Aims/hypothesis Interfering with the activation of receptor for AGE (RAGE) by using a soluble form of the AGE receptor (sRAGE) prevents or ameliorates the vascular complications of diabetes in ...experimental studies. Relatively little is known about factors that influence endogenous circulating sRAGE in humans. We investigated the impact of improving glycaemic control on serum total sRAGE and endogenous secretory RAGE (esRAGE), a splice variant of sRAGE, and compared the effect of rosiglitazone with that of sulfonylurea. Methods A randomised, open-label, parallel group study was performed with 64 participants randomised to receive add-on therapy with either rosiglitazone or sulfonylurea. Serum total sRAGE and esRAGE and metabolic parameters were measured before and after 6 months of treatment. Results At 6 months, both rosiglitazone and sulfonylurea resulted in a significant reduction in HbA₁c, fasting glucose and AGE. However, significant increases in total sRAGE and esRAGE were only seen in the rosiglitazone group. As a result, serum esRAGE was higher in the rosiglitazone group than in the sulfonylurea group at 6 months (p < 0.01), whereas the differences in sRAGE between the two groups did not reach statistical significance. Stepwise linear regression analysis showed that treatment modality made a greater contribution than the changes in HbA₁c to the subsequent changes in esRAGE levels at 6 months. Conclusions/interpretation Treating type 2 diabetic patients with thiazolidinedione can increase circulating levels of esRAGE and sRAGE. Whether modulation of circulating sRAGE has a beneficial effect on diabetic complications will have to be evaluated in long-term prospective studies. International Standard Randomised Controlled Trial Number ISRCTN05215453.
A linear, low-order input/output model is identified for a nonlinear distributed parameter system using a combination of singular value decomposition and the Karhunen Loève expansion. The model ...captures the dominant behavior of the system around a nominal operating point. A quadratic dynamic model-based controller (QDMC) is designed based on this low-order model. Sufficient conditions for closed-loop stability are presented and proven. The system identification method and the resulting QDMC controller are demonstrated on a nonlinear multiple-input multiple-output (MIMO) chemical reactor that produces benzene from the hydro-dealkylation of toluene.
Based on the cross-channel connections between auditory and pictorial representations, it has been proposed that the presentation of coherent narration along with the picture and text content may ...enhance children's story comprehension and vocabulary learning. The authors tested 40 four- to five-year-old Malaysian prereaders (17 Malays, 23 Chinese) for story comprehension while observing their eye movements to determine the degree to which the presence of pictures and/or text aids understanding of the narration and influences looking patterns. Both Malay and Chinese prereaders showed no interest in the printed text that was presented alongside the picture on the same page, which is consistent with earlier findings. This suggests that ethnic origins have little influence on how prereaders direct their visual attention to the relevant information for story comprehension. When there was no narration, they fixated longer on the text and less on the image, indicating that a significant amount of mental effort was required to process the words without verbal information. Regardless of stimulus congruency, storytelling performance affected how much children focused on target objects and keywords. More intriguingly, it was found that in Malay prereaders, there was a correlation between story comprehension and vocabulary skills across tasks. Additionally, Malay prereaders who performed well looked at the displayed stimuli longer than Chinese prereaders who performed well, especially when a narrator was presented alongside the visual stimulus. These novel findings are discussed along with their implications for multimedia learning and future research directions.
► We applied robust statistical theory to determine robust parameter estimates. ► We provide the theoretical foundation to prove the existence of a maximum likelihood model (ML). ► We demonstrate the ...development of an ML model using a chemical reactor process. ► We further demonstrate the robust properties of the ML model in a model predictive control framework.
Since model parameter uncertainties affect the accuracy of the model's outputs, this work describes the development of a maximum likelihood model based on robust parameter estimates to improve the model's results. A robust statistical theory framework is used to determine the robust parameter estimates. Next, it is proven that a process model parameterized by robust parameter estimates within their feasible ranges is a maximum likelihood model. A chemical reactor process is presented to demonstrate the development of the maximum likelihood model and its performance properties in a model-based predictive control framework.
Accurate solutions of distributed parameter systems may be represented as the sum of an infinite series. Control design however, requires low-order models primarily due to implementation limitations. ...As such, developing low-order models of high fidelity is important if the objective is accurate control of the DPS. This work addresses this issue by developing a method that assures a convergent and consistent projection to a finite space. The resulting model is then subsequently used to design finite dimensional state feedback controllers. The methodology is demonstrated on two quasi-linear processes under ideal and non-ideal conditions.
Accurate solutions of the distributed parameter system (DPS) may be represented as the sum of an infinite series. Control design however, requires low-order models primarily due to implementation ...limitations. As such, developing low-order models of high fidelity is important if the objective is accurate control of the DPS. When an exact model (system of partial differential equations (PDEs)) of the system is known, this work presents a method to develop a low-order model that assures convergent and consistent projection to a finite space. The resulting low-order model can then be used to design finite dimensional controllers. When there is no available first-principle model of the system, this work introduces a novel system identification method, that combines the characteristics of singular value decomposition (SVD) and the Karhunen-Loève (KL) expansion for DPS to arrive at a low-order model that captures the dominant characteristics of the system. Here as well, the final model form allows for the synthesis of finite order controllers. Two non-linear reactor systems that can be described by systems of PDEs are provided to demonstrate the model identification methods. Feedback controllers are then synthesized based on these models to demonstrate their accuracy for disturbance rejection.
This work proposes a closed-loop control strategy for a coupled set of biological reactors that was designed as part of a regenerative wastewater treatment system for NASA's advanced life support ...system for long-duration human space missions. Two types of control strategies are demonstrated, one that uses a set of decentralized single-loop controllers and another that uses a supervisory model-based control strategy. Using an experimental testbed that is 1/20th the actual size of the full-scale regenerative wastewater treatment system, the closed-loop performance of the biological reactors is compared in the presence of feed concentration disturbances.
Spray-drying technology is used in a wide variety of processes ranging from manufacture of food products to pharmaceuticals. Most recently, spray-drying technology has also been explored to make ...hollow microparticles. This work presents an approach that designs a spray-drying chamber using a rate-based description combined with a droplet size distribution model. The major criterion in the design is the desired moisture content of the final particle. The predictions of the final particle properties are compared to experimental data obtained from a laboratory spray-drying unit. The results show that the final spray-drying design is sensitive to liquid feed flow rate, inlet drying gas temperature, and heat loss.
We sought to determine whether intramuscular injection of a recombinant adeno-associated virus (rAAV) vector expressing human factor IX (hF.IX) could direct expression of therapeutic levels of the ...transgene in experimental animals. High titer (1012-1013 vector genomes/ml) rAAV expressing hF.IX was prepared, purified, and injected into hindlimb muscles of C57BL/6 mice and Rag 1 mice. In the immunocompetent C57BL/6 mice, immunofluorescence staining of muscle harvested 3 months after injection demonstrated the presence of hF.IX protein, and PCR analysis of muscle DNA was positive for AAV DNA, but no hF.IX was detected in mouse plasma. Further studies showed that these mice had developed circulating antibodies to hF.IX. In follow-up experiments in Rag 1 mice, which carry a mutation in the recombinase activating gene-1 and thus lack functional B and T cells, similar results were seen on DNA analysis of muscle, but these mice also demonstrated therapeutic levels (200-350 ng/ml) of F.IX in the plasma. The time course of F.IX expression demonstrates that levels gradually increase over a period of several weeks before reaching a plateau that is stable 6 months after injection. In other experiments we demonstrate colocalization of hF.IX and collagen IV in intersitial spaces between muscle fibers. Collagen IV has recently been identified as a F.IX-binding protein; this finding explains the unusual pattern of immunofluorescent staining for F.IX shown in these experiments. Thus rAAV can be used to direct stable expression of therapeutic levels of F.IX after intramuscular injection and is a feasible strategy for treatment of patients with hemophilia B.
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