Jadomycins are secondary metabolites produced by Streptomyces venezuelae ISP5230 VS1099 in response to conditions of stress such as heat or ethanol shock. They have been shown to exhibit antibiotic and anticancer activity. Unique structural features of the jadomycins include a rare 2,6-dideoxysugar, L-digitoxose, and an oxazolone ring with an amino acid component. Previous studies have revealed that jadomycin derivatives can be produced by altering the amino acid in S. venezuelae ISP5230 VS1099 culture media which becomes incorporated into the oxazolone ring. One jadomycin from a proteogenic amino acid and three new jadomycins from non-proteogenic amino acids have been successfully produced on a large scale (4 mg/L to 12 mg/L, 2 L) and characterized using mass spectrometry, infrared spectroscopy, UV-visible spectroscopy, and nuclear magnetic resonance spectroscopy. One of these contains a terminal alkyne functionality and has been used in cycloaddition reactions with various azides to produce a library of triazole-containing jadomycins.

Employee learning provides significant competitive advantage for organizations. Understanding how employees learn in different work contexts can support continuing, effective, and frequent learning. Although most workplace learning is done informally, the characteristics of that learning are minimally reported and the criteria used to define learning as informal are inconsistent. Research into continuing professional development in knowledge-intense environments or distributed workforces is sparse. The pharmaceutical sales industry is a previously unexamined knowledge-intense environment with a geographically distributed workforce. This qualitative case study sought a better understanding of how pharmaceutical sales representatives learn for work by documenting and describing those ways of learning reported as most effective and most frequent. Twenty sales agents from 11 organizations participated in a Delphi collaboration to create a comprehensive list of 64 ways they learn for work. In-depth individual interviews with five agents provided deep detail about learning in this industry, including the ways of learning that the participating agents perceive to be most effective and most frequent. The Colley, Hodkinson and Malcom (2003) framework was interpreted, applied, and extended in order to identify attributes of formality and informality and other characteristics inherent in the ways of learning reported as most effective and most frequent. This study showed that agents learn in a wide variety of ways and that most of those ways are self-initiated, self-directed, minimally structured, and often involve intentional incidental learning: agents are constantly alert to capture learning while engaged in work activities. Learning during customer interactions on the job was reported as particularly effective and frequent. Other reported effective ways of learning varied with the agent but usually involved self-directed learning with mixed formal and informal attributes. It was determined that learning plays a special role in this industry: much of what is learned for work is not being applied directly to the job of sales promotion. Instead, agents use learning to develop themselves as resources for physicians in order to gain the customer-access required to promote their products. In this way, learning on the job is the job. / Thesis (Master, Education) -- Queen's University, 2009-04-23 16:16:11.431

Of the organisms with sequenced genomes, plants appear to possess the most rhomboid protease-encoding genes. However, our knowledge of processes in plants that involve Regulated Intramembrane Proteolysis (RIP) and rhomboid proteases remains low. As expressed recently by other researchers, finding a natural substrate for a rhomboid protease represents the biggest experimental challenge. Using yeast mitochondria-based assays, a potential link between the plastid translocon component Tic40 and organellar rhomboid proteases was recently uncovered. In this particular link, rhomboid proteases appear capable of influencing the pattern of imported Tic40 in yeast mitochondria. Tic40 may thus represent a natural plant target of organellar rhomboid proteases. Here, we obtained further motif-oriented evidence supporting Tic40 as a natural plant rhomboid substrate. A comparative analysis of sequences revealed that Tic40 may also possess similar TMD motifs found in the model substrate, Spitz. Rhomboid proteases often require these motifs to cleave substrates within intramembrane environments. Using site-directed mutagenesis and yeast mitochondria assays, the impact of mutations occurring in the motifs ASISS, GV, QP, and GVGVG of Tic40 was assessed. In terms of cleavage and changing the pattern of imported Tic40, some of the mutations showed decreased activities and a few showed enhancements. More importantly, the overall observed pattern associated with select Tic40 mutations resembled the characteristics reported for the model substrates. In particular, mutations in the Tic40 GV motif produced similar results as that observed with Spitz, by drastically decreasing or increasing cleavage as a function of amino acid sequence. / Thesis (Master, Biology) -- Queen's University, 2010-05-30 10:22:07.72

No description available.

During domestication, the dog( Canis familiaris), have become skilful in understanding human communication and also in communicating with humans. The wolf ( Canis lupus), is not as skilled with this interspecific communication. When dogs are faced with an unsolvable problem, they seek help from human by e.g. gazing at them. This behaviour has been studied and both age and breed group differences have been showed. In this study, we presented dogs with a task that consisted of a solvable and unsolvable problem in order to see if they gazed at their owner and/or an unfamiliar person for help. Although we did not find any difference in breed groups regarding gazing at humans, we did find that adult dogs (dogs older than 2 years) gazed more frequently at their owner and for a longer duration than adolescent dogs (6 months to 2 years). This may be because the adult dogs have more experience of this communication with humans, as they have lived longer with them. These findings empathize the bond between a dog and its owner that seems to grow stronger during the dogs’ life.

Municipal wastewater treatment plants (MWWTPs) are point sources of environmental contamination that can cause adverse effects on fish species exposed to their effluents (MWWEs). Contaminants, such as endocrine disrupting compounds (EDCs), commonly found in MWWEs have been shown to induce many adverse reproductive effects. In the Grand River watershed of southern Ontario, three MWWTPs from the cities of Guelph, Waterloo and Kitchener have been identified to adversely alter molecular and cellular responses in fish, which have been previously associated with exposure to estrogenic EDCs. Currently these systems are undergoing process upgrades to address aging infrastructure as well as expanding capacities to serve rapidly increasing populations. Studies in this thesis were conducted to determine whether the Guelph and Waterloo MWWEs, as well as surrogate pilot plant effluents that modeled possible treatment process upgrades for MWWTPs were estrogenic in vivo in controlled laboratory exposures. Unfortunately, the Kitchener MWWE (conventional activated sludge and lagoon) was acutely toxic and could not be included in laboratory exposures. Rainbow trout (Oncorhynchus mykiss) were exposed to 20% to 90% effluent from both Guelph and Waterloo, for 2, 8 and 14 days and fish plasma was analyzed for vitellogenin (VTG) a biomarker for estrogenic exposure. These exposures indicated that neither the Guelph nor the Waterloo MWWE were estrogenic in vivo under the exposure conditions in this study. In contrast the total estrogenic equivalence measured using the yeast estrogen screen (YES) of the Guelph, Waterloo and Kitchener MWWEs increased respectively, inversely related to the degree of treatment. Three pilot plant effluents (Burlington MWWTP) including conventional activated sludge (CAS), nitrifying with CAS (CAS-N) and biological nutrient removal with CAS (CAS-BNR) were also tested in rainbow trout in vivo for plasma VTG induction. Only the CAS-BNR effluent caused weak (2-3.5 fold) induction of VTG relative to controls. Although the estrogenicity (YES) of the effluent was variable the VTG induction corresponded with the slightly higher 17??-estradiol equivalents measured in these pilot plant effluents. An effect-directed analysis (EDA) for estrogenic substances was carried out on the Waterloo and Kitchener MWWEs and revealed that the estrogenicity (YES) of the Waterloo MWWE was associated with estrone, while the estrogenicity of the Kitchener MWWE was associated with several chemicals (estrone > 17??-estradiol > bisphenol A ~ testosterone).

In the Directed Steiner Tree problem, we are given a directed graph G = (V,E) with edge costs, a root vertex r ∈ V, and a terminal set X ⊆ V . The goal is to find the cheapest subset of edges that contains an r-t path for every terminal t ∈ X. The only known polylogarithmic approximations for Directed Steiner Tree run in quasi-polynomial time and the best polynomial time approximations only achieve a guarantee of O(|X|^ε) for any constant ε > 0. Furthermore, the integrality gap of a natural LP relaxation can be as bad as Ω(√|X|).  We demonstrate that l rounds of the Sherali-Adams hierarchy suffice to reduce the integrality gap of a natural LP relaxation for Directed Steiner Tree in l-layered graphs from Ω( k) to O(l · log k) where k is the number of terminals. This is an improvement over Rothvoss’ result that 2l rounds of the considerably stronger Lasserre SDP hierarchy reduce the integrality gap of a similar formulation to O(l · log k). We also observe that Directed Steiner Tree instances with 3 layers of edges have only an O(logk) integrality gap bound in the standard LP relaxation, complementing the fact that the gap can be as large as Ω(√k) in graphs with 4 layers. Finally, we consider quasi-bipartite instances of Directed Steiner Tree meaning no edge in E connects two Steiner nodes V − (X ∪ {r}). By a simple reduction from Set Cover, it is still NP-hard to approximate quasi-bipartite instances within a ratio better than O(log|X|). We present a polynomial-time O(log |X|)-approximation for quasi-bipartite instances of Directed Steiner Tree. Our approach also bounds the integrality gap of the natural LP relaxation by the same quantity. A novel feature of our algorithm is that it is based on the primal-dual framework, which typically does not result in good approximations for network design problems in directed graphs.

Phonetic aspects of mother-infant interaction are discussed in light of a functionalist Mother-infant phonetic interaction (MIPhI) model. Adults addressing infants typically use a speech style (infant-directed speech, IDS) characterized by, for instance, extensive suprasegmental (prosodic) modulations. This type of speech seems to interest young infants whose active experience with the spoken language appears to focus their speech perception on the phonological properties of the ambient language during the first year of life. This thesis consists of four articles discussing phonetic modifications at the suprasegmental, segmental and phonological levels, based on data from six Swedish mothersí IDS to their 3-month-olds. The first study concerns the tonal word accent 2 in disyllabic words, and shows how the lexical, bimodal, tonal characteristics of this accent are enhanced in IDS as compared to adult-directed speech (ADS). The second is a cross-linguistic investigation of vowel formant frequencies in Swedish, Am. English and Russian IDS. It shows that vowels like /i/, /u/, and /a/ are more clearly separated in IDS than in ADS, in all three languages. The third study addresses the voiced /voiceless contrast in stop consonants as measured by voice onset time (VOT) and shows that stop consonants seem to be poorly separated in early IDS samples. The fourth study investigates the quantity distinction in V:C and VC: sequences and indicates that this phonological contrast is well maintained in the IDS. Adult data are discussed within the MIPhI model, assuming that suprasegmental and segmental specifications in IDS follow different phonetic specification paths adapted to the infantsí capacities as these develop over the first 18 months of life. The adultsí phonetic adaptations appear to reflect a selective strategy of presenting linguistic structure in a ìgift-wrappingî that is attractive and functional for the infant. / För att köpa boken skicka en beställning till exp@ling.su.se/ To order the book send an e-mail to exp@ling.su.se

Biocatalysts are increasingly prevalent in the large-scale synthesis of enantiomerically pure compounds. However, many sought-after reactions lack a suitable enzymatic production route. This work describes the development of a novel amine dehydrogenase through the application of directed evolution altering the substrate specificity of an existing leucine dehydrogenase scaffold. Eleven rounds of directed evolution completely altered the enzyme’s specificity and successfully created amination activity. The resulting amine dehydrogenase asymmetrically catalyzes methyl isobutyl ketone and free ammonia to 1, 3-dimethyl butyl amine. The enantioselectivity of the wild-type enzyme was maintained despite the drastic changes to the binding pocket and yielded (R)-1,3-DMBA with nearly complete conversion making it an attractive catalyst in the synthesis of chiral amines. This was the first example of a cofactor-dependent amine dehydrogenase capable of selectively synthesizing chiral amines from a prochiral ketone and free ammonia. Additionally, knowledge gained altering the specificity of the leucine dehydrogenase scaffold was applied to an analogous phenylalanine dehydrogenase scaffold allowing for rapid evolution of novel activity. A single mutational library resulted in a second amine dehydrogenase with enhanced activity toward significantly different substrates, while maintaining comparable conversion and enantioselectivity. These two scaffolds provide examples of the broad applicability of the identified mutations in creating amine dehydrogenase activity.

The purpose of this research was to establish the feasibility of delivering a 6-week long adapted Mindfulness for Academic Success (MAS) program to post-secondary students who were experiencing difficulties with their academic performance. Feasibility was established based on recruitment success (70%), program attendance (70% of participants attending at least four sessions), and homework compliance (70% homework completed). In addition, we hoped to establish the MAS program’s preliminary efficacy in improving executive and academic functioning and reducing mind wandering, inattention, symptoms of ADHD, and psychological distress. Forty participants from Carleton University were randomized to the MAS program (n = 20) or waitlist (WL) condition (n = 20). The overall dropout rate in this study was 38 %. Forty-five percent of the MAS program and 80% of the WL condition participants completed the study. MAS program completers complied with 32% of the overall homework during the five week reporting period and no student completed individually more than 57% of the assigned homework tasks. Accordingly, we did not meet the session attendance or homework completion feasibility requirements. Our preliminary efficacy results indicated significant improvements in some program outcomes in the intent-to-treat sample and results were more robust for MAS completers. Specifically executive functioning—self-management to time, self-organization, self monitoring, self-regulation of emotions, and executive function (EF) related ADHD symptoms—improved and ADHD symptoms decreased in the intent-to-treat sample and results were more robust in the completer sample. Psychological distress symptoms (depression and stress) and mind wandering decreased only in MAS program completers, but no changes were noted in students’ ability to pay attention to presented information during the mind wandering task. Academic functioning as measured by selecting main ideas, the use of study aids, and time management improved in both the intent-to-treat and completer samples. Changes in concentration and information processing were only evident for MAS program completers, however, changes were also noted in academic anxiety, motivation, and the use of test strategies, although effects were small. No changes were observed in participants’ self-restraint (EF), generalized anxiety, attitude toward school, and the use of self-testing in exam preparation. Although efficacy results suggest the MAS program may be beneficial, low program compliance and lack of change in students’ levels of mindfulness compromise the internal validity of this study and make drawing causal conclusions about the program’s efficacy difficult. Furthermore, while program attendance and homework compliance were correlated with some program outcomes, the lack of correlation between formal practices of mindfulness and program outcomes suggest that non-specific factors may have contributed to observed improvement in study outcomes.