Engineering the Virtual Enterprise: An Architecture-Driven Modeling Approach

The managerial and organization practices required by an increasingly dynamic competitive manufacturing, business, and industrial environment include the formation of “virtual enterprises.” A major concern in the management of virtual enterprises is the integration and coordination of business processes contributed by partner enterprises. The traditional methods of process modeling currently used for the design of business processes do not fully support the needs of the virtual enterprise. The design of these virtual enterprises imposes requirements that make it more complex than conventional intraorganizational business process design. This paper first describes an architecture that assists in the design of the virtual enterprise. Then it discusses business process reengineering (BPR) as a methodology for modeling and designing virtual organizations. While BPR presents many useful tools, the approach itself and the modeling tools commonly used for redesign have fundamental shortcomings when dealing with the virtual enterprise. However, several innovative modeling approaches provide promise for this problem. The paper discusses some of these innovative modeling approaches, such as object-oriented modeling of business processes, agent modeling of organizational players, and the use of ontological modeling to capture and manipulate knowledge about the players and processes. The paper concludes with a conceptual modeling methodology that combines these approaches under the enterprise architecture for the design of virtual enterprises.     

Technological developments and approaches to improving service quality

In summary, major paradigm shifts in the health care industry are altering the way technology is maintained and supported. Service organizations are now responsible for maintaining a broader base of technology within the health care delivery network and must to this on an extremely rapid, efficient, and productive basis. A number of new technologies are coming on-line, which can allow a health care technology service organization to experience significant improvements in profitability, efficiency, and productivity. To realize maximum benefit from these technologies, service organizations may find themselves re-engineering their service processes. The author believes that this is a requirement for many service organizations, regardless of whether new technology is implemented. The traditional approaches to service delivery are ineffective in managing the new structural realities and service requirements of today's health care environment. New strategies and tactics are required for ensuring that these requirements are met. These approaches will no doubt improve the overall quality, productivity, and efficiency of service and are based on best practices utilized by leading OEMs and ISOs in the medical electronics and other high technology service industry such as information technology and telecommunications, where the service organization is responsible for supporting a broad array of the technology over a large geography with a densely populated installed base, not unlike the typical health care delivery service environment. Once operational improvements are made, a service organization can take advantage of the productivity and efficiency gains brought on by new technology. Organizations interested in doing so are urged to thoroughly research the current state-of-the-art and best practices, because there are numerous systems currently available off-the-shelf. The author believes that new technology will be a basic requirement for competing in the health care technology service marketplace, because it can significantly affect the profitability of service organizations. This technology will help level the playing field between ISOs, OEMs, and biomedical personnel. As our research suggests, efficiently operating biomedical personnel can achieve a significantly higher utilization and profitability than efficiently operating OEMs, due to the advantages of lower overhead and operating cost structure. In general, the process to improve service productivity and efficiency involves a review of current service operations and understanding of the customer environment perceptions as well as understanding of key service factors parameters. From there, service organizations should identify the current state-of-the-art service and infrastructure systems and technology. Based on this assessment, a service organization can evaluate best practices and identify new strategies and tactics for improving service delivery. Through better service management control and education of users on the improvement in service, which the new processes and technologies provide, the service organization can realize real, quantifiable improvements in service quality, productivity, and profitability.     

Harnessing Nutrigenomics: Development of web-based communication, databases, resources, and tools

Nutrient - gene interactions are responsible for maintaining health and preventing or delaying disease. Unbalanced diets for a given genotype lead to chronic diseases such as obesity, diabetes, cardiovascular, and are likely to contribute to increased severity and/or early-onset of many age-related diseases. Many nutrition and many genetic studies still fail to properly include both variables in the design, execution, and analyses of human, laboratory animal, or cell culture experiments. The complexity ofnutrient-gene interactions has led to the realization that strategic international alliances are needed to improve the completeness of nutrigenomic studies - a task beyond the capabilities of a single laboratory team. Eighty-eight researchers from 22 countries recently outlined the issues and challenges for harnessing the nutritional genomics for public and personal health. The next step in the process of forming productive international alliances is the development of a virtual center for organizing collaborations and communications that foster resources sharing, best practices improvements, and creation of databases. We describe here plans and initial efforts of creating the Nutrigenomics Information Portal, a web-based resource for the international nutrigenomics society. This portal aims at becoming the prime source ofinformation and interaction for nutrigenomics scientists through a collaborative effort.     

Fully integrated downstream process to enable next-generation manufacturing

Next-generation manufacturing (NGM) has evolved over the past decade to a point where large biopharmaceutical organizations are making large investments in the technology and considering implementation in clinical and commercial processes. There are many well-considered reasons to implement NGM. For the most part, organizations will not fund NGM unless the implementation benefits the funding organization by providing reduced costs, reduced time, or additional needed capabilities. Productivity improvements gained from continuous purification are shown in this work, which used a new system that fully integrates and automates several downstream unit operations of a biopharmaceutical process to provide flexibility and easy implementation of NGM. The equipment and automation needed to support NGM can be complicated and expensive. Biopharmaceutical Process Development considered two options as follows: (1) design its own NGM system or (2) buy a prebuilt system. PAK BioSolutions offers a turn-key automated and integrated system that can operate up to four continuous purification stages simultaneously, while maintaining a small footprint in the manufacturing plant. The system provides significant cost benefits (~10× lower) compared with the alternative—integration of many different pieces of equipment through a Distributed Control System that would require significant engineering time for design, automation, and integration. Integrated and Continuous Biomanufacturing can lead to significant reductions in facility size, reduced manufacturing costs, and enhanced product quality when compared with the traditional batch mode of operation. The system uses new automation strategies that robustly link unit operations. We present the optimized process fit, sterility and bioburden control strategy, and automation features (such as pH feedback control and in-line detergent addition), which enabled continuous operation of a 14-day end-to-end monoclonal antibody purification process at the clinical manufacturing scale.     

Supply chain focus dependent safety stock placement

Increasing globalization, growing product range diversity, and rising consumer awareness are making markets highly competitive, forcing supply chains to adapt constantly to different stimuli. Growing competition between supply chains (as well as players within them) is also warranting a priority for overall supply chain performance over the goals of individual players. It is now well established in the literature that, among the many order winners, both overall supply chain cost and responsiveness (i.e., supply chain lead time) are the most significant determinants of supply chain competitiveness. The literature, however, mostly focuses on supply chain cost minimization with rather simplistic treatment of responsiveness. By introducing the concept of a coefficient of inverse responsiveness (CIR), we facilitate efficient introduction of responsiveness related costs into the scheme of supply chain (SC) performance evaluation and/or optimization. Thus, our model aids supply chain managers in achieving better strategic fit between individual business unit strategies and overall supply chain requirements in terms of cost efficiency and responsiveness. In particular, it aids in strategic placement of safety stocks at different stages in the supply chain. Our model also offers managerial insights that help improve our intuitions into supply chain dynamics. The model is more suited for strategic SC alignment, for example, when dealing with product changeovers or introduction of new product, rather than for operational control.     

A reference business process for ecological niche modelling

Ecological niche modelling combines species occurrence points with environmental raster layers in order to obtain models for describing the probabilistic distribution of species. The process to generate an ecological niche model is complex. It requires dealing with a large amount of data, use of different software packages for data conversion, for model generation and for different types of processing and analyses, among other functionalities. A software platform that integrates all requirements under a single and seamless interface would be very helpful for users. Furthermore, since biodiversity modelling is constantly evolving, new requirements are constantly being added in terms of functions, algorithms and data formats. This evolution must be accompanied by any software intended to be used in this area. In this scenario, a Service-Oriented Architecture (SOA) is an appropriate choice for designing such systems. According to SOA best practices and methodologies, the design of a reference business process must be performed prior to the architecture definition. The purpose is to understand the complexities of the process (business process in this context refers to the ecological niche modelling problem) and to design an architecture able to offer a comprehensive solution, called a reference architecture, that can be further detailed when implementing specific systems. This paper presents a reference business process for ecological niche modelling, as part of a major work focused on the definition of a reference architecture based on SOA concepts that will be used to evolve the openModeller software package for species modelling. The basic steps that are performed while developing a model are described, highlighting important aspects, based on the knowledge of modelling experts. In order to illustrate the steps defined for the process, an experiment was developed, modelling the distribution of Ouratea spectabilis (Mart.) Engl. (Ochnaceae) using openModeller. As a consequence of the knowledge gained with this work, many desirable improvements on the modelling software packages have been identified and are presented. Also, a discussion on the potential for large-scale experimentation in ecological niche modelling is provided, highlighting opportunities for research. The results obtained are very important for those involved in the development of modelling tools and systems, for requirement analysis and to provide insight on new features and trends for this category of systems. They can also be very helpful for beginners in modelling research, who can use the process and the experiment example as a guide to this complex activity.     

Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell

Constitutively expressed small heat shock protein HspB1 regulates many fundamental cellular processes and plays major roles in many human pathological diseases. In that regard, this chaperone has a huge number of apparently unrelated functions that appear linked to its ability to recognize many client polypeptides that are subsequently modified in their activity and/or half-life. A major parameter to understand how HspB1 is dedicated to interact with particular clients in defined cellular conditions relates to its complex oligomerization and phosphorylation properties. Indeed, HspB1 structural organization displays dynamic and complex rearrangements in response to changes in the cellular environment or when the cell physiology is modified. These structural modifications probably reflect the formation of structural platforms aimed at recognizing specific client polypeptides. Here, I have reviewed data from the literature and re-analyzed my own studies to describe and discuss these fascinating changes in HspB1 structural organization.     

Positive Interactions： Crucial Organizers in a Plant Community

For more than a century, ecologists have concentrated on competition as a crucial process for community organization. However, more recent experimental investigations have uncovered the striking Influence of positive Interactions on the organization of plant communities. Complex combinations of competition and positive interactions operating simultaneously among plant species seem to be widespread In nature. In the present paper, we reviewed the mechanism and ecological importance of positive Interactions In plant communities, emphasizing the certainties and uncertainties that have made It an attractive area of research. Positive Interactions, or facilitation, occur when one species enhances the survival, growth, or richness of another. The Importance of facilitation in plant organization increases with ablotlc stress and the relative Importance of competition decreases. Only by combining plant interactions and the many fields of biology can we fully understand how and when the positive Interactions occur.     

Joining forces: feedback and integration in plant development

Feedback and integration of information are of paramount importance for the robust functioning and dynamics of biological systems. In plant developmental biology, experimentation is increasingly combined with computational modeling to obtain a better understanding of how such regulatory interactions shape the systems' behavior. Here we highlight experimental and modeling studies on feedback loops and integration mechanisms involved in plant development. These studies have substantially expanded our understanding of previously characterized gene regulatory networks (GRNs). In addition, they illustrate the pervasiveness of regulatory interactions between seemingly unrelated processes and levels of organization. Modelers in plant development will increasingly face the challenges of what level of detail, which processes and how many levels of organization to incorporate when trying to understand a particular process.     

Linking science and practice in ecological research and management: How can we do it better?

Summary In conservation management, ensuring that the most appropriate research is conducted and results are actually put into practice is a complex and challenging process. While there are success stories, many hurdles can reduce the likelihood of appropriate research being initiated and its findings communicated and implemented. This article describes the ideal research–management cycle, summarizes the major factors that impede it and draws on the experiences of the authors to provide a series of examples of successful approaches to help keep the cycle going. We consider that the major impediments to a functioning research–management cycle relate to a lack of collaboration, poor communication, inappropriate funding and political timelines, change inertia and a lack of capacity. Although addressing structural difficulties such as matching funding timelines to those required for ecological research is a fundamental challenge, we can make incremental improvements to the way in which we operate that will improve the chances that research is both useful and used. The principles underpinning our success stories are (i) strategic development of capacity, (ii) increased breadth and depth of collaborations between researchers and managers and (iii) improved communications. Participants in the research–management cycle must seek to involve stakeholders through all project stages from project conception, to implementation, evaluation and knowledge updating. Finally, we should only see the first iteration of the research process as complete when new knowledge is applied operationally with monitoring and ongoing evaluation in place.     

JUSTIFIED COMMITMENTS? CONSIDERING RESOURCE ALLOCATION AND FAIRNESS IN MÉDECINS SANS FRONTIÈRES‐HOLLAND

Non-governmental aid programs are an important source of health care for many people in the developing world. Despite the central role non-governmental organizations (NGOs) play in the delivery of these vital services, for the most part they either lack formal systems of accountability to their recipients altogether, or have only very weak requirements in this regard. This is because most NGOs are both self-mandating and self-regulating. What is needed in terms of accountability is some means by which all the relevant stakeholders can have their interests represented and considered. An ideally accountable decision-making process for NGOs should identify acceptable justifications and rule out unacceptable ones. Thus, the point of this paper is to evaluate three prominent types of justification given for decisions taken at the Dutch headquarters of Médecins sans Frontières. They are: population health justifications, mandate-based justifications and advocacy-based justifications. The central question at issue is whether these justifications are sufficiently robust to answer the concerns and objections that various stakeholders may have. I am particularly concerned with the legitimacy these justifications have in the eyes of project beneficiaries. I argue that special responsibilities to certain communities can arise out of long-term engagement with them, but that this type of priority needs to be constrained such that it does not exclude other potential beneficiaries to an undesirable extent. Finally, I suggest several new institutional mechanisms that would enhance the overall equity of decisions and so would ultimately contribute to the legitimacy of the organization as a whole.     

Vacancy Chains Provide Aggregate Benefits To Coenobita clypeatus Hermit Crabs

Vacancy chain theory describes a unique mechanism for the sequential distribution of animal resources across multiple individuals. This theory applies to any resources, such as shelters or nest sites, that are discrete, reusable, and limited in use to single individuals or groups at one time. Hermit crabs rely on gastropod shells for shelter, and a single vacant shell can initiate a chain of sequential shell switches that distributes new resources across many individuals. Using the terrestrial hermit crab Coenobita clypeatus , we examined the previously untested theoretical prediction that this process will yield trickle-down resource benefits to vacancy chain participants (aggregate benefits). In laboratory experiments, we measured improvements in shell quality when a single vacant shell was provided to groups of eight crabs. We found that crabs participating in vacancy chains (averaging 3.2 individuals) gained significant reductions in their shell crowding. In addition, vacancy chains terminated early when experimental groups included a single crab occupying a damaged shell, because damaged vacancies always remained unoccupied. Hermit crabs in damaged shells were more likely to win resource contests for high quality shells against size-matched hermit crabs in crowded shells. Finally, field additions of many new shells to an island population of C. clypeatus hermit crabs reduced average shell crowding for crabs of all sizes, possibly from propagation of benefits through vacancy chains. These results provide empirical support for the theoretical prediction that vacancy chains should provide benefits distributed across many vacancy chain participants. Since shelter-based vacancy chains likely occur in other animals, additional studies of vacancy chain processes should provide new insights into resource acquisition behaviors in diverse animal groups.     

A tool for modeling strategic decisions in cell culture manufacturing

The development of a prototype tool for modeling manufacturing in a biopharmaceutical plant is discussed. A hierarchical approach to modeling a manufacturing process has been adopted to confer maximum user flexibility. The use of this framework for assessing the impact of manufacturing decisions on strategic technical and business indicators is demonstrated via a case study. In the case study, which takes the example of a mammalian cell culture process delivering a therapeutic for clinical trials, the dynamic modeling tool indicates how manufacturing options affect the demands on resources and the associated manufacturing costs. The example illustrates how the decision-support software can be used by biopharmaceutical companies to investigate the effects of working toward different strategic goals on the cost-effectiveness of the process, prior to committing to a particular option.     

Audio-Visual Speech Cue Combination

Background

Different sources of sensory information can interact, often shaping what we think we have seen or heard. This can enhance the precision of perceptual decisions relative to those made on the basis of a single source of information. From a computational perspective, there are multiple reasons why this might happen, and each predicts a different degree of enhanced precision. Relatively slight improvements can arise when perceptual decisions are made on the basis of multiple independent sensory estimates, as opposed to just one. These improvements can arise as a consequence of probability summation. Greater improvements can occur if two initially independent estimates are summated to form a single integrated code, especially if the summation is weighted in accordance with the variance associated with each independent estimate. This form of combination is often described as a Bayesian maximum likelihood estimate. Still greater improvements are possible if the two sources of information are encoded via a common physiological process.

Principal Findings

Here we show that the provision of simultaneous audio and visual speech cues can result in substantial sensitivity improvements, relative to single sensory modality based decisions. The magnitude of the improvements is greater than can be predicted on the basis of either a Bayesian maximum likelihood estimate or a probability summation.

Conclusion

Our data suggest that primary estimates of speech content are determined by a physiological process that takes input from both visual and auditory processing, resulting in greater sensitivity than would be possible if initially independent audio and visual estimates were formed and then subsequently combined.     

Network-Based Inference of Cancer Progression from Microarray Data

Cancer cells exhibit a common phenotype of uncontrolled cell growth, but this phenotype may arise from many different combinations of mutations. By inferring how cells evolve in individual tumors, a process called cancer progression, we may be able to identify important mutational events for different tumor types, potentially leading to new therapeutics and diagnostics. Prior work has shown that it is possible to infer frequent progression pathways by using gene expression profiles to estimate ldquodistancesrdquo between tumors. Here, we apply gene network models to improve these estimates of evolutionary distance by controlling for correlations among coregulated genes. We test three variants of this approach: one using an optimized best-fit network, another using sampling to infer a high-confidence subnetwork, and one using a modular network inferred from clusters of similarly expressed genes. Application to lung cancer and breast cancer microarray data sets shows small improvements in phylogenies when correcting from the optimized network and more substantial improvements when correcting from the sampled or modular networks. Our results suggest that a network correction approach improves estimates of tumor similarity, but sophisticated network models are needed to control for the large hypothesis space and sparse data currently available.     

钙信号基本单位和特征的研究进展

细胞内存在多种不同的Ｃａ＾２＋信号基本单位,这些Ｃａ＾２＋信号基本单位依赖于刺激浓度的等级体系组织。低水平的刺激激活单通道开放,产生Ｃａ＾２＋脉冲或Ｃａ＾２＋夸克;在等组织水平刺激则产生喷烟和火花,似乎与一小簇通道的激活有关;高浓度刺激时,Ｃａ＾２＋信号基本单位协同产生球形Ｃａ＾２＋波。这些Ｃａ＾２＋基本单位既本现了钙释放单位（Ｃａ＾２＋ｒｅｌｅａｓｅ ｕｎｉｔ）的特征,又导致Ｃａ＾２＋信号传播在     

Recent developments in software for the automation of crystallographic macromolecular structure determination

The automation of macromolecular structure determination by X-ray crystallography has long been a goal for many researchers. Recently, there have been improvements in the underlying algorithms, some of which have been implemented in software packages that deal with multiple stages of the structure determination process. These first steps towards complete automation have made X-ray crystallography more efficient.     

Prevalence of Metabolic Syndrome and Its Components among Japanese Workers by Clustered Business Category

The present study was a cross-sectional study conducted to reveal the prevalence of metabolic syndrome and its components and describe the features of such prevalence among Japanese workers by clustered business category using big data. The data of approximately 120,000 workers were obtained from a national representative insurance organization, and the study analyzed the health checkup and questionnaire results according to the field of business of each subject. Abnormalities found during the checkups such as excessive waist circumference, hypertension or glucose intolerance, and metabolic syndrome, were recorded. All subjects were classified by business field into 18 categories based on The North American Industry Classification System. Based on the criteria of the Japanese Committee for the Diagnostic Criteria of Metabolic Syndrome, the standardized prevalence ratio (SPR) of metabolic syndrome and its components by business category was calculated, and the 95% confidence interval of the SPR was computed. Hierarchical cluster analysis was then performed based on the SPR of metabolic syndrome components, and the 18 business categories were classified into three clusters for both males and females. The following business categories were at significantly high risk of metabolic syndrome: among males, Construction, Transportation, Professional Services, and Cooperative Association; and among females, Health Care and Cooperative Association. The results of the cluster analysis indicated one cluster for each gender with a higher prevalence of metabolic syndrome components; among males, a cluster consisting of Manufacturing, Transportation, Finance, and Cooperative Association, and among females, a cluster consisting of Mining, Transportation, Finance, Accommodation, and Cooperative Association. These findings reveal that, when providing health guidance and support regarding metabolic syndrome, consideration must be given to its components and the variety of its prevalence rates by business category and gender.