bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis
Authors: Boice Ashley , Pandita Raj K , Lopez Karla , Parsons Melissa J , Charendoff Chloe I , Charaka Vijay , Carisey Alexandre F. , Pandita Tej K. , Bouchier-Hayes Lisa 
Published: March 2021

AbstractIn addition to its classical role in apoptosis, accumulating evidence suggests that caspase-2 has non-apoptotic functions, including regulation of cell division. Loss of caspase-2 is known to increase proliferation rates but how caspase-2 is regulating this process is currently unclear. We show that caspase-2 is activated in dividing cells in G1- and early S-phase. In the absence of caspase-2, cells exhibit numerous S-phase defects including delayed exit from S-phase, S-phase-associated chromosomal aberrations, and increased DNA damage following S-phase arrest. In addition, caspase-2-deficient cells have a higher frequency of stalled replication forks, decreased DNA fiber length, and impeded progression of DNA replication tracts. This indicates that caspase-2 reduces replication stress and promotes replication fork protection to maintain genomic stability. These functions are independent of the pro-apoptotic function of caspase-2 because blocking caspase-2-induced cell death had no effect on cell division or DNA damage-induced cell cycle arrest. Thus, our data supports a model where caspase-2 regulates cell cycle events to protect from the accumulation of DNA damage independently of its pro-apoptotic function.
Exploring the role of glycans in the interaction of SARS-CoV-2 RBD and human receptor ACE2
Authors: Nguyen Kien , Chakraborty Srirupa , Mansbach Rachael A. , Korber Bette , Gnanakaran S. 
Published: March 2021

AbstractCOVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell receptor ACE2, enabling the virus to enter the host cell. Both the Spike and ACE2 are densely glycosylated, and it is unclear how distinctive glycan types may modulate the interaction of RBD and ACE2. Detailed understanding of these determinants is key for the development of novel therapeutic strategies. To this end, we perform extensive all-atom simulations of the (i) RBD-ACE2 complex without glycans, (ii) RBD-ACE2 with oligomannose MAN9 glycans in ACE2, and (iii) RBD-ACE2 with complex FA2 glycans in ACE2. These simulations identify the key residues at the RBD-ACE2 interface that form contacts with higher probabilities, thus providing a quantitative evaluation that complements recent structural studies. Notably, we find that this RBD-ACE2 contact signature is not altered by the presence of different glycoforms, suggesting that RBD-ACE2 interaction is robust. Applying our simulated results, we illustrate how the recently prevalent N501Y mutation may alter specific interactions with host ACE2 that facilitate the virus-host binding. Furthermore, our simulations reveal how the glycan on Asn90 of ACE2 can play a distinct role in the binding and unbinding of RBD. Finally, an energetics analysis shows that MAN9 glycans on ACE2 decrease RBD-ACE2 affinity, while FA2 glycans lead to enhanced binding of the complex. Together, our results provide a more comprehensive picture of the detailed interplay between virus and human receptor, which is much needed for the discovery of effective treatments that aim at modulating the physical-chemical properties of this virus.
Ovarian cancers with low CIP2A tumor expression constitute an APR-246 sensitive disease subtype
Authors: Cvrljevic Anna N. , Butt Umar , Huhtinen Kaisa , Grönroos Tove J. , Böckelman Camilla , Lassus Heini , Kaipio Katja , Arsiola Tiina , Laajala Teemu D. , Connolly Denise C. , Ristimäki Ari , Carpen Olli , Pouwels Jeroen , Westermarck Jukka 
Published: March 2021

AbstractIdentification of ovarian cancer (OvCa) patient subpopulations with increased sensitivity to targeted therapies could offer significant clinical benefit. We report that 22% of the high grade OvCa tumors at diagnosis express CIP2A oncoprotein at low levels. CIP2AlowOvCa tumors have significantly lower likelihood of disease relapse after standard chemotherapy, but yet a portion of relapsed tumors retain their CIP2Alowphenotype. We further discover that reactive oxygen species (ROS) inducing compound APR-246 (PRIMA-1Met/Eprenetapopt), currently in clinical development, preferentially kill CIP2AlowOvCa cells across multiple chemotherapy resistant cell lines. Consistent with CIP2AlowOvCa subtype in humans, CIP2A is dispensable for development of MISIIR-TAg-driven mouse OvCa tumors. Nevertheless, CIP2A deficient OvCa tumor cells from MISIIR-TAg mice displayed APR-246 hypersensitivity bothin vitroandin vivo. Mechanistically, the lack of CIP2A expression hypersensitizes the OvCa cells to APR-246 by inhibition of NF-kB activity. Accordingly, combination of APR-246 and Nf-kB inhibitor compounds strongly synergized in killing of CIP2A positive OvCa cells. Collectively, we discover low CIP2A expression as a vulnerability for APR-246 in OvCa. The results warrant consideration of clinical testing of APR-246 for CIP2AlowOvCa tumor subtype patients, and reveal CIP2A as a candidate APR-246 combination therapy target.
Comparison of Type-1 and Type-2 Fuzzy Systems for Mineralization of Bioprinted Bone
Authors: Sedigh Ashkan , Akbarzadeh-T Mohammad-R. , Tomlinson Ryan E. 
Published: March 2021

ABSTRACTBioprinting is an emerging tissue engineering method used to generate cell-laden scaffolds with high spatial resolution. Bioprinting parameters, such as pressure, nozzle size, and speed, have a large influence on the quality of the bioprinted construct. Moreover, cell suspension density, cell culture period, and other critical biological parameters directly impact the biological function of the final product. Therefore, an approximation model that can be used to find the values of bioprinting parameters that will result in optimal bioprinted constructs is highly desired. Here, we propose type-1 and type-2 fuzzy systems to handle the uncertainty and imprecision in optimizing the input values. Specifically, we focus on the biological parameters, such as culture period, that can be used to maximize the output value (mineralization volume). To achieve a more accurate approximation, we have compared a type-2 fuzzy system with a type-1 fuzzy system using two levels of uncertainty. We hypothesized that type-2 fuzzy systems may be preferred in biological systems, due to the inherent vagueness and imprecision of the input data. Here, our results demonstrate that the type-2 fuzzy system with a high uncertainty boundary (30%) is superior to type-1 and type-2 with low uncertainty boundary fuzzy systems in the overall output approximation error for bone bioprinting inputs.
Boundary-spanning search, knowledge integration capability and sustainable competitive advantage
Authors: Yang Miaomiao , Wang Juanru , Yang Jin 
Published: March 2021

PurposeThe purpose of this paper is to investigate how boundary-spanning search affects sustainable competitive advantage under the conditions that competitors also search and to test the moderating role of knowledge integration capability.Design/methodology/approachThis paper classifies boundary-spanning search into proactive search and responsive search by considering competition and develops a theoretical model in which knowledge integration capability moderates the effects of proactive and responsive searches on sustainable competitive advantage. Empirical analyses were conducted on the data of 245 Chinese advanced manufacturing firms.FindingsThe results show that proactive and responsive searches have inverted U-shaped relationships with sustainable competitive advantage. Moreover, the relationships between proactive and responsive searches and sustainable competitive advantage are moderated by knowledge integration capability. Specifically, as knowledge integration capability increases, the inverted U-shaped relationship between proactive search and sustainable competitive advantage becomes flatter, whereas the inverted U-shaped relationship between responsive search and sustainable competitive advantage becomes almost linear.Originality/valueThis paper enriches the research of boundary-spanning search by considering competition and uncovers how boundary-spanning search affects sustainable competitive advantage under the conditions that competitors also search. Furthermore, this paper sheds light on that the effects of proactive and responsive searches on sustainable competitive advantage are even more complex than inverted U-shaped patterns and provides a contingent viewpoint to deeply understand the relationship between boundary-spanning search and sustainable competitive advantage.
Familial altruism and reputation risk: evidence from China
Authors: Fang Hanqing “Chevy” , Shi Yulin , Wu Zhenyu 
Published: March 2021

PurposeThe authors study the effects of altruism and intention for succession on family firm's reputation risk-taking behaviors in Chinese publicly listed companies.Design/methodology/approachThe authors use earnings management as a proxy for reputation risk in family firms, and hand-collected relationship between family members to measure the closeness of incumbent family members and their potential successors as a proxy for the altruistic degree.FindingsResults show that, in developing countries like China, familial altruism in family firms with succession plans, which does not reduce the practice of earnings management, should be considered by practitioners while detecting it.Originality/valueThe hand collected data are very unique; the authors have focused on the relationship between incumbents and successors and the authors define their closeness by using genes shared between them.
Assessing large-scale digitization using Web analytics
Authors: Lapworth Emily 
Published: March 2021

Purpose
The purpose of this study is to assess the use of digital collections created via the large-scale digitization of archival collections. The large-scale digitization method specifically examined is the reuse of archival description from finding aids to create digital collections that consist mainly of compound digital objects, equivalent to a folder of items, minimally described at the aggregate level. This paper compares Web analytics data for two large-scale digital collections and one digital collection with rich, item-level description.

Design/methodology/approach
This study analyzed one year of Web analytics for three digital collections. The main research question of this study is: Are digital collections of minimally described compound objects used less than digital collections of richly described single objects?

Findings
This study found that the large-scale digital collections analyzed received less use than the traditional item-level collection, when examined at the item level. At the object level, the large-scale collections did not always receive less use than the traditional item-level collection.

Research limitations/implications
This study is limited to three different digital collections from one institution. Web analytics also represent a limited interpretation of “use.”

Practical implications
This study presents a method for other institutions to assess their own large-scale digitization efforts and contributes to the profession’s understanding of the impact of large-scale digitization.

Originality/value
This paper is unique because it uses Web analytics to compare the use of large-scale digital collections to the use of traditional boutique digital collections.
Traditional water knowledge: challenges and opportunities to build resilience to urban floods
Authors: Asad Rumana , Ahmed Iftekhar , Vaughan Josephine , von Meding Jason 
Published: March 2021

Purpose
Urban flooding in developing countries of the Global South is growing due to extreme rainfall and sea-level rise induced by climate change, as well as the proliferation of impervious, built-up areas resulting from unplanned urbanisation and development. Continuous loss of traditional knowledge related to local water management practices, and the de-valuing of such knowledge that goes hand-in-hand with globalised aspirations, is inhibiting flood resilience efforts. This paper aims to address the need to include traditional water knowledge (TWK) in urban living and development processes in the Global South.

Design/methodology/approach
This paper commences with a review of existing frameworks that focus on natural resource management, critically assessing two existing frameworks of traditional ecological knowledge (TEK). The assessment of the existing approaches contributes to this paper’s development of a novel framework to promote TWK with regard to resilience and risk reduction, specifically for developing flood adaptive strategies, which is the second stage of this paper. Finally, the paper explains how the framework can contribute to the field of urban design and planning using examples from the literature to demonstrate challenges and opportunities related to the adaptation of such a framework.

Findings
The framework developed in this paper reveals three proposed vertices of TWK, named as place-based landscape knowledge, water use and management and water values. This framework has the potential to produce context-specific knowledge that can contribute to flood-resilient built-environment through urban design and practices.

Research limitations/implications
The framework developed in this paper reveals three proposed vertices of TWK, named place-based landscape knowledge, water use and management and water values. This framework has the potential to produce context-specific knowledge that can contribute to flood-resilient built-environment through urban design and practices.

Originality/value
Within the field of TEK research, very few researchers have explored the field of developing flood resilience in an urban context. The proposed TWK framework presented in this paper will help to fill that gap.
Factors affecting transaction costs in megaprojects: a qualitative comparative analysis
Authors: Wang Dedong , Li Hui , Lu Yongqiang 
Published: March 2021

PurposeThe purpose of this study is to examine the factors influencing the transaction costs (TCs) in megaprojects to provide a basis for controlling project costs.Design/methodology/approachThis study selects six factors influencing the TCs in megaprojects from the perspective of TC theory and relational contract theory (RCT) through literature review. On the basis of crisp-set qualitative comparative analysis (QCA), this study tests combined factors influencing the TCs and the interaction between them.FindingsResults show that in megaprojects, TCs are affected by combination factors. The combination of asset specificity, uncertainty, transaction frequency and trust and the combination of asset specificity, reputation and trust will control TCs in certain situations. In the configuration leading to high project TCs, the combination of environmental and behavioral uncertainties is a necessary condition.Originality/valueThis paper fills up the research gap in the field of megaproject TCs, and researchers can focus on this field in the future.
Economic development, population and civil war: a Bayesian changepoint model
Authors: Luo Shali , Choi Seung-Whan 
Published: March 2021

PurposeThis study proposes a Bayesian approach to analyze structural breaks and examines whether structural changes have occurred, at the onset of civil war, with respect to economic development and population during the period from 1945 to 1999.Design/methodology/approachIn the Bayesian logit regression changepoint model, parameters of covariates are allowed to shift individually, regime transitions can move back and forth, and the model is applicable to cross-sectional, time-series data.FindingsContrary to popular belief that the causal process of civil war changed with the end of the Cold War, the empirical analysis shows that the regression relationships between civil war and economic development, as well as between civil war and population, remain quite stable during the study period.Originality/valueThis is the first to develop a Bayesian logit regression changepoint model and to apply it to studies of economic development and civil war.
An assessment of budgeting and budgetary controls among small and medium-sized enterprises: evidence from a developing economy
Authors: Matsoso Mamorena Lucia , Nyathi Moses , Nakpodia Franklin A. 
Published: March 2021

PurposeThe capacity to plan, manage and control small and medium-sized enterprises (SMEs) is critical to realising their organisational goals. This paper assesses the effectiveness and perception of budgeting and budgetary control systems among SMEs.Design/methodology/approachRelying on the goal-setting theory (GST) and a methodology that accommodates questionnaires, data were collected from 170 manufacturing SMEs located in Cape Town, South Africa.FindingsResearch results affirm that the deployment of budgeting benefits from a positive perception of the value of budgeting and budgetary controls by key SME stakeholders. The study also finds that the perception of budgeting mirrors the level of education of SME operators, as educated respondents understand the value of implementing robust budgeting systems. Despite its focus on manufacturing SMEs, this study suggests that the manufacturing budget is the least utilised budgeting system among these organisations.Practical implicationsThe study reinforces the communication power of budgeting and budgetary controls as SMEs and economic agents are not only aware of corporate objectives but are equally incentivised to support the attainment of these objectives.Originality/valueDespite the extensive application of GST among scholars, its use in budgeting and budgetary control literature, particularly among SMEs in developing contexts, is limited. In line with GST, this study indicates that when agents establish and implement a plan, they are motivated to pursue and realise the set expectations while consistently evaluating themselves for improvement opportunities.
The effects of government spending shocks on real exchange rate in Ethiopia
Authors: Gidey Hiluf Techane , Nuru Naser Yenus 
Published: March 2021

PurposeGovernment spending has inconclusive effect on real exchange rate. From the very beginning neoclassical economists argued that a rise in government spending brings depreciation in real exchange rate while neo-Keynesians claimed that government spending appreciates real exchange rate. Hence, the main purpose of this paper is to examine the effect of government spending shock and its components' shocks, namely government consumption and government investment on real exchange rate over the period 2001Q1–2016Q1 for Ethiopia.Design/methodology/approachTo examine the effects of government spending shocks on real exchange rate, Jordà's (2005) local projection method is employed in this study. The exogenous shocks, however, are identified recursively in a vector autoregressive model.FindingsThe impulse responses show that government spending shock leads to a statistically significant appreciation of real exchange rate in Ethiopia. This evidence supports the neo-Keynesian school of thought who predicts an appreciation of real exchange rate from a rise in government spending. While government investment shock depreciates real exchange rate on impact insignificantly, government consumption shock appreciates real exchange rate in this small open economy.Originality/valueThis research contributes to the scarce literature on the effect of fiscal policy shock on real exchange rate in small open economies like Ethiopia.
Refining a subsidiary evolution framework: clarifying key concepts
Authors: Jakobsson Johan , Lagerström Katarina , Schweizer Roger 
Published: March 2021

PurposeWhile the evolution of subsidiaries has received considerable research attention, the framework for understanding it has not evolved much since the late 1990s. The purpose of this paper is to add both clarity and depth to the work on the foundations for – as well as the processes of – capability creation and development as a subsidiary evolves.Design/methodology/approachThis conceptual paper takes as its point of departure the micro-foundation literature, with a specific emphasis on the capability development literature. To describe capability creation and development, both the resource-based view and the resource management perspective are used here.FindingsThe paper adds a conceptual layer to the drivers of subsidiary evolution. To add further clarity regarding how capabilities are actually formed, the resources for capability creation and development are specified herein as entities, abilities and capacity. Arguments are also presented for why capabilities ought to be viewed as patterned behavior to decrease the terminological ambiguity surrounding the concept of capabilities. The process of capability creation and development with an emphasis on learning is brought forward. Further, capability typologies, in terms of substantive, managerial and dynamic capabilities, are presented to add specificity to the kinds of capabilities that are created and developed within a subsidiary.Originality/valueClarifying the concept of capability and how capabilities are formed by using advancements in the literature is important to add precision to the literature on the evolution of subsidiaries.
Effect of 3D printer enabled surface morphology and composition on coral growth in artificial reefs
Authors: Matus Ilse Valenzuela , Lino Alves Jorge , Góis Joaquim , Barata da Rocha Augusto , Neto Rui , Da Silva Mota Carlos 
Published: March 2021

Purpose
The purpose of this paper is to prove and qualify the influence of textured surface substrates morphology and chemical composition on the growth and propagation of transplanted corals. Use additive manufacturing and silicone moulds for converting three-dimensional samples into limestone mortar with white Portland cement substrates for coral growth.

Design/methodology/approach
Tiles samples were designed and printed with different geometries and textures inspired by nature marine environment. Commercial coral frag tiles were analysed through scanning electron microscopy (SEM) to identify the main chemical elements. Raw materials and coral species were selected. New base substrates were manufactured and deployed into a closed-circuit aquarium to monitor the coral weekly evolution process and analyse the results obtained.

Findings
Experimental results provided positive statistical parameters for future implementation tests, concluding that the intensity of textured surface, interfered favourably in the coralline algae biofilm growth. The chemical composition and design of the substrates were determinant factors for successful coral propagation. Recesses and cavities mimic the natural rocks aspect and promoted the presence and interaction of other species that favour the richness of the ecosystem.

Originality/value
Additive manufacturing provided an innovative method of production for ecology restoration areas, allowing rapid prototyping of substrates with high complexity morphologies, a critical and fundamental attribute to guarantee coral growth and Crustose Coralline Algae. The result of this study showed the feasibility of this approach using three-dimensional printing technologies.