bluuebunny/crossref_metadata_2025 huggingface dataset:
Knotting nets: Molecular junctions of interconnecting endocrine axes identified by application of the adverse outcome pathway concept
Authors: Brüggemann Maria , Licht Oliver , Fetter Éva , Teigeler Matthias , Schäfers Christoph , Eilebrecht Elke
Published: October 2017

To be defined as an endocrine disruptor, a substance has to meet several criteria, including the induction of specific adverse effects, a specific endocrine mode of action, and a plausible link between both. The latter criterion in particular might not always be unequivocally determined, especially because the endocrine system consists of diverse endocrine axes. The axes closely interact with each other, and manipulation of one triggers effects on the other. The present review aimed to identify some of the many interconnections between these axes. The focus was on fish, but data obtained in studies on amphibians and mammals were considered if they assisted in closing data gaps, because most of the endocrine mechanisms are evolutionarily conserved. The review includes data both from ecotoxicological studies and on physiological processes and gives information on hormone/hormone receptor interactions or gene transcription regulation. The key events and key event relationships identified provide explanations for unexpected effects on one axis, exerted by substances suspected to act specifically on another axis. Based on these data, several adverse outcome pathway (AOP) segments are identified, describing connections between the hypothalamic–pituitary–gonadal (HPG) and hypothalamic–pituitary–thyroid (HPT) axes, the HPG and hypothalamic–pituitary–adrenal/interrenal (HPA/I) axes, and the HPT and HPA/I axes. Central key events identified across axes were altered aromatase activity as well as altered expression and function of the proteins 11β-hydroxysteroid dehydrogenase (11β-HSD) and steroidogenic acute regulatory (StAR) protein. Substance classes that act on more than one endocrine axis were, for example, goitrogens or aromatase inhibitors. Despite the wealth of information gathered, the present review only provides a few insights into the molecular nets of endocrine axes, demonstrating the complexity of their interconnections. Environ Toxicol Chem 2018;37:318–328. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Hybrid PLC‐VLC channel model and spectral estimation using a nonparametric approach
Authors: Ndjiongue Alain Richard , Ferreira Hendrik Christoffel , Song Jian , Yang Fang , Cheng Ling
Published: October 2017

Telecommunication engineering may substantially benefit from the integration of power line communication (PLC) and visible light communication (VLC) technologies. This integration is enabled firstly by the ubiquitous nature of PLC and VLC infrastructures and secondly by the recent advances made in both technologies, and it will be effective with the knowledge of the cascaded PLC‐VLC channel. This paper reports on the spectral analysis and estimation of the dual channel for hybrid systems involving PLC and VLC technologies. The channels are statistically analysed using the nonparametric windowed Welch method. Experimental results giving varieties of simulated PLC‐VLC channel are presented. They show the influence of the number of taps (PLC side) and the line‐of‐sight and the non–line‐of‐sight gains (VLC side) on the PLC‐VLC frequency response. It also indicates that the cascaded channel is influenced by propagation distance and room area. We also show the influence of PLC and VLC channel parameters on the gain and notches.
On the performance of a nonorthogonal multiple‐access technique for downlink MIMO cooperative networks
Authors: Zhang Yangyang , Ge Jianhua , Serpedin Erchin
Published: October 2017

Nonorthogonal multiple access (NOMA) has been regarded as an appropriate multiple‐access technique for fifth generation due to its radio‐frequency spectrum effective usage and significant capacity gains. In this paper, a cooperative network is considered, where 2 kinds of signal transmission links exist at the same time, ie, the direct link and the relaying link. The system performance is evaluated in a NOMA‐based downlink multiple‐input–multiple‐output relaying network in terms of 2 measures, ie, the outage probability and the ergodic rate. Due to the uncertainty of the signal‐to‐interference‐plus‐noise ratio (SINR) at the users reached by the direct links, at the base station, the best antenna that maximizes the instantaneous system SINR at the relay is selected to transmit the signals. Furthermore, for the receiving antennas at the multiple users, maximal ratio combining is used to exploit efficiently the diversity offered by the multiple antennas. Closed‐form expressions for the exact outage probability and the ergodic rate at high SINR are derived. Moreover, the diversity order is obtained by analyzing the asymptotic outage probability. Finally, the extensive simulations are performed to corroborate that NOMA, in combination with a successive interference canceller, represents a significant alternative to the orthogonal multiple access in catching up with the high demands for radio spectrum.
Slow adaptive energy‐efficient resource allocation in OFDMA HetNets considering demand uncertainty
Authors: Vaezpour Elaheh , Dehghan Mehdi
Published: October 2017

In this paper, we consider the downlink of a hybrid heterogeneous network with femtocells overlaid on a macrocell. Considering the rate requirements of femtocell users and interference thresholds for both co‐tier and cross‐tier users, we formulate the joint power and subchannel allocation problem to maximize the energy efficiency in orthogonal frequency‐division multiple access–based open‐access 2‐tier heterogeneous networks. Due to user's mobility and fluctuating data rate demand, data rate requirements of users are subject to uncertainty, which is ignored in previous works. Toward this end, we study the demand uncertainty by an error model in which femtocells do not have knowledge about the exact distributions and instead assume that each user demand follows a probability distribution function, which belongs to a set of distributions with specific properties (ie, mean and variance). Since these statistics are obtained from historical data, we also take into account the moment uncertainty. Under this error model, the distributionally robust energy‐efficient optimization problem is formulated, which is intractable. To make it tractable, we present the problem in an equivalent form by using the duality theory and then propose decomposition techniques to divide the problem into a fractional programming and a semi‐infinite subproblem. Moreover, we provide optimization methods to solve each one. Our extensive experimental results highlight the effectiveness of our robust solution in uncertain environments, examine the cost of robustness, and demonstrate the convergence of our proposed algorithm. As shown by simulations, our approach provides robustness while incurring minor loss (less than 5%) in optimality.
Joint uplink and downlink optimization of pilot assignment for massive MIMO with power control
Authors: Marinello Filho José Carlos , Panazio Cristiano Magalhães , Abrão Taufik
Published: October 2017

In this paper, we investigate the effects of pilot assignment (PA) in multicell massive multiple‐input–multiple‐output systems. When deploying linear detection/precoding algorithms and a large number of antennas at base station (BS), it is well‐known that system performance in both uplink (UL) and downlink (DL) is mainly restricted by pilot contamination. Such interference is proper of each pilot sequence, and thus, system performance can be improved by suitably assigning the pilots to the users within a given cell, according to a certain desired metric. We show in this paper that UL and DL performances constitute conflicting metrics, since it is not possible to achieve the best performance in UL and DL concomitantly. Thus, we propose an alternative metric, namely, total capacity, aiming to simultaneously achieve a suitable performance in both directions, ie, UL and DL. Since the PA problem is combinatorial, and the search space grows with the number of pilots in a factorial fashion, we also propose a low‐complexity suboptimal algorithm that achieves promising capacity performance avoiding the exhaustive search. In addition, to fully benefit from the large excess of BS antennas, we combine our proposed PA schemes with an efficient power control algorithm, unveiling the great potential of the proposed schemes to provide improved performance for more users, even with a not‐so‐large number of BS antennas. In a limit condition, for example, our numerical results demonstrate that with 64 BS antennas serving 10 users, our proposed method can assure a 95% likely rate of 4.2 Mbps for both DL and UL, and a symmetric 95% likely rate of 1.4 Mbps when serving 32 users. If a higher number of antennas is allowed at BS, the guaranteed rates can be significantly higher.
Dopamine cross‐reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation
Authors: Koppel Indrek , Jaanson Kaur , Klasche Airi , Tuvikene Jürgen , Tiirik Tõnis , Pärn Angela , Timmusk Tõnis
Published: October 2017

Expression of brain‐derived neurotrophic factor (BDNF) is induced in cultured rat cortical astrocytes by catecholamines norepinephrine and dopamine as well as selective α1 and β adrenergic agonists. However, it has remained unknown which receptors mediate dopamine‐induced BDNF upregulation in astrocytes. Here, we demonstrate that β adrenoreceptors are the main mediators of this effect in cultured cortical astrocytes, while α1 adrenoreceptors and D1 dopamine receptors contribute to a lesser extent. We show that in cortical astrocytes BDNF exon IV and exon VI containing mRNAs are induced by dopamine and norepinephrine via CREB‐dependent signaling and that this regulation is mediated by a mechanism that is distinct from activity‐dependent CREB‐mediated activation of BDNF transcription in neurons. We also show that regulation of BDNF promoters IV and VI by catecholamines requires a distal regulatory element in the BDNF locus. Finally, we demonstrate that dopamine‐induced astrocyte stellation and induction of CREB signaling are mediated by cross‐reaction of dopamine with β adrenoreceptors.
Solid‐Phase Synthesis of the Aged‐Nonapeptide‐Nerve‐Agent Adduct of Butyrylcholinesterase as Reference Materials for Analytical Verification
Authors: Bielmann Andreas , Curty Christophe , Bochet Christian G.
Published: October 2017

Two pathways were developed and investigated for the synthesis of the ‘aged’‐nonapeptide nerve‐agent bioadduct of human butyrylcholinesterase (BuChE). Considering the fast ageing of nerve‐agent adducts of BuChE in patients and biomedical samples this target molecule is of paramount relevance for quantitative analysis with respect to the Chemical Weapons Convention. Two approaches using a precursor bearing a hydroxyl on its phosphonyl moiety and a benzyl protected precursor were considered. Several impurities were identified and circumvented during the optimization of the peptide synthesis step. The ‘aged’‐nonapeptide adduct was successfully synthesized by solid‐phase‐peptide‐synthesis (SPPS).
Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences?
Authors: Ranchon Florence , Vantard Nicolas , Henin Emilie , Bachy Emmanuel , Sarkozy Clémentine , Karlin Lionel , Bouafia‐Sauvy Fadhela , Gouraud Aurore , Schwiertz Verane , Bourbon Estelle , Baudouin Amandine , Caffin Anne Gaelle , Vial Thierry , Salles Gilles , Rioufol Catherine
Published: October 2017

The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high‐dose methotrexate (≥1 g/m2) for haematological malignancy and to identify the impact of interacting drugs, especially proton‐pump inhibitors (PPIs) and ranitidine. All patients treated with high‐dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton‐pump inhibitors were co‐administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety‐three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton‐pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination.
Management of syphilis in pregnancy: Knowledge and practices of health care providers and barriers to the control of disease in Teresina, Brazil
Authors: Rodrigues Danielle Carvalho , Domingues Rosa Maria Soares Madeira
Published: October 2017

Aims

The aim of the study is to verify the knowledge and practices of health professionals working in prenatal care (PNC) related with syphilis during pregnancy and to identify the main barriers to the implementation of protocols for the control of this disease.

Methods

A cross‐sectional study in Teresina, Brazil, from January to May 2015, was conducted with 366 physicians and nurses working in PNC, corresponding to 70% of eligible professionals. We evaluated 20 knowledge and practice criteria related to the diagnosis and treatment of syphilis during pregnancy with a 95% compliance standard. We performed descriptive analysis of the data and used χ2 statistical test to verify differences according to professional category.

Results

Only 2 criteria, “knowledge about mother to child transmission according to gestational age” and “counselling on infection,” reached 95% compliance. Knowledge of the epidemiological profile of congenital syphilis and the goal of elimination of congenital syphilis and knowledge about serological tests had scores below 50%, while practices related with posttest counselling, cure control, and treatment of partners reached 60%. We identified organisational barriers related to the late initiation of PNC, to the delayed return of syphilis test results, to the application of benzathine penicillin in primary care units and to the treatment of partners.

Conclusions

Strategies for early initiation of PNC, implementation of rapid tests for syphilis, ensuring treatment of pregnant women with penicillin, adequate partner treatment, and continued education of health professionals on clinical management and counselling in sexually transmitted diseases are necessary to eliminate congenital syphilis.
Contribution of occult precipitation to the water balance of páramo ecosystems in the Colombian Andes
Authors: Cárdenas Maria Fernanda , Tobón Conrado , Buytaert Wouter
Published: October 2017

Páramos are high‐altitudinal neotropical ecosystems located in the upper regions of the northern Andes. Their hydrology is characterized by an extraordinarily high run‐off ratio. One major contributing mechanism is thought to be fog occurrence, which is common in the páramos and occurs by the cooling of near‐surface moist air, as it is forced to higher elevations by topography. However, field‐based observations and quantification of this flux are rare. We present results of monitoring of occult precipitation, understood as the combination of fog and drizzle inputs, combined with meteorological and soil moisture monitoring for periods between 7 to 17 months in 6 sites distributed over 3 páramos catchments in Colombia: three sites in Romerales (Quindío), two in Chingaza (Cundinamarca), and one in Belmira (Antioquia). Occult precipitation inputs were measured with cylindrical fog gauges with a cover on top. We estimate occult precipitation inputs to add between 7% and 28% to rainfall inputs in the study sites. Our results also show that occult precipitation has a large temporal and spatial variability, both within one site and between sites, which make it difficult to upscale and quantify at a catchment scale. Nevertheless, occult precipitation can be important for downstream water supply given that these inputs are especially concentrated during periods with low rainfall. Lastly, we also find evidence for an increase in soil moisture related to occult precipitation during a dry period in Romerales páramo.
Estimating daily lake evaporation from biweekly energy‐budget data
Authors: Andreasen Mie , Rosenberry Donald O. , Stannard David I.
Published: October 2017

Estimates of daily lake evaporation based on energy‐budget data are poor because of large errors associated with quantifying change in lake heat storage over periods of less than about 10 days. Energy‐budget evaporation was determined during approximately biweekly periods at a northern Minnesota, USA, lake for 5 years. Various combinations of shortwave radiation, air temperature, wind speed, lake‐surface temperature, and vapour‐pressure difference were related to energy‐budget evaporation using linear‐regression models in an effort to determine daily evaporation without requiring the heat‐storage term. The model that combined the product of shortwave radiation and air temperature with the product of vapour‐pressure difference and wind speed provided the second best fit based on statistics but provided the best daily data based on comparisons with evaporation determined with the eddy‐covariance method. Best‐model daily values ranged from −0.6 to 7.1 mm/day over a 5‐year period. Daily averages of best‐model evaporation and eddy‐covariance evaporation were nearly identical for all 28 days of comparisons with a standard deviation of the differences between the two methods of 0.68 mm/day. Best‐model daily evaporation also was compared with two other evaporation models, Jensen–Haise and a mass‐transfer model. Best‐model daily values were substantially improved relative to Jensen–Haise and mass‐transfer values when daily values were summed over biweekly energy‐budget periods for comparison with energy‐budget results.
Anthropometric factors and cutaneous melanoma: Prospective data from the population‐based Janus Cohort
Authors: Stenehjem Jo S , Veierød Marit B , Nilsen Lill Tove , Ghiasvand Reza , Johnsen Bjørn , Grimsrud Tom K , Babigumira Ronnie , Rees Judith R , Robsahm Trude E
Published: October 2017

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population‐based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non‐linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking status. During a mean follow‐up of 27 years, 3,000 incident CM cases were identified. In men, CM risk was positively associated with body mass index, body surface area (BSA), height and weight (all ptrends < 0.001), and the exposure‐response curves indicated an exponential increase in risk for all anthropometric factors. Weight loss of more than 2 kg in men was associated with a 53% lower risk (HR 0.47, 95% CI: 0.39, 0.57). In women, CM risk increased with increasing BSA (ptrend = 0.002) and height (ptrend < 0.001). The shape of the height‐CM risk curve indicated an exponential increase. Our study suggests that large body size, in general, is a CM risk factor in men, and is the first to report that weight loss may reduce the risk of CM among men.
Transcriptional variations in the wider peritumoral tissue environment of pancreatic cancer
Authors: Bauer Andrea S. , Nazarov Petr V. , Giese Nathalia A. , Beghelli Stefania , Heller Anette , Greenhalf William , Costello Eithne , Muller Arnaud , Bier Melanie , Strobel Oliver , Hackert Thilo , Vallar Laurent , Scarpa Aldo , Büchler Markus W. , Neoptolemos John P. , Kreis Stephanie , Hoheisel Jörg D.
Published: October 2017

Transcriptional profiling was performed on 452 RNA preparations isolated from various types of pancreatic tissue from tumour patients and healthy donors, with a particular focus on peritumoral samples. Pancreatic ductal adenocarcinomas (PDAC) and cystic tumours were most different in these non‐tumorous tissues surrounding them, whereas the actual tumours exhibited rather similar transcript patterns. The environment of cystic tumours was transcriptionally nearly identical to normal pancreas tissue. In contrast, the tissue around PDAC behaved a lot like the tumour, indicating some kind of field defect, while showing far less molecular resemblance to both chronic pancreatitis and healthy tissue. This suggests that the major pathogenic difference between cystic and ductal tumours may be due to their cellular environment rather than the few variations between the tumours. Lack of correlation between DNA methylation and transcript levels makes it unlikely that the observed field defect in the peritumoral tissue of PDAC is controlled to a large extent by such epigenetic regulation. Functionally, a strikingly large number of autophagy‐related transcripts was changed in both PDAC and its peritumoral tissue, but not in other pancreatic tumours. A transcription signature of 15 autophagy‐related genes was established that permits a prognosis of survival with high accuracy and indicates the role of autophagy in tumour biology.
How many cancer cases and deaths are potentially preventable? Estimates for Australia in 2013
Authors: Wilson Louise F. , Antonsson Annika , Green Adele C. , Jordan Susan J. , Kendall Bradley J. , Nagle Christina M. , Neale Rachel E. , Olsen Catherine M. , Webb Penelope M. , Whiteman David C.
Published: October 2017

Cancer is a leading cause of disease burden in Australia, particularly fatal burden, accounting for an estimated thirty percent of deaths. Many cancers develop because of exposure to lifestyle and environmental factors that are potentially modifiable. We aimed to quantify the proportions and numbers of cancer deaths and cases in Australia in 2013 attributable to 20 modifiable factors in eight broad groupings that are established causes of cancer, namely: tobacco smoke (smoking and second‐hand), dietary factors (low intake of fruit, non‐starchy vegetables and dietary fibre; and high intake of red and processed meat), overweight/obesity, alcohol, physical inactivity, solar ultraviolet radiation, infections (seven agents), and reproductive factors (lack of breastfeeding, menopausal hormone therapy use, combined oral contraceptive use). We estimated population attributable fractions (PAF) using standard formulae incorporating exposure prevalence and relative risk data. Of all cancer deaths in Australia in 2013, approximately 38% overall (males 41%, females 34%) could be attributed to the factors assessed; the corresponding PAF for cancer cases was 33% (males 34%, females 32%). Tobacco smoke was the leading cause of cancer deaths and cases, with PAFs of 23 and 13%, respectively, followed by dietary factors (5% deaths/5% cases), overweight/obesity (5%/4%) and infections (5%/3%). Cancer sites with the highest numbers of potentially preventable deaths/cases were lung (n = 6,776/9,272), colorectum (n = 1,974/7,380) and cutaneous melanoma (n = 1,390/7,918). We estimate that about 16,700 cancer deaths and 41,200 cancer cases could be prevented in Australia each year if people's exposures to 20 causal factors were aligned with levels recommended to minimise cancer risk.
Mean and variance equation dynamics: Time deformation, GARCH, and a robust analysis of the London housing market
Authors: Cook Steve , Watson Duncan
Published: October 2017

The potential relationship between time deformation and generalized autoregressive conditional heteroscedasticity (GARCH) is examined. Despite time deformation and GARCH being mean and variance equation phenomena, respectively, they are argued herein to share a common motivation relating to the examination of changes in the temporal evolution of time‐series processes. Via extensive simulation analysis, a close connection between the two concepts is established. It is found that the presence of GARCH can result in the spurious detection of time deformation, particularly when examining the heavy‐tailed distributions and volatile data typically considered in empirical finance. It is shown that although the application of heteroskedasticity corrected covariance matrix estimators often increases, rather than corrects, the detected oversizing of the tests of time deformation, the application of GARCH filters does provide a solution to size distortion. The findings of the experimental analysis are drawn upon to provide a robust empirical examination of the London housing market where evidence of overwhelming and widespread nonlinearity is detected in the form of time deformation. The implications of these findings for the conduct of future, and the interpretation of previous, research are discussed.
Impact of maternal vaccination timing and influenza virus circulation on birth outcomes in rural Nepal
Authors: Kozuki Naoko , Katz Joanne , Englund Janet A. , Steinhoff Mark C. , Khatry Subarna K. , Shrestha Laxman , Kuypers Jane , Mullany Luke C. , Chu Helen Y. , LeClerq Steven C. , Tielsch James M.
Published: October 2017

Objective

To describe the effect of maternal vaccination on birth outcomes in rural Nepal, modified by timing of vaccination in pregnancy and influenza virus activity.

Methods

A secondary analysis was conducted using data from two annual cohorts of a randomized controlled trial. A total of 3693 pregnant women from Sarlahi District were enrolled between April 25, 2011, and September 9, 2013. All participants were aged 15–40 years and received a trivalent inactivated influenza vaccine or placebo. The outcome measures included birth weight, pregnancy length, low birth weight (<2500 g), preterm birth, and small‐for‐gestational‐age birth.

Results

Data were available on birth weight for 2741 births and on pregnancy length for 3623 births. Maternal vaccination increased mean birthweight by 42 g (95% confidence interval [CI] 8–76). The magnitude of this increase varied by season but was greatest among pregnancies with high influenza virus circulation during the third trimester. Birth weight increased by 111 g (95% CI −51 to 273) when 75%–100% of a pregnancy's third trimester had high influenza virus circulation versus 38 g (95% CI −6 to 81) when 0%–25% of a pregnancy's third trimester had high influenza virus circulation. However, these results were nonsignificant.

Conclusion

Seasonal maternal influenza vaccination in rural Nepal increased birth weight; the magnitude appeared larger during periods of high influenza virus circulation.

ClinicalTrials.gov

NCT01034254.
AN INITIAL ONTOLOGY FOR SYSTEM QUALITIES
Authors: Boehm Barry , Kukreja Nupul
Published: October 2017

This paper presents an initial ontology for reasoning about a system's System Qualities (SQs), ilities, or non‐functional requirements (reliability, usability, affordability, and more). The need for such ontology is based primarily on two factors. One is the importance of getting the SQs sufficiently well defined such that the system's definition, development, and evolution result in a satisfactory balance of SQ values for the system's success‐critical stakeholders, given the frequent system shortfalls and overruns that occur when the system does not achieve this balance. The other is that current system acquisition and evolution guidance descriptions have numerous deficiencies and inconsistencies in their coverage of SQ considerations. This situation is becoming more serious as systems and their stakeholders become increasingly complex, dynamic, and diverse. This paper provides an elaboration of the needs, a set of initial SQ ontology elements and definitions, examples of their application to some key SQs and their relationships, and an identification of further research and development needed to make the ontology fully useful and evolvable.
SEMANTICALLY‐ENABLED MODEL‐BASED SYSTEMS
Authors: Petnga Leonard , Austin Mark , Blackburn Mark
Published: October 2017

This paper describes a novel approach to the development and integration of semantics to the model‐based systems engineering and operation of safety‐critical network of systems. Engineering models work directly with formal domain and meta‐domain (especially time and space) knowledge that are determinate, provable (ambiguity free), and executable. Engineers encode knowledge as semantic blocks, which are an integration of ontologies, rules, and communication and computation interfaces. This paper exercises these concepts in a collision avoidance problem involving autonomous agents at a traffic intersection.
Differential privacy‐guaranteed trajectory community identification over vehicle ad‐hoc networks
Authors: Zhou Zan , Qiao Yuansong , Zhu Liang , Guan Jianfeng , Liu Yang , Xu Changqiao
Published: October 2017

In vehicle ad‐hoc networks (VANETs), a large number of location‐based services can be provided for users according to their movement features. Meanwhile, privacy may be leaked when users publish true trajectory data to VANETs servers. Traditional privacy‐preserving methods have some limitations, for example, k‐anonymous have to predefine the adversaries' background knowledge. Therefore, this paper proposes a new algorithm to partition and cluster trajectories into a proper community with respect to the particularity of VANETs based on differential privacy. The experimental results show that our method outperforms the suppression algorithm and partition algorithm in perspective from information loss and operation efficiency.
Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique
Authors: Wang Jianfeng , Zheng Wei , Lin Kan , Huang Zhiwei
Published: October 2017

This study aims to characterize biochemical and morphological variations of the clinically relevant anatomical locations of in vivo oral tissue (ie, alveolar process, lateral tongue and floor of the mouth) by using hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) technique. A total of 1049 in vivo fingerprint (FP: 800‐1800 cm−1) and high wavenumber (HW: 2800‐3600 cm−1) Raman spectra were acquired from different oral tissue (alveolar process = 331, lateral tongue = 339 and floor of mouth = 379) of 26 normal subjects in the oral cavity under the OCT imaging guidance. The total Raman dataset were split into 2 parts: 80% for training and 20% for testing. Tissue optical attenuation coefficients of alveolar process, lateral tongue and the floor of the mouth were derived from OCT images, revealing the inter‐anatomical morphological differences; while RS uncovers subtle FP/HW Raman spectral differences among different oral tissues that can be attributed to the differences in inter‐ and intra‐cellular proteins, lipids, DNA and water structures and conformations, enlightening biochemical variability of different oral tissues at the molecular level. Partial least squares‐discriminant analysis implemented on the training dataset show that the integrated tissue optical attenuation coefficients and FP/HW Raman spectra provide diagnostic sensitivities of 99.6%, 82.3%, 50.2%, and specificities of 97.0%, 75.1%, 92.1%, respectively, which are superior to using either RS (sensitivities of 90.2%, 77.5%, 48.8%, and specificities of 95.8%, 72.1%, 88.8%) or optical attenuation coefficients derived from OCT (sensitivities of 75.0%, 78.2%, 47.2%, and specificities of 96.2%, 67.7%, 85.0%) for the differentiation among alveolar process, lateral tongue and the floor of the mouth. Furthermore, the diagnostic algorithms applied to the independent testing dataset based on hybrid RS‐OCT technique gives predictive diagnostic sensitivities of 100%, 76.5%, 51.3%, and specificities of 95.1%, 77.6%, 89.6%, respectively, for the classifications among alveolar process, lateral tongue and the floor of the mouth, which performs much better than either RS or optical attenuation coefficient derived from OCT imaging. This work suggests that inter‐anatomical morphological and biochemical variability are significant which should be considered as an important parameter in the interpretation and rendering of hybrid RS‐OCT technique for oral tissue diagnosis and characterization.
Nanostructured fumarate copolymer‐chitosan crosslinked scaffold: Anin vitroosteochondrogenesis regeneration study
Authors: Lastra María Laura , Molinuevo María Silvina , Blaszczyk‐Lezak Iwona , Mijangos Carmen , Cortizo María Susana
Published: October 2017

In the tissue engineering field, the design of the scaffold inspired on the natural occurring tissue is of vital importance. Ideally, the scaffold surface must promote cell growth and differentiation, while promote angiogenesis in thein vivoimplant of the scaffold. On the other hand, the material selection must be biocompatible and the degradation times should meet tissue reparation times. In the present work, we developed a nanofibrous scaffold based on chitosan crosslinked with diisopropylfumarate‐vinyl acetate copolymer using anodized aluminum oxide (AAO) templates. We have previously demonstrated its biocompatibility properties with low cytotoxicity and proper degradation times. Now, we extended our studies to demonstrate that it can be successfully nanostructured using the AAO templates methodology, obtaining a nanorod‐like scaffold with a diameter comparable to those of collagen fibers of the bone matrix (170 and 300 nm). The nanorods obtained presented a very homogeneous pattern in diameter and length, and supports cell attachment and growth. We also found that both osteoblastic and chondroblastic matrix production were promoted on bone marrow progenitor cells and primary condrocytes growing on the scaffolds, respectively. In addition, the nanostructured scaffold presented no cytotoxicity as it was evaluated using a model of macrophages on culture. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 570–579, 2018.
miR‐422a suppresses SMAD4 protein expression and promotes resistance to muscle loss
Authors: Paul Richard , Lee Jen , Donaldson Anna V. , Connolly Martin , Sharif Mohammad , Natanek Samantha Amanda , Rosendahl Ulrich , Polkey Michael I. , Griffiths Mark , Kemp Paul R.
Published: October 2017

Background

Loss of muscle mass and strength are important sequelae of chronic disease, but the response of individuals is remarkably variable, suggesting important genetic and epigenetic modulators of muscle homeostasis. Such factors are likely to modify the activity of pathways that regulate wasting, but to date, few such factors have been identified.

Methods

The effect of miR‐422a on SMAD4 expression and transforming growth factor (TGF)‐β signalling were determined by western blotting and luciferase assay. miRNA expression was determined by qPCR in plasma and muscle biopsy samples from a cross‐sectional study of patients with chronic obstructive pulmonary disease (COPD) and a longitudinal study of patients undergoing aortic surgery, who were subsequently admitted to the intensive care unit (ICU).

Results

miR‐422a was identified, by a screen, as a microRNA that was present in the plasma of patients with COPD and negatively associated with muscle strength as well as being readily detectable in the muscle of patients. In vitro, miR‐422a suppressed SMAD4 expression and inhibited TGF‐beta and bone morphogenetic protein‐dependent luciferase activity in muscle cells. In male patients with COPD and those undergoing aortic surgery and on the ICU, a model of ICU‐associated muscle weakness, quadriceps expression of miR‐422a was positively associated with muscle strength (maximal voluntary contraction r = 0.59, P < 0.001 and r = 0.51, P = 0.004, for COPD and aortic surgery, respectively). Furthermore, pre‐surgery levels of miR‐422a were inversely associated with the amount of muscle that would be lost in the first post‐operative week (r = −0.57, P < 0.001).

Conclusions

These data suggest that differences in miR‐422a expression contribute to the susceptibility to muscle wasting associated with chronic and acute disease and that at least part of this activity may be mediated by reduced TGF‐beta signalling in skeletal muscle.
Symmetry and stimulus class formation in humans: Control by temporal location in a successive matching task
Authors: Beurms Sarah , Traets Frits , De Houwer Jan , Beckers Tom
Published: October 2017

Symmetry refers to the observation that subjects will derive B‐A (e.g., in the presence of B, select A) after being trained on A‐B (e.g., in the presence of A, select B). Whereas symmetry is readily shown in humans, it has been difficult to demonstrate in nonhuman animals. This difficulty, at least in pigeons, may result from responding to specific stimulus properties that change when sample and comparison stimuli switch roles between training and testing. In three experiments with humans, we investigated to what extent human responding is influenced by the temporal location of stimuli using a successive matching‐to‐sample procedure. Our results indicate that temporal location does not spontaneously control responding in humans, although it does in pigeons. Therefore, the number of functional stimuli that humans respond to in this procedure may be half of the number of functional stimuli that the pigeons respond to. In a fourth experiment, we tested this assumption by doubling the number of functional stimuli controlling responding in human participants in an attempt to make the test more comparable to symmetry tests with pigeons. Here, we found that humans responded according to indirect class formation in the same manner as pigeons do. In sum, our results indicate that functional symmetry is readily observed in humans, even in cases where the temporal features of the stimuli prevent functional symmetry in pigeons. We argue that this difference in behavior between the two species does not necessarily reflect a difference in capacity to show functional symmetry between both species, but could also reflect a difference in the functional stimuli each species responds to.
Outcome and validation of a new clinically based staging system for predicting survival of perihilar cholangiocarcinoma patients
Authors: Laoveeravat Passisd , Jaruvongvanich Veeravich , Wongjarupong Nicha , Linlawan Sittikorn , Tanpowpong Natthaporn , Phathong Chonlada , Phatharacharukul Parkpoom , Treeprasertsuk Sombat , Rerknimitr Rungsun , Chaiteerakij Roongruedee
Published: October 2017

Background and Aim

Currently available staging systems for cholangiocarcinoma (CCA) are not applicable to patients with unresectable stage. A new clinical staging system for perihilar CCA (pCCA) subtype has been recently developed in a US cohort, with a good performance in predicting survival of all pCCA patients. We aimed to determine outcomes of pCCA patients and evaluate predictive performance of this staging system in an Asian population.

Methods

All 141 patients diagnosed with pCCA between 2003 and 2012 were identified. Clinical information was retrospectively abstracted. Patients were classified into four stages based on the new staging system. Survival predictors were analyzed using the Cox proportional hazard analysis.

Results

Of the 141 pCCA patients, 38 (27%), 101 (72%), and 2 (1%) received resection, palliative biliary drainage ± chemotherapy, and best supportive care, respectively. Survival predictors included resectable disease, tumor size, distant metastasis, and cancer antigen 19‐9 ≥ 1000 U/mL. When classified by clinical stages, 13, 4, 99, and 25 patients were in stages I, II, III, and IV, with median survivals of 18.4, 7.3, 6.3, and 2.6 months; and hazard ratio (95% confidence interval) of 1.0 (reference), 1.7 (0.5–5.5), 3.2 (1.5–6.7), and 10.8 (4.6–25.0), respectively.

Conclusion

The clinical staging system has a limited performance in differentiating stage II pCCA patients from stage III patients in the Thai cohort. This can be due to differences in patient characteristics and treatment modalities between the Asian and White pCCA populations. However, the median survivals of patients with other stages are significantly different.
The effects of gene polymorphisms on glioma prognosis
Authors: Cui Ying , Li Guolin , Yan Mengdan , Li Jing , Jin Tianbo , Li Shanqu , Mu Shijie
Published: October 2017

Background

Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma.

Methods

Forty‐three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan–Meier method, Cox regression analysis and the log‐rank test.

Results

The 1‐year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1‐year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1‐year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression‐free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low‐grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high‐grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low‐grade glioma.

Conclusions

Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis.
Age‐ and sex‐related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods
Authors: Goodrich‐Hunsaker Naomi J. , Abildskov Tracy J. , Black Garrett , Bigler Erin D. , Cohen Daniel M. , Mihalov Leslie K. , Bangert Barbara A. , Taylor H. Gerry , Yeates Keith O.
Published: October 2017

Although there are several techniques to analyze diffusion‐weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age‐ and sex‐related differences. Participants were children aged 8–15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract‐based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex‐related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age‐related changes across all white matter tracts. AFQ and TRACULA revealed age‐related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract‐specific results for identifying developmental and sex‐related differences within the brain.
Circulation weather types associated with extreme flood events in Northwestern Mediterranean
Authors: Gilabert Joan , Llasat María Carmen
Published: October 2017

The aim of this work was to identify the circulation weather types associated with flood events that occurred in Catalonia (Northeastern Spain) during the period 1900–2010. To achieve this objective, 261 extraordinary and catastrophic flood and flash flood events that were recorded during this period were characterized and classified based on impact data. A preliminary analysis of maximum precipitation and discharge was conducted in order to have some quantitative hydrometeorological indicators associated with these kinds of events. The objective classification developed by Jenkinson and Collison, which is based on differences in synoptic patterns according to surface pressure, was implemented. Once the weather regimes for each flood event had been established, a statistical and comparative analysis was performed that allowed us to determine which synoptic patterns were more frequently associated with the different flood types, their differences and their similarities. The results show that most synoptic situations were pure cyclonic structures, in both extraordinary and catastrophic events, although they were more frequent in the latter. Catastrophic floods generally had a synoptic origin enhanced by certain mesoscale factors, while extraordinary floods were usually associated with local flash floods that occurred primarily in summer and early autumn, highlighting the undetermined types that were not reflected at a synoptic scale. As the Mediterranean basin is a region where floods cause serious socio‐economic impacts, this work will help improve prevention measures and provide information for policymakers, mainly for land‐use planning and early warning systems.