bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatigue assessment of offshore wind turbines on monopile foundations using multi‐band modal expansion
Authors: Iliopoulos Alexandros , Weijtjens Wout , Van Hemelrijck Danny , Devriendt Christof
Published: March 2017

Offshore wind turbines (OWTs) are subjected to both quasi‐static loads originating from variations in the thrust force and dynamic loads linked to turbulence, waves and turbine dynamics. Both types of loads contribute to fatigue life progression and thus define the turbine's age. As a structural health monitoring solution, one could thus directly measure the stress history at fatigue critical locations. However, for OWTs on monopile foundations some fatigue critical locations are located below the seabed. Installing strain sensors at these hotspots is therefore impossible for existing wind turbines. This measurement restriction is overcome by reconstructing the full‐field response of the structure based on the limited number of accelerometers and strain sensors (installed at a few easily accessible locations) and a calibrated finite element model of the system. The system model uses a multi‐band modal expansion approach constituted of the quasi‐static and dynamic contributions. These contributions are superimposed to reconstruct the stress history at all degrees of freedom of the finite element model, and the subsequent assess fatigue life consumption at all fatigue hot spots of the OWT. In this paper, the proposed virtual sensing technique is validated by predicting the stresses in the transition piece with 12 days of consecutive measurements from an operational OWT. The data set contains both variations in environmental and operating conditions as well as extreme events. Finally, a full‐field strain assessment in the tower and foundation system of the OWT is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd.
Simulation relations for fault-tolerance
Authors: Demasi Ramiro , Castro Pablo F. , Maibaum Thomas S. E. , Aguirre Nazareno
Published: March 2017

We present a formal characterization of fault-tolerant behaviors of computing systems via simulation relations. This formalization makes use of variations of standard simulation relations in order to compare the executions of a system that exhibits faults with executions where no faults occur; intuitively, the latter can be understood as a specification of the system and the former as a fault-tolerant implementation. By employing variations of standard simulation algorithms, our characterization enables us to algorithmically check fault-tolerance in polynomial time, i.e., to verify that a system behaves in an acceptable way even subject to the occurrence of faults. Furthermore, the use of simulation relations in this setting allows us to distinguish between the different levels of fault-tolerance exhibited by systems during their execution. We prove that each kind of simulation relation preserves a corresponding class of temporal properties expressed in CTL; more precisely,
masking fault-tolerance
preserves liveness and safety properties,
nonmasking fault-tolerance
preserves liveness properties, while
failsafe fault-tolerance
guarantees the preservation of safety properties. We illustrate the suitability of this formal framework through its application to standard examples of fault-tolerance.
Advancement Flap for Treatment of Complex Cryptoglandular Anal Fistula: Prediction of Therapy Success or Failure Using Anamnestic and Clinical Parameters
Authors: Boenicke Lars , Karsten Eduard , Zirngibl Hubert , Ambe Peter
Published: March 2017

Background

Multiple new procedures for treatment of complex anal fistula have been described in the past decades, but an ideal single technique has yet not been identified. Factors that predict the outcome are required to identify the best procedure for each individual patient. The aim of this study was to find those predictors for advancement flap at midterm follow‐up.

Methods

From 2012 to 2015 in a tertiary university clinic, all patients who underwent advancement flap for treatment of complex cryptoglandular fistula were prospectively enrolled. Pre‐ and postoperatively standardized anamnestic and clinical examinations were performed. Predictive factors for therapy failure were identified using univariate and multivariate analysis.

Results

Out of 65 patients, 61 (93%) completed all examinations and were included in the study. Therapy failure after a mean follow‐up period of 25 months occurred in total n = 11 patients (18%). There was no significant disturbance of continence among the entire study cohort as shown by the incontinence score (preop 0.34 ± 0.91 pts., postop 0.37 ± 0.97 pts.; p = 0.59). Univariate analysis for risk factors for therapy failure revealed age (p = 0.004), history of surgical abscess drainage (p = 0.04), BMI (p = 0.002), suprasphincteric fistula (p = 0.019) and horseshoe abscess (p = 0.036) as independent parameters for therapy failure. During multivariate analysis, only history of surgical abscess drainage (OR = 8.09, p = 0.048, 95% CI 0.98–64.96), suprasphincteric fistula (OR = 6.83, p = 0.032, 95% CI 1.17–6.83) and BMI (OR = 1.23, p = 0.017, 95% CI 1.03–1.46) were independent parameters for therapy failure.

Conclusion

Advancement flap for treatment of complex fistula is effective and has low risk of disturbed continence. BMI, suprasphincteric fistula and history of surgical abscess drainage are predictors for therapy failure.
Earwax as an alternative specimen for forensic analysis
Authors: Shokry Engy , Marques Jair Gonzalez , Ragazzo Paulo César , Pereira Naiara Zedes , Filho Nelson Roberto Antoniosi
Published: March 2017

In this work, we presented, for the first time, earwax as an alternative forensic specimen for detecting 12 neuropsychotic drugs employing liquid chromatography–tandem mass spectrometry in positive and negative ion modes after straightforward extraction with methanol. The method was validated and standard curves were established by external calibration with correlation coefficients >0.99. All precision, accuracy, matrix effects, extraction recoveries, and carryover were within acceptable limits; limits of quantification were sufficiently low to quantify almost all the samples tested. To confirm the feasibility of the study, earwax specimens were collected from actual patients treated with different combinations of the 12 drugs and analyzed by our method; the 12 drugs could be quantified from the earwax specimens of the users successfully, showing usefulness of earwax specimens, because of its noninvasive sampling and the storage of drug(s) for relatively long time together with its being relatively less contaminated by environmental impurities. This study is pioneering; many detailed studies on earwax as an alternative specimen remain to be explored.
Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer's disease and frontotemporal dementia
Authors: Roncero Carlos , Kniefel Heike , Service Erik , Thiel Alexander , Probst Stephan , Chertkow Howard
Published: March 2017

Introduction

We evaluated whether transcranial direct current stimulation (tDCS) can improve picture‐naming abilities in subjects with anomic Alzheimer or frontotemporal dementias.

Methods

Using a double‐blind crossover design, 10 participants were trained on picture naming over a series of 10 sessions with either 30 minutes of anodal (2 mA) tDCS stimulation to the left inferior parieto‐temporal region (P3) or sham stimulation. We evaluated performance on a trained picture‐naming list, an equivalent untrained list, and additional neuropsychological tasks.

Results

Participants improved significantly more receiving real stimulation rather than sham stimulation (40% vs. 19%, P < .01), lasting at least 2 weeks after stimulation. Furthermore, these participants showed a small increase for untrained picture‐naming items and digit span when they received real stimulation but a decrease when sham stimulation was received.

Discussion

tDCS stimulation has promise as a treatment for anomia in demented individuals and the effect can generalize to unstudied items as well as other cognitive abilities.
Variations in late Quaternary wind intensity from grain-size partitioning of loess deposits in the Nenana River Valley, Alaska
Authors: DiPietro Lyndsay M. , Driese Steven G. , Nelson Tyler W. , Harvill Jane L.
Published: March 2017

A high-resolution column of 57 loess samples was collected from the Dry Creek archaeological site in the Nenana River Valley in central Alaska. Numerical grain-size partitioning using a mixed Weibull function was performed on grain-size distributions to obtain a reconstructed record of wind intensity over the last ~15,000 yr. Two grain-size components were identified, one with a mode in the coarse silt range (C1) and the other ranging from medium to very coarse sand (C2). C1 dominates most samples and records regional northerly winds carrying sediment from the Nenana River. These winds were strong during cold intervals, namely, the Carlo Creek glacial readvance (14.2–14 ka), a late Holocene Neoglacial period (4.2–2.7 ka), and recent glacier expansion; weak during the Allerød (14–13.3 ka) and Younger Dryas (12.9–11.7 ka); and variable during the Holocene thermal maximum (11.4–9.4 ka). Deposition of C2 was episodic and represents locally derived sand deposited by southerly katabatic winds from the Alaska Range. These katabatic winds occurred mainly prior to 12 ka and after 4 ka. This study shows that numerical grain-size partitioning is a powerful tool for reconstructing paleoclimate and that it can be successfully applied to Alaskan loess.
Application of Radiocarbon Dating to Forensic Investigation and Evaluation of Formaldehyde Influence on Radiocarbon Age
Authors: Hong Wan , Chung N-E , Park G , Sung K H , Lee J G , Park J-P
Published: March 2017

A radiocarbon (14C) dating technique with accelerator mass spectrometry (AMS) was applied to estimate the year of death and the year of birth of unidentified human remains. Because many of the samples have been preserved in formaldehyde, it was necessary to evaluate the influence of formaldehyde on carbon ages. Samples intentionally preserved in formaldehyde during the known period were measured, and their Δ14C values were compared with results obtained from fresh samples. The influence of formaldehyde on soft tissue was 14 times larger than that on cortical bone. Unfortunately, an effective method for removing the influence of formaldehyde has not yet been found. 14C ages could be obtained only from the samples not preserved in formaldehyde. The years of birth were determined by the ages of the dentin samples, while the years of death were determined by the ages of the bone and soft tissue samples. Multiple sampling from a body provides an advantage in determination of one of two possible ages of a sample obtained using the bomb peak. Victims of the Korean War were ascertained by the year of death. The year of death and the age at death of unidentified bodies were also determined for forensic investigation.
Prenatal maternal stress shapes children’s theory of mind: the QF2011 Queensland Flood Study
Authors: Simcock G. , Kildea S. , Elgbeili G. , Laplante D. P. , Cobham V. , King S.
Published: March 2017

Research shows that stress in pregnancy has powerful and enduring effects on many facets of child development, including increases in behavior problems and neurodevelopmental disorders. Theory of mind is an important aspect of child development that is predictive of successful social functioning and is impaired in children with autism. A number of factors related to individual differences in theory of mind have been identified, but whether theory of mind development is shaped by prenatal events has not yet been examined. In this study we utilized a sudden onset flood that occurred in Queensland, Australia in 2011 to examine whether disaster-related prenatal maternal stress predicts child theory of mind and whether sex of the child or timing of the stressor in pregnancy moderates these effects. Higher levels of flood-related maternal subjective stress, but not objective hardship, predicted worse theory of mind at 30 months (n=130). Further, maternal cognitive appraisal of the flood moderated the effects of stress in pregnancy on girls’ theory of mind performance but not boys’. These results illuminate how stress in pregnancy can shape child development and the findings are discussed in relation to biological mechanisms in pregnancy and stress theory.
Effects of Subtitles, Complexity, and Language Proficiency on	Learning From Online Education Videos
Authors: van der Zee Tim , Admiraal Wilfried , Paas Fred , Saab Nadira , Giesbers Bas
Published: March 2017

Abstract. Open online education has become increasingly popular. In Massive Open Online Courses (MOOCs) videos are generally the most used method of teaching. While most MOOCs are offered in English, the global availability of these courses has attracted many non-native English speakers. To ensure not only the availability, but also the accessibility of open online education, courses should be designed to minimize detrimental effects of a language barrier, for example by providing subtitles. However, with many conflicting research findings it is unclear whether subtitles are beneficial or detrimental for learning from a video, and whether this depends on characteristics of the learner and the video. We hypothesized that the effect of 2nd language subtitles on learning outcomes depends on the language proficiency of the student, as well as the visual-textual information complexity of the video. This three-way interaction was tested in an experimental study. No main effect of subtitles was found, nor any interaction. However, the student’s language proficiency and the complexity of the video do have a substantial impact on learning outcomes.
Video Game Use as Risk Exposure, Protective Incapacitation, or	Inconsequential Activity Among University Students
Authors: Ivory Adrienne Holz , Ivory James D , Lanier Madison
Published: March 2017

Abstract. While there is extensive literature exploring the possible negative effects of video games, and many such studies using college student samples, there is little research on how video game use impacts the unique risk environment of college students. This study focuses on the unique risk aspects of the college and university environment with a preregistered survey comparing three competing models of video games’ possible role (games as risk, incapacitation, or inconsequential) in predicting alcohol and substance use, sexual risk, interpersonal violence, bullying victimization, suicide, disordered eating, and exercise to provide a baseline measure of what role, if any, video games play in the college and university risk environment. Video game play was most consistently associated with outcomes related to suicide and interpersonal violence, and more sporadically associated with some other outcomes.
Interactive Narratives Affecting Social Change
Authors: Steinemann Sharon T. , Iten Glena H. , Opwis Klaus , Forde Seamus F. , Frasseck Lars , Mekler Elisa D.
Published: March 2017

Abstract. Interactive narratives offer interesting opportunities for the study of the impact of media on behavior. A growing amount of research on games advocating social change, including those focusing on interactive narratives, has highlighted their potential for attitudinal and behavioral impact. In this study, we examine the relationship between interactivity and prosocial behavior, as well as potential underlying processes. A yoked study design with 634 participants compared an interactive with a noninteractive narrative. Structural equation modeling revealed no significant differences in prosocial behavior between the interactive and noninteractive condition. However, support for the importance of appreciation for and engagement with a narrative on subsequent prosocial behavior was observed. In summary, while results shed light on processes underlying the relationship between both noninteractive and interactive narratives and prosocial behavior, they also highlight interactivity as a multifaceted concept worth examining in further detail.
The Impact of Immersive Technology on Nature Relatedness and	Pro-Environmental Behavior
Authors: Soliman Monica , Peetz Johanna , Davydenko Mariya
Published: March 2017

Abstract. Those who feel connected to nature tend to be more likely to engage in pro-environmental behavior. How can this connection with nature be created? We examined whether viewing nature-related videos – specifically, the immersiveness of the technological devices used to display these videos – can enhance connection with nature and increase pro-environmental behavior. Participants watched videos of either natural or built environments through a head-mounted display (immersive technology) or a regular computer screen. We predicted that watching a nature video would enhance nature relatedness and pro-environmental behaviors, particularly when presented with immersive technology than with a traditional computer monitor. There was limited support for the hypotheses; watching the nature video significantly enhanced nature relatedness but not pro-environmental behaviors. The type of technology used did not influence the effect of the videos.
Integrated metabolism in sponge–microbe symbiosis revealed by genome-centered metatranscriptomics
Authors: Moitinho-Silva Lucas , Díez-Vives Cristina , Batani Giampiero , Esteves Ana I S , Jahn Martin T , Thomas Torsten
Published: March 2017

Despite an increased understanding of functions in sponge microbiomes, the interactions among the symbionts and between symbionts and host are not well characterized. Here we reconstructed the metabolic interactions within the sponge Cymbastela concentrica microbiome in the context of functional features of symbiotic diatoms and the host. Three genome bins (CcPhy, CcNi and CcThau) were recovered from metagenomic data of C. concentrica, belonging to the proteobacterial family Phyllobacteriaceae, the Nitrospira genus and the thaumarchaeal order Nitrosopumilales. Gene expression was estimated by mapping C. concentrica metatranscriptomic reads. Our analyses indicated that CcPhy is heterotrophic, while CcNi and CcThau are chemolithoautotrophs. CcPhy expressed many transporters for the acquisition of dissolved organic compounds, likely available through the sponge’s filtration activity and symbiotic carbon fixation. Coupled nitrification by CcThau and CcNi was reconstructed, supported by the observed close proximity of the cells in fluorescence in situ hybridization. CcPhy facultative anaerobic respiration and assimilation by diatoms may consume the resulting nitrate. Transcriptional analysis of diatom and sponge functions indicated that these organisms are likely sources of organic compounds, for example, creatine/creatinine and dissolved organic carbon, for other members of the symbiosis. Our results suggest that organic nitrogen compounds, for example, creatine, creatinine, urea and cyanate, fuel the nitrogen cycle within the sponge. This study provides an unprecedented view of the metabolic interactions within sponge–microbe symbiosis, bridging the gap between cell- and community-level knowledge.
Biofilm formation enables free-living nitrogen-fixing rhizobacteria to fix nitrogen under aerobic conditions
Authors: Wang Di , Xu Anming , Elmerich Claudine , Ma Luyan Z
Published: March 2017

The multicellular communities of microorganisms known as biofilms are of high significance in agricultural setting, yet it is largely unknown about the biofilm formed by nitrogen-fixing bacteria. Here we report the biofilm formation by Pseudomonas stutzeri A1501, a free-living rhizospheric bacterium, capable of fixing nitrogen under microaerobic and nitrogen-limiting conditions. P. stutzeri A1501 tended to form biofilm in minimal media, especially under nitrogen depletion condition. Under such growth condition, the biofilms formed at the air–liquid interface (termed as pellicles) and the colony biofilms on agar plates exhibited nitrogenase activity in air. The two kinds of biofilms both contained large ovoid shape ‘cells’ that were multiple living bacteria embedded in a sac of extracellular polymeric substances (EPSs). We proposed to name such large ‘cells’ as A1501 cyst. Our results suggest that the EPS, especially exopolysaccharides enabled the encased bacteria to fix nitrogen while grown under aerobic condition. The formation of A1501 cysts was reversible in response to the changes of carbon or nitrogen source status. A1501 cyst formation depended on nitrogen-limiting signaling and the presence of sufficient carbon sources, yet was independent of an active nitrogenase. The pellicles formed by Azospirillum brasilense, another free-living nitrogen-fixing rhizobacterium, which also exhibited nitrogenase activity and contained the large EPS-encapsuled A1501 cyst-like ‘cells’. Our data imply that free-living nitrogen-fixing bacteria could convert the easy-used carbon sources to exopolysaccharides in order to enable nitrogen fixation in a natural aerobic environment.
Environmental fluctuation governs selection for plasticity in biofilm production
Authors: Yan Jing , Nadell Carey D , Bassler Bonnie L
Published: March 2017

Bacteria can grow in a free-swimming state, as planktonic cells, or in surface-attached communities, termed biofilms. The planktonic and biofilm growth modes differ dramatically with respect to spatial constraints, nutrient access, population density and cell–cell interactions. Fitness trade-offs underlie how successfully bacteria compete in each of these environments. Accordingly, some bacteria have evolved to be specialists in biofilm formation, while others specialize in planktonic growth. There are species, however, that possess flexible strategies: they can transition between the molecular programs required for biofilm formation and for planktonic growth. Such flexible strategies often sacrifice competitive ability against specialists in a given habitat. There is little exploration of the ecological conditions favoring the evolution of the flexible biofilm production strategy for bacteria in competition with specialist biofilm producers or specialist non-producers. Here, we study the human pathogen Vibrio cholerae, a flexible biofilm-former, as well as constitutive biofilm-producing and non-producing mutants. We assess the fitness of these strains under biofilm conditions, planktonic conditions and conditions that demand the ability to transition between the two growth modes. We show that, relative to the specialists, the wild type is superior at dispersal from biofilms to the planktonic phase; however, this capability comes at the expense of reduced competitive fitness against constitutive biofilm producers on surfaces. Wild-type V. cholerae can outcompete the constitutive biofilm producers and non-producers if habitat turnover is sufficiently frequent. Thus, selection for phenotypic flexibility in biofilm production depends on the frequency of environmental fluctuations encountered by bacteria.
Light-sensing via hydrogen peroxide and a peroxiredoxin
Authors: Bodvard Kristofer , Peeters Ken , Roger Friederike , Romanov Natalie , Igbaria Aeid , Welkenhuysen Niek , Palais Gaël , Reiter Wolfgang , Toledano Michel B. , Käll Mikael , Molin Mikael
Published: March 2017

Yeast lacks dedicated photoreceptors; however, blue light still causes pronounced oscillations of the transcription factor Msn2 into and out of the nucleus. Here we show that this poorly understood phenomenon is initiated by a peroxisomal oxidase, which converts light into a hydrogen peroxide (H2O2) signal that is sensed by the peroxiredoxin Tsa1 and transduced to thioredoxin, to counteract PKA-dependent Msn2 phosphorylation. Upon H2O2, the nuclear retention of PKA catalytic subunits, which contributes to delayed Msn2 nuclear concentration, is antagonized in a Tsa1-dependent manner. Conversely, peroxiredoxin hyperoxidation interrupts the H2O2 signal and drives Msn2 oscillations by superimposing on PKA feedback regulation. Our data identify a mechanism by which light could be sensed in all cells lacking dedicated photoreceptors. In particular, the use of H2O2 as a second messenger in signalling is common to Msn2 oscillations and to light-induced entrainment of circadian rhythms and suggests conserved roles for peroxiredoxins in endogenous rhythms.
Lateral orbitofrontal cortex anticipates choices and integrates prior with current information
Authors: Nogueira Ramon , Abolafia Juan M. , Drugowitsch Jan , Balaguer-Ballester Emili , Sanchez-Vives Maria V. , Moreno-Bote Rubén
Published: March 2017

Adaptive behavior requires integrating prior with current information to anticipate upcoming events. Brain structures related to this computation should bring relevant signals from the recent past into the present. Here we report that rats can integrate the most recent prior information with sensory information, thereby improving behavior on a perceptual decision-making task with outcome-dependent past trial history. We find that anticipatory signals in the orbitofrontal cortex about upcoming choice increase over time and are even present before stimulus onset. These neuronal signals also represent the stimulus and relevant second-order combinations of past state variables. The encoding of choice, stimulus and second-order past state variables resides, up to movement onset, in overlapping populations. The neuronal representation of choice before stimulus onset and its build-up once the stimulus is presented suggest that orbitofrontal cortex plays a role in transforming immediate prior and stimulus information into choices using a compact state-space representation.
Chasing the thermodynamical noise limit in whispering-gallery-mode resonators for ultrastable laser frequency stabilization
Authors: Lim Jinkang , Savchenkov Anatoliy A. , Dale Elijah , Liang Wei , Eliyahu Danny , Ilchenko Vladimir , Matsko Andrey B. , Maleki Lute , Wong Chee Wei
Published: March 2017

Ultrastable high-spectral-purity lasers have served as the cornerstone behind optical atomic clocks, quantum measurements, precision optical microwave generation, high-resolution optical spectroscopy, and sensing. Hertz-level lasers stabilized to high-finesse Fabry-Pérot cavities are typically used for these studies, which are large and fragile and remain laboratory instruments. There is a clear demand for rugged miniaturized lasers with stabilities comparable to those of bulk lasers. Over the past decade, ultrahigh-Q optical whispering-gallery-mode resonators have served as a platform for low-noise microlasers but have not yet reached the stabilities defined by their fundamental noise. Here, we show the noise characteristics of whispering-gallery-mode resonators and demonstrate a resonator-stabilized laser at this limit by compensating the intrinsic thermal expansion, allowing a sub-25 Hz linewidth and a 32 Hz Allan deviation. We also reveal the environmental sensitivities of the resonator at the thermodynamical noise limit and long-term frequency drifts governed by random-walk-noise statistics.
TIGAR knockdown radiosensitizes TrxR1-overexpressing glioma in vitro and in vivo via inhibiting Trx1 nuclear transport
Authors: Zhang Yushuo , Chen Fei , Tai Guomei , Wang Jiaojiao , Shang Jun , Zhang Bing , Wang Ping , Huang Baoxing , Du Jie , Yu Jiahua , Zhang Haowen , Liu Fenju
Published: March 2017

The up-regulation of thioredoxin reductase-1 (TrxR1) is detected in more than half of gliomas, which is significantly associated with increased malignancy grade and recurrence rate. The biological functions of NADPH-dependent TrxR1 are mainly associated with reduced thioredoxin-1 (Trx1) which plays critical roles in cellular redox signaling and tumour radio-resistance. Our previous work has proved that TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown could notably radiosensitize glioma cells. However, whether TrxR1-overexpressing glioma cells could be re-radiosensitized by TIGAR silence is still far from clear. In the present study, TrxR1 was stably over-expressed in U-87MG and T98G glioma cells. Both in vitro and in vivo data demonstrated that the radiosensitivity of glioma cells was considerably diminished by TrxR1 overexpression. TIGAR abrogation was able to radiosensitize TrxR1-overexpressing gliomas by inhibiting IR-induced Trx1 nuclear transport. Post-radiotherapy, TIGAR low-expression predicted significant longer survival time for animals suffering from TrxR1-overexpessing xenografts, which suggested that TIGAR abrogation might be a promising strategy for radiosensitizing TrxR1-overexpressing glial tumours.
Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis
Authors: Yan Wen-Ting , Cui Xiang , Chen Qing , Li Ya-Fei , Cui You-Hong , Wang Yan , Jiang Jun
Published: March 2017

Whether circulating tumor cells (CTCs) can be used as an indicator of treatment response in breast cancer (BC) needs to be clarified. We addressed this issue by a meta-analysis. PubMed, EMBase and Cochrane library databases were searched in June 2016. Effect measures were estimated as pooled risk ratio (RR), odds ratio (OR) or mean difference by fixed- or random-effect models, according to heterogeneity of included studies. In total, 50 studies with 6712 patients were recruited. Overall analysis showed that there was a significant reduction of CTC-positive rate (RR = 0.68, 95% CI: 0.61–0.76, P < 0.00001) after treatment. Subgroup analyses revealed that neoadjuvant treatment, adjuvant treatment, metastatic treatment or combination therapy could reduce the CTC-positive rate, but surgery could not; moreover, the reduction was only found in HER2+ or HER2- patients but not in the triple-negative ones. Reduction of CTC-positive rate was associated with lower probability of disease progression (OR = 0.54, 95% CI: 0.33–0.89, P = 0.01) and longer overall survival period (mean difference = 11.61 months, 95% CI: 8.63–14.59, P < 0.00001) as well as longer progression-free survival period (mean difference = 5.07 months, 95% CI: 2.70–7.44, P < 0.0001). These results demonstrate that CTC status can serve as an indicator to monitor the effectiveness of treatments and guide subsequent therapies in BC.
Integration of thermocouple microelectrode in the scanning electrochemical microscope at variable temperatures: simultaneous temperature and electrochemical imaging and its kinetic studies
Authors: Pan He , Zhang Hailing , Lai Junhui , Gu Xiaoxin , Sun Jianjun , Tang Jing , Jin Tao
Published: March 2017

We describe herein a method for the simultaneous measurement of temperature and electrochemical signal with a new type of thermocouple microelectrode. The thermocouple microelectrode can be used not only as a thermometer but also as a scanning electrochemical microscope (SECM) tip in the reaction between tip-generated bromine and a heated Cu sample. The influence of temperature on the SECM imaging process and the related kinetic parameters have been studied, such as kinetic constant and activation energy.
Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregation
Authors: Sant’Anna Ricardo , Almeida Maria Rosário , Varejāo Nathalia , Gallego Pablo , Esperante Sebastian , Ferreira Priscila , Pereira-Henriques Alda , Palhano Fernando L. , de Carvalho Mamede , Foguel Debora , Reverter David , Saraiva Maria João , Ventura Salvador
Published: March 2017

More than a hundred different Transthyretin (TTR) mutations are associated with fatal systemic amyloidoses. They destabilize the protein tetrameric structure and promote the extracellular deposition of TTR as pathological amyloid fibrils. So far, only mutations R104H and T119M have been shown to stabilize significantly TTR, acting as disease suppressors. We describe a novel A108V non-pathogenic mutation found in a Portuguese subject. This variant is more stable than wild type TTR both in vitro and in human plasma, a feature that prevents its aggregation. The crystal structure of A108V reveals that this stabilization comes from novel intra and inter subunit contacts involving the thyroxine (T4) binding site. Exploiting this observation, we engineered a A108I mutation that fills the T4 binding cavity, as evidenced in the crystal structure. This synthetic protein becomes one of the most stable TTR variants described so far, with potential application in gene and protein replacement therapies.
The miR-24-3p/p130Cas: a novel axis regulating the migration and invasion of cancer cells
Authors: Kang Hoin , Rho Jun Gi , Kim Chongtae , Tak Hyosun , Lee Heejin , Ji Eunbyul , Ahn Sojin , Shin A-Ri , Cho Hyun-Il , Huh Yun Hyun , Song Woo Keun , Kim Wook , Lee Eun Kyung
Published: March 2017

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay. Differential expression of miRNAs is involved in the pathogenesis of several diseases including cancer. Here, we investigated the role of-miR-24-3p as a downregulated miRNA in metastatic cancer. miR-24-3p was decreased in metastatic cancer and lower expression of miR-24-3p was related to poor survival of cancer patients. Consistently, ectopic expression of miR-24-3p suppressed the cell migration, invasion, and proliferation of MCF7, Hep3B, B16F10, SK-Hep1, and PC-3 cells by directly targeting p130Cas. Stable expression of p130Cas restored miR-24-3p-mediated inhibition of cell migration and invasion. These results suggest that miR-24-3p functions as a tumor suppressor and the miR-24-3p/p130Cas axis is a novel factor of cancer progression by regulating cell migration and invasion.
Protein interaction evolution from promiscuity to specificity with reduced flexibility in an increasingly complex network
Authors: Alhindi T. , Zhang Z. , Ruelens P. , Coenen H. , Degroote H. , Iraci N. , Geuten K.
Published: March 2017

A key question regarding protein evolution is how proteins adapt to the dynamic environment in which they function and how in turn their evolution shapes the protein interaction network. We used extant and resurrected ancestral plant MADS-domain transcription factors to understand how SEPALLATA3, a protein with hub and glue properties, evolved and takes part in network organization. Although the density of dimeric interactions was saturated in the network, many new interactions became mediated by SEPALLATA3 after a whole genome triplication event. By swapping SEPALLATA3 and its ancestors between dimeric networks of different ages, we found that the protein lost the capacity of promiscuous interaction and acquired specificity in evolution. This was accompanied with constraints on conformations through proline residue accumulation, which made the protein less flexible. SHORT VEGETATIVE PHASE on the other hand (non-hub) was able to gain protein-protein interactions due to a C-terminal domain insertion, allowing for a larger interaction interface. These findings illustrate that protein interaction evolution occurs at the level of conformational dynamics, when the binding mechanism concerns an induced fit or conformational selection. Proteins can evolve towards increased specificity with reduced flexibility when the complexity of the protein interaction network requires specificity.
Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments
Authors: Verdier-Pinard P. , Salaun D. , Bouguenina H. , Shimada S. , Pophillat M. , Audebert S. , Agavnian E. , Coslet S. , Charafe-Jauffret E. , Tachibana T. , Badache A.
Published: March 2017

Functions of septin cytoskeletal polymers in tumorigenesis are still poorly defined. Their role in the regulation of cytokinesis and cell migration were proposed to contribute to cancer associated aneuploidy and metastasis. Overexpression of Septin 9 (Sept9) promotes migration of cancer cell lines. SEPT9 mRNA and protein expression is increased in breast tumors compared to normal and peritumoral tissues and amplification of SEPT9 gene was positively correlated with breast tumor progression. However, the existence of multiple isoforms of Sept9 is a confounding factor in the analysis of Sept9 functions. In the present study, we analyze the protein expression of Sept9_i2, an uncharacterized isoform, in breast cancer cell lines and tumors and describe its specific impact on cancer cell migration and Sept9 cytoskeletal distribution. Collectively, our results showed that, contrary to Sept9_i1, Sept9_i2 did not support cancer cell migration, and induced a loss of subnuclear actin filaments. These effects were dependent on Sept9_i2 specific N-terminal sequence. Sept9_i2 was strongly down-regulated in breast tumors compared to normal mammary tissues. Thus our data indicate that Sept9_i2 is a negative regulator of breast tumorigenesis. We propose that Sept9 tumorigenic properties depend on the balance between Sept9_i1 and Sept9_i2 expression levels.
Post-Hoc Study: Intravenous Hydration Treatment in Chinese Patients with High Risk of Contrast-Induced Nephropathy Following Percutaneous Coronary Intervention
Authors: Bei Weijie , Li Hualong , Lin Kaiyang , Wang Kun , Chen Shiqun , Guo Xiaosheng , Liu Yong , Tan Ning , Chen Jiyan ,   TRUST investigators, Yang Xiangtai , Su Xi , Du Zhimin , Zeng Qiutang , Fang Zhenfei , Wang Yan , Jiang Hong , Xiong Longgen , Hou Yuqing , Yuan Yong , Li Tianfa , Hong Lang , Wu Yanqing , Liu Yin , Lin Wenhua , Jiang Tiemin , Fu Junhua , An Yi , Yu Bo , Tian Ye , Zheng Yang , Liu Bin , Yang Ping , Jiang Xianyan , Wang Hao , Qu Peng , Cui Lianqun , Li Xueqi , Qi Xiaoyong , Ma Zengcai , Li Jifu , Zhang Lili , Liu Shengquan , Pang Wenyue , Li Yibo , Yang Manguang , Ji Zheng , Zhao Pitian , Li Lu , Ge Junbo , Jin Huigen , Pan Weimin , Song Yaoming , Li Jianmei , Xiao Jianming , Liu Hanxiong , Tao Jianhong , Wu Zhongdong , Tuo Buxiong , Li Wei , Xu Yixian , Zhang Zhaoqi , Chen Yundai , Wang Lefeng , Zhang Jinying , Wang Fengling , Jia Yongping , Wang Bin , Tang Fakuan , Tang Qiang , Wang Wei , Sun Yuemin , Su Weiqing
Published: March 2017

Contrast-induced nephropathy (CIN) develops after the injection of iodinated contrast media. This is a post hoc analysis of the data obtained from the TRUST study, which was a prospective, multicentre, observational study conducted to evaluate the safety and tolerability of the contrast medium iopromide in patients undergoing cardiac catheterization from August 2010 to September 2011 in China, conducted to explore the current status, trends and risk predictors of hydration treatment. The status of hydration to prevent CIN in each patient was recorded. Of the total 17,139 patients from the TRUST study (mean age, 60.33 ± 10.38 years), the overall hydration usage was 46.1% in patients undergoing percutaneous coronary intervention (PCI) and 77.4%, 51.7%, and 48.5% in patients with pre-existing renal disease, diabetes mellitus, and hypertension, respectively. The proportion of hydration use increased from 36.5% to 55.5% from August 2010 to September 2011, which was independently associated with risk predictors like older age, pre-existing renal disease, hypertension, diabetes mellitus, prior myocardial infarction, ST segment elevation MI, high contrast dose, multi-vessel disease and reduced LVEF (<45%). Overall, the usage of intravenous hydration treatment for patients with a high risk of CIN following PCI was high in China.
Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus)
Authors: Blanco Ayelén Melisa , Bertucci Juan Ignacio , Ramesh Naresh , Delgado María Jesús , Valenciano Ana Isabel , Unniappan Suraj
Published: March 2017

Glucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish.
Microvasculature on a chip: study of the Endothelial Surface Layer and the flow structure of Red Blood Cells
Authors: Tsvirkun Daria , Grichine Alexei , Duperray Alain , Misbah Chaouqi , Bureau Lionel
Published: March 2017

Microvasculatures-on-a-chip,i.e. in vitromodels that mimic important features of microvessel networks, have gained increasing interest in recent years. Such devices have allowed investigating pathophysiological situations involving abnormal biophysical interactions between blood cells and vessel walls. Still, a central question remains regarding the presence, in such biomimetic systems, of the endothelial glycocalyx. The latter is a glycosaminoglycans-rich surface layer exposed to blood flow, which plays a crucial role in regulating the interactions between circulating cells and the endothelium. Here, we use confocal microscopy to characterize the layer expressed by endothelial cells cultured in microfluidic channels. We show that, under our culture conditions, endothelial cells form a confluent layer on all the walls of the circuit and display a glycocalyx that fully lines the lumen of the microchannels. Moreover, the thickness of this surface layer is found to be on the order of 600 nm, which compares well with measurements performedexorin vivoon microcapillaries. Furthermore, we investigate how the presence of endothelial cells in the microchannels affects their hydrodynamic resistance and the near-wall motion of red blood cells. Our study thus provides an important insight into the physiological relevance ofin vitromicrovasculatures.
In-situ Raman spectroscopy to elucidate the influence of adsorption in graphene electrochemistry
Authors: van den Beld Wesley T. E. , Odijk Mathieu , Vervuurt René H. J. , Weber Jan-Willem , Bol Ageeth A. , van den Berg Albert , Eijkel Jan C. T.
Published: March 2017

Electrochemistry on graphene is of particular interest due to graphene’s high surface area, high electrical conductivity and low interfacial capacitance. Because the graphene Fermi level can be probed by its strong Raman signal, information on the graphene doping can be obtained which in turn can provide information on adsorbed atoms or molecules. For this paper, the adsorption analysis was successfully performed using three electroactive substances with different electrode interaction mechanisms: hexaammineruthenium(III) chloride (RuHex), ferrocenemethanol (FcMeOH) and potassium ferricyanide/potassium ferrocyanide (Fe(CN)6). The adsorption state was probed by analysing the G-peak position in the measured in-situ Raman spectrum during electrochemical experiments. We conclude that electrochemical Raman spectroscopy on graphene is a valuable tool to obtain in-situ information on adsorbed species on graphene, isolated from the rest of the electrochemical behaviour.
Identification of hexose kinase genes in Kluyveromyces marxianus and thermo-tolerant one step producing glucose-free fructose strain construction
Authors: Zhang Guorong , Lu Min , Wang Jichao , Wang Dongmei , Gao Xiaolian , Hong Jiong
Published: March 2017

In yeast, the hexose assimilation is started at hexose phosphorylation. However, in Kluyveromyces marxianus, the hexokinase (HXK) and glucokinase (GLK) genes were not identified by experiments. Meanwhile, the glucose-free fructose product requires more cost-efficient method. In this study, the KmHXK1 and KmGLK1 genes were functionally identified through gene disruption, over-expression and recombinant enzymes characterization. Both glucose and fructose assimilation ability decreased significantly in KmHXK1 disrupted strain YLM001, however, this ability was not changed obviously in KmGLK1 disrupted strain YLM002. When over-expressing KmGLK1 in YLM001, only the glucose assimilation ability was recovered in obtained strain (YLM005). The kinetic constant analysis of recombinant enzymes also proved that KmHXK1 could phosphorylate glucose (Vmax 553.01 U/mg, Km 0.83 mM) and fructose (Vmax 609.82 U/mg, Km 0.52 mM), and KmGLK1 only phosphorylate glucose with a Vmax of 0.73 U/mg and a Km 4.09 mM. A thermo-tolerant strain YGR003 which produced glucose-free fructose from Jerusalem artichoke tuber in one step was constructed based on the obtained information. The highest production and fastest productivity were 234.44 g/L and 10.26 g/L/h, respectively, which were several folds of the results in previous reports.
Intermediate filament reorganization dynamically influences cancer cell alignment and migration
Authors: Holle Andrew W. , Kalafat Melih , Ramos Adria Sales , Seufferlein Thomas , Kemkemer Ralf , Spatz Joachim P.
Published: March 2017

The interactions between a cancer cell and its extracellular matrix (ECM) have been the focus of an increasing amount of investigation. The role of the intermediate filament keratin in cancer has also been coming into focus of late, but more research is needed to understand how this piece fits in the puzzle of cytoskeleton-mediated invasion and metastasis. In Panc-1 invasive pancreatic cancer cells, keratin phosphorylation in conjunction with actin inhibition was found to be sufficient to reduce cell area below either treatment alone. We then analyzed intersecting keratin and actin fibers in the cytoskeleton of cyclically stretched cells and found no directional correlation. The role of keratin organization in Panc-1 cellular morphological adaptation and directed migration was then analyzed by culturing cells on cyclically stretched polydimethylsiloxane (PDMS) substrates, nanoscale grates, and rigid pillars. In general, the reorganization of the keratin cytoskeleton allows the cell to become more ‘mobile’- exhibiting faster and more directed migration and orientation in response to external stimuli. By combining keratin network perturbation with a variety of physical ECM signals, we demonstrate the interconnected nature of the architecture inside the cell and the scaffolding outside of it, and highlight the key elements facilitating cancer cell-ECM interactions.