, carbon, water, and momentum between soils, vegetative canopies, and the atmosphere. The model can be driven either by site-specific meteorological data or by gridded climate datasets. Mechanistic crop models for corn, soybean, and wheat use physiologically-based representations of leaf photosynthesis, stomatal conductance, and plant respiration. Model validation has been performed using a variety of temporal scale data collected at the following spatial scales: (1) the precision-agriculture scale (5 m), (2) the individual field experiment scale (AmeriFlux), and (3) regional and continental scales using annual USDA county-level yield data and monthly satellite (AVHRR) observations of vegetation characteristics at 0.5 degree resolution. To date, the model has been used with great success to

  1. 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

  2. Evaluation of Progressive Failure Analysis and Modeling of Impact Damage in Composite Pressure Vessels

    Science.gov (United States)

    Sanchez, Christopher M.

    2011-01-01

    NASA White Sands Test Facility (WSTF) is leading an evaluation effort in advanced destructive and nondestructive testing of composite pressure vessels and structures. WSTF is using progressive finite element analysis methods for test design and for confirmation of composite pressure vessel performance. Using composite finite element analysis models and failure theories tested in the World-Wide Failure Exercise, WSTF is able to estimate the static strength of composite pressure vessels. Additionally, test and evaluation on composites that have been impact damaged is in progress so that models can be developed to estimate damage tolerance and the degradation in static strength.

  3. 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.

  4. 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.

  5. Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.

    Directory of Open Access Journals (Sweden)

    Shashank J Patel

    Full Text Available Neuroendocrine (NE differentiation has gained increased attention as a prostate cancer (PC prognostic marker. The aim of this study is to determine whether host germline genetic variation influences tumor progression and metastasis in C57BL/6-Tg(TRAMP8247Ng/J (TRAMP mouse model of aggressive NEPC. TRAMP mice were crossed to the eight progenitor strains of the Collaborative Cross recombinant inbred panel to address this. Tumor growth and metastasis burden were quantified in heterozygous transgene positive F1 male mice at 30 weeks of age. Compared to wild-type C57BL/6J-Tg(TRAMP824Ng/J males, TRAMP x CAST/EiJ, TRAMP x NOD/ShiLtJ and TRAMP x NZO/HlLtJ F1 males displayed significant increases in tumor growth. Conversely, TRAMP x WSB/EiJ and TRAMP x PWK/PhJ F1 males displayed significant reductions in tumor growth. Interestingly, despite reduced tumor burden, TRAMP x WSB/EiJ males had an increased nodal metastasis burden. Patterns of distant pulmonary metastasis tended to follow the same patterns as that of local dissemination in each of the strains. All tumors and metastases displayed positive staining for NE markers, synaptophysin, and FOXA2. These experiments conclusively demonstrate that the introduction of germline variation by breeding modulates tumor growth, local metastasis burden, and distant metastasis frequency in this model of NEPC. These strains will be useful as model systems to facilitate the identification of germline modifier genes that promote the development of aggressive forms of PC.

  6. The significance of using satellite imagery data only in Ecological Niche Modelling of Iberian herps

    Directory of Open Access Journals (Sweden)

    Neftalí Sillero

    2012-12-01

    Full Text Available The environmental data used to calculate ecological niche models (ENM are obtained mainly from ground-based maps (e.g., climatic interpolated surfaces. These data are often not available for less developed areas, or may be at an inappropriate scale, and thus to obtain this information requires fieldwork. An alternative source of eco-geographical data comes from satellite imagery. Three sets of ENM were calculated exclusively with variables obtained (1 from optical and radar images only and (2 from climatic and altitude maps obtained by ground-based methods. These models were compared to evaluate whether satellite imagery can accurately generate ENM. These comparisons must be made in areas with well-known species distribution and with available satellite imagery and ground-based data. Thus, the study area was the south-western part of Salamanca (Spain, using amphibian and reptiles as species models. Models’ discrimination capacity was measured with ROC plots. Models’ covariation was measured with a Spatial Spearman correlation. Four modelling techniques were used (Bioclim, Mahalanobis distance, GARP and Maxent. The results of this comparison showed that there were no significant differences between models generated using remotely sensed imagery or ground-based data. However, the models built with satellite imagery data exhibited a larger diversity of values, probably related to the higher spatial resolution of the satellite imagery. Satellite imagery can produce accurate ENM, independently of the modelling technique or the dataset used. Therefore, biogeographical analysis of species distribution in remote areas can be accurately developed only with variables from satellite imagery.

  7. 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

  8. Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model.

    Science.gov (United States)

    Higuchi, Yoshitoshi; Nishida, Yoshihiro; Kozawa, Eiji; Zhuo, Lisheng; Arai, Eisuke; Hamada, Shunsuke; Morita, Daigo; Ikuta, Kunihiro; Kimata, Koji; Ushida, Takahiro; Ishiguro, Naoki

    2017-08-01

    The catabolism of hyaluronan in articular cartilage remains unclear. The aims of this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown in articular cartilage on the development of osteoarthritis (OA) using genetic manipulated mice. Destabilization of the medial meniscus (DMM) model of Col2a promoter specific conditional Hyal2 knockout (Hyal -/- ) mice was established and examined. Age related and DMM induced alterations of articular cartilage of knee joint were evaluated with modified Mankin score and immunohistochemical staining of MMP-13, ADAMTS-5, KIAA11199, and biotinylated- hyaluronan binding protein staining in addition to histomorphometrical analyses. Effects of Hyal2 suppression were also analyzed using explant culture of an IL-1α induced articular cartilage degradation model. The amount and size of hyaluronan in articular cartilage were higher in Hyal2 -/- mice. Hyal2 -/- mice exhibited aggravated cartilage degradation in age-related and DMM induced mice. MMP-13 and ADAMTS-5 positive chondrocytes were significantly higher in Hyal2 -/- mice. Articular cartilage was more degraded in explant cultures obtained from Hyal2 -/- mice. Knockdown of Hyal2 in articular cartilage induced OA development and progression possibly mediated by an imbalance of HA metabolism. This suggests that Hyal2 knockdown exhibits mucopolysaccharidosis-like OA change in articular cartilage similar to Hyal1 knockdown.

  9. Examining a progressive model of self-stigma and its impact on people with serious mental illness.

    Science.gov (United States)

    Corrigan, Patrick W; Rafacz, Jennifer; Rüsch, Nicolas

    2011-10-30

    The self-esteem of some people with serious psychiatric disorders may be hurt by internalizing stereotypes about mental illness. A progressive model of self-stigma yields four stages leading to diminished self-esteem and hope: being aware of associated stereotypes, agreeing with them, applying the stereotypes to one's self, and suffering lower self-esteem. We expect to find associations between proximal stages - awareness and agreement - to be greater than between more distal stages: awareness and harm. The model was tested on 85 people with schizophrenia or other serious mental illnesses who completed measures representing the four stages of self-stigma, another independently-developed instrument representing self-stigma, proxies of harm (lowered self-esteem and hopelessness), and depression. These measures were also repeated at 6-month follow-up. Results were mixed but some evidence supported the progressive nature of self-stigma. Most importantly, separate stages of the progressive model were significantly associated with lowered self-esteem and hope. Implications of the model for stigma change are discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. 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.

  11. 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.

  12. A Parallelized Pumpless Artificial Placenta System Significantly Prolonged Survival Time in a Preterm Lamb Model.

    Science.gov (United States)

    Miura, Yuichiro; Matsuda, Tadashi; Usuda, Haruo; Watanabe, Shimpei; Kitanishi, Ryuta; Saito, Masatoshi; Hanita, Takushi; Kobayashi, Yoshiyasu

    2016-05-01

    An artificial placenta (AP) is an arterio-venous extracorporeal life support system that is connected to the fetal circulation via the umbilical vasculature. Previously, we published an article describing a pumpless AP system with a small priming volume. We subsequently developed a parallelized system, hypothesizing that the reduced circuit resistance conveyed by this modification would enable healthy fetal survival time to be prolonged. We conducted experiments using a premature lamb model to test this hypothesis. As a result, the fetal survival period was significantly prolonged (60.4 ± 3.8 vs. 18.2 ± 3.2 h, P lamb fetuses to survive for a significantly longer period when compared with previous studies. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals Inc.

  13. 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

  14. 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.

  15. Modeling of scanning laser polarimetry images of the human retina for progression detection of glaucoma

    NARCIS (Netherlands)

    Vermeer, Koen A.; Vos, Frans M.; Lo, Barrick; Zhou, Qienyuan; Lemij, Hans G.; Vossepoel, Albert M.; van Vliet, Lucas J.

    2006-01-01

    The development of methods to detect slowly progressing diseases is often hampered by the time-consuming acquisition of a sufficiently large data set. In this paper, a method is presented to model the change in images acquired by scanning laser polarimetry, for the detection of glaucomatous

  16. Relevance and clinical significance of serum resistin level in obese T2DM rhesus monkey models.

    Science.gov (United States)

    Qi, S-D; He, Z-L; Chen, Y; Ma, J; Yu, W-H; Li, Y-Y; Yang, F-M; Wang, J-B; Chen, L-X; Zhao, Y; Lu, S-Y

    2015-09-01

    Resistin is a type of hormone-like adipocytokines, which is secreted specifically by adipocytes. It may be a key factor in the development of type 2 diabetes mellitus (T2DM) from obesity- associated insulin resistance due to results that show that it has a close relationship with insulin resistance in rodents. We utilized the rhesus monkeys as study objects to preliminarily test the association with glucose metabolism and to conduct a correlation analysis for clinical parameters and serum resistin levels in obese rhesus monkey models of T2DM. The results suggested that resistin was significantly increased in T2DM monkeys (P insulin (FPI) and glycated hemoglobin (HbA1c), Insulin resistance index (HOA-IR), but a negative correlation with islet β-cell function (HOMA-β). In the course of glucose metabolism, reverse release change of resistin and insulin in T2DM monkeys occurred, but the phenomenon that was not observed in the control group, these findings indicated that resistin negatively regulated and interfered with carbohydrate metabolism in T2DM monkey models. The character of the releasing change of resistin might be a unique process in T2DM. Therefore, all of the results could provide references for clinical diagnostic criteria for human cases of T2DM, and could have clinical significance for obese T2DM diagnosis and degree of insulin resistance. © Georg Thieme Verlag KG Stuttgart · New York.

  17. 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)

  18. Applying Statistical Models to Mammographic Screening Data to Understand Growth and Progression of Ductal Carcinoma in Situ

    National Research Council Canada - National Science Library

    Gertig, Dorota M; Erbas, Bircan; Bymes, Gram; Dowty, James

    2005-01-01

    ... IS. Similar results were found for histological grade. We have developed a computer simulation for mammographic screening data which models progression and detection of Ductal carcinoma in situ...

  19. 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

  20. 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.

  1. Applying the Rule Space Model to Develop a Learning Progression for Thermochemistry

    Science.gov (United States)

    Chen, Fu; Zhang, Shanshan; Guo, Yanfang; Xin, Tao

    2017-12-01

    We used the Rule Space Model, a cognitive diagnostic model, to measure the learning progression for thermochemistry for senior high school students. We extracted five attributes and proposed their hierarchical relationships to model the construct of thermochemistry at four levels using a hypothesized learning progression. For this study, we developed 24 test items addressing the attributes of exothermic and endothermic reactions, chemical bonds and heat quantity change, reaction heat and enthalpy, thermochemical equations, and Hess's law. The test was administered to a sample base of 694 senior high school students taught in 3 schools across 2 cities. Results based on the Rule Space Model analysis indicated that (1) the test items developed by the Rule Space Model were of high psychometric quality for good analysis of difficulties, discriminations, reliabilities, and validities; (2) the Rule Space Model analysis classified the students into seven different attribute mastery patterns; and (3) the initial hypothesized learning progression was modified by the attribute mastery patterns and the learning paths to be more precise and detailed.

  2. 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

  3. 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

  4. 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.

  5. Forkhead box A3 attenuated the progression of fibrosis in a rat model of biliary atresia

    Science.gov (United States)

    Dong, Rui; Yang, Yifan; Shen, Zhen; Zheng, Chao; Jin, Zhu; Huang, Yanlei; Zhang, Zhien; Zheng, Shan; Chen, Gong

    2017-01-01

    Biliary atresia is a rare, devastating disease of infants where a fibroinflammatory process destroys the bile ducts, leading to fibrosis and biliary cirrhosis, and death if untreated. The cause and pathogenesis remain largely unknown. We tried to investigate factors involved in biliary atresia, especially forkhead box A3 (Foxa3), which might exert a role in the treatment of liver disease. We used RNA sequencing to sequence the whole transcriptomes of livers from six biliary atresia and six choledochal cysts patients. Then, we employed a rat disease model by bile duct ligation (BDL) and adenovirus transduction to address the function of Foxa3 in biliary atresia. We found that tight junction, adherence junction, cell cycle, apoptosis, chemokine singling, VEGF and MAPK signaling pathways were enriched in biliary atresia livers. We showed that Foxa3 expression was notably decreased in liver samples from biliary atresia patients. More importantly, we found that its lower expression predicted a poorer overall survival of biliary atresia patients. Rats that received BDL surgery and Foxa3 expression adenovirus resulted in a significant decrease in the deposition of collagen, and expression of profibrotic cytokines (transforming growth factor-β and connective tissue growth factor) and fibrosis markers (α-smooth muscle actin, collagen I and collagen III), as compared with rats that received BDL surgery and control adenovirus. Our data suggested a protection role for Foxa3 during the progression of liver fibrosis in biliary atresia, and thereby supported increasing Foxa3 as a targeted treatment strategy. PMID:28358366

  6. 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.

  7. 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

  8. 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.

  9. Folic acid supplementation promotes mammary tumor progression in a rat model.

    Directory of Open Access Journals (Sweden)

    Shaidah Deghan Manshadi

    Full Text Available Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (preneoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (preneoplastic mammary lesions is unknown. This is a critically important issue because breast cancer patients and survivors in North America are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis. We investigated whether folic acid supplementation can promote the progression of established mammary tumors. Female Sprague-Dawley rats were placed on a control diet and mammary tumors were initiated with 7,12-dimethylbenza[a]anthracene at puberty. When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks. The sentinel mammary tumor growth was monitored weekly. At necropsy, the sentinel and all other mammary tumors were analyzed histologically. The effect of folic acid supplementation on the expression of proteins involved in proliferation, apoptosis, and mammary tumorigenesis was determined in representative sentinel adenocarcinomas. Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumors and was associated with significantly higher sentinel mammary tumor weight and volume compared with the control diet. Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumors. The most significant and consistent mammary tumor-promoting effect was observed with the 2.5x supplemental level of folic acid. Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2. Our data suggest that folic acid supplementation may

  10. 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...

  11. Three-dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model.

    Science.gov (United States)

    Maguire, Sarah L; Peck, Barrie; Wai, Patty T; Campbell, James; Barker, Holly; Gulati, Aditi; Daley, Frances; Vyse, Simon; Huang, Paul; Lord, Christopher J; Farnie, Gillian; Brennan, Keith; Natrajan, Rachael

    2016-11-01

    The initiation and progression of breast cancer from the transformation of the normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a complex process involving the acquisition of genetic alterations and changes in gene expression, alongside microenvironmental and recognized histological alterations. Here, we sought to comprehensively characterise the genomic and transcriptomic features of the MCF10 isogenic model of breast cancer progression, and to functionally validate potential driver alterations in three-dimensional (3D) spheroids that may provide insights into breast cancer progression, and identify targetable alterations in conditions more similar to those encountered in vivo. We performed whole genome, exome and RNA sequencing of the MCF10 progression series to catalogue the copy number and mutational and transcriptomic landscapes associated with progression. We identified a number of predicted driver mutations (including PIK3CA and TP53) that were acquired during transformation of non-malignant MCF10A cells to their malignant counterparts that are also present in analysed primary breast cancers from The Cancer Genome Atlas (TCGA). Acquisition of genomic alterations identified MYC amplification and previously undescribed RAB3GAP1-HRAS and UBA2-PDCD2L expressed in-frame fusion genes in malignant cells. Comparison of pathway aberrations associated with progression showed that, when cells are grown as 3D spheroids, they show perturbations of cancer-relevant pathways. Functional interrogation of the dependency on predicted driver events identified alterations in HRAS, PIK3CA and TP53 that selectively decreased cell growth and were associated with progression from preinvasive to invasive disease only when cells were grown as spheroids. Our results have identified changes in the genomic repertoire in cell lines representative of the stages of breast cancer progression, and demonstrate that genetic dependencies can be uncovered when cells

  12. 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.

  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. 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.

  15. Urban Growth Causes Significant increase in Extreme Rainfall - A modelling study

    Science.gov (United States)

    Pathirana, Assela

    2010-05-01

    World's urban centers are growing rapidly causing the impact of extreme rainfall events felt much more severely due to relatively well unerstood phenomena like decreased infiltration and flow resistance. However, an increasing set of evidence (e.g. heavy rainfall event observed at Nerima, central part of Tokyo metropolitan area, on 21 July 1999) suggest that the extreme rainfall, the driving force itself increases as a result of the microclimatic changes due to urban growth. Urban heat islands(UHI) due to heat anomalies of urban sprawl act as virtual mountains resulting in a local atmosphere more conducive for heavy rainfall. In this study, we employ a popular mesoscale atmoshperic model to numerically simulate the UHI induced rainfall enhancement. Initial idealized experiments conducted under trophical atmospheric conditions indicated that the changes in landuse due to significant urban growth will indeed cause more intense rainfall events. This is largely due to increased convective breakup, causing a favourable situation for convective cloud systems. Five historical heavy rainfall events that caused floods in five urban centres (Dhaka, Mumbai, Colombo, Lyon and Taipei) were selected from historical records. Numerical simulations were setup to assertain what would be the amount of rainfall if the same large-scale atmospheric situations (forcings) occured under a hypothetical situation of doubled urbanization level these events. Significant increases (upto 50%) of extreme rainfall was indicated for many of the events. Under major assumptions, these simulations were used to estimate the anticipated changes in the Intensity-Duration-Frequency (IDF). The magnitude of the 30min event with 25 year return period increased by about 20 percent. Without considering any changes in the external forcing the urban growth alone could cause very significant increase in local rainfall.

  16. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

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    Francesca Colciaghi

    Full Text Available Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

  17. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

    Science.gov (United States)

    Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

    2014-01-01

    Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

  18. Modelling Tumor-induced Angiogenesis: Combination of Stochastic Sprout Spacing and Sprout Progression

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    Hosseini F.

    2017-09-01

    Full Text Available Background: Angiogenesis initiated by cancerous cells is the process by which new blood vessels are formed to enhance oxygenation and growth of tumor. Objective: In this paper, we present a new multiscale mathematical model for the formation of a vascular network in tumor angiogenesis process. Methods: Our model couples an improved sprout spacing model as a stochastic mathematical model of sprouting along an existing parent blood vessel, with a mathematical model of sprout progression in the extracellular matrix (ECM in response to some tumor angiogenic factors (TAFs. We perform simulations of the siting of capillary sprouts on an existing blood vessel using finite difference approximation of the dynamic equations of some angiogenesis activators and inhibitors. Angiogenesis activators are chemicals secreted by hypoxic tumor cells for initiating angiogenesis, and inhibitors of the angiogenesis are chemicals that are produced around every new sprout during tumor angiogenesis to inhibit the formation of further sprouts as a feedback of sprouting in angiogenesis. Moreover, for modelling sprout progression in ECM, we use three equations for the motility of endothelial cells at the tip of the activated sprouts, the consumption of TAF and the production and uptake of Fibronectin by endothelial cells. Results: Coupling these two basic models not only does provide a better time estimation of angiogenesis process, but also it is more compatible with reality. Conclusion: This model can be used to provide basic information for angiogenesis in the related studies. Related simulations can estimate the position and number of sprouts along parent blood vessel during the initial steps of angiogenesis and models the process of sprout progression in ECM until they vascularize a tumor.

  19. Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model.

    Science.gov (United States)

    Manzanares, Miguel Á; Campbell, Deanna J W; Maldonado, Gabrielle T; Sirica, Alphonse E

    2018-02-01

    Periostin and mesothelin have each been suggested to be predictors of poor survival for patients with intrahepatic cholangiocarcinoma, although the clinical prognostic value of both of these biomarkers remains uncertain. The aim of the current study was to investigate these biomarkers for their potential to act as tumor progression factors when assessed in orthotopic tumor and three-dimensional culture models of rat cholangiocarcinoma progression. Using our orthotopic model, we demonstrated a strong positive correlation between tumor and serum periostin and mesothelin and increasing liver tumor mass and associated peritoneal metastases that also reflected differences in cholangiocarcinoma cell aggressiveness and malignant grade. Periostin immunostaining was most prominent in the desmoplastic stroma of larger sized more aggressive liver tumors and peritoneal metastases. In comparison, mesothelin was more highly expressed in the cholangiocarcinoma cells; the slower growing more highly differentiated liver tumors exhibited a luminal cancer cell surface immunostaining for this biomarker, and the rapidly growing less differentiated liver and metastatic tumor masses largely showed cytoplasmic mesothelin immunoreactivity. Two molecular weight forms of mesothelin were identified, one at ∼40 kDa and the other, a more heavily glycosylated form, at ∼50 kDa. Increased expression of the 40-kDa mesothelin over that of the 50 kDa form predicted increased malignant progression in both the orthotopic liver tumors and in cholangiocarcinoma cells of different malignant potential in three-dimensional culture. Moreover, coculturing of cancer-associated myofibroblasts with cholangiocarcinoma cells promoted overexpression of the 40-kDa mesothelin, which correlated with enhanced malignant progression in vitro . Conclusion : Periostin and mesothelin are useful predictors of tumor progression in our rat desmoplastic cholangiocarcinoma models. This supports their relevance to human

  20. Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

    DEFF Research Database (Denmark)

    Almholt, Kasper; Hebsgaard, Josephine B; Nansen, Anneline

    2018-01-01

    Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test...... the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes...... mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target...

  1. Mucin (Muc expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy

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    Rachagani Satyanarayana

    2012-10-01

    Full Text Available Abstract Background Pancreatic cancer (PC is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients. Methods In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (KrasG12D;Pdx1-Cre (KC murine PC model from pancreatic intraepithelial neoplasia (PanIN to pancreatic ductal adenocarcinoma (PDAC by immunohistochemistry and quantitative real-time PCR. Results In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p CXCL1 (p CXCL2 (p  Conclusions Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC.

  2. 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.

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

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    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

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

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    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.

  5. [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.

  6. Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study

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    Herzog Sereina A

    2012-08-01

    Full Text Available Abstract Background Pelvic inflammatory disease (PID results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection. Methods We develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT. Results The predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13% in both processes. Conclusions The findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.

  7. Dynamic properties of the Solow model with bounded technological progress and time-to-build technology.

    Science.gov (United States)

    Guerrini, Luca; Sodini, Mauro

    2014-01-01

    We introduce a time-to-build technology in a Solow model with bounded technological progress. Our analysis shows that the system may be asymptotically stable, or it can produce stability switches and Hopf bifurcations when time delay varies. The direction and the stability criteria of the bifurcating periodic solutions are obtained by the normal form theory and the center manifold theorem. Numerical simulations confirms the theoretical results.

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

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    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

  9. Radiogenic heat production variability of some common lithological groups and its significance to lithospheric thermal modeling

    Science.gov (United States)

    Vilà, M.; Fernández, M.; Jiménez-Munt, I.

    2010-07-01

    Determining the temperature distribution within the lithosphere requires the knowledge of the radiogenic heat production (RHP) distribution within the crust and the lithospheric mantle. RHP of crustal rocks varies considerably at different scales as a result of the petrogenetic processes responsible for their formation and therefore RHP depends on the considered lithologies. In this work we address RHP variability of some common lithological groups from a compilation of a total of 2188 representative U, Th and K concentrations of different worldwide rock types derived from 102 published studies. To optimize the use of the generated RHP database we have classified and renamed the rock-type denominations of the original works following a petrologic classification scheme with a hierarchical structure. The RHP data of each lithological group is presented in cumulative distribution plots, and we report a table with the mean, the standard deviation, the minimum and maximum values, and the significant percentiles of these lithological groups. We discuss the reported RHP distribution for the different igneous, sedimentary and metamorphic lithological groups from a petrogenetic viewpoint and give some useful guidelines to assign RHP values to lithospheric thermal modeling.

  10. Hidden symmetry in asymmetric morphology: significance of Hjortsjo's anatomical model in liver surgery.

    Science.gov (United States)

    Shindoh, Junichi; Satou, Shoichi; Aoki, Taku; Beck, Yoshifumi; Hasegawa, Kiyoshi; Sugawara, Yasuhiko; Kokudo, Norihiro

    2012-01-01

    Several studies have recently reappraised the liver classification proposed by Hjortsjo in the 1940's and reported it as a surgically relevant theory. However, its clinical relevance and significance in liver surgery have not yet been well documented. Three-dimensional (3D) simulations of the livers of 100 healthy donors for living donor liver transplantation were reviewed. The adequacy of Hjortsjo's model was evaluated using 3D simulations and its clinical relevance was demonstrated in donor surgery. Both portal and hepatic venous branches exhibited symmetrical configuration on either side of the Rex-Cantlie line on the 3D images. In terms of the symmetry, the right paramedian sector seemed to be subdivided into two longitudinal parts, namely the "ventral" and "dorsal" parts. Volume analysis revealed that these longitudinal parts occupied relatively large areas of the liver (the ventral part, 15.7% and the dorsal part, 20.9% of the whole livers, respectively). Postoperative CT imaging confirmed marked congestion and/or impaired regeneration of these areas due to deprivation of the middle or right hepatic veins. Considering the symmetry of intrahepatic vascular distributions and clinical relevance, Hjortsjo's classification offers important viewpoint for surgeons to handle the liver based on both the portal and venous distributions.

  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. 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.

  13. 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.

  14. More Use of Peritoneal Dialysis Gives Significant Savings: A Systematic Review and Health Economic Decision Model.

    Science.gov (United States)

    Pike, Eva; Hamidi, Vida; Ringerike, Tove; Wisloff, Torbjorn; Klemp, Marianne

    2017-02-01

    Patients with end-stage renal disease (ESRD) are in need of renal replacement therapy as dialysis and/or transplantation. The prevalence of ESRD and, thus, the need for dialysis are constantly growing. The dialysis modalities are either peritoneal performed at home or hemodialysis (HD) performed in-center (hospital or satellite) or home. We examined effectiveness and cost-effectiveness of HD performed at different locations (hospital, satellite, and home) and peritoneal dialysis (PD) at home in the Norwegian setting. We conducted a systematic review for patients above 18 years with end-stage renal failure requiring dialysis in several databases and performed several meta-analyses of existing literature. Mortality and major complications that required were our main clinical outcomes. The quality of the evidence for each outcome was evaluated using GRADE. Cost-effectiveness was assessed by developing a probabilistic Markov model. The analysis was carried out from a societal perspective, and effects were expressed in quality-adjusted life-years. Uncertainties in the base-case parameter values were explored with a probabilistic sensitivity analysis. Scenario analyses were conducted by increasing the proportion of patients receiving PD with a corresponding reduction in HD patients in-center both for Norway and Europian Union. We assumed an annual growth rate of 4% in the number of dialysis patients, and a relative distribution between PD and HD in-center of 30% and 70%, respectively. From a societal perspective and over a 5-year time horizon, PD was the most cost-effective dialysis alternative. We found no significant difference in mortality between peritoneal and HD modalities. Our scenario analyses showed that a shift toward more patients on PD (as a first choice) with a corresponding reduction in HD in-center gave a saving over a 5-year period of 32 and 10,623 million EURO, respectively, for Norway and the European Union. PD was the most cost-effective dialysis

  15. College Affordability and the Emergence of Progressive Tuition Models: Are New Financial Aid Policies at Major Public Universities Working? Research and Occasional Paper Series: CSHE.7.16

    Science.gov (United States)

    Lapid, Patrick A.; Douglass, John Aubrey

    2016-01-01

    In an era of significant disinvestment in public higher education by state governments, many public universities are moving toward a "progressive tuition model" that attempts to invest approximately one-third of tuition income into institutional financial aid for lower-income and middle-class students. The objective is to mitigate the…

  16. User-defined Material Model for Thermo-mechanical Progressive Failure Analysis

    Science.gov (United States)

    Knight, Norman F., Jr.

    2008-01-01

    Previously a user-defined material model for orthotropic bimodulus materials was developed for linear and nonlinear stress analysis of composite structures using either shell or solid finite elements within a nonlinear finite element analysis tool. Extensions of this user-defined material model to thermo-mechanical progressive failure analysis are described, and the required input data are documented. The extensions include providing for temperature-dependent material properties, archival of the elastic strains, and a thermal strain calculation for materials exhibiting a stress-free temperature.

  17. 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

  18. Comparison of Far-field Noise for Three Significantly Different Model Turbofans

    Science.gov (United States)

    Woodward, Richard P.

    2008-01-01

    Far-field noise sound power level (PWL) spectra and overall sound pressure level (OASPL) directivities were compared for three significantly different model fan stages which were tested in the NASA Glenn 9 15 Low Speed Wind Tunnel. The test fans included the Advanced Ducted Propulsor (ADP) Fan1, the baseline Source Diagnostic Test (SDT) fan, and the Quiet High Speed Fan2 (QHSF2). These fans had design rotor tangential tip speeds from 840 to 1474 ft/s and stage pressure ratios from 1.29 to 1.82. Additional parameters included rotor-stator spacing, stator sweep, and downstream support struts. Acoustic comparison points were selected on the basis of stage thrust. Acoustic results for the low tip speed/low pressure ratio fan (ADP Fan1) were thrust-adjusted to show how a geometrically-scaled version of this fan might compare at the higher design thrust levels of the other two fans. Lowest noise levels were typically observed for ADP Fan1 (which had a radial stator) and for the intermediate tip speed fan (Source Diagnostics Test, SDT, R4 rotor) with a swept stator. Projected noise levels for the ADP fan to the SDT swept stator configuration at design point conditions showed the fans to have similar noise levels. However, it is possible that the ADP fan could be 2 to 3 dB quieter with incorporation of a swept stator. Benefits of a scaled ADP fan include avoidance of multiple pure tones associated with transonic and higher blade tip speeds. Penalties of a larger size ADP fan would include increased nacelle size and drag.

  19. Effects of fluoride on caries development and progression using intra-oral models.

    Science.gov (United States)

    Wefel, J S

    1990-02-01

    This paper reviews the use of intra-oral model systems to help elucidate the role of fluoride and its mechanism of action in caries prevention. The intra-oral models currently in use were found to be of three general types. The most widely used system has consisted of a removable appliance that relies on the use of dacron gauze or a recessed sample to enhance plaque formation. Similarly, the banding model of Ogaard requires the presence of orthodontic band material to produce a plaque accumulation niche for demineralization, while the crown single-section technique relies mainly on placement of the sections in plaque-retentive areas (below contact points). In general, the models may be used for the assessment of food cariogenicity, an evaluation of de- and re-mineralization, and measurement of fluoride incorporation into enamel or root substrates. On evaluation of lesion initiation and progression in vivo, it is apparent that few non-destructive in vivo techniques are available that offer the sensitivity of laboratory-based analysis. Thus, the use of intra-oral models that allow lesion formation and progression to occur in the oral environment, but can be measured with the sensitivity of in vitro techniques, has been extremely important. Although the magnitude of the fluoride dose, the longevity of fluoride in the oral environment, and the time required for remineralization are different from those found in vitro, it is apparent that the presence of fluoride in the aqueous phase is now thought to be of primary importance. Mechanistically, the presence of fluoride will both inhibit demineralization by acid and promote remineralization under more neutral conditions. Thus, one of fluoride's major contributions is to affect the rates of lesion formation and progression. It was concluded that low-concentration fluoride agents with a high frequency of application would best fulfill the above needs.

  20. 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

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

    Science.gov (United States)

    Luo, Gang

    2017-12-01

    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.

  2. Bayesian Inference for Step-Stress Partially Accelerated Competing Failure Model under Type II Progressive Censoring

    Directory of Open Access Journals (Sweden)

    Xiaolin Shi

    2016-01-01

    Full Text Available This paper deals with the Bayesian inference on step-stress partially accelerated life tests using Type II progressive censored data in the presence of competing failure causes. Suppose that the occurrence time of the failure cause follows Pareto distribution under use stress levels. Based on the tampered failure rate model, the objective Bayesian estimates, Bayesian estimates, and E-Bayesian estimates of the unknown parameters and acceleration factor are obtained under the squared loss function. To evaluate the performance of the obtained estimates, the average relative errors (AREs and mean squared errors (MSEs are calculated. In addition, the comparisons of the three estimates of unknown parameters and acceleration factor for different sample sizes and different progressive censoring schemes are conducted through Monte Carlo simulations.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Diagnostic significance of the newest biomarkers of steatosis progression in patients with stable coronary heart disease, combined with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    I. I. Vakalyuk

    2018-03-01

    Full Text Available The purpose was to determine the diagnostic value of selenoprotein P and M30 fragments of cytokeratin 18 in conjunction with proinflammatory cytokines for early diagnosis and progression of non-alcoholic fatty liver disease (NAFLD in patients with stable coronary heart disease (CHD. Materials and methods. 140 patients with NAFLD and stable CHD of II-III functional classes were examined: 89 patients with non-alcoholic steatosis (Group I; 51 patients with non-alcoholic steatohepatitis (Group II. General-clinical examination, electrocardiography, coronary angiography, echocardiography, liver ultrasound, determination of cytokeratin 18 M30, selenoprotein P, TNF-alpha, interleukin-6, high-sensitivity C-reactive protein serum levels were performed to all patients. Results. The presence of liver steatosis of different degrees was established in all examined patients. However, the majority of the patients of Group I had steatosis of 1 and 2 degrees; in group 2 – steatosis of 3 degree prevailed. Selenoprotein P level in patients with steatosis of 1 degree was on 39.6 % higher compared with 0 degree; at 2 degree – it was by 2.8 times higher vs. its level in the control group and by 1.9 times vs. its level at steatosis of 1 degree (P < 0.05. Cytokeratin 18 M30 level at steatosis of 1 degree was by 1.8 times higher than its value in the control group; at 2 degree – it exceed this value by 2.3 times; at 3 degree – it reached its highest value (P < 0.05. TNF-alpha level at 1 degree of steatosis was by 2.5 times higher than its value in the control group; at 2 degree – it exceed this value by 3.7 times; at 3 degree – it was by 5.4; 2.2 and 1.5 times higher vs. its value at steatosis 0, 1 and 2 degrees (P < 0.05. Similar patterns were observed by IL-6 and hsCRP levels. Positive correlation relationships between serum selenoprotein P, cytokeratin 18 M30 and proinflammatory cytokines levels were revealed. Conclusion. Increasing of serum selenoprotein

  8. 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

  9. 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

  10. 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

  11. Significance of predictive models/risk calculators for HBV-related hepatocellular carcinoma

    OpenAIRE

    DONG Jing

    2015-01-01

    Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is a major public health problem in Southeast Asia. In recent years, researchers from Hong Kong and Taiwan have reported predictive models or risk calculators for HBV-associated HCC by studying its natural history, which, to some extent, predicts the possibility of HCC development. Generally, risk factors of each model involve age, sex, HBV DNA level, and liver cirrhosis. This article discusses the evolution and clinical significa...

  12. 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.

  13. 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

  14. 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

  15. The gene copy number of c-MET has a significant impact on progression-free survival in Korean patients with ovarian carcinoma.

    Science.gov (United States)

    Kim, Wook Youn; Shim, Seung-Hyuk; Jung, Ho Young; Dong, Meari; Kim, Soo-Nyung; Lee, Sun Joo

    2017-06-01

    The aim of this study was to compare the protein overexpression and gene copy number (GCN) of c-MET in ovarian carcinoma and to assess their prognostic roles in Korean women. MET protein expression and GCN status were determined using immunohistochemistry (IHC) and silver in situ hybridization, respectively, in 105 ovarian carcinomas comprising 63 serous, 12 mucinous, 20 clear cell, and 10 endometrioid carcinomas. All cases had been treated and followed up at a single institute in Seoul, Korea. MET protein overexpression was observed in 35 of 105 (33.3%) ovarian carcinomas, with IHC 2+ in 27 and IHC 3+ in 8. The overexpression rates of serous, mucinous, clear cell, and endometrioid carcinomas were 14.3%, 83.3%, 65.0%, and 30.0%, respectively. MET protein overexpression was significant in mucinous carcinoma (P ovarian carcinomas, respectively. Eleven of 12 cases were high-grade serous carcinomas. The remaining case was clear cell carcinoma. HP and GA were associated with a poor PFS (P = .001). There was no significant correlation between a high level of protein expression and increased GCN of MET (r = -0.127, P = .197). In Korean women, HP and GA of MET were significantly correlated with a poor PFS. MET GCN may serve as a biomarker for poor prognosis in patients with ovarian carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Modeling Geometry and Progressive Failure of Material Interfaces in Plain Weave Composites

    Science.gov (United States)

    Hsu, Su-Yuen; Cheng, Ron-Bin

    2010-01-01

    A procedure combining a geometrically nonlinear, explicit-dynamics contact analysis, computer aided design techniques, and elasticity-based mesh adjustment is proposed to efficiently generate realistic finite element models for meso-mechanical analysis of progressive failure in textile composites. In the procedure, the geometry of fiber tows is obtained by imposing a fictitious expansion on the tows. Meshes resulting from the procedure are conformal with the computed tow-tow and tow-matrix interfaces but are incongruent at the interfaces. The mesh interfaces are treated as cohesive contact surfaces not only to resolve the incongruence but also to simulate progressive failure. The method is employed to simulate debonding at the material interfaces in a ceramic-matrix plain weave composite with matrix porosity and in a polymeric matrix plain weave composite without matrix porosity, both subject to uniaxial cyclic loading. The numerical results indicate progression of the interfacial damage during every loading and reverse loading event in a constant strain amplitude cyclic process. However, the composites show different patterns of damage advancement.

  17. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone

    Directory of Open Access Journals (Sweden)

    Chiara Arrigoni

    2016-08-01

    Full Text Available Advanced breast cancer frequently metastasizes to bone through a multistep process involving the detachment of cells from the primary tumor, their intravasation into the bloodstream, adhesion to the endothelium and extravasation into the bone, culminating with the establishment of a vicious cycle causing extensive bone lysis. In recent years, the crosstalk between tumor cells and secondary organs microenvironment is gaining much attention, being indicated as a crucial aspect in all metastatic steps. To investigate the complex interrelation between the tumor and the microenvironment, both in vitro and in vivo models have been exploited. In vitro models have some advantages over in vivo, mainly the possibility to thoroughly dissect in controlled conditions and with only human cells the cellular and molecular mechanisms underlying the metastatic progression. In this article we will review the main results deriving from in vitro co-culture models, describing mechanisms activated in the crosstalk between breast cancer and bone cells which drive the different metastatic steps.

  18. 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.

  19. 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.

  20. 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.

  1. 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

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

    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 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. An event-based model for disease progression and its application in familial Alzheimer's disease and Huntington's disease

    NARCIS (Netherlands)

    Fonteijn, H.M.; Modat, M.; Clarkson, M.J.; Barnes, J.; Lehmann, M.; Hobbs, N.Z.; Scahill, R.I.; Tabrizi, S.J.; Ourselin, S.; Fox, N.C.; Alexander, D.C.

    2012-01-01

    Understanding the progression of neurological diseases is vital for accurate and early diagnosis and treatment planning. We introduce a new characterization of disease progression, which describes the disease as a series of events, each comprising a significant change in patient state. We provide

  9. Significance of kinetics for sorption on inorganic colloids: modeling and experiment interpretation issues.

    Science.gov (United States)

    Painter, S; Cvetkovic, V; Pickett, D; Turner, D R

    2002-12-15

    A two-site kinetic model for solute sorption on inorganic colloids is developed. The model quantifies linear first-order sorption on two types of sites ("fast" and "slow") characterized by two pairs of rates (forward and reverse). We use the model to explore data requirements for long-term predictive calculations of colloid-facilitated transport and to evaluate laboratory kinetic sorption data of Lu et al.. Five batch sorption data sets are considered with plutonium as the tracer and montmorillonite, hematite, silica, and smectite as colloids. Using asymptotic results applicable on the time scale of limited duration experiments, a robust estimation procedure is developed for the fast-site partitioning coefficient K(C) and the slow forward rate alpha. The estimated range of K(C) is 1.1-76 L/g, and the range for alpha is 0.0017-0.02 1/h. The fast reverse rate k(r) is estimated in the range 0.012-0.1 1/h. Comparison of one-site and two-site sorption interpretations reveals the difficulty in discriminating between the two models for montmorillonite and to a lesser extent for hematite. For silica and smectite, the two-site model clearly provides a better representation of the data as compared with a single site model. Kinetic data for silica are available for different colloid concentrations (0.2 g/L and 1 g/L). For the range of experimental conditions considered, alpha appears to be independent of colloid concentration.

  10. Calibration of a groundwater flow and contaminant transport computer model: Progress toward model validation

    International Nuclear Information System (INIS)

    Lee, R.R.; Ketelle, R.H.; Bownds, J.M.; Rizk, T.A.

    1989-09-01

    A groundwater flow and contaminant transport model calibration was performed to evaluate the ability of a typical, verified computer code to simulate groundwater tracer migration in the shallow aquifer of the Conasauga Group. Previously, standard practice site data interpretation and groundwater modeling resulted in inaccurate simulations of contaminant transport direction and rate compared with tracer migration behavior. The site's complex geology, the presence of flow in both fractured and weathered zones, and the transient character of flow in the shallow aquifer combined to render inaccurate assumptions of steady-state, homogeneous groundwater flow. The improvement of previous modeling results required iterative phases of conceptual model development, hypothesis testing, site field investigations, and modeling. The activities focused on generating a model grid that was compatible with site hydrogeologic conditions and on establishing boundary conditions based on site data. An annual average water table configuration derived from site data and fixed head boundary conditions was used as input for flow modeling. The contaminant transport model was combined with the data-driven flow model to obtain a preliminary contaminant plume. Calibration of the transport code was achieved by comparison with site tracer migration and concentration data. This study documents the influence of fractures and the transient character of flow and transport in the shallow aquifer. Although compatible with porous medium theory, site data demonstrate that the tracer migration pathway would not be anticipated using conventional porous medium analysis. 126 figs., 22 refs., 5 tabs

  11. Middle-School Science Students' Scientific Modelling Performances Across Content Areas and Within a Learning Progression

    Science.gov (United States)

    Bamberger, Yael M.; Davis, Elizabeth A.

    2013-01-01

    This paper focuses on students' ability to transfer modelling performances across content areas, taking into consideration their improvement of content knowledge as a result of a model-based instruction. Sixty-five sixth grade students of one science teacher in an urban public school in the Midwestern USA engaged in scientific modelling practices that were incorporated into a curriculum focused on the nature of matter. Concept-process models were embedded in the curriculum, as well as emphasis on meta-modelling knowledge and modelling practices. Pre-post test items that required drawing scientific models of smell, evaporation, and friction were analysed. The level of content understanding was coded and scored, as were the following elements of modelling performance: explanation, comparativeness, abstraction, and labelling. Paired t-tests were conducted to analyse differences in students' pre-post tests scores on content knowledge and on each element of the modelling performances. These are described in terms of the amount of transfer. Students significantly improved in their content knowledge for the smell and the evaporation models, but not for the friction model, which was expected as that topic was not taught during the instruction. However, students significantly improved in some of their modelling performances for all the three models. This improvement serves as evidence that the model-based instruction can help students acquire modelling practices that they can apply in a new content area.

  12. Progress in Modeling Global Atmospheric CO2 Fluxes and Transport: Results from Simulations with Diurnal Fluxes

    Science.gov (United States)

    Collatz, G. James; Kawa, R.

    2007-01-01

    Progress in better determining CO2 sources and sinks will almost certainly rely on utilization of more extensive and intensive CO2 and related observations including those from satellite remote sensing. Use of advanced data requires improved modeling and analysis capability. Under NASA Carbon Cycle Science support we seek to develop and integrate improved formulations for 1) atmospheric transport, 2) terrestrial uptake and release, 3) biomass and 4) fossil fuel burning, and 5) observational data analysis including inverse calculations. The transport modeling is based on meteorological data assimilation analysis from the Goddard Modeling and Assimilation Office. Use of assimilated met data enables model comparison to CO2 and other observations across a wide range of scales of variability. In this presentation we focus on the short end of the temporal variability spectrum: hourly to synoptic to seasonal. Using CO2 fluxes at varying temporal resolution from the SIB 2 and CASA biosphere models, we examine the model's ability to simulate CO2 variability in comparison to observations at different times, locations, and altitudes. We find that the model can resolve much of the variability in the observations, although there are limits imposed by vertical resolution of boundary layer processes. The influence of key process representations is inferred. The high degree of fidelity in these simulations leads us to anticipate incorporation of realtime, highly resolved observations into a multiscale carbon cycle analysis system that will begin to bridge the gap between top-down and bottom-up flux estimation, which is a primary focus of NACP.

  13. AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of Huntington's Disease.

    Science.gov (United States)

    Billes, Viktor; Kovács, Tibor; Hotzi, Bernadette; Manzéger, Anna; Tagscherer, Kinga; Komlós, Marcell; Tarnóci, Anna; Pádár, Zsolt; Erdős, Attila; Bjelik, Annamaria; Legradi, Adam; Gulya, Károly; Gulyás, Balázs; Vellai, Tibor

    2016-05-07

    Autophagy, a lysosome-mediated self-degradation process of eukaryotic cells, serves as a main route for the elimination of cellular damage [1-3]. Such damages include aggregated, oxidized or misfolded proteins whose accumulation can cause various neurodegenerative pathologies, including Huntington's disease (HD). Here we examined whether enhanced autophagic activity can alleviate neurophatological features in a Drosophila model of HD (the transgenic animals express a human mutant Huntingtin protein with a long polyglutamine repeat, 128Q). We have recently identified an autophagy-enhancing small molecule, AUTEN-67 (autophagy enhancer 67), with potent neuroprotective effects [4]. AUTEN-67 was applied to induce autophagic activity in the HD model used in this study. We showed that AUTEN-67 treatment interferes with the progressive accumulation of ubiquitinated proteins in the brain of Drosophila transgenic for the pathological 128Q form of human Huntingtin protein. The compound significantly improved the climbing ability and moderately extended the mean life span of these flies. Furthermore, brain tissue samples from human patients diagnosed for HD displayed increased levels of the autophagy substrate SQSTM1/p62 protein, as compared with controls. These results imply that AUTEN-67 impedes the progression of neurodegenerative symptoms characterizing HD, and that autophagy is a promising therapeutic target for treating this pathology. In humans, AUTEN-67 may have the potential to delay the onset and decrease the severity of HD.

  14. 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...... 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....... The outcome of this study contributes to a better understanding of uncertainty in WWTPs, and explicitly demonstrates the significance of secondary settling processes that are crucial elements of model prediction under dry and wet-weather loading conditions....

  15. 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.

  16. An Ecological-Transactional Model of Significant Risk Factors for Child Psychopathology in Outer Mongolia

    Science.gov (United States)

    Kohrt, Holbrook E.; Kohrt, Brandon A.; Waldman, Irwin; Saltzman, Kasey; Carrion, Victor G.

    2004-01-01

    The present study examined significant risk factors, including child maltreatment, for child psychopathology in a cross-cultural setting. Ninety-nine Mongolian boys, ages 3-10 years, were assessed. Primary caregivers (PCG) completed structured interviews including the Emory Combined Rating Scale (ECRS) and the Mood and Feelings Questionnaire…

  17. 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

  18. A Comparative Study Evaluating the Impact of Physical Exercise on Disease Progression in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Maliszewska-Cyna, Ewelina; Xhima, Kristiana; Aubert, Isabelle

    2016-05-06

    Evidence suggests that physical exercise can serve as a preventive strategy against Alzheimer's disease (AD). In contrast, much less is known about the impact of exercise when it is introduced after cognitive deficits are established. Using the TgCRND8 mouse model of amyloidosis, we compared the effects of exercise as an intervention strategy aimed at altering disease progression. Voluntary running for 1 month or 2 months was introduced in 3-month-old TgCRND8 mice, which exhibit amyloid-beta (Aβ) plaque pathology and cognitive deficits at this age. Specifically, we examined Aβ plaque load, spatial memory, and neurogenesis in the dentate gyrus in the hippocampus. After 1 month of running, TgCRND8 mice spent more time in the novel arm of the Y-maze compared to the familiar arms, indicating improved memory. The levels of doublecortin (a marker of immature neurons) were increased in TgCRND8 mice running for 1 month, but with no significant difference in the number of new mature neurons or plaque burden. As the disease progressed, running prevented further deficits in the Y-maze performance and hippocampal neurogenesis and it reduced plaque load pathology in TgCRND8 mice running for 2 months, compared to non-running transgenics. Therefore, the impact of running on memory, neurogenesis, and amyloid pathology was of greater significance when sustained through later stages of the disease.

  19. Quantitative magnetic resonance imaging (MRI) assessments of autosomal recessive polycystic kidney disease (ARPKD) progression and response to therapy in an animal model.

    Science.gov (United States)

    Erokwu, Bernadette O; Anderson, Christian E; Flask, Chris A; Dell, Katherine M

    2018-03-14

    Autosomal Recessive Polycystic Kidney Disease (ARPKD) is associated with significant mortality and morbidity and there are currently no disease-specific treatments available for ARPKD patients. One major limitation in establishing new therapies for ARPKD is a lack of sensitive measures of kidney disease progression. Magnetic Resonance Imaging (MRI) can provide multiple quantitative assessments of disease. We applied quantitative image analysis of high resolution (non-contrast) T2-weighted MRI techniques to study cystic kidney disease progression and response to therapy in the PCK rat model of ARPKD. Serial imaging over a 2 month period demonstrated that renal cystic burden (RCB, %)=[total cyst volume (TCV)/total kidney volume (TKV) × 100], TCV and, to a lesser extent, TKV, detected cystic kidney disease progression as well as the therapeutic effect of octreotide, a clinically-available medication shown previously to slow both kidney and liver disease progression in this model. All 3 MRI measures correlated significantly with histologic measures of renal cystic area, although the correlation of RCB and TCV was stronger than that of TKV. These preclinical MRI results provide a basis for applying these quantitative MRI techniques in clinical studies, to stage and measure progression in human ARPKD kidney disease.Pediatric Research accepted article preview online, 14 March 2018. doi:10.1038/pr.2018.24.

  20. Evaluating Alzheimer’s disease progression by modeling crosstalk network disruption

    Directory of Open Access Journals (Sweden)

    Haochen eLiu

    2016-01-01

    Full Text Available Aβ, tau and P-tau have been widely accepted as reliable markers for Alzheimer’s disease (AD. The crosstalk between these markers forms a complex network. AD may induce the integral variation and disruption of the network. The aim of this study was to develop a novel mathematic model based on a simplified crosstalk network to evaluate the disease progression of AD. The integral variation of the network is measured by three integral disruption parameters. The robustness of network is evaluated by network disruption probability. Presented results show that network disruption probability has a good linear relationship with Mini Mental State Examination (MMSE. The proposed model combined with Support vector machine (SVM achieves a relative high 10-fold cross-validated performance in classification of AD vs normal and mild cognitive impairment (MCI vs normal (95% accuracy, 95% sensitivity, 95% specificity for AD vs normal; 90% accuracy, 94% sensitivity, 83% specificity for MCI vs normal. This research evaluates the progression of AD and facilitates AD early diagnosis.

  1. 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.

  2. 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.

  3. Research Progress on Dark Matter Model Based on Weakly Interacting Massive Particles

    Science.gov (United States)

    He, Yu; Lin, Wen-bin

    2017-04-01

    The cosmological model of cold dark matter (CDM) with the dark energy and a scale-invariant adiabatic primordial power spectrum has been considered as the standard cosmological model, i.e. the ΛCDM model. Weakly interacting massive particles (WIMPs) become a prominent candidate for the CDM. Many models extended from the standard model can provide the WIMPs naturally. The standard calculations of relic abundance of dark matter show that the WIMPs are well in agreement with the astronomical observation of ΩDM h2 ≈0.11. The WIMPs have a relatively large mass, and a relatively slow velocity, so they are easy to aggregate into clusters, and the results of numerical simulations based on the WIMPs agree well with the observational results of cosmic large-scale structures. In the aspect of experiments, the present accelerator or non-accelerator direct/indirect detections are mostly designed for the WIMPs. Thus, a wide attention has been paid to the CDM model based on the WIMPs. However, the ΛCDM model has a serious problem for explaining the small-scale structures under one Mpc. Different dark matter models have been proposed to alleviate the small-scale problem. However, so far there is no strong evidence enough to exclude the CDM model. We plan to introduce the research progress of the dark matter model based on the WIMPs, such as the WIMPs miracle, numerical simulation, small-scale problem, and the direct/indirect detection, to analyze the criterion for discriminating the ;cold;, ;hot;, and ;warm; dark matter, and present the future prospects for the study in this field.

  4. 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)

  5. Research Pearls: The Significance of Statistics and Perils of Pooling. Part 2: Predictive Modeling.

    Science.gov (United States)

    Hohmann, Erik; Wetzler, Merrick J; D'Agostino, Ralph B

    2017-07-01

    The focus of predictive modeling or predictive analytics is to use statistical techniques to predict outcomes and/or the results of an intervention or observation for patients that are conditional on a specific set of measurements taken on the patients prior to the outcomes occurring. Statistical methods to estimate these models include using such techniques as Bayesian methods; data mining methods, such as machine learning; and classical statistical models of regression such as logistic (for binary outcomes), linear (for continuous outcomes), and survival (Cox proportional hazards) for time-to-event outcomes. A Bayesian approach incorporates a prior estimate that the outcome of interest is true, which is made prior to data collection, and then this prior probability is updated to reflect the information provided by the data. In principle, data mining uses specific algorithms to identify patterns in data sets and allows a researcher to make predictions about outcomes. Regression models describe the relations between 2 or more variables where the primary difference among methods concerns the form of the outcome variable, whether it is measured as a binary variable (i.e., success/failure), continuous measure (i.e., pain score at 6 months postop), or time to event (i.e., time to surgical revision). The outcome variable is the variable of interest, and the predictor variable(s) are used to predict outcomes. The predictor variable is also referred to as the independent variable and is assumed to be something the researcher can modify in order to see its impact on the outcome (i.e., using one of several possible surgical approaches). Survival analysis investigates the time until an event occurs. This can be an event such as failure of a medical device or death. It allows the inclusion of censored data, meaning that not all patients need to have the event (i.e., die) prior to the study's completion. Copyright © 2017 Arthroscopy Association of North America. Published by

  6. 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 thermal and moisture management of electronic enclosures are fields of high interest in recent years. It is now generally accepted that the protection of electronic devices is dependent on avoiding critical levels of relative humidity (typically 60–90%) during operations. Leveraging...... focus the parameter-value space, before shifting to 3D CFD models for final evaluations and verification. The approach results in a system capable of predicting optimum design features for the thermal and moisture management of electronic enclosures in a time-efficient and practically implementable...... 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...

  7. A significant advantage for trapped field magnet applications—A failure of the critical state model

    Science.gov (United States)

    Weinstein, Roy; Parks, Drew; Sawh, Ravi-Persad; Carpenter, Keith; Davey, Kent

    2015-10-01

    Ongoing research has increased achievable field in trapped field magnets (TFMs) to multi-Tesla levels. This has greatly increased the attractiveness of TFMs for applications. However, it also increases the already very difficult problem of in situ activation and reactivation of the TFMs. The pulsed zero-field-cool (ZFC) method of activation is used in most applications because it can be accomplished with much lower power and more modest equipment than field-cool activation. The critical state model (CSM) has been a reliable theoretical tool for experimental analysis and engineering design of TFMs and their applications for over a half-century. The activating field, BA, required to fully magnetize a TFM to its maximum trappable field, BT,max, using pulsed-ZFC is predicted by CSM to be R ≡ BA/BT,max ≥ 2.0. We report here experiments on R as a function of Jc, which find a monotonic decrease of R to 1.0 as Jc increases. The reduction to R = 1.0 reduces the power needed to magnetize TFMs by about an order of magnitude. This is a critical advantage for TFM applications. The results also indicate the limits of applicability of CSM, and shed light on the physics omitted from the model. The experimental results rule out heating effects and pinning center geometry as causes of the decrease in R. A possible physical cause is proposed.

  8. The significance of parks to physical activity and public health: a conceptual model.

    Science.gov (United States)

    Bedimo-Rung, Ariane L; Mowen, Andrew J; Cohen, Deborah A

    2005-02-01

    Park-based physical activity is a promising means to satisfy current physical activity requirements. However, there is little research concerning what park environmental and policy characteristics might enhance physical activity levels. This study proposes a conceptual model to guide thinking and suggest hypotheses. This framework describes the relationships between park benefits, park use, and physical activity, and the antecedents/correlates of park use. In this classification scheme, the discussion focuses on park environmental characteristics that could be related to physical activity, including park features, condition, access, aesthetics, safety, and policies. Data for these categories should be collected within specific geographic areas in or around the park, including activity areas, supporting areas, the overall park, and the surrounding neighborhood. Future research should focus on how to operationalize specific measures and methodologies for collecting data, as well as measuring associations between individual physical activity levels and specific park characteristics. Collaboration among many disciplines is needed.

  9. 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

  10. 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

  11. Pathology of Rodent Models of Intestinal Cancer: Progress Report and Recommendations

    Science.gov (United States)

    Washington, Mary Kay; Powell, Anne E.; Sullivan, Ruth; Sundberg, John; Wright, Nicholas; Coffey, Robert J.; Dove, William F.

    2013-01-01

    In October 2010, a pathology review of rodent models of intestinal neoplasia was held at The Jackson Laboratory. This review complemented 2 other concurrent events: a workshop on methods of modeling colon cancer in rodents and a conference on current issues in murine and human colon cancer. We summarize the results of the pathology review and the committee’s recommendations for tumor nomenclature. A virtual high-resolution image slide box of these models has been developed. This report discusses significant recent developments in rodent modeling of intestinal neoplasia, including the role of stem cells in cancer and the creation of models of metastatic intestinal cancer. PMID:23415801

  12. Human Atrial Cell Models to Analyse Haemodialysis-Related Effects on Cardiac Electrophysiology: Work in Progress

    Directory of Open Access Journals (Sweden)

    Elisa Passini

    2014-01-01

    Full Text Available During haemodialysis (HD sessions, patients undergo alterations in the extracellular environment, mostly concerning plasma electrolyte concentrations, pH, and volume, together with a modification of sympathovagal balance. All these changes affect cardiac electrophysiology, possibly leading to an increased arrhythmic risk. Computational modeling may help to investigate the impact of HD-related changes on atrial electrophysiology. However, many different human atrial action potential (AP models are currently available, all validated only with the standard electrolyte concentrations used in experiments. Therefore, they may respond in different ways to the same environmental changes. After an overview on how the computational approach has been used in the past to investigate the effect of HD therapy on cardiac electrophysiology, the aim of this work has been to assess the current state of the art in human atrial AP models, with respect to the HD context. All the published human atrial AP models have been considered and tested for electrolytes, volume changes, and different acetylcholine concentrations. Most of them proved to be reliable for single modifications, but all of them showed some drawbacks. Therefore, there is room for a new human atrial AP model, hopefully able to physiologically reproduce all the HD-related effects. At the moment, work is still in progress in this specific field.

  13. Micromechanics Modeling of Composites Subjected to Multiaxial Progressive Damage in the Constituents

    Science.gov (United States)

    Bednarcyk, Brett A.; Aboudi, Jacob; Amold, Steven M.

    2010-01-01

    The high-fidelity generalized method of cells composite micromechanics model is extended to include constituent-scale progressive damage via a proposed damage model. The damage model assumes that all material nonlinearity is due to damage in the form of reduced stiffness, and it uses six scalar damage variables (three for tension and three for compression) to track the damage. Damage strains are introduced that account for interaction among the strain components and that also allow the development of the damage evolution equations based on the constituent material uniaxial stress strain response. Local final-failure criteria are also proposed based on mode-specific strain energy release rates and total dissipated strain energy. The coupled micromechanics-damage model described herein is applied to a unidirectional E-glass/epoxy composite and a proprietary polymer matrix composite. Results illustrate the capability of the coupled model to capture the vastly different character of the monolithic (neat) resin matrix and the composite in response to far-field tension, compression, and shear loading.

  14. Thermophysical modeling of asteroids from WISE thermal infrared data - Significance of the shape model and the pole orientation uncertainties

    Science.gov (United States)

    Hanuš, J.; Delbo', M.; Ďurech, J.; Alí-Lagoa, V.

    2015-08-01

    In the analysis of thermal infrared data of asteroids by means of thermophysical models (TPMs) it is a common practice to neglect the uncertainty of the shape model and the rotational state, which are taken as an input for the model. Here, we present a novel method of investigating the importance of the shape model and the pole orientation uncertainties in the thermophysical modeling - the varied shape TPM (VS-TPM). Our method uses optical photometric data to generate various shape models that map the uncertainty in the shape and the rotational state. The TPM procedure is then run for all these shape models. We apply the implementation of the classical TPM as well as our VS-TPM to the convex shape models of several asteroids together with their thermal infrared data acquired by the NASA's Wide-field Infrared Survey Explorer (WISE) and compare the results. These show that the uncertainties of the shape model and the pole orientation can be very important (e.g., for the determination of the thermal inertia) and should be considered in the thermophysical analyses. We present thermophysical properties for six asteroids - (624) Hektor, (771) Libera, (1036) Ganymed, (1472) Muonio, (1627) Ivar, and (2606) Odessa.

  15. Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction.

    Directory of Open Access Journals (Sweden)

    Benjamin D Heavner

    2015-11-01

    Full Text Available We have compared 12 genome-scale models of the Saccharomyces cerevisiae metabolic network published since 2003 to evaluate progress in reconstruction of the yeast metabolic network. We compared the genomic coverage, overlap of annotated metabolites, predictive ability for single gene essentiality with a selection of model parameters, and biomass production predictions in simulated nutrient-limited conditions. We have also compared pairwise gene knockout essentiality predictions for 10 of these models. We found that varying approaches to model scope and annotation reflected the involvement of multiple research groups in model development; that single-gene essentiality predictions were affected by simulated medium, objective function, and the reference list of essential genes; and that predictive ability for single-gene essentiality did not correlate well with predictive ability for our reference list of synthetic lethal gene interactions (R = 0.159. We conclude that the reconstruction of the yeast metabolic network is indeed gradually improving through the iterative process of model development, and there remains great opportunity for advancing our understanding of biology through continued efforts to reconstruct the full biochemical reaction network that constitutes yeast metabolism. Additionally, we suggest that there is opportunity for refining the process of deriving a metabolic model from a metabolic network reconstruction to facilitate mechanistic investigation and discovery. This comparative study lays the groundwork for developing improved tools and formalized methods to quantitatively assess metabolic network reconstructions independently of any particular model application, which will facilitate ongoing efforts to advance our understanding of the relationship between genotype and cellular phenotype.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Myriocin Significantly Increases the Mortality of a Non-Mammalian Model Host during Candida Pathogenesis

    Science.gov (United States)

    de Melo, Nadja Rodrigues; Abdrahman, Ahmed; Greig, Carolyn; Mukherjee, Krishnendu; Thornton, Catherine; Ratcliffe, Norman A.; Vilcinskas, Andreas; Butt, Tariq M.

    2013-01-01

    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. PMID:24260135

  1. 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......) 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...

  2. Advanced Communications Architecture Demonstration Made Significant Progress

    Science.gov (United States)

    Carek, David Andrew

    2004-01-01

    Simulation for a ground station located at 44.5 deg latitude. The Advanced Communications Architecture Demonstration (ACAD) is a concept architecture to provide high-rate Ka-band (27-GHz) direct-to-ground delivery of payload data from the International Space Station. This new concept in delivering data from the space station targets scientific experiments that buffer data onboard. The concept design provides a method to augment the current downlink capability through the Tracking Data Relay Satellite System (TDRSS) Ku-band (15-GHz) communications system. The ACAD concept pushes the limits of technology in high-rate data communications for space-qualified systems. Research activities are ongoing in examining the various aspects of high-rate communications systems including: (1) link budget parametric analyses, (2) antenna configuration trade studies, (3) orbital simulations (see the preceding figure), (4) optimization of ground station contact time (see the following graph), (5) processor and storage architecture definition, and (6) protocol evaluations and dependencies.

  3. 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

  4. A Western-type diet accelerates tumor progression in an autochthonous mouse model of prostate cancer.

    Science.gov (United States)

    Llaverias, Gemma; Danilo, Christiane; Wang, Yu; Witkiewicz, Agnes K; Daumer, Kristin; Lisanti, Michael P; Frank, Philippe G

    2010-12-01

    Epidemiological studies have provided evidence suggesting an important role for diet and obesity in the development of cancer. Specifically, lipid nutrients of the diet have been identified as important regulators of tumor development and progression. In the present study, we have examined the role of dietary fat and cholesterol in the initiation and progression of prostate cancer using the well-characterized TRAMP mouse model. Consumption of a Western-type diet--that is, enriched in both fat and cholesterol--accelerated prostate tumor incidence and tumor burden compared to mice fed a control chow diet. Furthermore, we also show that this diet increased the extent and the histological grade of prostate tumors. These findings were confirmed by the presence of increased levels of protein markers of advanced tumors in prostates obtained from animals fed a Western-type diet compared to those obtained from control animals. Increased lung metastases in animals fed a Western-type diet were also observed. In addition, we found that with a Western diet, animals bearing tumors presented with reduced plasma cholesterol levels compared with animals fed a control diet. Finally, we show that tumors obtained from animals fed a Western-type diet displayed increased expression of the high-density lipoprotein receptor SR-BI and increased angiogenesis. Taken together, our data suggest that dietary fat and cholesterol play an important role in the development of prostate cancer.

  5. Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model

    Directory of Open Access Journals (Sweden)

    Gopalakrishnan Velliyur K

    2005-03-01

    Full Text Available Abstract Background The changes in gene expression profile as prostate cancer progresses from an androgen-dependent disease to an androgen-independent disease are still largely unknown. Methods We examined the gene expression profile in the LNCaP prostate cancer progression model during chronic treatment with Casodex using cDNA microarrays consisting of 2305 randomly chosen genes. Results Our studies revealed a representative collection of genes whose expression was differentially regulated in LNCaP cells upon treatment with Casodex. A set of 15 genes were shown to be highly expressed in Casodex-treated LNCaP cells compared to the reference sample. This set of highly expressed genes represents a signature collection unique to prostate cancer since their expression was significantly greater than that of the collective pool of ten cancer cell lines of the reference sample. The highly expressed signature collection included the hypoxia-related genes membrane metallo-endopeptidase (MME, cyclin G2, and Bcl2/adenovirus E1B 19 kDa (BNIP3. Given the roles of these genes in angiogenesis, cell cycle regulation, and apoptosis, we further analyzed their expression and concluded that these genes may be involved in the molecular changes that lead to androgen-independence in prostate cancer. Conclusion Our data indicate that one of the mechanisms of Casodex action in prostate cancer cells is induction of hypoxic gene expression.

  6. Multidisciplinary model-based-engineering for laser weapon systems: recent progress

    Science.gov (United States)

    Coy, Steve; Panthaki, Malcolm

    2013-09-01

    We are working to develop a comprehensive, integrated software framework and toolset to support model-based engineering (MBE) of laser weapons systems. MBE has been identified by the Office of the Director, Defense Science and Engineering as one of four potentially "game-changing" technologies that could bring about revolutionary advances across the entire DoD research and development and procurement cycle. To be effective, however, MBE requires robust underlying modeling and simulation technologies capable of modeling all the pertinent systems, subsystems, components, effects, and interactions at any level of fidelity that may be required in order to support crucial design decisions at any point in the system development lifecycle. Very often the greatest technical challenges are posed by systems involving interactions that cut across two or more distinct scientific or engineering domains; even in cases where there are excellent tools available for modeling each individual domain, generally none of these domain-specific tools can be used to model the cross-domain interactions. In the case of laser weapons systems R&D these tools need to be able to support modeling of systems involving combined interactions among structures, thermal, and optical effects, including both ray optics and wave optics, controls, atmospheric effects, target interaction, computational fluid dynamics, and spatiotemporal interactions between lasing light and the laser gain medium. To address this problem we are working to extend Comet™, to add the addition modeling and simulation capabilities required for this particular application area. In this paper we will describe our progress to date.

  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. 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.

  9. A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis

    Science.gov (United States)

    Alli, Rajshekhar; Nguyen, Phuong; Boyd, Kelli; Sundberg, John P.; Geiger, Terrence L.

    2011-01-01

    Alopecia areata is among the most prevalent autoimmune diseases, yet compared with other autoimmune conditions is not well studied. This in part results from limitations in the C3H/HeJ mouse and DEBR rat model systems most commonly used to study the disease, which display a low frequency and late onset. We describe a novel high incidence model for spontaneous alopecia areata. The 1MOG244 T cell expresses dual TCRA chains, one of which, when combined with the single TCRB present, promotes the development of CD8+ T cells with specificity for hair follicles. Retroviral transgenic mice expressing this TCR develop spontaneous alopecia areata at nearly 100% incidence. Disease initially follows a reticular pattern, with regionally cyclic episodes of hair loss and regrowth, and ultimately progresses to alopecia universalis. Alopecia development is associated with CD8+ T cell activation, migration into the intrafollicular region, and hair follicle destruction. The disease may be adoptively transferred with T lymphocytes, and is class I and not class II MHC-dependent. Pathologic T cells primarily express IFNG and IL17 early in disease, with dramatic increases in cytokine production and recruitment of IL4 and IL10 production with disease progression. Inhibition of individual cytokines did not significantly alter disease incidence, potentially indicating redundancy in cytokine responses. These results therefore characterize a new high incidence model for alopecia areata in C57BL/6J mice, the first to apply a monoclonal TCR, and indicate that class I MHC-restricted CD8+ T lymphocytes can independently mediate the pathologic response. PMID:22116824

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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

  15. Experimental and theoretical modelling of sand-water-object interaction under nonlinear progressive waves

    Science.gov (United States)

    Testik, Firat Yener

    An experimental and theoretical study has been conducted to obtain a fundamental understanding of the dynamics of the sand, water and a solid object interaction as progressive gravity waves impinge on a sloping beach. Aside from obvious scientific interest, this exceedingly complex physical problem is important for naval applications, related to the behavior of disk/cylindrical shaped objects (mines) in the coastal waters. To address this problem, it was divided into a set of simpler basic problems. To begin, nonlinear progressive waves were investigated experimentally in a wave tank for the case of a rigid (impermeable) sloping bottom. Parameterizations for wave characteristics were proposed and compared with the experiments. In parallel, a numerical wave tank model (NWT) was calibrated using experimental data from a single run, and wave field in the wave tank was simulated numerically for the selected experiments. Subsequently, a layer of sand was placed on the slope and bottom topography evolution processes (ripple and sandbar dynamics, bottom topography relaxation under variable wave forcing, etc.) were investigated experimentally. Models for those processes were developed and verified by experimental measurements. Flow over a circular cylinder placed horizontally on a plane wall was also studied. The far-flow field of the cylinder placed in the wave tank was investigated experimentally and numerical results from the NWT simulations were compared with the experimental data. In the mean time, the near-flow velocity/vorticity field around a short cylinder under steady and oscillatory flow was studied in a towing tank. Horseshoe vortex formation and periodic shedding were documented and explained. With the understanding gained through the aforementioned studies, dynamics and burial/scour around the bottom objects in the wave tank were studied. Possible scenarios on the behavior of the disk-shaped objects were identified and explained. Scour around 3D cylindrical

  16. 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.

  17. A comparison of predictive models for the onset of significant void at low pressures in forced-convection subcooled boiling

    International Nuclear Information System (INIS)

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

    1998-01-01

    The 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 paper. 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 (1974) seems to be the best model to predict OSV in vertical subcooled boiling flow

  18. Recent Progress in Mountain Permafrost Modelling using BTS in North America

    Science.gov (United States)

    Bonnaventure, P. P.; Lewkowicz, A. G.

    2009-04-01

    This presentation reports on progress in mapping and modelling mountain permafrost in North America over the past 5 years using the Basal Temperature of Snow (BTS) technique. It describes the methodology and some of the challenges in our current study aimed at modelling permafrost at a resolution of 30 x 30 m, for the entire southern half of the Yukon Territory, an area of 250 x 103 km2. This mountainous region differs from those in Europe and Asia by having a sparse population, very limited base-line information (such as climate data) and relatively low levels of infrastructure. However, major infrastructure projects, such as pipelines, roads, railways and mines are being proposed and climate change is expected to affect permafrost distribution and characteristics, including potentially triggering landslides and other natural hazards. The research involves developing BTS-based models validated using late-summer ground-truthing. Models have been created for three areas and work is currently underway in five other locations in the Yukon with possible future sites in northern British Columbia. Work to date has examined the suitability of the method in differing climatic zones, the interchangeability of models between areas, and the potential effects of climatic change. Current data collection is focused on the potential impact of atmospheric temperature inversions on permafrost distribution: each of the study areas has been equipped with a network of air, ground surface and permafrost surface temperature sensors as well as snow-depth monitoring devices, located within different topographic situations. Another challenge is the interpolation of permafrost probabilities between distant study areas: information developed from a data-base of more than 1500 rock glaciers is expected to help in this regard. The project, which is scheduled for completion within the next 12 months, will provide essential information relating to the spatial attributes and sensitivities of

  19. NAP (davunetide) modifies disease progression in a mouse model of severe neurodegeneration: protection against impairments in axonal transport.

    Science.gov (United States)

    Jouroukhin, Yan; Ostritsky, Regina; Assaf, Yaniv; Pelled, Galit; Giladi, Eliezer; Gozes, Illana

    2013-08-01

    NAP (davunetide) is a novel neuroprotective compound with mechanism of action that appears to involve microtubule (MT) stabilization and repair. To evaluate, for the first time, the impact of NAP on axonal transport in vivo and to translate it to neuroprotection in a severe neurodegeneration, the SOD1-G93A mouse model for amyotrophic lateral sclerosis (ALS) was used. Manganese-enhanced magnetic resonance imaging (MRI), estimating axonal transport rates, revealed a significant reduction of the anterograde axonal transport in the ALS mice compared to healthy control mice. Acute NAP treatment normalized axonal transport rates in these ALS mice. Tau hyperphosphorylation, associated with MT dysfunction and defective axonal transport, was discovered in the brains of the ALS mice and was significantly reduced by chronic NAP treatment. Furthermore, in healthy wild type (WT) mice, NAP reversed axonal transport disruption by colchicine, suggesting drug-dependent protection against axonal transport impairment through stabilization of the neuronal MT network. Histochemical analysis showed that chronic NAP treatment significantly protected spinal cord motor neurons against ALS-like pathology. Sequential MRI measurements, correlating brain structure with ALS disease progression, revealed a significant damage to the ventral tegmental area (VTA), indicative of impairments to the dopaminergic pathways relative to healthy controls. Chronic daily NAP treatment of the SOD1-G93A mice, initiated close to disease onset, delayed degeneration of the trigeminal, facial and hypoglossal motor nuclei as was significantly apparent at days 90-100 and further protected the VTA throughout life. Importantly, protection of the VTA was significantly correlated with longevity and overall, NAP treatment significantly prolonged life span in the ALS mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. 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

  1. Multi-targeted DATS Prevents Tumor Progression and Promotes Apoptosis in an Animal Model of Glioblastoma via HDAC-inhibition

    Science.gov (United States)

    Wallace, Gerald C; Haar, Catherine P; Vandergrift, W Alex; Giglio, Pierre; Ray, Swapan K; Patel, Sunil J; Banik, Naren L; Das, Arabinda

    2015-01-01

    Glioblastoma, the most malignant and lethal of brain tumors, remains incurable despite aggressive chemotherapy and surgical interventions. Few new chemotherapeutics for glioblastoma therapy have been explored in preclinical models, and some agents approved for have reached the clinical setting. However success rates are not significant. Previous investigations involving diallyl trisulfide (DATS), a garlic constituent, have indicated significant anti-cancer effects in vitro, including: glioblastoma growth inhibition, extrinsic and intrinsic apoptotic pathway activation, and cell death. DATS has also been shown to inhibit histone deacetylase activity and impede glioblastoma tumor progression. We hypothesized that DATS would block ectopic U87MG induced tumors by inhibiting multiple pro-apoptotic pathways via HDAC. To this end, ectopic tumors were developed in SCID mice and subsequently treated with daily intraperitoneal injections of DATS. Results indicate that a range of DATS doses (10μg/kg-10mg/kg) dose-dependently reduced tumor volume and number of mitotic cells within tumors after seven days. Our histological and biochemical assays demonstrate that DATS reduces mitosis in tumors, decreases HDAC activity, increases in acetylation of H3 and H4, inhibits cell cycle progression, promotes apoptotic cascade activation (m-calpian, Bax, caspase-3) and decreases pro-survival markers (Survivin, Bcl-2, p-Akt, c-Myc, mTOR, EGFR, VEGF). Our data also demonstrates an increase in p21/WAF1 expression, which correlates with increased p53 expression and MDM2 degradation following DATS treatment. Finally, histological assessment and enzyme assays suggest that even the highest dose of DATS administered in this study did not negatively impact hepatic function. These in vivo findings strongly support orthotopic investigation into the therapeutic potential of DATS and further review of the epigenetic mechanisms behind its anti-cancer activities. PMID:23754639

  2. Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model.

    Science.gov (United States)

    Lu, Yi; Zhang, Xiaoxia; Zhao, Liangcai; Yang, Changwei; Pan, Linlin; Li, Chen; Liu, Kun; Bai, Guanghui; Gao, Hongchang; Yan, Zhihan

    2018-01-01

    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 vivo 1 H 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.

  3. Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa.

    Science.gov (United States)

    Scott, Patrick A; de Castro, Juan P Fernandez; DeMarco, Paul J; Ross, Jason W; Njoka, Josephat; Walters, Eric; Prather, Randall S; McCall, Maureen A; Kaplan, Henry J

    2017-03-01

    We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy. The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age. Miniswine were euthanized and their retinas processed for morphologic evaluation at the light and electron microscopic level. Retinal morphology of a 36-month-old Tg miniswine also was examined. Wild type littermates reached mature scotopic and photopic retinal function by 3 months, while TgP23H miniswine showed abnormal scotopic ffERGs at the earliest time point, 1 month, and depressed photopic ffERGs after 2 months. Rod and cone photoreceptors (PR) exhibited morphologic abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone PR somata remaining after 2 months. The retinas showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells. The TgP23H founder miniswine showed cone PR with relatively intact morphology exclusive to the area centralis. The F1 Tg miniswine and the TgP23H founder miniswine exhibit similar retinopathy. TgP23H miniswine are a useful large-eye model to study pathogenesis and preservation cone PRs in humans with retinitis pigmentosa.

  4. 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

  5. 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

  6. A multiscale agent-based in silico model of liver fibrosis progression

    Directory of Open Access Journals (Sweden)

    Joyeeta eDutta-Moscato

    2014-05-01

    Full Text Available 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 histopathologic 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 (DAMP 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 histopathologic features observed in liver sections from rats treated with carbon tetrachloride (CCl4. 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 CCl4-treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing TNF-a vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathologic and macroscopic properties of CCl4-injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant insights into live fibrosis.

  7. 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.

  8. Construction of predictive models for recurrence and progression in >1000 patients with non-muscle-invasive bladder cancer (NMIBC) from a single centre.

    Science.gov (United States)

    Ali-El-Dein, Bedeir; Sooriakumaran, Prasanna; Trinh, Quoc-Dien; Barakat, Tamer S; Nabeeh, Adel; Ibrahiem, El-Housseiny I

    2013-06-01

    To construct predictive models based on the objectively calculated risks of progression and recurrence of non-muscle-invasive bladder cancer (NMIBC) in a large cohort of patients from a single centre. Between October 1984 and March 2009 a cohort of 1019 patients (877 males; 142 females; median age 44 years) with histologically confirmed NMIBC was included in this study. Among these patients, 74% received bacillus Calmette-Guérin (BCG)-based therapy. Complete transurethral resection of bladder tumour of all visible tumours was carried out in all patients, and the stage and grade were determined. Univariate analysis and multivariate Cox regression were used to identify predictors of recurrence and progression. The studied predictors included age, sex, stage, grade, associated carcinoma in situ, tumour size, multiplicity, macroscopic appearance of the tumour, history of recurrence and type of adjuvant intravesical therapy. Multivariate logistic regression models were used to develop the 12- and 60-month recurrence and progression predictive models. The predictive accuracy of the models was assessed for discrimination as well as calibration. The median (range) follow-up was 44 (6-254) months. On multivariate analysis, stage, multiplicity, history of recurrence and adjuvant intravesical therapy were significantly associated with recurrence, whereas for progression only tumour grade and size were significant independent predictors. The constructed nomograms had a 64.9% and 69.4% chance of correctly distinguishing between two patients, one destined to have a recurrence and one not at 12 and 60 months, respectively. The constructed nomograms had a 70.2% and 73.5% chance of correctly distinguishing between two patients, one destined to progress and one not at 12 and 60 months, respectively. All predictive models were well calibrated. Based on multivariate analysis of the studied prognostic factors nomograms for predicting recurrence and progression in NMIBC were

  9. 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.

  10. 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

  11. 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%) (poleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of lenticular opacity (i.e. cataract-like changes) it did not prevent the progression nor ameliorated pathologic lesions in the retina. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. 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...

  13. A view of progress in the numerical modeling of physical characteristics of the World Ocean in the light of sixty-year experience

    Science.gov (United States)

    Sarkisyan, A. S.

    2015-05-01

    In view of the 60th anniversary of the pioneering oceanographic work on the numerical modeling of dynamical characteristics of the ocean [1], the author has decided to present his view of the principal milestones in the progress of the numerical modeling of climatic characteristics of the ocean. This progress is shown schematically and conventionally as a single a table consisting of two lines: (A) synthesis of measurement data models and (B) theory and calculation of sea currents. Line A consists of the following stages: reference surface method, diagnostic method, diagnostics-adaptation, and four-dimensional analysis. Line B is as follows: Ekman's school, numerical modeling of a barotropic and then baroclinic ocean, modeling of individual basins with high resolution, and modeling of the World Ocean with high resolution and allowance for ice cover. This paper briefly reviews and analyzes the results of each of the abovementioned stages. The author sympathizes with line A because he believes that the most realistic results for characteristics of scientific interest are obtained by a synthesis of models and measurement data, with an optimal choice of the model integration time. Unfortunately, studies in both directions have often used unreasonably long integration times (50-100 years). In this case, models even with a high resolution (0.1° of grid spacing) become inadequate and analyze strange characteristics, such as meridional overturning or kinetic energy averaged over the entire column of the world ocean, which actually have no scientific significance.

  14. 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.

  15. Will PEDF Therapy Reverse Chronic Demyelination and Prevent Axon Loss in a Murine Model of Progressive Multiple Sclerosis

    Science.gov (United States)

    2015-12-01

    Multiple Sclerosis ? PRINCIPAL INVESTIGATOR: David Pleasure MD CONTRACTING ORGANIZATION: University of California Davis, CA 95618 REPORT DATE...Murine Model of Progressive Multiple Sclerosis ? 5b. GRANT NUMBER W81XWH-12-1-0566 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Pleasure MD 5d...enhance central nervous system (CNS) remyelination and preserve CNS axons in mouse models of multiple sclerosis models. After determining the dosage of

  16. MAMM (Methane and other greenhouse gases in the Arctic - Measurements, process studies and Modelling) progress report

    Science.gov (United States)

    Nisbet, E. G.; Pyle, J. A.

    2012-12-01

    MAMM consortium (led by JA Pyle, Univ. Cambridge, with partners from Univ. East Anglia; Univ. Manchester; Royal Holloway, Univ. of London; NERC Centre for Ecology and Hydrology). The UK MAMM project (Methane and other greenhouse gases in the Arctic - Measurements, process studies and Modelling) is designed to improve quantitative knowledge of Arctic methane and other greenhouse gases from various sources (e.g. wetlands, natural gas, clathrates), to determine magnitudes and spatial distributions, and to develop process understanding (e.g. dependence of fluxes on temperature). In Arctic Finland, Sweden, Norway and Spitsbergen, intensive low-level aircraft campaigns (flights in spring, summer, autumn 2012 and 2013, with the UK FAAM BAe146 aircraft) are designed to measure concentrations of CH4 and other gases across the Arctic by time and location, with in situ sampling for δ13CCH4 at selected sites on land (Zeppelin, Pallas, Alert) and Keeling-plot diel determination of wetland source signatures. High altitude flights sampled stratosphere-troposphere exchange in the Arctic to assess the impact of the polar vortex on methane isotope budgets. Methane column profiles are measured by combining ground based eddy covariance and chamber measurements with aircraft measurements, using a landscape-scale box model approach and flying up and downwind of source regions. Airborne remote sensing is being used to retrieve CH4 columns for comparison with in-situ profiles and testing of hyperspectral retrieval methods from satellite platforms. Longer-term time series measurements are also being established in Kjølnes, northern Norway, for a range of greenhouse and related species via continuous or flask/bag sampling. Modelling studies are in progress to assess the overall Arctic influence on the global methane budget, including detailed back-trajectory analysis of the measurements, especially the isotopic data, to identify sources of methane by location, type (e.g. gasfield, wetland

  17. 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.

  18. 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)

  19. 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.

  20. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

    Science.gov (United States)

    Bobkova, N V; Lyabin, D N; Medvinskaya, N I; Samokhin, A N; Nekrasov, P V; Nesterova, I V; Aleksandrova, I Y; Tatarnikova, O G; Bobylev, A G; Vikhlyantsev, I M; Kukharsky, M S; Ustyugov, A A; Polyakov, D N; Eliseeva, I A; Kretov, D A; Guryanov, S G; Ovchinnikov, L P

    2015-01-01

    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.

  1. Durability Modeling of Environmental Barrier Coating (EBC Using Finite Element Based Progressive Failure Analysis

    Directory of Open Access Journals (Sweden)

    Ali Abdul-Aziz

    2014-01-01

    Full Text Available The necessity for a protecting guard for the popular ceramic matrix composites (CMCs is getting a lot of attention from engine manufacturers and aerospace companies. The CMC has a weight advantage over standard metallic materials and more performance benefits. However, these materials undergo degradation that typically includes coating interface oxidation as opposed to moisture induced matrix which is generally seen at a higher temperature. Additionally, other factors such as residual stresses, coating process related flaws, and casting conditions may influence the degradation of their mechanical properties. These durability considerations are being addressed by introducing highly specialized form of environmental barrier coating (EBC that is being developed and explored in particular for high temperature applications greater than 1100°C. As a result, a novel computational simulation approach is presented to predict life for EBC/CMC specimen using the finite element method augmented with progressive failure analysis (PFA that included durability, damage tracking, and material degradation model. The life assessment is carried out using both micromechanics and macromechanics properties. The macromechanics properties yielded a more conservative life for the CMC specimen as compared to that obtained from the micromechanics with fiber and matrix properties as input.

  2. Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

    Science.gov (United States)

    Chaplain, Mark A. J.; Powathil, Gibin G.

    Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.

  3. 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.

  4. Progressive Spatial Processing Deficits in a Mouse Model of the Fragile X Premutation

    Science.gov (United States)

    Hunsaker, Michael R.; Wenzel, H. Jürgen; Willemsen, Rob; Berman, Robert F.

    2012-01-01

    Fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that is the result of a CGG trinucleotide repeat expansion in the range of 55-200 in the 5’ UTR of the FMR1 gene. To better understand the progression of this disorder, a knock-in (CGG KI) mouse was developed by substituting the mouse CGG8 trinucleotide repeat with an expanded CGG98 repeat from human origin. It has been shown that this mouse shows deficits on the water maze at 52 weeks of age. In the present study, this CGG KI mouse model of FXTAS was tested on behavioral tasks that emphasize spatial information processing. The results demonstrate that at 12 and 24 weeks of age, CGG KI mice were unable to detect a change in the distance between two objects (metric task), but showed intact detection of a transposition of the objects (topological task). At 48 weeks of age, CGG KI mice were unable to detect either change in object location. These data indicate that hippocampal-dependent impairments in spatial processing may occur prior to parietal cortex-dependent impairments in FXTAS. PMID:20001115

  5. Nested arithmetic progressions of oscillatory phases in Olsen's enzyme reaction model

    Science.gov (United States)

    Gallas, Marcia R.; Gallas, Jason A. C.

    2015-06-01

    We report some regular organizations of stability phases discovered among self-sustained oscillations of a biochemical oscillator. The signature of such organizations is a nested arithmetic progression in the number of spikes of consecutive windows of periodic oscillations. In one of them, there is a main progression of windows whose consecutive number of spikes differs by one unit. Such windows are separated by a secondary progression of smaller windows whose number of spikes differs by two units. Another more complex progression involves a fan-like nested alternation of stability phases whose number of spikes seems to grow indefinitely and to accumulate methodically in cycles. Arithmetic progressions exist abundantly in several control parameter planes and can be observed by tuning just one among several possible rate constants governing the enzyme reaction.

  6. Building a Progressive-Situational Model of Post-Diagnosis Information Seeking for Parents of Individuals With Down Syndrome

    Science.gov (United States)

    Gibson, Amelia N.

    2016-01-01

    This grounded theory study used in-depth, semi-structured interview to examine the information-seeking behaviors of 35 parents of children with Down syndrome. Emergent themes include a progressive pattern of behavior including information overload and avoidance, passive attention, and active information seeking; varying preferences between tacit and explicit information at different stages; and selection of information channels and sources that varied based on personal and situational constraints. Based on the findings, the author proposes a progressive model of health information seeking and a framework for using this model to collect data in practice. The author also discusses the practical and theoretical implications of a responsive, progressive approach to understanding parents’ health information–seeking behavior. PMID:28462351

  7. Building a Progressive-Situational Model of Post-Diagnosis Information Seeking for Parents of Individuals With Down Syndrome.

    Science.gov (United States)

    Gibson, Amelia N

    2016-01-01

    This grounded theory study used in-depth, semi-structured interview to examine the information-seeking behaviors of 35 parents of children with Down syndrome. Emergent themes include a progressive pattern of behavior including information overload and avoidance, passive attention, and active information seeking; varying preferences between tacit and explicit information at different stages; and selection of information channels and sources that varied based on personal and situational constraints. Based on the findings, the author proposes a progressive model of health information seeking and a framework for using this model to collect data in practice. The author also discusses the practical and theoretical implications of a responsive, progressive approach to understanding parents' health information-seeking behavior.

  8. Methods for significance testing of categorical covariates in logistic regression models after multiple imputation: power and applicability analysis.

    Science.gov (United States)

    Eekhout, Iris; van de Wiel, Mark A; Heymans, Martijn W

    2017-08-22

    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 significantly contributes to the model, different methods are available. For example pooling chi-square tests with multiple degrees of freedom, pooling likelihood ratio test statistics, and pooling based on the covariance matrix of the regression model. These methods are more complex than RR and are not available in all mainstream statistical software packages. In addition, they do not always obtain optimal power levels. We argue that the median of the p-values from the overall significance tests from the analyses on the imputed datasets can be used as an alternative pooling rule for categorical variables. The aim of the current study is to compare different methods to test a categorical variable for significance after multiple imputation on applicability and power. In a large simulation study, we demonstrated the control of the type I error and power levels of different pooling methods for categorical variables. This simulation study showed that for non-significant categorical covariates the type I error is controlled and the statistical power of the median pooling rule was at least equal to current multiple parameter tests. An empirical data example showed similar results. It can therefore be concluded that using the median of the p-values from the imputed data analyses is an attractive and easy to use alternative method for significance testing of categorical variables.

  9. 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.

  10. 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

  11. Progressive refining of spatial and temporal resolutions in a hydrological model: how far should we go?

    Science.gov (United States)

    de Lavenne, Alban; Ficchi, Andrea; Goullet, Julien

    2017-04-01

    significantly improved at refined resolutions for events with convective trends. Indeed, a synergy between spatial and temporal resolutions is obtained when refining both of them at the same time. These encouraging results suggest that in a flood forecasting context, in particular for fast response catchments subject to intense events, a significant increase of model performance can be expected by refining both resolutions. References de Lavenne, A.; Thirel, G.; Andréassian, V.; Perrin, C. & Ramos, M.-H. (2016), 'Spatial variability of the parameters of a semi-distributed hydrological model', PIAHS 373, 87-94. Goullet, J. (2016) 'A la recherche des résolutions spatiales et temporelles caractéristiques du comportement hydrologique d'un bassin versant', Master's thesis, UPMC, Paris.

  12. Forward-looking infrared imaging predicts ultimate burn depth in a porcine vertical injury progression model.

    Science.gov (United States)

    Miccio, Joseph; Parikh, Shruti; Marinaro, Xavier; Prasad, Atulya; McClain, Steven; Singer, Adam J; Clark, Richard A F

    2016-03-01

    relevant criterion standard, temperature minima at 2 days after burn was found to be the most sensitive and specific test. FLIR imaging is a fast and simple tool that has been shown to predict burn wound outcome in a porcine vertical injury progression model. Data showed that more severe burn wounds get cooler between 1 and 2 days after burn. We found four analytic methods of FLIR images that were predictive of burn progression at 1 and 2 days after burn; however, temperature minima 2 days after burn appeared to be the best predictive test for injury progression to a full-thickness burn. Although these results must be validated in clinical studies, FLIR imaging has the potential to aid clinicians in assessing burn severity and thereby assisting in burn wound management. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  13. Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model.

    Science.gov (United States)

    Muhanna, Nidal; Mepham, Adam; Mohamadi, Reza M; Chan, Harley; Khan, Tahsin; Akens, Margarete; Besant, Justin D; Irish, Jonathan; Kelley, Shana O

    2015-10-01

    Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model. The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Adipose tissue-derived stem cells in combination with xanthan gum attenuate osteoarthritis progression in an experimental rat model.

    Science.gov (United States)

    Mei, Li; Shen, Bojiang; Xue, Jiajun; Liu, Shaoying; Ma, Aibin; Liu, Fuyan; Shao, Huarong; Chen, Jianying; Chen, Qixin; Liu, Fei; Ying, Yong; Ling, Peixue

    2017-12-09

    The current study explored the efficacy of an intra-articular (IA) injection of allogeneic adipose tissue-derived stem cells (ADSCs) combined with xanthan gum (XG) in a rat osteoarthritis (OA) model. We confirmed that XG significantly inproved proliferation of ADSCs in a dose dependent manner in vitro. The rat OA model was induced by an anterior cruciate ligament transection (ACLT), and at 4 weeks after surgery, rats were divided into four groups: the XG-ADSCs group, the ADSCs group, the XG group and the phosphate-buffered saline (PBS) group. A single dose of 1 × 10 6 allogeneic ADSCs suspended in 1% XG, ADSCs suspended in PBS, 1% XG alone or PBS alone was injected into the OA joint of rats in the respective treatment groups. Rats were sacrificed at 8 weeks after surgery. Treatment outcomes were evaluated by weight-bearing control of the hind limbs, gross morphological analysis, histological analysis and specific staining of articular cartilage, and measurement of inflammatory factors in synovial fluid. For the rats in the XG-ADSC-s and ADSCs-treated groups, the weight-bearing percentage of the right hind limb was significantly increased compared to that in the PBS group and was sustained over 4 weeks. However, the positive effect in the XG-ADSCs group was significantly greater than that in the ADSCs group. For the rats in the XG group, the efficacy decreased during the third week after surgery. The articular cartilage was relatively normal in the XG-ADSCs group, and moderate degeneration was observed in the ADSCs and XG groups. ADSCs and XG-ADSC treatments significantly decreased the concentrations of IL-1β, TNF-α, MMP-3 and MMP-13 in synovial fluid; however, the attenuating effect of the XG-ADSCs treatment was significantly enhanced compared with that of the ADSCs treatment alone. These results indicate that a single IA injection of allogeneic ADSCs combined with XG efficiently attenuated OA progression with a therapeutic effect that was significantly

  15. Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.

    Science.gov (United States)

    Zhang, W F; Li, Z T; Fang, J J; Wang, G B; Yu, Y; Liu, Z Q; Wu, Y N; Zheng, S S; Cai, L

    2017-01-01

    The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.

  16. PD-0332991, a CDK4/6 Inhibitor, Significantly Prolongs Survival in a Genetically Engineered Mouse Model of Brainstem Glioma

    Science.gov (United States)

    Barton, Kelly L.; Misuraca, Katherine; Cordero, Francisco; Dobrikova, Elena; Min, Hooney D.; Gromeier, Matthias; Kirsch, David G.; Becher, Oren J.

    2013-01-01

    Diffuse intrinsic pontine glioma (DIPG) is an incurable tumor that arises in the brainstem of children. To date there is not a single approved drug to effectively treat these tumors and thus novel therapies are desperately needed. Recent studies suggest that a significant fraction of these tumors contain alterations in cell cycle regulatory genes including amplification of the D-type cyclins and CDK4/6, and less commonly, loss of Ink4a-ARF leading to aberrant cell proliferation. In this study, we evaluated the therapeutic approach of targeting the cyclin-CDK-Retinoblastoma (Rb) pathway in a genetically engineered PDGF-B-driven brainstem glioma (BSG) mouse model. We found that PD-0332991 (PD), a CDK4/6 inhibitor, induces cell-cycle arrest in our PDGF-B; Ink4a-ARF deficient model both in vitro and in vivo. By contrast, the PDGF-B; p53 deficient model was mostly resistant to treatment with PD. We noted that a 7-day treatment course with PD significantly prolonged survival by 12% in the PDGF-B; Ink4a-ARF deficient BSG model. Furthermore, a single dose of 10 Gy radiation therapy (RT) followed by 7 days of treatment with PD increased the survival by 19% in comparison to RT alone. These findings provide the rationale for evaluating PD in children with Ink4a-ARF deficient gliomas. PMID:24098593

  17. PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma.

    Directory of Open Access Journals (Sweden)

    Kelly L Barton

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is an incurable tumor that arises in the brainstem of children. To date there is not a single approved drug to effectively treat these tumors and thus novel therapies are desperately needed. Recent studies suggest that a significant fraction of these tumors contain alterations in cell cycle regulatory genes including amplification of the D-type cyclins and CDK4/6, and less commonly, loss of Ink4a-ARF leading to aberrant cell proliferation. In this study, we evaluated the therapeutic approach of targeting the cyclin-CDK-Retinoblastoma (Rb pathway in a genetically engineered PDGF-B-driven brainstem glioma (BSG mouse model. We found that PD-0332991 (PD, a CDK4/6 inhibitor, induces cell-cycle arrest in our PDGF-B; Ink4a-ARF deficient model both in vitro and in vivo. By contrast, the PDGF-B; p53 deficient model was mostly resistant to treatment with PD. We noted that a 7-day treatment course with PD significantly prolonged survival by 12% in the PDGF-B; Ink4a-ARF deficient BSG model. Furthermore, a single dose of 10 Gy radiation therapy (RT followed by 7 days of treatment with PD increased the survival by 19% in comparison to RT alone. These findings provide the rationale for evaluating PD in children with Ink4a-ARF deficient gliomas.

  18. Progress in model development to quantify High Explosive Violent Response (HEVR) to mechancial insult

    Energy Technology Data Exchange (ETDEWEB)

    Reaugh, J E

    2008-07-29

    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.

  19. Significance of hypoxia for tumor response to radiation: Mathematical modeling and analysis of local control and clonogenic assay data

    International Nuclear Information System (INIS)

    Buffa, Francesca Meteora

    2002-01-01

    Various hypotheses for radiation local tumor control probability (ltcp) were modeled, and assessed against local tumor control (LTC) and clonogenic assay (CA) data. For head-and-neck tumors receiving low-LET external-beam irradiation, the best model was a Poisson ltcp accounting for cell repopulation, hypoxia, and tumor volume dependence of radiosensitivity (α). This confirmed that hypoxia is limiting LTC of these tumors, with the magnitude depending upon tumor volume. However, LTC of cervical carcinoma receiving external-beam irradiation and brachytherapy was well described by a model not accounting for hypoxia. Furthermore, when the survival fraction at 2 Gy (SF 2 ) and colony forming efficiency (CFE) measured for individual patients were incorporated into this model, very good correlation with LTC was seen (p=0.0004). After multivariate analysis, this model was the best independent prognostic factor for LTC and patient survival. Furthermore, no difference in prediction was seen when a model based on birth-and-death stochastic theory was used. Two forms of hypoxia are known to be present in tumors: diffusion-limited, chronic hypoxia (CH), and acute, transient hypoxia (TH). A modeling study on WiDr multicellular spheroids showed that the CH effect on LTC is significantly lower than expected from CA. This could arise from energy charge depletion accompanying CH, reducing the number of proliferating clonogenic cells that can repair radiation damage, and thus mitigating the radioresistance of CH cells. This suggests that TH, rather than CH, may be the limiting factor for in vivo LTC. Finally, by computing ltcp using Monte Carlo calculated dose distributions, it was shown that Monte Carlo statistical noise can cause an underestimation of ltcp, with the magnitude depending upon the model hypotheses

  20. 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.

  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. Analyzing Students' Learning Progressions Throughout a Teaching Sequence on Acoustic Properties of Materials with a Model-Based Inquiry Approach

    Science.gov (United States)

    Hernández, María Isabel; Couso, Digna; Pintó, Roser

    2015-04-01

    The study we have carried out aims to characterize 15- to 16-year-old students' learning progressions throughout the implementation of a teaching-learning sequence on the acoustic properties of materials. Our purpose is to better understand students' modeling processes about this topic and to identify how the instructional design and actual enactment influences students' learning progressions. This article presents the design principles which elicit the structure and types of modeling and inquiry activities designed to promote students' development of three conceptual models. Some of these activities are enhanced by the use of ICT such as sound level meters connected to data capture systems, which facilitate the measurement of the intensity level of sound emitted by a sound source and transmitted through different materials. Framing this study within the design-based research paradigm, it consists of the experimentation of the designed teaching sequence with two groups of students ( n = 29) in their science classes. The analysis of students' written productions together with classroom observations of the implementation of the teaching sequence allowed characterizing students' development of the conceptual models. Moreover, we could evidence the influence of different modeling and inquiry activities on students' development of the conceptual models, identifying those that have a major impact on students' modeling processes. Having evidenced different levels of development of each conceptual model, our results have been interpreted in terms of the attributes of each conceptual model, the distance between students' preliminary mental models and the intended conceptual models, and the instructional design and enactment.

  4. 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

  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. 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

  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. Impaired osteoclast homeostasis in the cystatin B-deficient mouse model of progressive myoclonus epilepsy

    Directory of Open Access Journals (Sweden)

    Otto Manninen

    2015-12-01

    Full Text Available Progressive myoclonus epilepsy of Unverricht–Lundborg type (EPM1 is an autosomal recessively inherited disorder characterized by incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures with onset at the age of 6 to 16 years. EPM1 patients also exhibit a range of skeletal changes, e.g., thickened frontal cranial bone, arachnodactyly and scoliosis. Mutations in the gene encoding cystatin B (CSTB underlie EPM1. CSTB is an inhibitor of cysteine cathepsins, including cathepsin K, a key enzyme in bone resorption by osteoclasts. CSTB has previously been shown to protect osteoclasts from experimentally induced apoptosis and to modulate bone resorption in vitro. Nevertheless, its physiological function in bone and the cause of the bone changes in patients remain unknown. Here we used the CSTB-deficient mouse (Cstb−/− model of EPM1 to evaluate the contribution of defective CSTB protein function on bone pathology and osteoclast differentiation and function. Micro-computed tomography of hind limbs revealed thicker trabeculae and elevated bone mineral density in the trabecular bone of Cstb−/− mice. Histology from Cstb−/− mouse bones showed lower osteoclast count and thinner growth plates in long bones. Bone marrow-derived osteoclast cultures revealed lower osteoclast number and size in the Cstb−/− group. Cstb−/− osteoclasts formed less and smaller resorption pits in an in vitro assay. This impaired resorptive capacity was likely due to a decrease in osteoclast numbers and size. These data imply that the skeletal changes in Cstb−/− mice and in EPM1 patients are a result of CSTB deficiency leading to impaired osteoclast formation and consequently compromised resorptive capacity. These results suggest that the role of CSTB in osteoclast homeostasis and modulation of bone metabolism extends beyond cathepsin K regulation.

  9. A review and synthesis of late Pleistocene extinction modeling: progress delayed by mismatches between ecological realism, interpretation, and methodological transparency.

    Science.gov (United States)

    Yule, Jeffrey V; Fournier, Robert J; Jensen, Christopher X J; Yang, Jinyan

    2014-06-01

    Late Pleistocene extinctions occurred globally over a period of about 50,000 years, primarily affecting mammals of > or = 44 kg body mass (i.e., megafauna) first in Australia, continuing in Eurasia and, finally, in the Americas. Polarized debate about the cause(s) of the extinctions centers on the role of climate change and anthropogenic factors (especially hunting). Since the late 1960s, investigators have developed mathematical models to simulate the ecological interactions that might have contributed to the extinctions. Here, we provide an overview of the various methodologies used and conclusions reached in the modeling literature, addressing both the strengths and weaknesses of modeling as an explanatory tool. Although late Pleistocene extinction models now provide a solid foundation for viable future work, we conclude, first, that single models offer less compelling support for their respective explanatory hypotheses than many realize; second, that disparities in methodology (both in terms of model parameterization and design) prevent meaningful comparison between models and, more generally, progress from model to model in increasing our understanding of these extinctions; and third, that recent models have been presented and possibly developed without sufficient regard for the transparency of design that facilitates scientific progress.

  10. Measurement and apportionment of radon source terms for modeling indoor environments. Final progress report, March 1990--August 1992

    Energy Technology Data Exchange (ETDEWEB)

    Harley, N.H.

    1992-12-31

    During the present 2 1/2 year contract period, we have made significant Progress in modeling the source apportionment of indoor {sup 222}Rn and in {sup 222}Rn decay product dosimetry. Two additional areas were worked on which we believe are useful for the DOE Radon research Program. One involved an analysis of the research house data, grouping the hourly house {sup 222}Rn measurements into 2 day, 7 day and 90 day intervals to simulate the response of passive monitors. Another area requiring some attention resulted in a publication of 3 years of our indoor/outdoor measurements in a high-rise apartment. Little interest has been evinced in apartment measurements yet 20% of the US population lives in multiple-family dwellings, not in contact with the ground. These data together with a summary of all other published data on apartments showed that apartments have only about 50% greater {sup 222}Rn concentration than the measured outdoor {sup 222}Rn. Apartment dwellers generally represent a low risk group regarding {sup 222}Rn exposure. The following sections describe the main projects in some detail.

  11. 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.

  12. Protective Effect of a Lipid-Based Preparation from Mycobacterium smegmatis in a Murine Model of Progressive Pulmonary Tuberculosis

    Science.gov (United States)

    García, Maria de los Angeles; Lanio, Maria E.; Tirado, Yanely; Alvarez, Nadine; Puig, Alina; Aguilar, Alicia; Canet, Liem; Mata Espinoza, Dulce; Barrios Payán, Jorge; Sarmiento, María Elena; Hernández-Pando, Rogelio; Norazmi, Mohd-Nor; Acosta, Armando

    2014-01-01

    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. PMID:25548767

  13. An automated nowcasting model of significant instability events in the flight terminal area of Rio de Janeiro, Brazil

    Science.gov (United States)

    Borges França, Gutemberg; Valdonel de Almeida, Manoel; Rosette, Alessana C.

    2016-05-01

    This paper presents a novel model, based on neural network techniques, to produce short-term and local-specific forecasts of significant instability for flights in the terminal area of Galeão Airport, Rio de Janeiro, Brazil. Twelve years of data were used for neural network training/validation and test. Data are originally from four sources: (1) hourly meteorological observations from surface meteorological stations at five airports distributed around the study area; (2) atmospheric profiles collected twice a day at the meteorological station at Galeão Airport; (3) rain rate data collected from a network of 29 rain gauges in the study area; and (4) lightning data regularly collected by national detection networks. An investigation was undertaken regarding the capability of a neural network to produce early warning signs - or as a nowcasting tool - for significant instability events in the study area. The automated nowcasting model was tested using results from five categorical statistics, indicated in parentheses in forecasts of the first, second, and third hours, respectively, namely proportion correct (0.99, 0.97, and 0.94), BIAS (1.10, 1.42, and 2.31), the probability of detection (0.79, 0.78, and 0.67), false-alarm ratio (0.28, 0.45, and 0.73), and threat score (0.61, 0.47, and 0.25). Possible sources of error related to the test procedure are presented and discussed. The test showed that the proposed model (or neural network) can grab the physical content inside the data set, and its performance is quite encouraging for the first and second hours to nowcast significant instability events in the study area.

  14. Blood pressure and the risk of chronic kidney disease progression using multistate marginal structural models in the CRIC Study.

    Science.gov (United States)

    Stephens-Shields, Alisa J; Spieker, Andrew J; Anderson, Amanda; Drawz, Paul; Fischer, Michael; Sozio, Stephen M; Feldman, Harold; Joffe, Marshall; Yang, Wei; Greene, Tom

    2017-11-20

    In patients with chronic kidney disease (CKD), clinical interest often centers on determining treatments and exposures that are causally related to renal progression. Analyses of longitudinal clinical data in this population are often complicated by clinical competing events, such as end-stage renal disease (ESRD) and death, and time-dependent confounding, where patient factors that are predictive of later exposures and outcomes are affected by past exposures. We developed multistate marginal structural models (MS-MSMs) to assess the effect of time-varying systolic blood pressure on disease progression in subjects with CKD. The multistate nature of the model allows us to jointly model disease progression characterized by changes in the estimated glomerular filtration rate (eGFR), the onset of ESRD, and death, and thereby avoid unnatural assumptions of death and ESRD as noninformative censoring events for subsequent changes in eGFR. We model the causal effect of systolic blood pressure on the probability of transitioning into 1 of 6 disease states given the current state. We use inverse probability weights with stabilization to account for potential time-varying confounders, including past eGFR, total protein, serum creatinine, and hemoglobin. We apply the model to data from the Chronic Renal Insufficiency Cohort Study, a multisite observational study of patients with CKD. Copyright © 2017 John Wiley & Sons, Ltd.

  15. The combined use of Building Information Modelling (BIM) and Unmanned Aerial Vehicle (UAV) technologies for the 3D illustration of the progress of works in infrastructure construction projects

    Science.gov (United States)

    Vacanas, Yiannis; Themistocleous, Kyriacos; Agapiou, Athos; Hadjimitsis, Diofantos

    2016-08-01

    Building Information Modelling (BIM) technology is already part of the construction industry and is considered by professionals as a very useful tool for all phases of a construction project. BIM technology, with the particularly useful 3D illustrations which it provides, can be used to illustrate and monitor the progress of works effectively through the entire lifetime of the project. Unmanned Aerial Vehicles (UAVs) have undergone significant advances in equipment capabilities and now have the capacity to acquire high resolution imagery from different angles in a cost effective and efficient manner. By using photogrammetry, characteristics such as distances, areas, volumes, elevations, object sizes, and object shape can be determined within overlapping areas. This paper explores the combined use of BIM and UAV technologies in order to achieve efficient and accurate as-built data collection and 3D illustrations of the works progress during an infrastructure construction project.

  16. 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.

  17. Evaluating the significance of paleophylogeographic species distribution models in reconstructing quaternary range-shifts of nearctic chelonians.

    Directory of Open Access Journals (Sweden)

    Dennis Rödder

    Full Text Available The climatic cycles of the Quaternary, during which global mean annual temperatures have regularly changed by 5-10°C, provide a special opportunity for studying the rate, magnitude, and effects of geographic responses to changing climates. During the Quaternary, high- and mid-latitude species were extirpated from regions that were covered by ice or otherwise became unsuitable, persisting in refugial retreats where the environment was compatible with their tolerances. In this study we combine modern geographic range data, phylogeny, Pleistocene paleoclimatic models, and isotopic records of changes in global mean annual temperature, to produce a temporally continuous model of geographic changes in potential habitat for 59 species of North American turtles over the past 320 Ka (three full glacial-interglacial cycles. These paleophylogeographic models indicate the areas where past climates were compatible with the modern ranges of the species and serve as hypotheses for how their geographic ranges would have changed in response to Quaternary climate cycles. We test these hypotheses against physiological, genetic, taxonomic and fossil evidence, and we then use them to measure the effects of Quaternary climate cycles on species distributions. Patterns of range expansion, contraction, and fragmentation in the models are strongly congruent with (i phylogeographic differentiation; (ii morphological variation; (iii physiological tolerances; and (iv intraspecific genetic variability. Modern species with significant interspecific differentiation have geographic ranges that strongly fluctuated and repeatedly fragmented throughout the Quaternary. Modern species with low genetic diversity have geographic distributions that were highly variable and at times exceedingly small in the past. Our results reveal the potential for paleophylogeographic models to (i reconstruct past geographic range modifications, (ii identify geographic processes that result in

  18. Corresponding decrease in neuronal markers signals progressive parvalbumin neuron loss in MAM schizophrenia model.

    Science.gov (United States)

    Gill, Kathryn M; Grace, Anthony A

    2014-10-01

    Alteration in normal hippocampal (HPC) function attributed to reduced parvalbumin (PV) expression has been consistently reported in schizophrenia patients and in animal models of schizophrenia. However, it is unclear whether there is an overall loss of interneurons as opposed to a reduction in activity-dependent PV content. Co-expression of PV and the constitutively expressed substance P (SP)-receptor protein has been utilized in other models to ascertain the degree of cell survival, as opposed to reduction in activity-dependent PV content, in the HPC. The present study measured the co-expression of PV and SP-receptors in the dentate and dorsal and ventral CA3 subregions of the HPC in the methylazoymethanol acetate (MAM) rat neurodevelopmental model of schizophrenia. In addition, these changes were compared at the post-natal day 27 (PND27) and post-natal day 240 (PND > 240) time points. Brains from PND27 and PND > 240 MAM (n = 8) and saline (SAL, n = 8) treated offspring were immunohistochemically processed for the co-expression of PV and SP-receptors. The dorsal dentate, dorsal CA3 and ventral CA3 subregions of PND27 and PND > 240 MAM rats demonstrated significant reductions in PV but not SP-receptor expression, signifying a loss of PV-content. In contrast, in the ventral dentate the co-expression of PV and SP-receptors was significantly reduced only in PND > 240 MAM animals, suggesting a reduction in cell number. While MAM-induced reduction of PV content occurs in CA3 of dorsal and ventral HPC, the most substantial loss of interneuron number is localized to the ventral dentate of PND > 240 animals. The disparate loss of PV in HPC subregions likely impacts intra-HPC network activity in MAM rats.

  19. Sentinel node positive melanoma patients: prediction and prognostic significance of nonsentinel node metastases and development of a survival tree model.

    Science.gov (United States)

    Wiener, Martin; Acland, Katharine M; Shaw, Helen M; Soong, Seng-Jaw; Lin, Hui-Yi; Chen, Dung-Tsa; Scolyer, Richard A; Winstanley, Julie B; Thompson, John F

    2010-08-01

    Completion lymph node dissection (CLND) following positive sentinel node biopsy (SNB) for melanoma detects additional nonsentinel node (NSN) metastases in approximately 20% of cases. This study aimed to establish whether NSN status can be predicted, to determine its effect on survival, and to develop survival tree models for the sentinel node (SN) positive population. Sydney Melanoma Unit (SMU) patients with at least 1 positive SN, meeting inclusion criteria and treated between October 1992 and June 2005, were identified from the Unit database. Survival characteristics, potential predictors of survival, and NSN status were assessed using the Kaplan-Meier method, Cox regression model, and logistic regression analyses, respectively. Classification tree analysis was performed to identify groups with distinctly different survival characteristics. A total of 323 SN-positive melanoma patients met the inclusion criteria. On multivariate analysis, age, gender, primary tumor thickness, mitotic rate, number of positive NSNs, or total number of positive nodes were statistically significant predictors of survival. NSN metastasis, found at CLND in 19% of patients, was only predicted to a statistically significant degree by ulceration. Multivariate analyses demonstrated that survival was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis revealed 4 prognostically distinct survival groups. Patients with NSN metastases could not be reliably identified prior to CLND. Prognosis following CLND was more closely related to number of positive NSNs than total number of positive nodes. Classification tree analysis defined distinctly different survival groups more accurately than use of single-factor analysis.

  20. How Significant is the Slope of the Sea-side Boundary for Modelling Seawater Intrusion in Coastal Aquifers?

    Science.gov (United States)

    Walther, Marc; Graf, Thomas; Kolditz, Olaf; Lield, Rudolf; Post, Vincent

    2017-04-01

    A large number of people live in coastal areas using the available water resources, which in (semi-)arid regions are often taken from groundwater resources as the only sufficient source. Compared to surface water, these usually provide a safe water supply due to the remediation and retention capabilities of the subsurface, their high yield, and potentially longer term stability. With a water withdrawal from a coastal aquifer, coastal water management, however, has to ensure that seawater intrusion is retained in order to keep the water salinity at an acceptable level for all water users (e.g. agriculture, industry, households). Besides monitoring of water levels and saline intrusion, it has become a common practice to use numerical modeling for evaluating the coastal water resources and projecting future scenarios. When applying a model, it is necessary for the simplifications implied during the conceptualization of the setup to include the relevant processes (here variable-density flow and mass transport) and sensitive parameters (for a steady state commonly hydraulic conductivity, density ratio, dispersivity). Additionally, the model's boundary conditions are essential to the simulation results. In order to reduce the number of elements, and thus, the computational burden, one simplification that is made in most regional scale saltwater intrusion applications, is to represent the sea-side boundary with a vertical geometry, contrary to the natural conditions, that usually show a very shallow decent of the interface between the aquifer and the open seawater. We use the scientific open-source modeling toolbox OpenGeoSys [1] to quantify the influence of this simplification on the saline intrusion, submarine groundwater discharge, and groundwater residence times. Using an ensemble of different shelf shapes for a steady state setup, we identified a significant dependency of saline intrusion length on the geometric parameters of the sea-side boundary. Results show that

  1. 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.

  2. Progression and recovery of Parkinsonism in a chronic progressive MPTP-induction model in the marmoset without persistent molecular and cellular damage.

    Science.gov (United States)

    Franke, S K; van Kesteren, R E; Wubben, J A M; Hofman, S; Paliukhovich, I; van der Schors, R C; van Nierop, P; Smit, A B; Philippens, I H C H M

    2016-01-15

    Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in marmoset monkeys was used to model the prodromal stage of Parkinson's disease (PD), and to investigate mechanisms underlying disease progression and recovery. Marmosets were subcutaneously injected with MPTP for a period of 12weeks, 0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor behaviors were recorded before, during and after exposure. In addition, postmortem immunohistochemistry and proteomics analysis were performed. MPTP-induced parkinsonian clinical symptoms increased in severity during exposure, and recovered after MPTP administration was ended. Postmortem analyses, after the recovery period, revealed no alteration of the number and sizes of tyrosine hydroxylase (TH)-positive dopamine (DA) neurons in the substantia nigra. Also levels of TH in putamen and caudate nucleus were unaltered, no differences were observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and proteomics analysis revealed no global changes in protein expression in these brain areas between treatment groups. Our findings indicate that parkinsonian symptoms can occur without detectable damage at the cellular or molecular level. Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and treated early. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. 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

  4. 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.

  5. Progress in K spectroscopy

    International Nuclear Information System (INIS)

    Leith, D.W.G.S.

    1977-07-01

    The progress in the field of K* spectroscopy is reviewed within the framework of the simple harmonic oscillator quark model, and contrasted with the recent progress made in the charmonium spectroscopy

  6. 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.

  7. A progressive compression model of thoracic spinal cord injury in mice: function assessment and pathological changes in spinal cord

    Directory of Open Access Journals (Sweden)

    Guo-dong Sun

    2017-01-01

    Full Text Available Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups: in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal (0.2 mm post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury.

  8. The murine angiotensin II-induced abdominal aortic aneurysm model: rupture risk and inflammatory progression patterns

    Directory of Open Access Journals (Sweden)

    Richard Y Cao

    2010-07-01

    Full Text Available An abdominal aortic aneurysm (AAA is an enlargement of the greatest artery in the body defined as an increase in diameter of 1.5-fold. AAAs are common in the elderly population and thousands die each year from their complications. The most commonly used mouse model to study the pathogenesis of AAA is the angiotensin II (Ang II infusion method delivered via osmotic mini-pump for 28 days. Here, we studied the site-specificity and onset of aortic rupture, characterized three-dimensional (3D images and flow patterns in developing AAAs by ultrasound imaging, and examined macrophage infiltration in the Ang II model using 65 apolipoprotein E deficient mice. Aortic rupture occurred in 16 mice (25 % and was nearly as prevalent at the aortic arch (44 % as it was in the suprarenal region (56 % and was most common within the first seven days after Ang II infusion (12 of 16; 75 %. Longitudinal ultrasound screening was found to correlate nicely with histological analysis and AAA volume renderings showed a significant relationship with AAA severity index. Aortic dissection preceded altered flow patterns and macrophage infiltration was a prominent characteristic of developing AAAs. Targeting the inflammatory component of AAA disease with novel therapeutics will hopefully lead to new strategies to attenuate aneurysm growth and aortic rupture.

  9. Optical polarization tractography revealed significant fiber disarray in skeletal muscles of a mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Wang, Y; Zhang, K; Wasala, N B; Duan, D; Yao, G

    2015-02-01

    Optical polarization tractography (OPT) was recently developed to visualize tissue fiber architecture with cellular-level resolution and accuracy. In this study, we explored the feasibility of using OPT to study muscle disease in the mdx4cv mouse model of Duchenne muscular dystrophy. The freshly dissected tibialis anterior muscles of mdx4cv and normal mice were imaged. A "fiber disarray index" (FDI) was developed to quantify the myofiber disorganization. In necrotic muscle regions of the mdx4cv mice, the FDI was significantly elevated and can be used to segment the 3D necrotic regions for assessing the overall muscle damage. These results demonstrated the OPT's capability for imaging microscopic fiber alternations in muscle research.

  10. Knockdown of aberrantly expressed nuclear localized decorin attenuates tumour angiogenesis related mediators in oral cancer progression model in vitro.

    Science.gov (United States)

    Dil, Nyla; Banerjee, Abhijit G

    2012-06-08

    Oral cancer accounts for roughly 3% of cancer cases in the world with about 350,000 newly reported cases annually and a 5-year survival rate of only 50%. Majority of oral cancers are squamous cell carcinomas that originate in the oral mucosal epithelial linings. We have previously shown that in human malignant squamous cells carcinoma (SCC-25) as well as in dysplastic oral keratinocytes (DOK), a small leucine-rich multifunctional proteoglycan decorin is aberrantly expressed and localized in the nucleus where it interacts with nuclear epidermal growth factor receptor (EGFR). Post-transcriptional silencing of nuclear decorin significantly reduced IL-8 and IL8-dependent migration and invasion in these dysplastic and malignant oral epithelia. The objective of this study was to further examine the effects of nuclear decorin silencing on angiogenesis and angiogenesis related mediators in this oral cancer progression cell line model. We have used multiplex PCR, western blotting, and in vitro endothelial tube formation assay to study angiogenesis and related pathways in nuclear decorin silenced (stable knockdown) DOK and SCC-25 cells. Nuclear decorin knockdown resulted in significant down regulation of IL-8 expression, however IL-10, and TGF-β expression was not affected in either DOK or SCC25 cells as measured by multiplex RT PCR. IL-8 receptor CXCR 1 and 2 expression was slightly lower in nuclear decorin silenced cells indicating a contributing mechanism in previously shown reduced IL-8 mediated migration and invasion phenotype in these cells. IL-8 is known to induce Matrix metalloproteinase 9 (MMP9) which not only plays a role in tumour migration and invasion but also induces angiogenic switch. We found MMP9 to be significantly reduced in nuclear decorin silenced dysplastic and malignant oral epithelia. Other potent angiogenic mediators, VEGF189 and ANG-1 were either significantly reduced or completely abrogated in these cells. Angiogenesis as measured by endothelial

  11. 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.

  12. 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

  13. Bacteriophage treatment significantly reduces viable Clostridium difficile and prevents toxin production in an in vitro model system.

    Science.gov (United States)

    Meader, Emma; Mayer, Melinda J; Gasson, Michael J; Steverding, Dietmar; Carding, Simon R; Narbad, Arjan

    2010-12-01

    Clostridium difficile is primarily a nosocomial pathogen, causing thousands of cases of antibiotic-associated diarrhoea in the UK each year. In this study, we used a batch fermentation model of a C. difficile colonised system to evaluate the potential of a prophylactic and a remedial bacteriophage treatment regime to control the pathogen. It is shown that the prophylaxis regime was effective at preventing the growth of C. difficile (p = viable C. difficile cells (p = <0.0001), but still resulted in a lower level of toxin production relative to the control. The numbers of commensal bacteria including total aerobes and anaerobes, Bifidobacterium sp., Bacteroides sp., Lactobacillus sp., total Clostridium sp., and Enterobacteriaceae were not significantly decreased by this therapy, whereas significant detrimental effects were observed with metronidazole treatment. Our study indicates that phage therapy has potential to be used for the control of C. difficile; it highlights the main benefits of this approach, and some future challenges. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. 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...... of the 11 candidate genes have overlapping biological functions and interact in a common network. Our results may help predict disease progression in newly diagnosed children with T1D which can be exploited for optimizing treatment....

  15. 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.

  16. Progression of Ocular Sulfur Mustard Injury: Development of a Model System

    Science.gov (United States)

    2010-01-01

    8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Thymosins in Health and Disease Progression of ocular sulfur mustard injury: development of a...suggesting either inmigration of CE cells or an expansion of the erosion. Changes in the size and shape of the margins between 24 and 48 h suggest a...dynamic interplay between ex- pansion and inmigration . The lesion is either sig- nificantly reduced in size or gone by 72 h, and is completely resolved

  17. High milk consumption does not affect prostate tumor progression in two mouse models of benign and neoplastic lesions.

    Directory of Open Access Journals (Sweden)

    Sophie Bernichtein

    Full Text Available Epidemiological studies that have investigated whether dairy (mainly milk diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH or high-grade prostatic intraepithelial neoplasia (HGPIN. We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl or pre-cancerous PIN lesions (KIMAP mice. Mice were fed high milk diets (skim or whole for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63. Our results show that high milk consumption (either skim or whole did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia. For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.

  18. Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.

    Science.gov (United States)

    MacKenzie, Isobel E R; Paquette, Valerie; Gosse, Frances; George, Sheenagh; Chappe, Frederic; Chappe, Valerie

    2017-05-01

    The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation. Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada. Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients. The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  19. Contextual niche signals towards colorectal tumor progression by mesenchymal stem cell in the mouse xenograft model.

    Science.gov (United States)

    Nakagaki, Suguru; Arimura, Yoshiaki; Nagaishi, Kanna; Isshiki, Hiroyuki; Nasuno, Masanao; Watanabe, Shuhei; Idogawa, Masashi; Yamashita, Kentaro; Naishiro, Yasuyoshi; Adachi, Yasushi; Suzuki, Hiromu; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

    2015-09-01

    The role of mesenchymal stem/stromal cells (MSCs) in tumorigenesis remains controversial. This study aimed to determine whether heterotypic interactions between MSCs and colon cancer cells can supply contextual signals towards tumor progression. Xenografts consisting of co-implanted human colorectal cancer cells with rat MSCs in immunodeficient mice were evaluated by tumor progression, angiogenic profiles, and MSC fate. Furthermore, we investigated how MSCs function as a cancer cell niche by co-culture experiments in vitro. Tumor growth progressed in two ways, either independent of or dependent on MSCs. Such cell line-specific dependency could not be explained by host immune competency. COLO 320 xenograft angiogenesis was MSC-dependent, but less dependent on vascular endothelial growth factor (VEGF), whereas HT-29 angiogenesis was not MSC-dependent, but was VEGF-dependent. MSCs and COLO 320 cells established a functional positive feedback loop that triggered formation of a cancer cell niche, leading to AKT activation. Subsequently, MSCs differentiated into pericytes that enhanced angiogenesis as a perivascular niche. In contrast, the MSC niche conferred an anti-proliferative property to HT-29 cells, through mesenchymal-epithelial transition resulting in p38 activation. In conclusion, MSCs demonstrate pleiotropic capabilities as a cancer cell or perivascular niche to modulate colorectal cancer cell fate in a cell line-dependent manner in a xenogeneic context.

  20. 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...

  1. Combined treatment with olmesartan medoxomil and amlodipine besylate attenuates atherosclerotic lesion progression in a model of advanced atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sievers P

    2015-07-01

    Full Text Available Philipp Sievers,1 Lorenz Uhlmann,2 Sevil Korkmaz-Icöz,3 Christian Fastner,1 Florian Bea,1 Erwin Blessing,1 Hugo A Katus,1 Michael R Preusch11Department of Internal Medicine III, 2Institute of Medical Biometry and Informatics, 3Department of Cardiac Surgery, University of Heidelberg, Heidelberg, GermanyIntroduction: Besides their blood pressure-lowering effects, olmesartan medoxomil and amlodipine besylate exhibit additional anti-inflammatory mechanisms in atherosclerosic disease. Most of the studies investigating the effects of atherosclerosis focused on early atherosclerotic lesions, whereas lesions in human disease, at the time when medical treatment is started, are already well established. Therefore, we set up a model of advanced atherosclerosis and investigated the effects of olmesartan medoxomil, amlodipine besylate, and the combination of both on atherosclerotic lesion size and lesion composition.Materials and methods: Olmesartan medoxomil (1 mg/kg/day, amlodipine besylate (1.5 mg/kg/day, and the combination of both was added to chow and was fed to apolipoprotein E-deficient (ApoE-/- mice at 25 weeks of age. Mice were sacrificed after 25 weeks of drug administration and perfused with formalin. Innominate arteries were dissected out and paraffin embedded. Serial sections were generated, and lesion sizes and their composition – such as minimal thickness of the fibrous cap, size of the necrotic core, and presence of calcification – were analyzed. Electrophoretic mobility shift assays were used to detect DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB in aortic tissue.Results: Treatment with the combination of olmesartan medoxomil and amlodipine besylate led to a significant reduction in atherosclerotic lesion size in ApoE-/- mice (olmesartan medoxomil/amlodipine besylate: 122,277±6,795 µm2, number [n]=14; versus control: 177,502±10,814 µm2, n=9; P<0.001. Treatment with amlodipine besylate (n=5 alone

  2. 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

  3. Genetic Deficiency of Complement Component 3 Does Not Alter Disease Progression in a Mouse Model of Huntington's Disease

    Science.gov (United States)

    Larkin, Paul B.; Muchowski, Paul J.

    2012-01-01

    Several genes and proteins of the complement cascade are present at elevated levels in brains of patients with Huntington's disease (HD). The complement cascade is well characterized as an effector arm of the immune system, and in the brain it is important for developmental synapse elimination. We hypothesized that increased levels of complement in HD brains contributes to disease progression, perhaps by contributing to synapse elimination or inflammatory signaling. We tested this hypothesis in the R6/2 mouse model of HD by crossing mice deficient in complement component 3 (C3), a crucial complement protein found at increased levels in HD brains, to R6/2 mice and monitoring behavioral and neuropathological disease progression. We found no alterations in multiple behavioral assays, weight or survival in R6/2 mice lacking C3. We also quantified the expression of several complement cascade genes in R6/2 brains and found that the large scale upregulation of complement genes observed in HD brains is not mirrored in R6/2 brains. These data show that C3 deficiency does not alter disease progression in the R6/2 mouse model of HD. PMID:23097680

  4. How does early detection by screening affect disease progression? Modeling estimated benefits in prostate cancer screening.

    Science.gov (United States)

    Wever, Elisabeth M; Draisma, Gerrit; Heijnsdijk, Eveline A M; de Koning, Harry J

    2011-01-01

    Simulation models are essential tools for estimating benefits of cancer screening programs. Such models include a screening-effect model that represents how early detection by screening followed by treatment affects disease-specific survival. Two commonly used screening-effect models are the stage-shift model, where mortality benefits are explained by the shift to more favorable stages, and the cure model, where early detection enhances the chances of cure from disease. This article describes commonly used screening-effect models and analyses their predicted mortality benefit in a model for prostate cancer screening. The MISCAN simulation model was used to predict the reduction of prostate cancer mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam. The screening-effect models were included in the model. For each model the predictions of prostate cancer mortality reduction were calculated. The study compared 4 screening-effect models, which are versions of the stage-shift model or the cure model. The stage-shift models predicted, after a follow-up of 9 years, reductions in prostate cancer mortality varying from 38% to 63% for ERSPC-Rotterdam compared with a 27% reduction observed in the ERSPC. The cure models predicted reductions in prostate cancer mortality varying from 21% to 27%. The differences in predicted mortality reductions show the importance of validating models to observed trial mortality data. The stage-shift models considerably overestimated the mortality reduction. Therefore, the stage-shift models should be used with care, especially when modeling the effect of screening for cancers with long lead times, such as prostate cancer.

  5. Hydrodynamic models for slurry bubble column reactors. Fifth technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    Gidaspow, D.

    1995-10-01

    The objective of this work is to convert our `learning gas-solid-liquid` fluidization model into a predictive design model. The IIT hydrodynamic model computes the phase velocities and the volume fractions of gas, liquid, and particulate phases. Model verification involves a comparison of these computed velocities and volume fractions to experimental values.

  6. 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.

  7. 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.

  8. Stochastic modelling of slow-progressing tumors: Analysis and applications to the cell interplay and control of low grade gliomas

    Science.gov (United States)

    Rodríguez, Clara Rojas; Fernández Calvo, Gabriel; Ramis-Conde, Ignacio; Belmonte-Beitia, Juan

    2017-08-01

    Tumor-normal cell interplay defines the course of a neoplastic malignancy. The outcome of this dual relation is the ultimate prevailing of one of the cells and the death or retreat of the other. In this paper we study the mathematical principles that underlay one important scenario: that of slow-progressing cancers. For this, we develop, within a stochastic framework, a mathematical model to account for tumor-normal cell interaction in such a clinically relevant situation and derive a number of deterministic approximations from the stochastic model. We consider in detail the existence and uniqueness of the solutions of the deterministic model and study the stability analysis. We then focus our model to the specific case of low grade gliomas, where we introduce an optimal control problem for different objective functionals under the administration of chemotherapy. We derive the conditions for which singular and bang-bang control exist and calculate the optimal control and states.

  9. 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.

  10. 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 .'

  11. 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.

  12. 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.

  13. PET Imaging of Disease Progression and Treatment Effects in the Experimental Autoimmune Encephalomyelitis Rat Model

    NARCIS (Netherlands)

    Faria, Daniele de Paula; Vlaming, Maria L. H.; Copray, Sjef C. V. M.; Tielen, Frans; Anthonijsz, Herma J. A.; Sijbesma, Jurgen W. A.; Buchpiguel, Carlos A.; Dierckx, Rudi A. J. O.; van der Hoorn, Jose W. A.; de Vries, Erik F. J.

    The experimental autoimmune encephalomyelitis model is a model of multiple sclerosis that closely mimics the disease characteristics in humans. The main hallmarks of multiple sclerosis are neuroinflammation (microglia activation, monocyte invasion, and T-cell infiltration) and demyelination. PET

  14. Experimental Model of Progressive Disseminated Trichosporonosis in Mice with Latent Trichosporonemia

    Science.gov (United States)

    Yamagata, Eiji; Kamberi, Perparim; Yamakami, Yuriko; Hashimoto, Atsuro; Nasu, Masaru

    2000-01-01

    Trichosporon asahii and Trichosporon mucoides are the most common strains of fungi that cause disseminated trichosporonosis, a severe opportunistic infection in immunocompromised hosts. We have previously established a nested PCR assay using serum samples for detection of both strains. Here we describe a new experimental animal model for investigating the underlying mechanisms of disseminated trichosporonosis. T. asahii (OMU239, a clinical isolate from a patient with acute myelogenous leukemia) and 8-week-old ICR male mice were used in all experiments. A suspension of T. asahii (3 × 106 CFU/animal) was injected into the caudal vein of each mouse after immunosuppression with cyclophosphamide (200 mg/kg of body weight/day for 2 days) and prednisolone (30 mg/kg/day for 1 day). Mice were then divided into four subgroups (R0, R1, R2, and R3) based on the time of reimmunosuppression. The latter was performed using the same drugs 1 week (group R1), 2 weeks (group R2), and 3 weeks (group R3) after fungal infection. Reimmunosuppression was not performed in group R0. The 5-week-survival rates of mice after T. asahii infection were 0% for group R1, 50% for group R2, 80% for group R3, and 80% for group R0. There was a significant difference in the survival rates between group R1 and either group R0 or R3 (P < 0.05). Fungal clearance in peripheral blood and various organs of group R1 and R2 was delayed relative to that of group R0 but was similar to the control in group R3 in spite of reimmunosuppression. Our results suggest that the critical period for the development of disseminated trichosporonosis in our model is shorter than 3 weeks after T. asahii infection. We concluded that mice during this critical period were in a state of latent trichosporonemia. Comparison of the survival rates suggests that the nested PCR assay was more useful than blood culture and glucuronoxylomannan antigen assay in the detection of this latent trichosporonemia. PMID:10970368

  15. How does early detection by screening affect disease progression?: Modeling estimated benefits in prostate cancer screening

    NARCIS (Netherlands)

    E.M. Wever (Elisabeth); G. Draisma (Gerrit); E.A.M. Heijnsdijk (Eveline); H.J. de Koning (Harry)

    2011-01-01

    textabstractBackground. Simulation models are essential tools for estimating benefits of cancer screening programs. Such models include a screening-effect model that represents how early detection by screening followed by treatment affects disease-specific survival. Two commonly used

  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...

  17. The overexpression of Twinkle helicase ameliorates the progression of cardiac fibrosis and heart failure in pressure overload model in mice.

    Directory of Open Access Journals (Sweden)

    Atsushi Tanaka

    Full Text Available Myocardial mitochondrial DNA (mtDNA copy number decreases in heart failure. In post-myocardial infarction mice, increasing mtDNA copy number by overexpressing mitochondrial transcription factor attenuates mtDNA deficiency and ameliorates pathological remodeling thereby markedly improving survival. However, the functional significance of increased mtDNA copy number in hypertensive heart disease remains unknown. We addressed this question using transgenic mice that overexpress Twinkle helicase (Twinkle; Tg, the mtDNA helicase, and examined whether Twinkle overexpression protects the heart from left ventricular (LV remodeling and failure after pressure overload created by transverse aortic constriction (TAC. Twinkle overexpression increased mtDNA copy number by 2.2 ± 0.1-fold. Heart weight, LV diastolic volume and wall thickness were comparable between Tg and wild type littermates (WT at 28 days after TAC operation. LV end-diastolic pressure increased in WT after TAC (8.6 ± 2.8 mmHg, and this increase was attenuated in Tg (4.6 ± 2.6 mmHg. Impaired LV fractional shortening after TAC operation was also suppressed in Tg, as measured by echocardiography (WT: 16.2 ± 7.2% vs Tg: 20.7 ± 6.2%. These LV functional improvements were accompanied by a decrease in interstitial fibrosis (WT: 10.6 ± 1.1% vs Tg: 3.0 ± 0.6%. In in vitro studies, overexpressing Twinkle using an adenovirus vector in cultured cardiac fibroblasts significantly suppressed mRNA of collagen 1a, collagen 3a and connective tissue growth factor, and angiotensin II-induced transforming growth factor β1 expression. The findings suggest that Twinkle overexpression prevents LV function deterioration. In conclusion, Twinkle overexpression increases mtDNA copy number and ameliorates the progression of LV fibrosis and heart failure in a mouse pressure overload model. Increasing mtDNA copy number by Twinkle overexpression could be a novel therapeutic strategy for hypertensive heart disease.

  18. 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.

  19. Progress and applications of MCAM. Monte Carlo automatic modeling program for particle transport simulation

    International Nuclear Information System (INIS)

    Wang Guozhong; Zhang Junjun; Xiong Jian

    2010-01-01

    MCAM (Monte Carlo Automatic Modeling program for particle transport simulation) was developed by FDS Team as a CAD based bi-directional interface program between general CAD systems and Monte Carlo particle transport simulation codes. The physics and material modeling and void space modeling functions were improved and the free form surfaces processing function was developed recently. The applications to the ITER (International Thermonuclear Experimental Reactor) building model and FFHR (Force Free Helical Reactor) model have demonstrated the feasibility, effectiveness and maturity of MCAM latest version for nuclear applications with complex geometry. (author)

  20. Progress in IEC 61400-27. Electrical simulation models for wind power generation

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen, Poul [DTU Wind Energy, Roskilde (Denmark); Andresen, Bjoern; Bech, John [Siemens Wind Power, Brande (Denmark). Electrical Systems and Generators; Fortmann, Jens [REpower Systems AG, Osterroenfeld (Germany). Wind Power Plant; Pourbeik, Pouyan [Electric Power Research Institute, Inc. (EPRI), Knoxville, TN (United States). Grid Operations and Planning

    2012-07-01

    This paper presents the status of the ongoing work in IEC Technical Committee 88 Working Group 27 (TC88 WG27) developing a standard IEC 61400-27 for ''Electrical simulation models for wind power generation''. The purpose of this standardization work is to define generic simulation models for wind turbines (part 1) and wind power plants (part 2), which are intended for short-term power system stability analyses. WG27 submitted the first CD of Part 1 in December 2012. The CD describes generic wind turbine models and a procedure for validation of wind turbine models. The generic model description consists of a general model structure intending to cover existing as well as future types of wind turbines, and specific fundamental frequency positive sequence models for the four wind turbine types which are widely used today. The validation procedure can be applied to the generic models specified in the standard, or to manufacturer specific fundamental frequency models. The paper will provide a general description of the wind turbine models, a more detailed description of type 4 models, a description of the validation procedure and finally a validation example. Part 2 is in an early stage of development. IEC has approved the New Work Item Proposal (NWIP) of part 2, and this work has officially started 1 October 2012. (orig.)

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. In vivo models in breast cancer research: progress, challenges and future directions

    Directory of Open Access Journals (Sweden)

    Ingunn Holen

    2017-04-01

    Full Text Available Research using animal model systems has been instrumental in delivering improved therapies for breast cancer, as well as in generating new insights into the mechanisms that underpin development of the disease. A large number of different models are now available, reflecting different types and stages of the disease; choosing which one to use depends on the specific research question(s to be investigated. Based on presentations and discussions from leading experts who attended a recent workshop focused on in vivo models of breast cancer, this article provides a perspective on the many varied uses of these models in breast cancer research, their strengths, associated challenges and future directions. Among the questions discussed were: how well do models represent the different stages of human disease; how can we model the involvement of the human immune system and microenvironment in breast cancer; what are the appropriate models of metastatic disease; can we use models to carry out preclinical drug trials and identify pathways responsible for drug resistance; and what are the limitations of patient-derived xenograft models? We briefly outline the areas where the existing breast cancer models require improvement in light of the increased understanding of the disease process, reflecting the drive towards more personalised therapies and identification of mechanisms of drug resistance.

  7. Electron energy dissipation model of gate dielectric progressive breakdown in n- and p-channel field effect transistors

    Science.gov (United States)

    Lombardo, S.; Wu, E. Y.; Stathis, J. H.

    2017-08-01

    We report the data and a model showing that the energy loss experienced by the carriers flowing through breakdown spots is the primary cause of progressive breakdown spot growth. The experiments are performed in gate dielectrics of metal-oxide-semiconductor (MOS) devices subjected to accelerated high electric field constant voltage stress under inversion conditions. The model is analytical and contains few free parameters of clear physical meaning. This is compared to a large set of data on breakdown transients at various oxide thicknesses, stress voltages, and temperatures, both in cases of n-channel and p-channel transistors and polycrystalline Si/oxynitride/Si and metal gate/high k dielectric/Si gate stacks. The basic idea is that the breakdown transient is due to the growth of one or more filaments in the dielectric promoted by electromigration driven by the energy lost by the electrons traveling through the breakdown spots. Both cases of polycrystalline Si/oxynitride/Si and metal gate/high-k dielectric/Si MOS structures are investigated. The best fit values of the model to the data, reported and discussed in the paper, consistently describe a large set of data. The case of simultaneous growth of multiple progressive breakdown spots in the same device is also discussed in detail.

  8. 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.

  9. 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),…

  10. 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

    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...

  11. Hydrodynamic models for slurry bubble column reactors. Fourth technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    Gidaspow, D.

    1995-07-01

    The objective of this investigation is to convert our ``learning gas-solid-liquid`` fluidization model into a predictive design model. The IIT hydrodynamic model computes the phase velocities and volume fractions of gas, liquid and particulate phases. Model verification involves a comparison of these computed velocities and volume fractions to experimental values. The simulation of Air Product methanol reactors described in this paper are continuing. Granular temperatures and viscosities have been computed. Preliminary measurements of granular temperatures using the Air Product catalysts were obtained using our CCD camera.

  12. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C

    2015-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants...... and previous association studies. RESULTS: A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (PFour loci were suggestive (P

  13. 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

  14. 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

  15. Evaluating Longitudinal Mathematics Achievement Growth: Modeling and Measurement Considerations for Assessing Academic Progress

    Science.gov (United States)

    Shanley, Lina

    2016-01-01

    Accurately measuring and modeling academic achievement growth is critical to support educational policy and practice. Using a nationally representative longitudinal data set, this study compared various models of mathematics achievement growth on the basis of both practical utility and optimal statistical fit and explored relationships within and…

  16. Progress and Outlooks in a Genetic Absence Epilepsy Model (WAG/Rij)

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Zobeiri, M.

    2014-01-01

    The WAG/Rij model is a well characterized and validated genetic animal epilepsy model in which the for absence epilepsy highly characteristic spike-wave discharges (SWDs) develop spontaneously. In this review we discuss first some older and many new studies, with an emphasis on pharmacological and

  17. 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

    2018-02-07

    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.

  18. Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome.

    Science.gov (United States)

    Yang, Shun-Min; Ka, Shuk-Man; Hua, Kuo-Feng; Wu, Tzu-Hua; Chuang, Yi-Ping; Lin, Ya-Wen; Yang, Feng-Ling; Wu, Shih-Hsiung; Yang, Sung-Sen; Lin, Shih-Hua; Chang, Jia-Ming; Chen, Ann

    2013-08-01

    High levels of reactive oxygen species (ROS), systemic T cell activation, and macrophage infiltration in the kidney are implicated in the acceleration and progression of IgA nephropathy (IgAN), the most frequent type of primary glomerulonephritis. However, the pathogenic mechanism of IgAN is still little understood, and it remains a challenge to establish a specific therapeutic strategy for this type of glomerular disorder. Recently, we showed that antroquinonol (Antroq), a pure active compound from Antrodia camphorata mycelium, inhibits renal inflammation and reduces oxidative stress in a mouse model of renal fibrosis. But the anti-inflammatory and immune-regulatory effects of Antroq on the acceleration and progression of primary glomerular disorders have not been determined. In this study, we show that Antroq administration substantially impeded the development of severe renal lesions, such as intense glomerular proliferation, crescents, sclerosis, and periglomerular interstitial inflammation, in mice with induced accelerated and progressive IgAN (AcP-IgAN). Further mechanistic analysis in AcP-IgAN mice showed that, early in the developmental stage of the AcP-IgAN model, Antroq promoted the Nrf2 antioxidant pathway and inhibited the activation of T cells and NLRP3 inflammasome. Significantly improved proteinuria/renal function and histopathology in AcP-IgAN mice of an established stage supported potential therapeutic effects of Antroq on the disease. In addition, Antroq was shown to inhibit activation of NLRP3 inflammasome in vitro by an IgA immune complex (IC) partly involving a reduced ROS production in IgA-IC-primed macrophages, and this finding may be helpful in the understanding of the mode of action of Antroq in the treated AcP-IgAN mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. 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.

  20. 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.

  1. 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

  2. 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 ).

  3. 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

    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...

  4. The AFTAC model integration project: An annual progress report. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, D.J.; Moore, R.M.

    1993-12-01

    The EXPRESS and ADPIC models have been designed to assist emergency personnel in their response to radiological accidents. Closure on the development of an operational version of the HADPIC Modeling System (HMS), a multi-faceted application that supports the hemispheric ADPIC (HADPIC) atmospheric dispersion model on a Sun workstation, was achieved toward the end of the fiscal year. The fulfilling tasks over the period encompassed by this report included: (1) the generation of software for calculating average concentrations at arbitrary locations in the model domain and displaying isopleths of concentration and (2) the comprehensive testing of major components of the HMS using IEEE standards. Scientists for Lawrence Livermore National Laboratory and the Institute of Experimental Meteorology in Obninsk, Russia, extensively evaluated their respective models (ADPIC/U.S. and EXPRESS/Russia) using perfluorocarbon tracer data from the Across North America Tracer Experiment (ANATEX). The results of both models are reported here because of the useful insights they provide regarding limits of performance as a function of model sophistication and the quality of the input meteorology.

  5. Ecological Modeling for Military Land Use Decision Support: Interim Progress Report for Ecological Modeling (Project CS/758/4567)

    National Research Council Canada - National Science Library

    Dale, Virginia

    1996-01-01

    .... The ecological models implemented as part of this project are components of the Conservation Thrust's "DoD Land Management Toolbox" and are compatible with the Integrated Dynamic Landscape Analysis and Modeling System ÎDLAMS...

  6. A descriptive model of the molten salt reactor experiment after shutdown: Review of FY 1995 progress

    Energy Technology Data Exchange (ETDEWEB)

    Williams, D.F.; Del Cul, G.D.; Toth, L.M.

    1996-01-01

    During FY 1995 considerable progress was made toward gaining a better understanding of the chemistry and transport processes that continue to govern the behavior of the Molten Salt Reactor Experiment (MSRE). As measurements in the MSRE proceed, laboratory studies continue, and better analyses are available, our understanding of the state of the MSRE and the best path toward remediation improves. Because of the immediate concern about the deposit in the auxiliary charcoal bed (ACB), laboratory studies in the past year focused on carbon-fluorine chemistry. Secondary efforts were directed toward investigation of gas generation from MSRE salts by both radiolytic and nonradiolytic pathways. In addition to the laboratory studies, field measurements at the MSRE provided the basis for estimating the inventory of uranium and fluorine in the ACB. Analysis of both temperature and radiation measurements provided independent and consistent estimates of about 2.6 kg of uranium deposited in the top of the ACB. Further analysis efforts included a refinement in the estimates of the fuel- salt source term, the deposited decay energy, and the projected rate of radiolytic gas generation. This report also provides the background material necessary to explain new developments and to review areas of particular interest. The detailed history of the MSRE is extensively documented and is cited where appropriate. This work is also intended to update and complement the more recent MSRE assessment reports.

  7. A descriptive model of the molten salt reactor experiment after shutdown: Review of FY 1995 progress

    International Nuclear Information System (INIS)

    Williams, D.F.; Del Cul, G.D.; Toth, L.M.

    1996-01-01

    During FY 1995 considerable progress was made toward gaining a better understanding of the chemistry and transport processes that continue to govern the behavior of the Molten Salt Reactor Experiment (MSRE). As measurements in the MSRE proceed, laboratory studies continue, and better analyses are available, our understanding of the state of the MSRE and the best path toward remediation improves. Because of the immediate concern about the deposit in the auxiliary charcoal bed (ACB), laboratory studies in the past year focused on carbon-fluorine chemistry. Secondary efforts were directed toward investigation of gas generation from MSRE salts by both radiolytic and nonradiolytic pathways. In addition to the laboratory studies, field measurements at the MSRE provided the basis for estimating the inventory of uranium and fluorine in the ACB. Analysis of both temperature and radiation measurements provided independent and consistent estimates of about 2.6 kg of uranium deposited in the top of the ACB. Further analysis efforts included a refinement in the estimates of the fuel- salt source term, the deposited decay energy, and the projected rate of radiolytic gas generation. This report also provides the background material necessary to explain new developments and to review areas of particular interest. The detailed history of the MSRE is extensively documented and is cited where appropriate. This work is also intended to update and complement the more recent MSRE assessment reports

  8. FHWA Traffic Noise Model (TNM) pavement effects implementation study : progress report 1

    Science.gov (United States)

    2012-01-31

    The Volpe Center Acoustics Facility, in support of the Federal Highway Administration (FHWA), investigated the implementation of pavement effects in the FHWA Traffic Noise Model (TNM). Three options were considered, resulting in the recommendation of...

  9. FY17 Progress in Modeling of Lanthanide Transport in Metallic Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Unal, Cetin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Matthews, Christopher [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-19

    A critical review of fuel-clad-chemical interactions along with modelling requirements is published. The mechanism of lanthanide transport is studied experimentally (NEUP collaboration) and using simulations and initial results are published in Refs.

  10. Progress Report 2008: A Scalable and Extensible Earth System Model for Climate Change Science

    Energy Technology Data Exchange (ETDEWEB)

    Drake, John B [ORNL; Worley, Patrick H [ORNL; Hoffman, Forrest M [ORNL; Jones, Phil [Los Alamos National Laboratory (LANL)

    2009-01-01

    This project employs multi-disciplinary teams to accelerate development of the Community Climate System Model (CCSM), based at the National Center for Atmospheric Research (NCAR). A consortium of eight Department of Energy (DOE) National Laboratories collaborate with NCAR and the NASA Global Modeling and Assimilation Office (GMAO). The laboratories are Argonne (ANL), Brookhaven (BNL) Los Alamos (LANL), Lawrence Berkeley (LBNL), Lawrence Livermore (LLNL), Oak Ridge (ORNL), Pacific Northwest (PNNL) and Sandia (SNL). The work plan focuses on scalablity for petascale computation and extensibility to a more comprehensive earth system model. Our stated goal is to support the DOE mission in climate change research by helping ... To determine the range of possible climate changes over the 21st century and beyond through simulations using a more accurate climate system model that includes the full range of human and natural climate feedbacks with increased realism and spatial resolution.

  11. Work, Health, Music: The enduring Rusyn model of a good life amid changing socioeconomic contexts of progress

    Directory of Open Access Journals (Sweden)

    K. M. Cantin

    2013-11-01

    Full Text Available Rusyns in Eastern and Central Europe have experience with two predominant models of “progress”: the Soviet-style communist and the neoliberal.  Proponents of each system promised to better the lives of all but did not take into account what “better” meant to local populations, including Rusyns.  Increasingly, European governmental and nongovernmental organizations are redefining notions of progress and development to accord with values of sustainability and a capability approach (CA to well-being.  Giovanola (2005 and Robeyns (2005 have argued that scholars of the CA need to better develop concepts of “personhood” and “human flourishing”, and to better explain the importance of social group membership and norms to living a valued life.  The emerging anthropological focus on well-being, emphasizing culturally specific definitions of what happiness and a good life mean, can provide these conceptualizations.  As a case in point, I use freelist and interview data obtained from residents in the Prešov Region of Slovakia and the Zakarpattia Oblast of Ukraine along with Rusyn cultural narratives drawn from poems, folktales, plays, songs, interviews, and speeches to identify prevalent models of “personhood” and “a good life”. I discuss how these narratives intersect and diverge with discourses of happiness and progress along with the implications for Rusyns' ability to flourish. 

  12. Prognostic models based on patient snapshots and time windows: Predicting disease progression to assisted ventilation in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Carreiro, André V; Amaral, Pedro M T; Pinto, Susana; Tomás, Pedro; de Carvalho, Mamede; Madeira, Sara C

    2015-12-01

    Amyotrophic Lateral Sclerosis (ALS) is a devastating disease and the most common neurodegenerative disorder of young adults. ALS patients present a rapidly progressive motor weakness. This usually leads to death in a few years by respiratory failure. The correct prediction of respiratory insufficiency is thus key for patient management. In this context, we propose an innovative approach for prognostic prediction based on patient snapshots and time windows. We first cluster temporally-related tests to obtain snapshots of the patient's condition at a given time (patient snapshots). Then we use the snapshots to predict the probability of an ALS patient to require assisted ventilation after k days from the time of clinical evaluation (time window). This probability is based on the patient's current condition, evaluated using clinical features, including functional impairment assessments and a complete set of respiratory tests. The prognostic models include three temporal windows allowing to perform short, medium and long term prognosis regarding progression to assisted ventilation. Experimental results show an area under the receiver operating characteristics curve (AUC) in the test set of approximately 79% for time windows of 90, 180 and 365 days. Creating patient snapshots using hierarchical clustering with constraints outperforms the state of the art, and the proposed prognostic model becomes the first non population-based approach for prognostic prediction in ALS. The results are promising and should enhance the current clinical practice, largely supported by non-standardized tests and clinicians' experience. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases.

    Science.gov (United States)

    Bacioglu, Mehtap; Maia, Luis F; Preische, Oliver; Schelle, Juliane; Apel, Anja; Kaeser, Stephan A; Schweighauser, Manuel; Eninger, Timo; Lambert, Marius; Pilotto, Andrea; Shimshek, Derya R; Neumann, Ulf; Kahle, Philipp J; Staufenbiel, Matthias; Neumann, Manuela; Maetzler, Walter; Kuhle, Jens; Jucker, Mathias

    2016-07-06

    A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Hydrodynamic models for slurry bubble column reactors. Seventh technical progress report, January--March 1996

    Energy Technology Data Exchange (ETDEWEB)

    Gidaspow, D.

    1996-04-01

    The objective of this investigation is to convert our ``learning gas solid-liquid`` fluidization model into a predictive design model. The IIT hydrodynamic model computes the phase velocities and the volume fractions of gas, liquid and particulate phase. Model verification involves a comparison of these computed velocities and volume fractions to experimental values. A hydrodynamic model for multiphase flows, based on the principles of mass, momentum and energy conservation for each phase, was developed and applied to model gas-liquid, gas-liquid-solid fluidization and gas-solid-solid separation. To simulate the industrial slurry bubble column reactors, a computer program based on the hydrodynamic model was written with modules for chemical reactions (e.g. the synthesis of methanol), phase changes and heat exchangers. In the simulations of gas-liquid two phases flow system, the gas hold-ups, computed with a variety of operating conditions such as temperature, pressure, gas and liquid velocities, agree well with the measurements obtained at Air Products` pilot plant. The hydrodynamic model has more flexible features than the previous empirical correlations in predicting the gas hold-up of gas-liquid two-phase flow systems. In the simulations of gas-liquid-solid bubble column reactors with and without slurry circulation, the code computes volume fractions, temperatures and velocity distributions for the gas, the liquid and the solid phases, as well as concentration distributions for the species (CO, H{sub 2}, CH{sub 3}0H, ... ), after startup from a certain initial state. A kinetic theory approach is used to compute a solid viscosity due to particle collisions. Solid motion and gas-liquid-solid mixing are observed on a color PCSHOW movie made from computed time series data. The steady state and time average catalyst concentration profiles, the slurry height and the rates of methanol production agree well with the measurements obtained at an Air Products` pilot plant.

  15. Recent Progress Validating the HADES Model of LLNL's HEAF MicroCT Measurements

    Energy Technology Data Exchange (ETDEWEB)

    White, W. T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bond, K. C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Lennox, K. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Aufderheide, M. B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Seetho, I. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Roberson, G. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-07-17

    This report compares recent HADES calculations of x-ray linear attenuation coefficients to previous MicroCT measurements made at Lawrence Livermore National Laboratory’s High Energy Applications Facility (HEAF). The chief objective is to investigate what impact recent changes in HADES modeling have on validation results. We find that these changes have no obvious effect on the overall accuracy of the model. Detailed comparisons between recent and previous results are presented.

  16. Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

    Science.gov (United States)

    Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

    2017-12-01

    Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Quality Circles: Determination of Significant Factors for Success an a General Model for Implementing a Quality Circle Process.

    Science.gov (United States)

    1981-06-01

    Quality Cir- cles?" First Annual IAQC Transactions, 1979, pp 59-65. 11. Beckhard , Richard . 0rganization Development: Strategies and Models. Reading...improve task accomplishment /57. Beckhard /T17 identifies three models that are commonly used in attempting to deal with a client’s problems. The...Jananese Challerfe. Addison-Wesley Publishing Co., Reading, Massachusetts, 1981. 84. Pascale, Richard T., Anthony G. Athos. The Art of Japaese

  18. SCDAP/RELAP5/MOD 3.1 code manual: Damage progression model theory. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    Davis, K.L. [ed.; Allison, C.M.; Berna, G.A. [Lockheed Idaho Technologies Co., Idaho Falls, ID (United States)] [and others

    1995-06-01

    The SCDAP/RELAP5 code has been developed for best estimate transient simulation of light water reactor coolant systems during a severe accident. The code models the coupled behavior of the reactor coolant system, the core, fission products released during a severe accident transient as well as large and small break loss of coolant accidents, operational transients such as anticipated transient without SCRAM, loss of offsite power, loss of feedwater, and loss of flow. A generic modeling approach is used that permits as much of a particular system to be modeled as necessary. Control system and secondary system components are included to permit modeling of plant controls, turbines, condensers, and secondary feedwater conditioning systems. This volume contains detailed descriptions of the severe accident models and correlations. It provides the user with the underlying assumptions and simplifications used to generate and implement the basic equations into the code, so an intelligent assessment of the applicability and accuracy of the resulting calculation can be made.

  19. Cross-flow turbines: progress report on physical and numerical model studies at large laboratory scale

    Science.gov (United States)

    Wosnik, Martin; Bachant, Peter

    2016-11-01

    Cross-flow turbines show potential in marine hydrokinetic (MHK) applications. A research focus is on accurately predicting device performance and wake evolution to improve turbine array layouts for maximizing overall power output, i.e., minimizing wake interference, or taking advantage of constructive wake interaction. Experiments were carried with large laboratory-scale cross-flow turbines D O (1 m) using a turbine test bed in a large cross-section tow tank, designed to achieve sufficiently high Reynolds numbers for the results to be Reynolds number independent with respect to turbine performance and wake statistics, such that they can be reliably extrapolated to full scale and used for model validation. Several turbines of varying solidity were employed, including the UNH Reference Vertical Axis Turbine (RVAT) and a 1:6 scale model of the DOE-Sandia Reference Model 2 (RM2) turbine. To improve parameterization in array simulations, an actuator line model (ALM) was developed to provide a computationally feasible method for simulating full turbine arrays inside Navier-Stokes models. Results are presented for the simulation of performance and wake dynamics of cross-flow turbines and compared with experiments and body-fitted mesh, blade-resolving CFD. Supported by NSF-CBET Grant 1150797, Sandia National Laboratories.

  20. Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

    Science.gov (United States)

    Gonzalez, Liara M.; Moeser, Adam J.

    2014-01-01

    Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury. PMID:25414098