bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of adaptive gene amplification by origin firing under replication fork constraint
Authors: Whale Alex J. , King Michelle , Hull Ryan M. , Krueger Felix , Houseley Jonathan 
Published: March 2021

AbstractAdaptive mutations can cause drug resistance in cancers and pathogens, and increase the tolerance of agricultural pests and diseases to chemical treatment. When and how adaptive mutations form is often hard to discern, but we have shown that adaptive copy number amplification of the copper resistance geneCUP1occurs in response to environmental copper due toCUP1transcriptional activation. Here we dissect the mechanism by whichCUP1transcription in budding yeast stimulates copy number variation (CNV). We show that transcriptionally stimulated CNV requires TREX-2 and Mediator, such that cells lacking TREX-2 or Mediator respond normally to copper but cannot acquire increased resistance. Mediator and TREX-2 cause replication stress by tethering transcribed loci to nuclear pores, a process known as gene gating, and transcription at theCUP1locus causes a TREX-2-dependent accumulation of replication forks indicative of replication fork stalling. TREX-2-dependentCUP1gene amplification occurs by a Rad52 and Rad51-mediated homologous recombination mechanism that is enhanced by histone H3K56 acetylation and repressed by Pol32, factors known to alter the frequency of template switching during break induced replication (BIR).CUP1amplification is also critically dependent on late firing replication origins present in theCUP1repeats, and mutations that remove or inactivate these origins strongly suppress the acquisition of copper resistance. We propose that replicative stress imposed by nuclear pore association causes replication bubbles from these origins to collapse soon after firing, leaving an epigenetic scar of H3K56 acetylation that promotes template switching during later break induced replication events. The capacity for inefficient replication origins to promote copy number variation renders certain genomic regions more fragile than others, and therefore more likely to undergo adaptive evolution throughde novogene amplification.
Stable nitrogen isotope analysis of amino acids as a new tool to clarify complex parasite-host interactions within marine food webs
Authors: Riekenberg Philip , Joling Tijs , IJsseldijk Lonneke L. , Waser Andreas M. , van der Meer Marcel , Thieltges David W. 
Published: March 2021

AbstractTraditional bulk isotopic analysis is a pivotal tool for mapping consumer-resource interactions in food webs but has largely failed to adequately describe parasite-host relationships. Thus, parasite-host interactions remain largely understudied in food web frameworks despite these relationships increasing linkage density, connectance, and ecosystem biomass. Compound-specific stable isotopes from amino acids provides a promising novel approach that may aid in mapping parasitic interactions in food webs. However, to date it has not been applied to parasitic trophic interactions.Here we use a combination of traditional bulk stable isotope analyses and compound-specific isotopic analysis of the nitrogen in amino acids to examine resource use and trophic interactions of five parasites from three hosts from a marine coastal food web (Wadden Sea, European Atlantic). By comparing isotopic compositions of bulk and amino acid nitrogen, we aimed to characterize isotopic fractionation occurring between parasites and their hosts and to clarify the trophic position of the parasites.Our results showed that parasitic trophic interactions were more accurately identified when using compound-specific stable isotope analysis due to removal of underlying source isotopic variation for both parasites and hosts, and avoidance of the averaging of amino acid variability in bulk analyses through use of multiple trophic amino acids. The compound-specific method provided clear trophic discrimination factors in comparison to bulk isotope methods, however, those differences varied significantly among parasite species.Amino acid compound specific isotope analysis has widely been applied to examine trophic position within food webs, but our analyses suggest that the method is particularly useful for clarifying the feeding strategies for parasitic species. Baseline isotopic information provided by source amino acids allows clear identification of the fractionation occurring due to parasite metabolism by integrating underlying isotopic variations from the host tissues. However, like for bulk isotope analysis, the application of a universal trophic discrimination factor to parasite-host relationships remains inappropriate for compound-specific stable isotope analysis. Despite this limitation, compound-specific stable isotope analysis is and will continue to be a valuable tool to increase our understanding of parasitic interactions in marine food webs.
An Essential Role of UBXN3B in B Lymphopoiesis
Authors: Geng Tingting , Yang Duomeng , Lin Tao , Harrison Andrew G. , Wang Binsheng , Torrance Blake , Wang Kepeng , Wang Yanlin , Yang Long , Haynes Laura , Cheng Gong , Vella Anthony T. , Fikrig Erol , Wang Penghua 
Published: March 2021

ABSTRACTHematopoiesis is finely regulated to enable timely production of the right numbers and types of mature immune cells to maintain tissue homeostasis. Dysregulated hematopoiesis may compromise antiviral immunity and/or exacerbate immunopathogenesis. Herein, we report an essential role of UBXN3B in maintenance of hematopoietic homeostasis and restriction of immunopathogenesis during respiratory viral infection.Ubxn3bdeficient (Ubxn3b−/−) mice are highly vulnerable to SARS-CoV-2 and influenza A infection, characterized by more severe lung immunopathology, lower virus-specific IgG, significantly fewer B cells, but more myeloid cells thanUbxn3b+/+littermates. This aberrant immune compartmentalization is recapitulated in uninfectedUbxn3b−/−mice. Mechanistically, UBXN3B controls precursor B-I (pre-BI) transition to pre-BII and subsequent proliferation in a cell-intrinsic manner, by maintaining BLNK protein stability and pre-BCR signaling. These results reveal an essential role of UBXN3B for the early stage of B cell development.
Decreased KATPchannel activity contributes to the low glucose threshold for insulin secretion of rat neonatal islets
Authors: Yang Juxiang , Hammoud Batoul , Li Changhong , Ridler Abigail , Yau Daphne , Kim Junil , Won Kyoung-Jae , Stanley Charles A. , Hoshi Toshinori , Stanescu Diana E. 
Published: March 2021

AbstractTransitional hypoglycemia in normal newborns occurs in the first 3 days of life and has clinical features consistent with hyperinsulinism. We found a lower threshold for glucose-stimulated insulin secretion from freshly isolated embryonic day (E)22 rat islets, which persisted into the first postnatal days. The threshold reached the adult level by postnatal day (P)14. Culturing P14 islets also decreased the glucose threshold. Freshly isolated P1 rat islets had a lower threshold for insulin secretion in response to BCH (2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid), a non-metabolizable leucine analog, and diminished insulin release in response to tolbutamide, an inhibitor of β-cell KATPchannels. These findings suggested that decreased KATPchannel function could be responsible for the lower glucose threshold for insulin secretion. Single-cell transcriptomic analysis did not reveal a lower expression of KATPsubunit genes in E22 compared to P14 β-cells. The investigation of electrophysiological characteristics of dispersed β-cells showed that early neonatal and cultured cells had fewer functional KATPchannels per unit membrane area. Our findings suggest that decreased surface density of KATPchannels may contribute to the observed differences in glucose threshold for insulin release.
DMWAS: Deep Machine learning omics Wide Association Study & Feature set optimization by clustering & univariate association for Biomarkers discovery as tested on GTEx pilot dataset for death due to heart-attack
Authors: Singh Abhishek Narain 
Published: March 2021

AbstractUnivariate and multivariate methods for association of the genomic variations with the end-or-endo phenotype have been widely used for genome wide association studies. In addition to encoding the SNPs, we advocate usage of clustering as a novel method to encode the structural variations, SVs, in genomes, such as the deletions and insertions polymorphism (DIPs), Copy Number Variations (CNVs), translocation, inversion, etc., that can be used as an independent feature variable value for downstream computation by artificial intelligence methods to predict the endo-or-end phenotype. We introduce a clustering based encoding scheme for structural variations and omics based analysis. We conducted a complete all genomic variants association with the phenotype using deep learning and other machine learning techniques, though other methods such as genetic algorithm can also be applied. Applying this encoding of SVs and one-hot encoding of SNPs on GTEx V7 pilot DNA variation dataset, we were able to get high accuracy using various methods of DMWAS, and particularly found logistic regression to work the best for death due to heart-attack (MHHRTATT) phenotype. The genomic variants acting as feature sets were then arranged in descending order of power of impact on the disease or trait phenotype, which we call optimization and that also uses top univariate association into account. Variant Id P1_M_061510_3_402_P at chromosome 3 & position 192063195 was found to be most highly associated to MHHRTATT. We present here the top ten optimized genomic variant feature set for the MHHRTATT phenotypic cause of death.
The influence of organizational justice and decision latitude on expatriate organizational commitment and job performance
Authors: AlMazrouei Hanan , Zacca Robert 
Published: March 2021

PurposeThe purpose of this paper is to study the influence of organizational justice and decision latitude on expatriate organization commitment and job performance.Design/methodology/approachData were collected from 175 nonmanagerial-level expatriate employees in Dubai, UAE using a purposive sampling approach. A structural equation model with partial least squared analysis was utilized to test the hypotheses.FindingsThe results show that decision latitude partially mediates the relationship between organization justice and organizational commitment and fully mediates the relationship between organization justice and job performance.Research limitations/implicationsData were collected from a cross sectional sample in UAE, and hence, the generalizability of the results to other contexts may be limited.Practical implicationsThe research study suggests ways in which human resource managers and practitioners can develop a stronger awareness of the importance of decision latitude in employee decision-making and the role it plays in promoting employees' commitment and job performance given perceived organizational justice.Originality/valueThe present research is among the first of its kind to examine the study variables within the nonmanagerial expatriate context.
Problems and Perspectives of a Theory of Transformational Processes of Bildung
Authors: Koller Hans‐Christoph 
Published: March 2021

AbstractIn this essay, Hans‐Christoph Koller presents a concept of transformational processes of Bildung in an attempt to redefine the German notion of Bildung referring to actual social conditions of educational processes. According to this conception, Bildung is a transformation of world‐ and self‐relations that can come about when subjects are confronted with problems for which they have no established routines of engagement. With reference to theories of Pierre Bourdieu, Bernhard Waldenfels, and Ulrich Oevermann, Koller looks for answers to three questions: (1) Which concepts and theories are able to adequately grasp the world‐ and self‐relations of subjects going through processes of Bildung? (2) How can the problems that trigger processes of Bildung and that challenge subjects to transform be determined more precisely? (3) How exactly does the emergence of new figures of world‐ and self‐relations take place when we “successfully” complete a process of Bildung? Finally, the essay concludes with an attempt to clarify the normative implications of this theory.
Scale‐dependent patterns and drivers of plant diversity in steppe grasslands of the Central Alborz Mts., Iran
Authors: Talebi Amir , Attar Farideh , Naqinezhad Alireza , Dembicz Iwona , Dengler Jürgen 
Published: March 2021

AbstractQuestionsWhich are the main environmental drivers of plot scale alpha‐diversity and beta‐diversity in arid steppes? Do they vary between functional groups and across grain sizes?LocationCentral Alborz Mts., N Iran.MethodsWe sampled vascular plants in 23 nested‐plot series with nine grain sizes from 0.0001 m2 to 1,000 m2 and 334 25‐m2 vegetation plots in different vegetation types of natural dry steppe grasslands. To assess beta‐diversity, we calculated overall and local z‐values of species–area relationships modelled with the power function. As potential drivers of species richness and z‐values, we used topographic, edaphic and climatic variables as well as management types. Generalised linear models (GLMs), and generalised linear mixed‐effect models (GLMMs) if spatial autocorrelation occurred, were used in a multi‐model inference framework to build statistical models.ResultsMean annual temperature was the most important predictor for total species richness and richness of functional groups across grain sizes, with a unimodal relationship for grains of 25–100 m2, but mostly increasing for finer grain sizes. Precipitation of the driest month and cover of gravel were influential drivers at the smallest grains. The explanatory power of regression models increased towards larger grain sizes. The overall z‐values showed a high positive relationship with precipitation of the driest month, mean annual temperature and mean soil depth.ConclusionsRelated to our more than 3,000‐m elevational gradient, mean annual temperature (highly negatively correlated with elevation) was the most influential and consistent driver across functional groups and grain sizes with mostly unimodal relationships for alpha‐diversity and a positive effect on beta‐diversity. Findings for other drivers were less consistent, and overall the explained variance of our models was relatively low, calling for additional studies to determine whether in the arid grasslands of Iran stochasticity is just higher or there are additional important variables.
Sirtuin GdSir2.4 participates in the regulation of rRNA transcription in the Giardia duodenalis parasite
Authors: Lagunas‐Rangel Francisco Alejandro , Yee Janet , Bazán‐Tejeda María Luisa , García‐Villa Enrique , Bermúdez‐Cruz Rosa María 
Published: March 2021

AbstractGiardia duodenalis is a parasite of great medical interest due to the number of infections it causes worldwide each year. Although research on epigenetic mechanisms in this protist has only begun recently, epigenetic regulation has already been shown to have important roles in encystation, antigenic variation, and resistance to antibiotics in Giardia. In this work, we show that a Giardia ortholog of Sir2, GdSir2.4, is involved in the silencing of rRNA expression. Our results demonstrate that GdSir2.4 localizes to the nucleolus, and its binding to the intergenic spacer region of the rDNA is associated with the deacetylation of the chromatin in this region. Given the importance of the regulation of rRNA expression to maintain adequate levels of ribosomes and genomic stability within the cells, GdSir2.4 can be considered a target to create new therapeutic agents against this parasite.
Validation of a novel patient‐operated device for measuring skin barrier function in atopic dermatitis
Authors: Grinich Erin E. , Topham Christina , Haynes Dylan , Chung Janice , Latour Emile , Simpson Eric L. 
Published: March 2021

AbstractBackgroundTransepidermal water loss (TEWL) and capacitance are used in atopic dermatitis (AD) trials to provide objective data on clinical change and response to therapy. Many barrier devices are costly, limiting their utility. GPSkin is a novel low‐cost, patient‐operable device that measures both TEWL and capacitance via smartphone application.ObjectiveThis validation study investigated the correlation of GPSkin with the AquaFlux and Corneometer, and the reliability of these devices, in patients with AD.MethodsFifty AD patients with varying disease severity performed self‐measurements with GPSkin, while investigators collected data with all 3 devices, on both nonlesional and lesional skin.ConclusionGPSkin and AquaFlux demonstrated strong correlation for TEWL on nonlesional and lesional skin by Spearman's correlation (rs), independent of device user. For capacitance, GPSkin and the Corneometer showed moderate correlation when obtained by patients, yet a strong correlation when obtained by a clinician. Despite good correlation, GPSkin showed poor agreement with both the AquaFlux and Corneometer in Bland‐Altman plots. GPSkin underestimated both TEWL and capacitance. Overall, the devices had good test‐retest reliability. None of the devices could discriminate between AD severity states. While GPSkin marks an exciting advancement in barrier technology, further study is needed for validation on AD skin.
Thermal Design of Material Quality in Rapid Prototyping Techniques
Authors: Doumanidis Charalabos C. , Fourligkas Nikolaos 
Published: March 2021

Abstract
In thermal rapid prototyping of mechanically functional products, their geometric design must be also combined to specification of their material quality features. The material structure and properties of these parts are generated and can be specified through the dynamic temperature distribution history during the process. Such a desired thermal field cycle, prescribed by computational modeling or direct experimental measurement, can be implemented by proper scheduling of the power and motion trajectory of a heat source, usually supplied by time-sharing the thermal process torch (arc, Laser etc.). This article presents such an off-line thermal design methodology of the process conditions, based on a numerical simulation of the temperature distribution, which tracks the reference thermal field by guiding the torch to the areas of highest thermal demand. This strategy was successfully implemented in simple laminated object manufacturing on a plasma-arc laboratory setup with infrared thermal monitoring. The effects of equipment bandwidth and the potential for closed-loop thermal control of various thermal rapid prototyping methods are also addressed.
Stiffened CFRP-Panels Under Buckling Loads: Modeling, Analysis, Optimization
Authors: Eschenauer Hans A. , Weber Christof M. 
Published: March 2021

Abstract
The present paper addresses the optimal layout of stiffened fiber composite plates (Fig. 1) considering buckling constraints; these plates are increasingly applied in many fields of engineering (air- and spacecraft technology, automotive industries, boatbuilding etc.).
This particular area of structural optimization still requires substantial investigations into its fundamentals. The structural analysis alone for the treatment of this type of problems may increase to such a degree that the complete optimization process requires extremely long computation times due to the processing of a high amount of data, a fact that calls for the development of “intelligent” procedures in order to reduce the computation effort to a tolerable measure and to maintain reduplicability of the whole process. For this purpose, a so-called “constructive design model” is introduced.
Algebraic Representation of Geometric and Size Tolerances
Authors: Mullins S. H. , Anderson D. C. 
Published: March 2021

Abstract
Presented is a method for mathematically modeling mechanical component tolerances. The method translates the semantics of ANSI Y14.5M tolerances into an algebraic form. This algebraic form is suitable for either worst-case or statistical tolerance analysis and seeks to satisfy the requirements of both dimensional metrology and design analysis and synthesis. The method is illustrated by application to datum systems, position tolerances, orientation tolerances, and size tolerances.
Synthesis of Optimal Non-Orthogonal Routes
Authors: Szykman Simon , Cagan Jonathan 
Published: March 2021

Abstract
This paper introduces a novel approach to three dimensional routing optimization. Examples of routing tasks for engineering applications include routing of pipes, wires and air ducts. Traditionally, routing algorithms perform Manhattan, or orthogonal, routing. Non-orthogonal routing can be less costly than Manhattan routing and for applications such as automotive or aerospace design, Manhattan routing is impractical due to spatial limitations. The research presented in this paper uses simulated annealing as the basis of a non-orthogonal routing optimization algorithm that avoids the drawbacks associated with Manhattan routing. Several examples comparing the two approaches are given.
Operational Envelopes for Working Bodies of Mechanisms and Manipulators
Authors: Haug Edward J. , Adkins Frederick A. , Luh Chi-Mei 
Published: March 2021

Abstract
The set of all points in space that can be occupied by any point in the working body of a mechanism or manipulator is defined as its operational envelope. Criteria for points in and on the boundary of the operational envelope of working bodies with smooth boundaries are developed, for both parametric and equation representations of domains and boundaries of working bodies in two- or three-dimensional space. The criteria derived involve kinematic constraint equations for the underlying mechanism and equations that characterize the shape of the working body. A row rank deficiency condition is derived as a criterion for the boundary of the operational envelope, and numerical methods based on this condition for mapping the boundary are presented. An example involving a planar Stewart platform with a dome attached is analyzed numerically.
Automated Generation of Fixture Configuration Design
Authors: Bai Yong , Rong Yiming (Kevin) 
Published: March 2021

Abstract
Flexible fixturing is a necessary aspect of flexible manufacturing systems (FMS) and computer-integrated manufacturing systems (CIMS). Modular fixtures are most widely used in industry for job and small batch production. Computer-aided fixture design (CAFD) has become a research focus in implementing FMS and CIMS. Fixture configuration design is an important issue in CAFD. A review of the current research in CAFD indicates that one major problem impeding the automated generation of fixture configuration design is the negligence of study on fixture structures. This paper investigates fundamental structures of dowel-pin modular fixtures and fixturing characteristics of commonly-used modular fixture elements. A modular fixture element assembly relationship graph (MFEARG) is designed to represent combination relationships between fixture elements. Based on MFEARG, algorithms are developed to search all suitable fixturing unit candidates and mount them into appropriate positions on baseplate with an interference checking. A prototype system for automated design of dowel-pin modular fixture configurations is presented in this paper. Fixture design examples are given in the end of the paper.
Branching and Immovable Configurations
Authors: Holte Jennifer E. , Chase Thomas R. 
Published: March 2021

Abstract
Improvements to Chase and Mirth’s (1993) definition of branches of planar linkage mechanisms are proposed. The improvements extend the definition of branches to mechanisms where the earlier definition fails. The new definition utilizes immovable configurations and uncertainty configurations to divide a circuit into branches. Several examples are presented to demonstrate the added versatility of the new definition.