Scale-down studies for the scale-up of a recombinant Corynebacterium glutamicum fed-batch fermentation:loss of homogeneity leads to lower levels of cadaverine production

BACKGROUND: The loss of efficiency and performance of bioprocesses on scale-up is well known, but not fully understood. This work addresses this problem, by studying the effect of some fermentation gradients (pH, glucose and oxygen) that occur at the larger scale in a bench-scale two-compartment reactor [plug flow reactor (PFR) + stirred tank reactor (STR)] using the cadaverine-producing recombinant Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT. The new scale-down strategy developed here studied the effect of increasing the magnitude of fermentation gradients by considering not only the average cell residence time in the PFR (τPFR), but also the mean frequency at which the bacterial cells entered the PFR (fm) section of the two-compartment reactor. RESULTS: On implementing this strategy the cadaverine production decreased on average by 26%, 49% and 59% when the τPFR was increased from 1 to 2 min and then 5 min respectively compared to the control fermentation. The carbon dioxide productivity was highest (3.1-fold that of the control) at a τPFR of 5 min, but no losses were observed in biomass production. However, the population of viable but non-culturable cells increased as the magnitude of fermentation gradients was increased. The new scale-down approach was also shown to have a bigger impact on fermentation performance than the traditional one. CONCLUSION: This study demonstrated that C. glutamicum DM1945 Δact3 Ptuf-ldcC_OPT physiological response was a function of the magnitude of fermentation gradients simulated. The adaptations of a bacterial cell within a heterogeneous environment ultimately result in losses in fermentation productivity as observed here

Static Generation of UML Sequence Diagrams

UML sequence diagrams are visual representations of object interactions in a system and can provide valuable information for program comprehension, debugging, maintenance, and software archeology. Sequence diagrams generated from legacy code are independent of existing documentation that may have eroded. We present a framework for static generation of UML sequence diagrams from object-oriented source code. The framework provides a query refinement system to guide the user to interesting interactions in the source code. Our technique involves constructing a hypergraph representation of the source code, traversing the hypergraph with respect to a user-defined query, and generating the corresponding set of sequence diagrams. We implemented our framework as a tool, StaticGen (supporting software: StaticGen), analyzing a corpus of 30 Android applications. We provide experimental results demonstrating the efficacy of our technique (originally appeared in the Proceedings of Fundamental Approaches to Software Engineering—20th International Conference, FASE 2017, Held as Part of the European Joint Conferences on Theory and Practice of Software, ETAPS 2017, Uppsala, Sweden, April 22–29, 2017)

Application of the migratory nature of human mesenchymal stem cells to optimise microcarrier-based expansion processes

As the number of mesenchymal stem cell based therapies proceeding through clinical trials increases so does the demand for well characterized, scalable expansion technologies that can yield the estimated number of cells required. Microcarriers used in conjunction with stirred tank bioreactors provide a suitable platform for this large scale expansion. Research has proven that mesenchymal stem cells migrate between microcarriers during culture in agitated systems. A series of experiments have been conducted using Pall SoloHill microcarriers to determine whether this bead-to-bead transfer mechanism can be exploited to streamline various unit operations of the expansion process such as the initial bioreactor inoculation. Please click Additional Files below to see the full abstract

Can an electronic textbooks be part of K-12 education?: Challenges, technological solutions and open issues

An electronic textbook (e-Textbook) is a digitized (or electronic) form of textbook, which normally needs an endorsement by the national or state government when it is used in the K-12 education system. E-Textbooks have been envisioned to replace existing paper-based textbooks due to its educational advantages. Hence, it is of paramount importance for the relevant parties (i.e. national and state governments, or school districts) to draw a comprehensive roadmap of technologies necessary for the successful adoption of e-Textbooks nationwide. This paper provides a brief overview of e-Textbooks and subsequently an extensive discussion on challenges associated with e-Textbooks in the pursuit of replacing traditional textbooks with e-Textbooks. This paper further provides an extensive review on how the challenges have been approached using existing e-Textbook technologies, such as multi-touch technology, e-Paper, Web 2.0 and cloud computing. Literature review and interview have been conducted to identify the challenges of e Textbooks implementation in terms of e-Textbook usage levels and the reasons of its refusal. There were 180 students and 20 academic staff participated as a sample for interviews. Eight categories of key challenges were identified. Subsequently, assessment was performed on how the evolving e-Textbook technology has been applied to address the key challenges and problems. This article aims to provide a strong foundation for further investigations in e-Textbooks for successful adoption of e-Textbooks in school education

Chemical Recycling of Consumer-Grade Black Plastic into Electrically Conductive Carbon Nanotubes

The global plastics crisis has recently focused scientists’ attention on finding technical solutions for the ever-increasing oversupply of plastic waste. Black plastic is one of the greatest contributors to landfill waste, because it cannot be sorted using industrial practices based on optical reflection. However, it can be readily upcycled into carbon nanotubes (CNTs) using a novel liquid injection reactor (LIR) chemical vapor deposition (CVD) method. In this work, CNTs were formed using black and white polystyrene plastics to demonstrate that off-the-shelf materials can be used as feedstock for growth of CNTs. Scanning electron microscopy analysis suggests the CNTs from plastic sources improve diameter distribution homogeneity, with slightly increased diameters compared with control samples. Slight improvements in quality, as determined by Raman spectroscopy of the D and G peaks, suggest that plastics could lead to increased quality of CNTs. A small device was constructed as a demonstrator model to increase impact and public engagement

Simpson's Paradox and Lagging Progress in Completion Trends of Underrepresented Students in Computer Science

It is imperative for the Computer Science (CS) community to ensure active participation and success of students from diverse backgrounds. This work compares CS to other areas of study with respect to success of students from three underrepresented groups: Women, Black and Hispanic or Latino. Using a data-driven approach, we show that trends of success over the years for underrepresented groups in CS are lagging behind other disciplines. Completion of CS programs by Black students in particular shows an alarming regression in the years 2011 through 2019. This national level decline is most concentrated in the Southeast of the United States and seems to be driven mostly by a small number of institutes that produce a large number of graduates. We strongly believe that more data-driven studies in this area are necessary to make progress towards a more equitable and inclusive CS community. Without an understanding of underlying dynamics, policy makers and practitioners will be unable to make informed decisions about how and where to allocate resources to address the problem

A graph-based approach to construct target-focused libraries for virtual screening

© 2016 Naderi et al. Background: Due to exorbitant costs of high-throughput screening, many drug discovery projects commonly employ inexpensive virtual screening to support experimental efforts. However, the vast majority of compounds in widely used screening libraries, such as the ZINC database, will have a very low probability to exhibit the desired bioactivity for a given protein. Although combinatorial chemistry methods can be used to augment existing compound libraries with novel drug-like compounds, the broad chemical space is often too large to be explored. Consequently, the trend in library design has shifted to produce screening collections specifically tailored to modulate the function of a particular target or a protein family. Methods: Assuming that organic compounds are composed of sets of rigid fragments connected by flexible linkers, a molecule can be decomposed into its building blocks tracking their atomic connectivity. On this account, we developed eSynth, an exhaustive graph-based search algorithm to computationally synthesize new compounds by reconnecting these building blocks following their connectivity patterns. Results: We conducted a series of benchmarking calculations against the Directory of Useful Decoys, Enhanced database. First, in a self-benchmarking test, the correctness of the algorithm is validated with the objective to recover a molecule from its building blocks. Encouragingly, eSynth can efficiently rebuild more than 80 % of active molecules from their fragment components. Next, the capability to discover novel scaffolds is assessed in a cross-benchmarking test, where eSynth successfully reconstructed 40 % of the target molecules using fragments extracted from chemically distinct compounds. Despite an enormous chemical space to be explored, eSynth is computationally efficient; half of the molecules are rebuilt in less than a second, whereas 90 % take only about a minute to be generated. Conclusions: eSynth can successfully reconstruct chemically feasible molecules from molecular fragments. Furthermore, in a procedure mimicking the real application, where one expects to discover novel compounds based on a small set of already developed bioactives, eSynth is capable of generating diverse collections of molecules with the desired activity profiles. Thus, we are very optimistic that our effort will contribute to targeted drug discovery. eSynth is freely available to the academic community at www.brylinski.org/content/molecular-synthesis. Graphical abstract Assuming that organic compounds are composed of sets of rigid fragments connected by flexible linkers, a molecule can be decomposed into its building blocks tracking their atomic connectivity. Here, we developed eSynth, an automated method to synthesize new compounds by reconnecting these building blocks following the connectivity patterns via an exhaustive graph-based search algorithm. eSynth opens up a possibility to rapidly construct virtual screening libraries for targeted drug discovery

Scale‐down studies for the scale‐up of a recombinant Corynebacterium glutamicum fed‐batch fermentation; loss of homogeneity leads to lower levels of cadaverine production

BACKGROUNDThe loss of efficiency and performance of bioprocesses on scale‐up is well known, but not fully understood. This work addresses this problem, by studying the effect of some fermentation gradients (pH, glucose and oxygen) that occur at the larger scale in a bench‐scale two‐compartment reactor (Plug flow reactor (PFR) + Stirred tank reactor (STR)) using the cadaverine‐producing recombinant Corynebacterium glutamicum DM1945 Δact3 Ptuf‐ldcC_OPT. The new scale‐down strategy developed here studied the effect of increasing the magnitude of fermentation gradients by considering not only the average cell residence time in the PFR (τPFR), but also the mean frequency at which the bacterial cells entered the PFR (fm) section of the two‐compartment reactor.RESULTSOn implementing this strategy the cadaverine production decreased on average by 26 %, 49 % and 59 % when the τPFR was increased from 1 min to 2 min and then 5 min respectively compared to the control fermentation. The CO2 productivity was highest (3.1‐fold that of the control) at a τPFR of 5 min, but no losses were observed in biomass production. However, the population of viable but non‐culturable cells increased as the magnitude of fermentation gradients was increased.CONCLUSIONThis study demonstrated that C. glutamicum DM1945 Δact3 Ptuf‐ldcC_OPT physiological response was a function of the magnitude of fermentation gradients simulated. The adaptations of a bacterial cell within a heterogeneous environment ultimately result in losses in fermentation productivity as observed here.</div