Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice.

Surfactant protein B (SP-B) is an 8.7-kDa, hydrophobic protein that enhances the spreading and stability of surfactant phospholipids in the alveolus. To further assess the role of SP-B in lung function, the SP-B gene was disrupted by homologous recombination in murine mouse embryonic stem cells. Mice with a single mutated SP-B allele (+/-) were unaffected, whereas homozygous SP-B -/- offspring died of respiratory failure immediately after birth. Lungs of SP-B -/- mice developed normally but remained atelectatic in spite of postnatal respiratory efforts. SP-B protein and mRNA were undetectable and tubular myelin figures were lacking in SP-B -/- mice. Type II cells of SP-B -/- mice contained no fully formed lamellar bodies. While the abundance of SP-A and SP-C mRNAs was not altered, an aberrant form of pro-SP-C, 8.5 kDa, was detected, and fully processed SP-C peptide was markedly decreased in lung homogenates of SP-B -/- mice. Ablation of the SP-B gene disrupts the routing, storage, and function of surfactant phospholipids and proteins, causing respiratory failure at birth.

B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes.

Treatment of small resting B cells with soluble F(ab')2 fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activation characterized by proliferation and the expression of surface CD5. In contrast, B cells induced to proliferate in response to thymus-dependent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein displayed elevated levels of CD23 (Fc epsilon II receptor) and no surface CD5. Treatment with anti-IgM and CD40L induced higher levels of proliferation and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclosporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these results are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surface IgM)- or T-dependent (CD40)-mediated activation. In response to different intracellular signals these cells are induced to enter alternative differentiation pathways.

Contribution à la validation du modèle cognitif du trouble obsessionnel- compulsif : le rôle des expériences de l’enfance et des états affectifs

Depuis une vingtaine d’années, le modèle cognitif basé sur les interprétations (Groupe de recherche sur la cognition dans le trouble obsessionnel compulsif [OCCWG], 1997, 2001, 2003, 2005) représente le modèle psychologique de l’étiologie et du maintien du TOC le plus étudié au plan empirique. Cependant, peu de recherches ont porté sur les deux postulats importants du modèle touchant respectivement le développement des croyances liées à l’obsessionnalité et la contribution des états affectifs au maintien des interprétations et des croyances (réactivité cognitive). L’objectif de cette thèse est de contribuer à la validation empirique de ces postulats. Fondé sur un devis corrélationnel dans un échantillon de participants mixte (participants troubles obsessionnels-compulsifs et participants non cliniques), le premier article étudie les liens entre les expériences de l’enfance et la présence de croyances obsessionnelles chez l’adulte. Deux modèles alternatifs sont comparés qui représentent d’une part un lien spécifique, et d’autre part un lien non spécifique entre les expériences de l’enfance et les croyances obsessionnelles adultes. Les résultats suggèrent la présence à la fois de relations spécifiques et non spécifiques entre les expériences de l’enfance et les croyances adultes. Les expériences de l’enfance et les domaines de croyance obsessionnels qui montrent des liens spécifiques sont ceux relatifs à la responsabilité, à la perception du danger, et au perfectionnisme. En contrepartie, les expériences de l’enfance relatives à la perception de danger et dans une moindre mesure la sociotropie, apparaissent étroitement liés à la plupart des domaines de croyances adultes (intolérance à l’incertitude, surestimation du danger, importance et contrôle des pensées). Dans la seconde étude, nous nous intéressons à la mesure et l’analyse longitudinales de la réactivité cognitive telle qu’elle s’exprime dans l’environnement naturel de huit participants troubles obsessionnels-compulsifs de type ruminateur. Par le biais de huit protocoles à cas uniques intensifs, l’analyse de contingence entre les scores quotidiens d’humeur (4 états émotionnels cotés par participant) et d’interprétations (une interprétation idiographique des intrusions par participant) permet d’établir une mesure de l’importance de la réactivité cognitive chez chaque participant. Ces résultats sont ensuite analysés du point de vue des postulats principaux de deux modèles spécifiques de la réactivité cognitive (modèle de l’Infusion de l’affect [Forgas, 2008] et modèle de l’Humeur comme intrant [Meeten & Davey, 2011]. Ainsi, les analyses intra-individuelles répétées trans-comportements) et interindividuelles (trans-participants) permettent d’illustrer le rôle proximal déterminant des stratégies de traitement de l’information (traitement systématique; traitement superficiel; traitement altéré) employées par les participants. En résumé, les résultats obtenus dans ces deux études fournissent des données utiles à la poursuite de la validation du modèle des interprétations du TOC. Dans la première étude, l’identification de liens spécifiques entre les EE et les croyances obsessionnelles soutient la séquence étiologique postulée, alors que l’identification de liens non spécifiques suggère que d’autres trajectoires étiologiques peuvent être pertinentes. Dans la seconde étude, l’analyse longitudinale et naturaliste des covariations humeur – interprétations se révèle d’abord féconde à identifier les phénomènes de réactivité cognitive postulés dans le modèle des interprétations. Ensuite, en conformité aux modèles intégrés de la réactivité cognitive, l’analyse des liens entre cette réactivité et les stratégies privilégiées de neutralisation des participants permet d’identifier le rôle clé des différentes stratégies de traitement de l’information dans la réactivité cognitive.

Contribution à la validation du modèle cognitif du trouble obsessionnel- compulsif : le rôle des expériences de l’enfance et des états affectifs

Depuis une vingtaine d’années, le modèle cognitif basé sur les interprétations (Groupe de recherche sur la cognition dans le trouble obsessionnel compulsif [OCCWG], 1997, 2001, 2003, 2005) représente le modèle psychologique de l’étiologie et du maintien du TOC le plus étudié au plan empirique. Cependant, peu de recherches ont porté sur les deux postulats importants du modèle touchant respectivement le développement des croyances liées à l’obsessionnalité et la contribution des états affectifs au maintien des interprétations et des croyances (réactivité cognitive). L’objectif de cette thèse est de contribuer à la validation empirique de ces postulats. Fondé sur un devis corrélationnel dans un échantillon de participants mixte (participants troubles obsessionnels-compulsifs et participants non cliniques), le premier article étudie les liens entre les expériences de l’enfance et la présence de croyances obsessionnelles chez l’adulte. Deux modèles alternatifs sont comparés qui représentent d’une part un lien spécifique, et d’autre part un lien non spécifique entre les expériences de l’enfance et les croyances obsessionnelles adultes. Les résultats suggèrent la présence à la fois de relations spécifiques et non spécifiques entre les expériences de l’enfance et les croyances adultes. Les expériences de l’enfance et les domaines de croyance obsessionnels qui montrent des liens spécifiques sont ceux relatifs à la responsabilité, à la perception du danger, et au perfectionnisme. En contrepartie, les expériences de l’enfance relatives à la perception de danger et dans une moindre mesure la sociotropie, apparaissent étroitement liés à la plupart des domaines de croyances adultes (intolérance à l’incertitude, surestimation du danger, importance et contrôle des pensées). Dans la seconde étude, nous nous intéressons à la mesure et l’analyse longitudinales de la réactivité cognitive telle qu’elle s’exprime dans l’environnement naturel de huit participants troubles obsessionnels-compulsifs de type ruminateur. Par le biais de huit protocoles à cas uniques intensifs, l’analyse de contingence entre les scores quotidiens d’humeur (4 états émotionnels cotés par participant) et d’interprétations (une interprétation idiographique des intrusions par participant) permet d’établir une mesure de l’importance de la réactivité cognitive chez chaque participant. Ces résultats sont ensuite analysés du point de vue des postulats principaux de deux modèles spécifiques de la réactivité cognitive (modèle de l’Infusion de l’affect [Forgas, 2008] et modèle de l’Humeur comme intrant [Meeten & Davey, 2011]. Ainsi, les analyses intra-individuelles répétées trans-comportements) et interindividuelles (trans-participants) permettent d’illustrer le rôle proximal déterminant des stratégies de traitement de l’information (traitement systématique; traitement superficiel; traitement altéré) employées par les participants. En résumé, les résultats obtenus dans ces deux études fournissent des données utiles à la poursuite de la validation du modèle des interprétations du TOC. Dans la première étude, l’identification de liens spécifiques entre les EE et les croyances obsessionnelles soutient la séquence étiologique postulée, alors que l’identification de liens non spécifiques suggère que d’autres trajectoires étiologiques peuvent être pertinentes. Dans la seconde étude, l’analyse longitudinale et naturaliste des covariations humeur – interprétations se révèle d’abord féconde à identifier les phénomènes de réactivité cognitive postulés dans le modèle des interprétations. Ensuite, en conformité aux modèles intégrés de la réactivité cognitive, l’analyse des liens entre cette réactivité et les stratégies privilégiées de neutralisation des participants permet d’identifier le rôle clé des différentes stratégies de traitement de l’information dans la réactivité cognitive.

Narrativ studie av sociala berättelser : Återberättning av perspektiv och mentala kausala samband för elev elever med autismspektrumtillstånd och lindrig utvecklingsstörning

Sammanfattning/Abstract Syftet med vår studie var att undersöka hur sociala berättelser kan öka färdigheter och förmågor av perspektivering och mentala kausala samband i återberättande av olika berättelser för elever med autismspektrumtillstånd (AST) och lindrig utvecklingsstörning. Metoden vi använde oss av var dels utifrån aktionsforskning att utgå från vår egen praktik och en single-case research-reversal design med två baslinjer och två interventionsfaser på fyra elever i åk 2 & 3 med AST och lindrig utvecklingsstörning på grundskolan och grundsärskolan.   Resultaten visade att interventionen med sociala berättelser utifrån bildstödsprogrammet Trippelverkstaden hade störst effekt på två elever i perspektivering. Interventionen med sociala berättelser utifrån symbol- och bildstödsprogrammet Inprint hade störst effekt av perspektivering på två av eleverna. Resultaten för mentala kausala samband gav störst effekt på två av eleverna i återberättande av sociala berättelser i interventionerna.   Slutsatserna vi kom fram till var att de rekommendationer och metoder ifrån sociala berättelser med basmeningar, enkelt språk, korta berättelser, bildstöd, användandet av fåtal karaktärer i berättelserna och relaterat till situationer/händelser eleven känner igen har gett effekt på elevernas återberättningar av perspektiv och mentala kausala samband. Interventionerna med sociala berättelser ger stöd för att användas som hjälpmedel för elever med AST och lindrig utvecklingsstörning i Theory of Mind (ToM), centrala koherens (CK) och exekutiva funktioner/arbetsminne (EF & AM) i att återberättningarna blir mer sammanhållna och ökad återberättning av perspektiv och mentala kausala samband. Vi hävdar utifrån undersökningens resultat och utfall att sociala berättelser kan utgöra ett återkommande inslag i undervisningen för att träna kognitiva-, språkliga- och kommunikativa färdigheter och förmågor av att göra olika perspektiveringar och mentala kausala samband i återberättningar av berättelser.    Nyckelord: sociala berättelser, narration, AST, lindrig utvecklingsstörning, single-case research design, aktionsforskning, perspektivering, mentala kausala samband, theory of mind, central koherens, exekutiva funktioner, arbetsminne.

Measuring and managing performance in extended enterprises

Purpose - The purpose of this research paper is to demonstrate how existing performance measurement may be adopted to measure and manage performance in extended enterprises. Design/methodology/approach - The paper reviews the literature in performance measurement and extended enterprises. It explains the collaborative architecture of an extended enterprise and demonstrates this architecture through a case study. A model for measuring and managing performance in extended enterprises is developed using the case study. Findings - The research found that due to structural differences between traditional and extended enterprises, the systems required to measure and manage the performance of extended enterprises, whilst being based upon existing performance measurement frameworks, would be structurally and operationally different. Based on this, a model for measuring and managing performance in extended enterprises is proposed which includes intrinsic and extrinsic inter-enterprise coordinating measures. Research limitations/implications - There are two limitations this research. First, the evidence is based on a single case, thus further cases should be studied to establish the generalisibility of the presented results. Second, the practical limitations of the EE performance measurement model should be established through longitudinal action research. Practical implications - In practice the model proposed requires collaborating organisations to be more open and share critical performance information with one another. This will require change in practices and attitudes. Originality/value - The main contribution this paper makes is that it highlights the structural differences between traditional and collaborative enterprises and specifies performance measurement and management requirements of these collaborative organisations. © Emerald Group Publishing Limited.

People management issues in Indian KPOs

Purpose: The business process outsourcing (BPO) industry in India is evolving rapidly, and one of the key characteristics of this industry is the emergence of high-end services offered by knowledge processing outsourcing (KPO) organizations. These organizations are set to grow at a tremendous pace. Given the people-intensive nature of this industry, efficient employee management is bound to play a critical role. The literature lacks studies offering insights into the HR challenges involved and the ways in which they are addressed by KPOs. The purpose of this paper is to attempt to fill this gap by presenting findings from an in-depth case study of a KPO organization. Design/methodology/ approach: To achieve the research objective we adopted an in-depth case study approach. The research setting was that of a KPO organization in India, which specialises in offering complex analytics, accounting and support services to the real estate and financial services industries. Findings: The results of this study highlight the differences in the nature of work characteristics in such organizations as compared to call centres. The study also highlights some of the key people management challenges that these organizations face like attracting and retaining talent. The case company adopts formal, structured, transparent and innovative human resource practices. The study also highlights that such enlightened human resource practices stand on the foundations laid by an open work environment and facilitative leadership. Research limitations/implications: One of the key limitations is that the analysis is based on primary data from a single case study and only 18 interviews. The analysis contributes to the fields of KPO, HRM and India and has key messages for policy makers. Originality/value: The literature on outsourcing has in general focused on call centres established in the developed world. However, the booming BPO industry in India is also beginning to offer high-end services, which are far above the typical call centres. These KPOs and their people management challenges are relatively unexplored territories in the literature. By conducting this study in an emerging market (India) and focusing on people-related challenges in KPOs, this study attempts to provide a fresh perspective to the extant BPO literature. © Emerald Group Publishing Limited.

Using QFD for e-business planning and analysis in a micro-sized enterprise

Purpose - The purpose of this paper is to show how QFD can be used as part of a structured planning and analysis framework for micro-sized enterprises to build-up their e-business capabilities. Design/methodology/approach - This case study has been produced using a new framework which integrates the balanced scorecard, value chain and quality function deployment techniques into an integrated framework known as the E-Business Planning and Analysis Framework (E-PAF). It has been produced using an action research approach. Findings - A new framework with a supporting case study is provided. This case study has demonstrated that the framework can be applied successfully to micro-sized enterprises (those with less than ten employees) to successfully plan new strategic and technical developments. This will enhance the online service that the company is able to provide. Research limitations/implications - This paper presents a single case study. The technical recommendations are currently being implemented. Originality/value - Such analytical techniques are most commonly associated with large organisations, and are not specifically associated with e-business planning. This paper provides a new framework that will be of general applicability to other similarly sized enterprises that are looking to improve e-business capabilities. © Emerald Group Publishing Limited.

Knowledge management in a New Zealand tree farming company:Ambiguity and resistance to the "technology solution"

Purpose - Managers at the company attempt to implement a knowledge management information system in an attempt to avoid loss of expertise while improving control and efficiency. The paper seeks to explore the implications of the technological solution to employees within the company. Design/methodology/approach - The paper reports qualitative research conducted in a single organization. Evidence is presented in the form of interview extracts. Findings - The case section of the paper presents the accounts of organizational participants. The accounts reveal the workers' reactions to the technology-based system and something of their strategies of resistance to the system. These accounts also provide glimpses of the identity construction engaged in by these knowledge workers. The setting for the research is in a knowledge-intensive primary industry. Research was conducted through observation and interviews. Research limitations/implications - The issues identified are explored in a single case-study setting. Future research could look at the relevance of the findings to other settings. Practical implications - The case evidence presented indicates some of the complexity of implementation of information systems in organizations. This could certainly be seen as more evidence of the uncertainty associated with organizational change and of the need for managers not to expect an easy adoption of intrusive IT solutions. Originality/value - This paper adds empirical insight to a largely conceptual literature. © Emerald Group Publishing Limited.

An application of decision process modelling to manufacturing system design

As levels of investment in advanced manufacturing systems increase, effective project management becomes ever more critical. This paper demonstrates how the model proposed by Mintzberg, Raisinghani and Theoret in 1976, which structures complicated strategic decision processes, can be applied to the design of new production systems for both descriptive and analytical research purposes. This paper sets a detailed case study concerning the design and development of an advanced manufacturing system within the Mintzberg decision model and so breaks down the decision sequence into constituent parts. It thus shows how a structured model can provide a framework for the researcher who wishes to study decision episodes in the design of manufacturing facilities in greater depth.

Design and synthesis of novel hydrogels for biological applications

The aims of this project were:1) the synthesis of a range of new polyether-based vinylic monomers and their incorporation into poly(2-hydroxyethyl methacrylate) (poly(HEMA)) based hydrogel networks, of interest to the contact lens industry.2) the synthesis of a range of alkyltartronic acids, and their derivatives. These molecules may ultimately be used to produce functionalised poly(-hydroxy acids) of potential interest in either drug delivery or surgical suture applications. The novel syntheses of a range of both methoxy poly(ethylene glycol) acrylates (MPEGAs) and poly(ethylene glycol) acrylates (PEGAs) are described. Products were obtained in very good yields. These new polyether-based vinylic monomers were copolymerised with 2-hydroxyethyl methacrylate (HEMA) to produce a range of hydrogels. The equilibrium water contents (EWC) and surface properties of these copolymers containing linear polyethers were examined. It was found that the EWC was enhanced by the presence of the hydrophilic polyether chains.Results suggest that the polyether side chains express themselves at the polymer surface, thus dictating the surface properties of the gels. Consequentially, this leads to an advantageous reduction in the surface adhesion of biological species. A synthesis of a range of alkyltartronic acids is also described. The acids prepared were obtained in very good yields using a novel four-stage synthesis. These acids were modified to give potassium monoethyl alkyltartronates. Although no polyesterification is described in this thesis, these modified alkyltartronic acid derivatives are considered to be potentially excellent starting materials for poly (alkyltartronic acid) synthesis via anhydrocarboxylate or anhydrosulphite cyclic monomers.

Design and synthesis of potential antimicrobial agents

Tuberculosis is one of the most devastating diseases in the world primarily due to several decades of neglect and an emergence of multidrug-resitance strains (MDR) of M. tuberculosis together with the increased incidence of disseminated infections produced by other mycobacterium in AIDS patients. This has prompted the search for new antimycobacterial drugs. A series of pyridine-2-, pyridine-3-, pyridine-4-, pyrazine and quinoline-2-carboxamidrazone derivatives and new classes of carboxamidrazone were prepared in an automated fashion and by traditional synthesis. Over nine hundred synthesized compounds were screened for their anti mycobacterial activity against M. fortutium (NGTG 10394) as a surrogate for M. tuberculosis. The new classes of amidrazones were also screened against tuberculosis H37 Rv and antimicrobial activities against various bacteria. Fifteen tested compounds were found to provide 90-100% inhibition of mycobacterium growth of M. tuberculosis H37 Rv in the primary screen at 6.25 μg mL-1. The most active compound in the carboxamidrazone amide series had an MIG value of 0.1-2 μg mL-1 against M. fortutium. The enzyme dihydrofolate reductase (DHFR) has been a drug-design target for decades. Blocking of the enzymatic activity of DHFR is a key element in the treatment of many diseases, including cancer, bacterial and protozoal infection. The x-ray structure of DHFR from M. tuberculosis and human DHFR were found to have differences in substrate binding site. The presence of glycerol molecule in the Xray structure from M. tuberculosis DHFR provided opportunity to design new antifolates. The new antifolates described herein were designed to retain the pharmcophore of pyrimethamine (2,4- diamino-5(4-chlorophenyl)-6-ethylpyrimidine), but encompassing a range of polar groups that might interact with the M. tuberculosis DHFR glycerol binding pockets. Finally, the research described in this thesis contributes to the preparation of molecularly imprinted polymers for the recognition of 2,4-diaminopyrimidine for the binding the target. The formation of hydrogen bonding between the model functional monomer 5-(4-tert-butyl-benzylidene)-pyrimidine-2,4,6-trione and 2,4-diaminopyrimidine in the pre-polymerisation stage was verified by 1H-NMR studies. Having proven that 2,4-diaminopyrimidine interacts strongly with the model 5-(4-tert-butylbenzylidene)- pyrimidine-2,4,6-trione, 2,4-diaminopyrimidine-imprinted polymers were prepared using a novel cyclobarbital derived functional monomer, acrylic acid 4-(2,4,6-trioxo-tetrahydro-pyrimidin-5- ylidenemethyl)phenyl ester, capable of multiple hydrogen bond formation with the 2,4- diaminopyrimidine. The recognition property of the respective polymers toward the template and other test compounds was evaluated by fluorescence. The results demonstrate that the polymers showed dose dependent enhancement of fluorescence emissions. In addition, the results also indicate that synthesized MIPs have higher 2,4-diaminopyrimidine binding ability as compared with corresponding non-imprinting polymers.

Model evaluation and case series data

We discuss aggregation of data from neuropsychological patients and the process of evaluating models using data from a series of patients. We argue that aggregation can be misleading but not aggregating can also result in information loss. The basis for combining data needs to be theoretically defined, and the particular method of aggregation depends on the theoretical question and characteristics of the data. We present examples, often drawn from our own research, to illustrate these points. We also argue that statistical models and formal methods of model selection are a useful way to test theoretical accounts using data from several patients in multiple-case studies or case series. Statistical models can often measure fit in a way that explicitly captures what a theory allows; the parameter values that result from model fitting often measure theoretically important dimensions and can lead to more constrained theories or new predictions; and model selection allows the strength of evidence for models to be quantified without forcing this into the artificial binary choice that characterizes hypothesis testing methods. Methods that aggregate and then formally model patient data, however, are not automatically preferred to other methods. Which method is preferred depends on the question to be addressed, characteristics of the data, and practical issues like availability of suitable patients, but case series, multiple-case studies, single-case studies, statistical models, and process models should be complementary methods when guided by theory development.

Developing critical understanding in HRM students:using innovative teaching methods to encourage deep approaches to study

Purpose – This paper aims to focus on developing critical understanding in human resource management (HRM) students in Aston Business School, UK. The paper reveals that innovative teaching methods encourage deep approaches to study, an indicator of students reaching their own understanding of material and ideas. This improves student employability and satisfies employer need. Design/methodology/approach – Student response to two second year business modules, matched for high student approval rating, was collected through focus group discussion. One module was taught using EBL and the story method, whilst the other used traditional teaching methods. Transcripts were analysed and compared using the structure of the ASSIST measure. Findings – Critical understanding and transformative learning can be developed through the innovative teaching methods of enquiry-based learning (EBL) and the story method. Research limitations/implications – The limitation is that this is a single case study comparing and contrasting two business modules. The implication is that the study should be replicated and developed in different learning settings, so that there are multiple data sets to confirm the research finding. Practical implications – Future curriculum development, especially in terms of HE, still needs to encourage students and lecturers to understand more about the nature of knowledge and how to learn. The application of EBL and the story method is described in a module case study – “Strategy for Future Leaders”. Originality/value – This is a systematic and comparative study to improve understanding of how students and lecturers learn and of the context in which the learning takes place.

Exploring demand and production planning challenges in the food processing industry:a case study

This paper explores demand and production management challenges in the food processing industry. The goal is to identify the main production planning constraints and secondly to explore how each of these constraints affects company’s performance in terms of costs and customer service level. A single case study methodology was preferred since it enabled the collection of in-depth data. Findings suggest that product shelf life, carcass utilization and production lead time are the main constraints affecting supply chain efficiency and hence, a single planning approach is not appropriate when different products have different technological and processing characteristics.