bluuebunny/crossref_metadata_2025 huggingface dataset:
Full Conformational Landscape of 3‐Methoxyphenol Revealed by Room Temperature mm‐wave Rotational Spectroscopy Supported by Quantum Chemical Calculations
Authors: Roucou Anthony , Fontanari Daniele , Dhont Guillaume , Jabri Atef , Bray Cédric , Hindle Francis , Mouret Gaël , Bocquet Robin , Cuisset Arnaud
Published: March 2018

Room temperature millimeter‐wave rotational spectroscopy supported by high level of theory calculations have been employed to fully characterise the conformational landscape of 3‐Methoxyphenol, a semi‐volatile polar oxygenated aromatic compound precursor of secondary organic aerosols in the atmosphere arising from biomass combustion. While previous rotationally‐resolved spectroscopic studies in the microwave and in the UV domains failed to observe the complete conformational landscape, the 70–330 GHz rotational spectrum measured in this study reveals the ground state rotational signatures of the four stable conformations theoretically predicted. Moreover, rotational transitions in the lowest energy vibrationally excited states were assigned for two conformers. While the inertial defect of methoxyphenol does not significantly change between conformers and isomers, the excitation of the methoxy out‐of‐plane bending is the main contribution to the non‐planarity of the molecule.
Cu2+‐doped Carbon Nitride/MWCNT as an Electrochemical Glucose Sensor
Authors: Zheng Weiran , Li Yong , Liu Mengjie , Tsang Chui‐Shan , Lee Lawrence Yoon Suk , Wong Kwok‐Yin
Published: March 2018

The rational design of electrocatalysts with abundant active sites and high conductivity is the key to the development of glucose sensors. Herein, we report the preparation of a Cu2+‐doped C3N4 supported on multi‐walled carbon nanotube (MWCNT) network (Cu2+‐C3N4/MWCNT) as a highly efficient non‐enzymatic glucose sensing system. The morphologic and structural investigations using TEM, AFM, XRD, XPS, EPR, and i‐V response indicate the successful insertion of Cu2+ into the C3N4 inter‐layers via an out‐of‐plane on‐top configuration and the consequent exfoliation of C3N4 layers without forming CuO or Cu(OH)2. Such material can act as an electrocatalyst for glucose electrooxidation, and MWCNT can greatly reduce the charge transfer resistance and enhances activity. An optimised Cu2+ doping level (12 wt%) in Cu2+‐C3N4/MWCNT was established to realise high sensitivity towards glucose sensing (929 mA/M cm2), large linear range (0.5 μM∼12 mM), low detection limit (0.35 μM), and short response time (<3 s). Excellent selectivity against the interferents, such as dopamine, ascorbic acid, sucrose, and lactose, is also observed. In the blood serum tests, as‐prepared glucose sensor reports comparable and reproducible results, demonstrating its practical potentials.
Quantitative assessment of mAb Fc glycosylation of CQA importance by capillary electrophoresis
Authors: Szigeti Marton , Chapman Jeff , Borza Beata , Guttman Andras
Published: March 2018

The attached carbohydrates at the highly conserved asparagine‐linked glycosylation site in the CH2 domain of the fragment crystallizable (Fc) region of monoclonal antibody therapeutics can play an essential role in their mechanism of action, including ADCC, CDC, anti‐inflammatory functions, and serum half‐life. Thus, this particular glycosylation represents one of the important critical quality attributes (CQA) of therapeutic monoclonal antibodies, which should be closely monitored and controlled during all stages of biopharmaceutical manufacturing. To study Fc glycosylation related quantitative critical quality attributes, the N‐glycan pool of adalimumab (Humira®) was spiked with increasing amounts of mannose‐5 oligosaccharide, a glycan with high CQA importance. The method enabled precise quantitative CQA assessment with high detection sensitivity.
On the stability relationships between tidal asymmetry and morphologies of tidal basins and estuaries
Authors: Zhou Zeng , Coco Giovanni , Townend Ian , Gong Zheng , Wang Zhengbing , Zhang Changkuan
Published: March 2018

Simple stability relationships are practically useful to provide a rapid assessment of coastal and estuarine landforms in response to human interventions and long‐term climate change. In this contribution, we review a variety of simple stability relationships which are based on the analysis of tidal asymmetry (TA). Most of the existing TA‐based stability relationships are derived using the one‐dimensional tidal flow equations assuming a certain regular shape of the tidal channel cross‐sections. To facilitate analytical solutions, specific assumptions inevitably need to be made, for example by linearizing the friction term and dropping some negligible terms in the tidal flow equations. We find that three major types of TA‐based stability relationships have been proposed between three non‐dimensional channel geometric ratios (represented by the ratio of channel widths, ratio of wet surface areas and ratio of storage volumes) and the tide‐related parameter a/h (i.e. the ratio between tidal amplitude and mean water depth). Based on established geometric relations, we use these non‐dimensional ratios to restate the existing relationships so that they are directly comparable. Available datasets are further extended to examine the utility of these TA‐based relationships. Although a certain agreement is shown for these relationships, we also observe a large scatter of data points which are collected in different types of landscape, hydrodynamic and sedimentological settings over the world. We discuss in detail the potential reasons for this large scatter and subsequently elaborate on the limited applicability of the various TA‐based stability relationships for practical use. We highlight the need to delve further into what constitutes equilibrium and what is needed to develop more robust measures to determine the morphological state of these systems. Copyright © 2018 John Wiley & Sons, Ltd.
Quantifying river incision into low‐relief surfaces using local and catchment‐wide 10Be denudation rates
Authors: Wolff Reinhard , Hetzel Ralf , Strobl Marcus
Published: March 2018

Relief generation in non‐glaciated regions is largely controlled by river incision into bedrock but datable fluvial terraces that allow quantifying incision rates are not always present. Here we suggest a new method to determine river incision rates in regions where low‐relief surfaces are dissected by streams. The approach consists of three steps and requires the 10Be concentrations of a stream sediment sample and a regolith sample from the low‐relief surface. In the first step, the spatial distribution of 10Be surface concentrations in the given catchment is modelled by assuming that denudation rates are controlled by the local hillslope angles. The slope–denudation rate relation for this catchment is then quantified by adjusting the relation between slope angle and denudation rate until the average 10Be concentration in the model is equal to the one measured in the stream sediment sample. In the second step, curved swath profiles are used to measure hillslope angles adjacent to the main river channel. Third, the mean slope angle derived from these swath profiles and the slope–denudation relation are used to quantify the river incision rate (assuming that the incision rate equals the denudation rate on adjacent hillslopes). We apply our approach to two study areas in southern Tibet and central Europe (Black Forest). In both regions, local 10Be denudation rates on flat parts of the incised low‐relief surface are lower than catchment‐wide denudation rates. As the latter integrate across the entire landscape, river incision rates must exceed these spatially averaged denudation rates. Our approach yields river incision rates between ~15 and ~30 m/Ma for the Tibetan study area and incision rates of ~70 to ~100 m/Ma in the Black Forest. Taking the lowering of the low‐relief surfaces into account suggests that relief in the two study areas increases at rates of 10–20 and 40–70 m/Ma, respectively. Copyright © 2018 John Wiley & Sons, Ltd.
Connectivity dynamics in typical development and its relationship to autistic traits and autism spectrum disorder
Authors: Rashid Barnaly , Blanken Laura M. E. , Muetzel Ryan L. , Miller Robyn , Damaraju Eswar , Arbabshirani Mohammad R. , Erhardt Erik B. , Verhulst Frank C. , van der Lugt Aad , Jaddoe Vincent W. V. , Tiemeier Henning , White Tonya , Calhoun Vince
Published: March 2018

Recent advances in neuroimaging techniques have provided significant insights into developmental trajectories of human brain function. Characterizations of typical neurodevelopment provide a framework for understanding altered neurodevelopment, including differences in brain function related to developmental disorders and psychopathology. Historically, most functional connectivity studies of typical and atypical development operate under the assumption that connectivity remains static over time. We hypothesized that relaxing stationarity assumptions would reveal novel features of both typical brain development related to children on the autism spectrum. We employed a “chronnectomic” (recurring, time‐varying patterns of connectivity) approach to evaluate transient states of connectivity using resting‐state functional MRI in a population‐based sample of 774 6‐ to 10‐year‐old children. Dynamic connectivity was evaluated using a sliding‐window approach, and revealed four transient states. Internetwork connectivity increased with age in modularized dynamic states, illustrating an important pattern of connectivity in the developing brain. Furthermore, we demonstrated that higher levels of autistic traits and ASD diagnosis were associated with longer dwell times in a globally disconnected state. These results provide a roadmap to the chronnectomic organization of the developing brain and suggest that characteristics of functional brain connectivity are related to children on the autism spectrum.
Human factors’ complexity measurement of human‐based station of assembly line
Authors: Fan Guoliang , Li Aiping , Zhao Yaxi , Moroni Giovanni , Xu Liyun
Published: March 2018

Cognitive heterogeneity causes operation time variability and high human error rates at human‐based stations of assembly lines. It will affect the performance of the production activities, the design process of which depends on reliable estimate of operation time. To quantify operator cognition, we measured the human factors’ complexity of human‐based stations using an information entropy approach in aspect of operation time. Initially, the influence of the operators’ cognition on the operation time is analyzed. Based on the analysis, the operation time model that considers cognition is presented. Then, the operation time model is modified by applying a correction method using the behavior correction factor, and, finally, the human factors’ complexity measurement model is built. A case study is used to illustrate the application of the proposed method in order to measure the influence of human cognition on the performance of the human‐based station.
Novel acquisitions on biology and management of transformed follicular lymphoma
Authors: Minoia Carla , Zucca Emanuele , Conconi Annarita
Published: March 2018

Follicular lymphoma (FL) generally has an indolent clinical course, but in some patients, a histological transformation (HT) into aggressive entities may take place and often lead to a poorer survival. The rituximab era has seen an improved outcome of FL, including those with HT. The current treatment strategies for transformed FL are based on immunochemotherapy for the cases with HT at the time of diagnosis or as the first event after watchful waiting. Patients transforming after prior treatment of FL usually benefit from autologous stem cell transplant. Unfortunately, early assessment of the transformation risk remains elusive. Recent studies delved the mechanisms of HT, showing that this is a complex process, resulting from a number of epigenetic and genetic lesions occurring in the tumour cell population as well as progressive changes in the tumour microenvironment. This novel knowledge has prompted clinical investigations on a variety of new therapeutic strategies.
Low serum level of epidermal growth factor in chronic ketamine users
Authors: Zhang Minling , He Hongbo , Ning Yuping , Ding Yi , Ke Xiaoyin , Wang Daping , Deng Xuefeng , Fan Ni
Published: March 2018

Background

Growth factors play an important role in brain development. Whether epidermal growth factor (EGF) plays a role in the pathophysiology of ketamine related disorders is unexplored. In this study, we examined the serum levels of EGF in chronic ketamine users as compared with healthy controls. The possible correlation between serum EGF levels with the demographic, ketamine use characteristics and psychopathological symptoms were analyzed.

Methods

Sixty‐seven chronic ketamine users and 40 healthy subjects were recruited. Serum EGF levels were measured by enzyme‐linked immunosorbent assay. Psychopathological symptoms were assessed using Positive and Negative Syndrome Scale, Beck Depression Inventory and Beck Anxiety Inventory.

Results

The serum level of EGF in the chronic ketamine users was significantly lower than that of healthy subjects (22.34 ± 4.81 pg/ml vs. 87.10 ± 2.96 pg/ml, F = 15.169, p < 0.01). The serum EGF level was negatively correlated with the current average dose of ketamine consumption per day of use (p = 0.015), and positively associated with the Positive and Negative Syndrome Scale positive symptom score (p = .022).

Conclusions

Serum level of EGF decreased in chronic ketamine users compared with healthy subjects, which may play a role in the pathophysiology of ketamine related disorders.
3D bone models to study the complex physical and cellular interactions between tumor and the bone microenvironment
Authors: Vanderburgh Joseph P. , Guelcher Scott A. , Sterling Julie A.
Published: March 2018

As the complexity of interactions between tumor and its microenvironment has become more evident, a critical need to engineer in vitro models that veritably recapitulate the 3D microenvironment and relevant cell populations has arisen. This need has caused many groups to move away from the traditional 2D, tissue culture plastic paradigms in favor of 3D models with materials that more closely replicate the in vivo milieu. Creating these 3D models remains a difficult endeavor for hard and soft tissues alike as the selection of materials, fabrication processes, and optimal conditions for supporting multiple cell populations makes model development a nontrivial task. Bone tissue in particular is uniquely difficult to model in part because of the limited availability of materials that can accurately capture bone rigidity and architecture, and also due to the dependence of both bone and tumor cell behavior on mechanical signaling. Additionally, the bone is a complex cellular microenvironment with multiple cell types present, including relatively immature, pluripotent cells in the bone marrow. This prospect will focus on the current 3D models in development to more accurately replicate the bone microenvironment, which will help facilitate improved understanding of bone turnover, tumor‐bone interactions, and drug response. These studies have demonstrated the importance of accurately modelling the bone microenvironment in order to fully understand signaling and drug response, and the significant effects that model properties such as architecture, rigidity, and dynamic mechanical factors have on tumor and bone cell response.
Climatology and trends of the Euro‐Mediterranean thermal bioclimate
Authors: Giannaros Theodore M. , Kotroni Vassiliki , Lagouvardos Konstantinos , Matzarakis Andreas
Published: March 2018

High‐resolution numerical simulations were carried out for the most recent 30‐year period (1987–2016), focusing on the Euro‐Mediterranean region. A sophisticated thermo‐physiologically significant thermal index, namely the physiologically equivalent temperature (PET), was computed for assessing the thermal bioclimate of the study area and for investigating the presence of long‐term trends, focusing on bioclimatic extremes. Results indicate that the Euro‐Mediterranean thermal bioclimate follows a zonal pattern, upon which topography acts to delineate regional maxima and minima. The conducted time series analysis reveals statistically significant trends that are generally more pronounced for cold extremes. In particular, it is found that the number of days with cold (hot) stress has decreased (increased), with the distribution of PET exhibiting warming of both its cold and warm tail. The south–east Mediterranean and the Balkans are found to be the most responsive to bioclimatic changes, showing coherent and statistically significant warming trends. Overall, the results of this study provide a new point of view of the Euro‐Mediterranean climate, which could be of usefulness in a wide range of future applications. The detailed spatio‐temporal bioclimatic data could be exploited, for instance, to support applications related to tourism and recreation, highlighting regions with favourable or less favourable thermal comfort conditions. Furthermore, the trend data could be employed for quantifying the vulnerability of certain regions to cold and heat stress, in the context of public health applications.
Drought characteristics over China during 1980–2015
Authors: Shao Dongguo , Chen Shu , Tan Xuezhi , Gu Wenquan
Published: March 2018

The self‐calibrating Palmer drought severity index (scPDSI) was computed based on the four atmospheric reanalysis data sets combined with observational data over China during 1980–2015. The discrepancies of scPDSI among the four reanalysis data sets show the necessity of integrating multiple data sets. Drought characteristics, such as drought area, severity, duration, and frequency were examined based on multi‐data set mean scPDSI. The results reveal that significant drying trends are found in Qinghai‐Tibet Plateau, southwest, southeast and entire China. Drought area (drought severity) has increased (decreased) by about 1.16% (0.015%) per decade over entire China. Trends in drought duration, temporally averaged severity and frequency also indicate that droughts become more serious in each region during the past 36 years. The identification of drought events in each month by the clustering algorithm shows that droughts over China are more and more frequent. In addition, 65 separate drought events with the duration longer than 3 months were identified under the area threshold of 150,000 km2. Through severity‐area‐duration analysis, the 2005–2015 drought is found to be the prominent event.
Post‐acute care use after major head and neck oncologic surgery with microvascular reconstruction
Authors: Parhar Harman S. , Chang Brent A. , Durham J. Scott , Anderson Donald W. , Hayden Richard E. , Prisman Eitan
Published: March 2018

Objectives

Post‐acute care (PAC) centers, such as skilled nursing facilities, unskilled nursing facilities, lower acuity hospitals, and rehabilitation centers, serve to optimize recovery after acute care hospitalization. We aimed to identify factors associated with PAC utilization among patients undergoing head and neck cancer surgery with microvascular reconstruction because it may be helpful for patient decision making, discharge planning, and resource allocation.

Methods

Retrospective linked analysis of the 2011 to 2015 National Surgical Quality Improvement Program. Eligible patients were identified and stratified by discharge disposition (home or PAC) after their postoperative acute‐care hospitalization. After an initial univariate screen of demographic and clinical variables, a multivariable logistic regression analysis was performed modelling discharge to PAC.

Results

Of the 1,652 identified patients, 261 (15.8%) were discharged to PAC. Those admitted to PAC were older, had a higher burden of comorbidity, and were more likely to be functionally dependent. They also had longer surgeries, longer hospitalizations, higher rates of reoperation, and higher rates of postoperative complications. After multivariate analysis, factors independently associated with PAC discharge included increasing age (odds ratio [OR] 2.12 per 10‐year increase; 95% confidence interval [CI], 1.81–2.48), active smoking status (odds ratio (OR) 1.61; 95% confidence interval (CI), 1.13–2.29), prolonged hospitalization (OR 1.04; 95% CI, 1.02–1.07), and postoperative pulmonary complications (OR 2.02; 95% CI, 1.36–2.99).

Conclusion

Of the patients undergoing surgery for head and neck cancers with microvascular reconstruction, 15.8% are discharged to PAC. Age, active smoking status, prolonged hospitalization, and postoperative pulmonary complications (vs. comorbidity, functional status, or primary tumor site) are independently associated with discharge to PAC.

Level of Evidence

Level 2c. Laryngoscope, 2532–2538, 2018
Estimates for a general fractional relaxation equation and application to an inverse source problem
Authors: Bazhlekova Emilia
Published: March 2018

A general fractional relaxation equation is considered with a convolutional derivative in time introduced by A. Kochubei (Integr. Equ. Oper. Theory 71 (2011), 583–600). This equation generalizes the single‐term, multiterm, and distributed‐order fractional relaxation equations. The fundamental and the impulse‐response solutions are studied in detail. Properties such as analyticity and subordination identities are established and employed in the proof of an upper and a lower bound. The obtained results extend some known properties of the Mittag‐Leffler functions. As an application of the estimates, uniqueness and conditional stability are established for an inverse source problem for the general time‐fractional diffusion equation on a bounded domain.
Dynamic pricing and replenishment: Optimality, bounds, and asymptotics
Authors: Xiao Yongbo
Published: March 2018

In many applications, managers face the problem of replenishing and selling products during a finite time horizon. We investigate the problem of making dynamic and joint decisions on product replenishment and selling in order to improve profit. We consider a backlog scenario in which penalty cost (resulting from fulfillment delay) and accommodation cost (resulting from shortage at the end of the selling horizon) are incurred. Based on continuous‐time and discrete‐state dynamic programming, we study the optimal joint decisions and characterize their structural properties. We establish an upper bound for the optimal expected profit and develop a fluid policy by resorting to the deterministic version of the problem (ie, the fluid problem). The fluid policy is shown to be asymptotically optimal for the original stochastic problem when the problem size is sufficiently large. The static nature of the fluid policy and its lack of flexibility in matching supply with demand motivate us to develop a “target‐inventory” heuristic, which is shown, numerically, to be a significant improvement over the fluid policy. Scenarios with discrete feasible sets and lost‐sales are also discussed in this article.
Analysis and improvement of motion encoding in magnetic resonance elastography
Authors: Guenthner Christian , Runge Jurgen Henk , Sinkus Ralph , Kozerke Sebastian
Published: March 2018

Magnetic resonance elastography (MRE) utilizes phase contrast magnetic resonance imaging (MRI), which is phase locked to externally generated mechanical vibrations, to measure the three‐dimensional wave displacement field. At least four measurements with linear‐independent encoding directions are necessary to correct for spurious phase contributions if effects from imaging gradients are non‐negligible. In MRE, three encoding schemes have been used: unbalanced four‐ and six‐point and balanced four‐point (‘tetrahedral’) encoding. The first two sensitize to motion with orthogonal gradients, with the four‐point method acquiring a single reference scan without motion sensitization, whereas three additional scans with inverted gradients are used with six‐point encoding, leading to two‐fold higher displacement‐to‐noise ratio (DNR) and 50% longer scan duration. Balanced four‐point (tetrahedral) encoding encodes along the four diagonals of a cube, with one direction serving as a reference for the other three encoding directions, similar to four‐point encoding. The objective of this work is to introduce a theoretical framework to compare different motion sensitization strategies with respect to their motion encoding efficiency in two fundamental encoding limits, the gradient strength limit and the dynamic range limit, which are both placed in relation to conventional gradient recalled echo (GRE)‐ and spin echo (SE)‐based MRE sequences. We apply the framework to the three aforementioned schemes and show that the motion encoding efficiency of unbalanced four‐ and six‐point encoding schemes in the gradient‐limited regime can be increased by a factor of 1.5 when using all physical gradient channels concurrently. Furthermore, it is demonstrated that reversing the direction of the reference in balanced four‐point (tetrahedral) encoding results in the Hadamard encoding scheme, which leads to increased DNR by
compared with balanced four‐point encoding and 2.8 compared with unbalanced four‐point encoding. As an example, we show that optimal encoding can be utilized to reduce the acquisition time of standard liver MRE in vivo from four to two breath holds.
Effect of European Medicines Agency's regulatory measures on nimesulide utilization in Portugal
Authors: Pinto Daniel , Silva Ana , Heleno Bruno , Rodrigues David Silvério , Santos Isabel , Caetano Pedro A.
Published: March 2018

Purpose

Severe hepatic adverse events led the European Medicines Agency to recommend restrictions on nimesulide use. Our aim was to determine their effect on nimesulide dispensing in Portugal.

Methods

Interrupted time‐series using pharmacy billing records of the Portuguese National Health Service. Regulatory actions, concurrent events, and nimesulide dispensing were recorded from 2006 to 2015. The primary outcome was the number defined daily doses (DDD) of nimesulide dispensed per month. Secondary outcomes were the number of adverse reactions to nimesulide and the variation of nimesulide prescriptions by prescribing site category.

Results

We defined 3 possible interruption periods: (1) May 2007 to March 2008: nimesulide was withdrawn from Ireland, the European Medicines Agency initiated a safety review, and this was reported by Portuguese media; (2) October 2009 to April 2010: the European Commission reached a decision and mandated a broader safety review; and (3) December 2010 to April 2012: the Commission's decision was implemented in Portugal, the broader safety review was concluded and implemented. Nimesulide use showed a declining trend at the start of the series (−12.2 thousand DDD/month). Interruptions 1 and 3 were associated with decreases in level (−824.7 thousand and −449.0 thousand DDD, respectively). Interruption 3 was associated with a greater decrease in primary care than in other sites. The number of reported adverse events did not decrease.

Conclusions

Nimesulide use decreased significantly following 2 complex interventions including regulatory measures, media reports, and other concurrent factors. However, this was not associated with a decrease in reported adverse drug reactions.
Efficacy and Safety of Rituximab for the Treatment of Graves' Orbitopathy: A Meta‐analysis of Randomized Controlled Trials
Authors: Shen Wan‐Chen , Lee Chia‐Hwa , Loh El‐Wui , Hsieh An‐Tsz , Chen Lawrence , Tam Ka‐Wai
Published: March 2018

Study Objective

To investigate the efficacy and safety of rituximab in patients with Graves' orbitopathy (GO).

Design

Systematic review and meta‐analysis of four randomized controlled trials.

Patients

A total of 293 patients with GO who received rituximab or control (either glucocorticoids, the established first‐line therapy [three trials], or saline [one trial]).

Measurements and Results

Relevant studies published before February 2018 were identified from the PubMed, EMBASE, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry. Individual effect sizes were standardized, and a meta‐analysis was conducted to calculate the pooled effect size by using a random‐effects model. Treatment efficacy was assessed by measuring the following outcomes: clinical activity score (CAS), sight visual acuity reduction (NOSPECS) score, proptosis, diplopia, changes in eye volume, quality of life, and adverse events. In the four included trials, 113 patients in the rituximab group and 108 patients in the control group were evaluated. Compared with the control group, CAS (weighted mean difference 0.57, 95% confidence interval 0.25–0.89) was significantly reduced at 24 weeks in the rituximab group. Compared with the control group, considerable proptosis reduction was also observed in the rituximab group; however, the difference was not significant. The proportion of adverse events in the rituximab group was not significantly higher than that in the glucocorticoid control group, but one of the included trials indicated that the rituximab group had more serious adverse events than the saline control group.

Conclusion

Rituximab is a relatively safe and viable treatment that is superior to glucocorticoids or saline for patients with moderate to severe GO. However, the incidence of serious adverse events was disparate among the included trials. Additional studies involving a larger sample size and investigating the optimal rituximab dosage, frequency, and method of administration are warranted.
Calpain‐2 triggers prostate cancer metastasis via enhancing CRMP4 promoter methylation through NF‐κB/DNMT1 signaling pathway
Authors: Gao Xin , Mao Yun‐Hua , Xiao Chutian , Li Ke , Liu Wei , Li Liao‐Yuan , Pang Jun
Published: March 2018

Background

Metastasis is the major cause of cancer‐specific death in patients with prostate cancer (PCa). We previously reported that collapsing response mediator protein‐4 (CRMP4) is a PCa metastasis‐suppressor gene and the hypermethylation in CRMP4 promoter is responsible for the transcription repression in metastatic PCa. However, the underlying mechanisms remain unknown. In this study, we aimed to investigate the role of calpain‐2 in CRMP4 promoter hypermethylation and its functional modulation in PCa metastasis.

Methods

Calpain‐2 expression in PCa tissues (n = 87) and its specific mechanisms of functional modulation in CRMP4 expression via limited enzymatic cleavage was investigated. We then focused on the cooperative crosstalk of calpain‐2 and NF‐κB RelA/p65 in CRMP4 promoter methylation for the initiation of PCa metastasis. Statistical differences between groups were determined using a two‐tailed Student's t‐test. P < 0.05 indicated statistically significant.

Results

Calpain‐2 was differentially upregulated in metastatic PCa compared with localized PCa. Moreover, calpain‐2 cleaved CRMP4 into the N‐terminally fragment which promoted migration and invasion in PCa cells via nuclear translocation and activation of E2F1‐mediated DNA methyltransferase 1 (DNMT1) expression. NF‐κB RelA/p65 recruited DNMT1 to bind to and methylate CRMP4 promoter in which Serine276 phosphorylation of p65 was essential. Furthermore, CRMP4 exhibited anti‐metastatic function via inhibiting the expression of VEGFC through Semaphorin3B‐Neuropilin2 signaling.

Conclusion

Calpain‐2 may contribute to the promoter methylation of CRMP4 to repress its transcription, leading to the metastasis of PCa via enhancing VEGFC expression.
The influence of the stratospheric state on North Atlantic weather regimes
Authors: Charlton‐Perez Andrew J. , Ferranti Laura , Lee Robert W.
Published: March 2018

Stratosphere–troposphere coupling is often viewed from the perspective of the annular modes and their dynamics. Despite the obvious benefits of this approach, recent work has emphasised the greater tropospheric sensitivity to stratospheric variability in the Atlantic basin than in the Pacific basin. In this study, a new approach to understanding stratosphere–troposphere coupling is proposed, with a focus on the influence of the stratospheric state on North Atlantic weather regimes (during extended winter, November to March). The influence of the strength of the lower‐stratospheric vortex on four commonly used tropospheric weather regimes is quantified. The negative phase of the North Atlantic Oscillation is most sensitive to the stratospheric state, occurring on 33% of days following weak vortex conditions but on only 5% of days following strong vortex conditions. An opposite and slightly weaker sensitivity is found for the positive phase of the North Atlantic Oscillation and the Atlantic Ridge regime. For the North Atlantic Oscillation regimes, stratospheric conditions change both the probability of remaining in each regime and the probability of transitioning to that regime from others. A logistic regression model is developed to further quantify the sensitivity of tropospheric weather regimes to the lower stratospheric state. The logistic regression model predicts an increase of 40–60% in the probability of transition to the negative phase of the North Atlantic Oscillation for a one standard deviation reduction in the strength of the stratospheric vortex. Similarly it predicts a 10–30% increase in the probability of transition to the positive phase of the North Atlantic Oscillation for a one standard deviation increase in the strength of the stratospheric vortex. The stratosphere–troposphere coupling in the European Centre for Medium‐range Weather Forecasts Integrated Forecasting System model is found to be consistent with the re‐analysis data by fitting the same logistic regression model.
10.3% Efficient CuIn(S,Se)2 Solar Cells from DMF Molecular Solution with the Absorber Selenized under High Argon Pressure
Authors: Jiang Jingjing , Yu Shaotang , Gong Yuancai , Yan Weibo , Zhang Rui , Liu Shujuan , Huang Wei , Xin Hao
Published: March 2018

Fabricating high performing chalcopyrite absorber material from environmental benign solvent is very important for large scale manufacturing production. Here, N, N‐dimethylformamide (DMF) is used as a single solvent to make CuIn(S,Se)2 (CIS) molecular precursor solution and fabricate CIS absorber material. A power conversion efficiency of 10.3% has been achieved from film selenized under 1.6 atmosphere Ar pressure which is 0% for film selenized under 1 atmosphere pressure. Characterizations using XRD, SEM, TEM, EDX reveal a Cu‐rich absorber material consisting of loosely connected grains with vertical holes in film selenized under 1 atmosphere and a Cu‐poor compact large‐grain top layer with large hole bottom layer in film selenized under high Ar pressure. Further optimization of precursor formulation and device fabrication conditions to address the non‐perfect double layer structure is expected to further improve DMF solution processed CIS solar cell efficiency. Our results demonstrate annealing precursor film under increased atmosphere pressure is a new and promising strategy to fabricate high performing thin film solar cells, which can be applied to all solution processed chalcogenide solar cells including CIS, CIGS and CZTS.
A System Dynamics Model of Resistance to Organizational Change: The Role of Participatory Strategies
Authors: Schweiger Sylvia , Stouten Hendrik , Bleijenbergh Inge L.
Published: March 2018

The literature on organizational change and resistance to change is contradictory. Some scholars find resistance a hindrance to successful change (traditional paradigm), whereas others find it a valuable source (modern paradigm). The objective of this study is to enhance our understanding of how resistance affects organizational change by providing a coherent system dynamics perspective. Based on interviews, expert modelling and group modelling, this inductive case study develops a causal loop diagram that displays eight interacting feedback loops to explain resistance to change and the role that participatory strategies play in addressing this. The model contributes to the theoretical debate on how resistance affects change by providing propositions that integrate the traditional and modern paradigms. When managers face decisions about when to increase, stabilize or decrease the use of participatory strategies, our findings imply to base these decisions upon currently dominating feedback loops, such as the Stress Trap or Slow Trap. © 2018 The Authors. Systems Research and Behavioral Science published by International Federation for Systems Research and John Wiley & Sons Ltd
When elephants fall asleep: A literature review on elephant rest with case studies on elephant falling bouts, and practical solutions for zoo elephants
Authors: Schiffmann Christian , Hoby Stefan , Wenker Christian , Hård Therese , Scholz Robert , Clauss Marcus , Hatt Jean‐Michel
Published: March 2018

Little attention has been paid to the resting and sleeping behavior of zoo elephants so far. An important concern is when elephants avoid lying down, due to degenerative joint and foot disease, social structure, or stressful environmental changes. Inability or unwillingness to lie down for resting is an important welfare issue, as it may impair sleep. We emphasize the importance of satisfying rest in elephants by reviewing the literature on resting behavior in elephants (Loxodonta africana and Elephas maximus) as well as the documentation of four cases from European zoos and our own direct observations in a zoo group of four female African elephants during 12 entire days. The common denominator in the case reports is the occurrence of a falling bout out of a standing position subsequently to a cessation of lying rest for different periods of time. Although well‐known in horses as “episodic collapse” or “excessive drowsiness,” this syndrome has not been described in elephants before. To enable its detection, we recommend nocturnal video monitoring for elephant‐keeping institutions. The literature evaluation as well as own observational data suggest an inverse relationship between lying rest and standing rest. Preventative measures consist of enclosure modifications that facilitate lying rest (e.g., sand hills) or standing rest in a leaning position as a substitute. Anecdotal observations suggest that the provision of appropriate horizontal environmental structures may encourage safe, sleep‐conducive standing rest. We provide drawings on how to install such structures. Effects of providing such structures should be evaluated in the future.
Gender-Based Violence Against Female Students in European University Settings
Authors: List Katrin
Published: March 2018

Due to their age and lifestyle, female students in general are at an increased risk of various forms of sexual violence. Particular sociocultural contexts also form the background of gender-based violence in professional and academic structures. Yet despite institutional and legal efforts to protect (potential) survivors of sexual violence from primary (and secondary) victimization, persistent assaults demonstrate the reluctance of organizations and individuals to fully accept women’s experiences as being physically and psychologically harmful. Based on quantitative and qualitative data obtained in the context of the European research project “Gender-Based Violence, Stalking and Fear of Crime”,1 this article presents a comparative analysis of the prevalence of sexual violence, feelings of safety (or a lack thereof) and the reasons for (non-)disclosure for five European countries. A dataset of about 21,000 responses from German, British, Italian, Spanish and Polish students indicates that sexualized violence is a major problem at universities and that it has yet to be recognized as such. This – added to the fact that it is generally suppressed or concealed by universities – makes it society’s problem as well. The article discusses widespread social myths about victims and perpetrators, the role of the new media in victimization, and the issues of universities’ responsibility for their students (through institutional policy and specific responses to incidents of gender-based violence). The results presented here demonstrate the contradictory perceptions that students have in regard to their experiences and the nature of sexualized violence in an academic environment.
Visualizing One of the Most Hazardous Formations in Nature
Authors: Witman Sarah
Published: March 2018

A network of buoys provides a first glimpse of the seafloor beneath a volatile Italian caldera.
Optimal diversification strategies in the networks of related products and of related research areas
Authors: Alshamsi Aamena , Pinheiro Flávio L. , Hidalgo Cesar A.
Published: March 2018

Countries and cities are likely to enter economic activities that are related to those that are already present in them. Yet, while these path dependencies are universally acknowledged, we lack an understanding of the diversification strategies that can optimally balance the development of related and unrelated activities. Here, we develop algorithms to identify the activities that are optimal to target at each time step. We find that the strategies that minimize the total time needed to diversify an economy target highly connected activities during a narrow and specific time window. We compare the strategies suggested by our model with the strategies followed by countries in the diversification of their exports and research activities, finding that countries follow strategies that are close to the ones suggested by the model. These findings add to our understanding of economic diversification and also to our general understanding of diffusion in networks.
Author Correction: Ultra-fast Hygrometer based on U-shaped Optical Microfiber with Nanoporous Polyelectrolyte Coating
Authors: Chen George Y. , Wu Xuan , Kang Yvonne Qiongyue , Yu Li , Monro Tanya M. , Lancaster David G. , Liu Xiaokong , Xu Haolan
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
In-vivo biomagnetic characterisation of the American cockroach
Authors: Kong Ling-Jun , Crepaz Herbert , Górecka Agnieszka , Urbanek Aleksandra , Dumke Rainer , Paterek Tomasz
Published: March 2018

We present a quantitative method, utilising a highly sensitive quantum sensor, that extends applicability of magnetorelaxometry to biological samples at physiological temperature. The observed magnetic fields allow for non-invasive determination of physical properties of magnetic materials and their surrounding environment inside the specimen. The method is applied to American cockroaches and reveals magnetic deposits with strikingly different behaviour in alive and dead insects. We discuss consequences of this finding to cockroach magneto-reception. To our knowledge, this work represents the first characterisation of the magnetisation dynamics in live insects and helps to connect results from behavioural experiments on insects in magnetic fields with characterisation of magnetic materials in their corpses.
Unexpected Crossover in the kinetics of mutarotation in the supercooled region: the role of H-bonds
Authors: Wolnica K. , Dulski M. , Kaminska E. , Tarnacka M. , Wrzalik R. , Śmiszek-Lindert W. E , Kaminski K. , Paluch M.
Published: March 2018

Intra- and intermolecular studies on the molten L-sorbose have been carried out at variable temperature conditions to determine the crosover temperature (T
c
). In addition, isothermal time-dependent FTIR and Raman measurements were performed to probe the pace of mutarotation and activation energy of this reaction in the studied saccharide, which varied from 53–62 kJ/mol up to 177–192 kJ/mol below and above T
c
, respectively. To explain the change in activation barrier for the mutarotation a complementary analysis using difference FTIR spectra collected around T
c
 = 365 K in the hydroxyl region has been done. It was found that the alteration of kinetic parameters and molecular dynamics around T
c
are strictly related to the variation in the strength of H-bonds which above T
c
are significantly weaken, increasing the freedom of rotation of functional groups and movement of individual molecules. That phenomenon most likely affects the proton transfer, underlying molecular mechanism of mutarotation, which may lead to the significant increase in activation barrier. The new insight into a molecular aspect of the mutarotation around T
c
has created an opportunity to better understanding the relationship between physics of condensed matter and the potential role of H-bonds dynamics on the progress of the chemical reaction in highly viscous systems.
Molecular Camouflage of Plasmodium falciparum Merozoites by Binding of Host Vitronectin to P47 Fragment of SERA5
Authors: Tougan Takahiro , Edula Jyotheeswara R. , Takashima Eizo , Morita Masayuki , Shinohara Miki , Shinohara Akira , Tsuboi Takafumi , Horii Toshihiro
Published: March 2018

The malaria parasitePlasmodium falciparumproliferates in the blood stream where the host immune system is most active. To escape from host immunity,P. falciparumhas developed a number of evasion mechanisms. Serine repeat antigen 5 (SERA5) is a blood stage antigen highly expressed at late trophozoite and schizont stages. The P47 N-terminal domain of SERA5, the basis of SE36 antigen of the blood stage vaccine candidate under clinical trials, covers the merozoite surface. Exploring the role of the P47 domain, screening of serum proteins showed that vitronectin (VTN) directly binds to 20 residues in the C-terminal region of SE36. VTN co-localized with P47 domain in the schizont and merozoite stages. Phagocytosis assay using THP-1 cells demonstrated that VTN bound to SE36 prevented engulfment of SE36-beads. In addition, several serum proteins localized on the merozoite surface, suggesting that host proteins camouflage merozoites against host immunity via binding to VTN.
Orthogonality of Pyrrolysine tRNA in the Xenopus oocyte
Authors: Infield Daniel T. , Lueck John D. , Galpin Jason D. , Galles Grace D. , Ahern Christopher A.
Published: March 2018

Chemical aminoacylation of orthogonal tRNA allows for the genetic encoding of a wide range of synthetic amino acids without the need to evolve specific aminoacyl-tRNA synthetases. This method, when paired with protein expression in the Xenopus laevis oocyte expression system, can extract atomic scale functional data from a protein structure to advance the study of membrane proteins. The utility of the method depends on the orthogonality of the tRNA species used to deliver the amino acid. Here, we report that the pyrrolysyl tRNA (pylT) from Methanosarcina barkeri fusaro is orthogonal and highly competent for genetic code expansion experiments in the Xenopus oocyte. The data show that pylT is amendable to chemical acylation in vitro; it is then used to rescue a cytoplasmic site within a voltage-gated sodium channel. Further, the high fidelity of the pylT is demonstrated via encoding of lysine within the selectivity filter of the sodium channel, where sodium ion recognition by the distal amine of this side-chain is essential. Thus, pylT is an appropriate tRNA species for delivery of amino acids via nonsense suppression in the Xenopus oocyte. It may prove useful in experimental contexts wherein reacylation of suppressor tRNAs have been observed.