The calpain family of intracellular Ca2+-dependent cysteine proteases is involved in a number of intracellular signaling processes. Calpain hyperactivity has also been implicated in ischemic injury, neurodegenerative diseases and cataract formation. However, the specific function of calpains in these normal and diseased states remains unclear. Competitive inhibition of calpain is useful for studying their functions and can lead to pharmacological treatments, while monitoring their activity with activity-based probes (ABPs) can reveal how calpain is regulated and be applied to screen for inhibitors in vivo. But these strategies are complicated by the similarity of the calpain active-site when compared to other intracellular cysteine proteases. Therefore, there is a need to design inhibitors and ABPs that selectively target calpain. Using X-ray crystallography, the interactions between the calpain active-site and each of two reversible inhibitors was studied. This led to the discovery of novel non-covalent aromatic stacking and hydrogen bonding interactions between the primed-side adenine group of one inhibitor and indole ring of an active-site Trp residue in μ-calpain. A substrate-based competition assay later confirmed that these interactions provided this compound with an inhibitory advantage over the other, which lacked any primed-side interactions, thereby providing insight into the development of new, more specific reversible calpain inhibitors. Next, a fluorescent ABP, containing features borrowed from an irreversible and presumably calpain-specific inhibitor, was evaluated for its ability to detect calpain activitiy. Although this probe appropriately targeted the calpain active site in its Ca2+-activated form, it was unable to detect calpain activity in a cell extract. Nevertheless, the results of this study have yielded insights into ways of improving the calpain detecting ability of this ABP. / Thesis (Master, Biochemistry) -- Queen's University, 2008-09-01 15:39:07.023

Bakgrund: Kontorens utformning påverkar hur organisationer upplevs internt och externt. Utformningen har förändrats genom tiden vilket till viss del beror på samhällsutvecklingen och moden. Aktivitetsbaserat arbetssätt är ett nytt sätt att utforma kontor på och allt fler organisationer väljer idag att implementera ett aktivitetsbaserat arbetssätt. Syfte: Att skapa förståelse för modets inverkan på organisationers utveckling genom att studera implementeringen av ett aktivitetsbaserat arbetssätt.  Metod: Studien bygger på en deduktiv forskningsansats med en kvalitativ forskningsstrategi. Studien är en tvärsnittsstudie med datainsamling från mer än ett fall. Åtta kvalitativa intervjuer och två observationer har genomförts.    Resultat, slutsatser: Det finns flera motiv till att implementera ett aktivitetsbaserat arbetssätt. Sänkta kostnader till följd av minskade lokalytor, ökad produktivitet, hänsyn till miljön, ökad attraktionskraft, ökat samarbete och innovationsskapande är exempel på motiv till implementeringen. Utifrån en modemetafor kan det ses en ökad spridning av begreppet aktivitetsbaserat arbetssätt, vilket sker genom konsulter, företag och media. Idén aktivitetsbaserat arbetssätt har rest in i diskursen organisation och håller på att förändra normen som upprätthåller bilden av vad som anses vara det bästa sättet att utforma arbetsplatsen på, det vill säga vad som ger organisationer legitimitet. / The design of the offices affect how organizations are perceived internal and externally. The design has changed over time that to some extents depend on the society development and fashion. Activity-based workplace is a new way to design offices and many more organizations choose to implement an activity-based workplace approach nowadays.  The purpose of the study is to create understanding of the influence of fashion in organizations development by studying the introduction of activity-based workplace. The study is based on a deductive research approach with a qualitative research methodology. The study is a cross-sectional research with data collection from more than one case. Eight qualitative interviews and two observations have been completed. There are several reasons for implementing an activity-based workplace. Reduced costs due to reduced workspace premises, increased productivity, being environmentally responsible, increased attractiveness, collaboration and innovation creation are examples of reasons for the implementation. In a fashion metaphor, the spread of the activity-based workplace concept is increasing provenly, which is done by consultants, companies and the media. The idea of activity-based workplace has entered the discourse of organization and it is about to change the norm that maintains the image of what is considered the best way to design the workplace; that is what gives organizations legitimacy.

Rhomboids are unique membrane proteins that use a serine protease hydrolysis mechanism to cleave a transmembrane substrate within the lipid bilayer. This remarkable proteolytic activity is achieved by a core domain comprised of 6 transmembrane segments that form a hydrophilic cavity submerged in the membrane. In addition to this core domain, many rhomboids also possess aqueous domains of varying sizes at the N- and/or C-terminus, the sequences of which tend to be rhomboid-type specific. The functional role of these extramembranous domains is generally not well understood, although it is thought that they may be involved in regulation of rhomboid activity and specificity. While extramembranous domains may be important for rhomboid activity, they are absent in all x-ray crystal structures available. For this reason, we have focused on uncovering the structural and functional relationship between the rhomboid cytoplasmic domain and its catalytic transmembrane core. To investigate the structure and function of the bacterial rhomboid cytoplasmic domain, full-length rhomboids from Escherichia coli and Pseudomonas aeruginosa were studied using solution nuclear magnetic resonance (NMR) spectroscopy, mutation and activity assays. The P. aeruginosa rhomboid was purified in a range of membrane-mimetic media, evaluated for its functional status in vitro and investigated for its NMR spectroscopic properties. Results from this study suggested that an activity-modulating interaction might occur between the catalytic core transmembrane domain and the cytoplasmic domain. Further investigation of this hypothesis with the E. coli rhomboid revealed that protease activity relies on a short but critical sequence N-terminal to the first transmembrane segment. This sequence was found to have a direct impact on the rhomboid active site, and should be included in future structural studies of this catalytic domain. The structure of the cytoplasmic domain from the E. coli rhomboid was also determined by solution NMR. We found that it forms slowly-exchanging dimers through an exchange of secondary structure elements between subunits, commonly known as three-dimensional domain swapping. Beyond this rare example of domain swapping in a membrane protein extramembranous domain, we found that the rate of exchange between monomeric and dimeric states could be accelerated by transient interactions with large detergent micelles with a phosphocholine headgroup, but not by exposure to other weakly denaturing conditions. This novel example of micelle-catalyzed domain swapping interactions raises the possibility that domain swapping interactions might be induced by similar interactions in vivo. Overall, the results of this thesis have identified detergent conditions that preserve the highest level of activity for bacterial rhomboids, defined the minimal functional unit beyond what had been identified in available x-ray crystal structures, and characterized a novel micelle-catalyzed domain-swapping interaction by the cytoplasmic domain.

This study aims to examine the characteristics of ABC in Thailand and to compare the important aspects of ABC in Thailand, as a developing country, to those in the UK, the US and Australia, as developed countries. A mail questionnaire survey was considered an appropriate method for this study. The sample was randomly selected from the directory of manufacturing firms of the Ministry of Industry of Thailand (1,000 firms). 219 questionnaires were returned, generating a 21.9% response rate.

Thesis (Ph.D.)--University of Western Australia, 2006.

Tez (Yüksek Lisans) - Süleyman Demirel Üniversitesi, Sosyal Bilimler Enstitüsü, İşletme Anabilim Dalı, 2007. / Bibliyografya var.

Studien undersökte hur tio anställda hos Försäkringskassan upplevde implementeringen av den aktivitetsbaserade kontorstypen som skedde 2014. Studien genomfördes i form av tio semi-strukturerade intervjuer som analyserades induktivt. Ur detta framkom tre teman: att arbeta aktivitetsbaserat, möjligheten att påverka samt social samvaro, varav de förstnämnda hade ett antal underteman. Slutsatsen av studien blev att Försäkringskassan inte anpassat deras version av ett aktivitetsbaserat kontor efter de arbetsuppgifter många av de anställda utför samt att Försäkringskassan inte behandlade implementeringen som en kontinuerlig process med möjlighet att forma kontorstypen efter hela organisationen. / The purpose of this study was to research the experience of ten employees of a Swedish administrative authority in regard to the implementation of an activity-based workplace 2014. The study was conducted in the form of ten semi-structured interviews which were analyzed inductively. From this, three themes emerged: working activity-based, the ability to influence and social cohesion. The former two with their own subcategories. The study concluded that the administrative authority did not adjust their version of an activity-based workplace to accommodate the tasks a large number of the employees perform on a daily basis. The implementation also was not considered a continuous process with the opportunity to shape the workplace to accommodate a larger part of the organisation.

abstract: Rapid developments are occurring in the arena of activity-based microsimulation models. Advances in computational power, econometric methodologies and data collection have all contributed to the development of microsimulation tools for planning applications. There has also been interest in modeling child daily activity-travel patterns and their influence on those of adults in the household using activity-based microsimulation tools. It is conceivable that most of the children are largely dependent on adults for their activity engagement and travel needs and hence would have considerable influence on the activity-travel schedules of adult members in the household. In this context, a detailed comparison of various activity-travel characteristics of adults in households with and without children is made using the National Household Travel Survey (NHTS) data. The analysis is used to quantify and decipher the nature of the impact of activities of children on the daily activity-travel patterns of adults. It is found that adults in households with children make a significantly higher proportion of high occupancy vehicle (HOV) trips and lower proportion of single occupancy vehicle (SOV) trips when compared to those in households without children. They also engage in more serve passenger activities and fewer personal business, shopping and social activities. A framework for modeling activities and travel of dependent children is proposed. The framework consists of six sub-models to simulate the choice of going to school/pre-school on a travel day, the dependency status of the child, the activity type, the destination, the activity duration, and the joint activity engagement with an accompanying adult. Econometric formulations such as binary probit and multinomial logit are used to obtain behaviorally intuitive models that predict children's activity skeletons. The model framework is tested using a 5% sample of a synthetic population of children for Maricopa County, Arizona and the resulting patterns are validated against those found in NHTS data. Microsimulation of these dependencies of children can be used to constrain the adult daily activity schedules. The deployment of this framework prior to the simulation of adult non-mandatory activities is expected to significantly enhance the representation of the interactions between children and adults in activity-based microsimulation models. / Dissertation/Thesis / M.S. Civil and Environmental Engineering 2010

Ao longo dos anos o desenvolvimento foi tratado apenas sob o aspecto econômico. Sob essa visão não havia limites para o crescimento. Porém, o esgotamento de alguns recursos e as crises que os sucederam, o aumento de acidentes ecológicos e conseqüente agravamento dos problemas ambientais, impulsionou a sociedade e os organismos que a representam a cobrar maior responsabilidade ambiental das organizações. Essa nova postura mundial impôs às empresas a incorporação em suas estratégias, além do fator econômico, também o fator ambiental como uma necessidade para garantir sua sobrevivência. Apesar da constatação da importância dos Sistemas de Gestão Ambiental e de sua incorporação por um grande número de empresas, são muito incipientes os efeitos alcançados pelos instrumentos utilizados para sua promoção, em especial os instrumentos de controle. Isso se deve especialmente pela não percepção do quanto a questão ambiental influencia na questão econômica das empresas. A gestão ambiental como qualquer prática administrativa requer instrumentos que possibilitem informações confiáveis. Este trabalho objetiva testar a utilização do custeio baseado em atividades como ferramenta para geração de elementos necessários à gestão ambiental. Para tal, foi desenvolvido um modelo para aplicação em uma área-piloto de um curtume. A escolha da empresa deu-se em função do alto nível de rejeitos gerados e por fazer uso de produtos químicos e de água limpa em seu processo produtivo. As conclusões deste estudo demonstram que o custeio ABC é um instrumento capaz de gerar informações úteis à Gestão Ambiental. / Throughout the years the development was treated only under the economic aspect. Analyzing in this way, the growth didn’t have limits. However, the exhaustion of some resources and the crises that had succeeded them, the increase of ecological accidents and as a result of that the worsening of the environmental problems, caused a boost in a society and the organisms that represent it. The community overcharges environmental responsibility of the organizations. This new world-wide view imposed to the companies the incorporation in its strategies, beyond the economic factor, also the environment factor as a necessity to assure its survival. Despite the observation of the importance of the Systems of Environmental Management and its incorporation for a great number of companies, the effects reached for the instruments used for its promotion are very beginning, in special the control instruments the effect reached for the instruments used for its promotion, in special the control instrument. It happens specially because of the lack of the perception of how the environment question influence in a economic question of the companies. The environment management as any practical administrative requires instruments that make possible trustworthy information. The purpose of this work is to test the use of the activity based costing as tool for generation of necessary elements the environment management. It was developed a model for application in tannery as an experimental area. The choice of the company was given in function of the high level of generated rejects and for making use of chemical products and clean water in its productive process. The conclusions of this study demonstrate that the ABC expenditure is an instrument capable to generate useful information to the Environment Management.

The diffusion of Activity Based Costing (ABC) has been researched extensively in developed countries. Research on these issues in Jordan in general and within the Jordanian industrial sector more specifically is limited. The aim of the current research is to contribute to the design and successful ABC implementation in the Jordanian industrial sector. To achieve the aim of the research, the research methodology included both quantitative and qualitative data. The first stage was a quantitative study. The questionnaire survey was developed and the primary aims were to determine the current state of ABC adoption and implementation. The factors that facilitate, motivate and create barriers to ABC implementation were examined. In the second stage, semistructured interviews were used to probe the significant results of the questionnaire survey. The interviews were conducted with 6 companies that have implemented ABC in full and currently using ABC information. The survey findings indicate that ABC implementation among Jordanian industrial companies is quite satisfactory. The rate of ABC implementation is about 50.8%. Within the Jordanian industrial sector, the interaction between the following factors facilitated and motivated the implementation of ABC, namely: top management support, both training and education about the system, higher information technology, increasing proportion of overhead costs, growing costs, including product costs and administrative costs, and an increasing number of product variants. The interviews with financial managers/heads of cost accounting departments are consistent with questionnaire survey findings and both reveal and emphasise the important effect of consultants, professional management/accounting bodies and cooperation between academics and professionals upon implementing ABC within the Jordanian industrial sector. Therefore, it can be concluded that it is not only demand but also supply factors that influence implementation of ABC within the Jordanian industrial companies.