Sara, age 15, plays the guitar

Inscriptions: Verso: [stamped] Photograph by Freda Leinwand. [463 West Street, Studio 229G, New York, NY 10014].

Sara, age 15, plays the guitar

Inscriptions: Verso: [stamped] Photograph by Freda Leinwand. [463 West Street, Studio 229G, New York, NY 10014].

Sara, age 15, plays the guitar

Inscriptions: Verso: [stamped] Photograph by Freda Leinwand. [463 West Street, Studio 229G, New York, NY 10014].

Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver.

A small portion of cellular glycogen is transported to and degraded in lysosomes by acid α-glucosidase (GAA) in mammals, but it is unclear why and how glycogen is transported to the lysosomes. Stbd1 has recently been proposed to participate in glycogen trafficking to lysosomes. However, our previous study demonstrated that knockdown of Stbd1 in GAA knock-out mice did not alter lysosomal glycogen storage in skeletal muscles. To further determine whether Stbd1 participates in glycogen transport to lysosomes, we generated GAA/Stbd1 double knock-out mice. In fasted double knock-out mice, glycogen accumulation in skeletal and cardiac muscles was not affected, but glycogen content in liver was reduced by nearly 73% at 3 months of age and by 60% at 13 months as compared with GAA knock-out mice, indicating that the transport of glycogen to lysosomes was suppressed in liver by the loss of Stbd1. Exogenous expression of human Stbd1 in double knock-out mice restored the liver lysosomal glycogen content to the level of GAA knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant that contains only the N-terminal 24 hydrophobic segment and the C-terminal starch binding domain (CBM20) interlinked by an HA tag. Our results demonstrate that Stbd1 plays a dominant role in glycogen transport to lysosomes in liver and that the N-terminal transmembrane region and the C-terminal CBM20 domain are critical for this function.

The works of Benjamin Disraeli, earl of Beaconsfield, embracing novels, romances, plays, poems, biography, short stories and great speeches : with a critical introduction /

Title within ornamental border in gold and colors.

ECONOMIC PROFITABILITY OF THE BAKKEN, NORTH DAKOTA UNCONVENTIONAL OIL PLAYS BASED ON A TYPICAL WELL PERFORMANCE WITH CURRENT MARKET CONDITIONS

Increases in oil prices after the economic recession have been surprising for domestic oil production in the United States since the beginning of 2009. Not only did the conventional oil extraction increase, but unconventional oil production and exploration also improved greatly with the favorable economic conditions. This favorable economy encourages companies to invest in new reservoirs and technological developments. Recently, enhanced drilling techniques including hydraulic fracturing and horizontal drilling have been supporting the domestic economy by way of unconventional shale and tight oil from various U.S. locations. One of the main contributors to this oil boom is the unconventional oil production from the North Dakota Bakken field. Horizontal drilling has increased oil production in the Bakken field, but the economic issues of unconventional oil extraction are still debatable due to volatile oil prices, high decline rates of production, a limited production period, high production costs, and lack of transportation. The economic profitability and viability of the unconventional oil play in the North Dakota Bakken was tested with an economic analysis of average Bakken unconventional well features. Scenario analysis demonstrated that a typical North Dakota Bakken unconventional oil well is profitable and viable as shown by three financial metrics; net present value, internal rate of return, and break-even prices.

Autoinducer-2 plays a crucial role in gut colonization and probiotic functionality of Bifidobacterium breve UCC2003

In the present study we show that luxS of Bifidobacterium breve UCC2003 is involved in the production of the interspecies signaling molecule autoinducer-2 (AI-2), and that this gene is essential for gastrointestinal colonization of a murine host, while it is also involved in providing protection against Salmonella infection in Caenorhabditis elegans. We demonstrate that a B. breve luxS-insertion mutant is significantly more susceptible to iron chelators than the WT strain and that this sensitivity can be partially reverted in the presence of the AI-2 precursor DPD. Furthermore, we show that several genes of an iron starvation-induced gene cluster, which are downregulated in the luxS-insertion mutant and which encodes a presumed iron-uptake system, are transcriptionally upregulated under in vivo conditions. Mutation of two genes of this cluster in B. breve UCC2003 renders the derived mutant strains sensitive to iron chelators while deficient in their ability to confer gut pathogen protection to Salmonella-infected nematodes. Since a functional luxS gene is present in all tested members of the genus Bifidobacterium, we conclude that bifidobacteria operate a LuxS-mediated system for gut colonization and pathogen protection that is correlated with iron acquisition.

Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

A systematic review of environmental correlates of obesity-related dietary behaviors in youth

There is increasing interest in the role the environment plays in shaping the dietary behavior of youth, particularly in the context of obesity prevention. An overview of environmental factors associated with obesity-related dietary behaviors among youth is needed to inform the development of interventions. A systematic review of observational studies on environmental correlates of energy, fat, fruit/ vegetable, snack/fast food and soft drink intakes in children (4–12 years) and adolescents (13–18 years) was conducted. The results were summarized using the analysis grid for environments linked to obesity. The 58 papers reviewed mostly focused on sociocultural and economical–environmental factors at the household level. The most consistent associations were found between parental intake and children’s fat, fruit/vegetable intakes, parent and sibling intake with adolescent’s energy and fat intakes and parental education with adolescent’s fruit/ vegetable intake. A less consistent but positive association was found for availability and accessibility on children’s fruit/vegetable intake. Environmental factors are predominantly studied at the household level and focus on sociocultural and economic aspects. Most consistent associations were found for parental influences (parental intake and education).More studies examining environmental factors using longitudinal study designs and validated measures are needed for solid evidence to inform interventions.

Why, how, what for? : motivations, actions and expectations in habitual entrepreneurship

Principal topic: Is habitual entrepreneurship different? Answering this is important to the field, however there is little systematic evidence, thus far. We addresses this by examining the role experience plays at three possible points of difference: motivations, actions and expectations; and by comparing those currently in the process of starting a business with those who have recent success in business creation. Firstly, we assess the balance of opportunity versus necessity motivation, internally versus externally stimulated decision processes and future growth aspirations. Literature suggests novices are more likely motivated to nascency out of necessity, and favour a manageable business size, while habitual entrepreneurs are more likely motivated by internally stimulated or idea driven processes. Secondly, we examine actions undertaken by successful experienced founders during gestation, contrasting ‘information collection’ and ‘opportunity definition’. Drawing on prior research we expect novices more likely to have enacted ‘information search’ while habitual entrepreneurs enact ‘opportunity definition’. Thirdly, we examine perceptions of venture success, where findings on overconfidence suggest that habitual entrepreneurs expect a higher chance of success for their ventures, while inexperience leads novices to underestimate the difficulty of entrepreneurial survival. Method: Empirical evidence to test these conjectures was drawn from a screened random sample of over 1100 Australian nascent and newly started business ventures. This information was collected during 2007/8 using a telephone survey. Results and Implications: Why do habitual entrepreneurs keep coming back? Findings suggest that while the pursuit of opportunity is shared by novice and experienced entrepreneur alike, consideration of repeat entrepreneurship may be motivated by a desire for growth. While idea driven motivations might not delineate a distinction during nascency, it does seem to be a factor contributing to the success of young firms. This warrants further research. How do habitual entrepreneurs behave differently? It seems they act to clearly define market opportunities as a matter of priority during venture gestation. What effect does entrepreneurial experience have on future expectations? Clearly a sense of realism is drawn over the difficulties that might be faced, and accords more circumspect judgements of venture survival. This finding informs practitioners considering entrepreneurship for the first time.

The importance of gestation process dynamics

Principal Topic In this paper we seek to highlight the important intermediate role that the gestation process plays in entrepreneurship by examining its key antecedents and its consequences for new venture emergence. In doing so we take a behavioural perspective and argue that it is not only what a nascent venture is, but what it does (Katz & Gartner, 1988; Shane & Delmar, 2004; Reynolds, 2007) and when it does it during start-up (Reynolds & Miller, 1992; Lichtenstein, Carter, Dooley & Gartner, 2007) that is important. To extend an analogy from biological development, what we suggest is that the way a new venture is nurtured is just as fundamental as its nature. Much prior research has focused on the nature of new ventures and attempted to attribute variations in outcomes directly to the impact resource endowments and investments have. While there is little doubt that venture resource attributes such as human capital, and specifically prior entrepreneurial experience (Alsos & Kolvereid, 1998), access to social (Davidsson & Honig, 2003) and financial capital have an influence. Resource attributes themselves are distal from successful start-up endeavours and remain inanimate if not for the actions of the nascent venture. The key contribution we make is to shift focus from whether or not actions are taken, but when these actions happen and how that is situated in the overall gestation process. Thus, we suggest that it is gestation process dynamics, or when gestation actions occur, that is more proximal to venture outcomes and we focus on this. Recently scholars have highlighted the complexity that exists in the start-up or gestation process, be it temporal or contextual (Liao, Welsch & Tan, 2005; Lichtenstein et al. 2007). There is great variation in how long a start-up process might take (Reynolds & Miller, 1992), some processes require less action than others (Carter, Gartner & Reynolds, 1996), and the overall intensity of the start-up effort is also deemed important (Reynolds, 2007). And, despite some evidence that particular activities are more influential than others (Delmar & Shane, 2003), the order in which events may happen is, until now, largely indeterminate as regard its influence on success (Liao & Welsch, 2008). We suggest that it is this complexity of the intervening gestation process that attenuates the effect of resource endowment and has resulted in mixed findings in previous research. Thus, in order to reduce complexity we shall take a holistic view of the gestation process and argue that it is its’ dynamic properties that determine nascent venture attempt outcomes. Importantly, we acknowledge that particular gestation processes of themselves would not guarantee successful start-up, but it is more correctly the fit between the process dynamics and the ventures attributes (Davidsson, 2005) that is influential. So we aim to examine process dynamics by comparing sub-groups of venture types by resource attributes. Thus, as an initial step toward unpacking the complexity of the gestation process, this paper aims to establish the importance of its role as an intermediary between attributes of the nascent venture and the emergence of that venture. Here, we make a contribution by empirically examining gestation process dynamics and their fit with venture attributes. We do this by firstly, examining that nature of the influence that venture attributes such as human and social capital have on the dynamics of the gestation process, and secondly by investigating the effect that gestation process dynamics have on venture creation outcomes. Methodology and Propositions In order to explore the importance that gestation processes dynamics have in nascent entrepreneurship we conduct an empirical study of ventures start-ups. Data is drawn from a screened random sample of 625 Australian nascent business ventures prior to them achieving consistent outcomes in the market. This data was collected during 2007/8 and 2008/9 as part of the Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE) project (Davidsson et al., 2008). CAUSEE is a longitudinal panel study conducted over four years, sourcing information from annually administered telephone surveys. Importantly for our study, this methodology allows for the capture and tracking of active nascent venture creation as it happens, thus reducing hindsight and selection biases. In addition, improved tests of causality may be made given that outcome measures are temporally removed from preceding events. The data analysed in this paper represents the first two of these four years, and for the first time has access to follow-up outcome measures for these venture attempts: where 260 were successful, 126 were abandoned, and 191 are still in progress. With regards to venture attributes as gestation process antecedents, we examine specific human capital measured as successful prior experience in entrepreneurship, and direct social capital of the venture as ‘team start-ups’. In assessing gestation process dynamics we follow Lichtenstein et al. (2007) to suggest that the rate, concentration and timing of gestation activities may be used to summarise the complexity dynamics of that process. In addition, we extend this set of measures to include the interaction of discovery and exploitation by way of changes made to the venture idea. Those ventures with successful prior experience or those who conduct symbiotic parallel start-up attempts may be able to, or be forced to, leave their gestation action until later and still derive a successful outcome. In addition access to direct social capital may provide the support upon which the venture may draw in order to persevere in the face of adversity, turning a seemingly futile start-up attempt into a success. On the other hand prior experience may engender the foresight to terminate a venture attempt early should it be seen to be going nowhere. The temporal nature of these conjectures highlight the importance that process dynamics play and will be examined in this research Statistical models are developed to examine gestation process dynamics. We use multivariate general linear modelling to analyse how human and social capital factors influence gestation process dynamics. In turn, we use event history models and stratified Cox regression to assess the influence that gestation process dynamics have on venture outcomes. Results and Implications What entrepreneurs do is of interest to both scholars and practitioners’ alike. Thus the results of this research are important since they focus on nascent behaviour and its outcomes. While venture attributes themselves may be influential this is of little actionable assistance to practitioners. For example it is unhelpful to say to the prospective first time entrepreneur “you’ll be more successful if you have lots of prior experience in firm start-ups”. This research attempts to close this relevance gap by addressing what gestation behaviours might be appropriate, when actions best be focused, and most importantly in what circumstances. Further, we make a contribution to the entrepreneurship literature, examining the role that gestation process dynamics play in outcomes, by specifically attributing these to the nature of the venture itself. This extension is to the best of our knowledge new to the research field.

Experiential knowledge representation and the design of product usability

The topic of designers’ knowledge and how they conduct design process has been widely investigated in design research. Understanding theoretical and experiential knowledge in design has involved recognition of the importance of designers’ experience of experiencing, seeing, and absorbing ideas from the world as points of reference (or precedents) that are consulted whenever a design problem arises (Lawson, 2004). Hence, various types of design knowledge have been categorized (Lawson, 2004), and the nature of design knowledge continues to be studied (Cross, 2006); nevertheless, the study of the experiential aspects embedded in design knowledge is a topic not fully addressed. In particular there has been little emphasis on the investigation of the ways in which designers’ individual experience influences different types of design tasks. This research focuses on the investigation of the ways in which designers inform a usability design process. It aims to understand how designers design product usability, what informs their process, and the role their individual experience (and episodic knowledge) plays within the design process. This paper introduces initial outcomes from an empirical study involving observation of a design task that emphasized usability issues. It discusses the experiential knowledge observed in the visual representations (sketches) produced by designers as part of the design tasks. Through the use of visuals as means to represent experiential knowledge, this paper presents initial research outcomes to demonstrate how designers’ individual experience is integrated into design tasks and communicated within the design process. Initial outcomes demonstrate the influence of designers’ experience in the design of product usability. It is expected that outcomes will help identify the causal relationships between experience, context of use, and product usability, which will contribute to enhance our understanding about the design of user-product interactions.

The central role of communication in developing trust and its effect on employee involvement

Communication plays an important role in the development of trust within an organization. While a number of researchers have studied the relationship of trust and communication, little is known about the specific linkages among quality of information, quantity of information, openness, trust, and outcomes such as employee involvement. This study tests these relationships using communication audit data from 218 employees in the oil industry. Using mediation analysis and structural equation modeling, we found that quality of information predicted trust of one's coworkers and supervisors while adequacy of information predicted one's trust of top management. Trust of coworkers, supervisors, and top management influenced perceptions of organizational openness, which in turn influenced employees' ratings of their own level of involvement in the organization's goals. This study suggests that the relationship between communication and trust is complex, and that simple strategies focusing on either quality or quantity of information may be ineffective for dealing with all members in an organization.

Life cycle modelling and design knowledge development in 3D virtual environments : final report

Experience plays an important role in building management. “How often will this asset need repair?” or “How much time is this repair going to take?” are types of questions that project and facility managers face daily in planning activities. Failure or success in developing good schedules, budgets and other project management tasks depend on the project manager's ability to obtain reliable information to be able to answer these types of questions. Young practitioners tend to rely on information that is based on regional averages and provided by publishing companies. This is in contrast to experienced project managers who tend to rely heavily on personal experience. Another aspect of building management is that many practitioners are seeking to improve available scheduling algorithms, estimating spreadsheets and other project management tools. Such “micro-scale” levels of research are important in providing the required tools for the project manager's tasks. However, even with such tools, low quality input information will produce inaccurate schedules and budgets as output. Thus, it is also important to have a broad approach to research at a more “macro-scale.” Recent trends show that the Architectural, Engineering, Construction (AEC) industry is experiencing explosive growth in its capabilities to generate and collect data. There is a great deal of valuable knowledge that can be obtained from the appropriate use of this data and therefore the need has arisen to analyse this increasing amount of available data. Data Mining can be applied as a powerful tool to extract relevant and useful information from this sea of data. Knowledge Discovery in Databases (KDD) and Data Mining (DM) are tools that allow identification of valid, useful, and previously unknown patterns so large amounts of project data may be analysed. These technologies combine techniques from machine learning, artificial intelligence, pattern recognition, statistics, databases, and visualization to automatically extract concepts, interrelationships, and patterns of interest from large databases. The project involves the development of a prototype tool to support facility managers, building owners and designers. This final report presents the AIMMTM prototype system and documents how and what data mining techniques can be applied, the results of their application and the benefits gained from the system. The AIMMTM system is capable of searching for useful patterns of knowledge and correlations within the existing building maintenance data to support decision making about future maintenance operations. The application of the AIMMTM prototype system on building models and their maintenance data (supplied by industry partners) utilises various data mining algorithms and the maintenance data is analysed using interactive visual tools. The application of the AIMMTM prototype system to help in improving maintenance management and building life cycle includes: (i) data preparation and cleaning, (ii) integrating meaningful domain attributes, (iii) performing extensive data mining experiments in which visual analysis (using stacked histograms), classification and clustering techniques, associative rule mining algorithm such as “Apriori” and (iv) filtering and refining data mining results, including the potential implications of these results for improving maintenance management. Maintenance data of a variety of asset types were selected for demonstration with the aim of discovering meaningful patterns to assist facility managers in strategic planning and provide a knowledge base to help shape future requirements and design briefing. Utilising the prototype system developed here, positive and interesting results regarding patterns and structures of data have been obtained.