bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity of Mountain Hydroclimate Simulations in Variable‐Resolution CESM to Microphysics and Horizontal Resolution
Authors: Rhoades Alan M. , Ullrich Paul A. , Zarzycki Colin M. , Johansen Hans , Margulis Steven A. , Morrison Hugh , Xu Zexuan , Collins William D. 
Published: May 2018

AbstractMountains are natural dams that impede atmospheric moisture transport and water towers that cool, condense, and store precipitation. They are essential in the western United States where precipitation is seasonal, and snowpack is needed to meet water demand. With anthropogenic climate change increasingly threatening mountain snowpack, there is a pressing need to better understand the driving climatological processes. However, the coarse resolution typical of modern global climate models renders them largely insufficient for this task, and signals a need for an advanced strategy. This paper continues the assessment of variable‐resolution in the Community Earth System Model (VR‐CESM) in modeling mountain hydroclimatology to understand the role of grid‐spacing at 55, 28, 14, and 7 km and microphysics, specifically the Morrison and Gettelman (, MG1, https://doi.org/10.1175/2008JCLI2105.1) scheme versus the Gettelman and Morrison (, MG2, https://doi.org/10.1175/JCLI-D-14-00102.1) scheme. Eight VR‐CESM simulations were performed from 1999 to 2015 with the F_AMIP_CAM5 component set, which couples the atmosphere‐land models and prescribes ocean data. Refining horizontal grid‐spacing from 28 to 7 km with the MG1 scheme did not improve the simulated mountain hydroclimatology. Substantial improvements occurred with the use of MG2 at grid‐spacings
28 km compared to MG1 as shown with subsequent statistics. Average SWE bias diminished by 9.4X, 4.9X, and 3.5X from 55 to 7 km. The range in minimum (maximum) DJF spatial correlations increased by 0.1–0.2 in both precipitation and SWE. Mountain windward/leeward distributions and elevation profiles improved across hydroclimate variables, however not always with model resolution alone. Disconcertingly, all VR‐CESM simulations exhibited a systemic mountain cold bias that worsened with elevation and will require further examination.
SNAIL is a key regulator of alveolar rhabdomyosarcoma tumor growth and differentiation through repression of MYF5 and MYOD function
Authors: Skrzypek Klaudia , Kusienicka Anna , Trzyna Elzbieta , Szewczyk Barbara , Ulman Aleksandra , Konieczny Pawel , Adamus Tomasz , Badyra Bogna , Kortylewski Marcin , Majka Marcin 
Published: May 2018

AbstractRhabdomyosarcoma (RMS) is a mesenchymal tumor of soft tissue in children that originates from a myogenic differentiation defect. Expression of SNAIL transcription factor is elevated in the alveolar subtype of RMS (ARMS), characterized by a low myogenic differentiation status and high aggressiveness. In RMS patients SNAIL level increases with higher stage. Moreover, SNAIL level negatively correlates with MYF5 expression. The differentiation of human ARMS cells diminishes SNAIL level. SNAIL silencing in ARMS cells inhibits proliferation and induces differentiation in vitro, and thereby completely abolishes the growth of human ARMS xenotransplants in vivo. SNAIL silencing induces myogenic differentiation by upregulation of myogenic factors and muscle-specific microRNAs, such as miR-206. SNAIL binds to the MYF5 promoter suppressing its expression. SNAIL displaces MYOD from E-box sequences (CANNTG) that are associated with genes expressed during differentiation and G/C rich in their central dinucleotides. SNAIL silencing allows the re-expression of MYF5 and canonical MYOD binding, promoting ARMS cell myogenic differentiation. In differentiating ARMS cells SNAIL forms repressive complex with histone deacetylates 1 and 2 (HDAC1/2) and regulates their expression. Accordingly, in human myoblasts SNAIL silencing induces differentiation by upregulation of myogenic factors. Our data clearly point to SNAIL as a key regulator of myogenic differentiation and a new promising target for future ARMS therapies.
Crosslinking of fibrous hydrogels
Authors: Schoenmakers Daniël C. , Rowan Alan E. , Kouwer Paul H. J. 
Published: May 2018

AbstractIn contrast to most synthetic hydrogels, biological gels are made of fibrous networks. This architecture gives rise to unique properties, like low concentration, high porosity gels with a high mechanical responsiveness as a result of strain-stiffening. Here, we used a synthetic polymer model system, based on polyisocyanides, that we crosslinked selectively inside the bundles. This approach allows us to lock in the fibrous network present at the crosslinking conditions. At minimum crosslink densities, we are able to freeze in the architecture, as well as the associated mechanical properties. Rheology and X-ray scattering experiments show that we able to accurately tailor network mechanics, not by changing the gel composition or architecture, but rather by tuning its (thermal) history. Selective crosslinking is a crucial step in making biomimetic networks with a controlled architecture.
The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
Authors: Yasmin  , Maskari Raya Al , McEniery Carmel M. , Cleary Sarah E. , Li Ye , Siew Keith , Figg Nichola L. , Khir Ashraf W. , Cockcroft John R. , Wilkinson Ian B. , O’Shaughnessy Kevin M. 
Published: May 2018

AbstractStiffening of the aorta is an important independent risk factor for myocardial infarction and stroke. Yet its genetics is complex and little is known about its molecular drivers. We have identified for the first time, tagSNPs in the genes for extracellular matrix proteins, aggrecan and fibulin-1, that modulate stiffness in young healthy adults. We confirmed SNP associations with ex vivo stiffness measurements and expression studies in human donor aortic tissues. Both aggrecan and fibulin-1 were found in the aortic wall, but with marked differences in the distribution and glycosylation of aggrecan reflecting loss of chondroitin-sulphate binding domains. These differences were age-dependent but the striking finding was the acceleration of this process in stiff versus elastic young aortas. These findings suggest that aggrecan and fibulin-1 have critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening.
Audible Feedback Improves Internal Model Strength and Performance of Myoelectric Prosthesis Control
Authors: Shehata Ahmed W. , Scheme Erik J. , Sensinger Jonathon W. 
Published: May 2018

AbstractMyoelectric prosthetic devices are commonly used to help upper limb amputees perform activities of daily living, however amputees still lack the sensory feedback required to facilitate reliable and precise control. Augmented feedback may play an important role in affecting both short-term performance, through real-time regulation, and long-term performance, through the development of stronger internal models. In this work, we investigate the potential tradeoff between controllers that enable better short-term performance and those that provide sufficient feedback to develop a strong internal model. We hypothesize that augmented feedback may be used to mitigate this tradeoff, ultimately improving both short and long-term control. We used psychometric measures to assess the internal model developed while using a filtered myoelectric controller with augmented audio feedback, imitating classification-based control but with augmented regression-based feedback. In addition, we evaluated the short-term performance using a multi degree-of-freedom constrained-time target acquisition task. Results obtained from 24 able-bodied subjects show that an augmented feedback control strategy using audio cues enables the development of a stronger internal model than the filtered control with filtered feedback, and significantly better path efficiency than both raw and filtered control strategies. These results suggest that the use of augmented feedback control strategies may improve both short-term and long-term performance.
Whole-genome sequencing and antimicrobial resistance in Brucella melitensis from a Norwegian perspective
Authors: Johansen Tone B. , Scheffer Lonneke , Jensen Veronica K. , Bohlin Jon , Feruglio Siri L. 
Published: May 2018

AbstractBrucellosis is a rarely encountered infection in Norway. The aim of this study was to explore allBrucella melitensisisolates collected in Norway from 1999 to 2016 in relation to origin of infection and antimicrobial resistance patterns. A total of 23 isolates were analysed by whole-genome sequencing and compared with selected sequences ofB. melitensisavailable from NCBI. Additionally, SNP analysis in antibiotic resistance determining genes was performed. The majority belonged to the East Mediterranean clade (genotype II), while the remaining isolates belonged to the African clade (genotype III). These results indicate that human brucellosis in Norway is related to travels or migration from the Middle East, Asia or Africa, in accordance with results from Germany, Denmark and Sweden. Antibiotic susceptibility patterns were determined by broth microdilution method and/or gradient strip method. All isolates were susceptible for all tested antibiotics, except for rifampicin where phenotypical results indicated resistance or intermediate resistance in all isolates based on broth microdilution method, and in four isolates based on gradient strip testing. In contrast, screening of therpoBgene did not reveal any mutations in the previously describedrpoB“hot spot” regions related to rifampicin resistance, indicating overestimation of resistance based on phenotypical results.
Thiazole Amides, A Novel Class of Algaecides against Freshwater Harmful Algae
Authors: Wang Ying , Liu Qisheng , Wei Zhigang , Liu Na , Li Yajuan , Li Duo , Jin Zhong , Xu Xiaohua 
Published: May 2018

AbstractCurrently, harmful algal blooms are being one of ever-increasing global environmental problems. Much attention has been paid to the use of natural products as the selective algaecides due to their low toxicity, high selectivity and eco-friendly properties. In the present study, the thiazole alkaloid (1), originally isolated from Thermoactino-myces strain TM-64, was shown to exhibit potent algicidal activity against three typically harmful cyanobacterial algae, S. obliqnus, M. aeruginosa, and C. pyrenoidosa. Based on our previous work, a practical, scalable synthesis of alkaloid (1) was developed and reaction could be readily scaled up to more than 100 g. In addition, twenty-six analogues of alkaloid (1) by replacement of tryptamine moiety with different aromatic and aliphatic amines were also prepared. The bioassay results showed that most of these derivatives displayed potent algicidal activity against three harmful algae S. obliqnus, M. aeruginosa, and C. pyrenoidosa with IC50 values in the range of 1.5–5.0 μg/mL. Amongst them, compounds (10) and its hydrochloric salt (10S) were found to reveal powerful growth inhibitory activity against harmful cyanobacterial algae with IC50 values as low as 0.08 μg/mL, comparable to those of commercial algicide CuSO4 and herbicide Diuron.
Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice
Authors: Robinson Jennifer L. , Soria Paola , Xu Manshan , Vrana Mark , Luchetti Jeffrey , Lu Helen H. , Chen Jing , Wadhwa Sunil 
Published: May 2018

AbstractTemporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2-macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.
A rapid response magnitude scale for timely assessment of the high frequency seismic radiation
Authors: Picozzi M. , Bindi D. , Spallarossa D. , Di Giacomo D. , Zollo A. 
Published: May 2018

AbstractIn this work the scaling of seismic moment (M0) and radiated energy (Er) is investigated for almost 800 earthquakes of the 2016–17 Amatrice-Norcia sequences in Italy, ranging in moment magnitude (Mw) from 2.5 to 6.5. The analysis of the M0-to-Erscaling highlights a breaking of the source self-similarity, with higher stress drops for larger events. Our results show the limitation of using M0, and in turn Mw, to capture the variability of the high frequency ground motion. Since the observed seismicity does not agree with the assumptions on stress drop in the definition of Mw, we exploit the availability of both Erand M0to modify the definition of Mwand introduce a rapid response magnitude (Mr), which accounts for the dynamic properties of rupture. The new Mrscale allows us to improve the prediction of the earthquake shaking potential, as shown by the reduction of the between-event residuals computed for the peak ground velocity. The procedure we propose is therefore a significant step towards a quick assessment of earthquakes damage potential and timely implementation of emergency plans.
Quantification of Water Flux in Vesicular Systems
Authors: Hannesschläger Christof , Barta Thomas , Siligan Christine , Horner Andreas 
Published: May 2018

AbstractWater transport across lipid membranes is fundamental to all forms of life and plays a major role in health and disease. However, not only typical water facilitators like aquaporins facilitate water flux, but also transporters, ion channels or receptors represent potent water pathways. The efforts directed towards a mechanistic understanding of water conductivity determinants in transmembrane proteins, the development of water flow inhibitors, and the creation of biomimetic membranes with incorporated membrane proteins or artificial water channels depend on reliable and accurate ways of quantifying water permeabilities Pf. A conventional method is to subject vesicles to an osmotic gradient in a stopped-flow device: Fast recordings of scattered light intensity are converted into the time course of vesicle volume change. Even though an analytical solution accurately acquiring Pf from scattered light intensities exists, approximations potentially misjudging Pf by orders of magnitude are used. By means of computational and experimental data we point out that erroneous results such as that the single channel water permeability pf depends on the osmotic gradient are direct results of such approximations. Finally, we propose an empirical solution of which calculated permeability values closely match those calculated with the analytical solution in the relevant range of parameters.
Cross-talk among HMGA1 and FoxO1 in control of nuclear insulin signaling
Authors: Chiefari Eusebio , Arcidiacono Biagio , Palmieri Camillo , Corigliano Domenica Maria , Morittu Valeria Maria , Britti Domenico , Armoni Michal , Foti Daniela Patrizia , Brunetti Antonio 
Published: May 2018

AbstractAs a mediator of insulin-regulated gene expression, the FoxO1 transcription factor represents a master regulator of liver glucose metabolism. We previously reported that the high-mobility group AT-hook 1 (HMGA1) protein, a molecular switch for the insulin receptor gene, functions also as a downstream target of the insulin receptor signaling pathway, representing a critical nuclear mediator of insulin function. Here, we investigated whether a functional relationship existed between FoxO1 and HMGA1, which might help explain insulin-mediated gene transcription in the liver. To this end, as a model study, we investigated the canonical FoxO1-HMGA1-responsive IGFBP1 gene, whose hepatic expression is regulated by insulin. By using a conventional GST-pull down assay combined with co-immunoprecipitation and Fluorescence Resonance Energy Transfer (FRET) analyses, we provide evidence of a physical interaction between FoxO1 and HMGA1. Further investigation with chromatin immunoprecipitation, confocal microscopy, and Fluorescence Recovery After Photobleaching (FRAP) technology indicated a functional significance of this interaction, in both basal and insulin-stimulated states, providing evidence that, by modulating FoxO1 transactivation, HMGA1 is essential for FoxO1-induced IGFBP1 gene expression, and thereby a critical modulator of insulin-mediated FoxO1 regulation in the liver. Collectively, our findings highlight a novel FoxO1/HMGA1-mediated mechanism by which insulin may regulate gene expression and metabolism.
Why an intrinsic magnetic field does not protect a planet against atmospheric escape
Authors: Gunell Herbert , Maggiolo Romain , Nilsson Hans , Stenberg Wieser Gabriella , Slapak Rikard , Lindkvist Jesper , Hamrin Maria , De Keyser Johan 
Published: May 2018

The presence or absence of a magnetic field determines the nature of how a planet interacts with the solar wind and what paths are available for atmospheric escape. Magnetospheres form both around magnetised planets, such as Earth, and unmagnetised planets, like Mars and Venus, but it has been suggested that magnetised planets are better protected against atmospheric loss. However, the observed mass escape rates from these three planets are similar (in the approximate (0.5–2) kg s−1 range), putting this latter hypothesis into question. Modelling the effects of a planetary magnetic field on the major atmospheric escape processes, we show that the escape rate can be higher for magnetised planets over a wide range of magnetisations due to escape of ions through the polar caps and cusps. Therefore, contrary to what has previously been believed, magnetisation is not a sufficient condition for protecting a planet from atmospheric loss. Estimates of the atmospheric escape rates from exoplanets must therefore address all escape processes and their dependence on the planet’s magnetisation.
Des perturbateurs endocriniens « légalisés ». Le cas d’un phtalate dans le règlement européen REACH
Authors: Boullier Henri 
Published: May 2018

Comment comprendre la persistance de controverses sur les perturbateurs endocriniens alors que des dispositifs réglementaires les prennent déjà en charge ? Le cas d’une molécule aux propriétés bien connues de perturbation endocrinienne, comme le DEHP, un plastifiant omniprésent dans des produits que nous utilisons quotidiennement, illustre certaines limites des dispositifs légaux qui régissent la commercialisation des substances chimiques. Dans le cadre du règlement européen REACH, des compromis politiques, diplomatiques et économiques conduisent ainsi à catégoriser les usages du DEHP de manière à ménager la contrainte qui pèse sur l’industrie chimique.
Recent Advances in the Regioselective Synthesis of Indoles via C–H Activation/Functionalization
Authors: Sharma Upendra , Kumar Inder , Kumar Rakesh 
Published: May 2018

Indole is an important heterocyclic motif that occurs ubiquitously in bioactive natural products and pharmaceuticals. Immense efforts have been devoted to the synthesis of indoles starting from the Fisher indole synthesis to the recently developed C–H activation/functionalization-based methods. Herein, we have reviewed the progress made on the regioselective synthesis of functionalized indoles, including 2-substituted, 3-substituted and 2,3-disusbstituted indoles, since the year 2010.1	Introduction2	Metal-Catalyzed Synthesis of 2-Substituted Indoles3	Metal-Catalyzed Synthesis of 3-Substituted Indoles4	Metal-Free Synthesis of 3-Substituted Indoles5	Metal-Catalyzed 2,3-Disubstituted Indole Synthesis5.1	Metal-Catalyzed Intramolecular 2,3-Disubstituted Indole Synthesis5.2	Metal-Catalyzed Intermolecular 2,3-Disubstituted Indole Synthesis6	Metal-Free 2,3-Disubstituted Indole Synthesis6.1	N-Protected 2,3-Disubstituted Indole Synthesis6.2	N-Unprotected 2,3-Disubstituted Indole Synthesis7	Applications8	Summary and Outlook
Surgical Outcomes, Complications, and Management Strategies for Foramen Magnum Meningiomas
Authors: Magill Stephen , Shahin Maryam , Lucas Calixto-Hope , Yen Adam , Lee David , Raleigh David , Aghi Manish , Theodosopoulos Philip , McDermott Michael 
Published: May 2018

Objectives Foramen magnum meningiomas (FMM) are complex lesions because of their proximity to the brain stem and posterior cerebrovasculature. The objective of this study is to report surgical outcomes and complications after resection of FMM.
Methods A retrospective chart review was conducted on patients with FMM from 1998 to 2015. Univariate logistic regression and recursive partitioning analysis were used to identify risk factors associated with complications and extent of resection (EOR).
Results We identified 28 patients with FMM. Median follow-up was 5.9 years. Tumors were World Health Organization grade I (92.9%) or grade II (7.1%). The vertebral artery was completely encased (25%), partially encased (11%), or not encased (64%). Median size was 11.9 cm3. EOR was gross total (39%) and subtotal (61%). The observed recurrence rate was 4% (n = 1). There were 38 complications in 12 patients (43%), and 6 patients (21%) had complications requiring additional surgery. Complications included cerebrospinal fluid leak/hydrocephalus (n = 7, 25%), weakness (n = 4, 14%), numbness (n = 4, 14%), and cranial nerve deficits: IX, X (n = 4, 14%), XI (n = 2, 7%), XII (n = 5, 18%). Medical complications included pneumonia (n = 1, 4%) and meningitis (n = 1, 4%). Tumor volume greater than 14 cm3 (odds ratio [OR] = 21.7, p = 0.0010), any vertebral artery encasement (OR 6.1, p = 0.0386), and subtotal resection (OR 6.4, p = 0.0398) were significantly associated with complications. Tumor volume greater than 14 cm3 was also significantly associated with subtotal resection (OR 8.3, p = 0.0201).
Conclusions Resection of FMM carries perioperative morbidity that increases with larger tumor size. Despite the morbidity, long-term recurrence-free survival is achievable with maximal safe resection and adjuvant radiation.