36 research outputs found

    Моделирование радиальных колебаний подпружиненного валка вальц-пресса

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    Carried out simulation of oscillations of a spring-loaded roll in a roll compactor when interacting the powder being compacted with the rolls. Considering the separation of the feed and compaction areas in the contact area of the roll with the material being compacted, we obtain the dependence of the force acting on the roll on the gap size between the rolls. It is shown that this dependence is non-linear, and it can be described with a sufficiently high accuracy degree by an exponential function with a negative exponent in the working range. The given numerical solution of the equation of free nonlinear oscillations of the spring-loaded roll has shown that considering the deformation of the material being compacted leads to a reduction of the natural frequency of the system by 20–25 % compared to the case, where the pressure force of the powder on the roll is assumed to be independent of the gap size. The nonlinearity of the dependence of the pressure force on the gap also leads to the increase by 10 % in the calculated values of the maximum displacements. The developed approach to the calculation of oscillations of the spring-loaded roll in the roll compactor enables to take into account the peculiarities of deformation of the powder being compacted during its interaction with the rolls. In addition, it allows estimating the frequencies and oscillation amplitudes and setting the optimum range of spring rate values, at which the occurrence of resonance in the machine is not possible.Выполнено моделирование колебаний подпружиненного валка вальц-пресса при взаимодействии прессуемого порошка с валками. С учетом выделения в области контакта валка с прессуемым материалом зон подачи и прессования, получена зависимость силы, действующей на валок, от величины зазора между валками. Показано, что эта зависимость имеет нелинейный характер, причем в рабочем диапазоне с достаточно высокой степенью точности может быть описана степенной функцией с отрицательным показателем степени. Приведено численное решение уравнения свободных нелинейных колебаний подпружиненного валка, которое продемонстрировало, что учет деформирования сжимаемого материала приводит к снижению частот собственных колебаний системы на 20–25 % по сравнению со случаем, при котором сила давления порошка на валок принимается не зависящей от величины зазора. Нелинейность зависимости силы давления от зазора приводит также к увеличению на 10 % расчетных значений максимальных смещений. Разработанный подход к расчету колебаний подрессоренного валка вальц-пресса позволяет учесть особенности деформирования прессуемого порошка при его взаимодействии с валками, а также позволяет, наряду с оценкой частот и амплитуд колебаний, установить оптимальный диапазон значений коэффициента жесткости пружины, при котором появление резонанса в машине будет невозможно

    ВЛИЯНИЕ ДИНАМИЧЕСКОЙ НАГРУЖЕННОСТИ НА ДОЛГОВЕЧНОСТЬ ЗУБЧАТОЙ ПЕРЕДАЧИ ТРАНСМИССИИ ТЯЖЕЛОНАГРУЖЕННЫХ ПРОХОДЧЕСКИХ МАШИН

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    The article proposes a new method of calculation of the indicators of the durability of the gear transmission of heavy-loaded roadheading machines, allowing a more accurate assessment of the dynamic loading of the teeth. Within the framework of this technique, the elastic moment amplification factors determined by the amplitude-frequency characteristic of transmission are used instead of the specific circumferential dynamic force in the calculation of the maximum operating voltages. The maximum stresses in the bending of teeth and the probability of failure-free operation of the technical system are determined. A spur transmission used in the drive of the Executive body of roadheader is considered as an example of application of the proposed design technique. The comparison of calculated estimations of gear transmission reliability obtained on the basis of the standard method and using amplitude-frequency characteristics is carried out. In the considered design example durability of transfer for a step cycle of loading is more than 2 times higher in comparison with a continuous cycle of loading. It is shown that using a standard calculated coefficient that takes into account dynamic load, the calculated estimations of the durability of the transmission are significantly overestimated. At the same time, the error of the standard method will depend on the frequency range at which the transmission operates, and this error is most significant when the transmission operates near its own frequencies.Расчет максимальных напряжений при изгибе и контактном взаимодействии зубьев шестерен осуществляется на основе известных соотношений, содержащих стандартным образом определяемые коэффициенты. Предложена новая методика расчетного определения показателей долговечности зубчатой передачи трансмиссии тяжелонагруженных проходческих машин, позволяющая более точно оценить динамическую нагруженность зубьев. В рамках данной методики при вычислении максимальных действующих напряжений вместо удельной окружной динамической силы используются коэффициенты усиления упругого момента, определяемые по амплитудно- частотной характеристике передачи. Определены максимальные напряжения при изгибе зубьев, дана оценка вероятности безотказной работы технической системы. В качестве примера использования предложенной расчетной методики рассмотрена прямозубая цилиндрическая передача, используемая в приводе исполнительного органа проходческого комбайна. Проведено сопоставление расчетных оценок показателей надежности зубчатой передачи, полученных на основе стандартной методики и с использованием амплитудно-частотных характеристик. На графиках представлены амплитудно-частотная характеристика передачи, полученная с использованием динамической модели трансмиссии, а также кривые функций распределения ресурса передачи с различными циклами нагружения, построенные с использованием предложенной методики. В рассмотренном расчетном примере долговечность передачи для ступенчатого цикла нагружения выше более чем в 2 раза по сравнению с непрерывным циклом нагружения. Показано, что при использовании стандартно вычисляемого коэффициента, учитывающего динамическую нагрузку, расчетные оценки долговечности передачи оказываются значительно завышены. При этом погрешность стандартной методики будет зависеть от диапазона частот, при которых работает передача, и наиболее существенна эта погрешность при работе передачи вблизи собственных частот

    Prognostic gene expression signature for high-grade serous ovarian cancer.

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    BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate \u3c 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P \u3c 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P \u3c 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches

    Prognostic gene expression signature for high-grade serous ovarian cancer

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    BACKGROUND:Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS:Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS:Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION:The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches

    Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

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    PURPOSE: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. RESULTS: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.Core funding for this project was provided by the National Institutes of Health (R01-CA172404, PI: S.J. Ramus; and R01-CA168758, PIs: J.A. Doherty and M.A.Rossing), the Canadian Institutes for Health Research (Proof-of-Principle I program, PIs: D.G.Huntsman and M.S. Anglesio), the United States Department of Defense Ovarian Cancer Research Program (OC110433, PI: D.D. Bowtell). A. Talhouk is funded through a Michael Smith Foundation for Health Research Scholar Award. M.S. Anglesio is funded through a Michael Smith Foundation for Health Research Scholar Award and the Janet D. Cottrelle Foundation Scholars program managed by the BC Cancer Foundation. J. George was partially supported by the NIH/National Cancer Institute award number P30CA034196. C. Wang was a Career Enhancement Awardee of the Mayo Clinic SPORE in Ovarian Cancer (P50 CA136393). D.G. Huntsman receives support from the Dr. Chew Wei Memorial Professorship in Gynecologic Oncology, and the Canada Research Chairs program (Research Chair in Molecular and Genomic Pathology). M. Widschwendter receives funding from the European Union’s Horizon 2020 European Research Council Programme, H2020 BRCA-ERC under Grant Agreement No. 742432 as well as the charity, The Eve Appeal (https://eveappeal.org.uk/), and support of the National Institute for Health Research (NIHR) and the University College London Hospitals (UCLH) Biomedical Research Centre. G.E. Konecny is supported by the Miriam and Sheldon Adelson Medical Research Foundation. B.Y. Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. H.R. Harris is 20 supported by the NIH/National Cancer Institute award number K22 CA193860. OVCARE (including the VAN study) receives support through the BC Cancer Foundation and The VGH+UBC Hospital Foundation (authors AT, BG, DGH, and MSA). The AOV study is supported by the Canadian Institutes of Health Research (MOP86727). The Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group, was funded by the National Health and Medical Research Council Enabling Grants ID 310670 & ID 628903 and the Cancer Institute NSW Grants ID 12/RIG/1-17 & 15/RIG/1-16. The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of Western Australia (Multi-State Applications 191, 211 and 182) and the National Health and Medical Research Council of Australia (NHMRC; ID199600; ID400413 and ID400281). BriTROC-1 was funded by Ovarian Cancer Action (to IAM and JDB, grant number 006) and supported by Cancer Research UK (grant numbers A15973, A15601, A18072, A17197, A19274 and A19694) and the National Institute for Health Research Cambridge and Imperial Biomedical Research Centres. Samples from the Mayo Clinic were collected and provided with support of P50 CA136393 (E.L.G., G.L.K, S.H.K, M.E.S.)

    Prognostic gene expression signature for high-grade serous ovarian cancer.

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    BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches

    Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE)

    Get PDF
    PURPOSE: Gene-expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by non-standardized methods which are not applicable in a clinical setting. We sought to generate a clinical-grade minimal gene-set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene-expression data from 1650 tumors. We applied resulting models to NanoString data on 3829 HGSOCs from the Ovarian Tumor Tissue Analysis Consortium. We further developed, confirmed, and validated a reduced, minimal gene-set predictor, with methods suitable for a single patient setting. RESULTS: Gene-expression data was used to derive the Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor infiltrating lymphocytes, and outcome. The locked-down clinical-grade PrOTYPE test includes a model with 55 genes that predicted gene-expression subtype with >95% accuracy that was maintained in all analytical and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical-grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications
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