Response surface optimization for joint contact model evaluation

When optimization is used to evaluate a joint contact model's ability to reproduce experimental measurements, the high computational cost of repeated contact analysis can be a limiting factor. This paper presents a computationally-efficient response surface optimization methodology to address this limitation. Quadratic response surfaces were fit to contact quantities (contact force, maximum pressure, average pressure, and contact area) predicted by a discrete element contact model of the tibiofemoral joint for various combinations of material modulus and relative bone pose (i.e., position and orientation). The response surfaces were then used as surrogates for costly contact analyses in optimizations that minimized differences between measured and predicted contact quantities. The methodology was evaluated theoretically using six sets of synthetic (i.e., computer-generated) contact data, and practically using one set of experimental contact data. For the synthetic cases, the response surface optimizations recovered all contact quantities to within 3.4% error. For the experimental case, they matched all contact quantities to within 6.3% error except for maximum contact pressure, which was in error by up to 50%. Response surface optimization provides rapid evaluation of joint contact models within a limited range of relative bone poses and can help identify potential weaknesses in contact model formulation and/or experimental data quality.     

The surface structure of well-ordered native cellulose fibrils in contact with water

CP/MAS ¹³C NMR spectroscopy was used in combination with spectral fitting to examine the surface structure of hydrated cellulose I fibrils from Halocynthia and Gluconoacetobacter xylinus. To increase the spectral intensities and minimize signal overlap, G. xylinus celluloses site-specifically enriched in ¹³C either on C4 or on both C1 and C6 were examined. The experimental data showed multiple C4 and C6 signals for the water accessible fibril surfaces in the highly crystalline celluloses. These signal multiplicities were attributed to structural features in the surface layers induced by the fibril interior, and could not be extracted by spectral fitting in celluloses with a lower degree of crystallinity such as cellulose from cotton.     

A methodology for in silico endovascular repair of abdominal aortic aneurysms

Endovascular aneurysm repair (EVAR) can involve some unfavorable complications such as endoleaks or stent-graft (SG) migration. Such complications, resulting from the complex mechanical interaction of vascular tissue, SG and blood flow or incompatibility of SG design and vessel geometry, are difficult to predict. Computational vascular mechanics models can be a predictive tool for the selection, sizing and placement process of SGs depending on the patient-specific vessel geometry and hence reduce the risk of potential complications after EVAR. In this contribution, we present a new in silico EVAR methodology to predict the final state of the deployed SG after intervention and evaluate the mechanical state of vessel and SG, such as contact forces and wall stresses. A novel method to account for residual strains and stresses in SGs, resulting from the precompression of stents during the assembly process of SGs, is presented. We suggest a parameter continuation approach to model various different sizes of SGs within one in silico EVAR simulation which can be a valuable tool when investigating the issue of SG oversizing. The applicability and robustness of the proposed methods are demonstrated on the example of a synthetic abdominal aortic aneurysm geometry.     

X-ray morphology of coronary arteries in patients with arterial hypertension in late periods after endovascular treatment

An association of arterial hypertension (AH) and late angiographic outcomes of endovascular interventions was studied in coronary heart disease. Forty two patients with or without AH underwent repeated coronary angiography within 2 months after the procedure. The total number of restenoses was found to be significantly greater in patients with AH than in those without it. The diameter of restenoses was significantly smaller (70.2 +/- 24.7 vs 48.2 +/- 29.2%) and their area is significantly larger (82.6 +/- 19.6 vs 66.9 +/- 28.8). Absence probability of restenosis was significantly smaller in patients with AH (7 vs 27%); at the same time there was the greatest reduction in this probability in the first 8 months following the intervention.     

Critical evaluation of endovascular surgery for limb salvage

Rest pain, tissue loss, and gangrene are manifestations of critical limb ischemia caused by peripheral arterial disease and define a patient subgroup at highest risk for major limb amputation. Patients with nonhealing lower extremity wounds should be screened for the risk factors for peripheral arterial disease and offered noninvasive vascular testing. The diagnosis of critical limb ischemia mandates prompt institution of medical and surgical management to achieve the best chance of limb salvage. Surgical intervention has evolved from primary amputation to open bypass to the present era of endovascular therapy. The goals of surgical bypass and endovascular therapy are to improve perfusion sufficiently to permit healing. Despite poorer patency rates and the more frequent need for reintervention, endovascular therapy has been shown in multiple retrospective studies to achieve limb salvage similar to open bypass. Only one large, prospective, randomized controlled trial exists comparing open bypass with endovascular therapy: The Bypass versus Angioplasty in Severe Limb Ischemia of the Leg (BASIL) trial. Close clinical surveillance and serial monitoring of limb perfusion by means of noninvasive arterial studies are needed to determine the need for further vascular intervention. Limb salvage patients suffer from multiple comorbidities and benefit from a multidisciplinary, team approach to care.     

Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models

Background  

Abdominal aortic aneurysm (AAA) is a dilatation of the aortic wall, which can rupture, if left untreated. Previous work has shown that, maximum diameter is not a reliable determinant of AAA rupture. However, it is currently the most widely accepted indicator. Wall stress may be a better indicator and promising patient specific results from structural models using static pressure, have been published. Since flow and pressure inside AAA are non-uniform, the dynamic interaction between the pulsatile flow and wall may influence the predicted wall stress. The purpose of the present study was to compare static and dynamic wall stress analysis of patient specific AAAs.     

Microscale methodology for structure elucidation of natural products

Advances in microscale spectroscopic techniques, particularly microcryoprobe NMR, allow discovery and structure elucidation of new molecules down to only a few nanomole. Newer methods for utilizing circular dichroism (CD) have pushed the limits of detection to picomole levels. NMR and CD methods are complementary to the task of elucidation of complete stereostructures of complex natural products. Together, integrated microprobe NMR spectroscopy, microscale degradation and synthesis, are synergistic tools for the discovery of bioactive natural products and have opened new realms for discovery among extreme sources including compounds from uncultured microbes, rare invertebrates and environmental samples.     

Fibrillar structure and charge determine the interaction of polyglutamine protein aggregates with the cell surface

The pathogenesis of most neurodegenerative diseases, including transmissible diseases like prion encephalopathy, inherited disorders like Huntington disease, and sporadic diseases like Alzheimer and Parkinson diseases, is intimately linked to the formation of fibrillar protein aggregates. It is becoming increasingly appreciated that prion-like intercellular transmission of protein aggregates can contribute to the stereotypical spread of disease pathology within the brain, but the mechanisms underlying the binding and uptake of protein aggregates by mammalian cells are largely uninvestigated. We have investigated the properties of polyglutamine (polyQ) aggregates that endow them with the ability to bind to mammalian cells in culture and the properties of the cell surface that facilitate such uptake. Binding and internalization of polyQ aggregates are common features of mammalian cells and depend upon both trypsin-sensitive and trypsin-resistant saturable sites on the cell surface, suggesting the involvement of cell surface proteins in this process. polyQ aggregate binding depends upon the presence of a fibrillar amyloid-like structure and does not depend upon electrostatic interaction of fibrils with the cell surface. Sequences in the huntingtin protein that flank the amyloid-forming polyQ tract also influence the extent to which aggregates are able to bind to cell surfaces.     

Response surface methodology for optimization of Mucor fermentation medium

采用响应面分析方法优化毛霉菌B的发酵培养基,首先通过单因素试验筛选出葡萄糖为最适碳源,酵母膏和玉米浆为最适氮源,用Plackett-Burman试验对葡萄糖、酵母膏、玉米浆、MgSO4、FeSO4、NH4Cl、K2 HPO4进行评估并筛选出具有显著效应的3个因素:葡萄糖、酵母膏、玉米浆,再通过最陡爬坡试验逼近其最大响应区域,最后采用Box-Behnken试验对其用量进行优化,得到毛霉菌最佳发酵培养基(g/L):葡萄糖51.54,酵母膏5.22,玉米浆14.31,MgSO4 0.5,FeSO40.1,NH4Cl3,K2HPO43,pH 6.0～6.5.培养基优化后,毛霉生物量由23.51 g/L提高至31.13g/L,比对照组提高32.41％,腺嘌呤转化率由53.59％提高至59.97％,ATP产率由6.56 g/L提高至7.34g/L,比对照组提高11.89％.     

响应面法优化多杀菌素发酵培养基的研究

采用响应面分析方法,对刺糖多孢茵（Saccharopolyspora spinosa）H-2产多杀菌素的发酵培养基进行优化研究。运用单因子试验筛选出葡萄糖和棉籽粉为最适碳源和氮源,通过Plack—ett—Burman设计试验,对影响发酵培养基的8个相关因子进行评估并筛选出具有显著效应的4个因子：葡萄糖、棉籽粉、黄豆饼粉及玉米浆。通过最陡爬坡实验逼近以上4个因子的最大响应区域后,采用Box-Behnken响应面分析法,确定发酵产多杀菌素最佳培养基为葡萄糖64．5g,麦芽糖20g,玉米浆2g,大豆油40g,棉籽粉25g,黄豆饼粉2．4g,蛋白胨25g,CaCO35g,定容至1L,pH7．0。培养基优化后多杀菌素产量由278．1mg／L提高到508．7mg／L,比初始多杀茵素产量提高了1．83倍。     

阿托伐他汀治疗高血压并颈动脉粥样硬化的临床疗效观察

目的:观察阿托伐他汀治疗高血压并颈动脉粥样硬化的临床疗效。方法:选择高血压并颈动脉粥样硬化患者64例,按照自愿的原则分为对照组和观察组,对照组给予常规治疗,观察组在常规治疗的基础上给以阿托伐他汀治疗。治疗6个月后,比较两组患者血压、血脂及颈动脉斑块分级情况。结果:治疗6周后,两组患者在上述方面比较,差异均具有统计学意义,观察组优于对照组。结论:在高血压并颈动脉粥样硬化患者药物治疗过程中,应加行阿托伐他汀治疗,可提高临床疗效。     

响应面优化紫萍黄酮提取工艺及其抗氧化活性

采用响应面法优化微波提取紫萍黄酮的条件。在单因素实验的基础上,选取乙醇体积分数、微波功率、液料比为影响因子,应用Box-Behnken中心组合法进行三因素三水平的试验设计,以紫萍黄酮得率为响应值,进行响应面分析(RSM),结果表明:微波提取紫萍黄酮的最佳提取条件为乙醇体积分数62%、液料比17∶1(mL/g)、微波功率500 W、微波时间9 min;在优化工艺下,紫萍黄酮的得率达到4.14%。对微波提取的紫萍黄酮进行抗氧化性研究发现紫萍黄酮对DPPH.清除作用较好,其抗氧化活性要优于相同浓度的抗坏血酸(VC)和2,6-二叔丁基对甲酚(BHT)。     

Response surface methodology for the evaluation of glucose-6-phosphate dehydrogenase enrichment process by soybean lecithin reversed micelles

Glucose-6-phosphate dehydrogenase (G6PD) present in Saccahromyces cerevisiae is an enzyme of the pentose pathway. An effective enrichment of this intracellular enzyme can be achieved with the reversed micellar methodology. In this work, this methodology was employed with soybean lecithin, a biocompatible surfactant. A factorial design was used to evaluate the influence of pH (A) and extraction runs (B) on the G6PD purification factor. After statistical analysis and process optimization, a mathematical model representing G6PD enrichment was obtained: Y=4.89-0.83A+0.092B+0.27AB-1.37B2 with an enzyme purification factor of about 5.2.     

A repeated sampling bone chamber methodology for the evaluation of tissue differentiation and bone adaptation around titanium implants under controlled mechanical conditions

A repeated sampling bone chamber methodology was developed for the study of the influence of the mechanical environment on skeletal tissue differentiation and bone adaptation around titanium implants. Via perforations, bone grows into the implanted outer bone chamber, containing an inner bone chamber with a central test implant. An actuator—easily mounted on the outer bone chamber—allows a controlled mechanical stimulation of the test implant. After each experiment, the inner bone chamber—with its content—can be harvested and analysed. A new inner bone chamber with a central implant can be inserted consecutively in the outer bone chamber and a new experiment can start. Pilot studies led to a reliable surgical protocol and showed the applicability of the methodology, offering the possibility to study skeletal tissue differentiation and adaptation around implants under well-controlled mechanical conditions, and this protected from external loading. Repeated sampling of the bone chamber allows conducting several experiments within the same animal at the same site, thereby excluding subject- and site-dependent variability and reducing the amount of experimental animals.     

The interaction of surface geometry with morphogens

Expressions are given for the Gauss and Mean curvatures of a surface of thickness h. The two curvatures, (K and H), which are given at each point of the middle surface, are adequate to describe the surface. The sheet thickness varies with position in the middle surface bisecting the apical and basal surfaces. The definitions of K and H are in terms of radii of curvature, but such radii are not appropriate variables for determining how morphogens in the surface may couple to the geometry. More suitable expressions are developed here. Two important geometrical constraints must be satisfied, namely the famous Gauss-Bonnet theorem, and an inequality stemming from the definition of the two curvatures. It is argued that these constraints are of great usefulness in determining the form of the coupling of morphogens to the geometry. In particular, when two key morphogens suffice to determine surface geometry, explicit expressions are suggested to determine both Gauss (K) and Mean (H) curvatures as functions of invariant morphogen densities.     

Radiologic endovascular prosthesis of the renal arteries in patients with renovascular hypertension]

A high percentage of restenoses after roentgenovascular dilatation of the renal arteries laid the basis of a search for new therapeutic methods for these patients. Experiments on implantation of nitinol spiral endoprostheses showed their ability for long-term permeability of renal arteries, not causing their thrombosis and intimal spreading, destruction of formed elements of the blood, change in plasma proteins. Morphological investigations have shown rapid formation (during 14 days) of connective tissue neointima, covered on the side of the blood flow with the true vascular endothelium (ensuring a nonadhesive surface and laminar blood flow), around the coils of an endoprosthesis. This method after its experimental development started to be used in clinical practice. The authors reported the first experience in the clinical use of this method (12 patients with vasorenal hypertension). A 15-month follow-up revealed a stable antihypertensive effect in all patients.