bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scalable dynamic characterization of synthetic gene circuits
Authors: Dalchau Neil , Grant Paul K. , Vaidyanathan Prashant , Spaccasassi Carlo , Gravill Colin , Phillips Andrew 
Published: May 2019

AbstractThe dynamic behavior of synthetic gene circuits plays a key role in ensuring their correct function. Although there has been substantial work on modeling dynamic behavior after circuit construction, the forward engineering of dynamic behavior remains a major challenge. Previous engineering methods have focused on quantifying average behaviors of circuits over an extended time window, however this provides a static characterization of behavior that is a poor predictor of dynamics. Here we present a method for characterizing the dynamic behavior of synthetic gene circuits, using parameter inference of dynamical system models applied to time-series measurements of cell cultures growing in microtiter plates. We demonstrate that the behaviors of simple devices can be characterized dynamically and used to predict the behaviors of more complex circuits. Specifically, we compose 23 biological parts into 9 devices and use them to design 9 synthetic gene circuits in E. coli that provide core functionality for engineering cell behavior at the population level, including relays, receivers and a degrader. We embody our method in a software package and corresponding programming language. Our method supports the notion of an inference graph for iterative inference of models as new circuits are constructed, without the need to infer all models from scratch, and lays the foundation for characterizing large libraries of synthetic gene circuits in a scalable manner.
Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis
Authors: Allen Richard J , Guillen-Guio Beatriz , Oldham Justin M , Ma Shwu-Fan , Dressen Amy , Paynton Megan L , Kraven Luke M , Obeidat Ma’en , Li Xuan , Ng Michael , Braybrooke Rebecca , Molina-Molina Maria , Hobbs Brian D , Putman Rachel K , Sakornsakolpat Phuwanat , Booth Helen L , Fahy William A , Hart Simon P , Hill Mike R , Hirani Nik , Hubbard Richard B , McAnulty Robin J , Millar Ann B , Navaratnam Vidyia , Oballa Eunice , Parfrey Helen , Saini Gauri , Whyte Moira K B , Gudmundsson Gunnar , Gudnason Vilmundur , Hatabu Hiroto , Lederer David J , Manichaikul Ani , Newell John D , O’Connor George T , Ortega Victor E , Xu Hanfei , Fingerlin Tasha E , Bossé Yohan , Hao Ke , Joubert Philippe , Nickle David C , Sin Don D , Timens Wim , Furniss Dominic , Morris Andrew P , Zondervan Krina , Hall Ian P , Sayers Ian , Tobin Martin D , Maher Toby M , Cho Michael H , Hunninghake Gary M , Schwartz David A , Yaspan Brian L , Molyneaux Philip L , Flores Carlos , Noth Imre , Jenkins R Gisli , Wain Louise V 
Published: May 2019

AbstractRationaleIdiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. The mechanisms by which this arises are poorly understood and it is likely that multiple pathways are involved. The strongest genetic association with IPF is a variant in the promoter of MUC5B where each copy of the risk allele confers a five-fold risk of disease. However, genome-wide association studies have reported additional signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion.ObjectivesTo improve our understanding of mechanisms that increase IPF susceptibility by identifying previously unreported genetic associations.Methods and measurementsWe performed the largest genome-wide association study undertaken for IPF susceptibility with a discovery stage comprising up to 2,668 IPF cases and 8,591 controls with replication in an additional 1,467 IPF cases and 11,874 controls. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF.Main resultsWe identified and replicated three new genome-wide significant (P<5×10-8) signals of association with IPF susceptibility (near KIF15, MAD1L1 and DEPTOR) and confirm associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF risk variants contribute to IPF susceptibility.ConclusionsNovel association signals support the importance of mTOR signalling in lung fibrosis and suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility.
The representation of two-body shapes in the human visual cortex
Authors: Etienne Abassi , Liuba Papeo 
Published: May 2019

AbstractHuman social nature has shaped visual perception. A signature of the relationship between vision and sociality is a particular visual sensitivity to social entities such as faces and bodies. We asked whether human vision also exhibits a special sensitivity to spatial relations that reliably correlate with social relations. In general, interacting people are more often situated face-to-face than back-to-back. Using functional MRI and behavioral measures in female and male human participants, we show that visual sensitivity to social stimuli extends to images including two bodies facing toward (vs. away from) each other. In particular, the inferior lateral occipital cortex, which is involved in visual-object perception, is organized such that the inferior portion encodes the number of bodies (one vs. two) and the superior portion is selectively sensitive to the spatial relation between bodies (facing vs. non-facing). Moreover, functionally localized, body-selective visual cortex responded to facing bodies more strongly than identical, but non-facing, bodies. In this area, multivariate pattern analysis revealed an accurate representation of body dyads with sharpening of the representation of single-body postures in facing dyads, which demonstrates an effect of visual context on the perceptual analysis of a body. Finally, the cost of body inversion (upside-down rotation) on body recognition, a behavioral signature of a specialized mechanism for body perception, was larger for facing vs. non-facing dyads. Thus, spatial relations between multiple bodies are encoded in regions for body perception and affect the way in which bodies are processed.Public Significance StatementHuman social nature has shaped visual perception. Here, we show that human vision is not only attuned to socially relevant entities, such as bodies, but also to socially relevant spatial relations between those entities. Body-selective regions of visual cortex respond more strongly to multiple bodies that appear to be interacting (i.e., face-to-face), relative to unrelated bodies, and more accurately represent single body postures in interacting scenarios. Moreover, recognition of facing bodies is particularly susceptible to perturbation by upside-down rotation, indicative of a particular visual sensitivity to the canonical appearance of facing bodies. This encoding of relations between multiple bodies in areas for body-shape recognition suggests that the visual context in which a body is encountered deeply affects its perceptual analysis.
Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage
Authors: Masoli Stefano , Tognolina Marialuisa , Laforenza Umberto , Moccia Francesco , D’Angelo Egidio 
Published: May 2019

AbstractThe cerebellar granule cells (GrCs) form an anatomically homogeneous neuronal population which, in its canonical description, discharges regularly without adaptation. We show here that GrCs in fact generate diverse response patterns to current injection and synaptic activation, ranging from adaptation to acceleration of firing. Adaptation was predicted by parameter optimization in detailed GrC computational models based on the available knowledge on GrC ionic channels. The models also predicted that acceleration required the involvement of additional mechanisms. We found that yet unrecognized TRPM4 currents in accelerating GrCs could specifically account for firing acceleration. Moreover, adapting GrCs were better in transmitting high-frequency mossy fiber (MF) bursts over a background discharge than accelerating GrCs. This implied that different electroresponsive patterns corresponded to specific synaptic properties reflecting different neurotransmitter release probability. The correspondence of pre- and post-synaptic properties generated effective MF-GrC transmission channels, which could enrich the processing of input spike patterns and enhance spatio-temporal recoding at the cerebellar input stage.
Animal model and therapeutic prospects for left ventricular hypertrophy and associated renal complication
Authors: Ahmad Ashfaq , Riaz Zainab , Sattar Munavvar Abdul , Khan Safia Akhtar , John Edward James , Arshad Sumbal , Shah Syed Tahir Abbas , Rafiq Muhammad Arshad , Azam Maleeha , Qamar Raheel 
Published: May 2019

AbstractCardiac and renal dysfunction often co-occur and considerably worsen the prognosis leading to difficulty in therapy in left ventricular hypertrophy (LVH). The aim of this study was to elucidate changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and gasotransmitter, H2S (hydrogen sulphide) and NO (nitric oxide) and combined (H2S+NO), treatment of rat myocardium and renal tissues. LVH rat models were generated and were treated with H2S and NO. Relative gene expression was quantified. Heart and renal physical indices were significantly modified under individual as well as combined H2S+NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly increased (P<0.05) in myocardia and kidneys of LVH rats, while individual and combined H2S+NO treatment reduced gene expression to normal/near to normal values. The cardiac remodeling genes MYH7, TGFβ, SMAD4 and BRG1 expression were significantly up-regulated (P<0.05) in the myocardia of LVH and combined H2S+NO treatment, which recovered the normal/near to normal expression more effectively as compared to individual treatments. Interestingly, individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was significantly up-regulated in LVH rats (P<0.05). The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment in LVH rat model indicates important therapeutic potential of combined treatment with H2S+NO gasotransmitters in hypertension and cardiac hypertrophy associated with renal complications.
Computational simulation of the reactive oxygen species and redox network in the regulation of chloroplast metabolism
Authors: Gerken Melanie , Kakorin Sergej , Chibani Kamel , Dietz Karl-Josef 
Published: May 2019

AbstractCells contain a thiol redox regulatory network to coordinate metabolic and developmental activities with exogenous and endogenous cues. This network controls the redox state and activity of many target proteins. Electrons are fed into the network from metabolism and reach the target proteins via redox transmitters such as thioredoxin (TRX) and NADPH-dependent thioredoxin reductases (NTR). Electrons are drained from the network by reactive oxygen species (ROS) through thiol peroxidases, e.g., peroxiredoxins (PRX). Mathematical modeling promises access to quantitative understanding of the network function and was implemented for the photosynthesizing chloroplast by using published kinetic parameters combined with fitting to known biochemical data. Two networks were assembled, namely the ferredoxin (FDX), FDX-dependent TRX reductase (FTR), TRX, fructose-1,6-bisphosphatase pathway with 2-cysteine PRX/ROS as oxidant, and separately the FDX, FDX-dependent NADP reductase (FNR), NADPH, NTRC-pathway for 2-CysPRX reduction. Combining both modules allowed drawing several important conclusions of network performance. The resting H2O2 concentration was estimated to be about 30 nM in the chloroplast stroma. The electron flow to metabolism exceeds that into thiol regulation of FBPase more than 7000-fold under physiological conditions. The electron flow from NTRC to 2-CysPRX is about 5.46-times more efficient than that from TRX-f1 to 2-CysPRX. Under severe stress (30 μM H2O2) the ratio of electron flow to the thiol network relative to metabolism sinks to 1:251 whereas the ratio of electron flow from NTRC to 2-CysPRX and TRX-f1 to 2-CysPRX rises up to 1:80. Thus, the simulation provides clues on experimentally inaccessible parameters and describes the functional state of the chloroplast thiol regulatory network.Authors summaryThe state of the thiol redox regulatory network is a fundamental feature of all cells and determines metabolic and developmental processes. However, only some parameters are quantifiable in experiments. This paper establishes partial mathematical models which enable simulation of electron flows through the regulatory system. This in turn allows for estimating rates and states of components of the network and to tentatively address previously unknown parameters such as the resting hydrogen peroxide levels or the expenditure of reductive power for regulation relative to metabolism. The establishment of such models for simulating the performance and dynamics of the redox regulatory network is of significance not only for photosynthesis but also, e.g., in bacterial and animal cells exposed to environmental stress or pathological disorders.
Immune state networks of wild and laboratory mice
Authors: Fonseca dos Reis Elohim , Viney Mark , Masuda Naoki 
Published: May 2019

AbstractThe mammalian immune system protects individuals from infection and disease. It is a complex system of interacting cells and molecules and extensive work, principally with laboratory mice, has investigated its function. Wild and laboratory animals lead very different lives, and this is reflected in there being substantial immunological differences between them. Here we use network analyses to study a unique data set of 120 immune measures of wild and laboratory mice, where immune measures define nodes and correlations of immune measures across individual mice define edges between immune measures. To date, there has only been very limited network analyses of the immune system, which is surprising because such analyses may be important to better understand its organisation and functionality. We found that the immunological networks of wild and laboratory mice were similar in some aspects of their mesoscale structure, particularly concerning cytokine response communities. However, we also identified notable differences in node membership of network communities between the wild and laboratory networks, pointing to how the same immune system acts and interacts differently in wild and in laboratory mice. These results show the utility of network analysis in understanding immune responses and also the importance of studying wild animals in additional to laboratory animals.Author summaryThe mammalian immune system is a complex system that protects individuals from infection and disease. Most of our understanding of the immune system comes from studies of laboratory animals, particularly mice. However, wild and laboratory animals lead very different lives, potentially leading to substantial immunological differences between them and so possibly limiting the utility of laboratory animals as informative model systems. As a complex interacting set of cells and molecules, the immune system is a biological network. Therefore, we used network analyses to study the immune system, specifically a unique data set of immune measures of wild and laboratory mice, where 120 different immune measures define nodes of the network. We found that the networks of wild and laboratory mice were similar in some aspects of their grouping structure, particularly concerning communities of nodes of cytokine responses. However, we also identified notable differences in node membership of communities between the wild and laboratory networks, pointing to how the same immune system behaves differently in wild and in laboratory mice. These results show the utility of network analysis in understanding immune responses and also the importance of studying wild animals in addition to laboratory animals.
A development process for extending buildings vertically – based on a case study of four extended buildings
Authors: Sundling Rikard 
Published: May 2019

Purpose
The purpose of the study, upon which this paper is based, was to contribute an improved understanding of the vertical extension of buildings, by presenting a development process for its implementation in which the key aspects to consider when planning such extensions are highlighted.

Design/methodology/approach
The approach is based on linking the diffusion of innovation together with case study research to stimulate further development in vertically extending buildings. Four cases of vertically extended buildings in Sweden were selected for the study.

Findings
The development process highlights seven key areas for decisions when planning a vertical extension. These areas are: opportunities for vertical extension; strategies for implementation; detailed planning process; concept development; evaluation; building permit; and procurement. The development processes and lessons learnt from each case are presented, covering both success and failure.

Research limitations/implications
The research is based on four cases of vertically extended buildings. The findings offer valuable insights into the development process which should provide the research community with an improved understanding of the challenges faced.

Practical implications
The findings will help planners, housing owners, housing developers and facility managers better understand the conditions that favour successful implementation of vertical extensions.

Originality/value
The paper provides the reader with an understanding of the challenges faced in the vertical extension of a building and the means of overcoming them to create a simplified development process.
Actions for relationship value: a mission impossible?
Authors: Munksgaard Kristin B. , Frandsen Kirsten 
Published: May 2019

Purpose
The form and content of relationship value dominates the literature. This paper contributes by studying companies’ actions based on their value perceptions, a field which has attracted less attention. Scholars advocate more studies on how companies’ value perceptions shape actions in relationships and how this leads to outcomes.

Design/methodology/approach
A longitudinal critical case study of a customer/supplier relationship constitutes the empirical basis of the paper. Interviews and observation studies were conducted over a period of three years, giving access to special insight into the actors’ value perceptions and related actions.

Findings
Value perceptions shape actions performed individually, jointly or in the wider network. Moreover, misperceptions of the counterparty’s value perceptions may result in a maelstrom of interactions with no specific value outcome. Acting based on value perceptions is a complex matter due to its evolving nature, which leads to development becoming a value driver.

Research limitations/implications
The interdependencies between different value perceptions and their relational value drivers have special effects on actions and outcomes, also, value in actions needs to be studied.

Practical implications
Management needs to explore value from different perspectives to understand the counterparty’s value perceptions and communicate own perceptions. It is not sufficient to create value based on one value driver. Instead, it is vital to be able to connect value drivers to balance and prioritise relevant actions.

Originality/value
This paper stands out as one of the first contributions to relationship value literature that addresses and analyses value from both a customer perspective and a supplier perspective in a dyadic business relationship.
Knowledge management, the missing piece in the 2030 agenda and SDGs puzzle
Authors: Barrantes Briceño Christian Eric , Almada Santos Fernando César 
Published: May 2019

Purpose
This paper aims to analyze some knowledge management (KM) frameworks that sustainable development goals (SDGs) can apply to such a challenging implementation.

Design/methodology/approach
To accomplish this, a systematic scientific literature review was carried out about the KM concept. Searching, analyzing and collecting different KM frameworks were crossed and compared to achieve a standard KM framework list, based on the most important and relevant information collected.

Findings
The study outlines how and which KM frameworks may be applied in an effort to reach the 2030 Agenda for Sustainable Development and SDGs, so it can overcome the barriers and pitfalls related to the knowledge management use.

Research limitations/implications
The paper shows some SDG areas that deserve future attention and deep implementation with KM frameworks.

Originality/value
With the enormous potential and vision of the sustainable development goals (SDGs), there is a barrier in its progress and development: the knowledge use, in both the local knowledge aspects and general knowledge management. This paper creates a Knowledge Management Excellence Model (KMEM) linked to SDGs, which will help and promote its use to educate and involve all those interested in meeting these goals.
Ownership and control over publicly accessible platform data
Authors: Scassa Teresa 
Published: May 2019

Purpose
The purpose of this paper is to examine how claims to “ownership” are asserted over publicly accessible platform data and critically assess the nature and scope of rights to reuse these data.

Design/methodology/approach
Using Airbnb as a case study, this paper examines the data ecosystem that arises around publicly accessible platform data. It analyzes current statute and case law in order to understand the state of the law around the scraping of such data.

Findings
This paper demonstrates that there is considerable uncertainty about the practice of data scraping, and that there are risks in allowing the law to evolve in the context of battles between business competitors without a consideration of the broader public interest in data scraping. It argues for a data ecosystem approach that can keep the public dimension issues more squarely within the frame when data scraping is judicially considered.

Practical implications
The nature of some sharing economy platforms requires that a large subset of their data be publicly accessible. These data can be used to understand how platform companies operate, to assess their compliance with laws and regulations and to evaluate their social and economic impacts. They can also be used in different kinds of data analytics. Such data are therefore sought after by civil society organizations, researchers, entrepreneurs and regulators. This paper considers who has a right to control access to and use of these data, and addresses current uncertainties in how the law will apply to scraping activities, and builds an argument for a consideration of the public interest in data scraping.

Originality/value
The issue of ownership/control over publicly accessible information is of growing importance; this paper offers a framework for approaching these legal questions.