bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling noisy expression through auto regulation of burst frequency and protein stability
Authors: Bokes Pavol , Singh Abhyudai 
Published: January 2019

AbstractProtein levels can be controlled by regulating protein synthesis or half life. The aim of this paper is to investigate how introducing feedback in burst frequency or protein decay rate affects the stochastic distribution of protein level. Using a tractable hybrid mathematical framework, we show that the two feedback pathways lead to the same mean and noise predictions in the small-noise regime. Away from the small-noise regime, feedback in decay rate outperforms feedback in burst frequency in terms of noise control. The difference is particularly conspicuous in the strong-feedback regime. We also formulate a fine-grained discrete model which reduces to the hybrid model in the large system-size limit. We show how to approximate the discrete protein copy-number distribution and its Fano factor using hybrid theory. We also demonstrate that the hybrid model reduces to an ordinary differential equation in the limit of small noise. Our study thus contains a comparative evaluation of feedback in burst frequency and decay rate, and provides additional results on model reduction and approximation.
Somatic mutation landscape reveals differential variability of cell-of-origin for primary liver cancer
Authors: Ha Kyungsik , Fujita Masashi , Karlić Rosa , Yang Sungmin , Hoshida Yujin , Polak Paz , Nakagawa Hidewaki , Kim Hong-Gee , Lee Hwajin 
Published: January 2019

AbstractBackgroundPrimary liver tissue cancers display consistent increase in global disease burden and mortality. Identification of cell-of-origins for primary liver cancers would be a necessity to expand options for designing relevant therapeutics and preventive medicine for these cancer types. Previous reports on cell-of-origin for primary liver cancers was mainly from animal studies, and integrative research utilizing human specimen data was poorly established.MethodsWe analyzed a whole-genome sequencing data set for a total of 363 tumor and progenitor tissues along with 423 normal tissue epigenomic marks to predict the cell-of-origin for primary liver cancer subtypes.ResultsDespite the mixed histological features, the predicted cell-of-origin for mixed hepatocellular carcinoma / intrahepatic cholangiocarcinoma were uniformly predicted as a hepatocytic origin. Individual sample-level prediction revealed differential level of cell-of-origin heterogeneity depending on the primary liver cancer types, with more heterogeneity observed in intrahepatic cholangiocarcinomas. Additional analyses on the whole genome sequencing data of hepatic progenitor cells suggest these progenitor cells might not a direct cell-of-origin for liver cancers.ConclusionsThese results provide novel insights on the heterogeneous nature and potential contributors of cell-of-origin predictions for primary liver cancers.
Functional Near-Infrared Spectroscopy (fNIRS) informed neurofeedback: regional-specific modulation of lateral orbitofrontal activation and cognitive flexibility
Authors: Li Keshuang , Jiang Yihan , Gong Yilong , Zhao Weihua , Zhao Zhiying , Liu Xiaolong , Kendrick Keith M. , Zhu Chaozhe , Becker Benjamin 
Published: January 2019

AbstractCognitive flexibility and reward processing critically rely on the orbitofrontal cortex. Dysregulations in these domains and orbitofrontal activation have been reported in major psychiatric disorders. Haemodynamic brain imaging informed neurofeedback allows regional-specific control over brain activation and thus may represent an innovative intervention to regulate orbitofrontal dysfunctions. Against this background the present proof-of-concept study evaluated the feasibility and behavioral relevance of functional Near-Infrared Spectroscopy (fNIRS) assisted neurofeedback training of the lateral orbitofrontal cortex (lOFC). In a randomized sham-controlled between-subject design 60 healthy participants underwent four subsequent runs of training to enhance lOFC activation. Training-induced changes in the lOFC, attentional set shifting performance and reward experience served as primary outcomes. Feedback from the target channel significantly increased regional-specific lOFC activation over the four training runs in comparison with sham feedback. The experimental group demonstrated a trend for faster responses during set shifting relative to the sham group. Within the experimental group stronger training-induced lOFC increases were associated with higher reward experience. The present results demonstrate that fNIRS-informed neurofeedback allows regional-specific regulation of lOFC activation and may have the potential to modulate associated behavioral domains. As such fNIRS-informed neurofeedback may represent a promising strategy to regulate OFC dysfunctions in psychiatric disorders.
BMP4 patterns Smad activity and generates stereotyped cell fate organisation in spinal organoids
Authors: Duval Nathalie , Vaslin Célia , Barata Tiago , Nédélec Stéphane , Ribes Vanessa 
Published: January 2019

AbstractBone Morphogenetic Proteins (BMP) are secreted regulators of cell fate in several developing tissues. In the embryonic spinal cord, they control the emergence of the neural crest, roof plate and distinct subsets of dorsal interneurons. Although a gradient of BMP activity has been proposed to determine cell type identity invivo, whether this is sufficient for pattern formation invitrois unclear. Here, we demonstrate that exposure to BMP4 initiates distinct spatial dynamics of BMP signalling within the self-emerging epithelia of both mouse and human pluripotent stem cells derived spinal organoids. The pattern of BMP signalling results in the stereotyped spatial arrangement of dorsal neural tube cell types and concentration, timing and duration of BMP4 exposure modulate these patterns. Moreover, differences in the duration of competence time-windows between mouse and human account for the species specific tempo of neural differentiation. Together the study describes efficient methods to generate patterned subsets of dorsal interneurons in spinal organoids and supports the conclusion that graded BMP activity orchestrates the spatial organization of the dorsal neural tube cellular diversity in mouse and human.
Modelling the transport of fluid through heterogeneous, whole tumours in silico
Authors: Sweeney Paul W. , d’Esposito Angela , Walker-Samuel Simon , Shipley Rebecca J. 
Published: January 2019

AbstractIt is critically important to understand and predict fluid transport within both physiological and pathological tissues in order to develop effective treatment strategies. Recent advances in high-resolution optical imaging allow the acquisition of whole tumour vascular networks which can be used to parameterise computational models to predict the fluid dynamics at all length scales across the tissue. This enables hypothesis testing around the role of the tumour microenvironment in determining transport characteristics, which would otherwise be unavailable using traditional experiments.In this study, we present a novel computational framework for the efficient simulation of vascular blood flow and interstitial fluid transport based on complete three-dimensional, whole tumour vasculature obtained using high-resolution optical imaging. This framework comprises a Poiseuille flow model which simulates vascular blood flow within the vessel network, coupled via point sources of flux to a porous medium model describing interstitial fluid transport. We develop a computational algorithm for prescription of network boundary conditions and validation of tissue-scale fluid transport against measured in vivo perfusion data acquired using biomedical imaging tools. We present simulations of the model on orthoptic murine glioma and human colorectal carcinoma xenograft data (GL261 and LS147T, respectively), and perform sensitivity analysis on key unknown parameters relating to the tissue microenvironment, to understand their impact in predicting vascular and interstitial flow. Finally, we simulate radially varying vascular normalisation in a LS147T tumour and hypothesise that uniform normalisation is required to lower tumour interstitial fluid pressure.Our computational framework permits predictions of whole tumour fluid dynamics which incorporate the inherent architectural heterogeneities appearing at the micron-scale, and outputs three-dimensional spatial maps detailing these flow properties from micro to macro length scales. This provides vital information on the tumour microenvironment which could enable the design and delivery of future anti-cancer therapies.Author summaryThe structure of tumours varies widely, with dense and chaotically-formed networks of blood vessels that differ between each individual tumour and even between different regions of the same tumour. This atypical environment can inhibit the delivery of anti-cancer therapies. Computational tools are urgently required which incorporate micron-scale tumour biomechanics to predict tissue-scale fluid dynamics, and consequently the efficacy of cancer therapies.We have developed a computational framework which integrates the complex tumour vascular architecture to predict fluid transport across all lengths scales in whole tumours. This enables computationally efficient hypothesis testing of cancer therapies which manipulate the tumour microenvironment in order to improve drug delivery to tumours.
Dynamics of bacterial cell proliferation inhibited by specific proteins for effective horizontal transmission of the integrative and conjugative element ICEclc
Authors: Takano Sotaro , Koto Akiko , Miyazaki Ryo 
Published: January 2019

AbstractThe integrative and conjugative element ICEclc, a prevalent mobile element in proteobacteria, is one of the experimental models for horizontal gene transfer. ICEclc is usually retained in a bacterial chromosome, but can be excised and transferred from the donor to other bacterial lineages. The horizontal transmission is accomplished by developing specialized transfer competent (tc) cells in the donor population. The tc cells entirely dedicate to the ICE transmission by sacrificing their proliferation, which results in an increase in the transfer frequency. The cell growth impairment is mediated by two specific genes, parA and shi, on ICEclc, but its mechanistic details and cellular dynamics are still unknown. We here developed fluorescence reporter strains to monitor intracellular behavior of ParA and Shi proteins as well as host cellular proliferation at the single-cell level. Superresolution imaging revealed that ParA colocalized with the host nucleoid while Shi diffused in cytoplasm during the growth impairment. Mutations in the Walker A motif of ParA diminished the inhibitory effect. Combining quantitative time-lapse microscopy and numerical simulations using mathematical models, we found that ParA and Shi initially blocked cell division and then, as time elapsed, inhibited cellular elongation. The parA-shi locus is highly conserved in other ICEs, and the ParA-Shi-mediated growth inhibition was still observed in different proteobacterial species, suggesting that the ICEs have evolved the system to efficiently distribute themselves in the niche. The results of our study provide mechanistic insight into the novel and unique system on ICEs and help to understand such epistatic interaction between ICE genes and host physiology that entails efficient horizontal gene transfer.Author summaryHorizontal gene transfer is a major diving force for bacterial evolution, which is frequently mediated by mobile DNA vectors, such as plasmids and bacteriophages. Integrative and conjugative elements (ICEs) are a relatively new class of mobile vectors, which normally integrate in a host chromosome but under certain conditions can be excised and transferred from the host to a new recipient cell via conjugation. Recent genomic studies estimated that ICEs are more abundant than plasmids among bacteria. Why so prevalent? One of the characteristics of ICEclc, an ICE model in proteobacteria, is that it develops specialized cells which entirely dedicate to the ICE horizontal transmission by repressing their proliferation. Here, we qualitatively and quantitatively describe two proteins, which are expressed from ICEclc when it transfers, and how they actually inhibit the host cell growth. Our results suggest that the system has evolved for the efficient horizontal transmission and is widely conserved in the ICE family.
Molecular basis of P[6] and P[8] major human rotavirus VP8* domain interactions with histo-blood group antigens
Authors: Xu Shenyuan , Liu Yang , Tan Ming , Zhong Weiming , Zhao Dandan , Jiang Xi , Kennedy Michael A. 
Published: January 2019

AbstractInitial cell attachment of rotavirus (RV) to specific cell surface glycans, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as ligands or receptors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b and H type 1 antigens, while P[6], which is one of the other genotypes in P[II], only recognizes the H type 1 antigen. The molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leband type 1 HBGAs and for P[6] recognition of H type 1 HBGAs. Unlike P[6] VP8* that recognizes H type 1 HGBAs in a binding surface composed of an α-helix and a β-sheet, referred as “βα binding domain”, the P[8] VP8* binds the type 1 HBGAs requiring the presence of the Lewis epitope in a previously undescribed pocket formed by two β-sheets, referred as “ββ binding domain”. The observation that P[6] and P[8] VP8* domains recognize different glycan structures at distinct binding sites supports the hypothesis that RV evolution is driven, at least in part, by selective pressure driven adaptation to HBGA structural diversity of their natural hosts living in the world. Recognition of the role that HBGAs play in driving RV evolution is essential to understanding RV diversity, host ranges, disease burden and zoonosis and to developing strategies to improve vaccines against RV infections.Author summaryRotaviruses (RV)s are the main cause of severe diarrhea in humans and animals. Significant advances in understanding RV diversity, evolution and epidemiology have been made after discovering that RVs recognize histo-blood group antigens (HBGAs) as host cell receptors. While different RV strains are known to have distinct binding preferences for HBGA receptors, the molecular basis in controlling strain-specific host ranges remains unclear. In this study, we used solution nuclear magnetic resonance to determine the molecular level details for interactions of the human P[8] and P[6] RV VP8* domains with their HBGA receptors. The distinct binding patterns observed between these major human RVs and their respective receptor ligands provides insight into the evolutionary relationships between different P[II] genotypes that ultimately determine host ranges, disease burden, zoonosis and epidemiology, which may impact future strategies for vaccine development against RVs.
Business process architecture design methodologies – a literature review
Authors: Gonzalez-Lopez Fernanda , Bustos Guillermo 
Published: January 2019

PurposeThe purpose of this paper is to describe the current state of the research field of business process architecture (BPA) and its design methodologies.Design/methodology/approachA systematic literature review (SLR) was conducted using meta- and content-based perspectives.FindingsFrom over 6,000 candidate studies, 89 were selected. A fifth of these primary works corresponded to BPA design methodologies. Though the BPA research field remains in an early stage of development, it bears promising growth potential. Regarding BPA design methodologies, the following aspects susceptible for further research were detected: identification and modeling of business process relationships; specification of inputs; standardization of models, notations and tool support; consideration of managerial concerns; integration of knowledge from other areas; and validation of methodological and product quality aspects.Research limitations/implicationsThe main limitation of the work lies in not being fully reproducible due to the fixed number of data sources and their digital nature, together with subjective decisions in work selection, data extraction and data analysis.Originality/valueTo the best of the authors’ knowledge no study has yet analyzed the BPA research field by means of an SLR. This study will benefit practitioners and research groups working on this topic by allowing them to get a rigorous overview of the BPA research field with an emphasis on available BPA design methodologies, and become aware of research gaps within the BPA field to position further research.
Soft skills for sustainable employment of business graduates of Bangladesh
Authors: Nusrat Mansura , Sultana Nafia 
Published: January 2019

Purpose
The purpose of this paper is to examine whether soft skill requirements found in employer job postings (advertisements) within different roles of business are similar to the soft skills practically needed in the workplace and the perception of faculties at schools of business in Bangladesh.

Design/methodology/approach
A two-phased study was administered. Phase 1 involved reviewing the latest relevant literature and hundreds of job advertisements; and in phase 2, questionnaires were administered to elicit responses from executives and faculty members from different universities in Bangladesh. Judgment sampling and the snowball technique were used to develop the sample of 84 respondents with a response rate of 56 percent. In total, 15 soft skills were used to develop the instrument. Descriptive statistics and a Kruskal–Wallis test were performed to analyze the collected data, where factors that retained α at or below 0.05, a family-wise Bonferroni adjustment (Mann–Whitney U test) was applied.

Findings
All the mentioned soft skills are found to be desirable by the recruiters and faculties also agreed with them. However, there exist disparities on the perceived importance of four soft skills among faculties and recruiters, and a gap was found between the business curriculum and industry expectations from fresh-out business graduates.

Originality/value
This study could be a basis for future studies and would help business education institutions guide their students to master the skills, and to develop and prepare them for real life battle in the job market. Moreover, the study indicates the gap between executives’ expectations from the graduates and the institutional teaching provided by higher education institutions (for business majors), which would help practitioners reform their business curriculum to better ensure employability for their business graduates. Moreover, the study opens an avenue for further research in this field for implementing training programs for attaining the most desired soft skills among higher education institutions.
Analysis of mixed convection in water boundary layer flows over a moving vertical plate with variable viscosity and Prandtl number
Authors: Singh Abhishek Kumar , Singh A.K. , Roy S. 
Published: January 2019

Purpose
The purpose of the present study is to analyze the mixed convection water boundary layer flows over moving vertical plate with variable viscosity and Prandtl number. The non-linear partial differential equation governing the flow and thermal fields are presented in non-dimensional form by using appropriate transformation. The quasi-linearization technique in combination with implicit finite difference scheme has been adopted to solve the nonlinear-coupled partial differential equation. The numerical results are displayed graphically to illustrate the influence of various non-dimensional physical parameters on velocity and temperature. Further, the numerical results for local skin-friction coefficient and local Nusselt number are also reported. The present findings are compared with previously reported results, and these comparisons are found to be in excellent agreement.

Design/methodology/approach
The nonlinear partial differential equations governing the flow and thermal fields have been solved numerically using the implicit finite difference scheme in combination with the quasi-linearization technique. The numerical results are presented in terms of skin friction and heat transfer rate which are useful in determining the surface heat requirements for stabilizing the laminar boundary layer flow over a moving plate in water.

Findings
The effect of the ratio of free-stream velocity to the composite reference velocity is significant on the velocity profile. Near the wall region, as ratio of free stream velocity to composite reference velocity increases form 0.1 to 0.5, the velocity overshoot gets enhanced from 3 per cent to 41 per cent. The influence of buoyancy parameter and ration of free stream velocity to composite reference velocity on temperature profile is comparatively less than on velocity profiles. The increase in the skin friction coefficient is dependent on the increase in the value of ratio of free stream velocity to composite reference velocity if the buoyancy parameter λ is fixed and vice versa and increases in ΔT results in a decrease in N and Pr.

Originality/value
The present investigation is to deal with the solution of steady laminar water boundary layer flows over a moving plate with temperature-dependent viscosity and Prandtl number applicable for water using practical data. The fluid considered here is water, as it is one of the most common working fluids found in engineering applications.
Integrating lesson study in Myanmar teacher training
Authors: Shepherd Alison Victoria 
Published: January 2019

Purpose
This paper documents a case study implementing Lesson Study (LS) study into a two-year teacher training project in an education university training secondary school teachers in Lower Myanmar. The purpose of this paper is to stimulate interest and discussion about whether Lesson Study is a useful tool in continuing professional development (CPD), particularly within the unique context of developing country educational development.

Design/methodology/approach
Two LS cycles were evaluated by participants using a quantitative-qualitative questionnaire and the case study analysed by the author.

Findings
LS was a useful tool to encourage structured collaboration between university-level teacher educators, however, continued supported practice is needed to expand the benefits and ensure sustainability.

Research limitations/implications
A limitation of the case study is that the respondents were small in number compared to the number of participants. Furthermore, the questionnaire was not in respondents’ native language which will have affected how well they could communicate. Finally, it was difficult to separate the impact of other project activities from the perceived effects of LS.

Practical implications
This paper has practical implications not only for educators within Myanmar as the country continues its journey of education reform, but also for others implementing LS as a form of CPD, particularly in contexts where it is being introduced for the first time.

Originality/value
Until recently, little was known about Myanmar’s education system internationally. The paper documents the country’s first collaboration with outsiders since the start of the dictatorship to improve educational standards and the effects of introducing LS into this context.