bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic polymorphism related to monocyte-macrophage function is associated with graft-versus-host disease
Authors: Hyvärinen Kati , Ritari Jarmo , Koskela Satu , Niittyvuopio Riitta , Nihtinen Anne , Volin Liisa , Gallardo David , Partanen Jukka 
Published: November 2017

AbstractDespite detailed human leukocyte antigen (HLA) matching and modern immunosuppressive therapy, severe graft-versus-host disease (GvHD) remains a major hurdle for successful allogeneic hematopoietic stem cell transplantation (HSCT). As the genetic diversity in GvHD complicates the systematic discovery of associated variants across populations, we studied 122 GvHD-associated single nucleotide polymorphisms (SNPs) in 492 HLA-matched sibling HSCT donor-recipient pairs from Finland and Spain. The association between these candidate SNPs and grade III–IV acute GvHD and extensive chronic GvHD was assessed. The functional effects of the variants were determined using expression and cytokine quantitative trait loci (QTL) database analyses. Clear heterogeneity was observed in the associated markers between the two populations. Interestingly, the majority of markers, such as those annotated to IL1, IL23R, TLR9, TNF, and NOD2 genes, are related to the immunological response by monocytes-macrophages to microbes, a step that precedes GvHD as a result of intestinal lesions. Furthermore, cytokine QTL analysis showed that the GvHD-associated markers regulate IL1β, IFNγ, and IL6 responses. These results support a crucial role for the anti-microbial response in GvHD risk. Furthermore, despite apparent heterogeneity in the genetic markers associated with GvHD, it was possible to identify a biological pathway shared by most markers in both populations.
Inner Ear Otolith Asymmetry in Late-Larval Cichlid Fish (Oreochromis mossambicus, Perciformes) Showing Kinetotic Behaviour Under Diminished Gravity
Authors: Anken Ralf , Knie Miriam , Hilbig Reinhard 
Published: November 2017

AbstractThe inner ears of all vertebrates are designed to perceive auditory and vestibular inputs. Although a tremendous diversity in the inner ear can be found even among bony fishes, the morphologies of the utricle and of the semicircular canals are rather conservative among vertebrates. Fish show kinetoses under reduced gravity (spinning movements and looping responses) and are regarded model organisms concerning the performance of the otolithic organs. Otoliths can be analysed easily because they are compact, in contrast to the otoconial masses of other vertebrates. Here, late-larval Oreochromis mossambicus were subjected to 0.0001 × g and 0.04 × g aboard a sounding rocket, their behaviour was observed and morphometrical analyses on otoliths were carried out. Fish swimming kinetotically at 0.0001 × g had a higher asymmetry of utricular otoliths (gravity perception) but not of saccular otoliths (hearing process) than specimens behaving normally at this gravity level (p = 0.0055). Also, asymmetries of lapilli in animals swimming normally at 0.0001 × g were lower than asymmetries in specimens swimming normally at 0.04 × g (p = 0.06). This supports the “otolith asymmetry hypothesis”, an explanation for the susceptibility to kinetosis, particularly concerning the utricular otoliths. It would be interesting to identify processes generating asymmetric otoliths, also in regard to human motion sickness.
Characterizing the conformational landscape of MDM2-binding p53 peptides using Molecular Dynamics simulations
Authors: Yadahalli Shilpa , Li Jianguo , Lane David P. , Gosavi Shachi , Verma Chandra S. 
Published: November 2017

AbstractThe conformational landscapes of p53 peptide variants and phage derived peptide (12/1) variants, all known to bind to MDM2, are studied using hamiltonian replica exchange molecular dynamics simulations. Complementing earlier observations, the current study suggests that the p53 peptides largely follow the ‘conformational selection’ paradigm in their recognition of and complexation by MDM2 while the 12/1 peptides likely undergo some element of conformational selection but are mostly driven by ‘binding induced folding’. This hypothesis is further supported by pulling simulations that pull the peptides away from their bound states with MDM2. This data extends the earlier mechanisms proposed to rationalize the entropically driven binding of the p53 set and the enthalpically driven binding of the 12/1 set. Using our hypothesis, we suggest mutations to the 12/1 peptide that increase its helicity in simulations and may, in turn, shift the binding towards conformational selection. In summary, understanding the conformational landscapes of the MDM2-binding peptides may suggest new peptide designs with bespoke binding mechanisms.
Coupling of emergent octahedral rotations to polarization in (K,Na)NbO3 ferroelectrics
Authors: Levin I. , Krayzman V. , Cibin G. , Tucker M. G. , Eremenko M. , Chapman K. , Paul R. L. 
Published: November 2017

AbstractPerovskite potassium sodium niobates, K1−xNaxNbO3, are promising lead-free piezoelectrics. Their dielectric and piezoelectric characteristics peak near x = 0.5, but the reasons for such property enhancement remain unclear. We addressed this uncertainty by analyzing changes in the local and average structures across the x = 0.5 composition, which have been determined using simultaneous Reverse Monte Carlo fitting of neutron and X-ray total-scattering data, potassium EXAFS, and diffuse-scattering patterns in electron diffraction. Within the A-sites, Na cations are found to be strongly off-centered along the polar axis as a result of oversized cube-octahedral cages determined by the larger K ions. These Na displacements promote off-centering of the neighboring Nb ions, so that the Curie temperature and spontaneous polarization remain largely unchanged with increasing x, despite the shrinking octahedral volumes. The enhancement of the properties near x = 0.5 is attributed to an abrupt increase in the magnitude and probability of the short-range ordered octahedral rotations, which resembles the pre-transition behavior. These rotations reduce the bond tension around Na and effectively soften the short Na-O bond along the polar axis – an effect that is proposed to facilitate reorientation of the polarization as external electric field is applied.
Urinary volatile organic compounds in overweight compared to normal-weight children: results from the Italian I.Family cohort
Authors: Cozzolino Rosaria , De Giulio Beatrice , Marena Pasquale , Martignetti Antonella , Günther Kathrin , Lauria Fabio , Russo Paola , Stocchero Matteo , Siani Alfonso 
Published: November 2017

AbstractAccumulating evidence shows that urinary volatile organic compounds (VOCs) could be perturbed in many physiological and pathological states, including several diseases and different dietary exposures. Few studies investigated the urinary metabolic signature associated to excess body weight and obesity in adult populations, while a different VOCs profile was found in exhaled breath in obese as compared to lean children. Aim of this study was to evaluate the VOCs profile in the urine of 21 overweight/obese (OW/Ob) and 28 normal-weight (NW) children belonging to the Italian cohort of the I. Family study. Urine samples were analysed by Solid Phase Micro-Extraction (SPME) GC-MS under both acidic and alkaline conditions, in order to profile a wider range of urinary volatiles with different physicochemical properties. Multivariate statistics techniques were applied to bioanalytical data to visualize clusters of cases and detect the VOCs able to differentiate OW/Ob from NW children. Under alkaline conditions, fourteen VOCs were identified, distinguishing OW/Ob from NW children. Our results suggest that VOCs signatures differ between OW/Ob and NW children. However, the biological and pathophysiological meaning of the observed differences needs to be elucidated, in order to better understand the potential of urinary VOCs as early metabolic biomarkers of obesity.
Magnetoresistance and robust resistivity plateau in MoAs2
Authors: Wang Jialu , Li Lin , You Wei , Wang Tingting , Cao Chao , Dai Jianhui , Li Yuke 
Published: November 2017

AbstractWe have grown the MoAs2 single crystal which crystallizes in a monoclinic structure with C2/m space group. Transport measurements show that MoAs2 displays a metallic behavior at zero field and undergoes a metal-to-semiconductor crossover at low temperatures when the applied magnetic field is over 5 T. A robust resistivity plateau appears below 18 K and persists for the field up to 9 T. A large positive magnetoresistance (MR), reaching about 2600% at 2 K and 9 T, is observed when the field is perpendicular to the current. The MR becomes negative below 40 K when the field is rotated to be parallel to the current. The Hall resistivity shows the non-linear field-dependence below 70 K. The analysis using two-band model indicates a compensated electron-hole carrier density at low temperatures. A combination of the breakdown of Kohler’s rule, the abnormal drop and the cross point in Hall data implies that a possible Lifshitz transition has occurred between 30 K and 60 K, likely driving the compensated electron-hole density, the large MR as well as the metal-semiconductor transition in MoAs2. Our results indicate that the family of centrosymmetric transition-metal dipnictides has rich transport behavior which can in general exhibit variable metallic and topological features.
Biomechanics of an Articulated Screw in Acute Scapholunate Ligament Disruption
Authors: Schiffman Corey , Muriuki Muturi , Havey Robert , Voronov Leonard , Bindra Randy , Hiro Matthew 
Published: November 2017

Background An injury to the scapholunate interosseous ligament (SLIL) leads to instability in the scapholunate joint. Temporary fixation is used to protect the ligament during reconstruction or healing of the repair. Rigid screw fixation—by blocking relative physiological motion between the scaphoid and lunate—can lead to screw loosening, pullout, and fracture.
Purpose This study aims to evaluate changes in scaphoid and lunate kinematics following SLIL injury and the effectiveness of an articulating screw at restoring preinjury motion.
Materials and Methods The kinematics of the scaphoid and lunate were measured in 10 cadaver wrists through three motions driven by a motion simulator. The specimens were tested intact, immediately following SLIL injury, after subsequent cycling, and after fixation with a screw.
Results Significant changes in scaphoid and lunate motion occurred following SLIL injury. Postinjury cycling increased motion changes in flexion-extension and radial-ulnar deviation. The motion was not significantly different from the intact scapholunate joint after placement of the articulating screw.
Conclusion In agreement with other studies, sectioning of the SLIL led to significant kinematic changes of the scaphoid and lunate in all motions tested. Compared with intact scapholunate joint, no significant difference in kinematics was found after placement of the screw indicating a correction of some of the changes produced by SLIL transection. These findings suggest that the articulating screw may be effective for protecting a SLIL repair while allowing the physiological rotation to occur between the scaphoid and lunate.
Clinical Relevance A less rigid construct, such as the articulating screw, may allow earlier wrist rehabilitation with less screw pullout or failure.
Redox Changes in Amateur Race Car Drivers Before and After Racing
Authors: Bjugstad Kimberly , Gutowski Paul , Pekarek Jennifer , Bourg Pamela , Mains Charles , Bar-Or David 
Published: November 2017

AbstractDespite the unique opportunity race car driving provides to study exercise in extreme conditions, the sport of racing is under-represented. A better understanding of how racing changes physiological measures combined with driver demographics may help reduce driver risks and expand the field of driver science. This study charted the changes in heart rate, body temperature, blood pressure, static oxidation reduction potential (sORP), and antioxidant capacity in drivers before and after racing (n=23). The interaction between racing and driver characteristics on physiological variables were evaluated. Heart rate, body temperature, and sORP were elevated after racing (P<0.05). Age, cockpit temperature, experience, and speed did not correlate with physiological or oxidative measures (P>0.05). Elevated post-race sORP values were associated with higher pre-race systolic blood pressure and lower antioxidant capacity (P<0.05). We conclude that racing alters the redox response in drivers and that drivers’ pre-race systolic blood pressure and antioxidant capacity can further alter it. A better understanding of the physical and oxidative changes which result from racing may help minimize the unique risks
Screening for Type 1 Diabetes Risk in Newborns: The Freder1k Pilot Study in Saxony*
Authors: Hommel Angela , Haupt Florian , Delivani Petrina , Winkler Christiane , Stopsack Marina , Wimberger Pauline , Nitzsche Katharina , Heinke Sophie , Naeke Andrea , Ceglarek Uta , Thiery Joachim , Bergert Renate , Stadthaus Daniel , Groeger Katrin , Heubner Georg , Schramm Ursula , Dziambor Ullrich , Zirkel Agnes , Kiess Wieland , Mueller Iris , Lange Karin , Berner Reinhard , Bonifacio Ezio , Ziegler Anette-Gabriele ,   and the Freder1k Study Group
Published: November 2017

AbstractAn increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB1*03 (DR3), HLA DRB1*04 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.
Identification of Bioactive Compounds in Polar and Nonpolar Extracts of Araujia sericifera
Authors: Palomino-Schätzlein Martina , Montaño Mary , Escrig Pablo , Boira Herminio , Corma Avelino , Pineda-Lucena Antonio , Primo Jaime , Cabedo Nuria 
Published: November 2017

Abstract
Araujia sericifera is a native perennial, climbing laticiferous shrub from South America that is currently naturalized in many other countries. Previous data describe promising properties for A. sericifera, but no systematic study of its bioactive compounds and possible medicinal applications has been conducted to date. In the present study, aerial parts of A. sericifera (leaves, stems, and fruits) were explored by combining GC-MS and NMR spectroscopy analysis for both nonpolar (hexane) and polar (methanol) extracts. The hexanic extracts contained high amounts of pentacyclic triterpenes including two new metabolites, 3-tigloyl germanicol (18) and 3-tigloyl lupeol (19). The methanolic extracts revealed the presence of luteolin-7-glucoside (24), trigonelline (22), and conduritol F (23) as the main constituents. A multivariate study of a meaningful number of extracts allowed us to determine the distribution of compounds inside the plant. A cytotoxic evaluation in vitro showed that both leaf and fruit hexanic extracts presented a moderate activity against human breast carcinoma cell lines (MDA-MB-453 and MCF-7) and human colon carcinoma cell line (HCT-116) by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay.
In vivo measurements of interindividual differences in DNA glycosylases and APE1 activities
Authors: Chaim Isaac A. , Nagel Zachary D. , Jordan Jennifer J. , Mazzucato Patrizia , Ngo Le P. , Samson Leona D. 
Published: November 2017

SignificanceThe DNA in each cell is damaged thousands of times daily. Consequently, a battery of DNA repair pathways exist that allow repair of this damage. Failure to repair can lead to devastating diseases, including cancer and neurodegeneration. Each individual’s DNA repair capacity (DRC) is inherently different. Being able to measure an individual’s DRC could contribute to a personalized approach to prevent and treat disease. Here we present powerful tools for measuring in vivo base excision repair capacity for five distinct DNA lesions. We use these methods to predict the cellular responses to a variety of DNA damaging agents, and to monitor differences in DRC in primary human lymphocytes. Additionally, we unveil previously unknown transcriptional mutagenesis induced by DNA lesions.
Higher education governance in France, Germany, and Italy: Change and variation in the impact of transnational soft governance
Authors: Dobbins Michael , Knill Christoph 
Published: November 2017

Abstract
There is a consensus that transnational soft governance has unleashed the forces of change in higher education. However, individual national HE systems are still anchored in country-specific regulatory regimes, which reflect national-historical, institutional, and cultural developments. Against this background, three crucial questions guide our study: How does the state react to transnational pressures for change? How is transnationally inspired policy change ‘digested’ by the preexisting country-specific governance structures? And to what extent have national HE systems converged on a common governance model? To address these questions, we conduct a multi-level comparative analysis of developments in Germany, France, and Italy. We first break down the concept of higher education governance into sub-dimensions and derive concrete policy indicators for three historically embedded governance ideal types. Drawing on historical institutionalism and institutional isomorphism, we explore how historical legacies and transnational communication have impacted policy pathways over the past 30 years. We graphically illustrate the policy trajectories using our ‘governance triangles’, which encompass the balance of power between multiple actors, including the state and universities, university management and the academic profession, and external stakeholders.
Governance change and governance learning in Europe: stakeholder participation in environmental policy implementation
Authors: Challies Edward , Newig Jens , Kochskämper Elisa , Jager Nicolas W 
Published: November 2017

AbstractCurrent European Union (EU) policies require policy-makers on different levels of government to engage with new forms of governance such as participatory planning, aiming to improve environmental policy delivery. We address the central issue of how policy-makers learn about the appropriateness of different modes of governance. By way of example, we examine recent innovations in EU water governance – primarily through the enactment of the Water Framework Directive (2000) and the Floods Directive (2007), and their requirements for stakeholder participation in the planning process. We discuss scope for policy-induced ‘governance learning’, wherein policy-makers draw on evidence and experience to learn about how to design and execute effective participatory planning and decision-making. In doing so, we aim to extend work on policy learning by focusing on the procedural dimensions of governance, and make a case for more coordinated and systematic approaches to gathering evidence and learning from ongoing EU environmental policy implementation.
How does policy learning occur? The case of Belgian mental health care reforms
Authors: Thunus Sophie , Schoenaers Frédéric 
Published: November 2017

AbstractThis article asks how policy learning is achieved and whether and how it impacts on policy change. By drawing on the empirical case of Belgian mental health reforms, it shows that policy learning occurs through the very practice of policy-making. In-depth analyses of the process of preparing and devising, a current reform of mental health care delivery, called Reform 107, evidence that the transformation of policy learning – through verbal expression, inscription in documents or enactment in social situations such as meetings – is crucial to its impact on policy change. A phenomenological approach to knowledge in policy helps to perceive and describe the transformation of policy learning through practical actions and interactions involved in devising policy change. Analytically, looking at this transformation entails shifting the focus from big and visible changes in policy objectives and instruments to micro policy practices such as meeting and writing documents. Placing the focus on micro policy practices should not lead, however, to a disregard for the social context in which they develop. The interactionist concept of linked ecologies provides the means to consider social regulations influencing policy learning without underestimating their very ephemeral and contingent nature.
Wicked and less wicked problems: a typology and a contingency framework
Authors: Alford John , Head Brian W 
Published: November 2017

Abstract
This paper addresses shortcomings in the scholarship about ‘wicked problems’, and suggests ways of tackling them. Firstly, accounts of these problems tend to ‘totalise’, regarding them as intractable masses of complexity, so conflict-prone and/or intractable that they defy definition and solution. By contrast, we put forward a more nuanced analysis, arguing that complex problems vary in the extent of their wickedness, via such dimensions as their cognitive complexity or the diversity and irreconcilability of the actors or institutions involved. We propose a typology of different forms of wicked problems. A second shortcoming, linked to intractability, is that the favoured means of tackling wicked problems has tended towards ‘one best way’ approaches, most commonly collaboration with key stakeholders. Moreover, particular forms of collaboration tend to be routinely applied in ‘one-size-fits-all’ fashion to a variety of situations – notably with a plethora of actors, and a focus on governance rather than implementation management. We put forward a contingency framework, based on our typology, proposing which types of collaboration are suitable for which types of problem. Finally, we argue for a more realistic standard of success in dealing with wicked problems, especially the most difficult ones. To call for the ‘solving’ of these problems is to set up a standard which is not only impossible but also perhaps unnecessary. We argue that we do not so much ‘solve’ wicked problems as make progress towards improvement or towards better managing them. We spell out a more realistic version of ‘progress’.