The implementation of a design of experiments strategy to increase recombinant protein yields in yeast (review)

Biological processes are subject to the influence of numerous factors and their interactions, which may be non-linear in nature. In a recombinant protein production experiment, understanding the relative importance of these factors, and their influence on the yield and quality of the recombinant protein being produced, is an essential part of its optimisation. In many cases, implementing a design of experiments (DoE) approach has delivered this understanding. This chapter aims to provide the reader with useful pointers in applying a DoE strategy to improve the yields of recombinant yeast cultures.

Multi-criteria logistics distribution network design using SAS/OR

This paper explores the use of the optimization procedures in SAS/OR software with application to the contemporary logistics distribution network design using an integrated multiple criteria decision making approach. Unlike the traditional optimization techniques, the proposed approach, combining analytic hierarchy process (AHP) and goal programming (GP), considers both quantitative and qualitative factors. In the integrated approach, AHP is used to determine the relative importance weightings or priorities of alternative warehouses with respect to both deliverer oriented and customer oriented criteria. Then, a GP model incorporating the constraints of system, resource, and AHP priority is formulated to select the best set of warehouses without exceeding the limited available resources. To facilitate the use of integrated multiple criteria decision making approach by SAS users, an ORMCDM code was implemented in the SAS programming language. The SAS macro developed in this paper selects the chosen variables from a SAS data file and constructs sets of linear programming models based on the selected GP model. An example is given to illustrate how one could use the code to design the logistics distribution network.

Early cognitive profiles of emergent readers:a longitudinal study

This longitudinal study examined the contribution of phonological awareness, phonological memory, and visuospatial ability to reading development in 142 English-speaking children from the start of kindergarten to the middle of Grade 2. Partial cross-lagged analyses revealed significant relationships between early performance on block design and matching letter-like forms tasks and later reading ability. Rhyme awareness correlated with later reading ability during the earliest stages, but onset awareness did not emerge as important until after the children had started reading. Digit span correlated significantly with future reading ability at every stage. These findings indicate that although phonological awareness, phonological memory, and visuospatial ability are all necessary for emergent reading, their relative importance varies across the first 2 years of reading development.

Governance of open content creation:a conceptualization and analysis of control and guiding mechanisms in the open content domain

The open content creation process has proven itself to be a powerful and influential way of developing text-based content, as demonstrated by the success of Wikipedia and related sites. Distributed individuals independently edit, revise, or refine content, thereby creating knowledge artifacts of considerable breadth and quality. Our study explores the mechanisms that control and guide the content creation process and develops an understanding of open content governance. The repertory grid method is employed to systematically capture the experiences of individuals involved in the open content creation process and to determine the relative importance of the diverse control and guiding mechanisms. Our findings illustrate the important control and guiding mechanisms and highlight the multifaceted nature of open content governance. A range of governance mechanisms is discussed with regard to the varied levels of formality, the different loci of authority, and the diverse interaction environments involved. Limitations and opportunities for future research are provided.

Structure of glassy GeO2

The full set of partial structure factors for glassy germania, or GeO2, were accurately measured by using the method of isotopic substitution in neutron diffraction in order to elucidate the nature of the pair correlations for this archetypal strong glass former. The results show that the basic tetrahedral Ge(O-1/2)(4) building blocks share corners with a mean inter-tetrahedral Ge-O-Ge bond angle of 132(2)degrees. The topological and chemical ordering in the resultant network displays two characteristic length scales at distances greater than the nearest neighbour. One of these describes the intermediate range order, and manifests itself by the appearance of a first sharp diffraction peak in the measured diffraction patterns at a scattering vector k(FSDP) approximate to 1.53 angstrom(-1), while the other describes so-called extended range order, and is associated with the principal peak at k(PP) = 2.66( 1) angstrom(-1). We find that there is an interplay between the relative importance of the ordering on these length scales for tetrahedral network forming glasses that is dominated by the extended range ordering with increasing glass fragility. The measured partial structure factors for glassy GeO2 are used to reproduce the total structure factor measured by using high energy x-ray diffraction and the experimental results are also compared to those obtained by using classical and first principles molecular dynamics simulations.

Glass fragility and atomic ordering on the intermediate and extended range

The relation between the fragility of glass-forming systems, a parameter which describes many of their key physical characteristics, and atomic scale structure is investigated by using neutron diffraction to measure the topological and chemical ordering for germania, or GeO2, which is an archetypal strong glass former. We find that the ordering for this and other tetrahedral network-forming glasses at distances greater than the nearest neighbor can be rationalized in terms of an interplay between the relative importance of two length scales. One of these is associated with an intermediate range, the other with an extended range and, with increasing glass fragility, it is the extended range ordering which dominates.

The implementation of a design of experiments strategy to increase recombinant protein yields in yeast (review)

Biological processes are subject to the influence of numerous factors and their interactions, which may be non-linear in nature. In a recombinant protein production experiment, understanding the relative importance of these factors, and their influence on the yield and quality of the recombinant protein being produced, is an essential part of its optimisation. In many cases, implementing a design of experiments (DoE) approach has delivered this understanding. This chapter aims to provide the reader with useful pointers in applying a DoE strategy to improve the yields of recombinant yeast cultures.

Multiple criteria optimization of contemporary logistics distribution network problems

In the contemporary customer-driven supply chain, maximization of customer service plays an equally important role as minimization of costs for a company to retain and increase its competitiveness. This article develops a multiple-criteria optimization approach, combining the analytic hierarchy process (AHP) and an integer linear programming (ILP) model, to aid the design of an optimal logistics distribution network. The proposed approach outperforms traditional cost-based optimization techniques because it considers both quantitative and qualitative factors and also aims at maximizing the benefits of deliverer and customers. In the approach, the AHP is used to determine the relative importance weightings or priorities of alternative warehouses with respect to some critical customer-oriented criteria. The results of AHP prioritization are utilized as the input of the ILP model, the objective of which is to select the best warehouses at the lowest possible cost. In this article, two commercial packages are used: including Expert Choice and LINDO.

Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities

Elevated serum cholesterol concentrations in mid-life increase risk for Alzheimer's disease (AD) in later life. However, lower concentrations of cholesterol-carrying high density lipoprotein (HDL) and its principal apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the hypothesis that lower HDL and oxocarotenoid concentrations during AD may render HDL susceptible to nitration and oxidation and in turn reduce the efficiency of reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples were obtained from subjects with 1) AD without cardiovascular comorbidities and risk factors (AD); 2) AD with cardiovascular comorbidities and risk factors (AD Plus); 3) normal cognitive function; for carotenoid determination by HPLC, analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to isolated HDL. HDL concentration in the plasma from AD Plus patients was significantly lower compared to AD or control subject HDL levels. Similarly, lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD Plus patients compared to those in control subjects or AD patients, and oxocarotenoid concentrations correlated with Mini-Mental State Examination scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects irrespective of diagnosis was equally effective at mediating RCT. HDL concentration is lower in AD Plus patients' plasma and thus capacity for RCT is compromised. In contrast, HDL from patients with AD-only was not different in concentration, modifications, or function from HDL of healthy age-matched donors. The relative importance of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia should be investigated in patients with early signs of dementia.

Coordinating expertise across knowledge boundaries in offshore-outsourcing projects:the role of codification

The coordination of effort within and among different expert groups is a central feature of contemporary organizations. Within the existing literature, however, a dichotomy has emerged in our understanding of the role played by codification in coordinating expert groups. One strand of literature emphasizes codification as a process that supports coordination by enabling the storage and ready transfer of knowledge. In contrast, another strand highlights the persistent differences between expert groups that create boundaries to the transfer of knowledge, seeing coordination as dependent on the quality of the reciprocal interactions between groups and individuals. Our research helps to resolve such contested understandings of the coordinative role played by codification. By focusing on the offshore-outsourcing of knowledge-intensive services, we examine the role played by codification when expertise was coordinated between client staff and onsite and offshore vendor personnel in a large-scale outsourcing contract between TATA Consultancy Services (TCS) and ABN AMRO bank. A number of theoretical contributions flow from our analysis of the case study, helping to move our understanding beyond the dichotomized views of codification outlined above. First, our study adds to previous work where codification has been seen as a static concept by demonstrating the multiple, coexisting, and complementary roles that codification may play. We examine the dynamic nature of codification and show changes in the relative importance of these different roles in coordinating distributed expertise over time. Second, we reconceptualize the commonly accepted view of codification as focusing on the replication and diffusion of knowledge by developing the notion of the codification of the “knower” as complementary to the codification of knowledge. Unlike previous studies of expertise directories, codification of the knower does not involve representing expertise in terms of occupational skills or competences but enables the reciprocal interrelating of expertise required by more unstructured tasks.

Is more capability always beneficial for firm performance? Market orientation, core business process capabilities, and business environment

This study examines the role of capabilities in core marketing-related business processes–product development management (PDM), supply chain management (SCM) and customer relationship management (CRM)–in translating a firm’s market orientation (MO) into firm performance. The study is the first to examine the interplay of all three business process capabilities simultaneously, while investigating how environmental conditions moderate their performance effects. A moderated mediation analysis of 468 product-focused firms finds that PDM and CRM process capabilities play important mediating roles, whereas SCM process capability does not mediate the relationship between MO and performance. However, the relative importance of the capabilities as mediators varies along the degree of environmental turbulence, and under certain conditions, an increase in the level of business process capability may even turn detrimental.

A strategic perspective of cross-listing by emerging market firms:evidence from Indonesia, Mexico, Poland and South Africa

This paper develops an approach to the analysis of cross-listing that brings together the financial and non-financial benefits of the phenomenon. We employ the real options framework, which offers a detailed characterisation of the strategic issues associated with cross-listing, in the context of internationalisation of emerging market firms. The associated hypotheses are tested using firm-level data from four large emerging market economies with different profiles in terms of institutional quality and financial development. This allows us to extend the existing literature by isolating the relative importance of institutional quality and financial development for the benefits of cross-listing.

Quantification of white matter abnormalities in neurodegenerative disease

Degeneration of white matter fibre tracts occurs in several neurodegenerative disorders and results in various histological abnormalities including loss of axons, vacuolation, gliosis, axonal varicosities and spheroids, corpora amylacea, extracellular protein deposits, and glial inclusions (GI). This chapter describes quantitative studies that have been carried out on white matter pathology in a variety of neurodegenerative disease. First, in Alzheimer’s disease (AD), axonal loss quantified in histological sections stained with toluidine blue, occurs in several white matter fibre tracts including the optic nerve, olfactory tract, and corpus callosum. Second, in Creutzfeldt-Jakob disease (CJD), sections of cerebral cortex stained with haematoxylin and eosin (H/E) or immunolabelled with antibodies against the disease form of prion protein (PrPsc), reveal extensive vacuolation, gliosis of white matter, and deposition of PrPsc deposits. Third, GI immunolabelled with antibodies against various pathological proteins including tau, -synuclein, TDP-43, and FUS, have been recorded in white matter of a number of disorders including frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and neuronal intermediate filament inclusion disease (NIFID). Axonal varicosities have also been observed in NIFID. There are two important questions regarding white matter pathology that need further investigation: (1) what is the relative importance of white and gray matter pathologies in different disorders and (2) do white matter abnormalities precede or are they the consequence of gray matter pathology?

Does the subject content of the pharmacy degree course influence the community pharmacist’s views on competencies for practice?

Do community pharmacists coming from different educational backgrounds rank the importance of competences for practice differently-or is the way in which they see their profession more influenced by practice than university education? A survey was carried out on 68 competences for pharmacy practice in seven countries with different pharmacy education systems in terms of the relative importance of the subject areas chemical and medicinal sciences. Community pharmacists were asked to rank the competences in terms of relative importance for practice; competences were divided into personal and patient-care competences. The ranking was very similar in the seven countries suggesting that evaluation of competences for practice is based more on professional experience than on prior university education. There were some differences for instance in research-related competences and these may be influenced, by education.

Leadership and organisational outcomes in healthcare

This research examined to what extent and how leadership is related to organisational outcomes in healthcare. Based on the Job Demands-Resource model, a set of hypotheses was developed, which predicted that the effect of leadership on healthcare outcomes would be mediated by job design, employee engagement, work pressure, opportunity for involvement, and work-life balance. The research focused on the National Health Service (NHS) in England, and examined the relationships between senior leadership, first line supervisory leadership and outcomes. Three years of data (2008 – 2010) were gathered from four data sources: the NHS National Staff Survey, the NHS Inpatient Survey, the NHS Electronic Record, and the NHS Information Centre. The data were drawn from 390 healthcare organisations and over 285,000 staff annually for each of the three years. Parallel mediation regressions modelled both cross sectional and longitudinal designs. The findings revealed strong relationships between senior leadership and supervisor support respectively and job design, engagement, opportunity for involvement, and work-life balance, while senior leadership was also associated with work pressure. Except for job design, there were significant relationships between the mediating variables and the outcomes of patient satisfaction, employee job satisfaction, absenteeism, and turnover. Relative importance analysis showed that senior leadership accounted for significantly more variance in relationships with outcomes than supervisor support in the majority of models tested. Results are discussed in relation to theoretical and practical contributions. They suggest that leadership plays a significant role in organisational outcomes in healthcare and that previous research may have underestimated how influential senior leaders may be in relation to these outcomes. Moreover, the research suggests that leaders in healthcare may influence outcomes by the way they manage the work pressure, engagement, opportunity for involvement and work-life balance of those they lead.