bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational design of nanoscale rotational mechanics in de novo protein assemblies
Authors: Courbet A. , Hansen J. , Hsia Y. , Bethel N. , Park YJ. , Xu C. , Moyer A. , Boyken S.E. , Ueda G. , Nattermann U. , Nagarajan D. , Silva D. , Sheffler W. , Quispe J. , King N. , Bradley P. , Veesler D. , Kollman J. , Baker D. 
Published: November 2021

AbstractNatural nanomachines like the F1/F0-ATPase contain protein components that undergo rotation relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein rotary machinery from designed axle and ring components. Using cryoelectron microscopy, we find that axle-ring systems assemble as designed and populate diverse rotational states depending on symmetry match or mismatch and the designed interface energy landscape. These mechanical systems with internal rotational degrees of freedom are a step towards the systematic design of genetically encodable nanomachines.One-Sentence SummaryComputationally designed self-assembling protein rotary machines sample internal degrees of freedom sculpted within the energy landscape.
Multi-omic rejuvenation and lifespan extension upon exposure to youthful circulation
Authors: Zhang Bohan , Lee David E. , Trapp Alexandre , Tyshkovskiy Alexander , Lu Ake T. , Bareja Akshay , Kerepesi Csaba , Katz Lauren H. , Shindyapina Anastasia V. , Dmitriev Sergey E. , Baht Gurpreet S. , Horvath Steve , Gladyshev Vadim N. , White James P. 
Published: November 2021

SUMMARYHeterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on the biological age of organisms and their long-term health remains unknown. Here, we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs. Old detached mice exhibited improved physiological parameters and lived longer than control isochronic mice. HPB drastically reduced the biological age of blood and liver based on epigenetic analyses across several clock models on two independent platforms; remarkably, this rejuvenation effect persisted even after 2 months of detachment. Transcriptomic and epigenomic profiles of anastomosed mice showed an intermediate phenotype between old and young, suggesting a comprehensive multi-omic rejuvenation effect. In addition, old HPB mice showed transcriptome changes opposite to aging, but akin to several lifespan-extending interventions. Altogether, we reveal that long-term HPB can decrease the biological age of mice, in part through long-lasting epigenetic and transcriptome remodeling, culminating in the extension of lifespan and healthspan.
The abiotic and biotic environment together predict plant, mammal, and bird diversity and turnover across the United States
Authors: Gallinat Amanda S. , Pearse William D. 
Published: November 2021

AbstractThe distribution of taxonomic, phylogenetic, and functional biodiversity results from a combination of abiotic and biotic drivers which are scale dependent. Parsing the relative influence of these drivers is critical to understanding the processes underlying species assembly and generating predictions of biodiversity across taxonomic groups and for novel sites. However, doing so requires data that capture a spatial extent large enough to reflect broad-scale dynamics such as speciation and biogeography, and a spatial grain fine enough to detect local-scale dynamics like environmental filtering and biotic interactions. We used species inventories of vascular plants, birds, and mammals collected by the U.S. National Ecological Observatory Network (NEON) at 38 terrestrial field sites, to explore the processes underlying taxonomic, phylogenetic, and functional diversity and turnover. We found that, for both species richness (alpha-diversity) and turnover (beta-diversity), taxonomic, phylogenetic, and functional diversity are weak proxies for one-another, and thus may capture different species assembly processes. All diversity metrics were best predicted by a combination of abiotic and biotic variables. Taxonomic and phylogenetic richness tended to be higher at warmer, wetter sites, reflecting the role energy inputs play in driving broad-scale diversity. However, plant diversity was negatively correlated with bird phylogenetic and mammal functional diversity, implying trait conservation in plant communities may limit niche availability for consumer species. Equally, turnover in bird and mammal species across sites were associated with plant turnover. That the biodiversity of one taxon is predictive of another across these North American sites, even when controlling for environment, supports a role for the cross-clade biotic environment in driving species assembly.
Multiscale profiling of enzyme activity in cancer
Authors: Soleimany Ava P. , Kirkpatrick Jesse D. , Wang Cathy S. , Jaeger Alex M. , Su Susan , Naranjo Santiago , Zhong Qian , Cabana Christina M. , Jacks Tyler , Bhatia Sangeeta N. 
Published: November 2021

AbstractDiverse processes in cancer are mediated by enzymes, which most proximally exert their function through their activity. Methods to quantify enzyme activity, rather than just expression, are therefore critical to our ability to understand the pathological roles of enzymes in cancer and to harness this class of biomolecules as diagnostic and therapeutic targets. Here we present an integrated set of methods for measuring specific enzyme activities across the organism, tissue, and cellular levels, which we unify into a methodological hierarchy to facilitate biological discovery. We focus on proteases for method development and validate our approach through the study of tumor progression and treatment response in an autochthonous model of Alk-mutant lung cancer. To quantitatively measure activity dynamics over time, we engineered multiplexed, peptide-based nanosensors to query protease activity in vivo. Machine learning analysis of sensor measurements revealed dramatic protease dysregulation in lung cancer, including significantly enhanced proteolytic cleavage of one peptide, S1 (Padj < 0.0001), which returned to healthy levels within three days after initiation of targeted therapy. Next, to link these organism-level observations to the in situ context, we established a multiplexed assay for on-tissue localization of enzyme activity and pinpointed S1 cleavage to endothelial cells and pericytes of the tumor vasculature. Lastly, to directly link enzyme activity measurements to cellular phenotype, we designed a high-throughput method to isolate and characterize proteolytically active cells, uncovering profound upregulation of pro-angiogenic transcriptional programs in S1-positive cells. Together, these methods allowed us to discover that protease production by angiogenic vasculature responds rapidly to targeted therapy against oncogene-addicted tumor cells, identifying a highly dynamic interplay between tumor cells and their microenvironment. This work provides a generalizable framework to functionally characterize enzyme activity in cancer.
BeeDNA: microfluidic environmental DNA metabarcoding as a tool for connecting plant and pollinator communities
Authors: Harper Lynsey R. , Niemiller Matthew L. , Benito Joseph B. , Paddock Lauren E. , Knittle E. , Molano-Flores Brenda , Davis Mark A. 
Published: November 2021

AbstractPollinators are imperiled by global declines that can reduce plant reproduction, erode essential ecosystem services and resilience, and drive economic losses. Monitoring pollinator biodiversity trends is key for adaptive conservation and management, but conventional surveys are often costly, time consuming, and require taxonomic expertise. Environmental DNA (eDNA) metabarcoding surveys are booming due to their rapidity, non-invasiveness, and cost efficiency. Microfluidic technology allows multiple primer sets from different markers to be used in eDNA metabarcoding for more comprehensive species inventories whilst minimizing biases associated with individual primer sets. We evaluated microfluidic eDNA metabarcoding for pollinator community monitoring by introducing a bumblebee colony to a greenhouse flower assemblage and sampling natural flower plots. We collected nectar draws, flower swabs, or whole flower heads from four flowering species, including two occurring in both the greenhouse and field. Samples were processed using two eDNA isolation protocols before amplification with 15 primer sets for two markers (COI and 16S). Microfluidic eDNA metabarcoding detected the target bumblebee and greenhouse insects as well as common regional arthropods. Pollinator detection was maximized using whole flower heads preserved in ATL buffer and extracted with a modified Qiagen®DNeasy protocol for amplification with COI primers. eDNA surveillance could enhance pollinator assessment by detecting protected and endangered species and being more applicable to remote, inaccessible locations, whilst reducing survey time, effort, and expense. Microfluidic eDNA metabarcoding requires optimization to address remaining efficacy concerns but this approach shows potential in revealing complex networks underpinning critical ecosystem functions and services, enabling more accurate assessments of ecosystem resilience.
Lactate production can function to increase human epithelial cell iron concentration
Authors: Ghio Caroline , Soukup Joleen M. , Dailey Lisa A. , Ghio Andrew J. , Schreinemachers Dina M. , Koppes Ryan A. , Koppes Abigail N. 
Published: November 2021

AbstractIron is an essential micronutrient required by every cell, inclusive of both prokaryotes and eukaryotes. Under conditions of limited iron availability, plants and microbes evolved mechanisms to acquire iron which include carbon metabolism reprogramming, with the activity of several enzymes involved in the Krebs cycle and the glycolytic pathway being stimulated by metal deficiency. Following release, resultant carboxylates/hydroxycarboxylates can function as ligands to complex iron and facilitate its solubilization and uptake, reversing the deficiency. Human epithelial tissue may produce lactate, a hydroxycarboxylate, during absolute and functional iron deficiency in an attempt to import metal to reverse limited availability. Here we investigate 1) if lactate can increase cell metal import, 2) if lactic dehydrogenase (LDH) activity in and lactate production by cells correspond to metal availability, and 3) if blood concentrations of LDH in a human cohort correlate with indices of iron homeostasis. Exposures of Caco-2 cells to both Na lactate and ferric ammonium citrate (FAC) increased metal import relative to FAC alone. Fumaric, isocitric, malic, and succinic acid exposure revealed that FAC co-incubation similarly increased iron import relative to FAC alone. Increased iron import following exposures to Na lactate and FAC elevated both ferritin and metal associated with mitochondria. LDH in Caco-2 cell scrapings did not change after exposure to deferoxamine but decreased with 24 hr exposure to FAC. Lactate levels in both the supernatants and cell scrapings revealed decreased levels at 4, 8, and 24 hr with FAC. In the National Health and Nutrition Examination Survey (NHANES 2005-2010), Spearman correlations demonstrated significant negative relationships between LDH concentrations and serum iron. We conclude that iron import in human cells can involve lactate, LDH activity can reflect the availability of this metal, and blood LDH concentrations can correlate with indices of iron homeostasis.
Functionalizing silica sol-gel with entrapped plant virus-based immunosorbent nanoparticles
Authors: McNulty Matthew J. , Hamada Naomi , Delzio Jesse , McKee Liber , Nandi Somen , Longo Marjorie L. , McDonald Karen A. 
Published: November 2021

AbstractAdvancements in understanding and engineering of virus-based nanomaterials (VBNs) for biomedical applications motivate a need to explore the interfaces between VBNs and other biomedically-relevant chemistries and materials. While several strategies have been used to investigate some of these interfaces with promising initial results, including VBN-containing slow-release implants and VBN-activated bioceramic bone scaffolds, there remains a need to establish VBN-immobilized three dimensional materials that exhibit improved stability and diffusion characteristics for biosensing and other analyte-capture applications. Silica sol-gel chemistries have been researched for biomedical applications over several decades and are well understood; various cellular organisms and biomolecules (e.g., bacteria, algae, enzymes) have been immobilized in silica sol-gels to improve viability, activity, and form factor (i.e., ease of use). Here we present the immobilization of an antibody-binding VBN in silica sol-gel by pore confinement. We have shown that the resulting system is sufficiently diffuse to allow antibodies to migrate in and out of the matrix. We also show that the immobilized VBN is capable of antibody binding and elution functionality under different buffer conditions for multiple use cycles. The promising results of the VBN and silica sol-gel interface indicate a general applicability for VBN-based bioseparations and biosensing applications.
Competition and coevolution drive the evolution and the diversification of CRISPR immunity
Authors: Guillemet Martin , Chabas Hélène , Nicot Antoine , Gatchich François , Ortega-Abboud Enrique , Buus Cornelia , Hindhede Lotte , Rousseau Geneviève M. , Bataillon Thomas , Moineau Sylvain , Gandon Sylvain 
Published: November 2021

AbstractThe diversity of resistance challenges the ability of pathogens to spread and to exploit host populations [1–3]. Yet, how this host diversity evolves over time remains unclear because it depends on the interplay between intraspecific competition among host genotypes and coevolution with pathogens. Here we study experimentally the effect of coevolving phage populations on the diversification of bacterial CRISPR immunity across space and time. We demonstrate that the negative-frequency-dependent selection generated by coevolution is a powerful force that maintains host resistance diversity and selects for new resistance mutations in the host. We also find that host evolution is driven by asymmetries in competitive abilities among different host genotypes. Even if the fittest host genotypes are targeted preferentially by the evolving phages they often escape extinctions through the acquisition of new CRISPR immunity. Together, these fluctuating selective pressures maintain diversity, but not by preserving the pre-existing host composition. Instead, we repeatedly observe the introduction of new resistance genotypes stemming from the fittest hosts in each population. These results highlight the importance of competition on the transient dynamics of host-pathogen coevolution.
How bank capital structure decision-making change in recessions: Covid-19 evidence from Pakistan
Authors: Mohammad Khalil Ullah 
Published: November 2021

PurposeThis study contributes to existing literature by investigating bank capital structure dynamics during the Covid-19 pandemic. The role of contemporary bank-specific determinants of capital structure during this period is analyzed.Design/methodology/approachAn independent t-test is carried out to check the response of bank leverage to the crisis. Using fixed effect estimation and difference general method of moments (GMM), the impact of the shock is examined. An unbalanced quarterly data set from 2016q1 to 2020q3 of all commercial banks in Pakistan is used.FindingsThe study finds that due to procyclicality of capital, during the Covid-19 crisis, the banks preempted a fall in capital and improved their capital positions. The role of bank specific variables in determining capital structure like profitability, size and competition weakened during this period. Evidence suggests that policy rate intervention by the central bank was a significant factor in capital structure decisions during the Covid-19 period. The study finds that macroeconomic shocks have significant impact on capital structure decision-making of banks which goes beyond the bank-specific factors.Originality/valueIt finds evidence of a moderating role of monetary policy in capital structure decision-making which has not been previously highlighted in literature. Monetary policy is found to become an important factor deciding the capital structure of banks during the Covid-19 first 3 quarters. This study also explores the impact of Covid-19 on the bank-specific determinants of capital structure of banks.
Obtaining secure business process models from an enterprise architecture considering security requirements
Authors: San Martín Luis , Rodríguez Alfonso , Caro Angélica , Velásquez Ignacio 
Published: November 2021

PurposeSecurity requirements play an important role in software development. These can be specified both in enterprise architecture models and in business processes. Enterprises increasingly carry out larger amounts of business processes where security plays a major role. Business processes including security can be automatically obtained from enterprise architecture models by applying a model-driven architecture approach, through a CIM to CIM transformation. The aim of this article is to present the specification of transformation rules for the correspondence between enterprise architecture and business process model elements focusing on security.Design/methodology/approachThis work utilizes motivational aspects of the ArchiMate language to model security in the business layer of enterprise architectures. Next, a set of transformation rules defined with the Atlas Transformation Language are utilized to obtain the correspondence of the enterprise architecture elements in a business process, modelled with a security extension of BPMN.FindingsA total of 19 transformation rules have been defined. These rules are more complex than element to element relations, as they take into consideration the context of the elements for establishing the correspondence. Additionally, the prototype of a tool that allows the automatic transformation between both models has been developed.Originality/valueThe results of this work demonstrate the possibility to tackle complex transformations between both models, as previous literature focuses on semantic correspondences. Moreover, the obtained models can be of use for software developers applying the model-driven approach.
Two-dimensional steady-state thermal analytical model of permanent-magnet synchronous machines operating in generator mode
Authors: Djelloul Khedda Zakarya , Boughrara Kamel , Dubas Frédéric , Guo Baocheng , Ailam El Hadj 
Published: November 2021

Purpose
Thermal analysis of electrical machines is usually performed by using numerical methods or lumped parameter thermal networks depending on the desired accuracy. The analytical prediction of temperature distribution based on the formal resolution of thermal partial differential equations (PDEs) by the harmonic modeling technique (or the Fourier method) is uncommon in electrical machines. Therefore, this paper aims to present a two-dimensional (2D) analytical model of steady-state temperature distribution for permanent-magnet (PM) synchronous machines (PMSM) operating in generator mode.

Design/methodology/approach
The proposed model is based on the multi-layer models with the convolution theorem (i.e. Cauchy’s product theorem) by using complex Fourier’s series and the separation of variables method. This technique takes into the different thermal conductivities of the machine parts. The heat sources are determined by calculating the different power losses in the PMSM with the finite-element method (FEM).

Findings
To validate the proposed analytical model, the analytical results are compared with those obtained by thermal FEM. The comparisons show good results of the proposed model.

Originality/value
A new 2D analytical model based on the PDE in steady-state for full prediction of temperature distribution in the PMSM takes into account the heat transfer by conduction, convection and radiation.
A model to guide the effective use of a business case for IT projects
Authors: Einhorn Frank David , Meredith Jack , Marnewick Carl 
Published: November 2021

PurposeThe paper responds to calls in recent research for a model that shows how the business case should be used throughout the project's lifetime to achieve sound governance and thereby project success. The aim of the paper is to advance theory about the effective use of the business case.Design/methodology/approachBesides the processes and information required, the literature identified 43 organizational facilitating factors, structured into 5 categories, which are required for effective use of the business case. To offer a useful model, the authors' approach was to do a factor analysis, based on existing survey data, to reduce the number of facilitators and to validate their categorization.FindingsThe findings of the paper were as follows: (1) the classification of the proposed facilitating factors was validated; (2) the number of facilitators needed to ensure that the business case is used effectively was substantially reduced and (3) a “business case effectiveness model” is proposed to clarify the relationship between the organizational facilitating factors, the business case processes and the information required to effectively use the business case.Originality/valueThis is the first time that a business case effectiveness model has been proposed. Besides consolidating business case theory, it can be used to guide people and organizations on simple, affordable ways to improve their use of the business case to achieve sound governance and hence business/information technology project success.
Conception of circular economy obstacles in context of supply chain: a case of rubber industry
Authors: Agarwal Somesh , Tyagi Mohit , Garg R.K. 
Published: November 2021

PurposeAdopting the circular economy (CE) notion in the supply chain perspective is necessary for the sustainability viewpoint. However, such practices are deficient, especially in developing countries like India, because of several obstacles. The purpose of this study was to create an approach for circular supply chain management (CSCM) adaption in Indian rubber industries by identifying and evaluating its associated obstacles.Design/methodology/approachA hybrid approach of analytic hierarchy process (AHP) and the grey-based ELECTRE method had been employed in this research to obtain the mutual rankings of the identified obstacles based on their impressions on the CSCM prosperity criteria through a case study and involving diverse expert's opinions.FindingsPresented study's findings illustrate that “Lack of consumer knowledge and consciousness towards environmental sustainability” was found to be the top-ranked obstacle followed by “Unwillingness towards supply chain re-structuring”.Research limitations/implicationsThe obstacles' prioritized rankings could help leaders to create sequential strategies for adapting a resilient CSCM structure by systematically eliminating these obstacles. Moreover, the pinpointed critical obstacles could be investigated further in separate studies and generate future studies' scope.Originality/valueDuring the extensive literature survey, it had been found that the CSCM practices are in the fledgling stage in the developing country's context. Moreover, studies related to CSCM adaption in rubber-based manufacturing industries were much lacking. Presented work is peculiar, aiming to accelerate the CSCM adaption in the industrial rubber sector in developing countries like India.