bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial impairment and rescue in riboflavin responsive neuropathy
Authors: Manole Andreea , Jaunmuktane Zane , Hargreaves Iain , Pandraud Amelie , Salpietro Vincenzo , Pope Simon , Ludtmann Marthe H. R. , Horga Alejandro , Scalco Renata S. , Li Abi , Ashokkumar Balasubramaniem , Lourenço Charles M. , Heales Simon , Horvath Rita , Chinnery Patrick F. , Toro Camilo , Singleton Andrew B. , Jacques Thomas S. , Abramov Andrey Y. , Muntoni Francesco , Hanna Michael G. , Reilly Mary M. , Revesz Tamas , Kullmann Dimitri M. , Jepson James E.C. , Houlden Henry 
Published: February 2017

AbstractBrown-Vialetto-Van Laere syndrome (BVVLS) represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter (RFVT) genes,SLC52A2andSLC52A3,have recently been linked to BVVLS. However, the genetic frequency, neuropathology and downstream consequences of RFVT mutations have previously been undefined. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between RFVT mutations and BVVLS, identifying twenty-two pathogenic mutations inSLC52A2andSLC52A3,fourteen of which were novel. Brain and spinal cord neuropathological examination of two cases withSLC52A3mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain (ETC), we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this usingin vitroandin vivomodels. ETC complex I and complex II activity were decreased inSLC52A2patient fibroblasts, while global knockdown of the singleDrosophilaRFVT homologue revealed reduced levels of riboflavin, downstream metabolites, and ETC complex I activity. RFVT knockdown inDrosophilaalso resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings indicate mitochondrial dysfunction as a downstream consequence of RFVT gene defects in BVVLS and validate riboflavin esters as a potential therapeutic strategy.
Functional Connectivity Between Somatosensory and Motor Brain Areas Predicts Individual Differences in Motor Learning by Observing
Authors: McGregor Heather R. , Gribble Paul L. 
Published: February 2017

AbstractAction observation can facilitate the acquisition of novel motor skills, however, there is considerable individual variability in the extent to which observation promotes motor learning. Here we tested the hypothesis that individual differences in brain function or structure can predict subsequent observation-related gains in motor learning. Subjects underwent an anatomical MRI scan and resting-state fMRI scans to assess pre-observation grey matter volume and pre-observation resting-state functional connectivity (FC), respectively. On the following day, subjects observed a video of a tutor adapting her reaches to a novel force field. After observation, subjects performed reaches in a force field as a behavioral assessment of gains in motor learning resulting from observation. We found that individual differences in resting-state FC, but not grey matter volume, predicted post-observation gains in motor learning. Pre-observation resting-state FC between left S1 and bilateral PMd, M1, S1 and left SPL was positively correlated with behavioral measures of post-observation motor learning. Sensory-motor resting-state FC can thus predict the extent to which observation will promote subsequent motor learning.New & NoteworthyWe show that individual differences in pre-observation brain function can predict subsequent observation-related gains in motor learning. Pre-observation resting-state functional connectivity within a sensory-motor network may be used as a biomarker for the extent to which observation promotes motor learning. This kind of information may be useful if observation is to be used as a way to boost neuroplasticity and sensory motor recovery for patients undergoing rehabilitation for diseases that impair movement such as stroke.
Do maternal antibodies facilitate hemagglutinin imprinting to influenza A viruses encountered early in childhood?
Authors: Gostic Katelyn M. , Ambrose Monique , Worobey Michael , Lloyd-Smith James O. 
Published: February 2017

In a recent study, we showed evidence for childhood HA imprinting, a phenomenon in which children develop preferential, lifelong immune memory against zoonotic influenza viruses with hemagglutinin (HA) antigens in the same phylogenetic group as the first influenza virus encountered in childhood (Gostic et al. 2016). Although our original study showed strong, population-level HA imprinting effects, it did not resolve the underlying immunological mechanisms.Similar immune imprinting phenomena, where individuals preferentially recall immune responses primed early in life, also influence seasonal influenza epidemiology via antigenic seniority (Lessler et al. 2012) and original antigenic sin (Francis 1960), yet the mechanisms underlying all these childhood immune imprinting phenomena remain poorly understood (Cobey & Hensley 2017). A recent letter from Dr. H. Lemke (Lemke 2017) suggested that these childhood imprinting effects might be mediated by the combined action of maternal antibodies (mAbs) and influenza antigen. In other words, that imprinting may require that children are exposed to influenza A virus in the first year of life, while maternal antibodies are still present.
Genetic Architecture and Molecular Networks Underlying Leaf Thickness in Desert-Adapted TomatoSolanum pennellii
Authors: Coneva Viktoriya , Frank Margaret H. , de Luis Balaguer Maria A. , Li Mao , Sozzani Rosangela , Chitwood Daniel H. 
Published: February 2017

AbstractThicker leaves allow plants to grow in water-limited conditions. However, our understanding of the genetic underpinnings of this highly functional leaf shape trait is poor. We used a custom-built confocal profilometer to directly measure leaf thickness in a set of introgression lines (ILs) derived from the desert tomato speciesSolanum pennellii, and identified quantitative trait loci (QTL). We report evidence of a complex genetic architecture of this trait and roles for both genetic and environmental factors. Several ILs with thick leaves have dramatically elongated palisade mesophyll cells and, in some cases, increased leaf ploidy. We characterized thick ILs 2-5 and 4-3 in detail and found increased mesophyll cell size and leaf ploidy levels, suggesting that endoreduplication underpins leaf thickness in tomato. Next, we queried the transcriptomes and inferred Dynamic Bayesian Networks of gene expression across early leaf ontogeny in these lines to compare the molecular networks that pattern leaf thickness. We show that thick ILs shareS. pennellii-like expression profiles for putative regulators of cell shape and meristem determinacy, as well as a general signature of cell cycle related gene expression. However, our network data suggest that leaf thickness in these two lines is patterned by at least partially distinct mechanisms. Consistent with this hypothesis, double homozygote lines combining introgression segments from these two ILs show additive phenotypes including thick leaves, higher ploidy levels and larger palisade mesophyll cells. Collectively, these data establish a framework of genetic, anatomical, and molecular mechanisms that pattern leaf thickness in desert-adapted tomato.
Tuning transcriptional regulation through signaling: A predictive theory of allosteric induction
Authors: Razo-Mejia Manuel , Barnes Stephanie L. , Belliveau Nathan M. , Chure Griffin , Einav Tal , Lewis Mitchell , Phillips Rob 
Published: February 2017

AbstractAllosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model not only accurately captures the induction profiles of these strains but also enables us to derive analytic expressions for key properties such as the dynamic range and [EC50]. Finally, we derive an expression for the free energy of allosteric repressors which enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.
The role of accounting for managing innovation processes when relationships matter
Authors: Lind Johnny 
Published: February 2017

PurposeThis paper studies how accounting information is used by actors in an innovation process. It investigates how accounting information influences and is influenced by the different actors. The purpose of this paper is to develop a more thorough understanding of the role of accounting in making the choices that form temporary solutions.Design/methodology/approachAn in-depth case study of the development of a standard software release within the telecom industry.FindingsThis study has shown that accounting was a key ingredient when temporary solutions were formed in the innovation processes. Actors used accounting to stabilize the content of the release in the formation of the gate documents and used accounting to destabilize the content between the temporary solutions. It is difficult to evaluate whether the use of accounting improved or harmed the innovation. Further, the study also revealed that the use of accounting influenced and was influenced by previous and prospective future deals. This put new challenges on the use of accounting because it involved negotiation processes that influenced the accounting figures.Practical implicationsThe findings provide insights into the procedures for finding temporary solutions in the innovation process and the role of accounting in these procedures.Originality/valueThis paper contributes by providing a more thorough understanding of the role of accounting regarding the choices that comprise the temporary solutions within the innovation process. In addition, it shows how accounting has a critical role both for settling on and modifying temporary solutions. Hence, the research demonstrated how studies of the role of accounting in innovation processes can contribute to the industrial network approach by giving a more thorough understanding of network dynamics and the process of attaining stability and instability in business networks.
Health monitoring impact on non-repairable component supply methods
Authors: Vandawaker Robert M. , Jacques David R. , Ryan Erin T. , Huscroft Joseph R. , Freels Jason K. 
Published: February 2017

Purpose
From on-board automotive diagnostics to real-time aircraft state of health, the implementation of health monitoring and management systems are an increasing trend. Further, reductions in operating budgets are forcing many companies and militaries to consider new operating and support environments. Combined with longer service lives for aircraft and other systems, maintenance and operations processes must be reconsidered. The majority of research efforts focus on health monitoring techniques and technologies, leaving others to determine the maintenance and logistics impact on the systems. The paper aims to discuss these issues.

Design/methodology/approach
This research analyzes the impact of a health monitoring system on a squadron of aircraft. Flight, maintenance and logistics operations are stochastically modeled to determine the impact of program decisions on supply metrics. An arena discrete event simulation is utilized to conduct this research on 20 components on each of the 12 aircraft modeled. Costs and availability are recorded for comparison across three sparing scenarios to include economic order quantity (EOQ) for baseline and health monitoring cases and a just-in-time (JIT) health monitoring set of simulations.

Findings
Data are presented for EOQ and JIT supply methods. A comparison of health monitoring enabled supply to current methods shows cost savings and availability gains. The different methodologies are compared and discussed as a trade-space for programmatic decisions.

Originality/value
This work demonstrates the ability of health monitoring systems and condition based maintenance to affect supply ordering decisions. The development of trade-spaces within operating environments is demonstrated along with the ability to conduct cost benefit analyses.
Operational integration in a craft-oriented small enterprise
Authors: Gamme Inger , Seim Eva Amdahl , Lodgaard Eirin , Andersen Bjørn 
Published: February 2017

Purpose
Many leisure boat manufacturers have thrived on designing and building highly customized boats based on longstanding traditions of craftsmanship. To achieve efficient value chains, it is not enough to optimize each process step, but also important to achieve a smooth flow through the dependencies between each process steps. The purpose of this paper is to focus on assessing enablers and disablers for operational integration in a craft-oriented small enterprise.

Design/methodology/approach
One case company has been studied, to identify enablers and disablers for operational integration in the value chain. The research methodology is based on semi-structured interviews with selected persons from different levels within the company.

Findings
The results indicate the importance of management promotion and support of integration and a strong relationship between foremen and operators. Furthermore, to avoid functional myopias, mechanisms to encourage horizontal integration could be useful. Small company and informal culture make integration easier. However, to further establish a common standardized platform, could be necessary. Even small physical barriers in the layout were experienced to affect the integration negatively.

Research limitations/implications
This has been an exploratory study of one single craft-oriented enterprise; hence it is difficult to generalize.

Practical implications
Based on empirical findings from the case study, recommendations on how to achieve better operational integration will be presented.

Originality/value
The research initiative provides knowledge experience of operational integration from a case study in one company within craft and artisan sector in Norway.
An Unexpected Finding in SUDEP Involving a Child: Focal Myocardial Infarct Adjacent to Bundle of His
Authors: Neff Jadee L. , Lin Peter T. 
Published: February 2017

AbstractSudden unexpected death in epilepsy (SUDEP) is a nontraumatic, nondrowning death of an individual with epilepsy in which an autopsy with appropriate ancillary studies does not identify a cause of death. The mechanism of death in SUDEP is unknown, but is thought to involve cardiac and/or respiratory mechanisms. Research in SUDEP is hindered by a lack of consensus regarding required components of a death investigation before a cause of death may be certified as SUDEP. Histopathologic examination of the cardiac conduction system is not routinely performed in SUDEP death investigations. We present a case of SUDEP where histopathologic examination of the cardiac conduction system revealed a focal myocardial infarct of the summit of the ventricular septum abutting the bundle of His, which potentially provides insight into the mechanism of SUDEP for this particular case, and suggests that routine examination of the cardiac conduction system in SUDEP may be beneficial.
Suppression of anti‐drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease
Authors: Strik A. S. , van den Brink G. R. , Ponsioen C. , Mathot R. , Löwenberg M. , D'Haens G. R. 
Published: February 2017

SummaryBackgroundLoss of response to anti‐tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti‐drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response.AimTo investigate whether addition of an immunomodulator to anti‐TNF monotherapy could lead to anti‐drug antibody suppression and regained clinical response in IBD patients.MethodsWe retrospectively collected measurements of infliximab or adalimumab serum concentrations and anti‐drug antibodies to identify anti‐drug positive patients with loss response who were given an immunomodulator.ResultsAnti‐drug antibodies against infliximab and adalimumab were detected in 98/376 (26%) and in 61/226 (27%) patients, respectively. Immunomodulators were given to 17/159 patients. Clinical response was recaptured in 6/10 patients receiving a thiopurine and in all (7/7) patients receiving methotrexate. In 7/8 patients on infliximab, serum concentrations increased (median 2.84 μg/mL; IQR: 1.19–4.98) and in 6/9 patients on adalimumab (median 3.10 μg/mL; IQR: 1.45–4.45). This was accompanied by a decrease in anti‐drug antibodies to undetectable levels (median 11 months for both anti‐TNF agents). In 23 patients, no immunomodulator was added but anti‐TNF interval was shortened (17/23) or dosage was increased (6/23), which resulted in a clinical response in 10/17 and 2/6 patients, respectively.ConclusionIn 77% of IBD patients with loss of response due to immunogenicity, addition of immunomodulator resulted in undetectable anti‐drug antibody levels, increased serum drug concentrations and regained clinical response. This strategy should be considered in this patient population before switching to other agents.
Desire to be ethical or ability to self‐control: Which is more crucial for ethical behavior?
Authors: Rua Tuvana , Lawter Leanna , Andreassi Jeanine 
Published: February 2017

AbstractPromoting ethical decisions and behaviors is challenging for any organization. Yet managers are still required to make ethical decisions under conditions which deplete their self‐control resources, such as high stress and long hours. This study examines the relationships among symbolic and internal moral identity, self‐control, and ethical behavior, and investigates whether self‐control acts as the mechanism through which moral identity leads to ethical behavior. Findings indicate that internal moral identity overrides symbolic moral identity in the relationship with self‐control and that self‐control fully mediates the relationship between internal moral identity and ethical behavior. The implications for organizations is that while rules, procedures, and ethics training are useful, managers with a strong moral compass will be more likely to practice self‐control leading to more ethical behaviors.
From piloting e‐submission to electronic management of assessment (EMA): Mapping grading journeys
Authors: Vergés Bausili Anna 
Published: February 2017

AbstractThe increasing interest in electronic management of assessment is a sign of a gradual institutionalisation of e‐submission and e‐marking technologies in UK Higher Education. The effective adoption of these technologies requires a managed approach, especially a detailed understanding of current assessment practices within the institution and the development of new or adapted business processes. The findings from close participant observation of assessment processes over a 2‐year period across a large Faculty reveal that three independent variables around (1) initial marking, (2) internal quality assurance and (3) the timing of the return of e‐feedback to students, determine variance in grading journeys. Despite the apparent wide variety of processes, five major grading journeys prevail: three varieties of moderation (moderation of multiple markers and moderation of single markers either before or after grades and feedback are released to students); and two forms of second marking (either blind or open to peers). Within an institution, the identification of major workflows is fundamental to both an effective implementation of assessment technologies and in conducting change. The identification of major workflows across UK Higher Education Institutions remains critical to attain the necessary software development from global vendors.
Drinkers' identification with varying alcohol consumption prototypes
Authors: Pettigrew Simone , Jongenelis Michelle I. , Pratt Iain S. , Slevin Terry , Chikritzhs Tanya 
Published: February 2017

AbstractIntroduction and AimsEfforts to reduce excessive alcohol consumption need to take into account drinkers' perceptions of their risk of alcohol‐related harm. The aim of the present study was to profile adult Australian drinkers according to their self‐identification with various drinker prototypes to determine the extent to which these prototypes are associated with perceived and actual risk of alcohol‐related harm.Design and MethodsA large web panel provider disseminated an online survey to a national sample of 2168 drinkers aged 18+ years who consumed alcohol at least twice per month. Respondents reported whether they considered themselves to be a light, occasional, social, heavy or binge drinker. The nominated category was compared with perceived and actual risk of alcohol‐related harm.ResultsThe prototype most commonly nominated by respondents was ‘social drinker’ (45%), and the least common was ‘binge drinker’ (7%). Although the heaviest drinkers in terms of actual reported consumption typically selected prototypes indicative of harmful consumption, many of those selecting prototypes indicative of moderate consumption were at risk of alcohol‐related harm.Discussion and ConclusionsMany adult drinkers may be unaware of their risk of alcohol‐related harm. The results suggest that there may be a need to recalibrate Australian drinkers' perceptions of high‐risk drinking. [Pettigrew S, Jongenelis MI, Pratt IS, Slevin T, Chikritzhs T. Drinkers' identification with varying alcohol consumption prototypes. Drug Alcohol Rev 2017;36:464‐467]