Seamless Design Research Articles

Study on Temperature Effect of the Super-Long Concrete Structure in Electrolytic Aluminum Plants

Due to the demand of the architectural features and production processes, so that the structure can’t be constructed according to specification requirements to set corresponding expansion joints. This leads to the structure to form a super-long concrete structure. Such structures have large force and deformation under the action of temperature, and even cause cracking of the structure, which seriously impacts on the safe and proper use of structure. Further, if the structure is longer than the specification maximum spacing of joints, just relying on the qualitative construction measures to deal with the impact of the temperature effect on the structure can’t meet the requirements of structural design. Meanwhile, now the quantitative calculation of temperature effect isn’t unified at home and abroad，the adverse effect of the structural temperature effect is an urgent problem. In this paper, regarded the actual electrolytic aluminum plant long concrete structure as the research object, and used finite element analysis program to study the quantitative analysis to explore the laws of temperature stress and deformation size of the long concrete structure. It provides a reference for the construction and seamless design of future similar structure.

Multi-coil approach to reduce electromagnetic energy absorption for wirelessly powered implants.

Near-field inductive coupling is a commonly used technique for wireless power transfer (WPT) in biomedical implants. Owing to the close proximity of the implant coil(s) with the tissue ( ∼1 mm) and high current ( ∼100-300 mA) in the magnetic coil(s), a significant induced electric field can be generated for the operating frequency (1-20 MHz). In this Letter, a multi-coil-based WPT technique is proposed to selectively control the currents in the external and implant coils to reduce the specific absorption rate (SAR). A three-coil WPT system, that can achieve 26% reduction in peak 1-g SAR and 15% reduction in peak 10-g SAR, as compared to a two-coil WPT system with the same dimensions, is implemented and used to demonstrate the effectiveness of the proposed approach. To achieve the seamless design for the external and implant electronics, the multi-coil system achieves the same voltage gain and bandwidth as the two-coil design with 46% improvement in the power transfer efficiency.

On Two-Stage Adaptive Seamless Design with Count Data from Different Study Durations under Weibull Distribution

In clinical development, a two-stage design combining two separate studies (e.g., a phase II dose finding study and a phase III confirmatory study) into a single trial is commonly considered. The purpose of a two-stage design is not only to reduce lead time between the two studies, but also to evaluate the treatment effect in a more efficient way. In practice, one of the difficulties in utilizing a two-stage design is that the study endpoints at different stages may be different. For example, a biomarker (or the same study endpoint with different duration) may be considered at the first stage, while a regular study endpoint is used at the second stage. As per the studies the case where both study endpoints are continuous variables with certain correlation structure. In this paper, our attention is on the case where the study endpoints are count data which are obtained at the two stages with different time intervals. Statistical procedure for combining data observed from the two different stages are proposed. Furthermore, results on hypotheses testing and sample size calculation are derived for the comparison of two treatments based on data observed from a two-stage design.

The Study of Technology and DSC Temperature Adjusting Performance on Outlast Viscose Seamless Knitted Fabric

Combined with seamless knitting technology, the temperature adjusting performance of Outlast viscose seamless knitted fabric is researched. Accepting differential scanning calorimetry (DSC), the temperature adjusting performance tests of samples determined by the seamless knitting process design are done. Comparative analysis of endothermic and exothermic temperature ranges, peak temperatures, influence of interwoven ratios and weave structures on fabric ability of heat absorption, accumulation and release is studied. DSC results show that Outlast viscose seamless knitted fabrics have good temperature adjusting performance, provide a certain value on improving the wearing comfort of seamless knitted fabric.

The Creep Impact on the Performance of Super-Long Reinforced Concrete Structures

In order to study the deformation of super-long structures under the influence of creep , take fully advantage of orthogonal design to make nine series reinforced concrete beams of shrinkage-compensating to deeply analyze the function performanced by creep of the reinforced concrete structure and obtain that the time-deflection curves of volume deformation and creep deformation of shrinkage-compensating reinforced concrete beams. The results show that the creep of beams develops rapidly early and the slow development of the late. The greater the expansion stress is in the early, the greater the shrinkage strain in the late, the greater the deformation of volume. So, the appropriate mixing ratio of expansive agent is given by the experiment. It provides a scientific basis for seamless design of super-long structures.

O.11 Personalized therapy in Duchenne muscular dystrophy: An integrated approach

Exon skipping, a promising new approach for the treatment for Duchenne muscular dystrophy (DMD), relies on the systemic administration of exon-specific antisense oligonucleotides (AONs) to reframe genetic mutations. As the targeted exon is relevant to specific subpopulations of patients with DMD, a number of AONs targeting increasingly smaller patient populations are required. Orphan drug designation and development is ongoing for six compounds, and a comprehensive development program is underway for the most prevalent subpopulation, representing approximately 13% of patients with DMD. Such a program is not feasible for less prevalent groups. Discussions with regulators, clinicians, and scientists are underway to find appropriate ways to develop these compounds, building on information gained from the lead molecule. Concepts such as abrogated preclinical development packages, manufacturing design space, and seamless trial designs may facilitate this process. Central to this theme is the patient’s perception of risk, which is being pursued independently by patient advocacy groups. Here we will discuss the seamless design accepted by the EMA and FDA for two exon skipping programs targeting sub-populations too limited to carry out fully powered, placebo-controlled pivotal Phase III studies and how future programs may be further accelerated in the ‘ultra-orphan’ DMD space.

From UML to SIMULINK CAAM: Formal Specification and Transformation Analysis

UML and Simulink are attractive languages for embedded systems design and modeling. An automatic mapping from UML models to Simulink would be an interesting resource in a seamless design flow, allowing designers to use UML as modeling language for the whole system and at same time to use facilities for code generation based on Simulink. In a previous work, the UML to Simulink translation was prototyped using a Java implementation. In this paper, we present the formal definition of this translation using graph grammars, as well as its automation, which is supported by the AGG system. With the formalization of the metamodels and translation rules, we can guarantee the correctness of the translation. We also illustrate the effectiveness of our methodology by means of a case study.

Automated Geoprocessing Mechanism, Processes and Workflow for Seamless Online Integration of Geodata Services and Creating Geoprocessing Services

This paper presents an automated mechanism, processes and workflow for the seamless integration of distributed geographical information services for the creation of an automated data processing service, known as a geoprocessing service. It describes generic principles for designing and developing real-time geoprocessing services and covers key aspects of seamless service integration and design for an automated geoprocessing service. These include brief descriptions of a `total object-oriented' approach, unified national adoption of the Open GIS Consortium's operational framework and specifications, implementation of standardised coding systems for geo-referenced data, design for service application interfaces, geodata fusion of assured integrity and quality and automation of data processing for service delivery. Automation is achieved by programmatically utilising modular software resources in compliance with the Component Object Model. This paper draws on a proven approach of relevance to specialists working in similar areas related to the design and development of Internet-based geoinformation service systems.

Analysis of Time-to-Event Data with Nonuniform Patient Entry and Loss to Follow-Up under a Two-Stage Seamless Adaptive Design with Weibull Distribution

In the pharmaceutical industry, a two-stage seamless adaptive design that combines two separate independent clinical trials into a single clinical study is commonly employed in clinical research and development. In practice, in the interest of shortening the development process, it is not uncommon to consider study endpoints with different treatment durations at different stages (Chow and Chang, 2006; Maca et al., 2006). In this study, our attention is placed on the case where the study endpoints of interest are time-to-event data where the durations at the two stages are different with nonuniform patient entry and losses to follow-up or dropouts. Test statistics for the final analysis based on the combined data are developed under various hypotheses for testing equality, superiority, noninferiority, and equivalence. In addition, formulas for sample size calculation and allocation between the two stages based on the proposed test statistic are derived.

Constructing Service-Oriented Integrated EDA Environment with Agent Technology

In modern IC design, circuit designers often need to manually operate and move data among different EDA (Electronic Design Automation) tools. If these tools were installed in separate computers, due to the license and system requirements, the design flow will be frequently interrupted, to handle the dreary data movement work, and the design efficiency will thus be reduced. To alleviate the above problem, a seamless and efficient design flow would be a must. The aim of this paper is to propose a service-oriented integrated EDA environment that can improve the smoothness of the design flow and consequently increase the overall design productivity. In our approach, a multi-agent framework based on JADE platform is used to manage distributed EDA tools, which are encapsulated as agent services. Mobile agents are allowed to autonomously and concurrently migrate among computers to access services for IC designers. To facilitate that, a scripting language is designed for mobile agents to allocate tasks, cooperate with each other, and select appropriate services. To demonstrate the feasibility of our method, an Integrated Circuit Design Cycle Assistant System (ICDCAS) for simplifying the manual operations in IC design cycles is developed by combining two EDA tools: ModelSim and Xilinx ISE. The implemented system proves to have the features of time saving and being free of mistakes incurred by manually operating and configuring the sophisticated EDA tools.

A novel optimization-based bandwidth-aware minimum power multicast routing algorithm in green wireless networks

Multicast routing in wireless networks that possess the wireless multicast advantage could significantly reduce the power and energy consumption. However, this kind of multicast routing that only addresses the transmission radius coverage might not be able to meet the bandwidth requirement of the users. As a result, additional transmissions are required to incur more energy consumption and carbon dioxide emissions that make existing algorithms not applicable to bandwidth constrained applications. In this paper, for the first time, we address the bandwidth aware minimum power multicast routing problem in wireless networks where the objective function is to minimize the total power consumption subject to the users’ bandwidth requirements. This problem is a challenging cross-layer design problem that requires seamless and sophisticated integrated design in the network layer (multicast routing) and physical layer (bandwidth-aware wireless transmission and power control). We first formulate this problem as a mixed integer linear programming problem and then propose a Lagrangian relaxation based algorithm to solve this problem. Numerical results demonstrate that the proposed approach is a sound green networking algorithm that outperforms the existing power efficient multicast routing approaches under all tested cases, especially in large bandwidth request, fine radius granularity, large group size and sparse network.

Adaptive seamless design for an efficacy trial of replication-competent adenovirus-mediated suicide gene therapy and radiation in newly-diagnosed prostate cancer (ReCAP Trial)

Purpose Cumulative evidence has suggested investigation of the efficacy of Replication-Competent Adenovirus-mediated Suicide Gene Therapy in newly-diagnosed Prostate Cancer (ReCAP). There is a challenge in designing an efficacy trial for newly-diagnosed prostate cancer given its long natural history. The regulatory agency recommended a Phase II trial for safety before conducting the efficacy trial. Experimental design The ReCAP trial is an adaptive seamless, multi-site open-label, randomized Phase II/III trial. Two hundred eighty men will be randomized to receive either replication-competent adenovirus-mediated suicide gene therapy followed by radiation (Arm 1) or radiation alone (Arm 2). Phase II trial component will include the first 21 patients in Arm 1 with complete toxicity through day 90 for safety evaluation. The primary efficacy endpoint is the time free from biochemical and/or clinical failure (FFF). The secondary efficacy endpoints are 2-year prostate biopsies and overall survival. Unequal spaced interim looks are proposed with the adaptive sample-size re-estimation. Results This trial has been approved by the FDA for the study therapy investigation and is currently recruiting patients. Conclusions Challenges remain in designing newly-diagnosed prostate cancer trials. Adaptive seamless design is time-saving and a cost-effective design in the development of novel medical therapies, but requires a specified statistical plan in the decision process involved.

Refinement of the Clinical Scenario Evaluation Framework for Assessment of Competing Development Strategies with an Application to Multiple Sclerosis

When competing strategies for development programs, clinical trial designs, or data analysis methods exist, the alternatives need to be evaluated in a systematic way to facilitate informed decision making. Here we describe a refinement of the recently proposed clinical scenario evaluation framework for the assessment of competing strategies. The refinement is achieved by subdividing key elements previously proposed into new categories, distinguishing between quantities that can be estimated from preexisting data and those that cannot and between aspects under the control of the decision maker from those that are determined by external constraints. The refined framework is illustrated by an application to a design project for an adaptive seamless design for a clinical trial in progressive multiple sclerosis.

Analysis of Time-to-Event Data Under a Two-Stage Survival Adaptive Design in Clinical Trials

In recent years, the use of a two-stage seamless design in clinical trials has attracted much attention. A two-stage seamless trial design is referred to as a study design that combines two separate clinical studies that are normally conducted to achieve separate objectives, such as a phase II study for treatment selection and a phase III study for efficacy confirmation. Furthermore, it is not uncommon to consider study endpoints with different treatment durations at different stages (see, e.g., Chow and Chang, 2006; Maca et al., 2006). Chow et al. (2007) and Lu et al. (2009) considered the cases where the study endpoints are continuous variables and binary responses, respectively. In this article, our attention is placed on the case where the study endpoints are time-to-event data with different treatment durations. For testing equality, superiority, and noninferiority/equivalence of two treatments, test statistics for the analysis of the combined data collected from the two stages are developed for Weibull distributed data. In addition, formulas for sample size calculation and sample size allocation between the two stages for each of the hypotheses are derived. Corresponding results are also derived under Cox's proportional hazards model.

Integrating indacaterol dose selection in a clinical study in COPD using an adaptive seamless design

Background The drug development process can be streamlined by combining the traditionally separate stages of dose-finding (Phase IIb) and confirmation of efficacy and safety (Phase III) using an adaptive seamless design. This approach was used in a clinical study of indacaterol, a novel once-daily (od) inhaled long-acting β 2-adrenoreceptor agonist bronchodilator for the treatment of COPD (chronic obstructive pulmonary disease). Methods The study comprised a dose-finding stage with dose selection after 14 days of treatment, and a second stage evaluating efficacy and safety during 26 weeks of treatment. The dose-finding stage included seven randomized treatment arms: double-blind indacaterol 75 μg, 150 μg, 300 μg or 600 μg od, the β 2-adrenoceptor agonist formoterol 12 μg twice-daily or placebo, or the anticholinergic tiotropium 18 μg od open-label. An independent data monitoring committee selected two indacaterol doses based on unblinded results of an interim analysis performed by an independent statistician. The sponsor, investigators and patients remained blinded to the results. The indacaterol doses were selected using pre-set efficacy criteria for trough (24-h post-dose) and early (1–4 h post-dose) bronchodilator effect after 14 days, and all safety data. To qualify for selection, the doses had to exceed a threshold for clinical relevance or be superior to either tiotropium or formoterol, whichever was the highest value. Selected doses were continued into the second, 26-week stage. The two other indacaterol doses not selected, and formoterol, were discontinued following dose selection. Results 801 patients with moderate-to-severe COPD were evaluated. Indacaterol 150 μg was the lowest effective dose, exceeding criteria for trough FEV 1 (reference value 140 mL vs placebo) and FEV 1 AUC 1–4h (reference value 220 mL vs placebo). No safety signal was observed with any dose of indacaterol. Thus, indacaterol 150 and 300 μg were selected to continue into the second, 26-week stage. Conclusion The adaptive seamless design is a novel and efficient way to combine dose selection with efficacy evaluation and safety confirmation in a single trial.

FP36-WE-01 Adaptive seamless trial designs in neurology: a case study in secondary progressive multiple sclerosis

Purpose: Adaptive seamless Phase II/III designs are attractive, and have been proposed for neurological settings such as: stroke, amyotrophic lateral sclerosis and pain control. In essence, they commence with a multi-arm stage, stopping treatments or treatment doses, for futility in an interim analysis (eg based on early biological markers), whilst taking the promising compound(s)/ dose(s) through to the final stage. Despite the advent of a raft of novel drug strategies in multiple sclerosis (MS) which reduce relapse rate, the problem of trying to slow or stop disease progression remains intractable. We explored the feasibility of implementing an adaptive seamless design (ASD) in the context of secondary progressive multiple sclerosis (SPMS).

Sample Size Estimation Based on Event Data for a Two-Stage Survival Adaptive Trial with Different Durations

In clinical development, an adaptive design combining results from two separate studies (e.g., a seamless adaptive design with a dose finding study phase and a confirmatory study phase) is commonly considered. The purpose of an adaptive design is not only to reduce lead time between the two studies, but also to evaluate the treatment effect in a more efficient way. In this paper, the focus is on the case where the study objectives are the same but the time durations of the study periods are different in the two stages. In particular, event data are collected in both stages. Statistical procedure for combining data observed from the two different stages is discussed. Furthermore, results on hypotheses testing and sample size calculation are derived for the comparison of two treatments.

Mining metadata for composability of IPs from SystemC IP library

Exploring the design space when constructing a system is vital to realize a well performing design. Design complexity has made building high-level system models to explore the design space an essential but time-consuming and tedious part of the system design. Reduction in design time and acceleration of design exploration can be provided through reusing IP-cores to construct system models. As a result, it is common to have high-level SoC design flow based on IP libraries promoting reuse. However, the success of these would be dependent on how introspection and reflection capabilities are provided as well as what are the interoperability standard defined. This leads to the important question of what kind of IP metadata must be available to allow CAD tools to effectively manipulate these designs as well as allow for a seamless integration and exchange design information between tools and design flows. In this article, we describe our tools and methodology, which allow introspection of SystemC designs, such that the extracted metadata enables IP composition. We discuss the issues related to extraction of metadata from IPs specified in SystemC and show how our methodology combines C++ and XML parsers and data structures to achieve the above.

Statistical Analysis for Two-Stage Seamless Design with Different Study Endpoints

In the pharmaceutical industry, it is desirable to apply an adaptive seamless trial design to combine two separate clinical studies that are normally conducted for achieving separate objectives such as a Phase II study for dose finding and a Phase III confirmatory study for efficacy. As a result, an adaptive seamless Phase II{/}III trial design consisting of two phases, namely a learning phase and a confirmatory phase, is commonly considered in pharmaceutical development. In some cases, however, the study endpoints for the two separate studies may be different due to long treatment duration. In this case, test statistics for the final analysis based on the combined data are necessary developed. In this paper, a test statistic utilizing data collected from both phases is proposed assuming that there is a well established relationship between the two different study endpoints. Formula for sample size calculation based on the proposed test statistic is derived. Sample size allocation at the two phases is also discussed.

Seamless Phase II/III Combination Study Through Response Adaptive Randomization

In clinical trials, multiple doses of a new drug are often tested in a Phase II dose finding study. A promising dose then is chosen for further testing and confirmation of its effectiveness in a Phase III study. Although this approach is pragmatically sound, it is known to be inefficient and unreliable because of the time and resource spent on and the very limited information generated from the Phase II study. In this research, a seamless design based on adaptive patient allocation is proposed to combine the traditional Phase II and Phase III steps to achieve the objectives of dose identification and confirmation at the same time within one study. The control of type I error rate is discussed and simulations show that with the proposed method the type I error rate of the study is controlled, and its efficiency and reliability are greatly improved as compared to the traditional approach.