bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol interaction sites on the transmembrane domain of the hedgehog signal transducer and Class F G protein-coupled receptor Smoothened
Authors: Hedger George , Koldsø Heidi , Chavent Matthieu , Siebold Christian , Rohatgi Rajat , Sansom Mark S. P. 
Published: August 2018

AbstractTransduction of hedgehog signals across the plasma membrane is a key process during animal development. This is facilitated by the Class F G-protein-coupled-receptor (GPCR) Smoothened (SMO), a major drug target in the treatment of basal cell carcinomas. Recent studies have suggested that SMO is modulated via interactions of its transmembrane (TM) domain with cholesterol. Long time scale (>0.35 ms of simulation time) molecular dynamics simulations of SMO embedded in two different cholesterol containing lipid bilayers reveal direct interactions of cholesterol with the transmembrane domain at regions distinct from those observed in Class A GPCRs. In particular the extracellular tips of helices TM2 and TM3 form a well-defined cholesterol interaction site, robust to changes in membrane composition and in force field parameters. Potential of mean force calculations for cholesterol interactions yield a free energy landscape for cholesterol binding. Combined with analysis of equilibrium cholesterol occupancy these results reveal the existence of a dynamic ‘greasy patch’ interaction with the TM domain of SMO, which may be compared to previously identified lipid interaction sites on other membrane proteins. These predictions provide molecular level insights into cholesterol interactions with a biomedically relevant Class F GPCR, suggesting potential druggable sites.
Theileria highjacks JNK2 into a complex with the macroschizont GPI-anchored surface protein p104
Authors: De Laté Perle Latré , Haidar Malak , Ansari Hifzur , Tajeri Shahin , Szarka Eszter , Alexa Anita , Woods Kerry , Reményi Attila , Pain Arnab , Langsley Gordon 
Published: August 2018

AbstractTheileria is a unique apicomplexan parasite capable of transforming its host cell into a disseminating tumour. Constitutive JNK activity characterizes bovine T and B cells infected with T. parva, and B cells and macrophages infected with T. annulata. Here, we show that T. annulata manipulates JNK activation by recruiting JNK2, and not JNK1, to the parasite surface, whereas JNK1 is found predominantly in the host cell nucleus. In silico analysis identified 3 potential JNK-binding motifs in the previously characterized GPI-anchored macroschizont surface protein (p104), and we demonstrate here that JNK2 is recruited to the parasite via physical interaction with p104. A cell penetrating peptide harbouring a p104 JNK-binding motif also conserved in T. parva p104 competitively ablated binding, whereupon liberated JNK2 became ubiquitinated and degraded. Sequestration of JNK2 depended on PKA-mediated phosphorylation of the conserved JNK-binding motif and upon disruption of the p104/JNK2 complex loss of JNK2 resulted in diminished matrigel traversal of T. annulata-transformed macrophages. Loss of JNK2 also resulted in upregulation of small mitochondrial ARF that promoted autophagy consistent with cytosolic sequestration of JNK2 sustaininf not only JNK2, but also nuclear JNK1 levels that combined contribute to both survival and dissemination of Theileria-transformed macrophages.Author SummaryTheileria annulata parasites infect and transform their host bovine leukocytes into tumourlike cells that disseminate throughout infected animals causing a widespread disease called tropical theileriosis. Virulence has been ascribed to the parasite’s ability to constitutively activate leukocyte c-Jun N-terminal Kinase (JNK) leading to permanent induction of Matrix Metallo-Proteinase 9 (MMP9) that promotes transformed macrophage dissemination. In attenuated live vaccines JNK-mediated AP-1-driven transcriptional activity is reduced so dampening dissemination. However, in leukocytes JNK exists as two isoforms JNK1 and JNK2 and here, we show for the first time that in T. annulata-transformed macrophages they have different subcellular localisations and perform separate functions. Surprisingly, JNK2 associates with the parasite and is not in the nucleus like JNK1. JNK2 is hijacked by the parasite and sequestered in a complex with a macroschizont surface protein called p104. Upon forced complex dissociation JNK2 gets degraded and its loss negatively affects infected macrophage survival and ability to disseminate.
Genetic draft and valley crossing
Authors: Kessinger Taylor , Van Cleve Jeremy 
Published: August 2018

ABSTRACTLiving systems are characterized by complex adaptations which require multiple coordinated mutations in order to function. Empirical studies of fitness landscapes that result from the many possible mutations in a gene region reveal many fitness peaks and valleys that connect them. Thus, it is possible that some complex adaptations have arisen by evolutionary paths whose intermediate states are neutral or even deleterious. When intermediates are deleterious, traversing such an evolutionary path is known as “crossing a fitness valley”. Previous efforts at studying this problem have rigorously characterized the rate at which such complex adaptations evolve in populations of roughly equally fit individuals. However, populations that are very large or have broad fitness distributions, such as many microbial populations, adapt quickly, which substantially alters the fate and dynamics of individual mutations due to the action of genetic draft. We investigate the rate at which complex adaptations evolve in these rapidly adapting populations in regions without recombination. We confirm that rapid adaptation overall increases the time required to cross a valley; however, rapid adaptation can make it easier for deeper valleys to be crossed relative to the time required for single beneficial mutations to sweep to fixation.
YcjW: a transcription factor that controls the emergency generator of H2S inE. coli
Authors: Luhachack Lyly , Shamovsky Ilya , Nudler Evgeny 
Published: August 2018

AbstractHydrogen sulfide (H2S) is a ubiquitous gaseous molecule that is endogenously produced in both eukaryotes and prokaryotes. Its role as a pleiotropic signaling molecule has been well characterized in mammals1,2. In contrast, the physiological role of H2S in bacteria only recently became apparent; H2S acts as a cytoprotectant against antibiotics-induced stress and affect the cell’s ability to maintain redox homeostasis3-5. InE. coli, endogenous H2S production is primarily dependent on 3-mercaptopyruvate sulfurtransferase (3MST), encoded bymstA, previously known assseA3,4. Here, we show that cells lacking 3MST acquired a unique phenotypic suppressor mutation resulting in compensatory H2S production and tolerance to antibiotics and oxidative stress. Using whole genome sequencing, we mapped a non-synonymous single nucleotide polymorphism (SNP) to uncharacterized Laci-type transcription factor, YcjW. We identified transcriptional regulatory targets of YcjW and discovered a major target, thiosulfate sulfurtransferase PspE, as an alternative mechanism for H2S biosynthesis. Deletion ofpspEwas sufficient to antagonize phenotypic suppression. Our results reveal a complex interaction between cell metabolism and H2S production and the role, a hithero uncharacterized transcription factor, YcjW, plays in linking the two.
Autopilot design for an aircraft by using Luenberger observer design
Authors: Taimoor Muhammad , Aijun Li , Amin Rooh ul , Lu Hongshi 
Published: August 2018

Purpose
The purpose of this paper is to design linear quadratic regulator (LQR) based Luenberger observer for the estimation of unknown states of aircraft.

Design/methodology/approach
In this paper, the LQR-based Luenberger observer is deliberated for autonomous level flight of unmanned aerial vehicle (UAV) which has been attained productively. Various modes like phugoid and roll modes are exploited for controlling the rates of UAV. The Luenberger observer is exploited for estimation of the mysterious states of the system. The rates of roll, yaw and pitch are used as an input to the observer, while the remaining states such as velocities and angles have been anticipated. The main advantage of using Luenberger observer was to reduce the cost of the system which has been achieved lucratively. The Luenberger observer proposes sturdiness at the rate of completion to conquest over the turmoil and insecurities to overcome the privileged recital. The FlightGear simulator is exploited for the endorsement of the recital of the Luenberger observer-based autopilot. The level flight has been subjugated lucratively and has been legitimated by exploiting the FlightGear simulator. The authenticated and the validated results are offered in this paper. Microsoft Visual Studio has been engaged as a medium between the MATLAB and FlightGear Simulator.

Findings
The suggested observer based on LQR ensures the lucrative approximation of the unknown states of the system as well as the successful level flight of the system. The Luenberger observer is used for approximation of states while LQR is used as controller.

Originality/value
In this research work, not only the estimation of unknown states of both longitudinal and lateral model is made but also the level flight is achieved by using those estimated states and the autopilot is validated by using the FlightGear, while in most of the research work only the estimation is made of only longitudinal or lateral model.
Entrepreneurs’ individual-level resources and social value creation goals
Authors: Brieger Steven A. , De Clercq Dirk 
Published: August 2018

PurposeThe purpose of this paper is to provide a better understanding of how the interplay of individual-level resources and culture affects entrepreneurs’ propensity to adopt social value creation goals.Design/methodology/approachUsing a sample of 12,685 entrepreneurs in 35 countries from the Global Entrepreneurship Monitor, it investigates the main effects of individual-level resources – measured as financial, human and social capital – on social value creation goals, as well as the moderating effects of the cultural context in which the respective entrepreneur is embedded, on the relationship between individual-level resources and social value creation goals.FindingsDrawing on the resource-based perspective and Hofstede’s cultural values framework, the results offer empirical evidence that individual-level resources are relevant for predicting the extent to which entrepreneurs emphasise social goals for their business. Furthermore, culture influences the way entrepreneurs allocate their resources towards social value creation.Originality/valueThe study sheds new light on how entrepreneurs’ individual resources influence their willingness to create social value. Moreover, by focussing on the role of culture in the relationship between individual-level resources and social value creation goals, it contributes to social entrepreneurship literature, which has devoted little attention to the interplay of individual characteristics and culture.
Interstate migration and human capital formation in Brazil
Authors: Pais Paloma Santana Moreira , de Mattos Leonardo Bornacki , Teixeira Evandro Camargos 
Published: August 2018

Purpose
The purpose of this paper is to analyze the impact of interstate migration of individuals with different qualification levels on human capital formation in the migrant’s place of origin.

Design/methodology/approach
A dynamic panel model with data from the National Household Sample Survey (Pesquisa Nacional por Amostra de Domicílios (PNAD)), between 2001 and 2013, is used.

Findings
The results indicate that the migration of high-skilled people boosts school attendance in fifth grade elementary school and first year high school, but it does not affect the levels of those entering first year in higher education. However, the migration of low-skilled workers discourages people from entering higher education, as those living in less developed areas do not need higher education qualifications to get higher incomes. Thus, they migrate to developed areas with the education levels they already have. The brain gain hypothesis is not, therefore, confirmed in the context of higher education attendance.

Originality/value
This paper’s contribution is its investigation into the effect of interstate migration on human capital formation in Brazil, through testing the brain gain hypothesis in a national context. In addition, it also analyzes the impact of the migration of people of low and intermediate qualification levels on human capital, with a view to verifying if the mobility of people with other levels of qualification could discourage the formation of human capital.
Some risks of informal business in Russia – a case study from Saint Petersburg
Authors: Mannila Simo , Eremicheva Galina 
Published: August 2018

PurposeThe purpose of this paper is to describe some risks and risk-taking when launching and running business in Russia during the socio-economic transformation. The risks are related to informal economy.Design/methodology/approachThe research material consists of 11 thematic interviews of families, who launched and ran a business during the turn of the millennium and follow-up interviews. The interviews were extracted from a larger material of 100 interviews and 40 follow-ups focusing on household coping in Russian socio-economic transformation.FindingsThe paper focusses on risky shuttle trade as well as crime-related risks of business, as poignant illustrations of problems of entrepreneurship linked with informal economy. The risks are seen as social facts, objective or constructed, in some cases pointing out also how people speak about them. The testimonial stories of business show an individual or family focus on the risks, without major concern for legitimacy of action, albeit a need for distinction toward other corresponding risk-takers.Research limitations/implicationsThe findings illustrate important aspects of informal economy in Russia, but they cannot be generalized. It would be most useful to carry out qualitative studies of small business to assess perception and construction of risks and coping with them, capturing the views of entrepreneurs themselves.Originality/valueThere is rather little micro-level information concerning the risks or uncertainty when launching and running business in the Russian Federation. Qualitative data enable deeper understanding of sensitive issues. The paper wants to introduce the concept of risk into the social research of informal economy.
Tribological properties of ionic liquids for steel/aluminum, steel/copper and steel/Si3N4ceramic contacts under boundary lubrication
Authors: Zhang Hao-bo , Chen Hui , Shi Xiao-ning , Liu Xiong , Duan Guo-jian 
Published: August 2018

PurposeThe purpose of this paper is to study the influence of alkyl chain length and kind of anions of ionic liquids on the tribological properties with different materials as friction pairs (steel-aluminum, steel-copper and steel-Si3N4 ceramic).Design/methodology/approachTribological properties were evaluated by an optimol-SRV-IV reciprocation friction tester with a ball-on-block configuration at room temperature and high temperature, respectively. Friction-reducing and anti-wear properties of the ionic liquids for steel/aluminum, steel/copper and steel/ceramic contacts were evaluated on the ball-on-block reciprocating UMT-2MT tribometer. The morphologies of the worn surfaces were observed by a scanning electron microscope. The chemical states of several typical elements on the worn surfaces were examined by X-ray photoelectron spectroscopy.FindingsBoth the alkyl chain length and kind of anion influence the tribological properties of ionic liquids, especially for the length of alkyl chains. With the increase of alkyl chain length, the load carrying capacity of ionic liquids is improved at both room temperature and high temperature, and the friction reducing and antiwear behaviors are also significantly enhanced.Research limitations/implicationsThe paper presents potentially useful and highly efficient lubricants.Practical implicationsOwing to their good friction-reducing and wear resistance properties, these ionic liquids are promising candidates for versatile applications.Originality/valueThis work might provide a promising research direction for design and application of ionic liquids as lubricants.
Caveats for high reliability in healthcare
Authors: Martelli Peter F. , Rivard Peter E. , Roberts Karlene H. 
Published: August 2018

Purpose
Given the pace of industry change and the rapid diffusion of high reliability organization (HRO) approaches, lags and divergences have arisen between research and practice in healthcare. The purpose of this paper is to explore several of these theory-practice gaps and propose implications for research and practice.

Design/methodology/approach
Classic and cutting-edge HRO literature is applied to analyze two industry trends: delivery system integration, and the confluence of patient-as-consumer and patient-centered care.

Findings
Highly reliable integrated delivery systems will likely function very differently from classic HRO organizations. Both practitioners and researchers should address conditions such as how a system is bounded, how reliable the system should be and how interdependencies are handled. Additionally, systems should evaluate the added uncertainty and variability introduced by enhanced agency on the part of patients/families in decision making and in processes of care.

Research limitations/implications
Dramatic changes in the sociotechnical environment are influencing the coupling and interactivity of system elements in healthcare. Researchers must address the maintenance of reliability across organizations and the migration of decision-making power toward patients and families.

Practical implications
As healthcare systems integrate, managers attempting to apply HRO principles must recognize how these systems present new and different reliability-related challenges and opportunities.

Originality/value
This paper provides a starting point for the advancement of research and practice in high-reliability healthcare by providing an in-depth exploration of the implications of two major industry trends.
Electro-thermal buckling of elastically supported double-layered piezoelectric nanoplates affected by an external electric voltage
Authors: Malikan Mohammad 
Published: August 2018

Purpose
Thermal buckling of double-layered piezoelectric nanoplates has been analyzed by applying an external electric voltage on the nanoplates. The paper aims to discuss this issue.

Design/methodology/approach
Double-layered nanoplates are connected to each other by considering linear van der Waals forces. Nanoplates are placed on a polymer matrix. A comprehensive thermal stress function is used for investigating thermal buckling. A linear electric function is used for taking external electric voltages into account. For considering the small-scale effect, the modified couple stress theory has been applied. An analytical solution has been used by taking various boundary conditions.

Findings
EEV has a considerable impacted on the results of various half-waves in all boundary conditions. By increasing EEV, the reduction of critical buckling temperature in higher half-waves is remarkably slower than lower half-waves. By considering long lengths, the effect of EEV on the critical temperature will be markedly decreased.

Originality/value
This paper uses electro-thermal stability analysis. Double-layered piezoelectric nanoplates are analyzed. A comprehensive thermal stress function is applied for taking into account critical temperature.
Life history characteristics may be as important as climate projections for defining range shifts: An example for common tree species in the intermountain western US
Authors: Copeland Stella M. , Bradford John B. , Duniway Michael C. , Butterfield Bradley J. 
Published: August 2018

AbstractAimPredictions of future suitable habitat for plant species with climate change are known to be affected by uncertainty associated with statistical approaches, climate models and occurrence records. However, life history characteristics related to dispersal and establishment processes as well as sensitivity to barriers created by land‐use may also play important roles in shaping future distributions with climate change. We compared the uncertainty in predicted distributions associated with climate projections to uncertainty associated with species interactions related to dispersal and establishment and land‐use barriers with four common animal‐dispersed tree species in pinyon–juniper woodlands in the western United States, a region experiencing increasing fragmentation due to land‐use.LocationWestern USA.MethodsWe compared the effects of life history characteristics related to species interactions (long‐distance dispersal and facilitation), land‐use fragmentation and variation in climate projections on species distributions with climate change using a simulation model. We evaluated the impacts of these factors on three characteristics of species distributions, area occupied, range size, and distance between patches, across four 30‐year intervals centred on 2020, 2040, 2060 and 2080.ResultsWe found that uncertainty associated with climate projections and the potential effects of facilitation on establishment had the greatest impact in distribution characteristics. The effects of all factors varied by species, despite their overlapping initial distributions and relatively similar dispersal traits, highlighting the impact of life history characteristics on model outcomes.Main conclusionsThese results suggest that assessments of species future range shifts and vulnerability to climate change should incorporate land‐use barriers and life history traits related to dispersal and establishment, particularly for species with strong facilitative interactions.
Dielectric relaxation in glass and glass‐ceramic materials of the system La2O3‐Gd2O3‐PbO‐MnO‐B2O3
Authors: Raykov Radoslav , Staneva Anna , Dimitriev Yanko , Slavov Stanislav , Soreto Teixeira Silvia , Prezas Pedro R. , Costa Luis C. 
Published: August 2018

AbstractThe electrical properties of new borate‐based glasses in the system La2O3‐Gd2O3‐PbO‐MnO2‐B2O3, prepared by the melt‐quenching technique, were investigated. All of these glasses have a fixed content of B2O3 (%mol = 30). The electrical measurements were carried out by impedance spectroscopy in the frequency range from 100 Hz to 1 MHz, and temperatures from 100 to 400°C, below the glass temperature. The AC conductivity increases with temperature according to the Arrhenius law, with a single activation energy. The structural and thermal properties of the glasses were investigated by performing infrared spectroscopy, X‐ray diffraction, and differential thermal analysis. The dependence of the various electrical parameters as a function of the glass composition and temperature was discussed. Evaluations of models and theory of the relaxation mechanisms were predominantly made through comparison with experimental data and a set of phenomenological parameters.