bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vivarium: an Interface and Engine for Integrative Multiscale Modeling in Computational Biology
Authors: Agmon Eran , Spangler Ryan K. , Skalnik Christopher J. , Poole William , Peirce Shayn M. , Morrison Jerry H. , Covert Markus W. 
Published: April 2021

AbstractMotivationThis paper introduces Vivarium – software born of the idea that it should be as easy as possible for computational biologists to define any imaginable mechanistic model, combine it with existing models, and execute them together as an integrated multiscale model. Integrative multiscale modeling confronts the complexity of biology by combining heterogeneous datasets and diverse modeling strategies into unified representations. These integrated models are then run to simulate how the hypothesized mechanisms operate as a whole. But building such models has been a labor-intensive process that requires many contributors, and they are still primarily developed on a case-by-case basis with each project starting anew. New software tools that streamline the integrative modeling effort and facilitate collaboration are therefore essential for future computational biologists.ResultsVivarium is a Pythonic software for building integrative multiscale models. It provides an interface that makes individual models into modules that can be wired together in large composite models, parallelized across multiple CPUs, and run with Vivarium’s simulation engine. Vivarium’s utility is demonstrated by building composite models that combine several modeling frameworks: agent based models, ordinary differential equations, stochastic reaction systems, constraint-based models, solid-body physics, and spatial diffusion. This demonstrates just the beginning of what is possible – future efforts can integrate many more types of models and at many more biological scales.AvailabilityThe models, simulation pipelines, and notebooks developed for this paper are available at the vivarium-notebooks repository:https://github.com/vivarium-collective/vivarium-notebooks. Vivarium-core is available athttps://github.com/vivarium-collective/vivarium-core, and has been released on PyPI. The Vivarium Collective (https://vivarium-collective.github.io) is a repository of freely-available Vivarium processes and composites, including the processes used in Section 3. Supplementary materials provide with an extensive methodology section, with several code listings that demonstrate the basic interfaces.
Enhanced lipogenesis through Pparγ helps cavefish adapt to food scarcity
Authors: Xiong Shaolei , Wang Wei , Kenzior Alexander , Olsen Luke , Krishnan Jaya , Persons Jenna , Medley Kyle , Peuß Robert , Wang Yongfu , Chen Shiyuan , Zhang Ning , Thomas Nancy , Miles John M. , Sánchez Alvarado Alejandro , Rohner Nicolas 
Published: April 2021

AbstractNutrient availability varies seasonally and spatially in the wild. The resulting nutrient limitation or restricted access to nutrients pose a major challenge for every organism. While many animals, such as hibernating animals, evolved strategies to overcome periods of nutrient scarcity, the cellular mechanisms of these strategies are poorly understood. Cave environments represent an extreme example of nutrient deprived environments since the lack of sunlight and therefore primary energy production drastically diminishes the nutrient availability. Here, we usedAstyanax mexicanus, which includes river-dwelling surface fish and cave adapted cavefish populations to study the genetic adaptation to nutrient limitations. We show that cavefish populations store large amounts of fat in different body regions when fed ad libitum in the lab. We found higher expression of lipogenesis genes in cavefish livers when fed the same amount of food as surface fish, suggesting an improved ability of cavefish to use lipogenesis to convert available energy into triglycerides for storage into adipose tissue. Moreover, the lipid metabolism regulator, Peroxisome proliferator-activated receptor γ (Pparγ), is upregulated at both transcript and protein levels in cavefish livers. Chromatin Immunoprecipitation sequencing (ChIP seq) showed that Pparγ binds cavefish promoter regions of genes to a higher extent than surface fish. Finally, we identified two possible regulatory mechanisms of Pparγ in cavefish: higher amounts of ligands of the nuclear receptor, and nonsense mutations inper2, a known repressor of Pparγ. Taken together, our study reveals that upregulated Pparγ promotes higher levels of lipogenesis in the liver and contributes to higher body fat accumulation in cavefish populations, an important adaptation to nutrient limited environments.
Liver Endothelium Promotes HER3-mediated Cell Survival inKRASWild-type and Mutant Colorectal Cancer Cells
Authors: Rathore Moeez , Wright Michel’le , Bhattacharya Rajat , Fan Fan , Vaziri-Gohar Ali , Winter Jordan , Wang Zhenghe , Markowitz Sanford D , Willis Joseph , Ellis Lee M. , Wang Rui 
Published: April 2021

ABSTRACTWe previously showed that liver endothelial cells (ECs) secreted soluble factors in a paracrine fashion and activated human epidermal growth factor receptor 3 (HER3, also known as ERBB3) for promoting colorectal cancer (CRC) growth and chemoresistance. However, RAS proteins play a critical role in receptor tyrosine kinase signaling pathways, andKRASmutations mediate CRC resistance to therapies targeting EGFR, another HER protein. Therefore, the role ofKRASmutation status in EC-induced HER3 activation and CRC survival was investigated as it has therapeutic implications. We used CRC cell lines and patient-derived xenografts harboringKRASwild-type or mutant genes and demonstrated that liver EC-secreted factors promoted HER3-mediated CRC cell growth independent ofKRASmutation status. Also, blocking HER3 in CRC cells by siRNAs or a HER3 antibody seribantumab blocked EC-induced CRC survival. Our findings highlight the potential of utilizing HER3 targeted therapies for treating patients with mCRC independent ofRASmutational status.
Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
Authors: Ryu Dong-Kyun , Song Rina , Kim Minsoo , Kim Young-Il , Kim Cheolmin , Kim Jong-In , Kwon Ki-Sung , Tijsma Aloys SL , Nuijten Patricia M , van Baalen Carel A , Hermanus Tandile , Kgagudi Prudence , Gwete-Moyo Thandeka , Moore Penny L , Choi Young Ki , Lee Soo-Young 
Published: April 2021

AbstractThe global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform asin vitrobinding and neutralization assays, andin vivoanimal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However,in vivoferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reducedin vitroneutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.HighlightsCT-P59 significantly inhibit B.1.1.7 variant to a similar extent as to wild type virusCT-P59 showed reduced potency against the B.1.351 variant inin vitrostudiesTherapeutic dosage of CT-P59 showedin vivoneutralizing potency against B.1.351 in ferret challenge study.
Role of Gasdermins in the Biogenesis of Apoptotic Cell–Derived Exosomes
Authors: Hur Jaehark , Kim Yeon Ji , Choi Da Ae , Kang Dae Wook , Kim Jaeyoung , Yoo Hyo Soon , Shahriyar Sk Abrar , Mustajab Tamanna , Kim Dong Young , Chwae Yong-Joon 
Published: April 2021

AbstractThe gasdermins, GSDMA, GSDMB, GSDMC, GSDMD, DFNA5, and DFNB59, are a family of pore-forming proteins that has recently been suggested to play a central role in the pyroptosis and the release of inflammatory cytokines. Here, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell–derived exosomes. In apoptotic cells, GADMA, GSDMC, GSDMD, and DFNA5 increased the release of ApoExos, and both their full-length and cleaved forms were localized in the exosomal membrane. GSDMB and DFNB59, on the other hand, negatively affected the release of ApoExos. The caspase-mediated cleavage of gasdermins, especially DFNA5, is suggested to enable cytosolic Ca2+to flow through endosomal pores and thus increase the biogenesis of ApoExos. In addition, the DFNA5-meidiated biogenesis of ApoExos depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins: annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of ApoExos begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that Dfna5-bearing tumors released ApoExos to induce inflammatory responses in thein vivo4T1 orthotropic model of breast cancer. The data presented in this study indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.
Competition, performance and financial stability in US agricultural banking
Authors: Regmi Madhav , Featherstone Allen M. 
Published: April 2021

PurposeThe number of US commercial banks has declined by about 50% over the last two decades. This change could lead to a potential decline in competition and a potential increase in market power in the agricultural banking market. The focus of this study is to examine whether the risk of failure and the performance of agricultural banks has been affected by bank consolidations.Design/methodology/approachThe impact of bank competition on performance and financial stability of agricultural banks is studied using a Lerner index as a measure of market power. A Z-score is constructed to measure bank stability. Similarly, the return on assets (net income to total assets ratio), return on equity (net income to the total equity ratio), agricultural loan ratio and agricultural loan volume are used as performance measures for agricultural banks. Two-way fixed effect regression models are estimated to measure the impact of competition on financial stability and performance.FindingsResults indicate that bank competition has a U-shaped effect on the probability of default and an inverted U-shaped effect on volume and proportion of agricultural lending. There also exists evidence of a positive but non-linear effect of bank market power on the profitability of agricultural banks.Originality/valueThere is limited literature on the impact of bank competition on financial stability and performance of US agricultural banks. Agricultural banks hold more than 40% of US farm debt. A decrease in the number of banks or the level of competition in agricultural banking may cause an adverse effect on relationship lending. The key findings imply that bank regulatory strategies should focus on enhancing (reducing) competition in more (less) concentrated banking markets to improve the financial health and performance of agricultural banks.
Sources and flow of healthcare built environment design evidence
Authors: Wanigarathna Nadeeshani , Sherratt Fred , Price Andrew D.F. , Austin Simon 
Published: April 2021

PurposeA substantial amount of research argues that built environmental interventions can improve the outcomes of patients and other users of healthcare facilities, supporting the concept of evidence-based design (EBD). However, the sources of such evidence and its flow into healthcare design are less well understood. This paper aims to provide insights to both the sources and flow of EBD used in three healthcare projects, to reveal practicalities of use and the relationships between them in practice.Design/methodology/approachThree healthcare case study projects provided empirical data on the design of a number of different elements. Inductive thematic analysis was used to identify the source and flow of evidence used in this design, which was subsequently quantised to reveal the dominant patterns therein.FindingsHealthcare design teams use evidence from various sources, the knowledge and experience of the members of the design team being the most common due to both ease of access and thus flow. Practice-based research and peer-reviewed published research flow both directly and indirectly into the design process, whilst collaborations with researchers and research institutions nurture the credibility of the latter.Practical implicationsThe findings can be used to enhance activities that aim to design, conduct and disseminate future EBD research to improve their flow to healthcare designers.Originality/valueThis research contributes to understandings of EBD by exploring the flow of research from various sources in conflation and within real-life environments.
Procurement 4.0 to the rescue: catalysing its adoption by modelling the challenges
Authors: Joseph Jerome Jude Jegan , Saxena Disha , Sonwaney Vandana , Foropon Cyril 
Published: April 2021

PurposeThe pandemic crisis has resulted in global chaos that had caused massive disruption to the supply chain. The pharmaceutical industry, in particular, has been working tirelessly to ensure that they can cater to the people who need them. With restrictions being imposed to prevent the spread of the COVID-19 virus, the movement of raw materials required has been affected, thus creating the need for the procurement function to be innovative. This study proposes the application of Industry 4.0 concepts into the procurement activities of an organization to make it more resilient and efficient.Design/methodology/approachTo study the intensity of the challenges, Total Interpretive Structural Modelling is used alongside the “Matrice des Impacts Croises Multiplication Appliquee a un Classement” (MICMAC) technique.FindingsResilience can be achieved through the collaboration between the organization and its network of suppliers. This is however easier said than done. High and unclear investments have been identified as the challenge that is taking a toll on all technological investments in the pandemic era. The study also shows that organizational inertia which is present in established and structured firms are a deterrent as well.Originality/valueThis study is based on the application of procurement 4.0 to ensure that pharmaceutical supply chains stay least affected since they are essentials. This study using a multi-criteria decision-making approach to prioritize the challenges. This will help practitioners make decisions faster.
Governance modes in supply chains and financial performance at buyer, supplier and dyadic levels: the positive impact of power balance
Authors: Marques Leonardo , Lontra Paulo , Wanke Peter , Antunes Jorge Junio Moreira 
Published: April 2021

PurposeThis study analyzes whether power in the supply chain, based on governance modes and network centrality, explain financial performance at different levels of analysis: buyers, suppliers and dyads.Design/methodology/approachThe study employs a dual macro-micro lens based on global value chain (i.e. market, modular, relational and captive governance modes) and social network analysis (network centrality) to assess the impact of power (im)balance onto financial performance. Different from previous research, this study adopts information reliability techniques – such as information entropy – to differentiate the weights of distinct financial performance metrics in terms of the maximal entropy principle. This principle states that the probability distribution that best represents the current state of knowledge given prior data is the one with largest entropy. These weights are used in TOPSIS analysis.FindingsResults offer insightful reflections to SCM research. We show that buyers outperform suppliers due to power asymmetry. We ground our findings both analyzing across governance modes and comparing network centrality. We show that market and modular governances (where power balance prevails) outperform relational and captive modes at the dyadic level – thus inferring that in the long run these governance modes may lead to financially healthier supply chains.Originality/valueThis study advances SCM research by exploring the impact of governance modes and network centrality on performance at both firm and dyadic levels while employing an innovative combination of secondary data and robust set of techniques including TOPSIS, WASPAS and information entropy.
Supplier development under cooperative and non-cooperative investment structures
Authors: Srivastava Abhishek , Kumar Parimal , Mateen Arqum 
Published: April 2021

PurposeThis study analyzes supplier development investment decisions under a triadic setting (two buyers and a common supplier). In a triadic setting, the supplier development investment decision of one buyer can have a spillover effect of the benefits on other buyer. Therefore, it is utmost important for the investing buyer to understand the impact of benefit spillover on other competing buyers'. Therefore, one of the purposes of this study to analyze the supplier development investment decision of buyers under two scenarios. First, under cooperative development structure where both buyers jointly invest in supplier and share equal benefits. Second, non-cooperative investment structure where both buyers individually invest in supplier development and share unequal benefits.Design/methodology/approachIn order to assess the impact of supplier development investment decisions on the profitability of buyers and the common supplier, the authors used game-theoretic approach. The authors design a Stackelberg leader-follower game where the supplier acts as Stackelberg leader and buyers follow the supplier's pricing decision to maximize their profit level. Additionally, both buyers decide either to cooperate or non-cooperate while investing in supplier development.FindingsThe results show that the cooperative investment is always an optimal strategy for buyers and supplier. Interestingly, the efficient buyer's share of investment level is lower under non-cooperative investment structure and he is better-off due to its capability of taking advantage from the other buyer's investment. However, the inefficient buyer, on the other hand, is worse-off under non-cooperative investment. Furthermore, comparative analysis between the two shows that initially, the buyer who extracts more profit because of the other buyers' development investment tends to prefer the non-cooperative development investment set up. However, after a certain point, the same buyer is better-off under cooperative development investment through cooperation, and sharing equal benefit of the supplier's development, as the supplier in turn, starts charging a higher wholesale price under non-cooperative investment case.Originality/valueTo the best of authors’ knowledge, extant literature on supplier development has mostly focused on. One supplier-one buyer; thus, the learning spillover effect has almost been unexplored. In real-life, different buyers often purchase from the shared supplier. Therefore, it is important to analyze the spillover of supplier development benefits due to investment of one buyer on other buyer and deriving the condition under which buyers would be incentivized to invest jointly or individually.
Synergistic effect of cooperation and coordination to enhance the firm's supply chain adaptability and performance
Authors: Feizabadi Javad , Alibakhshi Somayeh 
Published: April 2021

PurposeTo address how organizations should be malleable, the purpose herein is to draw on complementarity theory to examine the interaction effect of customer integration (i.e. coordination) and shared relationship governance (i.e. cooperation) on supply chain adaptability and firm's performance.Design/methodology/approachA survey research design is adopted to collect primary data from 177 automotive components suppliers. After assessing the measures' psychometric properties, the hypothesized relationships are evaluated using hierarchical regression analysis supplemented by structural equation modeling and complementarity test.FindingsIn the context of industrial markets, and specifically the automotive component industry, a complementary interaction effect is found between coordination and cooperation. The complementary impact was significant in affecting the supply chain adaptability and the firm's performance. Our results refine the existing supply chain integration by highlighting the complementary effect of coordination and cooperation.Practical implicationsUnderstanding the true interaction effect between cooperation and coordination to develop supply chain integration avoids decision-makers' misperception over or underinvesting in activities. This research also provides key insights on the complementary effect of coordination and cooperation to establish structural flexibility in the supply chain and the ability to respond to the disruptions, such as the COVID-19 pandemic.Originality/valueUnderstanding the true interaction effect between cooperation and coordination to develop supply chain integration avoids decision-makers' misperception over or underinvesting in activities. The implications for theory and practice are also presented.
R-BPMN for abstract modeling of business process patterns
Authors: Kim Dae-Kyoo , Chung Yeasun K. 
Published: April 2021

PurposeThe authors use the extension mechanism provided by the Business Process Model and Notation (BPMN) to define roles, which allows roles to be fully aligned with the BPMN standard. The authors describe how a pattern can be defined in terms of roles and present the formal semantics of pattern realization and refinement to support systematic reuse of patterns in business process development.Design/methodology/approachIt is widely agreed that the use of business process patterns improves the efficiency and quality of business process development. However, few techniques are available to describe business process patterns at an appropriate level of abstraction to facilitate the reuse of patterns. To address this, this paper presents the role-based Business Process Model and Notation (R-BPMN), an extension of BPMN for abstract modeling of business process patterns based on a novel notion of role.FindingsThe authors apply R-BPMN in case studies for pattern realization and refinement and discuss tool support via an existing tool. The case studies demonstrate the practical benefits of R-BPMN in capturing pattern variability and facilitating pattern reuse.Practical implicationsThe findings imply a potential impact of R-BPMN on practical benefits when it is supported at the metamodel level in tool development.Originality/valueThis study addresses the need for abstract modeling of process patterns at the metamodel level, which facilitates the formalization of pattern variability and tool development to support various realizations of process patterns at the model level.