bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asparagine availability is an essential limiting factor for poxvirus protein synthesis
Authors: Pant Anil , Cao Shuai , Yang Zhilong 
Published: September 2018

AbstractVirus actively interfaces with host metabolism because viral replication relies on host cells to provide nutrients and energy. For efficient viral replication in culture, vaccinia virus (VACV; the prototype poxvirus) prefers glutamine to glucose, to the extent that in glutamine-free medium, VACV replication is inefficient. Remarkably, VACV replication can be fully rescued from glutamine depletion by asparagine supplementation. By global metabolic profiling, genetic and chemical intervening of asparagine supply, we provide evidence demonstrating that the requirement of asparagine for efficient viral replication accounts for VACV’s preference of glutamine to glucose, rather than because glutamine is superior to glucose in feeding the tricarboxylic acid (TCA) cycle. Further, we show that asparagine availability is a critical factor for efficient viral protein synthesis. Our study highlights that the asparagine metabolism, whose regulation has been evolutionarily tailored in mammalian cells, presents a critical barrier to poxvirus replication, suggesting new directions of anti-viral strategy development.
Imaging human cortical responses to intraneural microstimulation using magnetoencephalography
Authors: O’Neill George C. , Watkins Roger H. , Ackerley Rochelle , Barratt Eleanor L. , Sengupta Ayan , Asghar Michael , Sanchez Panchuelo Rosa Maria , Brookes Matthew J. , Glover Paul M. , Wessberg Johan , Francis Susan T. 
Published: September 2018

AbstractThe sensation of touch in the glabrous skin of the human hand is conveyed by thousands of fast-conducting mechanoreceptive afferents, which can be categorised into four distinct types. The spiking properties of these afferents in the periphery in response to varied tactile stimuli are well-characterised, but relatively little is known about the spatiotemporal properties of the neural representations of these different receptor types in the human cortex. Here, we use the novel methodological combination of single-unit intraneural microstimulation (INMS) with magnetoencephalography (MEG) to localise cortical representations of individual touch afferents in humans, by measuring the extracranial magnetic fields from neural currents. We found that by assessing the modulation of the beta (13-30 Hz) rhythm during single-unit INMS, significant changes in oscillatory amplitude occur in the contralateral primary somatosensory cortex within and across a group of fast adapting type I mechanoreceptive 20 afferents, which corresponded well to the induced response from matched vibrotactile stimulation. Combining the spatiotemporal specificity of MEG with the selective single-unit stimulation of INMS enables the interrogation of the central representations of different aspects of tactile afferent signalling within the human cortices. The fundamental finding that single-unit INMS ERD responses are robust and consistent with natural somatosensory stimuli will permit us to more dynamically probe the central nervous system responses in humans, to address questions about the processing of touch from the different classes of mechanoreceptive afferents and the effects of varying the stimulus frequency and patterning.
Effects of BMP-2 dose and delivery of microvascular fragments on healing of bone defects with concomitant volumetric muscle loss
Authors: Ruehle Marissa A. , Krishnan Laxminarayanan , Vantucci Casey E. , Wang Yuyan , Stevens Hazel Y. , Roy Krishnendu , Guldberg Robert E. , Willett Nick J. 
Published: September 2018

ABSTRACTTraumatic composite bone-muscle injuries, such as open fractures, often require multiple surgical interventions and still typically result in long-term disability. Clinically, a critical indicator of composite injury severity is vascular integrity; vascular damage alone is sufficient to assign an open fracture to the most severe category. Challenging bone injuries are often treated with bone morphogenetic protein 2 (BMP-2), an osteoinductive growth factor, delivered on collagen sponge. Previous studies in a composite defect model found that a minimally bridging dose in the segmental defect model was unable to overcome concomitant muscle damage, but the effect of BMP dose on composite injuries has not yet been studied. Here, we test the hypotheses that BMP-2-mediated functional regeneration of composite extremity injuries is dose dependent and can be further enhanced via co-delivery of adipose-derived microvascular fragments (MVF), which have been previously shown to increase tissue vascular volume. Although MVF treatment did not improve healing outcomes, we observed a significant BMP-2 dose-dependent increase in regenerated bone volume and biomechanical properties. While high dose BMP-2 delivery can induce heterotopic ossification (HO) and increased inflammation, the maximum 10 μg dose used in this study did not result in HO and was associated with a lower circulating inflammatory cytokine profile than the low dose (2.5 μg) group. These data support the potential benefits of an increased, though still moderate, BMP-2 dose for treatment of bone defects with concomitant muscle damage. Future work to improve vascularization may further improve healing.
Real-time whole-plant dynamics of heavy metal transport inArabidopsis halleriandArabidopsis thalianaby gamma-ray imaging
Authors: Kajala Kaisa , Walker Katherine L. , Mitchell Gregory S. , Krämer Ute , Cherry Simon R. , Brady Siobhan M. 
Published: September 2018

ABSTRACTHeavy metals such as zinc are essential for plant growth, but toxic at high concentrations. Despite our knowledge of the molecular mechanisms of heavy metal uptake by plants, experimentally addressing the real-time whole-plant dynamics of heavy metal uptake and partitioning has remained a challenge. To overcome this, we applied a high sensitivity gamma-ray imaging system to image uptake and transport of radioactive65Zn in whole-plant assays ofArabidopsis thalianaand the Zn hyperaccumulatorA. halleri. We show that our system can be used to quantitatively image and measure uptake and root-to-shoot translocation dynamics of zinc in real time. In the metal hyperaccumulatorArabidopsis halleri,65Zn uptake and transport from its growth media to the shoot occurs rapidly and on time scales similar to those reported in rice. In transgenicA. halleriplants in which expression of the zinc transporter geneHMA4is suppressed by RNAi,65Zn uptake is completely abolished.HIGHLIGHTWe have used gamma-ray imaging to visualize the stark differences of real-time whole-plant dynamics of zinc root-to-shoot transport in heavy metal hyperaccumulating and non-accumulatingArabidopsis.
Retinal direction selectivity in the absence of asymmetric starburst amacrine cell responses
Authors: Hanson Laura , Sethuramanujam Santhosh , deRosenroll Geoff , Awatramani Gautam B. 
Published: September 2018

SummaryIn the mammalian retina, asymmetric inhibitory signals arising from the direction-selective dendrites of GABAergic/cholinergic starburst amacrine cells are thought to be crucial for originating direction selectivity. Contrary to this notion, however, we found that direction selectivity in downstream ganglion cells remains remarkably unaffected when starburst output is rendered non-directional (using a novel strategy combining a conditional GABAA α2 receptor knockout mouse with optogenetics). We show that temporal asymmetries between excitation/inhibition, arising from the differential connectivity patterns of starburst cholinergic and GABAergic synapses to ganglion cells, form the basis for a parallel mechanism generating direction selectivity. We further demonstrate that these distinct mechanisms work in a coordinated way to refine direction selectivity as the stimulus crosses the ganglion cell’s receptive field. Thus, precise spatiotemporal patterns of inhibition and excitation that shape directional responses in ganglion cells are shaped by two ‘core’ mechanisms, both arising from distinct specializations of the starburst network.
Astrocytes Regulate the Development and Maturation of Retinal Ganglion Cells Derived from Human Pluripotent Stem Cells
Authors: Langer Kirstin B. , Vij Ridhima , Ohlemacher Sarah K. , Sridhar Akshayalakshmi , Fligor Clarisse M. , Feder Elyse M. , Edler Michael C. , Baucum Anthony J. , Cummins Theodore R. , Meyer Jason S. 
Published: September 2018

SummaryRetinal ganglion cells (RGCs) form the connection between the eye and the brain, with this connectivity disrupted in numerous blinding disorders. Previous studies have demonstrated the ability to derive RGCs from hPSCs; however these cells exhibited some characteristics that indicated a limited state of maturation. Among the many factors known to influence RGC development in the retina, astrocytes are known to play a significant role in their functional maturation. Thus, efforts of the current study examined the functional maturation of hPSC-derived RGCs, including the ability of astrocytes to modulate this developmental timeline. Morphological and functional properties of RGCs were found to increase over time, with astrocytes significantly accelerating the functional maturation of hPSC-derived RGCs. The results of this study are the first of its kind to extensively study the functional and morphological maturation of RGCs in vitro, including the effects of astrocytes upon the maturation of hPSC-derived RGCs.
A mathematical model of viral oncology as an immuno-oncology instigator
Authors: Cassidy Tyler , Humphries Antony R. 
Published: September 2018

AbstractWe develop and analyse a mathematical model of tumour-immune interaction that explicitly incorporates heterogeneity in tumour cell cycle duration by using a distributed delay differential equation. Our necessary and sufficient conditions for local stability of the cancer free equilibrium completely characterise the importance of tumour-immune interaction in disease progression. Consistent with the immunoediting hypothesis, we show that decreasing tumour-immune interaction leads to tumour expansion. Finally, we show that immune involvement is crucial in determining the long-term response to viral therapy.
Glucosinolates promote initial population establishment of feral oilseed rape
Authors: Hesse Elze , Hodgson Dave J. , de Jong Tom J. 
Published: September 2018

AbstractBackgroundCrops are often selected for traits that confer a selective disadvantage in the wild. A key trait that has been greatly altered by domestication is investment in herbivore defence. It remains unclear, however, whether variation in chemical defence affects a crop’s ability to colonize semi-natural habitats where it typically has to compete with a resident community. Here, we investigate how breeding efforts aimed at reducing glucosinolate levels in seeds – canonical herbivore deterrents – influence initial establishment of Brassica populations spanning a wild-feral-domesticated gradient.MethodsWe followed the dynamics of twenty-nine Brassica accessions in two experimental fields by recording life table parameters and vegetation cover biannually over a two-year period. Accessions were selected to vary in their glucosinolate content, and included lines of wild turnip (B. rapa), feral B. napus as well as modern canola and historical oilseed rape cultivars. Populations were established by sowing seeds on bare soil after which the natural vegetation was allowed to regenerate, providing a temporal gradient in the degree of interspecific competition.ResultsPopulations flourished in the first year, but many perished during a second year of growth, in particular those of oilseed rape. Declines coincided with an increase in vegetation cover, but were slower in populations harbouring more glucosinolates. These compounds had opposing effects on different life cycle stages: seedling establishment was greater in high-glucosinolate lines, which traded off with reduced post-recruitment survival. Crucially, the effect of glucosinolates on persistence was lost when focussing on oilseed rape only, but the underlying demographic trade-off remained.DiscussionOur study illustrates that initial establishment of feral oilseed rape is governed by glucosinolate-mediated trade-offs between seedling recruitment and subsequent survival, with low-glucosinolate lines (modern canola) being most successful when post-recruitment conditions are relatively benign. Such demographic trade-offs likely extend to other species, and must be considered when managing escaped crops and invasive plants.
Particle-based simulation reveals macromolecular crowding effects on the Michaelis-Menten mechanism
Authors: Weilandt Daniel R. , Hatzimanikatis Vassily 
Published: September 2018

AbstractMany computational models for analyzing and predicting cell physiology rely onin vitrodata, collected in dilute and cleanly controlled buffer solutions. However, this can mislead models because about 40% of the intracellular volume is occupied by a dense mixture of proteins, lipids, polysaccharides, RNA, and DNA. These intracellular macromolecules interact with enzymes and their reactants and affect the kinetics of biochemical reactions, makingin vivoreactions considerably more complex than thein vitrodata indicates. In this work, we present a new type of kinetics that captures and quantifies the effect of volume exclusion and any other spatial phenomena on the kinetics of elementary reactions. We further developed a framework that allows for the efficient parameterization of this type of kinetics using particle simulations. Our formulation, entitled GEneralized Elementary Kinetics (GEEK), can be used to analyze and predict the effect of intracellular crowding on enzymatic reactions and was herein applied to investigate the influence of crowding on phosphoglycerate mutase inEscherichia coli, which exhibits prototypical reversible Michaelis-Menten kinetics. Current research indicates that many enzymes are reaction limited and not diffusion limited, and our results suggest that the influence of fractal diffusion is minimal for these reaction-limited enzymes. Instead, increased association rates and decreased dissociation rates lead to a strong decrease in the effective maximal velocitiesVmaxand the effective Michaelis-Menten constantsKMunder physiologically relevant volume occupancies. Finally, the effects of crowding in the context of a linear pathway were explored, with the finding that crowding can have a redistributing effect, relative to ideal conditions, on the effective flux responses in the case of two-fold enzyme overexpression. We suggest that the presented framework in combination with detailed kinetics models will improve our understanding of enzyme reaction networks under non-ideal conditions.
Novel coupled model for power loss prediction in a record-breaking electric aircraft motor
Authors: Goraj Robert 
Published: September 2018

PurposeThe purpose of this paper is to devise an analytical approach to calculate conductor winding losses, considering multiple contributing aspects simultaneously. These include the geometric configuration of coil windings, frequency of the electric current and the dependency on the coil temperature, derived studying a coupled fluid–solid model considering the cooling system characteristics. The obtained results allow identifying power loss trends according to such system variables as coolant inlet temperature or overall flow rate of the motor.Design/methodology/approachAn easy-to-use coupled analytical approach is applied, which is suitable for rapid estimations of the impact of parameter variation on the resulting conductor winding power losses that facilitates decision-making in the design process of electric aircraft engines.FindingsIn the considered cooling parameters, the overall conductor winding power losses vary approximately between 6 kW and 7.2 kW. More than 95 per cent of this loss is because of direct current losses. These losses cause the variation in maximal coil temperature ranging between 115°C and 170°C.Practical implicationsThe SP260D motor is set and was currently tested in Extra 330. It recently broke two world records.Social implicationsOne of the current trends in aircraft engineering is electric aircraft. Advantages of electric aircraft include improved manoeuvrability because of greater torque from electric motors, increased safety because of decreased chance of mechanical failure, less risk of explosion or fire in the event of a collision and less noise. There will be environmental and cost benefits associated with the elimination of dependency on fossil fuels and resultant emissions.Originality/valueThe use of a novel fluid–solid interaction model for predicting conductor winding power loss of the SP260D electric aircraft motor has not been done earlier. A novel alternative derivation of the widely applied Dowell’s formula (Dowell, 1966) is presented for the estimation of proximity losses in square winding conductors.
HR’s role in organizational effectiveness
Authors: Vanderpyl Tim H. 
Published: September 2018

Purpose
HR leaders need to see their role as one of building and valuing personal networks that bolster their organization’s effectiveness.

Design/methodology/approach
This paper discusses three primary ways that HR departments can bolster their organization’s effectiveness, namely, harnessing social power, empowering alpha employees, and influencing organizational design.

Findings
These three focuses will give HR leaders’ opportunities to further contribute to the overall effectiveness of the organization.

Originality/value
In the conceptual literature, the author’s own viewpoints and other ideas are weaved together to present a unique perspective on HR’s role in creating effective organizations.
Analysing student perceptions to enhance engagement
Authors: Schaddelee Marjolein , McConnell Christine 
Published: September 2018

Purpose
The purpose of this paper is to better understand what helps and hinders the engagement of students in a project-based learning (PjBL) approach as the sole mode of teaching and learning for the entire first year of a Bachelor of Applied Management.

Design/methodology/approach
This study takes an action research approach by investigating the perceptions of students of an interdisciplinary PjBL programme, and then taking action and responding to the students. Students were asked to share their experiences through a series of surveys spanning the first two years of the programme’s introduction.

Findings
Results indicate that there were significant challenges associated with the introduction of a PjBL programme. Students expressed both their positive and negative experiences in relation to working in groups, the way the programme and projects were designed and how the programme was communicated and integrated. The comments and suggestions students made led to a number of recommendations to further improve student engagement and learning outcomes.

Research limitations/implications
The research was conducted at a state-funded tertiary provider located in New Zealand and may not necessarily be applied to other geographical regions or cultures.

Practical implications
The results and recommendations have value for international education in business providers that are interested to introduce or further develop an interdisciplinary PjBL approach.

Social implications
Further understanding of how students may be further engaged has value for a variety of different contexts where engagement and motivation feature as a desired outcome.

Originality/value
This research study contributes to the understanding of how PjBL can be implemented to increase student motivation and engagement, and the insights provided practical suggestions for similar programmes of an interdisciplinary nature.
Feminine futures: female initiation and aspiration in matrilineal Malawi
Authors: Johnson Jessica 
Published: September 2018

AbstractA vibrant recent literature documents the challenges of achieving social adulthood in the context of economic decline and high youth unemployment in Africa and beyond. Those who have already made this transition, however, tend to reside in the margins of these texts, casting disapproving shadows. This article seeks to redress the balance by focusing on the significant efforts of social adults to shape young girls’ transitions to adult womanhood. In rural Malawi, this takes the form of female initiation rites, which have been adapted to include messages about the importance of formal education and the potential benefits of ‘waithood’. Rather than constituting a problem, delayed marriage is lauded as an alternative to the real social limbo entailed in early marriage and childbearing in a context of widespread poverty. Subtle alterations to initiation rites are thus embraced in an attempt to guide young women towards a more desirable future, at the same time as they are prepared, in moral and practical terms, for lives much like their elders.
Real rates and consumption smoothing in a low interest rate environment: The case of Japan
Authors: Lecznar Jonathon , Lubik Thomas A. 
Published: September 2018

AbstractWe study the dynamics of consumption, the real interest rate and measures of labour input in Japan over the period from 1985 to 2014. We identify structural breaks in macroeconomic aggregates during the 1990s and associate them with the zero interest‐rate policy pursued by the Bank of Japan and the surprise increase in the consumption tax rate in April 1997. Formal estimation using the generalized methods of moments shows that the mid‐1990s are characterized by breaks in the structural parameters governing household consumption and labour supply decisions. Specifically, following the tax hike and during the low nominal rate period, Japanese households became less risk averse and exhibited a higher degree of habit formation.
The effectiveness of refutation with logic vs. indignation in restoring the credibility of and trust in a government organization: A heuristic‐systematic model of crisis communication processing
Authors: Lim Joon Soo 
Published: September 2018

AbstractAcross two experiments, this study examines the relative effectiveness of refutational messages employing different rhetorical modes in mitigating the reputational damage from an activist’s accusation of which validity can be contentious. Experiment 1 reveals that an appeal to logic generates more positive evaluations than an appeal to indignation in the message evaluations of transparency and reliability. Experiment 2 shows that an appeal to logic yields more positive attitude, higher perceptions of credibility and trust in the organization than an appeal to indignation when crisis involvement is high. The results of this study support the theoretical proposition of a dual‐process model of persuasion—individuals’ processing of crisis discourse is greatly affected by their level of involvement with the crisis.
Hospital quality indicators are not unidimensional: A reanalysis of Lieberthal and Comer
Authors: Cefalu Matthew S. , Elliott Marc N. , Setodji Claude M. , Cleary Paul D. , Hays Ron D. 
Published: September 2018

ObjectiveTo evaluate the dimensionality of hospital quality indicators treated as unidimensional in a prior publication.Data Source/Study DesignPooled cross‐sectional 2010‐2011 Hospital Compare data (10/1/10 and 10/1/11 archives) and the 2012 American Hospital Association Annual Survey.Data ExtractionWe used 71 indicators of structure, process, and outcomes of hospital care in a principal component analysis of Ridit scores to evaluate the dimensionality of the indicators. We conducted an exploratory factor analysis using only the indicators in the Centers for Medicare & Medicaid Services' Hospital Value‐Based Purchasing.Principal FindingsThere were four underlying dimensions of hospital quality: patient experience, mortality, and two clinical process dimensions.ConclusionsHospital quality should be measured using a variety of indicators reflecting different dimensions of quality. Treating hospital quality as unidimensional leads to erroneous conclusions about the performance of different hospitals.