Stages Of Development Process Research Articles

Continuous Nanofiltration and Recycle of an Asymmetric Ketone Hydrogenation Catalyst

The continuous nanofiltration and recycle of a ruthenium diphosphine/diamine catalyst for the asymmetric hydrogenation of α-tetralone is demonstrated in a small scale flow system. Batch experiments show that the catalyst can be recycled under hydrogen pressure. Subsequent transient packed bed experiments serve to characterize the reaction and inform the design of the recycle experiments. The total internal volume of the resulting system is ∼50 mL, making this pilot useful for testing catalyst recyclability via nanofiltration during the early stages of process development. The high-pressure catalyst recycle system is run with an automatic control system to respond to membrane flux decline during the course of operation and enable long duration runs. In 24 h, we achieved a turnover number approaching 5000 for ruthenium diphosphine/diamine catalyst used in the asymmetric hydrogenation of α-tetralone, demonstrating significant reuse of the catalyst since the substrate-to-catalyst ratio in the reactor approach...

IJARCCE - Computer and Communication Engineering

The quality of any object oriented design is critical because it has a great influence on overall quality of finally delivered software product. Testability quantification early in the software development process is a criterion of crucial important to software development team. Testability has always been an indefinable concept its correct measurement, quantification or evaluation is a difficult task because of its potential factors. Testability analysis of object oriented software at an initial stage of software development process has been identified as a key factor for high quality product. A best suited object oriented design (OOD) properties and its associated metrics are helpful if applied in the early stage of development process .This paper describes an improved testability quantification framework using the identified set of potential factors, OOD properties and OOD metrics for software products at early phase, exclusively at design time. The proposed framework relates OOD properties to high level quality attributes/constructs using appropriate information to develop quality product and it may used to benchmark software products according to their key attribute. The objective of this research work to encourage researchers and developers to provide a framework to access and quantify software testability at early stage of development life cycle.

Novel shortcut estimation method for regeneration energy of amine solvents in an absorption-based carbon capture process.

Among various CO2 capture processes, the aqueous amine-based absorption process is considered the most promising for near-term deployment. However, the performance evaluation of newly developed solvents still requires complex and time-consuming procedures, such as pilot plant tests or the development of a rigorous simulator. Absence of accurate and simple calculation methods for the energy performance at an early stage of process development has lengthened and increased expense of the development of economically feasible CO2 capture processes. In this paper, a novel but simple method to reliably calculate the regeneration energy in a standard amine-based carbon capture process is proposed. Careful examination of stripper behaviors and exploitation of energy balance equations around the stripper allowed for calculation of the regeneration energy using only vapor-liquid equilibrium and caloric data. Reliability of the proposed method was confirmed by comparing to rigorous simulations for two well-known solvents, monoethanolamine (MEA) and piperazine (PZ). The proposed method can predict the regeneration energy at various operating conditions with greater simplicity, greater speed, and higher accuracy than those proposed in previous studies. This enables faster and more precise screening of various solvents and faster optimization of process variables and can eventually accelerate the development of economically deployable CO2 capture processes.

Calculation methods of investigating the surface layer of thin-walled shafts hardened by methods of surface plastic deformation

Calculation methods of investigating the residual stress-strain state of the surface layer of shafts hardened by shot peening and diamond burnishing are discussed in the paper. Shafts manufactured at aircraft plants are mostly thin-walled. In addition high requirements are imposed on the accuracy of their geometric dimensions and shape. Ensuring the fatigue resistance of shafts is achieved by applying hardening treatment. Hardening treatment residual stresses result in residual deformation of shafts often exceeding manufacturing tolerances. The models and approaches proposed in this paper make it possible to predict computationally the residual stress-strain state of the surface layer after diamond burnishing as well as technological residual deformations of the shafts caused by residual stress. They also allow adjusting the modes of shot peening and diamond burnishing at the stage of process development. The work was carried out for a shaft made of VT-22 and EP517-SH materials. The results of the investigation show that the use of preliminary numerical analysis of treatment modes makes it possible to ensure residual deformations of the most critical sections of the shafts and seating surfaces for bearings within manufacturing tolerances and also to reduce tensile residual stress on the shaft surface after diamond burnishing.

Communication Protocol for Implementation of Target Value Design (TVD) in Building Projects

One of the main objectives of Lean Construction is the generation of value for all building project stakeholders. Based on this approach, value can be generated by reducing the cost of products or services delivered and/or by improving the performance or satisfaction of participants involved in the project. The Target Value Design (TVD) is a Lean tool that enables the design to meet such an important purpose. The objective of this article is to present a protocol for the implementation of the TVD during the Project Definition and the Lean Design in building projects with a particular emphasis on office and housing construction.For such purpose, a Value Stream Mapping is presented including the most important areas intervening in a building project. Through the use of flow charts, the various stages and activities are shown from the point in which the project idea arises up to the stage where plans and technical specifications are submitted. These charts display the moments when the best opportunities take place to add value by eliminating waste, reducing lead time, optimizing costs, and/or improving the quality of products. Along with the charts, a cost structure following the same sequence as that of the design process is also shown, which allows economic valuations at any stage of process development. This prevents the frequent need for re-work that results from having such cost available just at the end of the whole design process.The contribution of this study is to provide the project design team with this protocol together with its corresponding cost structure. We are sure this will be useful for promoting the TVD implementation during the Project Definition and Lean Design phases, which may be subject to improvements or customized for each project case.

Exploring design space in embodiment design with consideration of models accuracy

Rework tasks in collaborative development projects dealing with immature design concepts are very frequent and are responsible of cost overruns and schedule delays. Taking into account uncertainty and accuracy of models (and data) improves decision making according to strategic orientation for product development. Based on a real design of light, slender but rigid solar collector supports, multiple tools have been developed and tested to support decision making at different stages of development process. The objective of this paper is to investigate the integration of these accuracy evaluations into the design process. This proposal is validated by the industrial development and validation.

A Method to Set up a Complexity Index to Improve Decision-making Performance

Engineering companies face the challenges of increasing product variety and technology induced increasing complexity of products. If the company is not able to manage this complexity within the design process it will cause productivity losses and rising complexity costs along the value-chain. Lack of information and information asymmetries lead to sub-optimal decision-making and thus to sub-optimal product-production-system designs. Companies struggle to evaluate product designs out of a broader, multi-functional perspective to derive the optimal design for the customer and company. The central question which needs to be solved is how companies can overcome these disadvantages in the early stages of product and process development. Based on the existing product design assessment methodologies proposed by academic and industrial communities this paper addresses these problems by developing a novel concept to improve decision-making performance in the early design phase by integrating the complexity perspective into decision-making. The paper delivers a guideline how to build up a complexity index to condense complex information.

Software Testing Process Model from Requirement Analysis to Maintenance

is infeasible to develop quality software without software testing. Software testing typically consumes 40-50% of development efforts, even more efforts for systems that require higher levels of reliability. It is a significant part of the software development process. If a software defect is found in latter stages of development process it costs more than if it is found in earlier stages of development. Thus the earlier we introduce testing, the less the defects found, which in turn reduces the development time and cost. Risk minimization is another approach for efficient software development. Traditionally risk management and test management are addressed separately, but if the two approaches were integrated it would further reduce time and cost of software development. There are a number of testing approaches and models for software development but no testing process model addresses defect prevention and risk minimization simultaneously. In this paper we propose a methodical or formal approach of software testing that introduces testing from the very beginning of software development life cycle as well as integrates risk management with test management. The proposed model has been evaluated in a number of software and it outperforms the existing models.

Chromatin-mediated depression of fractionation performance on electronegative multimodal chromatography media, its prevention, and ramifications for purification of immunoglobulin G

Chromatin heteroaggregates comprising nucleosomal arrays, DNA, histone and non-histone host cell proteins contributed 28% of the host contaminant mass in an IgG cell culture harvest. A subset comprising soluble particles of 50–400nm was retained through its histone component by an electronegative multimodal chromatography adsorbent. Accumulated heteroaggregates hindered pore access and depressed IgG capacity by 69% compared with capacity determined with purified IgG. Heteroaggregate retention persisted in 2M NaCl but some associations within them were dissociated. This manifested during IgG elution as contaminant leaching from the retained heteroaggregate mass, which contributed more than 95% of the contaminants in the IgG. Retained heteroaggregates also interfered with pore egress of eluted IgG, increasing peak width ∼3-fold. IgG recovery was 80%. Remaining heteroaggregates were removed with 1M NaOH. Advance reduction of heteroaggregates with a hybrid fatty acid–solid phase clarification method reduced DNA more than 3 logs, histones beneath the level of detectability, and non-histone proteins by 90% while conserving 90% of the IgG. Non-lipid-enveloped virus was reduced by 5 logs and lipid-enveloped virus by 9 logs. IgG capacity on the multimodal adsorbent was 94mg/mL, compared with 95mg/mL when loaded with protein A-purified IgG. Non-histone host protein reduction increased to 98%. IgG eluted in a sharp concentrated peak and step recovery was >95%. Residual fatty acids did not bind the adsorbent and were mostly eliminated during sample loading. A single polishing step with an electropositive multimodal adsorbent reduced non-histone host proteins to <100ppm, DNA to <10ppb, and aggregates to <0.05%. IgG recovery across the entire process was >80%. These results qualify electronegative multimodal adsorbents as an IgG capture option, but more importantly reveal chromatin heteroaggregate content as a keystone process variable at all stages of purification process development.

Application of environmental and economic metrics to guide the development of biocatalytic processes

Abstract The increasing industrial interest in biocatalytic processes is predominantly driven by the need for selective chemistry, with high reaction yield (Yreaction) and few side reactions, as well as the need for optically pure chiral molecules (in particularly in the pharmaceutical industry). Interestingly, it is often argued that the mild conditions frequently used in biocatalytic reactions (ambient temperature and pressure, neutral pH and aqueous-based media) automatically lead to environmentally-friendly and cost-effective production processes. However, such a conclusion is not justified without the use of adequate tools to evaluate the performance of a process, in particular during process development. Nevertheless, at the early development stage, evaluation of biocatalytic processes is not a trivial task, not only due to the lack of data, but also because at this stage many of the biocatalytic processes are not yet fully optimized. Hence, in this paper we propose the use of a range of tools which can be used to guide process development, research tasks and support decision-making. Three sets of metrics are identified, each for use at different stages of process development (route selection, early development and late development), each with different objectives.

Business process modelling challenges and solutions: a literature review

We have presented a review of the challenges facing business PM. These challenges are categorized into three challenges: (1) between business and IT, difficulty of deriving IT goals from business goals challenges; (2) security issues on business PM challenges; and (3) managing customer power, the rapidly changing business environment and business process (BP) challenges. Also, it presents the limitations of existing business PM frameworks. For example, in the first challenge, the existing literature is limited because they fail to capture the real business environment. Also, it is hard for IT analysts to understand BPs. In the second challenges, the existing methods of IS development fail to successfully integrate security during all development process stages and only deal with specific security requirements, goals and constraints. In the third challenges, no research has been conducted in the area of separating customers into different priority groups to provide services according to their required delivery time, payment history and feedback. Finally, we outline possible further research directions in the business PM domain. A systematic literature review method was used. Our review reports on academic publications on business PM challenges over the 13 years from 2000 to 2012. There are 31 journals as well as the IEEE and ACM databases being searched to identify relevant papers. Our systematic literature review results in that there are 53 journal papers as being the most relevant to our topic. In conclusion, it is not easy to create a good business PM. However, the research have to pay much attention on the area of creating successful business PM by creating secure business PM, manage customer power and create business PM where IT goals can be easily derived from business goals.

Tools for an enhanced solvent properties screening in the early stages of pharmaceutical process development

The objective of this research was the implementation of tools for the evaluation of solvents trough property screening in the early stages of process development. An important feature of the tools is that the implementation of indexes, scores, or weights is avoided. Information already available from the literature was stored in a database in order to turn raw data into decision making information. As a result, a solvent radar chart, a solvent representation table, and a solvent telescopying tool were developed in an ASP.NET application. The synthesis of Propranolol was used as study case in order to explore the selection of solvents in the early stages of process development. The replacement of diethyl ether was possible in the extraction step, while solvent choices were detected for potential telescoping for extraction and crystallisation steps. Solubility was found as a critical parameter in telescoping analysis. The methodology proposed enhanced the view towards a more holistic perspective and a more robust solvent screening process. As a consequence, the next steps into solvent evaluation and process development can be reduced.

Supercritical fluids and gas-expanded liquids as tunable media for multiphase catalytic reactions

Solvents play a vital role in multiphase catalysis. They are selected to perform several functions during liquid phase catalytic transformations such as solubilizing reactants, facilitating product/catalyst separation, increasing reaction rates, enhancing solubilities of gaseous reactants (such as O2, CO, H2) in the liquid phase, and providing heat capacity to effectively manage the heat of reaction. This review discusses such roles of conventional solvents in multiphase catalytic processes such as hydroformylation, carbonylation, hydrogenation and oxidation. For each of these chemistries, industrially relevant examples are presented, highlighting the advantages and limitations of the conventional solvents used therein. Further, it is shown how the pressure-tunable properties of supercritical fluids (SCFs) and gas-expanded liquids (GXLs) have been exploited in such systems to develop novel multiphase catalytic technology concepts. GXLs in particular provide advantages such as rate intensification, efficient feedstock utilization, enhanced process safety, waste minimization and reduced use of volatile organic solvents, all at relatively mild pressures and temperatures. Conventional reactors and reaction engineering tools that integrate phase behavior (for reactions and separations), catalytic kinetics and multiphase reactor modeling may be applied for the rational development of multiphase reactors using GXLs. Quantitative economic and environmental impact analyses during early stages of process development provide valuable research and process engineering guidance for developing practically viable GXL processes. The Rh catalyzed hydroformylation in CO2-expanded liquids and methyltrioxorhenium-based ethylene epoxidation are highlighted as exemplars of GXL-based technology concepts. Emerging feedstocks, such as plant-based biomass, shale gas and sequestered CO2, that require new catalytic conversion technologies to produce chemical intermediates, offer excellent opportunities for using tunable solvents.

Selection of Technical Reactor Equipment for Modular, Continuous Small-Scale Plants

Fast process development, flexible production and the utilization of advanced process conditions are the main goals of modular and continuous small-scale plants (MCSPs). A configurable layout of the modules and the use of predefined equipment enable a quick and reliable conceptual process development and scale-up of continuous processes. Therefore, a computer-assisted selection methodology was developed and is presented, which allows the quick selection of plug flow reactor equipment for homogeneous liquid phase reactions. It identifies a favorable technical apparatus and the configuration in the early stages of process development. This can lead to the effective planning and guiding of scale-up experiments and closes the gap between lab and process development.

Employees' involvement in developing service product innovations in Islamic banks

Purpose – The purpose of this paper is to explore how two Islamic banks have involved employees in developing service product innovations. Design/methodology/approach – The case studies describe the roles of employees during specific stages of development process of service product innovations. The data were collected through face-to-face oral interviews with senior product development managers and marketing managers. Findings – The results suggest that employees' involvement is encouraged in the selected banks through the presence of a product champion, involvement of front-line employees, support from the management, multifunctional team structure and employee external contacts. A Sharia board was at the heart of the development process of service product innovations in Islamic banks. It was also revealed that employees are more involved in developing service product innovation for retail customers in comparison to the corporate customers. Originality/value – Given the focus of current literature on con...

A novel secure business process modeling approach and its impact on business performance

The existing information system (IS) development methods do not meet the requirements to resolve security-related IS problems and they fail to provide for the successful integration of security and systems engineering during all development process stages. Security should be considered during the whole software development process and the requirements specifications should be identified. This paper aims to propose an integrated security and IS engineering approach in all software development process stages by using the i* language. The proposed framework is divided into three separate parts: modeling the business environment, modeling the information technology system and modeling IS security. A mobile phone order management process in a telecommunication company is used as a case study to validate the proposed framework. An empirical analysis based on data from 130 business and IT managers is used to evaluate and investigate if it has an impact on business process performance. The results were subjected to reliability and validity analyses. Bivariate correlation analysis was used to test four hypotheses. The results show that considering security IS goals in the whole system development process can have a positive influence on system implementation, better meet business expectations and positively impact on business process performance.

A Xml-based Representation Of Timing Information For Wcet Analysis

The Worst-Case Execution Time (WCET) analysis is an important stage in development process and verification of hard real-time systems. In this article the use of XML as a standard for exchanging timing information amongst timing analysis tools is proposed. Timing information resulted from automatic analysis of programs can be represented in XML format. Considering the type of information required for estimating the worst case execution time of programs, a set of XML tags is offered in this paper. Timing information resulted from analyzing a program by a timing analysis tool could be annotated within the program. The annotated code could be simply applied by other tools for relatively more accurate estimation of the worst case execution times. The paper also clears the way for future studies on using XML-based representation for extraction of information.

Profiling and Characterization of Sialylated N-glycans by 2D-HPLC (HIAX/PGC) with Online Orbitrap MS/MS and Offline MSn

Glycosylation is a critical parameter used to evaluate protein quality and consistency. N-linked glycan profiling is fundamental to the support of biotherapeutic protein manufacturing from early stage process development through drug product commercialization. Sialylated glycans impact the serum half-life of receptor-Fc fusion proteins (RFPs), making their quality and consistency a concern during the production of fusion proteins. Here, we describe an analytical approach providing both quantitative profiling and in-depth mass spectrometry (MS)-based structural characterization of sialylated RFP N-glycans. Aiming to efficiently link routine comparability studies with detailed structural characterization, an integrated workflow was implemented employing fluorescence detection, online positive and negative ion tandem mass spectrometry (MS/MS), and offline static nanospray ionization-sequential mass spectrometry (NSI-MS(n)). For routine use, high-performance liquid chromatography profiling employs established fluorescence detection of 2-aminobenzoic acid derivatives (2AA) and hydrophilic interaction anion-exchange chromatography (HIAX) charge class separation. Further characterization of HIAX peak fractions is achieved by online (-) ion orbitrap MS/MS, offering the advantages of high mass accuracy and data-dependent MS/MS. As required, additional characterization uses porous graphitized carbon in the second chromatographic dimension to provide orthogonal (+) ion MS/MS spectra and buffer-free liquid chromatography peak eluants that are optimum for offline (+)/(-) NSI-MS(n) investigations to characterize low-abundance species and specific moieties including O-acetylation and sulfation.

A quantitative and mechanistic model for monoclonal antibody glycosylation as a function of nutrient availability during cell culture

Monoclonal antibodies (mAbs) are currently the highest-selling products of the biopharmaceutical industry, having had global sales of over $45 billion in 2012 [1]. All commercially-available mAbs contain a consensus N-linked glycosylation site on each of the Cγ2 domains of their constant fragment (Fc). The monosaccharide composition and distribution of these N-linked carbohydrates (glycans) has been widely reported to directly impact the safety and efficacy of mAbs when administered to patients. Many studies have also shown that manufacturing bioprocess conditions (e.g. nutrient availability, metabolite accumulation, dissolved oxygen, pH, temperature and stirring speed) directly influence the composition and distribution of N-linked glycans bound to mAbs and other recombinant proteins. Given this tight interconnection between manufacturing process conditions, product quality and ensuing safety and therapeutic efficacy, mAbs and their glycosylation present a clear opportunity where process development can be guided by quality by design (QbD) principles. QbD is a conceptual framework that aims to build quality into drug products at every stage of process development. Specifically, implementation of QbD to pharmaceutical process development requires identifying critical quality attributes (CQAs) that define the drug's safety and therapeutic efficacy. QbD then uses all available information on the mechanisms that quantitatively relate process inputs with product quality to control the manufacturing process so that product CQAs are maintained and end-product quality is ensured. Within the QbD context, composition and distribution of the glycans present on the Fc of mAbs is defined as a CQA, and thus, the processes employed in their manufacture must be controlled so that their glycan distribution ensures the required safety and efficacy profiles. Under this perspective, we have defined a mathematical model that mechanistically and quantitatively describes mAb Fc glycosylation as a function of nutrient availability during cell culture. Such a model aims to be used for bioprocess design, control and optimisation, thus facilitating the manufacture of mAbs with built-in glycosylation-associated quality under the QbD scope.

Ultra scale‐down device to predict dewatering levels of solids recovered in a continuous scroll decanter centrifuge

During centrifugation operation, the major challenge in the recovery of extracellular proteins is the removal of the maximum liquid entrapped within the spaces between the settled solids-dewatering level. The ability of the scroll decanter centrifuge (SDC) to process continuously large amounts of feed material with high concentration of solids without the need for resuspension of feeds, and also to achieve relatively high dewatering, could be of great benefit for future use in the biopharmaceutical industry. However, for reliable prediction of dewatering in such a centrifuge, tests using the same kind of equipment at pilot-scale are required, which are time consuming and costly. To alleviate the need of pilot-scale trials, a novel USD device, with reduced amounts of feed (2 mL) and to be used in the laboratory, was developed to predict the dewatering levels of a SDC. To verify USD device, dewatering levels achieved were plotted against equivalent compression (Gtcomp ) and decanting (Gtdec ) times, obtained from scroll rates and feed flow rates operated at pilot-scale, respectively. The USD device was able to successfully match dewatering trends of the pilot-scale as a function of both Gtcomp and Gtdec , particularly for high cell density feeds, hence accounting for all key variables that influenced dewatering in a SDC. In addition, it accurately mimicked the maximum dewatering performance of the pilot-scale equipment. Therefore the USD device has the potential to be a useful tool at early stages of process development to gather performance data in the laboratory thus minimizing lengthy and costly runs with pilot-scale SDC.