bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graph–based integration of histone modifications profiles: haematopoietic cell differentiation as a case study
Authors: Baccini Federica , Bianchini Monica , Geraci Filippo 
Published: October 2020

AbstractIn this paper, we show that quantifying histone modifications by counting the number of high– resolution peaks in each gene allows to build profiles of these epigenetic marks, associating them to a phenotype. The significance of this approach is verified by applying graph–cut techniques for assessing the differentiation between myeloid and lymphoid cells in haematopoiesis, i.e. the process through which all the different types of blood cells originate starting from a unique cell type. The experiments are conducted on a population of samples from 24 cell types involved in haematopoiesis. Six profiles are constructed for each cell type, based on a different histone modification signal. Following the experimentally verified idea that the peak number distribution per gene behaves similarly to gene expression, the profile computation employs standard differential analysis tools to find genes whose epigenetic modifications are related to a given phenotype. Next, six similarity networks of cell types are constructed, based on each histone modification, and then combined into a unique one through similarity network fusion. Finally, the similarity networks are transformed into dissimilarity graphs, to which two different cuts are applied and compared to evaluate the classic differentiation between myeloid and lymphoid cells. The results show that all histone modifications contribute almost equally to the myeloid/lymphoid differentiation, and this is also confirmed by the analysis of the fused network. However, they also suggest that histone modifications may not be the only mechanism for regulating the differentiation of hematopoietic cells.
Lymphatic PD-L1 expression restricts tumor-specific CD8+ T cell responses
Authors: Cousin Nikola , Cap Stefan , Dihr Manuel , Tacconi Carlotta , Detmar Michael , Dieterich Lothar C. 
Published: October 2020

ABSTRACTLymph node (LN)-resident lymphatic endothelial cells (LECs) mediate peripheral tolerance by self-antigen presentation on MHC-I and constitutive expression of T cell inhibitory molecules, including PD-L1. Tumor-associated LECs also upregulate PD-L1 but the specific role of lymphatic PD-L1 in tumor immunity is not well understood. We generated a mouse model lacking lymphatic PD-L1 expression and challenged these mice with two orthotopic tumor models, B16F10 melanoma and MC38 colorectal carcinoma. Lymphatic PD-L1 deficiency resulted in a consistent expansion of tumor-specific CD8+ T cells in tumor-draining LNs in both tumor models, reduced primary tumor growth in the MC38 model, and increased the efficacy of adoptive T cell therapy in the B16F10 model. Strikingly, lymphatic PD-L1 primarily acted via apoptosis induction in tumor-specific CD8+ central memory T cells. Our findings demonstrate that LECs restrain tumor-specific immunity via PD-L1 and may explain why some cancer patients without PD-L1 expression in the tumor microenvironment still respond to PD-L1 / PD-1 targeting immunotherapy.
Systematic characterization and genetic interaction analysis of adhesins inCandida albicansvirulence
Authors: Rosiana Sierra , Zhang Liyang , Kim Grace H. , Revtovich Alexey V. , Sukumaran Arjun , Geddes-McAlister Jennifer , Kirienko Natalia V. , Shapiro Rebecca S. 
Published: October 2020

AbstractCandida albicansis a microbial fungus that exists as a commensal member of the human microbiome and an opportunistic pathogen. Cell surface-associated adhesin proteins play a crucial role inC. albicans’ability to undergo cellular morphogenesis, develop robust biofilms, colonize, and cause infection in a host. However, a comprehensive analysis of the role and relationships between these adhesins has not been explored. We previously established a CRISPR-based platform for efficient generation of single- and double-gene deletions inC. albicans, which was used to construct a library of 144 mutants, comprising 12 unique adhesin genes deleted singly, or in every possible combination of double deletions. Here, we exploit this adhesin mutant library to explore the role of adhesin proteins inC. albicansvirulence. We perform a comprehensive, high-throughput screen of this library, usingCaenorhabditis elegansas a simplified model host system, which identified mutants critical for virulence and significant genetic interactions. We perform follow-up analysis to assess the ability of high- and low-virulence strains to undergo cellular morphogenesis and form biofilmsin vitro, as well as to colonize theC. eleganshost. We further perform genetic interaction analysis to identify novel significant negative genetic interactions between adhesin mutants, whereby combinatorial perturbation of these genes significantly impairs virulence, more than expected based on virulence of the single mutant constituent strains. Together, this yields important new insight into the role of adhesins, singly and in combinations, in mediating diverse facets of virulence of this critical fungal pathogen.SummaryCandida albicansis a human fungal pathogen and cause of life-threatening systemic infections. Cell surface-associated adhesins play a central role in this pathogen’s ability to establish infection. Here, we provide a comprehensive analysis of adhesin factors, and their role in fungal virulence. Exploiting a high-throughput workflow, we screened an adhesin mutant library usingC. elegansas a simple model host, and identified mutants and genetic interactions involved in virulence. We found that adhesin mutants are impaired inin vitropathogenicity, irrespective of their virulence. Together, this work provides new insight into the role of adhesin factors in mediating fungal virulence.
Mechanistic picture for chemo-mechanical couplings in a bacterial proton-coupled oligopeptide transporter from Streptococcus thermophilus
Authors: Immadisetty Kalyan , Moradi Mahmoud 
Published: October 2020

AbstractProton-coupled oligopeptide transporters (POTs) use the proton electrochemical gradient to transport peptides across the cell membrane. Despite the significant biological and biomedical relevance of these proteins, a detailed mechanistic picture for chemo-mechanical couplings involved in substrate/proton transport and protein structural changes is missing. We therefore performed microsecond-level molecular dynamics (MD) simulations of bacterial POT transporter PepTSt, which shares ~80% sequence identity with the human POT, PepT1, in the substrate binding region. Three different conformational states of PepTStwere simulated including, (i) occluded,apo, (ii) inward-facing,apo, and (iii) inward-facingoccluded, Leu-Ala bound. We propose that the interaction of R33 with E299 and E300 acts as a conformational switch (i.e., to trigger the conformational change from an inward-to outward-facing state) in the substrate transport. Additionally, E299 and E400 should disengage from interacting with the substrate either through protonation or through co-ordination with a cation for the substrate to get transported.
Resonance Raman spectra for the in-situ identification of bacteria strains and their inactivation mechanism
Authors: Dhankhar Dinesh , Nagpal Anushka , Li Runze , Chen Jie , Cesario Thomas C. , Rentzepis Peter M. 
Published: October 2020

AbstractThe resonance Raman spectra of bacterial carotenoids have been employed to identify bacterial strains and their intensity changes as a function of ultraviolet(UV) radiation dose have been used to differentiate between live and dead bacteria. The enhanced resonance Raman spectra of color-pigmented bacteria were recorded after excitation with visible light diode lasers. In addition, the resonance enhanced Raman spectra enabled us to detect bacteria in water at much lower concentrations (~108cells/mL) than normally detected spectroscopically. A handheld spectrometer capable of recording resonance Raman spectra in-situ was designed, constructed and was used to record the spectra. In addition to bacteria, the method presented in this paper may also be used to identify fungi, viruses and plants, in-situ, and detect infections within a very short period of time.
X-ray structure analysis of a unique D-amino-acid oxidase from the thermophilic fungus Rasamsonia emersonii strain YA
Authors: Shimekake Yuya , Hirato Yuki , Funabashi Rikako , Okazaki Sayoko , Goto Masaru , Furuichi Takehiro , Suzuki Hideyuki , Kera Yoshio , Takahashi Shouji 
Published: October 2020

D-Amino-acid oxidases (DAAOs) catalyze the oxidative deamination of neutral and basic D-amino acids. The DAAO from the thermophilic fungus Rasamsonia emersonii strain YA (ReDAAO) has a high thermal stability and a unique broad substrate specificity that includes the acidic D-amino acid D-Glu as well as various neutral and basic D-amino acids. In this study, ReDAAO was crystallized by the hanging-drop vapor-diffusion method and its crystal structure was determined at a resolution of 2.00 Å. The crystal structure of the enzyme revealed that unlike other DAAOs, ReDAAO forms a homotetramer and contains an intramolecular disulfide bond (Cys230–Cys285), suggesting that this disulfide bond is involved in the higher thermal stability of ReDAAO. Moreover, the structure of the active site and its vicinity in ReDAAO indicates that Arg97, Lys99, Lys114 and Ser231 are candidates for recognizing the side chain of D-Glu.
A systematic literature review on the usage of eye-tracking in understanding process models
Authors: Batista Duarte Rafael , Silva da Silveira Denis , de Albuquerque Brito Vinícius , Lopes Charlie Silva 
Published: October 2020

PurposeBusiness process modeling can involve multiple stakeholders, so it is natural that problems may occur during the designing and understanding processes. One way to perceive these problems is to evaluate the comprehension of business process models through the collection of data related to the readers' eye movement via an eye-tracking device. The purpose of this paper is to provide a comprehensive overview of the use of eye-trackers in understanding process models and to offer a research roadmap to challenge the community to address the identified limitations and open issues that require further investigation.Design/methodology/approachTo achieve this goal, Systematic Literature Review (SLR) was performed following good practices from the Evidence-Based Software Engineering's (EBSE) field.FindingsThis study resulted in 10 primary studies selected for analysis and data extraction, from the 1,482 initially retrieved. The major findings indicate that the business process community still benefits little from the use of eye-tracking, e.g. not offering sufficient support for inexperienced designers and not having an explicit standardization in its use. These and other findings are synthesized in a research roadmap which results would benefit researchers and practitioners.Originality/valueIn the studies found, the methods used to explore eyes' movement in process models' comprehension analysis were presented as an advantage of the current study. Additionally, another aspect presented in this SRL as an originality is presenting a set of open questions, suggesting valuable topics for future research through a research script (research roadmap).
Can joint-contract functions promote PPP project sustainability performance? A moderated mediation model
Authors: Cheng Mengyuan , Liu Guoliang , Xu Yongshun 
Published: October 2020

PurposeThe role of conventional contracts in achieving sustainability goals in public–private partnership (PPP) projects has been questioned. From the multifunctional perspective of contract theory, joint-contract functions that combine contractual control, coordination and adaptation may be a potential approach for improving PPP project sustainability performance. This research intends to investigate the link between the joint-contract functions and PPP project sustainability performance, and their underlying mechanism, by analyzing the mediating role of relationship quality and moderating roles of environmental uncertainty and behavioral uncertainty.Design/methodology/approachBased on 170 valid survey data collected from the Chinese PPP professionals, partial least squares structural equation modeling (PLS-SEM) was adopted to test the hypothesis.FindingsThe results reveal that joint-contract functions are positively associated with the PPP project sustainability performance. This relationship is strengthened by environmental and behavioral uncertainty. Moreover, the relationship between the joint-contract functions and PPP project sustainability performance is mediated by relationship quality.Research limitations/implicationsThis research extends contract governance theory and sustainability research in PPP projects. The research implications are as follows: (1) joint-contract functions are a second-order construct consisting of three first-order dimensions: control, coordination and adaptation and are positively associated with PPP project sustainability performance; (2) joint-contract functions enhance the sustainable benefits of PPP projects during environmental uncertainty and behavioral uncertainty; (3) informal relationships are a critical bridge connecting formal institutions with the sustainability performance of PPP projects.Practical implicationsIn general, these findings guide project participants who aim to achieve sustainable outcomes in PPP projects. (1) Project participants should consider the process of contract design and sign contracts that focus on joint-contract functions. (2) Project participants should investigate the degree of uncertainty of a PPP project before designing contracts, and design the contracts with corresponding complexity. (3) Project participants should work to enhance PPP sustainable benefits by improving the relationship between partners, such as encouraging mutual trust and joint problem-solving.Originality/valueThis research verifies the relationship between joint-contract functions and PPP project sustainability performance, and the boundary and intermediary conditions between them.
South Sudanese perceptions of health and illness in South Australia
Authors: Mude William Wingard , Fisher Christopher M. , Gautier Roslyn Le , Wallace Jack , Richmond Jacqueline A. 
Published: October 2020

PurposeSouth Sudanese people form the largest number of resettled refugees in Australia between 2003 and 2004. This study aims to explore how this community understands and responds to health and illness. No study has specifically examined the concept of health and illness in the broader socio-cultural context of the South Sudanese people in Australia.Design/methodology/approachThe design was a qualitative study using interviews and focus group discussions with 33 South Sudanese people in Adelaide, South Australia. Participants were asked to reflect on their understanding of health and illness and influences on their access and use of health and other services. Data were electronically audio-recorded, transcribed verbatim and analysed thematically.FindingsThree main themes emerged from the analysis demonstrating complex and multifaceted views on health and illness. Participants described health as both a lack of disease and wider issues involving social belonging and participation, cultural well-being, living conditions and harmony in the society. They revealed that illnesses are predetermined by God or caused by a curse, breaking a cultural taboo, disharmony with the environment, community and ancestral spirits. Participants deeply tied their beliefs about illness causation and treatment to their historical, social and cultural lived realities, shaping their responses and health-care-seeking decisions.Originality/valueThe current study revealed a complex understanding of health and health-care-seeking practices amongst South Sudanese Australians. The multifaceted views of health and health-care-seeking practices underscore the importance of person-centred care for culturally and linguistically diverse people.
Safeguarding adults and COVID-19: a sector-led improvement response
Authors: Cooper Adi 
Published: October 2020

Purpose
This study aims to describe the sector-led response to the COVID-19 pandemic and national lockdown in terms of safeguarding adults.

Design/methodology/approach
This study uses a case study method to examine a sector-led improvement response to COVID-19 and safeguarding adults.

Findings
The study describes how safeguarding issues and concerns were identified and brought together, and then responded to. It reviews this initiative in the context of crisis intervention theory and discusses the achievements of this initiative regarding COVID-19 and safeguarding adults during the period April–July 2020.

Originality/value
The study describes a unique joint initiative between the Local Government Association and the Association of Directors of Adult Social Services, which worked with the Networks of Chairs of Safeguarding Adults Boards, Safeguarding Adults Boards’ managers and Principal Social Workers. This initiative developed resources and shared information and good practice to support a response in unprecedented circumstances.
Political discourse of President Bashar Al-Assad after the Syrian revolution (analytical vision)
Authors: Gaber Shireen 
Published: October 2020

PurposeThere is no doubt that the political speech of the Syrian President Bashar Al-Assad is of exceptional importance in understanding the developments of the war in Syria, and clarifies the position of all parties involved in the war, whether local, regional or international. Accordingly, and based on the dismantling of political discourse, the identification of its core, as well as its variables and major themes of this discourse, this study aims to understand the levels of complexity, paths and the fate of the war in Syria that certainly does not come free of charge, the hardest of which is the human cost whether for the victims or the displaced persons.Design/methodology/approachAfter a careful study of all the resilient factors in the literature review to categorize the primary data based on Assad’s discourses in the media, through a “qualitative research study” of his “interviews and discourses,” it is found that the Assad’s rhetoric is highly relevant to his tenacious presidency. The research reveals the themes that dominated Assad’s interview responses and speeches and his strategy of framing the revolution as a foreign insurgency against his government. In fact, Assad delegitimizes any semblance of the uprisings as a “pro-democracy movement” or “revolution,” denying the presence of a rebellion against his government.FindingsBy the analysis the study found out that Bashar Al-Assad continued to focus on certain reasons and issues that led to the crisis and the continuation of the war, such as the Muslim Brotherhood’s involvement, considering the Syrian opposition abroad as agents of Western countries, Syria is subject to a regional and international conspiracy, terrorism is a major scourge that must be fought and that the army is essential in resolving the battles taking place there. Likewise, emphasizing the internal dialogue with all stakeholders and involved parties is the way to solve the crisis.The Syrian President’s speeches do not focus much on the accusations against his regime from the opposition or the international parties involved in the conflict.Originality/valueAssad’s resiliency has made him a distinct leader in the region. This paper analyzes the factors contributing to Assad’s resiliency. The literature review consists of the existing theories on authoritarian persistence and Assad’s power base in particular. The literature review discusses the factors that helped Assad adopts his resiliency strategies to the conflict environment. The research focuses on how Assad used the media as a platform for displaying his own manipulative narrative of the conflict. It concludes that Assad’s use of the media as his propaganda tool legitimized his rule, making it highly relevant to his persistence.
Cross-nationality importance performance analysis of Middle East all-inclusive mass tourism destination image
Authors: Ceylan Demet , Cizel Beykan , Karakas Hatice 
Published: October 2020

PurposeThe paper aims to analyze cognitive attributes affecting the overall destination image perception of British, German and Russian tourists toward Antalya, a well-positioned mass tourism destination in the East Mediterranean region dominated by an all-inclusive (AI) system.Design/methodology/approachThe paper is an empirical study using a structured questionnaire conducted in the summer of 2018 with 274 British, 179 German and 231 Russian tourists departing to their respective source markets from Antalya International Airport. The mean values are used as performance and correlation coefficients of the relationship between each cognitive image dimension and overall image evaluation is used to express importance.FindingsThe paper provides empirical insights that these three nationalities prefer Antalya as an AI holiday destination for different reasons and that each nationality demands attention to different factors of the destination for improvement or preservation.Research limitations/implicationsThis study provides specific recommendations for AI destinations such as Antalya for the German, British and Russian source markets. When other source markets or types of destinations are considered, the findings of this study should be re-considered. Utilization of the original and modernized importance performance analysis (IPA) plot interpretations in this research reveals a deeper understanding of current findings and provides a new perspective for further research and guidance for destination managers and marketers.Practical implicationsUtilization of both original and modernized IPA plot interpretation in this research not only reveals a deeper understanding of current findings but also provides a new perspective for future studies and guidance for destination managers and marketers.Originality/valueUnlike the majority of destination image research, this study of destination image based on individual nationalities enables tailor-made destination image development according to diversified importance and performance of destination attributes affecting the overall destination image for each nationality.
Tacit vs explicit knowledge as antecedents for organizational change
Authors: Gamble Jordan R. 
Published: October 2020

PurposeThe aim of this paper is to explore the dichotomous role of knowledge through an examination of tacit and explicit knowledge in organizational change contexts.Design/methodology/approachThe study's aim is achieved by an analytical review of the seminal and contemporary knowledge management literature.FindingsThe paper contributes to the current body of knowledge management literature by analyzing a wide range of key literature and presenting a contemporary overview that compares the role of tacit and explicit knowledge within organizational change contexts.Research limitations/implicationsThe findings contribute toward theoretical development in the knowledge management field by providing researchers with future research directions to build upon previous theoretical understandings and advance our collective knowledge of the research domain.Practical implicationsThe paper offers practical and pragmatic insights that will help firm managers to use tacit and/or explicit knowledge to manage organizational change.Originality/valueThis article presents an original comparative table that summarizes and compares the key understandings and insights from across the literature sources on a range of important aspects, and then presents implications for the two knowledge typologies. The paper also presents an original research framework containing a structured database of related calls for research by the latest academic publications. Furthermore, it provides specific and informed managerial recommendations for best practice in the integration of these knowledge typologies into organizational change management.