Mechanistic Analysis of an Engineered Enzyme that Catalyzes the Formose Reaction

An enzyme that catalyzes the formose reaction, termed “formolase”, was recently engineered through a combination of computational protein design and directed evolution. We have investigated the kinetic role of the computationally designed residues and further characterized the enzyme's product profile. Kinetic studies illustrated that the computationally designed mutations were synergistic in their contributions towards enhancing activity. Mass spectrometry revealed that the engineered enzyme produces two products of the formose reaction—dihydroxyacetone and glycolaldehyde—with the product profile dependent on the formaldehyde concentration. We further explored the effects of this product profile on the thermodynamics and yield of the overall carbon assimilation from the formolase pathway to help guide future efforts to engineer this pathway.     

Uncertainty modeling and robust minimax LQR control of multivariable nonlinear systems with application to hypersonic flight

For a class of multi‐input and multi‐output nonlinear uncertainty systems, a novel approach to design a nonlinear controller using minimax linear quadratic regulator (LQR) control is proposed. The proposed method combines a feedback linearization method with the robust minimax LQR approach in the presence of time‐varying uncertain parameters. The uncertainties, which are assumed to satisfy a certain integral quadratic constraint condition, do not necessarily satisfy a generalized matching condition. The procedure consists of feedback linearization of the nominal model and linearization of the remaining nonlinear uncertain terms with respect to each individual uncertainty at a local operating point. This two‐stage linearization process, followed by a robust minimax LQR control design, provides a robustly stable closed loop system. To demonstrate the effectiveness of the proposed approach, an application study is provided for a flight control problem of an air‐breathing hypersonic flight vehicle (AHFV), where the outputs to be controlled are the longitudinal velocity and altitude, and the control variables are the throttle setting and elevator deflection. The proposed method is used to derive a linearized uncertainty model for the longitudinal motion dynamics of the AHFV first, and then a robust minimax LQR controller is designed, which is based on this uncertainty model. The controller is synthesized considering seven uncertain aerodynamic and inertial parameters. The stability and performance of the synthesized controller is evaluated numerically via single scenario simulations for particular cruise conditions as well as a Monte‐Carlo type simulation based on numerous cases. It is observed that the control scheme proposed in this paper performs better, especially from the aspect of robustness to large ranges of uncertainties, than some controller design schemes previously published in the literature. Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Constructing a Complex Precast Tilt-Up-Panel Structure Utilizing an Optimization Model, 3D CAD, and Animation

This paper presents the concept used to construct a complex residential tilt-up-panel structure utilizing three-dimensional (3D) modeling and animations. The residence comprises of 108 precast concrete panels of varying rectangular shapes with “dog legs” and window and door “cutouts” that look like an assembled jigsaw puzzle. The erection and installation procedure called for a maximum panel-to-panel joint tolerance of 1.27?cm (0.5?in.), often in 90° joints between panels. 3D animations were used to experiment with the construction process on the computer screen prior to construction in order to avoid potential costly on-site errors. In addition, the 3D animations were also used as a training tool for the contractors. This paper focuses on describing the methodology used to integrate a crane selection algorithm and optimization model with 3D modeling and animation for the selection, utilization, and location of cranes on construction sites. Analytical optimization processes were used to decrease the traveling time and distance of the selected crane, to improve the crane lifting sequence and to minimize the use of panel casting slabs.     

An experimental design approach to the optimisation of a flow injection analysis method for glycine

A flow injection analysis method for the determination of glycine, based on the reaction with ortho-phtalaldehyde and N-acetylcysteine in a basic buffer, was optimised. In the first step screening of the variables, to select the most important ones, was performed using: (i) a half-fraction factorial design and (ii) a quarter-fraction factorial design, for five factors at two levels. The effects of the factors on the peak height were calculated from both screening designs and compared. For the half-fraction factorial design (resolution IV), the significance of the factor effects on the peak height was checked by: (i) comparing them with a critical effect, calculated from two-factor interactions and based on a t-test, (ii) using a non parametric approach and (iii) drawing a normal probability plot. For the quarter-fraction factorial design (resolution III) the significance of the effects of the factors on the peak height was checked using: (i) a randomization test method, (ii) the non parametric method and (iii) a normal probability plot. In the second step, the factor found to be of importance was optimised using the uniplex method.     

Mechanically based models: Adaptive refinement for B‐spline finite element

This article presents two new methods for adaptive refinement of a B‐spline finite element solution within an integrated mechanically based computer aided engineering system. The proposed techniques for adaptively refining a B‐spline finite element solution are a local variant of np‐refinement and a local variant of h‐refinement. The key component in the np‐refinement is the linear co‐ordinate transformation introduced into the refined element. The transformation is constructed in such a way that the transformed nodal configuration of the refined element is identical to the nodal configuration of the neighbour elements. Therefore, the assembly proceeds as with classic finite elements, while the solution approximation conforms exactly along the inter‐element boundaries. For the h‐refinement, this transformation is introduced into a construction that merges the super element from the finite element world with the hierarchical B‐spline representation from the computational geometry. In the scope of developing sculptured surfaces, the proposed approach supports C⁰ as well as the Hermite B‐spline C¹ continuous shapes. For sculptured solids, C⁰ continuity only is considered in this article. The feasibility of the proposed methods in the scope of the geometric design is demonstrated by several examples of creating sculptured surfaces and volumetric solids. Numerical performance of the methods is demonstrated for a test case of the two‐dimensional Poisson equation. Copyright © 2003 John Wiley & Sons, Ltd.     

High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer

PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION: HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.     

Queue Lengths and Waiting Times for Multiserver Queues with Abandonment and Retrials

We consider a Markovian multiserver queueing model with time dependent parameters where waiting customers may abandon and subsequently retry. We provide simple fluid and diffusion approximations to estimate the mean, variance, and density for both the queue length and virtual waiting time processes arising in this model. These approximations, which are generated by numerically integrating only 7 ordinary differential equations, are justified by limit theorems where the arrival rate and number of servers grow large. We compare our approximations to simulations, and they perform extremely well.     

KvLQT1 potassium channel but not IsK is the molecular target for trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl- chromane

Several authors have considered two-locus models as a basis for the inheritance of complex diseases. The purpose of this paper is to give a simple general formulation to derive the additive, dominant, and epistatic effects, and hence the corresponding variance components, for any multilocus model. These variance components should be useful for investigating the power of model-free linkage analysis to detect various modes of multilocus inheritance.     

Cerebral infarction in Crohn's disease

Thromboembolic complications in Crohn's disease are not rare. Most of them are disseminated vascular thrombosis or pulmonary emboli. Cerebral artery thrombosis is a rare complication of Crohn's disease. We describe a 27-year-old woman who had Crohn's disease for 8 years, with exacerbation 3 months before admission. She had bloody diarrhea, abdominal pain, weight loss, weakness, and anemia. Hemoglobin was 6.3 g/dl and she received 3 packed cell transfusions the day of admission. Her hemoglobin level rose to 13 g/dl. 2 days after admission she had generalized tonic-clonic convulsions, followed by hemiparesis. EEG and CT examinations showed right temporal lobe infarction. Many studies report a hypercoagulable state in Crohn's disease, which results in a thromboembolic tendency that is potentially fatal.