GEM Model Research Articles

The GEM model of health: a model based on generalized empirical method –Part 3 – Fleshing out the model

In this paper, I discuss Lonergan’s account of the structure of the human good and then demonstrate how it works in reference to a doctor’s description of her experience at a New Orleans’ hospital in the aftermath of Hurricane Katrina. Next, I proceed to define health and disease on the basis of Lonergan’s accounts of the human good, emergent probability and generalized empirical method. Then, I lay out the generic levels of human living in a table of terms whose interrelations embody the multiple dimensions of health and their dynamic potential for integration (and breakdown) in the GEM model of health.

Patient asynchrony modelling during controlled mechanical ventilation therapy

Background and objectiveMechanical ventilation therapy of respiratory failure patients can be guided by monitoring patient-specific respiratory mechanics. However, the patient's spontaneous breathing effort during controlled ventilation changes airway pressure waveform and thus affects the model-based identification of patient-specific respiratory mechanics parameters. This study develops a model to estimate respiratory mechanics in the presence of patient effort. MethodsGaussian effort model (GEM) is a derivative of the single-compartment model with basis function. GEM model uses a linear combination of basis functions to model the nonlinear pressure waveform of spontaneous breathing patients. The GEM model estimates respiratory mechanics such as Elastance and Resistance along with the magnitudes of basis functions, which accounts for patient inspiratory effort. Results and discussionThe GEM model was tested using both simulated data and a retrospective observational clinical trial patient data. GEM model fitting to the original airway pressure waveform is better than any existing models when reverse triggering asynchrony is present. The fitting error of GEM model was less than 10% for both simulated data and clinical trial patient data. ConclusionGEM can capture the respiratory mechanics in the presence of patient effect in volume control ventilation mode and also can be used to assess patient-ventilator interaction. This model determines basis functions magnitudes, which can be used to simulate any waveform of patient effort pressure for future studies. The estimation of parameter identification GEM model can further be improved by constraining the parameters within a physiologically plausible range during least-square nonlinear regression.

Validation and Application of a Kinetic Model for Downdraft Biomass Gasification Simulation

AbstractBiomass gasification is widely recognized as an effective method to obtain renewable energy. To accurately predict the syngas and tar compositions is a challenge. A chemical reaction kinetics model based on comprehensive gasification kinetics is proposed to simulate downdraft biomass gasification. The kinetic model is validated by direct comparison to experimental results of two downdraft gasifiers available in the literature and is found to be more accurate than the widely used Gibbs energy‐minimizing model (GEM model). The kinetic model is then applied to investigate the effects of equivalence ratio (ER), gasification temperature, biomass moisture content, and biomass composition on syngas and tar production. Accurate water‐gas shift and CO shift reaction kinetics are found critical to achieve good agreement with experimental results.

Experimental study of fast-neutron production and moderation for accelerator-based BNCT system

This work aims to study the fast-neutron production and moderation for the development of a compact accelerator-based multi-port Boron Neutron Capture Therapy (AB-mBNCT) system. An initial energy distribution and the efficiency of a test moderator assembly (TMA) for fast neutrons from a tungsten (W) target bombarded with a 53 MeV proton beam were measured using organic scintillators. The experimental results were reproduced with reasonable accuracy by simulations using the PHITS code. This paper will discuss about the experimental outcome and the related benchmark calculations by PHITS code.

The Research on Promoting Characteristic Agricultural Industry Competitiveness Based on GEM Model

The Research on Promoting Characteristic Agricultural Industry Competitiveness Based on GEM Model

A AÇÃO DO GÊNERO PUBLICITÁRIO MULTIMODAL NA MÍDIA DIGITAL FACEBOOK

Neste trabalho, realizamos uma análise multimodal de dois anúncios publicitários de O Boticário, veiculados na mídia digital Facebook, em junho de 2018, de modo a perceber o gênero como ação social e a intencionalidade publicitária. Metodologicamente, nos valemos de uma análise qualitativa-interpretativa com base nos conceitos de Jewitt (2013) e das camadas do modelo GeM, proposto por Hiipalla (2014), considerando-se a atuação das funções da linguagem de Halliday (2004) presentes nos modos semióticos, partindo de suas considerações sobre a linguagem como um sistema multifuncional, o qual representa a realidade, ordena as relações sociais e estabelece identidades (FAIRCLOUGH, 2001, P.27). Também levamos em conta alguns conceitos de Kress e van Leeuwen (2001 e 2006) e Fairclough (2001), expandidos a partir de Halliday para o modo visual e discursivo. Concluímos que as affordances multimodais do gênero publicitário imprimem significados em camadas individuais e na junção dos conjuntos multimodais na geração de efeitos que incentivam o consumo, interligando produtos ao self, ou seja, à identidade pessoal da consumidora.

Complex forecasts of heavy snowfalls in the Urals with global and mesoscale numerical models

This paper presents an assessment of short-term numerical forecasts of precipitation in the cold period of the Urals. The use of global (GEM and GFS) and mesoscale (WRF) models in forecasting of heavy snowfalls is considered. The reliability levels of the 15-h and 27-h forecasts with the GEM, GFS, and WRF models are approximately equal. The 39-h forecasts with the WRF model are least accurate. The dependences of the quality of model forecasting on synoptic-scale environments, seasonal patterns, geographical location, and topography are obtained. The heavy snowfall events formed by a warm front, a cold front, and in the northern part of a cyclone are predicted with satisfactory accuracy. The least successful numerical forecasts are obtained for non-frontal precipitation in the warm sector of a cyclone. All three models tend to overestimate the precipitation amount during the cold period: the number of false alarms exceeds the number of missed events. The numerical forecasts of precipitation during the cold period have higher reliability levels for the territory of Western Urals than for the Eastern Urals region.

Modeling of electrical conductive graphene filled epoxy coatings

Electrical conductive coatings were prepared by incorporating various fractions of graphene nanoplatelets (GNPs) into epoxy resin, i.e. 0–2.5 wt.%. High stability of GNPs as dispersed form in chloroform and their uniform distribution in epoxy matrix were proved by UV–vis spectroscopy, turbidimetry and optical microscopy techniques. SEM images were also used to check the GNPs state in each step of fabrication. All epoxy coatings underwent electrical conductivity measurement, the conductivity of epoxy coating increased 13 orders of magnitude by addition of 2.5 wt.% GNP. Through this experiment, GNP fraction as low as 0.5 wt.% was defined as percolation threshold. Four types of conductivity models were analyzed (i.e. Kirkpatrick and Zellen, GEM, updated Mamunya and additive model) to select the most precise one for predicting epoxy/GNP coating conductivity behavior. It was finally demonstrated that the additive model presented the best correlation with the experimental data. We also revised the additive model parameters to further promote its accuracy. Finally, mechanical properties of coatings studied by DMTA demonstrated relative increase of about 100% in storage modulus of coating at percolation threshold with respect to neat coating, approving the desired conductivity and mechanical attributes for graphene containing epoxy coating.

Export competitiveness analysis of Pakistan garments industry based on GEM Model

The main purpose of this research study is to investigate export competitiveness of Pakistani garment industry in the global markets by applying the GEM Model. GEM model is vastly applied in many industries to analyse the export competitiveness of the particular cluster. Survey technique applies to primary data collection through a structured questionnaire. Pakistani garments industry export competitiveness based on GEM Model is analysed by using the analytic hierarchy process (AHP) technique. After thorough analysis, overall calculated GEM score is 382 for Pakistani garment industry. GEM score 382 means that Pakistani garment industry is above the national average level and possess country wide competitive advantages. The future research scope is that there can be studied the associations between one or many other factors to check the competitiveness level of Pakistani garment industry. This research work has very important practical implications for all stakeholders to evaluate the export competitiveness level of the garment industry. By applying the GEM model, the organization can evaluate its strengths and weaknesses, so that organizations can cope with the international competition accordingly which is supportive to make decisions for their businesses.

Abstract 2759: Rational combinations for immune checkpoint blockade using β-catenin RNAi therapy

Abstract Recent research has shown that Wnt/β-catenin signaling drives resistance to cancer immunotherapy by promoting the exclusion of T-cells from the tumor microenvironment. DCR-BCAT is an RNAi-based experimental medicine targeting β-catenin, formulated in a tumor-selective nanoparticle. We had previously reported that systemic administration of DCR-BCAT increased tumor-associated cytotoxic T-cells and dramatically improved responses to immunotherapy agents, in murine syngeneic models and GEM models. In this new work, we explore the mechanisms by which Wnt/β-catenin signaling promotes resistance to immune checkpoint blockade, and propose context-specific therapeutic combinations using RNAi therapy. We will present novel in vivo experimentation demonstrating that DCR-BCAT significantly enhances sensitivity to immunotherapy using different drug regimens in multiple tumor types. Citation Format: Shanthi Ganesh, Serena Shui, Kevin Craig, Weimin Wang, Bob D. Brown, Marc Abrams. Rational combinations for immune checkpoint blockade using β-catenin RNAi therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2759.

Determining porosity and pore network connectivity of cement-based materials by a modified non-contact electrical resistivity measurement: Experiment and theory

A modified non-contact electrical resistivity measurement is proposed to determine porosity and pore network connectivity of cement-based materials. The porosity of mortar with different water-to-cement ratios was tested by mercury intrusion porosimetry (MIP) and the tortuosity was calculated from pore entrapment volume fraction. The relationship between pore structure and resistivity was studied using the three most commonly used theories. It was observed that the multi-phase phenomenological model can indicate the effect of porosity and pore connectivity on the resistivity of cement-based materials. The parameter m in Archie's Law as an index of pore connectivity can be expressed as a variable that varies with the tortuosity. The parameters in the GEM model are closely related to the nature of the material: the parameter M should be related to the composition of the material and the degree of hydration of the cement, and the parameter t is a variable that varies with the pore connectivity. Based on these theories, equations are derived to correlate the porosity and pore network connectivity to the formation factor of cement based materials. The developed approach thus has a potential to be used as a simple and effective tool for pore structure investigation of cement based materials.

Soluble stroma‐related biomarkers of pancreatic cancer

The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of reliable biomarkers. This study investigated the value of soluble stroma‐related molecules as PDAC biomarkers. In the first exploratory phase, 12 out of 38 molecules were associated with PDAC in a cohort of 25 PDAC patients and 16 healthy subjects. A second confirmatory phase on an independent cohort of 131 PDAC patients, 30 chronic pancreatitis patients, and 131 healthy subjects confirmed the PDAC association for MMP7, CCN2, IGFBP2, TSP2, sICAM1, TIMP1, and PLG. Multivariable logistic regression model identified biomarker panels discriminating respectively PDAC versus healthy subjects (MMP7 + CA19.9, AUC = 0.99, 99% CI = 0.98–1.00) (CCN2 + CA19.9, AUC = 0.96, 99% CI = 0.92–0.99) and PDAC versus chronic pancreatitis (CCN2 + PLG+FN+Col4 + CA19.9, AUC = 0.94, 99% CI = 0.88–0.99). Five molecules were associated with PanIN development in two GEM models of PDAC (PdxCre/LSL‐KrasG12D and PdxCre/LSL‐KrasG12D/+/LSL‐Trp53R172H/+), suggesting their potential for detecting early disease. These markers were also elevated in patient‐derived orthotopic PDAC xenografts and associated with response to chemotherapy. The identified stroma‐related soluble biomarkers represent potential tools for PDAC diagnosis and for monitoring treatment response of PDAC patients.

Abstract IA24: Identification of therapies for plexiform neurofibromas, a precursor of malignant peripheral nerve sheath tumors

Abstract Plexiform neurofibromas (PNs) are complex nerve and soft tissue tumors that affect 25-50% of individuals with neurofibromatosis type 1 (NF1), the most common genetic disease in man with a predisposition to cancer. PNs cause lifelong morbidity ranging from deformity to paralysis and mortality due to organ compression, and progress to MPNST in ~8-13% of patients. The generation of genetically engineered mouse models that closely recapitulate the development of human plexiform neurofibromas has allowed our laboratory and others to pursue genetic and pharmacologic studies to identify novel therapies. Genetic and adoptive transfer studies conducted by our lab in collaboration with Dr. Luis Parada identified a key role for c-kit/kit-ligand in tumor initiation and progression. These data led to a clinical trial administering imatinib mesylate to target aberrant stem cell factor (SCF)/c-kit signaling in the tumor microenvironment, which induced the only objective clinical responses ever obtained in a therapeutic clinical trial in pNF. Based on the observation that young children with head, neck, and airway tumors were most likely to have partial tumor regression, a registration trial in this patient population is currently being pursued. Further, additional phase 2 trials using other receptor tyrosine kinases that include c-kit are under way as well. More recently, studies in GEM models informed clinical trials of MEK inhibitors led by Dr. Brigitte Widemann (Pediatric Branch of NCI) to directly inhibit aberrant Ras signaling in PN cells. Studies are ongoing to extend these promising initial clinical findings to investigate the developmental, molecular, and pharmacokinetic effects of c-kit and MEK inhibition alone and in combination in preclinical models. Specifically, studies to explore adaptive responses to MEK inhibition monotherapy in mice and patients treated with selumetinib via integrated exome, RNAseq, and kinome studies in pre- and post-treatment tumor tissue are under way. Citation Format: D. Wade Clapp. Identification of therapies for plexiform neurofibromas, a precursor of malignant peripheral nerve sheath tumors [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA24.

Highlights of This Issue

Many solid tumors demonstrate dysregulation of fibroblast growth factor receptors (FGFRs) but currently no selective inhibitors of FGFR are approved for cancer treatment. Here, Venetsanakos et al. describe the characterization of a pan-FGFR inhibitor PRN1371 that forms a covalent bond with a cysteine in the FGFR active site. The authors describe the high selectivity and strong anti-tumor activity of PRN1371 and further highlight that covalent binding enables PRN1371 to sustain inhibition of FGFR even after the compound is no longer present in circulation. PRN1371 is currently undergoing clinical trials to explore the benefits that these attributes provide to patients with solid tumors.Histone deacetylase (HDAC) inhibition in synovial sarcoma has been found to disrupt the driving SS18-SSX protein complex, resulting in apoptosis. To better understand the molecular effects of HDAC inhibitors, Laporte and colleagues used RNA-seq transcriptome analysis to uncover mechanisms of cell death in six human synovial sarcoma cells lines. Specific to SS18-SSX positive cell lines, polycomb-group targets were reactivated resulting in pro-apoptotic transcriptional patterns, which was mediated by ROS activity. Furthermore, HDAC inhibition in a GEM model of synovial sarcoma resulted in significantly decreased tumor burden following treatment with novel HDAC inhibitor quisinostat. This study provides mechanistic support for clinical proposals to use HDAC inhibitors in synovial sarcoma and related diseases.Increased MET activity is linked to poor prognosis of several human cancers. In this study, Grandal, Havrylov and colleagues present Sym015, an antibody mixture composed of two IgG1 antibodies against non-overlapping epitopes on MET. Synergistic inhibitory activity of the two antibodies comprising Sym015 was demonstrated in vitro and in vivo. Sym015 was found to block ligand binding and downstream signaling and to induce MET degradation. Sym015 also potently induces secondary effector functions. The enhanced effect of Sym015 is predicted to render Sym015 superior to single antibodies targeting MET. Clinical activity of Sym015 is currently being evaluated in a phase I trial.TRAIL has been considered as promising anti-cancer therapeutic. Clinical studies with soluble TRAIL, however, were largely disappointing. Here, Hutt and colleagues applied defined oligomerization and tumor targeting to improve the activity of a single-chain version of TRAIL (scTRAIL) and compared three EGFR-targeting as well as two non-targeted hexavalent scTRAIL formats. All EGFR-targeted molecules showed similar and improved activity compared to non-targeted formats in vitro, while in vivo studies highlighted superior efficacy of Fc-comprising molecules. Furthermore, depending on the tumor entity, Fc-scTRAIL may induce equally effective anti-tumor activity as targeted counterparts. This study supports the rational development of potent hexavalent TRAIL-based therapeutics.

Institutional-driven dimensions and the capacity to start a business

PurposeDrawing insights from institutional theory, the purpose of this paper is to analyse the synergistic effects of a range of entrepreneurial framework conditions (EFCs) on the capacity to start a business within different types of economies.Design/methodology/approachThis is a preliminary study that uses data from the National Expert Survey-Global Entrepreneurship Monitor (NES-GEM). Specifically, the data were gathered through the application of a questionnaire to National Entrepreneurship Experts in a cross-cultural context. Two countries – Portugal and Angola – are analysed.FindingsAmong the five structural relationships involving institutional drivers analysed, four are found to be statistically significant in the Portuguese sample. Three are found to be statistically significant in the Angolan sample. The results from the multigroup analysis did not support most of the proposed relationship between the two countries.Research limitations/implicationsThis study is limited by the number and type of countries selected and by the fact that each sub-sample covers several years. It also relies on the perceptions of national experts on entrepreneurship covering several areas. Another limitation is based on the fact that this study emphasises mainly a macro perspective. Therefore, interpretation of these findings and their generalisation should be made with caution.Originality/valueFirst, this study addresses an area of the GEM model that is believed to be under-researched (NES). Second, the model presented is based on latent variables and analysed through a variance-based method, PLS-structural equation modelling. Third, this study compares the proposed relationships between two sub-sample data sets that represent a factor-driven economy and an innovation-driven economy. Fourth, and most importantly, this study responds to the call for the need to use a new procedure for measurement invariance assessment for composite modelling.

Preparation and performance of conductive mortar based on lightweight conductive aggregates

In this study, lightweight conductive aggregates (CA) loaded with modified agar gel was prepared, and their influence on the resistivity of conductive cement-based materials was investigated. Results indicate that by impregnation treatment, agar gel was efficiently loaded in porous lightweight aggregates, thus CA with a resistivity of 0.5Ω·m was obtained. The prepared CA significantly improved the conductivity of cement-based materials, and the modification effect was and related to the altered microstructure of cement matrix and conductive network established by CA, and can be characterized by GEM model. The prepared CA have promising potential for applications related to cement-based composites.

Abstract 5112: Evaluation of FF-10502-01, a new pyrimidine nucleoside analogue, in pancreatic (PANC) patient-derived xenograft (PDX) models compared to gemcitabine and in combination with nab-paclitaxel

Abstract Introduction FF-10502-01 is a synthetic pyrimidine nucleoside analogue structurally similar to gem with a substitution of sulfur for oxygen in the pentose sugar. In previous studies, FF-10502-01 demonstrated preclinical efficacy across multiple solid tumors, including PANC cancer. In this study, we investigated the anti-tumor effect of FF-10502-01 in PANC PDX models. Methods 10 PANC PDX tumors were sourced from primary (2) or metastatic sites (8). 7 demonstrated high resistance (HR) to gem, 1 intermediate, and 2 low. In the dose-finding study, 3 PDX models were studied in 9 grps of NOD-SCID mice (n=10/grp), treated with 240 or 480 mg/kg FF-10502-01, 3 or 6 mg/kg nab-pac or 240 mg/kg gem, alone and in combination for 28d, followed by 28d observation. The definitive study consisted of 7 PDX models. 6 grps (n=10/grp) were treated with 240 or 480 mg/kg FF-10502-01, 6 mg/kg nab-pac or 240 mg/kg gem, alone and/or in combination for 28d, followed by 28d observation. After subcutaneous transplantation, animals were left undisturbed for 7d. Animals were monitored weekly and tumor volume measured with calipers. Average tumor volume (mm3) for each group at randomization into treatment grps ranged from 184.34 – 199.51 (SD ± 20.94 – 30.40). Statistical significance was determined using one-way ANOVA and Tukey’s test. Results At clinically relevant doses, FF-10502-01, alone and in combination with nab-pac demonstrated greater tumor growth suppression than vehicle-treated animals (p≤0.0001). In 7 models, FF-10502-01/nab-pac demonstrated higher tumor growth suppression than gem/nab-pac (p≤0.5, p≤0.01 or p≤0.001), irrespective of resistance to gem. In 3 models, there was no difference, but these models were highly responsive to gem/nab-pac, thus minimizing the effects of FF-10502-01/nab-pac. Despite statistical insignificance, FF-10502-01/nab-pac still demonstrated greater tumor growth inhibitory activity to gem/nab-pac. In HR gem models, FF-10502-01 was superior to gem (p≤0.0001, p≤0.001, p≤0.05) in 3 of 7, and FF-10502-01/nab-pac was superior to gem/nab-pac in 6 of 7 (p nab-pac (p≤0.0001, p≤0.0001, p≤0.01, p≤0.05). FF-10502-01/nab-pac also was more tolerable than gemcitabine/nab-pac, as demonstrated by less weight loss. Conclusions FF-10502-01 is a new pyrimidine nucleoside analogue with demonstrated preclinical efficacy in solid tumors, including PANC cancer. In PANC PDX models, FF-10502-01 alone and in combination with nab-pac demonstrated higher efficacy and better tolerability than gem alone or gem/nab-pac. FF-10502-01 is in Phase 1 clinical development. Citation Format: Takeaki Suzuki, Linda J. Paradiso, Jill Ricono, Jonathan Nakashima, Yoshihide Iwaki, Shinji Mima, Takayuki Yamada, Chihaya Kakinuma, Hiroyuki Iwamura, Shinichi Watanabe. Evaluation of FF-10502-01, a new pyrimidine nucleoside analogue, in pancreatic (PANC) patient-derived xenograft (PDX) models compared to gemcitabine and in combination with nab-paclitaxel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5112. doi:10.1158/1538-7445.AM2017-5112

Study on The Industrial Cluster of Tropical Bananas Based on Gem Model

Abstract In recent years, the development of agricultural industry clusters is rapid in China. As a main producing area of bananas, the Hainan Ledong Industrial Cluster’s competitiveness is of great significance to the development of the whole banana industry in China. This paper first analyzed the cultivation of tropical banana and the market share of bananas in each region, and then analyzed the competitiveness of Ledong banana industry cluster through the GEM (Groundings- Enterprises- Markets) model. The results showed that the GEM model score was 456 points, and the domestic cluster competitiveness exceeded the average level. The “factor pair” socre suggested that the scores of the structure, strategy and competition of the enterprise were low, which restricted the development of Ledong banana industry cluster.

Comprehensive evaluation of airport economic zone development quality based on OWA operator weights

Based on GEMS model and the quality development of airport economic zone is defined firstly, the quality development evaluation index system is set up which included four first-degree indexes. The indexes obtain basic conditions, industrial development, radiation effects and development environment, and combines the methods of OWA operators and Fuzzy comprehensive assessment method to establish the evaluation model. Finally, though empirical analysis, evaluation result of the model is close to current situation of quality development of Zhengzhou airport economic zone, which shows that the model is effective and feasible.

The Compared Study of Competitiveness of Electron Industry Clusters: Case of Wuhan, Shanghai and Guangzhou

With electronic information product manufacturing in the world transferring to China, the electron industrial clusters have become the main form, of which regional economy gain competitive advantages. So we selected Wuhan, Shanghai and Guangzhou as samples. Then we figured out electron industrial clusters’ competitiveness score of the three cities, using the GEM model. At the same time, we systematically analyzed electron industry clusters of Wuhan Optical Valley from the advantages and disadvantages of the six aspects.