1,721,064 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
An In silico Investigation of the Metabolic Capabilities of Anaeromyxobacter Dehalogenans and Field-scale Applications
No full textIn recent years, uranium pollution in the environment has been recognized as a serious threat, and novel in situ microbial bioremediation strategies have been incorporated into field-scale contaminated sites. The Oak Ridge Integrated Field-scale Subsurface Research Challenge (IFC) site is one of the largest uranium contaminated areas in the United States, and a literature review has revealed the potential of uranium reduction by dominant Anaeromyxobacter dehalogenans species that respire during bioremediation. A genome-scale model of A. dehalogenans, a unique microbe with diverse metabolic capabilities that thrives in the natural environment, has been developed, and applied to an in silico field-scale computational setting for evaluation of the biotic uranium reduction in the Oak Ridge IFC site. The metabolic model of A. dehalogenans was integrated into an expanded microbial community framework for the prediction of chemical profiles, and subsequent scenario evaluation of in situ measured data.MAS
Metabolic Engineering of Escherichia coli for Production of Adipic Acid through 2-Hexenedioate Pathway
No full textAdipic acid is one of the most important platform chemicals in industry. Bio-based production of adipic acid is a promising alternative to the current petrochemical production routes which cause environment and energy concerns. This work describes efforts to construct a platform strain of Escherichia coli for production of adipic acid. First, we constructed an E. coli strain harbouring part of the α-aminoadipate pathway from Saccharomyces cerevisiae. Through fed-batch fermentation, the strain showed its capability of producing α-ketoadipate, a precursor of adipic acid, from its native metabolite α-ketoglutarate. Second, we constructed an E. coli strain harbouring a pathway converting α-ketoadipate to adipic acid. Through various studies, we were able to illustrate that all enzymes of the pathway are active in vivo. This work demonstrates the capability of E. coli for production of α-ketoadipate and paves the way for further studies on conversion of α-ketoadipate to adipic acid.M.A.S.2018-03-15 00:00:0
On the Effectiveness and Challenges of Electrosynthesis Strategies in Escherichia coli
No full textConventional bioprocesses that aim to convert CO2 to fuels and chemicals do so through a supply chain that begins with agricultural products such as corn, intermediaries like dextrose, and eventually produce chemicals by fermentation. However, it has long been desired that bioprocesses be established to convert CO2 point source emissions to chemicals. Fundamentally, this is a thermodynamics problem since the use of CO2 as a feedstock requires an efficient mechanism to deliver energy to produce chemicals. The focus of this work is to examine several strategies for microbial electrosynthesis, the delivery of electrical energy to microbial cell factories, for producing chemicals. The study encompasses four areas type of microbial electrosynthesis and the results are summarized here:
1) Experimental work was performed to evaluate the affect of neutral red mediated charge transfer in mutant strains of Escherichia coli for the purpose of producing succinic acid. The results of this task showed wild-type cells exhibited the greatest molar increase in succinate yield with an 89% increase while an ldhA deficient strain showed 40% increase. The lack of direct charge transfer was implicated as the cause since an electron balance was not able to account for an increase in succinate.
2) We explored the use of mediators such has formate that can be generated from carbon dioxide and renewable electricity as a carbon source for cell growth and chemical production. An auxotrophic strategy was employed to engineer formate assimilation, and growth rate on formate as a C1 donor for folate was determined to be 0.33 h-1. This was 78% of the wild-type strain.
3) We developed a framework for analyzing how metabolic pathways can be efficiently engineered into microbes to produce chemicals. This orthogonality framework showed ethylene glycol to be a highly promising substrate for electrosynthesis applications.
4) Finally, a bioprocess for the conversion of ethylene glycol to glycolic acid was characterized and its suitability to replace glucose as a feedstock was examined. The maximum glycolate titres for the best performing conditions reached 10.6 g/L. The highest substrate uptake rate for ethylene glycol was determined to be ca. 5 mmol/gDW-h.Ph.D.2019-12-19 00:00:0
Metabolic Engineering of Lyase-Based Biosynthetic Pathways for Non-Natural Chemical Production
No full textMetabolic engineering efforts have led to the development of bioprocesses implemented at an industrial scale for the production of natural and non-natural chemicals. However, several challenges need to be addressed in order to develop more bioprocesses that can reduce our reliance on petroleum-based feedstocks. One area of improvement is to expand the types of chemicals that can be produced. Often, the limitation lies in the unavailability of known enzymes to catalyze steps in novel biosynthetic pathways. This thesis investigates the application of carbon-carbon bond-forming enzymes in biosynthetic pathways to produce chemicals from renewable resources. In addition, this thesis provides insights into aldehyde metabolism in microbes by elucidating side reactions that need to be addressed in order to utilize aldehyde-associated reactions. First, we demonstrated the production of a non-natural chemical, 1,3-butanediol, from glucose in Escherichia coli using an aldolase-based pathway that also produced acetaldehyde via pyruvate decarboxylase. By combining strain and pathway engineering strategies, 1,3-butanediol reached a titer of 2.4 g/L and 11 % of the maximum theoretical yield from glucose in strain BD24. We suspected that a combination of challenges remained in the engineered strain including poor NADPH balancing and carboligation activity of pyruvate decarboxylase resulting in acetoin and 2,3-butanediol production. Therefore, we designed an alternative acetaldehyde production module from glucose, using an acetylating acetaldehyde dehydrogenase in attempt to prevent acetoin production. In combination with a metabolic model-guided approach, we identified gene knockouts that could further improve 1,3-butanediol yield on glucose. Deleting the following genes predicted by the model: ilvB, pykF, sfcA, and sthA led to the highest 1,3-butanediol yield in our study (16.8 % of the maximum theoretical yield). Finally, we demonstrated the tuning of 2,3-butanediol isomer production in E. coli using a shorter and novel pathway via the carboligation activity on acetaldehyde to produce acetoin. The final strain BD38 led to the production of 2S,3S-butanediol directly from glucose with a yield of 21 % of the maximum theoretical yield. Harnessing the potential of lyases, including aldolases and carboligases, has led to the production of a non-natural chemical, 1,3-butanediol, and a non-inherent chemical, 2S,3S-butanediol, in E. coli.Ph.D.2019-11-19 00:00:0
Integrative Approaches in Synthetic Biology and Computational Design for Advancing Therapeutics
No full textRecent advances in synthetic biology have catalyzed the exploration of engineered microbes for therapeutic applications, highlighting their potential to overcome traditional therapy limitations. This study presents a collaborative approach between computational methods and synthetic biology to enhance therapeutic strategies and microbial understanding in the context of inflammatory bowel disease (IBD). This research illustrates the development of an E. coli Nissle 1917 strain engineered to increase Muramyl Dipeptide (MDP) production, targeting the activation of the NOD2 receptor, which is crucial in IBD pathophysiology. By enhancing MDP output, this engineered strain offers a direct method to counteract the NOD2 signaling deficits observed in IBD, setting a precedent for the next generation of probiotics. Complementing this, we developed Framework for Optimized Customizable User-Informed Synthesis (FOCUS) which employed ML algorithms to design new ligands with improved drug-like and interaction profiles, representing a diverse pool of therapeu- tic candidates poised for experimental exploration. Furthermore, our platform FOCUS revealed molecular patterns that enhance drug-likeness and target binding, expanding our knowledge around the ligand-receptor interaction. Bridging from molecular innovation to community dynamics, in our third study, we created DyMMM-LEAPS which combined metabolic modeling and ML to adeptly explore the design space of synthetic microbial communities, identifying the parameters necessary for the development of stable and even microbial populations. By optimizing these communities, we aim to maintain gut home- ostasis, a key factor in IBD management. Overall, these multidisciplinary projects lay a foundation for future advancements in microbial engineering, offering a pathway to more personalized, responsive therapies, and emphasizing the significant role of machine learning and synthetic biology in therapeutic innovation.Ph.D
An in silico Characterization of Microbial Electrosynthesis for Metabolic Engineering of Biochemicals
Full text linkA critical concern in metabolic engineering is the need to balance the demand and supply of redox intermediates. Bioelectrochemical techniques offer a promising method to alleviate redox imbalances during the synthesis of biochemicals. Broadly, these techniques reduce intracellular NAD+ to NADH and therefore manipulate the cell’s redox balance. The cellular response to such redox changes and the additional reducing can be harnessed to produce desired metabolites. In the context of microbial fermentation, these bioelectrochemical techniques can improve product yields and/or productivity.
We have developed a method to characterize the role of bioelectrosynthesis in chemical production using the genome-scale metabolic model of E. coli. The results elucidate the role of bioelectrosynthesis and its impact on biomass growth, cellular ATP yields and biochemical production. The results also suggest that strain design strategies can change for fermentation processes that employ microbial electrosynthesis and suggest that dynamic operating strategies lead to maximizing productivity.MAS
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