bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic control of pathway expression with riboregulated switchable feedback promoters
Authors: Glasscock Cameron J. , Lazar John T. , Biggs Bradley W. , Arnold Jack H. , Kang Min Kyoung , Tullman-Ercek Danielle , Tyo Keith , Lucks Julius B. 
Published: January 2019

AbstractDynamic pathway regulation has emerged as a promising strategy in metabolic engineering for improved system productivity and yield, and continues to grow in sophistication. Bacterial stress-response promoters allow dynamic gene regulation using the host’s natural transcriptional networks, but lack the flexibility to control the expression timing and overall magnitude of pathway genes. Here, we report a strategy that uses RNA transcriptional regulators to introduce another layer of control over the output of natural stress-response promoters. This new class of gene expression cassette, called a riboregulated switchable feedback promoter (rSFP), can be modularly activated using a variety of mechanisms, from manual induction to quorum sensing. We develop and apply rSFPs to regulate a toxic cytochrome P450 enzyme in the context of a Taxol precursor biosynthesis pathway and show this leads to 2.4x fold higher titers than from the best reported strain. We envision that rSFPs will become a valuable tool for flexible and dynamic control of gene expression in metabolic engineering, protein and biologic production, and many other applications.
Mapping of transgenic alleles in plants using a Nanopore-based sequencing strategy
Authors: Li Shengjun , Jia Shangang , Hou Lili , Nguyen Hanh , Sato Shirley , Holding David , Cahoon Edgar , Zhang Chi , Clemente Tom , Yu Bin 
Published: January 2019

AbstractTransgenic technology was developed to introduce transgenes into various organisms to validate gene function and add genetic variation for the development of beneficial input or output trait over 40 years ago. However, the identification of the transgene insertion position in the genome, while doable, can be cumbersome in the organisms with complex genomes. Here, we report a Nanopore-based sequencing method to rapidly map transgenic alleles in the soybean genome. This strategy is high-throughput, convenient, reliable, and cost-efficient. The transgenic allele mapping protocol outlined herein can be easily translated to other higher eukaryotes with complex genomes.
Genetic analysis of the Arabidopsis TIR1/AFB auxin receptors reveals both overlapping and specialized functions
Authors: Prigge Michael J. , Platre Matthieu , Kadakia Nikita , Zhang Yi , Greenham Kathleen , Szutu Whitnie , Pandey Bipin K. , Bhosale Rahul , Bennett Malcolm J. , Busch Wolfgang , Estelle Mark 
Published: January 2019

ABSTRACTThe TIR1/AFB auxin co-receptors mediate diverse responses to the plant hormone auxin. The Arabidopsis genome encodes six TIR1/AFB proteins representing three of the four clades that were established prior to angiosperm radiation. To determine the role of these proteins in plant development we performed an extensive genetic analysis involving the generation and characterization of all possible multiply mutant lines. We find that loss of all six TIR1/AFB proteins results in defects in embryogenesis as early as the 8-cell stage, and possibly earlier. Mutant embryos progress but exhibit frequent cell division errors followed by proliferation of the suspensor, and eventually seed abortion. Despite this dramatic phenotype, a single wild-type allele ofTIR1orAFB2is sufficient to support growth throughout plant development. Further, gametophytic expression of theTIR1/AFBgenes is not essential for development of the male or female gametophyte. Our analysis reveals extensive functional overlap between even the most distantly relatedTIR1/AFBgenes except forAFB1. Surprisingly, the AFB1 protein has a specialized function in rapid auxin-dependent inhibition of root growth and early phase of root gravitropism. This activity may be related to a difference in subcellular localization compared to the other members of the family.
Proteome and Secretome Dynamics of Stem Cell-Derived Retinal Pigmented Epithelium in Response to Acute and Chronic ROS
Authors: Meyer Jesse G. , Garcia Thelma , Schilling Birgit , Gibson Bradford W. , Lamba Deepak A. 
Published: January 2019

AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in developed countries, and is characterized by slow retinal degeneration linked to chronic oxidative stress in the retinal pigmented epithelium (RPE). The exact molecular mechanisms that lead to RPE death and dysfunction in response to chronic reactive oxygen species (ROS) are still unclear. In this work, human stem cell-derived RPE samples were treated with a low dose of paraquat (PQ) for 1 week or 3 weeks to induce chronic reactive oxygen species (ROS) stress. Cells were then harvested and both the intracellular and secreted RPE proteomes were quantified by mass spectrometry. Inside the RPE, chronic ROS caused concerted increase of glycolytic proteins but decreased mitochondrial proteins, as well as decreased extracellular matrix proteins and membrane proteins required for endocytosis. From the secreted proteins, we found that stressed RPE secrete over 1,000 detectable proteins, and the composition of the proteins secreted from RPE changes due to chronic ROS. Notably, secreted APOE is decreased 4-fold due to 3 weeks of chronic ROS stress, and urotensin-II, the strongest known vasoconstrictor, doubles. Further, secreted TGF-beta is increased, and its cognate signaler BMP1 decreased in the secretome. Together, these alterations of the RPE proteome and protein secretome paint a detailed molecular picture of the retinal stress response in space and time.
Redefining the medicago sativa alphapartitivirus genome sequences
Authors: Bejerman Nicolás , Humberto Debat , Trucco Verónica , Breuil Soledad de , Lenardon Sergio , Giolitti Fabián 
Published: January 2019

AbstractIn alfalfa samples analyzed by hightroughput sequencing, four de novo assembled contigs encoding gene products showing identities to alphapartitiviruses proteins were found based on BlastX analysis. The predicted amino acid (aa) sequences of two contigs presented 99-100% identity to the RNA-dependent RNA polymerase (RdRp) and the capsid protein (CP) of the recently reported medicago sativa alphapartitivirus 1 (MsAPV1). In addition, the remaining two contigs shared only 56% (CP) and 70% (RdRp) pairwise aa identity with the proteins of MsAPV1, suggesting that these samples presented also a novel Alphapartitivirus species. Further analyses based on complete genome segments termini and the presence/absence of alphapartitivirus RNA in several samples and public alfalfa RNA datasets corroborated the identification of two different alphapartitivirus members. Our results also likely indicate that the reported MsAPV1 genome was previously reconstructed with genome segments of two different alphapartitiviruses. Overall, we not only revisited the MsAPV1 genome sequence but also report a new tentative alphapartitivirus species, which we propose the name medicago sativa alphapartitivirus 2. In addition, the RT-PCR detection of both MsAPV1 and MsAPV2 in several alfalfa cultivars suggests a broad distribution of both viruses.
Targeting extracellular glycans: Tuning multimeric boronic acids for pathogen-selective killing of Mycobacterium tuberculosis
Authors: Guy Collette S. , Gibson Matthew I. , Fullam Elizabeth 
Published: January 2019

AbstractInnovative chemotherapeutic agents that are active against Mycobacterium tuberculosis (Mtb) are urgently required to control the tuberculosis (TB) epidemic. The Mtb cell envelope has distinct (lipo)polysaccharides and glycolipids that play a critical role in Mtb survival and pathogenesis and disruption of pathways involved in the assembly of the Mtb cell envelope are the primary target of anti-tubercular agents. Here we introduce a previously unexplored approach whereby chemical agents directly target the extracellular glycans within the unique Mtb cell envelope, rather than the intracellular biosynthetic machinery. We designed and synthesised multimeric boronic acids that are selectivity lethal to Mtb and function by targeting these structurally unique and essential Mtb cell envelope glycans. By tuning the number of, and distance between, boronic acid units high selectivity to Mtb, low cytotoxicity against mammalian cells and no observable resistance was achieved. This non-conventional approach may prevent the development of drug-resistance and will act as a platform for the design of improved, pathogen-specific, next generation antibiotics.
Effects of flavorless electronic cigarette aerosol on the survival and growth of common oral commensal streptococci
Authors: Cuadra Giancarlo A. , Smith Maxwell , Nelson John M. , Loh Emma , Palazzolo Dominic 
Published: January 2019

AbstractThe use of electronic cigarettes (ECIG) has become very common. Consequently, critical analysis of the biological effects of ECIG aerosol deserves attention. Since the mouth is the first anatomical cavity exposed to aerosol, the oral bacteria within are also exposed. We hypothesize that while cigarette smoke has a detrimental effect on the survival and growth of oral commensal streptococci, flavorless ECIG aerosol does not. Survival and growth of several strains of commensal streptococci were measured after exposure to flavorless ECIG aerosol ± nicotine and smoke. Peristaltic pumps were used to transport flavorless aerosol ± nicotine or cigarette smoke into chambers containing recently seeded colony forming units of four strains of oral commensal streptococci on agar plates. Bacterial survival and growth, based on colony counts and sizes, were determined 24 hours post-exposure. Lastly, aerosol or smoke were delivered into chambers containing the four strains of streptococci pre-adhered to plastic coverslips. Bacterial survival and growth, as indicated by biofilm formation, were determined 24 hours post-exposure via scanning electron microscopy. The results suggest that flavorless aerosol ± nicotine has a modest effect on bacterial growth both as colonies on agar and as biofilms. In contrast, smoke dramatically decrease bacterial survival and growth in all parameters measured. Therefore, unlike cigarette smoke, flavorless ECIG aerosol has only a small effect on the survival and growth of oral commensal streptococci.
Predicting diabetes second-line therapy initiation in the Australian population via timespan-guided neural attention network
Authors: Fiorini Samuele , Hajati Farshid , Barla Annalisa , Girosi Federico 
Published: January 2019

AbstractIntroductionThe first line of treatment for people with diabetes is metformin. However, over the course of the disease metformin may fail to achieve appropriate glycemic control, and a second-line therapy becomes necessary. In this paper we introduce Tangle, a timespan-guided neural attention model that can accurately and timely predict the upcoming need for a second-line diabetes therapy from administrative data in the Australian adult population. The method could be used to design automatic therapy review recommendations for patients and their providers without the need to collect clinical measures.DataWe analyzed seven years of deidentified records (2008-2014) of the 10% publicly available linked sample of Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) electronic databases of Australia.MethodsBy design, Tangle can inherit the representational power of pre-trained word embedding, such as GloVe, to encode sequences of claims with the related MBS codes. The proposed attention mechanism can also natively exploit the information hidden in the timespan between two successive claims (measured in number of days). We compared the proposed method against state-of-the-art sequence classification methods.ResultsTangle outperforms state-of-the-art recurrent neural networks, including attention-based models. In particular, when the proposed timespan-guided attention strategy is coupled with pre-trained embedding methods, the model performance reaches an Area Under the ROC Curve of 90%, an improvement of almost 10 percentage points over an attentionless recurrent architecture.ImplementationTangle is implemented in Python using Keras and it is hosted on GitHub at https://github.com/samuelefiorini/tangle.
Intra-species diversity ensures the maintenance of functional microbial communities under changing environmental conditions
Authors: García-García Natalia , Tamames Javier , Linz Alexandra M. , Pedrós-Alió Carlos , Puente-Sánchez Fernando 
Published: January 2019

AbstractIntra-species diversity comprises different ecotypes within the same species. These are assumed to provide stability in time and space to those species. However, the role that microdiversity plays in the stability of whole microbial communities remains underexplored. Understanding the drivers of microbial community stability is necessary to predict community response to future disturbances. Here, we analyzed 16S rRNA gene amplicons from eight different temperate bog lakes at OTU-97% and amplicon sequence variant (ASV) levels, and we found ecotypes within the same species with different distribution patterns in space and time. We observed that these ecotypes are adapted to different values of environmental factors such as water temperature and oxygen concentration. Our results showed that the existence of several ASVs within a species favored its persistence across changing environmental conditions. We propose that microdiversity aids the stability of microbial communities in the face of fluctuations in environmental factors.
A survey of reverse mergers in the Chinese stock market
Authors: Xin Qingquan , Li Ruitao , Wong Sonia 
Published: January 2019

Purpose
The purpose of this paper is to provide an introduction to the reverse mergers (RMs) conducted in the Chinese stock market by summarizing the regulatory system, surveying the literature on RMs and analyzing the major characteristics of 161 RM cases.

Design/methodology/approach
This paper introduces the characteristics and evolution of the regulatory framework governing RM activity in China. Then the paper reviews relevant academic studies on the RMs in China and other countries. Finally, the paper identifies and discusses the major characteristics of 161 RM cases in the Chinese stock market from 2006 to 2016.

Findings
Private companies that go public via RMs in China not only have superior asset quality but also demonstrate good accounting and stock price performance after listing, and these results are unlike those of studies on the quality of RMs in other countries.

Research limitations/implications
This paper is based on a survey of 161 RM cases in China’s stock market, with the major characteristics of the RMs being identified and analyzed. The limitations of previous studies and suggestions for further research are discussed.

Originality/value
This paper suggests that the relative superior performance of RMs in the Chinese stock market is caused by the interplay of market forces and regulatory oversight. The Chinese regulator’s pragmatic and flexible approach plays an important role in formulating regulatory policies that respond to the changing macroeconomic environment and financial markets.
Explaining user experience in mobile gaming applications: an fsQCA approach
Authors: Pappas Ilias O. , Mikalef Patrick , Giannakos Michail N. , Kourouthanassis Panos E. 
Published: January 2019

Purpose
In the complex ecosystem of mobile applications multiple factors have been used to explain users’ behavior, without though focusing on how different combinations of variables may affect user behavior. The purpose of this paper is to show how price value, game content quality, positive and negative emotions, gender and gameplay time interact with each other to predict high intention to download mobile games.

Design/methodology/approach
Building on complexity theory, the authors present a conceptual model followed by research propositions. The propositions are empirically validated through configurational analysis, employing fuzzy-set qualitative comparative analysis (fsQCA) on 531 active users of mobile games.

Findings
Findings identify ten solutions that explain high intention to download mobile games. Alternative paths are identified depending on the gender and the time users spend playing mobiles games. The authors highlight the role of price value and game content quality, as well as that of positive emotions, which are always core factors when present.

Originality/value
To identify complex interactions among the variables of interest, fsQCA is employed, differentiating from traditional studies using variance-based methods, leading to multiple solutions explaining the same outcome. None of the variables explains the intention to download on its own, but only when they combine with each other. The authors extend existing knowledge on how price value, game content quality, emotions, gender and gameplay time combine to lead to high intention to download mobile games; and present a methodology for how to bridge complexity theory with fsQCA, improving our understanding of intention to adopt mobile applications.
Inflation volatility, monetary policy signaling and clarity of the central bank communication
Authors: Nicolay Rodolfo , de Oliveira Ana Jordânia 
Published: January 2019

PurposeStudies about the determinants of the clarity of central bank communication are still scarce. To the authors’ knowledge, there are no studies regarding emerging economies. The purpose of this paper is to contribute to the literature in the following aspects: to analyze the determinants of the clarity of the central bank communication in an inflation targeting emerging economy; observe the influence of inflation volatility over the clarity; and observe the effect of the monetary policy signaling over the clarity.Design/methodology/approachThe work uses readability indexes to measure the clarity of central bank communication. The empirical analysis uses ordinary least squares and the Generalized Method of Moments with one- and two-step estimations.FindingsThe findings suggest the inflation volatility reduces the clarity of central bank communication. Moreover, the monetary policy signaling also affects the clarity, but the effect depends on the direction of the signal.Practical implicationsThis paper observes the determinants of the clarity considering an emerging economy environment. The clarity of central bank communications is an important tool to access transparency. Hence, the analysis of what determines the clarity of central bank communication is a debate about the level of transparency accessed by the central bank.Originality/valueThere are no studies about the determinants of the clarity of central bank communication in emerging economies. Moreover, the novelty are the effects of inflation volatility and monetary policy signaling over the clarity.
The role of the expectations channel in the quantitative easing in the Eurozone
Authors: Apergis Nicholas 
Published: January 2019

PurposeThe purpose of this paper is to explore the direct and exclusive effects of this rather unconventional monetary policy on financial markets, economic activity and labor markets across the Eurozone.Design/methodology/approachUsing a range of variables, the analysis employed the Markov-switching dynamic regression methodological approach.FindingsThe findings provided evidence in favor of the reduction of short- and log-term credit spreads, increased stock prices, improved market expectations, recovered labor market conditions and economic productivity, while the primary transmission channel of the quantitative easing policy is the expectations channel.Originality/valueThe novelties of this paper are twofold: it makes use of a wide data set to investigate the effect of economic and financial variables on productivity, labor markets, bond markets and equity markets in the Eurozone; and the analysis focuses on the direct effects of monetary base increases on the Eurozone economy, as well as on Eurozone financial markets.
The relationship between organizational commitment, knowledge transfer and knowledge management maturity
Authors: Marques Juliano Martins Ramalho , La Falce Jefferson Lopes , Marques Fernanda Machado Fonseca Ramalho , De Muylder Cristiana Fernandes , Silva Jersone Tasso Moreira 
Published: January 2019

PurposeThis paper aims to analyse the relationship between the organizational commitment, the knowledge transfer and the knowledge management maturity at a Brazilian public university. As indicated in the literature, the organizational commitment and the influence on knowledge management in the public sector, especially in developing countries, configures an important gap to be filled (Razzaq et al., 2018).Design/methodology/approachThe research has a descriptive and quantitative nature, and to run the analysis, an exploratory factorial analysis was conducted and after that a structural equations modelling was carried out.FindingsThe results indicated a significant relationship between the organizational commitment to the knowledge transfer and, consequently, to the knowledge management maturity.Originality/valueIn the first place, the model including all dimensions of commitment: affective, calculative and normative with knowledge transfer and knowledge maturity was not tested before. Second, data on the public sector in developing countries are still rare and studies in this field encouraged (Razzaq et al., 2018). In this case, the present study contributes in this field, specifically in the education sector. Finally, understanding the individual commitment profile helps to understand the extent to which that person contributes both to the knowledge transfer, and therefore, in the same analogy, to the knowledge management maturity level.
Heuristic algorithm for optimal redundancy allocation in complex systems
Authors: Aggarwal Sudhanshu 
Published: January 2019

PurposeThe purpose of this paper is to present an efficient heuristic algorithm based on the 3-neighborhood approach. In this paper, search is made from sides of both feasible and infeasible regions to find near-optimal solutions.Design/methodology/approachThe algorithm performs a series of selection and exchange operations in 3-neighborhood to see whether this exchange yields still an improved feasible solution or converges to a near-optimal solution in which case the algorithm stops.FindingsThe proposed algorithm has been tested on complex system structures which have been widely used. The results show that this 3-neighborhood approach not only can obtain various known solutions but also is computationally efficient for various complex systems.Research limitations/implicationsIn general, the proposed heuristic is applicable to any coherent system with no restrictions on constraint functions; however, to enforce convergence, inferior solutions might be included only when they are not being too far from the optimum.Practical implicationsIt is observed that the proposed heuristic is reasonably proficient in terms of various measures of performance and computational time.Social implicationsReliability optimization is very important in real life systems such as computer and communication systems, telecommunications, automobile, nuclear, defense systems, etc. It is an important issue prior to real life systems design.Originality/valueThe utilization of 3-neighborhood strategy seems to be encouraging as it efficiently enforces the convergence to a near-optimal solution; indeed, it attains quality solutions in less computational time in comparison to other existing heuristic algorithms.