bluuebunny/crossref_metadata_2025 huggingface dataset:
The Future of Sustainable Tourism in Developing Countries
Authors: Yfantidou Georgia , Matarazzo Michela
Published: October 2016

The term ‘green tourism’ is often used in conjunction with the desire for a balanced approach to tourism planning. ‘Green tourism’ is defined as tourism that enhances the local cultural elements, operating under the control of local communities, providing employment and maintaining the economic benefits within the local communities. In fact, the above definition is often poorly attested, since there are times when the economic benefits escape from local communities. For its part the tourist industry uses the term ‘green tourism’ as a message to tourists on energy saving, avoiding coastal pollution etc. Sometimes the same tourist businesses are accused of using the label ‘green’ primarily for marketing purposes. This paper shows that governments have a crucial role regarding encouragement to use cleaner technologies in the tourism sector and presenting different approaches for sustainability to be achieved in developing countries. Copyright © 2016 John Wiley & Sons, Ltd and ERP Environment
An empirical examination of vacillation theory
Authors: Kang Jingoo , Kang Ribuga , Kim Sang‐Joon
Published: October 2016

Research summary: Since Nickerson and Zenger (2002) proposed how vacillation may lead to organizational ambidexterity, large‐sample empirical tests of their theory have been missing. In this paper, we empirically examine the performance implications of vacillation. Building upon vacillation theory, we predict that the frequency and scale of vacillation will have inverted U‐shaped relationships with firm performance. We test our hypotheses using patent‐based measures of exploration and exploitation in the context of technological innovation and knowledge search.

Managerial summary: Firms often shift their focus on technological innovation and knowledge search from seeking new and novel knowledge (i.e., exploration) to extending and refining existing knowledge (i.e., exploitation) or vice versa. We examine how the frequency and scale of firms vacillating between exploration and exploitation may affect their performance. We find that both too infrequent or too frequent changes and a too small or too large scale of changes are not desirable. Copyright © 2016 John Wiley & Sons, Ltd.
Pattern‐based multi‐cloud architecture migration
Authors: Jamshidi Pooyan , Pahl Claus , Mendonça Nabor C.
Published: October 2016

Many organizations migrate on‐premise software applications to the cloud. However, current coarse‐grained cloud migration solutions have made such migrations a non transparent task, an endeavor based on trial‐and‐error. This paper presents Variability‐based, Pattern‐driven Architecture Migration (V‐PAM), a migration method based on (i) a catalogue of fine‐grained service‐based cloud architecture migration patterns that target multi‐cloud, (ii) a situational migration process framework to guide pattern selection and composition, and (iii) a variability model to structure system migration into a coherent framework. The proposed migration patterns are based on empirical evidence from several migration projects, best practice for cloud architectures and a systematic literature review of existing research. Variability‐based, Pattern‐driven Architecture Migration allows an organization to (i) select appropriate migration patterns, (ii) compose them to define a migration plan, and (iii) extend them based on the identification of new patterns in new contexts. The patterns are at the core of our solution, embedded into a process model, with their selection governed by a variability model. Copyright © 2016 John Wiley & Sons, Ltd.
A low‐cost real‐time face tracking system for ITSs and SDASs
Authors: Liu Leyuan , Chen Jingying , Gao Changxin , Sang Nong
Published: October 2016

It is important to track people's face efficiently and accurately in many Intelligent Transportation Systems (ITSs) and Safety Driving Assistant Systems (SDASs). This paper presents a high‐performance and low‐cost real‐time face tracking system, which runs on general onboard computer with very low CPU consumption. The proposed face tracking system is composed of four modules: the motion detector, face detector, face tracker, and face validator. The motion detector extracts motion areas by using a spatial‐temporal bi‐differential method with a very low computational cost. The face detector integrates motions into a cascade face detection framework to reject most of non‐face scanning‐windows to ensure efficient face localization. The face tracker fuses motion feature with color feature to alleviate the drifting problem during tracking. The face validator builds face appearance models online and identifies each specific tracked face to avoid confusion. Experimental results on three challenging video sequences show that the proposed face tracking system outperforms the state‐of‐the‐art face tracker and consumes only 5–13% CPU resources of a low‐spec onboard computer while processing in real time. Copyright © 2016 John Wiley & Sons, Ltd.
Temporal patterns of induction and recovery of biomarker transcriptional responses to 4‐Nonylphenol and 17β‐estradiol in the estuarine arrow goby, Clevelandia ios
Authors: Johnson Kaitlin M. , Lema Sean C.
Published: October 2016

Several estuaries along the Pacific Ocean coast of North America were identified recently as having elevated 4‐nonylphenol (4‐NP) in sediments and biota, raising concerns about reproductive impacts for wildlife given 4‐NP's established estrogenic activity as an endocrine‐disrupting compound. Here we characterize 4‐NP mediated induction and recovery of estrogen‐sensitive gene transcripts in the arrow goby (Clevelandia ios), an intertidal fish abundant in estuarine mud flats on the west coast of North America. Male gobies were exposed to waterborne 4‐NP at 10 μg/L or 100 μg/L for 20 days followed by a 20 day depuration period. Additional males were treated with 17β‐estradiol (E2; 50 ng/L). 4‐NP at 100 μg/L elevated hepatic mRNAs encoding vitellogenins A (vtgA) and C (vtgC) and choriogenin L (chgL) within 72 h, and choriogenin H minor (chgHm) within 12 days. Hepatic mRNAs encoding estrogen receptor alpha (esr1) were also elevated after 12 days of 4‐NP exposure, but returned to pre‐exposure levels at 20 days even under continuing 4‐NP treatment. 4‐NP did not alter mRNA levels of estrogen receptor gamma (esr2a) in the liver, or of esr1, esr2a, and cytochrome P450 aromatase B (cyp19a1b) in the brain. The temporal pattern of initial induction for hepatic vtgA, vtgC, and chgL transcripts by 4‐NP mirrored the pattern by E2, while chgHm and esr1 mRNA induction by 4‐NP lagged 2–11 days behind the responses of these transcripts to E2. These findings establish 4‐NP concentration‐ and time‐dependent induction patterns of choriogenin and vitellogenin transcription following exposure to environmentally relevant 4‐NP concentrations, while concurrently demonstrating tissue‐specific induction patterns for esr1 by estrogenic compounds. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1513–1529, 2017.
A Clear Difference Between the Outcomes After a Major Hepatectomy With and Without an Extrahepatic Bile Duct Resection
Authors: Takagi Takehiro , Yokoyama Yukihiro , Kokuryo Toshio , Ebata Tomoki , Ando Masahiko , Nagino Masato
Published: October 2016

Background

The procedure of a simple hepatectomy and a hepatectomy with an extrahepatic bile duct resection and subsequent choledocho‐jejunostomy is largely different. However, these two procedures are sometimes included in the same category. There are no studies comparing postoperative course and liver regeneration rate after a major hepatectomy with and without an extrahepatic bile duct resection.

Methods

We retrospectively reviewed medical records of 245 patients who underwent a right hepatectomy (RH, n = 55) or RH with an extrahepatic bile duct resection (RHEBR, n = 190). Postoperative complications, including incidence of posthepatectomy liver failure (PHLF) and hepatic regeneration rates after surgery, were evaluated.

Results

The incidence of PHLF was considerably higher in the RHEBR group than in the RH group (39.5 vs. 16.4 %, p = 0.001). The percentage of newly regenerated liver volume after the hepatectomies on postoperative days 6–8 was significantly lower in the RHEBR group than in the RH group (14.0 % in the RH; 7.9 % in the RHEBR group, p < 0.001). Especially type of surgery (RHEBR) was the only independent risk factor for an impaired liver regeneration rate by univariate and multivariate analyses. Furthermore, estimated hepatic regeneration rate by stepwise linear regression analysis in the RHEBR group was 7.1 % lower (95 % confidence interval 1.8–12.3, p = 0.011) than in the RH group.

Conclusion

These results suggest that the procedure of extrahepatic bile duct resection has a possibility of adverse impact on the postoperative outcome after major hepatectomy.
Cardiomyopathy as presenting sign of glycogenin‐1 deficiency—report of three cases and review of the literature
Authors: Hedberg‐Oldfors Carola , Glamuzina Emma , Ruygrok Peter , Anderson Lisa J. , Elliott Perry , Watkinson Oliver , Occleshaw Chris , Abernathy Malcolm , Turner Clinton , Kingston Nicola , Murphy Elaine , Oldfors Anders
Published: October 2016

We describe a new type of cardiomyopathy caused by a mutation in the glycogenin‐1 gene (GYG1). Three unrelated male patients aged 34 to 52 years with cardiomyopathy and abnormal glycogen storage on endomyocardial biopsy were homozygous for the missense mutation p.Asp102His in GYG1. The mutated glycogenin‐1 protein was expressed in cardiac tissue but had lost its ability to autoglucosylate as demonstrated by an in vitro assay and western blot analysis. It was therefore unable to form the primer for normal glycogen synthesis. Two of the patients showed similar patterns of heart dilatation, reduced ejection fraction and extensive late gadolinium enhancement on cardiac magnetic resonance imaging. These two patients were severely affected, necessitating cardiac transplantation. The cardiomyocyte storage material was characterized by large inclusions of periodic acid and Schiff positive material that was partly resistant to alpha‐amylase treatment consistent with polyglucosan. The storage material had, unlike normal glycogen, a partly fibrillar structure by electron microscopy. None of the patients showed signs or symptoms of muscle weakness but a skeletal muscle biopsy in one case revealed muscle fibres with abnormal glycogen storage. Glycogenin‐1 deficiency is known as a rare cause of skeletal muscle glycogen storage disease, usually without cardiomyopathy. We demonstrate that it may also be the cause of severe cardiomyopathy and cardiac failure without skeletal muscle weakness. GYG1 should be included in cardiomyopathy gene panels.
Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry
Authors: Kubaski Francyne , Mason Robert W. , Nakatomi Akiko , Shintaku Haruo , Xie Li , van Vlies Naomi N. , Church Heather , Giugliani Roberto , Kobayashi Hironori , Yamaguchi Seiji , Suzuki Yasuyuki , Orii Tadao , Fukao Toshiyuki , Montaño Adriana M. , Tomatsu Shunji
Published: October 2016

Background

Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis.

Methods

This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono‐ and di‐sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC‐MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns.

Results

The cutoffs were as follows: HS‐0S > 90 ng/mL; HS‐NS > 23 ng/mL, DS > 88 ng/mL; mono‐sulfated KS > 445 ng/mL; di‐sulfated KS > 89 ng/mL and ratio di‐KS in total KS > 32 %. All MPS I and II samples were above the cutoffs for HS‐0S, HS‐NS, and DS, and all MPS III samples were above cutoffs for HS‐0S and HS‐NS. The rate of false positives for MPS I and II was 0.03 % based on a combination of HS‐0S, HS‐NS, and DS, and for MPS III was 0.9 % based upon a combination of HS‐0S and HS‐NS.

Conclusions

Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS.
A Pilot Study of Fragile X Syndrome Screening in Pregnant Women and Women Planning Pregnancy: Implementation, Acceptance, Awareness, and Geographic Factors
Authors: Alfaro Arenas Ramona , Rosell Andreo Jordi , Heine Suñer Damián ,   Group for the study of FXS in the Balearic Islands
Published: October 2016

We report herein results of a study performed in the Balearic Islands which had the following goals: 1) Determine the proportion of pregnant or non‐pregnant women planning pregnancy, who would choose to undergo a screening test for Fragile X Syndrome (FXS), if it is accompanied by the appropriate information; 2) Assess satisfaction and any increase in stress among women who participate in screening; 3) Collect epidemiological information about the incidence of the disease in our population; and 4) Collect demographic and health history data and assess participants’ awareness of the disease. Screening was performed on 3,731 pregnant and non‐pregnant women of childbearing age and the results indicate: a very high voluntary rate of participation; a high level of self‐reported satisfaction and low levels of stress because of the test; a very high incidence of premutation (1/106) in our population; and a low level of awareness about the existence of FXS (25 %). Additional findings indicate no significant correlation between self‐reported health history and premutation detection, and the high premutation incidence does not seem to be specific to the indigenous Balearic population. Based on these results, we discuss the pros and cons of an implementation of preconception and pregnant women screening for FXS within a public health screening program.
A single-machine scheduling problem with multiple unavailability constraints: A mathematical model and an enhanced variable neighborhood search approach
Authors: Yazdani Maziar , Khalili Seyed Mohammad , Babagolzadeh Mahla , Jolai Fariborz
Published: October 2016

This research focuses on a scheduling problem with multiple unavailability periods and distinct due dates. The objective is to minimize the sum of maximum earliness and tardiness of jobs. In order to optimize the problem exactly a mathematical model is proposed. However due to computational difficulties for large instances of the considered problem a modified variable neighborhood search (VNS) is developed. In basic VNS, the searching process to achieve to global optimum or near global optimum solution is totally random, and it is known as one of the weaknesses of this algorithm. To tackle this weakness, a VNS algorithm is combined with a knowledge module. In the proposed VNS, knowledge module extracts the knowledge of good solution and save them in memory and feed it back to the algorithm during the search process. Computational results show that the proposed algorithm is efficient and effective.

Highlights A scheduling problem with multiple unavailability is proposed and formulated. A knowledge-based variable neighborhood search algorithm is proposed. Extensive computational tests confirm the good capability of the proposed model and algorithm.
Spatio-temporal changes in glacier-wide mass balance quantified by optical remote sensing on 30 glaciers in the French Alps for the period 1983–2014
Authors: RABATEL ANTOINE , DEDIEU JEAN PIERRE , VINCENT CHRISTIAN
Published: October 2016

Remote sensing is a powerful method to reconstruct annual mass-balance series over past decades by exploiting archives of available images, as well as to study glaciers in inaccessible regions. We present the application of a methodological framework based only on optical satellite images to retrieve glacier-wide annual mass balances for 30 glaciers in the French Alps. The glacier-wide annual mass balance for the period 1983–2014 was reconstructed by combining changes in glacier volumes computed from remote-sensing derived DEMs with annual measurements of the snow line altitude on satellite images. Data from direct observations on two of the glaciers confirmed the accuracy of the annual mass balances quantified by remote sensing with an average difference of ~0.3 m w.e., within the uncertainty range of the methods. Our results confirm the significant increase in mass loss since the early 2000s, with a difference >1 m w.e. a−1 between the periods 1983–2002 and 2003–14. The region-wide mass balance for the French Alps over the period 1979–2011 was −0.66 ± 0.27 m w.e. a−1, close to that of the European Alps. We also show that changes in glacier surface area or length are not representative of changes in mass balance at the scale of a few decades.
Large-sized Early Permian “caninioid” corals from the Karavanke Mountains, Slovenia
Authors: Kossovaya Olga L. , Novak Matevž , Weyer Dieter
Published: October 2016

A new monospecific “caninioid” genus,Preisingerellan. gen., from the lower Permian of the Karavanke Mountains (Southern Alps, Slovenia) is erected. The type species isPreisingerella stegovnikensisn. sp. The new taxon can be differentiated from otherCaninia-type genera by its specific ontogeny and features of its dissepimentarium. Corals with such morphology had a wide distribution during the Carboniferous and early Permian, occurring in mostly shallow-water carbonate rocks. The phylogenetic relationships within this group are mostly unclear due to similarities in the adult stages. The earlier stages reveal the main distinguishing features that are decisive for a generic assignment, but these have rarely been well preserved and properly considered. The new taxon is compared with related genera of the Cyathopsidae and species ofCaninellaGorskiy, 1938 characterized by lateral dissepiments. Large numbers of specimens of the new species, representing a monospecific assemblage, have been collected from the Born Formation at Mt. Stegovnik. Sedimentological and microfacies characteristics, as well as macro- and microfossil assemblages, underline this correlation. The fusulinoidean assemblage of the Born Formation, withSphaeroschwagerina carniolica(Kahler and Kahler, 1937), as the predominant species, corresponds to the time span between theSphaeroschwagerina moelleri-Schwagerina fecundaandPseudofusulina moellerizones, indicating a late Asselian to early Sakmarian age in the Southern Urals.
The phacopid trilobiteEchidnops taphomimusn. sp. from the Lower Devonian of Argentina: insights into infaunal molting, eye architecture and geographic distribution
Authors: Rustán Juan José , Balseiro Diego
Published: October 2016

Some Silurian-Devonian Argentinian trilobites characterized by infaunal behavior during molting are considered. After a taxonomic reappraisal, a species previously referred to a lineage of the phacopidPaciphacopsis proposed asEchidnops taphomimusnew species, from the Lower Devonian (probably late Lochkovian) of the Talacasto Formation, Argentine Precordillera. The visual surface ofE.taphomimusindicates that a irregular pattern of lens arrangement, typical of early phacopids such as the OrdovicianOrmathops, can also be recognized in more derived Devonian relatives, providing new insights on some evolutionary aspects of visual development.Echidnopsis recognized in Australia and Argentina, recording an unusual distribution pattern in trilobites from the Lower Devonian of southern South America, otherwise mostly linked to faunas of related Gondwanan, austral circum-polar Devonian basins of the Malvinokaffric Realm. In accordance with proposed increasing predation pressure in the context of the Mid Paleozoic Marine Revolution, evidence indicates that the infaunal molting behavior, as defensive strategy, arose in several trilobite groups during Silurian-Devonian times, rather than in a single endemic lineage ofPaciphacopsspecies.
Theory of pulsar magnetosphere and wind
Authors: Pétri Jérôme
Published: October 2016

Neutron stars are fascinating astrophysical objects immersed in strong gravitational and electromagnetic fields, at the edge of our current theories. These stars manifest themselves mostly as pulsars, emitting a timely very stable and regular electromagnetic signal. Even though discovered almost fifty years ago, they still remain mysterious compact stellar objects. In this review, we summarize the most fundamental theoretical aspects of neutron star magnetospheres and winds. The main competing models explaining their radiative properties like multi-wavelength pulse shapes and spectra and the underlying physical processes such as pair creation and radiation mechanisms are scrutinized. A global but still rather qualitative picture slowly emerges thanks to recent advances in numerical simulations on the largest scales. However considerations about pulsar magnetospheres remain speculative. For instance, the exact composition of the magnetospheric plasma is not yet known. Is it solely filled with a mixture of$e^{\pm }$ leptons or does it contain a non-negligible fraction of protons and/or ions? Is it almost entirely filled or mostly empty except for some small anecdotal plasma filled regions? Answers to these questions will strongly direct the description of the magnetosphere to seemingly contradictory results leading sometimes to inconsistencies. Nevertheless, accounts are given as to the latest developments in the theory of pulsar magnetospheres and winds, the existence of a possible electrosphere and physical insight obtained from related observational signatures of multi-wavelength pulsed emission.
Development and Validation of a Performance-Based Test to Assess	Instrumental Activities of Daily Living in Spanish Older Adults
Authors: Labra Pérez José Antonio , Menor Julio
Published: October 2016

Abstract. A key feature of the autonomy and quality of life of the elderly is their ability to perform instrumental activities of daily living (IADLs). When older people have difficulty in performing IADLs, many of their social and community activities may be affected, leading to their progressive isolation from society. This study describes the development and validation of a test that assesses six areas of daily functioning in the elderly: use of medication and healthcare management, administrative, financial management, transportation, meal preparation, and shopping. The study evaluated 164 healthy individuals without cognitive impairment using an extensive cognitive battery. The construct validity and reliability of test were examined. Findings revealed a good internal consistency and high inter-rater and test-retest reliability. As for construct validity, the instrument tasks were grouped into two dimensions, based on the cognitive components involved in each task: fluid and episodic memory tasks and crystallized tasks. The developed instrument may be useful for evaluating IADLs in those elderly who live at home and are somewhat dependent.
Retrospective Paternal and Maternal Parenting Styles in Greece,	Italy, and Sweden
Authors: Tagliabue Semira , Olivari Maria Giulia , Wahn Elisabeth Hertfelt , Maridaki-Kassotaki Katerina , Antonopoulou Katerina , Confalonieri Emanuela
Published: October 2016

Abstract. Discrepancies in perceived parenting and parental roles across European countries could be due to the use of different assessment techniques or due to mean level differences in the authoritative, authoritarian, or permissive parenting styles. The present study aimed to examine the psychometric characteristics of the Parenting Styles and Dimensions Questionnaire (PSDQ; Robinson, Mandleco, Olsen, & Hart, 1995 , 2001 ) in a sample of 225 Greek, 301 Italian, and 279 Swedish adolescents aged 16–19 years, who evaluated their father’s and mother’s parenting styles during their childhood. A confirmatory factor analysis (CFA), multigroup CFA, and modified version of the correlated uniqueness model were used to evaluate the structure and invariance of the scale across countries. Measurement and structural invariance was found in the 8-item authoritative scale and 6-item authoritarian scale. A mixed ANOVA (Country × Style × Role) showed that Swedish mothers scored lower than Italian or Greek mothers, and that, in the three countries, mothers were perceived as more authoritative than were fathers.
Self-Efficacy in Retrieving Positive Emotional Experience and Using	Humor
Authors: Gerbino Maria , Milioni Michaela , Alessandri Guido , Eisenberg Nancy , Caprara Mariagiovanna , Kupfer Anne , Pastorelli Concetta , Vittorio Caprara Gian
Published: October 2016

Abstract. Recent research has pointed to the benefits of positive emotions and their appropriate modulation in buffering the impact of negative experience, and in promoting well-being. Two studies examined the psychometric properties of a new scale that was designed to assess perceived self-efficacy in using memories of positive emotional experiences and humor to face challenges and to cope with stressful experiences. In the first study, we examined the factor structure and internal validity of two scales in youths from the United States (N = 1,277), Italy (N = 363), and Spain (N = 223). In the second study, we examined correlations of the two scales with positive affect, as well as other indicators of well-being and adjustment in the three countries (US: N = 499; Italian and Spanish samples of Study 1). The results of the exploratory and confirmatory factor analyses supported two distinct factors and showed acceptable partial invariance of the scales across countries. Correlations supported the scales’ construct and discriminant validity. Overall, the findings corroborated the psychometric properties of the two scales and the view of retrieval of positive emotional experiences and humor as distinct self-regulatory strategies.
Factor Structure and Longitudinal Factorial Validity of the Core	Self-Evaluation Scale
Authors: Mäkikangas Anne , Kinnunen Ulla , Mauno Saija , Selenko Eva
Published: October 2016

Abstract. The personality high-order concept of core self-evaluations (CSE), which refers to a basic evaluation of one’s worth, capability, and effectiveness, has attracted a lot of research interest. Yet little is known about the construct validity of the core self-evaluation scale (CSES) while information on its longitudinal factorial validity is wholly lacking. This study investigated the factor structure of the CSES using both confirmatory and exploratory factor analysis implemented in Mplus program. In addition, the factor loading invariance over time was investigated using exploratory structural equation modeling. Longitudinal data with three follow-ups over 2 years, gathered among university employees (n = 926 (T3)–2,137 (T1)), were used. The results showed that a two-factor solution comprising the sub-dimensions Internal and External self-evaluations fitted to the data better than the alternative factor models. The two-factor solution was also invariant across the three measurements. It is concluded that the CSES could be used as a two-dimensional instead of a one-dimensional scale. Splitting the scale into the two sub-dimensions of Internal and External self-evaluations revealed that the concept has a finer-grained structure than hitherto thought.
An interdigit signalling centre instructs coordinate phalanx-joint formation governed by 5′Hoxd–Gli3 antagonism
Authors: Huang Bau-Lin , Trofka Anna , Furusawa Aki , Norrie Jacqueline L. , Rabinowitz Adam H. , Vokes Steven A. , Mark Taketo M. , Zakany Jozsef , Mackem Susan
Published: October 2016

The number of phalanges and joints are key features of digit ‘identity’ and are central to limb functionality and evolutionary adaptation. Prior chick work indicated that digit phalanges and their associated joints arise in a different manner than the more sparsely jointed long bones, and their identity is regulated by differential signalling from adjacent interdigits. Currently, there is no genetic evidence for this model, and the molecular mechanisms governing digit joint specification remain poorly understood. Using genetic approaches in mouse, here we show that functional 5′Hoxd–Gli3 antagonism acts indirectly, through Bmp signalling from the interdigital mesenchyme, to regulate specification of joint progenitors, which arise in conjunction with phalangeal precursors at the digit tip. Phalanx number, although co-regulated, can be uncoupled from joint specification. We propose that 5′Hoxd genes and Gli3 are part of an interdigital signalling centre that sets net Bmp signalling levels from different interdigits to coordinately regulate phalanx and joint formation.
Bimodal antagonism of PKA signalling by ARHGAP36
Authors: Eccles Rebecca L. , Czajkowski Maciej T. , Barth Carolin , Müller Paul Markus , McShane Erik , Grunwald Stephan , Beaudette Patrick , Mecklenburg Nora , Volkmer Rudolf , Zühlke Kerstin , Dittmar Gunnar , Selbach Matthias , Hammes Annette , Daumke Oliver , Klussmann Enno , Urbé Sylvie , Rocks Oliver
Published: October 2016

Protein kinase A is a key mediator of cAMP signalling downstream of G-protein-coupled receptors, a signalling pathway conserved in all eukaryotes. cAMP binding to the regulatory subunits (PKAR) relieves their inhibition of the catalytic subunits (PKAC). Here we report that ARHGAP36 combines two distinct inhibitory mechanisms to antagonise PKA signalling. First, it blocks PKAC activity via a pseudosubstrate motif, akin to the mechanism employed by the protein kinase inhibitor proteins. Second, it targets PKAC for rapid ubiquitin-mediated lysosomal degradation, a pathway usually reserved for transmembrane receptors. ARHGAP36 thus dampens the sensitivity of cells to cAMP. We show that PKA inhibition by ARHGAP36 promotes derepression of the Hedgehog signalling pathway, thereby providing a simple rationale for the upregulation of ARHGAP36 in medulloblastoma. Our work reveals a new layer of PKA regulation that may play an important role in development and disease.
Striatal prediction errors support dynamic control of declarative memory decisions
Authors: Scimeca Jason M. , Katzman Perri L. , Badre David
Published: October 2016

Adaptive memory requires context-dependent control over how information is retrieved, evaluated and used to guide action, yet the signals that drive adjustments to memory decisions remain unknown. Here we show that prediction errors (PEs) coded by the striatum support control over memory decisions. Human participants completed a recognition memory test that incorporated biased feedback to influence participants’ recognition criterion. Using model-based fMRI, we find that PEs—the deviation between the outcome and expected value of a memory decision—correlate with striatal activity and predict individuals’ final criterion. Importantly, the striatal PEs are scaled relative to memory strength rather than the expected trial outcome. Follow-up experiments show that the learned recognition criterion transfers to free recall, and targeting biased feedback to experimentally manipulate the magnitude of PEs influences criterion consistent with PEs scaled relative to memory strength. This provides convergent evidence that declarative memory decisions can be regulated via striatally mediated reinforcement learning signals.
Thermally-nucleated self-assembly of water and alcohol into stable structures at hydrophobic interfaces
Authors: Voïtchovsky Kislon , Giofrè Daniele , José Segura Juan , Stellacci Francesco , Ceriotti Michele
Published: October 2016

At the interface with solids, the mobility of liquid molecules tends to be reduced compared with bulk, often resulting in increased local order due to interactions with the surface of the solid. At room temperature, liquids such as water and methanol can form solvation structures, but the molecules remain highly mobile, thus preventing the formation of long-lived supramolecular assemblies. Here we show that mixtures of water with methanol can form a novel type of interfaces with hydrophobic solids. Combiningin situatomic force microscopy and multiscale molecular dynamics simulations, we identify solid-like two-dimensional interfacial structures that nucleate thermally, and are held together by an extended network of hydrogen bonds. On graphite, nucleation occurs above ∼35 °C, resulting in robust, multilayered nanoscopic patterns. Our findings could have an impact on many fields where water-alcohol mixtures play an important role such as fuel cells, chemical synthesis, self-assembly, catalysis and surface treatments.
Nanoscale probing of electron-regulated structural transitions in silk proteins by near-field IR imaging and nano-spectroscopy
Authors: Qin Nan , Zhang Shaoqing , Jiang Jianjuan , Corder Stephanie Gilbert , Qian Zhigang , Zhou Zhitao , Lee Woonsoo , Liu Keyin , Wang Xiaohan , Li Xinxin , Shi Zhifeng , Mao Ying , Bechtel Hans A. , Martin Michael C. , Xia Xiaoxia , Marelli Benedetto , Kaplan David L. , Omenetto Fiorenzo G. , Liu Mengkun , Tao Tiger H.
Published: October 2016

Silk protein fibres produced by silkworms and spiders are renowned for their unparalleled mechanical strength and extensibility arising from their high-β-sheet crystal contents as natural materials. Investigation of β-sheet-oriented conformational transitions in silk proteins at the nanoscale remains a challenge using conventional imaging techniques given their limitations in chemical sensitivity or limited spatial resolution. Here, we report on electron-regulated nanoscale polymorphic transitions in silk proteins revealed by near-field infrared imaging and nano-spectroscopy at resolutions approaching the molecular level. The ability to locally probe nanoscale protein structural transitions combined with nanometre-precision electron-beam lithography offers us the capability to finely control the structure of silk proteins in two and three dimensions. Our work paves the way for unlocking essential nanoscopic protein structures and critical conditions for electron-induced conformational transitions, offering new rules to design protein-based nanoarchitectures.
Non-enzymatic pyridine ring formation in the biosynthesis of the rubrolone tropolone alkaloids
Authors: Yan Yijun , Yang Jing , Yu Zhiyin , Yu Mingming , Ma Ya-Tuan , Wang Li , Su Can , Luo Jianying , Horsman Geoffrey P. , Huang Sheng-Xiong
Published: October 2016

The pyridine ring is a potent pharmacophore in alkaloid natural products. Nonetheless, its biosynthetic pathways are poorly understood. Rubrolones A and B are tropolone alkaloid natural products possessing a unique tetra-substituted pyridine moiety. Here, we report the gene cluster and propose a biosynthetic pathway for rubrolones, identifying a key intermediate that accumulates upon inactivation of sugar biosynthetic genes. Critically, this intermediate was converted to the aglycones of rubrolones by non-enzymatic condensation and cyclization with either ammonia or anthranilic acid to generate the respective pyridine rings. We propose that this non-enzymatic reaction occurs via hydrolysis of the key intermediate, which possesses a 1,5-dione moiety as an amine acceptor capable of cyclization. This study suggests that 1,5-dione moieties may represent a general strategy for pyridine ring biosynthesis, and more broadly highlights the utility of non-enzymatic diversification for exploring and expanding natural product chemical space.
Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2
Authors: Baik June , Magli Alessandro , Tahara Naoyuki , Swanson Scott A. , Koyano-Nakagawa Naoko , Borges Luciene , Stewart Ron , Garry Daniel J. , Kawakami Yasuhiko , Thomson James A. , Perlingeiro Rita C. R.
Published: October 2016

Mechanisms of haematopoietic and cardiac patterning remain poorly understood. Here we show that the BMP and Wnt signalling pathways are integrated in an endoglin (Eng)-dependent manner in cardiac and haematopoietic lineage specification. Eng is expressed in early mesoderm and marks both haematopoietic and cardiac progenitors. In the absence of Eng, yolk sacs inappropriately express the cardiac marker, Nkx2.5. Conversely, high levels of Eng in vitro and in vivo increase haematopoiesis and inhibit cardiogenesis. Levels of Eng determine the activation of both BMP and Wnt pathways, which are integrated downstream of Eng by phosphorylation of Smad1 by Gsk3. By interrogating Eng-dependent Wnt-mediated transcriptional changes, we identify Jdp2 as a key Eng-dependent Wnt target, sufficient to establish haematopoietic fate in early mesoderm when BMP and Wnt crosstalk is disturbed. These studies provide mechanistic insight into the integration of BMP and Wnt signalling in the establishment of haematopoietic and cardiac progenitors during embryogenesis.
Experimental creation of quantum Zeno subspaces by repeated multi-spin projections in diamond
Authors: Kalb N. , Cramer J. , Twitchen D. J. , Markham M. , Hanson R. , Taminiau T. H.
Published: October 2016

Repeated observations inhibit the coherent evolution of quantum states through the quantum Zeno effect. In multi-qubit systems this effect provides opportunities to control complex quantum states. Here, we experimentally demonstrate that repeatedly projecting joint observables of multiple spins creates quantum Zeno subspaces and simultaneously suppresses the dephasing caused by a quasi-static environment. We encode up to two logical qubits in these subspaces and show that the enhancement of the dephasing time with increasing number of projections follows a scaling law that is independent of the number of spins involved. These results provide experimental insight into the interplay between frequent multi-spin measurements and slowly varying noise and pave the way for tailoring the dynamics of multi-qubit systems through repeated projections.
Carbon-Coated, Diatomite-Derived Nanosilicon as a High Rate Capable Li-ion Battery Anode
Authors: Campbell Brennan , Ionescu Robert , Tolchin Maxwell , Ahmed Kazi , Favors Zachary , Bozhilov Krassimir N. , Ozkan Cengiz S. , Ozkan Mihrimah
Published: October 2016

Silicon is produced in a variety of ways as an ultra-high capacity lithium-ion battery (LIB) anode material. The traditional carbothermic reduction process required is expensive and energy-intensive; in this work, we use an efficient magnesiothermic reduction to convert the silica-based frustules within diatomaceous earth (diatomite, DE) to nanosilicon (nanoSi) for use as LIB anodes. Polyacrylic acid (PAA) was used as a binder for the DE-based nanoSi anodes for the first time, being attributed for the high silicon utilization under high current densities (up to 4C). The resulting nanoSi exhibited a high BET specific surface area of 162.6 cm2 g−1, compared to a value of 7.3 cm2 g−1 for the original DE. DE contains SiO2 architectures that make ideal bio-derived templates for nanoscaled silicon. The DE-based nanoSi anodes exhibit good cyclability, with a specific discharge capacity of 1102.1 mAh g−1 after 50 cycles at a C-rate of C/5 (0.7 A gSi−1) and high areal loading (2 mg cm−2). This work also demonstrates the fist rate capability testing for a DE-based Si anode; C-rates of C/30 - 4C were tested. At 4C (14.3 A gSi−1), the anode maintained a specific capacity of 654.3 mAh g−1 – nearly 2x higher than graphite’s theoretical value (372 mAh g−1).
Erratum: Insight into the template effect of vesicles on the laccase-catalyzed oligomerization of N-phenyl-1,4-phenylenediamine from Raman spectroscopy and cyclic voltammetry measurements
Authors: Ležaić Aleksandra Janoševic , Luginbühl Sandra , Bajuk-Bogdanović Danica , Pašti Igor , Kissner Reinhard , Rakvin Boris , Walde Peter , Ćirić-Marjanović Gordana
Published: October 2016

Scientific Reports 6: Article number: 30724; published online: 26 August 2016; updated: 07 October 2016 In the original version of this Article, Peter Walde was incorrectly affiliated with: University of Belgrade-Faculty of Pharmacy, Department of Physical Chemistry and Instrumental Methods, VojvodeStepe 450, 11221 Belgrade, Serbia.
A study of the temporal robustness of the growing global container-shipping network
Authors: Wang Nuo , Wu Nuan , Dong Ling-ling , Yan Hua-kun , Wu Di
Published: October 2016

Whether they thrive as they grow must be determined for all constantly expanding networks. However, few studies have focused on this important network feature or the development of quantitative analytical methods. Given the formation and growth of the global container-shipping network, we proposed the concept of network temporal robustness and quantitative method. As an example, we collected container liner companies’ data at two time points (2004 and 2014) and built a shipping network with ports as nodes and routes as links. We thus obtained a quantitative value of the temporal robustness. The temporal robustness is a significant network property because, for the first time, we can clearly recognize that the shipping network has become more vulnerable to damage over the last decade: When the node failure scale reached 50% of the entire network, the temporal robustness was approximately −0.51% for random errors and −12.63% for intentional attacks. The proposed concept and analytical method described in this paper are significant for other network studies.
Testing multi-scale processing in the auditory system
Authors: Teng Xiangbin , Tian Xing , Poeppel David
Published: October 2016

Natural sounds contain information on multiple timescales, so the auditory system must analyze and integrate acoustic information on those different scales to extract behaviorally relevant information. However, this multi-scale process in the auditory system is not widely investigated in the literature and existing models of temporal integration are mainly built upon detection or recognition tasks on a single timescale. Here we use a paradigm requiring processing on relatively ‘local’ and ‘global’ scales and provide evidence suggesting that the auditory system extracts fine-detail acoustic information using short temporal windows and uses long temporal windows to abstract global acoustic patterns. Behavioral task performance that requires processing fine-detail information does not improve with longer stimulus length, contrary to predictions of previous temporal integration models such as the multiple-looks and the spectro-temporal excitation pattern model. Moreover, the perceptual construction of putatively ‘unitary’ auditory events requires more than hundreds of milliseconds. These findings support the hypothesis of a dual-scale processing likely implemented in the auditory cortex.
Hepatic Deletion of Janus Kinase 2 Counteracts Oxidative Stress in Mice
Authors: Themanns Madeleine , Mueller Kristina M. , Kessler Sonja M. , Golob-Schwarzl Nicole , Mohr Thomas , Kaltenecker Doris , Bourgeais Jerome , Paier-Pourani Jamile , Friedbichler Katrin , Schneller Doris , Schlederer Michaela , Zebedin-Brandl Eva , Terracciano Luigi M. , Han Xiaonan , Kenner Lukas , Wagner Kay-Uwe , Mikulits Wolfgang , Kozlov Andrey V. , Heim Markus H. , Gouilleux Fabrice , Haybaeck Johannes , Moriggl Richard
Published: October 2016

Genetic deletion of the tyrosine kinase JAK2 or the downstream transcription factor STAT5 in liver impairs growth hormone (GH) signalling and thereby promotes fatty liver disease. Hepatic STAT5 deficiency accelerates liver tumourigenesis in presence of high GH levels. To determine whether the upstream kinase JAK2 exerts similar functions, we crossed mice harbouring a hepatocyte-specific deletion of JAK2 (JAK2Δhep) to GH transgenic mice (GHtg) and compared them to GHtgSTAT5Δhep mice. Similar to GHtgSTAT5Δhep mice, JAK2 deficiency resulted in severe steatosis in the GHtg background. However, in contrast to STAT5 deficiency, loss of JAK2 significantly delayed liver tumourigenesis. This was attributed to: (i) activation of STAT3 in STAT5-deficient mice, which was prevented by JAK2 deficiency and (ii) increased detoxification capacity of JAK2-deficient livers, which diminished oxidative damage as compared to GHtgSTAT5Δhep mice, despite equally severe steatosis and reactive oxygen species (ROS) production. The reduced oxidative damage in JAK2-deficient livers was linked to increased expression and activity of glutathione S-transferases (GSTs). Consistent with genetic deletion of Jak2, pharmacological inhibition and siRNA-mediated knockdown of Jak2 led to significant upregulation of Gst isoforms and to reduced hepatic oxidative DNA damage. Therefore, blocking JAK2 function increases detoxifying GSTs in hepatocytes and protects against oxidative liver damage.
Glibenclamide impairs responses of neutrophils against Burkholderia pseudomallei by reduction of intracellular glutathione
Authors: Kewcharoenwong Chidchamai , Rinchai Darawan , Nithichanon Arnone , Bancroft Gregory J. , Ato Manabu , Lertmemongkolchai Ganjana
Published: October 2016

The major risk factor for melioidosis, an infectious disease caused by B. pseudomallei, is diabetes mellitus. More than half of diabetic melioidosis patients in Thailand were prescribed glibenclamide. Recent evidence demonstrates that glibenclamide reduces pro-inflammatory cytokine production by polymorphonuclear neutrophils (PMNs) of diabetic individuals in response to this bacterial infection. However, the mechanisms by which glibenclamide affects cytokine production are unknown. We found that PMNs from glibenclamide-treated diabetic individuals infected with live B. pseudomallei in vitro showed lower free glutathione (GSH) levels compared with those of healthy individuals. Glibenclamide decreased GSH levels and glutathione peroxidase (GPx) of PMNs after exposed to live B. pseudomallei. Moreover, glibenclamide reduced cytokine production and migration capacity of infected PMNs, whereas GSH could restore these functions. Taken together, our data show a link between the effect of glibenclamide on GSH and PMN functions in response to B. pseudomallei that may contribute to the susceptibility of diabetic individuals to B. pseudomallei infection.
Implementation of Arithmetic and Nonarithmetic Functions on a Label-free and DNA-based Platform
Authors: Wang Kun , He Mengqi , Wang Jin , He Ronghuan , Wang Jianhua
Published: October 2016

A series of complex logic gates were constructed based on graphene oxide and DNA-templated silver nanoclusters to perform both arithmetic and nonarithmetic functions. For the purpose of satisfying the requirements of progressive computational complexity and cost-effectiveness, a label-free and universal platform was developed by integration of various functions, including half adder, half subtractor, multiplexer and demultiplexer. The label-free system avoided laborious modification of biomolecules. The designed DNA-based logic gates can be implemented with readout of near-infrared fluorescence, and exhibit great potential applications in the field of bioimaging as well as disease diagnosis.