bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐based derivation of peptide inhibitors to target TGF‐β1 receptor for the suppression of hypertrophic scarring fibroblast activation
Authors: Hu Huan , Yang Songlin , Zheng Jianghong , Mao Guangyu 
Published: January 2017

The intermolecular recognition and interaction between human transforming growth factor β‐1 (TGF‐β1) and its cognate receptor TβRII have been implicated in the pathological condition of hypertrophic scarring (HS). Here, we attempted to rationally derive peptide inhibitors from the complex interface of TGF‐β1 with TβRII to disrupt such interaction for the suppression of fibroblast activation involved in HS. A synthetic strategy that integrated computational design and fluorescence‐based assay was described to examine the structural basis and energetic property of TGF‐β1–TβRII crystal structure, from which a small peptide segment in the complex binding site was stripped artificially. Molecular dynamics simulations revealed that the linear peptide possesses a large intrinsic disorder that would incur considerable entropy penalty upon binding to TβRII; the peptide segment was then extended and cyclized by introducing a disulfide bond across its terminal residues that were premutated to cysteine. Normal mode analysis indicated that, as expected, the peptide flexibility was largely reduced upon the cyclization, and thus, the entropy penalty was minimized substantially, consequently promoting the spontaneous binding of peptide to TβRII. Fluorescence polarization assay confirmed that all linear peptides are typical non‐binders of TβRII (Kd = ND), while the designed cyclic peptides exhibit moderate or high affinity with Kd at micromolar level.
Design, synthesis and cytotoxic evaluation of nitric oxide‐releasing derivatives of isosteviol
Authors: Liu Yan , Wang Tingting , Ling Yong , Bao Na , Shi Wei , Chen Li , Sun Jianbo 
Published: January 2017

Twenty‐six novel isosteviol derivatives coupled with two types of nitric oxide (NO) donors (furoxans and NONOates) were synthesized and screened for cytotoxic activities against four human cancer cell lines with sunitinib as the positive control. The results showed that seven furoxan‐based derivatives (8a, 8b, 8c, 8d, 8e, 9e, and 9f) exhibited desirable cytotoxic activities, while NONOate‐based derivatives displayed poor potency because of unstability. Compared with sunitinib, compounds 8a and 8e were more active on all tested cell lines, especially in HCT116 (8a, IC50 = 0.48 ± 0.02 μm; 8e, IC50 = 0.94 ± 0.01 μm); compounds 8b and 8d were more potent on HCT116 (IC50 = 3.39 ± 0.06 and 3.29 ± 0.03 μm), HepG2 (IC50 = 1.05 ± 0.03 and 5.37 ± 0.08 μm), and SW620 (IC50 = 1.33 ± 0.02 and 4.11 ± 0.05 μm) cell lines, and 8c exhibited higher activities on HepG2 cells with an IC50 = 4.76 ± 0.14 μm. NO‐releasing experiment of compounds 8a–e, 17a, 18a, 19a, and 21a reminded us that NO‐releasing amount of this series of isosteviol derivatives positively correlates with their cytotoxic activities.
Early life travelling does not increase risk of atopic outcomes until 15 years: results fromGINIplus andLISAplus
Authors: Markevych I. , Baumbach C. , Standl M. , Koletzko S. , Lehmann I. , Bauer C.‐P. , Hoffmann B. , von Berg A. , Berdel D. , Heinrich J. 
Published: January 2017

SummaryBackgroundWesternized lifestyle has been blamed for allergy epidemics. One of its characteristics is increased distances and frequency of travelling from early life onwards. Early life travelling to places which substantially differ from home environment in terms of climate, vegetation and food could increase the exposure to further unknown allergens and hence promote the development of allergies, but no epidemiological study has investigated this speculation.MethodsDetailed data on travelling during the first 2 years of life as well as a range of atopic outcomes along with potential confounders up to age 15 years were collected prospectively within two large population‐based multicentre German birth cohorts –GINIplus andLISAplus. Farthest travelling destination (within Germany; middle/northern/eastern Europe; southern Europe; outside Europe), total number of trips and their combination were considered as exposures. Six atopic outcomes were used: (1) doctor‐diagnosed asthma, (2) doctor‐diagnosed allergic rhinitis, (3) nose and eye symptoms, (4) sensitization to food allergens, (5) sensitization to indoor and (6) outdoor inhalant allergens. Longitudinal associations between each exposure and health outcome pair were analysed using generalized estimation equations (GEEs).ResultsThe results of our longitudinal analyses of 5674 subjects do not support the research hypothesis that travelling abroad to different regions in Europe or beyond Europe and frequency of travelling increase prevalence of doctor‐diagnosed asthma and allergic rhinitis, nose and eye symptoms and allergic sensitization up to 15 years of age. Furthermore, there was no indication of age‐varying effects.ConclusionsEarly life travelling does not seem to increase risk of atopic outcomes. Nevertheless, as we could not account for the type of visited environment or length of stay, these first findings should be interpreted with caution.
Information‐Theoretic Properties of Auditory Sequences Dynamically Influence Expectation and Memory
Authors: Agres Kat , Abdallah Samer , Pearce Marcus 
Published: January 2017

AbstractA basic function of cognition is to detect regularities in sensory input to facilitate the prediction and recognition of future events. It has been proposed that these implicit expectations arise from an internal predictive coding model, based on knowledge acquired through processes such as statistical learning, but it is unclear how different types of statistical information affect listeners’ memory for auditory stimuli. We used a combination of behavioral and computational methods to investigate memory for non‐linguistic auditory sequences. Participants repeatedly heard tone sequences varying systematically in their information‐theoretic properties. Expectedness ratings of tones were collected during three listening sessions, and a recognition memory test was given after each session. Information‐theoretic measures of sequential predictability significantly influenced listeners’ expectedness ratings, and variations in these properties had a significant impact on memory performance. Predictable sequences yielded increasingly better memory performance with increasing exposure. Computational simulations using a probabilistic model of auditory expectation suggest that listeners dynamically formed a new, and increasingly accurate, implicit cognitive model of the information‐theoretic structure of the sequences throughout the experimental session.
Assessment of left and right ventricular rotational interdependence: A speckle tracking echocardiographic study
Authors: Alizadehasl Azin , Sadeghpour Anita , Hali Reza , Bakhshandeh Abkenar Hooman , Badano Luigi 
Published: January 2017

ObjectiveWe sought to investigate the possible interdependence of the left (LV) and right ventricular (RV) rotational mechanics.BackgroundAlthough myocardial fiber architecture and the effect of various pathologic conditions on LV torsional mechanics have already been investigated through multiple studies using different methods, there is still a significant debate about the actual presence and functional significance of RV rotational mechanics.MethodsWe perform a cross‐sectional prospective study of 118 subjects, including 19 normal subjects (NS, 35±7 years), 34 patients with severe aortic stenosis (AS, 44±16 years), 26 patients with nonobstructive hypertrophic cardiomyopathies (HCM, 46±18), and 39 patients with nonischemic dilated cardiomyopathies (DCM, 39±13 years). LV and RV rotational parameters were measured using velocity vector imaging. Total LV and RV apical segment rotations as well as the rotation of the free wall of RV apex were measured separately. Interdependence of the LV and RV rotational mechanics was assessed using the Spearman rho test.ResultsBoth LV (7.3°±4.1° in NS, 11°±4.6° in AS, 7.7°±5.2° in HCM, and 1.9°±2° in DCM, P=<.0001) and RV apexes (4.7°±2° in NS, 6.1°±4° in AS, 3.2°±3.7° in HCM, and 2.4°±3.6° in DCM, P=<.0001) rotated counterclockwise in all the four study groups. Interventricular apical rotation interdependence was stronger in the AS (Spearman rho [ρ]: .716; P=.000) and in the HCM (ρ: .395; P=.04) subgroups than in the NS (ρ: .26; P=.27) and DCM (ρ: .215; P=.18). In DCM patients, RV apex rotation appeared to be independent of LV rotation. RV free wall apical rotation was larger than its corresponding value for the total apical segments in all studied groups. This difference was significant only in the AS (P=.007).ConclusionOur findings demonstrated a close correlation between RV and LV apical rotation parameters in different cardiac conditions as well as in normal subjects. However, in DCM patients, we also showed some independent rotation of the RV from the LV apex.
Effects of total dissolved solids on growth and mortality predict distributions of stream macroinvertebrates
Authors: Olson John R. , Hawkins Charles P. 
Published: January 2017

Summary

Spatial distributions of many freshwater invertebrates are associated with the concentration of total dissolved solids (TDS) in streams (usually measured as specific electrical conductivity – EC). These patterns are presumably caused by taxon‐specific effects of TDS on the maintenance of ion and water balance, which is energetically expensive and thus could affect fitness. However, no studies have assessed if TDS‐related effects on fitness metrics, such as growth and survival, are predictive of distributions.

We used stream‐side, flow‐through microcosms to experimentally determine how TDS concentration influenced three life‐history performance measures (growth, mortality and emergence) of 13 species of aquatic insects. We then modelled the relationship between experimentally derived performance measures and both EC optima and minima estimated from field surveys.

In the streamside experiment, we exposed taxa to stream water with naturally low (<25 μS cm−1) and moderate (>125 μS cm−1) EC for 83 days, controlling for differences in habitat, temperature, food availability and pH. We measured performance as the differences in specific growth rates, survival and adult emergence between the two treatments.

Treatment effects on performance varied among taxa and with performance metric. Survival differences between treatments varied from 1 to 21 days, and specific growth rates differed by 0.07–1.5 day−1. Emergence success was less variable (>20% for only two taxa). Three taxa performed better in the low EC treatment, six in the moderate EC treatment, one had a mixed response and three taxa did not differ between treatments.

The best model predicting field‐derived EC optima included both survival and specific growth rate as predictors (R2 = 0.68). Estimates of EC minima were not as strongly related to performance measures as were optima estimates. Taxa with greater performance in the moderate EC treatment had the highest EC optima, indicating that low TDS concentrations could restrict the distributions of taxa adapted to higher TDS concentrations. In contrast to taxa with higher EC preferences, taxa that can tolerate low EC environments will likely be increasingly stressed as stream TDS increases in response to climate and land–use change expected this century.
Drought causes reduced growth of trembling aspen in western Canada
Authors: Chen Lei , Huang Jian‐Guo , Alam Syed Ashraful , Zhai Lihong , Dawson Andria , Stadt Kenneth J. , Comeau Philip G. 
Published: January 2017

AbstractAdequate and advance knowledge of the response of forest ecosystems to temperature‐induced drought is critical for a comprehensive understanding of the impacts of global climate change on forest ecosystem structure and function. Recent massive decline in aspen‐dominated forests and an increased aspen mortality in boreal forests have been associated with global warming, but it is still uncertain whether the decline and mortality are driven by drought. We used a series of ring‐width chronologies from 40 trembling aspen (Populus tremuloides Michx.) sites along a latitudinal gradient (from 52° to 58°N) in western Canada, in an attempt to clarify the impacts of drought on aspen growth by using Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI). Results indicated that prolonged and large‐scale droughts had a strong negative impact on trembling aspen growth. Furthermore, the spatiotemporal variability of drought indices is useful for explaining the spatial heterogeneity in the radial growth of trembling aspen. Due to ongoing global warming and rising temperatures, it is likely that severer droughts with a higher frequency will occur in western Canada. As trembling aspen is sensitive to drought, we suggest that drought indices could be applied to monitor the potential effects of increased drought stress on aspen trees growth, achieve classification of eco‐regions and develop effective mitigation strategies to maintain western Canadian boreal forests.
Estimating River Conductance from Prior Information to Improve Surface‐Subsurface Model Calibration
Authors: Cousquer Yohann , Pryet Alexandre , Flipo Nicolas , Delbart Célestine , Dupuy Alain 
Published: January 2017

AbstractMost groundwater models simulate stream‐aquifer interactions with a head‐dependent flux boundary condition based on a river conductance (CRIV). CRIV is usually calibrated with other parameters by history matching. However, the inverse problem of groundwater models is often ill‐posed and individual model parameters are likely to be poorly constrained. Ill‐posedness can be addressed by Tikhonov regularization with prior knowledge on parameter values. The difficulty with a lumped parameter like CRIV, which cannot be measured in the field, is to find suitable initial and regularization values. Several formulations have been proposed for the estimation of CRIV from physical parameters. However, these methods are either too simple to provide a reliable estimate of CRIV, or too complex to be easily implemented by groundwater modelers. This paper addresses the issue with a flexible and operational tool based on a 2D numerical model in a local vertical cross section, where the river conductance is computed from selected geometric and hydrodynamic parameters. Contrary to other approaches, the grid size of the regional model and the anisotropy of the aquifer hydraulic conductivity are also taken into account. A global sensitivity analysis indicates the strong sensitivity of CRIV to these parameters. This enhancement for the prior estimation of CRIV is a step forward for the calibration and uncertainty analysis of surface‐subsurface models. It is especially useful for modeling objectives that require CRIV to be well known such as conjunctive surface water‐groundwater use.
The governance of Ottonian Germany in historiographical perspective
Authors: Wangerin Laura 
Published: January 2017

AbstractThe historiographic tradition for the tenth‐century Saxon Ottonian dynasty has without doubt been influenced by Germany's more recent past. Events in the nineteenth and twentieth centuries shaped the worldviews of historians both within Germany and without. These events also had a direct effect on the methodologies employed by those historians in studying medieval Germany, and helped to suppress interest in the field by non‐German historians. But in the last decades of the twentieth century, there was a kind of watershed for Ottonian studies. Historians who remain influential yet today began to ask new questions and approach the field with new methodologies that took work on the Ottonians in new directions. Additionally, these new approaches have stimulated lively and often contentious debates. There is much about Ottonian government that continues to puzzle scholars. This article provides a sketch of some of the main institutions of Ottonian governance, using these as a way to introduce the reader to the historiography and historiographical debates in the field.
India's many Puritans: Connectivity and friction in the study of modern Hinduism
Authors: Hatcher Brian A. 
Published: January 2017

AbstractTaking note of the widespread usage of terms such as puritan, puritanical, and puritanism in the study of modern religious movements in South Asia, this essay builds upon the work of J. Barton Scott and Anna Tsing to open up reflection on the trans‐colonial passage and critical operation of such terms. Learning that Max Weber's famous invocation of the Protestant ethic was preceded by colonial‐era reflections on puritanism in South Asia, we are led to explore patterns of connectivity and friction associated with the global circulation of discourse surrounding the puritan. By coining (after Scott) the concept of a puritan assemblage and considering how it shapes scholarship on the Swaminarayan Sampraday and the Brahmo Samaj, we call attention to the way processes of redescription and translation work to create enabling and exclusionary frames for understanding modern Hinduism.
The Unbelieved and Historians, Part II: Proposals and solutions
Authors: Clossey Luke , Jackson Kyle , Marriott Brandon , Redden Andrew , Vélez Karin 
Published: January 2017

AbstractTaking a cue from their less‐than‐marginal place in scholarship today, we call supernatural beings the “Unbelieved” and the explicit or implicit denial of them “Dogmatic Secularism.” We argue that objective historians should not discount, in advance, evidence that points to the existence or involvement of the Unbelieved in history; instead, we should cultivate a sceptical attitude towards all sources. In this, the second half of a two‐part essay, we first highlight the work of recent scholars who have pioneered a trail beyond Dogmatic Secularism. We conclude with practical suggestions towards a more truly empirical attitude towards sources involving the Unbelieved.
Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system
Authors: Boxberg Melanie , Jesinghaus Moritz , Dorfner Christiane , Mogler Carolin , Drecoll Enken , Warth Arne , Steiger Katja , Bollwein Christine , Meyer Petra , Wolff Klaus D , Kolk Andreas , Weichert Wilko 
Published: January 2017

AimsOral squamous cell carcinoma (OSCC) is a common malignancy with a variable clinical course. One of the established survival predictors in carcinomas in general is tumour grade; in OSCC, however, grading according to the World Health Organization (WHO) has no independent prognostic impact. Recently, a novel grading scheme associated with high impact on patient outcome has been proposed for squamous cell carcinoma of the lung.Methods and resultsTo probe whether this scheme could be applied to the upper aerodigestive tract, we retrospectively evaluated 157 chemo‐ and radiotherapy‐naive OSCCs with complete clinical follow‐up data and standardized treatment for tumour budding activity (BA), cell nest size (CNS), extent of keratinization, stromal content, nuclear size and mitotic count. Histomorphological characteristics were correlated with clinicopathological data and patient outcome. As in squamous cell carcinoma of the lung, high BA and small CNS were correlated significantly with shortened overall, disease‐specific and disease‐free survival. A three‐tiered grading system based on a sum score of these two prognostic markers proved to be a strong age‐, stage‐ and sex‐independent prognosticator for survival with a hazard ratio for overall survival of 2.1 for intermediately differentiated (G2) tumours and 3.4 for poorly differentiated (G3) tumours compared to well‐differentiated (G1) tumours (P < 0.001).ConclusionsWe recapitulated and validated almost exactly the strong prognostic impact of a grading algorithm proposed recently for squamous cell carcinoma of the lung in OSCC. Our data may pave the way for a prognostically highly relevant future squamous cell carcinoma grading system broadly applicable in the aerodigestive tract.
Identification of ecdysteroidogenic enzyme genes and their expression during pupal diapause in the cabbage armyworm, Mamestra brassicae
Authors: Ogihara M. H. , Ikeda H. , Yamada N. , Hikiba J. , Nakaoka T. , Fujimoto Y. , Suzuki Y. , Saito K. , Mizoguchi A. , Kataoka H. 
Published: January 2017

AbstractIn this study, we identified ecdysteroidogenic enzymes in the cabbage armyworm, Mamestra brassicae, and demonstrated reduced expression of these genes during diapause. Some insects employ a temporary developmental arrest, diapause, to survive in severe environments. The titres of the moulting hormone ecdysteroid were reduced in diapause pupae of M. brassicae; therefore, ecdysteroidogenesis might be suppressed by a diapause‐specific mechanism. To clarify expression changes of ecdysteroidogenic enzyme genes during diapause in M. brassicae, we first identified the genes for seven ecdysteroidogenic enzymes: Neverland, Non‐molting glossy (Nm‐g), CYP307A1 (Spook), CYP306A1 (Phantom), CYP302A1 (Disembodied), CYP315A1 (Shadow) and CYP314A1 (Shade). Enzymatic assays using heterologous expression in Drosophila Schneider 2 (S2) cells and analysis of mRNA distribution indicated that the identified genes were ecdysteroidogenic enzymes of M. brassicae. Expression levels of these ecdysteroidogenic enzyme genes were compared between prothoracic glands in different pupal stages throughout diapause. Immediately after pupation, diapause‐destined pupae showed similar expression levels of ecdysteroidogenic enzyme genes to those of nondiapause pupae. All of these genes showed reduced gene expression after diapause initiation. Expression was immediately increased in diapause‐destined pupae at the postdiapause quiescence phase. These results indicate that reduced expression of ecdysteroidogenic enzyme genes suppresses ecdysteroidogenesis and maintains developmental arrest during diapause.
Enterovirus D68 and other enterovirus serotypes identified in South African patients with severe acute respiratory illness, 2009–2011
Authors: Hellferscee Orienka , Treurnicht Florette K. , Tempia Stefano , Variava Ebrahim , Dawood Halima , Kahn Kathleen , Cohen Adam L. , Pretorius Marthi , Cohen Cheryl , Madhi Shabir A. , Venter Marietjie 
Published: January 2017

BackgroundHuman enteroviruses (EV) have been associated with severe acute respiratory illness (SARI) in South Africa.ObjectivesWe aimed to describe the molecular epidemiology of EV serotypes among patients hospitalized with SARI during 2009‐2011.Patients/MethodsStudy samples from patients were tested for the presence of enterovirus using a polymerase chain reaction assay.Results8.2% (842/10 260) of SARI cases tested positive for enterovirus; 16% (7/45) were species EV‐A, 44% (20/45) EV‐B, 18% (8/45) EV‐C and 22% (10/45) EV‐D. Seventeen different EV serotypes were identified within EV‐A to EV‐D, of which EV‐D68 (22%; 10/45) and Echovirus 3 (11%; 5/45) were the most prevalent.ConclusionsEV‐D68 should be monitored in South Africa to assess the emergence of highly pathogenic strains.