Modelling Ultra High Pressure Compaction of Powder

The use of high pressure high temperature (HPHT) equipment varies; in mineral physics research the equipment is used for investigation of the earth’s interior and in industry it is used for commercially produced synthetic diamonds and other polycrystalline products. The common denominator for almost all high pressure systems is to use capsules where a powder material encloses the core material. Numerical analysis of the manufacturing processes with working conditions which reaches ultra high pressure (above 10 GPa) requires a constitutive model which can handle the specific behaviours of the powder from a low density to solid state. Calcium carbonate (CaCO3) is a mineral that can be used in high pressure processes and is very common in the earth core. A constitutive model for calcium carbonate applied to high pressure compaction is presented. The plastic response of powder is non-linear and described in a rate-independent cap plasticity model. The cap model has been developed to capture the behaviour of minerals in high pressure applications. The yield function consists of a failure envelope fitted to a strain-hardening cap. Experimental tests with a Bridgman anvil set-up using calcium carbonate powder discs are performed. Numerical analysis using the finite element method is done to virtually reproduce the experiments. Results from the analysis are compared to measured experimental results. The numerical analyses agree reasonably well with the experimental results

Modelling of internal stresses in grinding charges

Physically realistic methods are a necessity to close the gap between reality and numerical result in modelling of tumbling mills. A problem is that tumbling mills often operate in a metastable state because of the difficulty to balance the rate of replenishment of large ore particles from the feed with the consumption in the charge. Understanding of the charge motion within the mill is of significance in mill optimisation. Both the breakage of ore particles and the wear of liners/ball media are closely linked to the charge motion. In this work, a ball charge and its interaction with the mill structure is modelled with the smoothed particle hydrodynamic (SPH) method. The mesh free formulation and the adaptive nature of the SPH method result in a method that handles extremely large deformations and thereby suits modelling of grinding charges and pulp liquids. The flexible rubber lifter and the lining are modelled with the finite element method (FEM). A hyper-elastic model governs the elastic behaviour of the rubber. The comminution process is complex and to include all phenomena that occur in a single numerical model is today not possible. Therefore, modelling the physical interaction between charge, mill structure and pulp liquid is the major goal in this work. The SPH-FEM model can predict responses of the mill structure e.g. stress and strain. All parts of the mill system will affect its response and the model gives the opportunity to study the influence of the mill structure and e.g. pressure and shear stresses in the charge. This computational model also makes it possible to predict, the contact forces for varying mill dimensions, liner combinations and pulp densities. By comparing numerical results with experimental measurement from grinding in a pilot mill equipped with an instrumented rubber lifter a validation is done. The deflection profile of the lifters obtained from SPH-FEM simulation shows a reasonably good correspondence to pilot mill measurements as measured by an embedded strain gauge sensor. This model gives information on the grinding process in tumbling mills and better correlation with experimental measurements

PFEM-based modeling of industrial granular flows

The potential of numerical methods for the solution and optimization of industrial granular flows problems is widely accepted by the industries of this field, the challenge being to promote effectively their industrial practice. In this paper, we attempt to make an exploratory step in this regard by using a numerical model based on continuous mechanics and on the so-called Particle Finite Element Method (PFEM). This goal is achieved by focusing two specific industrial applications in mining industry and pellet manufacturing: silo discharge and calculation of power draw in tumbling mills. Both examples are representative of variations on the granular material mechanical response—varying from a stagnant configuration to a flow condition. The silo discharge is validated using the experimental data, collected on a full-scale flat bottomed cylindrical silo. The simulation is conducted with the aim of characterizing and understanding the correlation between flow patterns and pressures for concentric discharges. In the second example, the potential of PFEM as a numerical tool to track the positions of the particles inside the drum is analyzed. Pressures and wall pressures distribution are also studied. The power draw is also computed and validated against experiments in which the power is plotted in terms of the rotational speed of the drum

Design-build experiences and student-centered-learning in biomedical engineering curricula

ABSTRACT The field of biomedical engineering (BME) is progressing rapidly into new areas, demanding the BME students to develop multidisciplinary skills, knowledge and a possibility for life-long learning. Changing the educational arena from teacher-centered to studentcentered-learning is a challenge in the BME domain. CDIO (Conceive Design Implement Operate) design-build courses, starting at the freshman year, makes laboratory and research environment enhance student-centered-learning resulting in communicative skills and teamwork. BME specialization, student-centered-learning and design-build experiences are introduced as an integrative part during the third and fourth academic year. Student-centeredlearning is often recognized as a situation where the learning possibilities are relevant to the students and where the students themselves determine the short-term goals. The expert or authority teaching has to be replaced by mentorship and facilitators. This is recognized in design-build courses. BME cases without a known solution can be treated and solved through integrative thinking and problem identification. The cognitive tasks require the acquisition and synthesis of information. It prepares students to participate in research laboratories as undergraduates and it prepares them for time-constrained problem-solving in the real world. For research studies and developments in working life, skills including dynamic group processes and awareness of the affective domain are necessary. BME education has three years experience of design-build courses from the freshman to the last academic year. Directives for the projects are based on clinical settings or demands engaging students to solve real world problems. Interaction with real customers or experts in the field encourages, stimulate and enhance all parts of the CDIO framework. To get a prosperous and successful work throughout the project cycle the project teams as we believe should be built on heterogeneous skill, age and gender, the affective domain all harmonized using a team contract. Project groups have also been enrolled with exchange students creating international groups. Feedback of the group process is given throughout the design-build project but especially after completion. Theoretical parts supplement the project and the group both in-depth but also to focus and harmonize the group towards the designbuild project outcome. Experts working in the field validate and test the project. Assessment is conformant to a student-centered-learning process as an integrative part of the course. Development of assessment protocols and strategies as an integrative part of the learning process must be stimulated and emphasized

A scalable adenovirus production process, from cell culture to purified bulk

Adenovirus (AdV) vectors are commonly used in cancer gene therapy trials, evaluated in gene therapy and used as vaccines for various diseases. AdV vectors are well studied and are suitable as vaccine vectors due to their ability to infect different cell types, remain episomal and produce stable high titer material. Manufacturing of safe and efficacious clinical-grade virus relies on a scalable and cost-effective production process. In this study, we have combined experimental work and process economy calculations, from AdV production in cell culture to purified bulk product up to 10L scale. An efficient and scalable process for AdV production was developed by evaluation of each process step. The most studied vector is serotype 5, making this a suitable system for process development of AdV vectors. Human AdV5 expressing the green fluorescent protein (GFP) was used for process development. First, suspension HEK 293 cells adapted to serum-free cell culture medium were optimized for AdV production and evaluated in different single use bioreactor systems. Tween 20 was used for cell lysis as a replacement for the traditionally used Triton X-100 (now on the Authorization list (Annex XIV) of REACH, the regulation on Registration, Evaluation, Authorization and restriction of Chemicals). A residual Tween 20 assay with low detection limit was set-up. Filters and conditions for clarification, concentration and buffer exchange by tangential flow filtration were optimized. Anion exchange based capture step alternatives were compared, including different chromatography resins and membrane formats. Finally, core bead technology was evaluated as an alternative to size exclusion chromatography for the polishing step before the final formulation. Analytical methods for virus titer are challenging and depend on purity and quality of the sample. For total virus titer, qPCR and HPLC methods were used. Furthermore, a method based on surface plasmon resonance (Biacore) was developed for analysis of adenovirus titer. For infectious virus titer, we have used a cell based assay with automatic image analysis. Based on analytical data different downstream process alternatives were compared regarding load capacity, recovery and purity and we propose a robust and scalable process with a favorable process economy. Please click Additional Files below to see the full abstract

Enforcing the Federal Water Resource Servitude on Submerged and Riparian Lands

The epidermal growth factor receptor (EGFR) is frequently overexpressed in colorectal cancer and is therefore an attractive target for treatment. (ZEGFR:1907)2 is a newly developed dimeric affibody molecule with high affinity to the extracellular part of EGFR. In this study, we evaluated the cytotoxic effects of (ZEGFR:1907)2 in combination with external radiation and the possible inhibitory effects in the EGFR signalling pathways in the colon cancer cell lines HT-29 and HCT116. The effects were compared with an EGFR antibody (cetuximab) and the tyrosine kinase inhibitors (erlotinib and sunitinib). These cell lines are genotypically different with respect to e.g. KRAS and BRAF mutational status, recently shown to be of clinical significance for therapeutic effects. Both cell lines express approximately 100,000-150,000 EGFRs per cell but differ in the radiation response (HCT116, SF2=0.28 and HT-29, SF2=0.70). Exposure to (ZEGFR:1907)2 produced a small, but significant, reduction in survival in HCT116 but did not affect HT-29 cells. Similar results were obtained after exposure to EGF and the EGFR antibody cetuximab. The EGFR tyrosine kinase targeting inhibitor erlotinib and the multi-tyrosine kinase inhibitor sunitinib reduced survival in both cell lines. However, none of the drugs had any significant radiosensitizing effects in combination with radiation. Akt and Erk are central proteins in the EGFR downstream signalling and in the cellular response to ionizing radiation. The activation of Akt (Ser 473) and Erk (Thr202/Tyr204) by radiation was both dose- and time-dependent. However the activation of EGFR was not clearly affected by radiation. Neither (ZEGFR:1907)2 nor any of the other drugs were able to completely inactivate Akt or Erk. On the contrary, erlotinib stimulated Akt phosphorylation in both cell lines and in HCT116 cells Erk was activated. Overall the results illustrate the complexity in response to radiation and drugs in cells with differential phenotypic status.Online ISSN:1791-2423</p

The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ

Background: PolyQ diseases are autosomal dominant neurodegenerative disorders caused by the expansion of CAG repeats. While of slow progression, these diseases are ultimately fatal and lack effective therapies. Methods: A high-throughput chemical screen was conducted to identify drugs that lower the toxicity of a protein containing the first exon of Huntington's disease (HD) protein huntingtin (HTT) harbouring 94 glutamines (Htt-Q). Candidate drugs were tested in a wide range of in vitro and in vivo models of polyQ toxicity. Findings: The chemical screen identified the anti-leprosy drug clofazimine as a hit, which was subsequently validated in several in vitro models. Computational analyses of transcriptional signatures revealed that the effect of clofazimine was due to the stimulation of mitochondrial biogenesis by peroxisome proliferator-activated receptor gamma (PPARγ). In agreement with this, clofazimine rescued mitochondrial dysfunction triggered by Htt-Q expression. Importantly, clofazimine also limited polyQ toxicity in developing zebrafish and neuron-specific worm models of polyQ disease. Interpretation: Our results support the potential of repurposing the antimicrobial drug clofazimine for the treatment of polyQ diseases. Funding: A full list of funding sources can be found in the acknowledgments section.We thank the Chemical Biology Consortium Sweden for their help with the chemical libraries. Research was funded by grants from the Cancerfonden foundation (CAN 21/1529) and the Swedish Research Council (VR) (538-2014-31) to OF; and the Spanish Ministry of Science and Innovation and Spanish Ministry of Science (PID2021-123141OBI00 MCIU/AEI/FEDER, UE) to JJL, and the ICGEB CRP/HUN21-05_EC and the TKP-NVA-20 to KP. None of the funders contributed to the design, analysis or reporting of this study

Preparation, characterization and catalytic behavior for propanepartial oxidation of Ga-promoted MoVTeO catalysts

[EN] Two sets of Ga-promoted MoVTeO catalysts were synthesized hydrothermally and heat-treated at 600 degrees C in N-2: (i) materials prepared from gels with Mo/V/Te/Ga atomic ratios of 1/0.60/0.17/x (x=0-0.12) (A-series) and (ii) materials prepared from gels with Mo/V/Te/Ga atomic ratios of 1/0.60-x/0.17/x (x=0.15 or 0.25) (B-series). In addition, a Ga-containing MoVTeO catalyst was also prepared from M1-containing MoVTeO material by impregnation with aqueous solution of gallium and heat-treated at 450 degrees C in N-2. Catalysts were characterized by means of powder XRD, TEM, Raman spectroscopy, NH3-TPD and XPS and tested in the partial oxidation of propane. The results showed that the addition of small amount of gallium significantly increase the selectivity to acrylic acid (AA) at low propane conversion. However, at high propane conversion, the selectivity to AA strongly depends on both the catalyst composition and the gallium incorporation method. The higher selectivity to acrylic acid over Ga-containing MoVTeO catalysts has been related to: (i) structural changes in the M1 phase by the incorporation of Ga3+ into the octahedral structural framework and/or (ii) incorporation of Ga3+ species on the catalyst surface thus modifying catalysts acid properties. (C) 2014 Elsevier B.V. All rights reserved.Financial support from DGICYT in Spain (Project CTQ2012-37925-C03-1 and Program Severo Ochoa SEV-2012-0267) is gratefully acknowledged. EGG acknowledges finantial support through spanish project MAT2010-19837-C06-05 and the ICTS-Microscopia Electronica in Madrid for facilities.Hernández Morejudo, S.; Massó Ramírez, A.; García-González, E.; Concepción Heydorn, P.; López Nieto, JM. (2015). Preparation, characterization and catalytic behavior for propanepartial oxidation of Ga-promoted MoVTeO catalysts. Applied Catalysis A: General. 504:51-61. https://doi.org/10.1016/j.apcata.2014.12.039S516150