ADVANCED MODELLING OF EMULSION TERPOLYMERISATION FOR ONLINE OPTIMISATION AND CONTROL

Polymer manufacturing is a major worldwide industry, attracting the attention of numerous industrial units and research institutes. Increasing demands on polymer quality, process safety and cost reduction are the main reasons for growing interest in the design and control of emulsion polymerisation. Emulsion polymerisation process implemented with free radical polymerisation has significant advantages over other processes, such as the production of polymer of higher molecular weights at high conversion rates, easier temperature control due to the low viscosity of the reaction media, high degree of selectivity and more friendly to environment due to the use of an aqueous medium. It allows for the production of particles with specially-tailored properties, including size, composition, morphology, and molecular weights. Introducing two or more different monomers to the polymerisation process (named multi-polymerisation) can lead to the synthesis of an almost unlimited number of new polymers types. Emulsion polymers are products by process, meaning that the manner in which the polymerisation is carried out is perhaps more important than the raw materials in determining the form of the final product. This highlights the significance of the systematic approach in online process control which requires thorough understanding of the process phenomena as a prerequisite for development of a mathematical description of the process as the model. It is thus evident and based on research observations that process control for emulsion terpolymerisation is a particularly difficult task because of the lack of validated models and the lack of online measurements of most of polymer properties of interest. Therefore, a well validated model is crucial for optimising and controlling the emulsion terpolymerisation operations allowing for design of the polymer product properties. In this study, a framework for process design and control of emulsion terpolymerisation reactors was developed. This framework consisted of three consecutive stages, dynamic modelling of the process, optimising the process for finding the optimal operating strategies and final online controlling the obtained optimal trajectories through multivariable constrained model predictive control. Within this framework, a comprehensive dynamic model was developed. Then a test case of emulsion terpolymerisation of styrene, methyl methacrylate and methyl acrylate was investigated on state of the art facilities for predicting, optimising and control end-use product properties including global and individual conversions, terpolymer composition, the average particle diameter and concentration, glass transition temperature, molecular weight distribution, the number- and weight-average molecular weights and particle size distribution. The resulting model was then exploited to understand emulsion terpolymerisation behavior and to undertake model-based optimization to readily develop optimal feeding recipes. The model equations include diffusion-controlled kinetics at high monomer conversions, where transition from a ‘zero-one’ to a ‘pseudo-bulk’ regime occurs. Transport equations are used to describe the system transients for batch and semi-batch processes. The particle evolution is described by population balance equations which comprise of a set of integro-partial differential and nonlinear algebraic equations. Backward finite difference approximation method is used to discretise the population equation and convert them from partial differential equations to ordinary differential equations. The model equations were solved using the advanced simulation environment of the gPROMS package. The dynamic model was then used to determine optimal control policies for emulsion terpolymerisation in a semi-batch reactor using the multiobjective dynamic optimisation method. The approach used allows the implementation of constrained optimisation procedures for systems described by complex mathematical models describing the operation of emulsion terpolymerisation reactors. The control vector parameterisation approach was adopted in this work. Styrene monomer feed rate, MMA monomer feed rate, MA monomer feed rate, surfactant feed rate, initiator feed rate and the temperature of reactor were used as the manipulating variables to produce terpolymers of desired composition, molecular weight distribution (MWD) and particle size distribution (PSD). The particle size polydispersity index (PSPI), molecular weight polydispersity index (MWPI) and the overall terpolymer composition ratios were incorporated as the objective functions to optimise the PSD, MWD and terpolymer composition, respectively. The optimised operational policies were successively validated with experiments via one stirred tank polymerisation reactor. Due to the lack of online measurements of key process product attributes for emulsion terpolymerisation, an inferential calorimetric soft sensor was developed based on temperature measurements. The calorimetric soft sensor obtains online measurements of reactor temperature, jacket inlet and outlet temperatures helped estimate the rate of polymerisation. The model includes the mass and energy balance equations over the reactor and its peripherals. Energy balance equations include the heat of reaction, internal and external heat transfer effects, as well as external heat losses. An online multivariable constrained model predictive control was formulated and implemented for online control of the emulsion terpolymerisation process. To achieve this implementation, a novel generic multilayer control architecture for real-time implementation of optimal control policies for particulate processes was developed. This strategy implements the dynamic model for the emulsion terpolymerisation as a real-time soft sensor which is incorporated within the implemented MPC. The methodology was successively validated using six case studies within the on-line control of terpolymerisation reactors. The cases were online controlled the composition of terpolymers, PSD and Mn with specific constraints for the operation conversion and particle average radius. An advanced Supervisory Control Architecture named ROBAS was used in this work. It provides a completely automated architecture allowing for the real time advanced supervisory monitoring and control of complex systems. The real time control application strategy was developed within MATLAB, Simulink, gPROMS and Excel Microsoft softwares and implemented on line through ROBAS Architecture. The manipulated variables are measured using on-line measurements connected to the DCS system through Honeywell. These measurements were sent to MATLAB and then to the dynamic model in gPROMS through an excel spread-sheet interface. Then the dynamic model used them to estimate the controlled variables of the MPC. The estimated values of the controlled variables obtained from the dynamic model, were then sent to the Simulink and fed through the DCS system to the MPC developed in MATLAB. The MPC would then calculate optimal trajectories, which are then sent as set point signals through the DCS system to the regulatory controller. The MPC formulation was found to be robust and handles disturbances to the process. The result showed that the online multivariable constrained MPC controller was able to control the desired composition and Mn as specified set points with great accuracy. The MPC algorithm succeeded under constrained conditions, in driving the PSD to the desired target. Although some offset was observed with a certain degree of model mismatch, the experimental results agreed well with predictions

Multi-Tap Mobile Phone Text Entry : Key-Press Operators For Keystroke Level Model

The Keystroke Level Model (KLM) has been utilized to predict the user behaviors and activities with desktop system. Recently, the mobile device application designers could use updated KLM model to predict the consumed time while users use mobile devices, but when designers use this method to evaluate the text entry they still face some difficulties with the calculation of long equations, due to multi-tap technology. This study proposes new KLM operators to facilitate the time calculation process for text entry using traditional mobile keypad. Updated KLM operators are used to predict the user behavior in interacting with mobile devices in general and text entry in specific. The expected results contribute in estimating the consumed time accurately

Detection of a highly prevalent and potentially virulent strain of Pseudomonas aeruginosa from nosocomial infections in a medical center

BACKGROUND: We correlated genotypes, virulence factors and antimicrobial susceptibility patterns of nosocomially identified Pseudomonas aeruginosa isolates from clinical specimens to those of environmental isolates encountered in the same units of a medical center. Antibiotic susceptibility testing, RAPD analysis and detection of enzymatic activities of extracellular virulence factors, were done on these isolates. RESULTS: Data showed that most of the clinical and environmental isolates were susceptible to tested antimicrobial agents. RAPD analysis determined the presence of 31 genotypes, with genotype 1 detected in 42% of the clinical isolates and 43% of the environmental isolates. Enzymatic activity testing showed that genotype 1 produced all virulence factors tested for. CONCLUSION: In conclusion, our data demonstrated the predominant prevalence of a potentially virulent P. aeruginosa genotype, circulating in a number of units of the medical center and emphasize the need to reinforce infection control measures

Parafoveal OCT Angiography Features in Diabetic Patients without Clinical Diabetic Retinopathy: A Qualitative and Quantitative Analysis

Purpose. To evaluate the capacity of OCT angiography (OCTA) for detecting infraclinical lesions in parafoveal capillaries in diabetic patients without diabetic retinopathy (DR). Methods. This prospective observational cross-sectional case-control study analyzed the superficial and deep capillary plexuses (SCP and DCP) on macular OCTA scans (3 × 3 mm) centered on the fovea. We compared 22 diabetic patients (34 eyes included) without DR diagnosis on color fundus photographs, with 22 age- and gender-matched nondiabetic controls (40 eyes included). Qualitative analysis concerned morphological ischemic capillary alterations. Quantitative analysis measured foveal avascular zone (FAZ) size, parafoveal capillary density, and enlargement coefficient of FAZ between SCP and DCP. Results. Neither the qualitative nor quantitative parameters were significantly different between both groups. No microaneurysms or venous tortuosity was observed in any of the analyzed images. On the SCP, the mean FAZ area was 0.322 ± 0.125 mm2 in diabetic patients and 0.285 ± 0.150 mm2 in controls, P=0.31. On the DCP, the mean FAZ area was 0.444 ± 0.153 mm2 in cases and 0.398 ± 0.138 mm2 in controls, P=0.20. Conclusion. OCTA did not detect infraclinical qualitative or quantitative differences in parafoveal capillaries of diabetic patients without DR in comparison with nondiabetic controls

Absence of cardiomyocyte differentiation following transplantation of adult cardiac-resident Sca-1+ cells into infarcted mouse hearts

Although several lines of evidence suggest that the glycosyl phosphatidylinositol-anchored cell surface protein Sca-1 marks cardiac-resident stem cells, a critical analysis of the literature raises some concerns regarding their cardiomyogenic potential.1 Here, isolated adult cardiac-resident Sca-1+ cells were engrafted into infarcted hearts and monitored for cardiomyogenic differentiation. Donor cells were prepared from ACT-EGFP; MHC-nLAC double-transgenic mice ([C57/Bl6J x DBA/2J]F1 genetic background; all procedures followed were in accordance with Institutional Guidelines). The ACT-EGFP transgene targets ubiquitous expression of an enhanced green fluorescent protein reporter, and the MHC-nLAC transgene targets cardiomyocyte-restricted expression of a nuclear-localized β-galactosidase reporter. Donor cell survival was monitored via EGFP fluorescence, while cardiomyogenic differentiation was monitored by reacting with the chromogenic β-galactosidase substrate 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-GAL), which gives rise to a blue product.2 Double-transgenic hearts were dispersed with Blendzyme and the resulting cells reacted with an APC-conjugated anti-Sca-1 antibody and a PE-conjugated cocktail of antibodies recognizing hematopoietic lineage markers.3 Sca-1+, EGFP+, lineage- cells were then isolated via fluorescence-activated cell sorting (FACS; characterization of the donor cells is provided in Figure 1A), and 100,000 cells were injected into the infarct border zone of non-transgenic [C57/Bl6J x DBA/2J]F1 mice immediately following permanent coronary artery occlusion

The receptor like kinase at Rhg1-a/Rfs2 caused pleiotropic resistance to sudden death syndrome and soybean cyst nematode as a transgene by altering signaling responses

Background: Soybean (Glycine max (L. Merr.)) resistance to any population of Heterodera glycines (I.), or Fusarium virguliforme (Akoi, O’Donnell, Homma & Lattanzi) required a functional allele at Rhg1/Rfs2. H. glycines, the soybean cyst nematode (SCN) was an ancient, endemic, pest of soybean whereas F. virguliforme causal agent of sudden death syndrome (SDS), was a recent, regional, pest. This study examined the role of a receptor like kinase (RLK) GmRLK18-1 (gene model Glyma_18_02680 at 1,071 kbp on chromosome 18 of the genome sequence) within the Rhg1/Rfs2 locus in causing resistance to SCN and SDS. Results: A BAC (B73p06) encompassing the Rhg1/Rfs2 locus was sequenced from a resistant cultivar and compared to the sequences of two susceptible cultivars from which 800 SNPs were found. Sequence alignments inferred that the resistance allele was an introgressed region of about 59 kbp at the center of which the GmRLK18-1 was the most polymorphic gene and encoded protein. Analyses were made of plants that were either heterozygous at, or transgenic (and so hemizygous at a new location) with, the resistance allele of GmRLK18-1. Those plants infested with either H. glycines or F. virguliforme showed that the allele for resistance was dominant. In the absence of Rhg4 the GmRLK18-1 was sufficient to confer nearly complete resistance to both root and leaf symptoms of SDS caused by F. virguliforme and provided partial resistance to three different populations of nematodes (mature female cysts were reduced by 30–50%). In the presence of Rhg4 the plants with the transgene were nearly classed as fully resistant to SCN (females reduced to 11% of the susceptible control) as well as SDS. A reduction in the rate of early seedling root development was also shown to be caused by the resistance allele of the GmRLK18-1. Field trials of transgenic plants showed an increase in foliar susceptibility to insect herbivory. Conclusions: The inference that soybean has adapted part of an existing pathogen recognition and defense cascade (H.glycines; SCN and insect herbivory) to a new pathogen (F. virguliforme; SDS) has broad implications for crop improvement. Stable resistance to many pathogens might be achieved by manipulation the genes encoding a small number of pathogen recognition proteins

Adult Bone Marrow–derived Cells Do Not Acquire Functional Attributes of Cardiomyocytes When Transplanted into Peri-infarct Myocardium

(BM) cells after being directly transplanted into the ischemically injured heart remains a controversial issue. In this study, we investigated the ability of transplanted BM cells to develop intracellular calcium ([Ca2+] i ) transients in response to membrane depolarization in situ. Low-density mononuclear (LDM) BM cells, c-kit-enriched (c-kitenr) BM cells, and highly enriched lin– c-kit+ BM cells were obtained from adult transgenic mice ubiquitously expressing enhanced green fluorescent protein (EGFP), and injected into peri-infarct myocardiums of nontransgenic mice. After 9–10 days the mice were killed, and the hearts were removed, perfused in Langendorff mode, loaded with the calcium-sensitive fluorophore rhod-2, and subjected to two-photon laser scanning fluorescence microscopy (TPLSM) to monitor action potential–induced [Ca2+] i transients in EGFP-expressing donor-derived cells and non-expressing host cardiomyocytes. Whereas spontaneous and electrically evoked [Ca2+] i transients were found to occur synchronously in host cardiomyocytes along the graft–host border and in areas remote from the infarct, they were absent in all of the >3,000 imaged BM-derived cells that were located in clusters throughout the infarct scar or peri-infarct zone. We conclude that engrafted BM-derived cells lack attributes of functioning cardiomyocytes, calling into question the concept that adult BM cells can give rise to substantive cardiomyocyte regeneration within the infarcted heart

New pyridine and chromene scaffolds as potent vasorelaxant and anticancer agents

Based on studies that have reported the association between cancer and cardiovascular diseases, new series of pyridine- (3a-o) and/or chromene- (4a-e) carbonitrile analogous were designed, synthesized and screened for their vasodilation and cytotoxic properties. The majority of the new chemical entities demonstrated significant vasodilation efficacies, compounds 3a, 3h, 3j, 3m, 3o, 4d and 4e exhibited the most promising potency with IC50 = 437.9, 481.0, 484.5, 444.8, 312.1, 427.6 and 417.2 µM, respectively, exceeding prazosin hydrochloride (IC50 = 487.3 μM). Compounds 3b-e, 3k and 3l also, revealed moderate vasodilation activity with IC50 values ranging from 489.7 to 584.5 µM. In addition, the anti-proliferative activity evaluation of the experimental compounds at 10 µM on the MCF-7 and MDA-MB 231 breast cancer cell lines illustrated the excellent anti-proliferative properties of derivatives 3d, 3g and 3i. Compound 3d was the most potent analogue with IC50 = 4.55 ± 0.88 and 9.87 ± 0.89 µM against MCF-7 and MDA-MB 231, respectively. Moreover, compound 3d stimulated apoptosis and cell cycle arrest at the S phase in MCF-7 cells in addition to its capability in accumulation of cells in pre-G1phase and activating caspase-3. Furthermore, the molecular docking of 3d was performed to discover the binding modes within the active site of caspase-3. 3d, as the only common bi-functional agent among the tested hits, demonstrated that new pyridine-3-carbonitrile derivatives bearing cycloheptyl ring systems offer potential as new therapeutic candidates with combined vasodilation and anticancer properties

Conjugation with L, L-diphenylalanine Self-Assemblies Enhances In Vitro Antitumor Activity of Phthalocyanine Photosensitizer

We present the synthesis and characterization of new peptide conjugates obtained by hierarchical co-assembly of L,L-diphenylalanine (FF) and zinc phthalocyanine complexes (ZnPc) in water. Self-assembly capabilities under defined conditions were investigated by scanning electron microscopy, and photophysical properties were evaluated using UV-Vis and fluorescence spectroscopy. AFM observations demonstrated that these ZnPcs form different highly ordered arrays on the crystalline faces of the FF microplates and that surface roughness significantly changes with the presence of differently substituted phthalocyanine units. XRD assays showed that the overall molecular packing of the conjugates is organized according to a hexagonal symmetry, with ZnPcs hosted in the interstices of the peptide phase. In vitro photodynamic studies were conducted on human breast cancer MCF-7 cells to investigate both cellular uptake and cytotoxicity. It was shown that FF self-assemblies are not toxicity and enhance accumulation of ZnPc in MCF-7 cells, improving apoptotic cell death upon irradiation. Our findings demonstrate enhancement of ZnPc antitumor efficiency by FF conjugates and a proof-of-concept for new photosensitizer carriers based on peptide conjugates