bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospitalitas: Barbarian settlements and constitutional foundations of medieval Europe
Authors: YOUNG ANDREW T.
Published: August 2017

A rough balance of political power between monarchs and a militarized landed aristocracy characterized medieval Western Europe. Scholars have argued that this balance of power contributed to a tradition of limited government and constitutional bargaining. I argue that 5th- and 6th-century barbarian settlements created a foundation for this balance of power. The settlements provided barbarians with allotments of lands or taxes due from the lands. The allotments served to align the incentives of barbarian warriors and Roman landowners, and realign the incentives of barbarian warriors and their leadership elite. Barbarian military forces became decentralized and the warriors became political powerful shareholders of the realm.
Asymptotic tail behaviour of phase-type scale mixture distributions
Authors: Rojas-Nandayapa Leonardo , Xie Wangyue
Published: August 2017

We consider phase-type scale mixture distributions which correspond to distributions of a product of two independent random variables: a phase-type random variable Y and a non-negative but otherwise arbitrary random variable S called the scaling random variable. We investigate conditions for such a class of distributions to be either light- or heavy-tailed, we explore subexponentiality and determine their maximum domains of attraction. Particular focus is given to phase-type scale mixture distributions where the scaling random variable S has discrete support – such a class of distributions has been recently used in risk applications to approximate heavy-tailed distributions. Our results are complemented with several examples.
ACTION TYPES IN STIT SEMANTICS
Authors: HORTY JOHN , PACUIT ERIC
Published: August 2017

Stit semantics grows out of a modal tradition in the logic of action that concentrates on an operator representing the agency of an individual in seeing to it that some state of affairs holds, rather than on the actions the individual performs in doing so. The purpose of this paper is to enrich stit semantics, and especially epistemic stit semantics, by supplementing the overall framework with an explicit treatment of action types. We show how the introduction of these new action types allows us to define a modal operator capturing an epistemic sense of agency, and how this operator can be used to express an epistemic sense of ability.
Effects of Metribuzin Applied Lay-by on Weed Control and Sweetpotato Crop Response
Authors: Meyers Stephen L. , Shankle Mark W.
Published: August 2017

Field studies were conducted at the Pontotoc Ridge-Flatwoods Branch Experiment Station in Pontotoc, MS in 2015 and 2016 to determine the influence of lay-by metribuzin application on weed control and sweetpotato crop response. With the exception of weedy and hand-weeded checks, all plots received flumioxazin at 107 gaiha−1pre-transplanting followed by (fb) clomazone at 1,120 gaiha−1immediately after transplanting. Lay-by treatments consisted ofS-metolachlor (800 gaiha−1), metribuzin (210 or 315 gaiha−1), metribuzin (210 gha−1) plus napropamide (1,120 gaiha−1), and metribuzin (210 gha−1) plusS-metolachlor (800 gha−1). At 4 weeks after transplanting, sweetpotato crop injury was 3 to 15%, but was transient and not evident after 6 (2015) to 8 weeks after transplanting (2016). Season-long weed control was excellent (≥98%) for all herbicide treatments used in the study. Hand-weeded check plots yielded 4,600; 18,350; 28,770; and 1,520 kgha−1of jumbo, No. 1, marketable, and cull grades, respectively. Jumbo, No. 1, and marketable yields from all herbicide-containing treatments in the study were greater than the weedy check and similar to the hand-weeded check. For all treatments, the portion of yield graded as cull was similar to the hand-weeded check. Canner yield response differed between years. In general, canner yield was greater in 2016 (8,460 to 10,670 kgha−1) than 2015 (1,570 to 3,570 kgha−1). In both years, canner yield in all treatments was similar to the hand-weeded check with one exception: in 2015 sweetpotato receiving metribuzin plus napropamide yielded more canners (3,570 kgha−1) than the hand-weeded check (2,300 kgha−1).
Environmental Correlates with Germinable Weed Seedbanks on Organic Farms across Northern New England
Authors: Smith Richard G. , Birthisel Sonja K. , Bosworth Sidney C. , Brown Bryan , Davis Thomas M. , Gallandt Eric R. , Hazelrigg Ann , Venturini Eric , Warren Nicholas D.
Published: August 2017

The northern New England region includes the states of Vermont, New Hampshire, and Maine and encompasses a large degree of climate and edaphic variation across a relatively small spatial area, making it ideal for studying climate change impacts on agricultural weed communities. We sampled weed seedbanks and measured soil physical and chemical characteristics on 77 organic farms across the region and analyzed the relationships between weed community parameters and select geographic, climatic, and edaphic variables using multivariate procedures. Temperature-related variables (latitude, longitude, mean maximum and minimum temperature) were the strongest and most consistent correlates with weed seedbank composition. Edaphic variables were, for the most part, relatively weaker and inconsistent correlates with weed seedbanks. Our analyses also indicate that a number of agriculturally important weed species are associated with specific U.S. Department of Agriculture plant hardiness zones, implying that future changes in climate factors that result in geographic shifts in these zones will likely be accompanied by changes in the composition of weed communities and therefore new management challenges for farmers.
Halosulfuron-Methyl Degradation from the Surface of Low-Density Polyethylene Mulch Using Analytical and Bioassay Techniques
Authors: Grey Timothy L. , Culpepper A. Stanley , Li Xiao , Vencill William K.
Published: August 2017

Vegetable injury and yield loss has occurred when applying halosulfuron to low-density polyethylene mulch (LDPE) prior to transplanting. Research determined vegetable crop response to halosulfuron applied over LDPE mulch from 1 to 28 d prior to transplanting using (1) temperature effects in aqueous solution in laboratory experiments, (2) analytical evaluation of degradation from LDPE under field conditions, and (3) a field bioassay. Halosulfuron stability was evaluated on a thermal gradient table for temperatures at 10 to 42 C for 15 d. Half-life was inversely related to temperatures ranging from 38.5 d at 20 C to 3.2 d at 42 C, with little to no degradation at temperatures of 11 and 15 C. Analytical data indicated that the field half-life of halosulfuron at 26 or 52 g ha−1applied to LDPE mulch under dry conditions was 2.6 and 2.8 d, respectively. Given the changes in the microclimate effects at the mulch surface by absorption of solar radiation, daily thermal energy quantified halosulfuron degradation (at the same rates) to be 51 and 55 MJ m−2, respectively. At 21 d after treatment (DAT), 90% of halosulfuron had dissipated from the mulch, with none detectable 35 DAT under dry conditions. When watermelon or yellow crookneck squash was transplanted into mulch previously treated with halosulfuron at 79 g ha−1, plant growth and development were equal to nontreated controls as long as there was a 14 d prior to transplant (DPT) interval accompanied by 13.5 cm of rain, or a 17 DPT interval accompanied by 6.2 cm of rain. However, at 79 g ha−1applied at 9 or 1 DPT in 2013, and 1 DPT in 2014, halosulfuron injured yellow squash and reduced yield and fruit number. Halosulfuron at 79 g ha−1applied 1 DPT significantly reduced watermelon yield in 2013, which was confirmed by vine length and plant biomass reductions in 2014. Halosulfuron POST controlsCyperusspp. in mulch vegetable production, but time and rainfall are required for dissipation to occur in order to prevent injury and yield loss.
Misalignment with the external light environment drives metabolic and cardiac dysfunction
Authors: West Alexander C. , Smith Laura , Ray David W. , Loudon Andrew S. I. , Brown Timothy M. , Bechtold David A.
Published: August 2017

Most organisms use internal biological clocks to match behavioural and physiological processes to specific phases of the day–night cycle. Central to this is the synchronisation of internal processes across multiple organ systems. Environmental desynchrony (e.g. shift work) profoundly impacts human health, increasing cardiovascular disease and diabetes risk, yet the underlying mechanisms remain unclear. Here, we characterise the impact of desynchrony between the internal clock and the external light–dark (LD) cycle on mammalian physiology. We reveal that even under stable LD environments, phase misalignment has a profound effect, with decreased metabolic efficiency and disrupted cardiac function including prolonged QT interval duration. Importantly, physiological dysfunction is not driven by disrupted core clock function, nor by an internal desynchrony between organs, but rather the altered phase relationship between the internal clockwork and the external environment. We suggest phase misalignment as a major driver of pathologies associated with shift work, chronotype and social jetlag.
Higher-order assembly of crystalline cylindrical micelles into membrane-extendable colloidosomes
Authors: Dou Hongjing , Li Mei , Qiao Yan , Harniman Robert , Li Xiaoyu , Boott Charlotte E. , Mann Stephen , Manners Ian
Published: August 2017

Crystallization-driven self-assembly of diblock copolymers into cylindrical micelles of controlled length has emerged as a promising approach to the fabrication of functional nanoscale objects with high shape anisotropy. Here we show the preparation of a series of crystallizable diblock copolymers with appropriate wettability and chemical reactivity, and demonstrate their self-assembly into size-specific cylindrical micelle building blocks for the hierarchical construction of mechanically robust colloidosomes with a range of membrane textures, surface chemistries and optical properties. The colloidosomes can be structurally elaborated post assembly by in situ epitaxial elongation of the membrane building blocks to produce microcapsules covered in a chemically distinct, dense network of hair-like outgrowths. Our approach provides a route to hierarchically ordered colloidosomes that retain the intrinsic growth activity of their constituent building blocks to permit biofunctionalization, and have potential applications in areas such as biomimetic encapsulation, drug delivery, catalysis and biosensing.
Erratum: Genomic landscape of high-grade meningiomas
Authors: Bi Wenya Linda , Greenwald Noah F. , Abedalthagafi Malak , Wala Jeremiah , Gibson Will J. , Agarwalla Pankaj K. , Horowitz Peleg , Schumacher Steven E. , Esaulova Ekaterina , Mei Yu , Chevalier Aaron , A. Ducar Matthew , Thorner Aaron R. , van Hummelen Paul , O. Stemmer-Rachamimov Anat , Artyomov Maksym , Al-Mefty Ossama , Dunn Gavin P. , Santagata Sandro , Dunn Ian F. , Beroukhim Rameen
Published: August 2017

A correction to this article has been published and is linked from the HTML version of this article.
Attempts to replicate genetic associations with schizophrenia in a cohort from north India
Authors: Prasad Suman , Bhatia Triptish , Kukshal Prachi , Nimgaonkar Vishwajit L. , Deshpande Smita N. , Thelma B. K.
Published: August 2017

Schizophrenia is a chronic, severe, heritable disorder. Genome-wide association studies, conducted predominantly among Caucasians, have indicated > 100 risk alleles, with most significant SNPs on chromosome 6. There is growing interest as to whether these risk alleles are relevant in other ethnic groups as well. Neither an Indian genome-wide association studies nor a systematic replication of GWAS findings from other populations are reported. Thus, we analyzed 32 SNPs, including those associated in the Caucasian ancestry GWAS and other candidate gene studies, in a north Indian schizophrenia cohort (n = 1009 patients; n = 1029 controls) using a Sequenom mass array. Cognitive functioning was also assessed using the Hindi version of the Penn Computerized Neuropsychological Battery in a subset of the sample. MICB (rs6916394) a previously noted Caucasian candidate, was associated with schizophrenia at the p = 0.02 level. One SNP, rs2064430, AHI1 (6q23.3, SZ Gene database SNP) was associated at the p = 0.04 level. Other candidates had even less significance with rs6932590, intergenic (p = 0.07); rs3130615, MICB (p = 0.08); rs6916921, NFKBIL1 (p = 0.08) and rs9273012, HLA-DQA1 (p = 0.06) and haplotypic associations (p = 0.01–0.05) of 6p SNPs were detected. Of note, nominally significant associations with cognitive variables were identified, after covarying for age and diagnostic status. SNPs with p < 0.01 were: rs3130375, with working memory (p = 0.007); rs377763, with sensorimotor (p = 0.004); rs6916921, NFKBIL1 with emotion (p = 0.01). This relative lack of significant positive associations is likely influenced by the sample size and/or differences in the genetic architecture of schizophrenia across populations, encouraging population specific studies to identify shared and unique genetic risk factors for schizophrenia.
Long-distance impact of Iceland plume on Norway’s rifted margin
Authors: Koptev Alexander , Cloetingh Sierd , Burov Evgueni , François Thomas , Gerya Taras
Published: August 2017

Results of a 3D modeling study inspired by recent seismic tomography of the Northern Atlantic mantle suggest that a complex pattern of hot mantle distribution with long horizontal flows originating from the Iceland mantle plume has been the norm in the geological past. In the Northern Atlantic the Iceland plume has a strong long-distance impact on intraplate deformation affecting both onshore and offshore parts of Norway’s rifted margin. As a result, this margin is characterized by large magnitude differential topography sustained over at least several tens of Myr. Here we use high-resolution 3D thermo-mechanical modeling to demonstrate that the long-distance plume impact can be explained by its fast lateral propagation controlled by pre-existing lithosphere structures. Numerical models show that these structures strongly affect the style of horizontal flow of plume head material. This results in long-distance propagation of hot material emplaced at the lithosphere-asthenosphere boundary causing long-wavelength anomalies in onshore topography of Norway’s rifted margin. Short-wavelength offshore topographic domes are likely caused by joint occurrence of plume-related thermal perturbations and gravitational forces related to plate thickening (ridge push). Our 3D modeling brings together plume impingement, spreading ridge dynamics, and the formation of anomalous intraplate structures offshore Norway in one scenario.
Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy
Authors: Georgakopoulos Nikolaos D. , Frison Michele , Alvarez Maria Soledad , Bertrand Hélène , Wells Geoff , Campanella Michelangelo
Published: August 2017

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control.
Spatial localization of sound elicits early responses from occipital visual cortex in humans
Authors: Campus Claudio , Sandini Giulio , Concetta Morrone Maria , Gori Monica
Published: August 2017

Much evidence points to an interaction between vision and audition at early cortical sites. However, the functional role of these interactions is not yet understood. Here we show an early response of the occipital cortex to sound that it is strongly linked to the spatial localization task performed by the observer. The early occipital response to a sound, usually absent, increased by more than 10-fold when presented during a space localization task, but not during a time localization task. The response amplification was not only specific to the task, but surprisingly also to the position of the stimulus in the two hemifields. We suggest that early occipital processing of sound is linked to the construction of an audio spatial map that may utilize the visual map of the occipital cortex.
Fatty Acid Concentration and Phase Transitions Modulate Aβ Aggregation Pathways
Authors: Rana Pratip , Dean Dexter N. , Steen Edward D. , Vaidya Ashwin , Rangachari Vijayaraghavan , Ghosh Preetam
Published: August 2017

Aggregation of amyloid β (Aβ) peptides is a significant event that underpins Alzheimer disease (AD) pathology. Aβ aggregates, especially the low-molecular weight oligomers, are the primary toxic agents in AD and hence, there is increasing interest in understanding their formation and behavior. Aggregation is a nucleation-dependent process in which the pre-nucleation events are dominated by Aβ homotypic interactions. Dynamic flux and stochasticity during pre-nucleation renders the reactions susceptible to perturbations by other molecules. In this context, we investigate the heterotypic interactions between Aβ and fatty acids (FAs) by two independent tool-sets such as reduced order modelling (ROM) and ensemble kinetic simulation (EKS). We observe that FAs influence Aβ dynamics distinctively in three broadly-defined FA concentration regimes containing non-micellar, pseudo-micellar or micellar phases. While the non-micellar phase promotes on-pathway fibrils, pseudo-micellar and micellar phases promote predominantly off-pathway oligomers, albeit via subtly different mechanisms. Importantly off-pathway oligomers saturate within a limited molecular size, and likely with a different overall conformation than those formed along the on-pathway, suggesting the generation of distinct conformeric strains of Aβ, which may have profound phenotypic outcomes. Our results validate previous experimental observations and provide insights into potential influence of biological interfaces in modulating Aβ aggregation pathways.
GENFIRE: A generalized Fourier iterative reconstruction algorithm for high-resolution 3D imaging
Authors: Pryor Alan , Yang Yongsoo , Rana Arjun , Gallagher-Jones Marcus , Zhou Jihan , Lo Yuan Hung , Melinte Georgian , Chiu Wah , Rodriguez Jose A. , Miao Jianwei
Published: August 2017

Tomography has made a radical impact on diverse fields ranging from the study of 3D atomic arrangements in matter to the study of human health in medicine. Despite its very diverse applications, the core of tomography remains the same, that is, a mathematical method must be implemented to reconstruct the 3D structure of an object from a number of 2D projections. Here, we present the mathematical implementation of a tomographic algorithm, termed GENeralized Fourier Iterative REconstruction (GENFIRE), for high-resolution 3D reconstruction from a limited number of 2D projections. GENFIRE first assembles a 3D Fourier grid with oversampling and then iterates between real and reciprocal space to search for a global solution that is concurrently consistent with the measured data and general physical constraints. The algorithm requires minimal human intervention and also incorporates angular refinement to reduce the tilt angle error. We demonstrate that GENFIRE can produce superior results relative to several other popular tomographic reconstruction techniques through numerical simulations and by experimentally reconstructing the 3D structure of a porous material and a frozen-hydrated marine cyanobacterium. Equipped with a graphical user interface, GENFIRE is freely available from our website and is expected to find broad applications across different disciplines.
Aggregated mesoporous nanoparticles for high surface area light scattering layer TiO2 photoanodes in Dye-sensitized Solar Cells
Authors: Al-Attafi Kadhim , Nattestad Andrew , Yamauchi Yusuke , Dou Shi Xue , Kim Jung Ho
Published: August 2017

Hierarchically structured aggregates, consisting of TiO2 nanoparticles were produced via one-step solvothermal syntheses with a mixed solvent system containing both acetic acid and ethanol. Two of the resulting structures, one ~700 nm and the other ~300 nm in diameter, were found to be comprised of 8.5 nm and 10.5 nm anatase crystals, and possess specific surface areas of 138 and 106 m2 g−1 respectively. These particles were incorporated into Dye-sensitized Solar Cells (DSCs) as high surface area scattering layers, along with a layer of a transparent material. Solar-to-electric conversion efficiencies (PCE) of 9.1% and 8.2% were recorded using these aggregated particles as compared to those of commonly used large particles scattering layer 7.4%.
Exposure to arousal-inducing sounds facilitates visual search
Authors: Asutay Erkin , Västfjäll Daniel
Published: August 2017

Exposure to affective stimuli could enhance perception and facilitate attention via increasing alertness, vigilance, and by decreasing attentional thresholds. However, evidence on the impact of affective sounds on perception and attention is scant. Here, a novel aspect of affective facilitation of attention is studied: whether arousal induced by task-irrelevant auditory stimuli could modulate attention in a visual search. In two experiments, participants performed a visual search task with and without auditory-cues that preceded the search. Participants were faster in locating high-salient targets compared to low-salient targets. Critically, search times and search slopes decreased with increasing auditory-induced arousal while searching for low-salient targets. Taken together, these findings suggest that arousal induced by sounds can facilitate attention in a subsequent visual search. This novel finding provides support for the alerting function of the auditory system by showing an auditory-phasic alerting effect in visual attention. The results also indicate that stimulus arousal modulates the alerting effect. Attention and perception are our everyday tools to navigate our surrounding world and the current findings showing that affective sounds could influence visual attention provide evidence that we make use of affective information during perceptual processing.
Evaluating the Sources of Graphene’s Resistivity Using Differential Conductance
Authors: Somphonsane R. , Ramamoorthy H. , He G. , Nathawat J. , Kwan C.-P. , Arabchigavkani N. , Lee Y.-H. , Fransson J. , Bird J. P.
Published: August 2017

We explore the contributions to the electrical resistance of monolayer and bilayer graphene, revealing transitions between different regimes of charge carrier scattering. In monolayer graphene at low densities, a nonmonotonic variation of the resistance is observed as a function of temperature. Such behaviour is consistent with the influence of scattering from screened Coulomb impurities. At higher densities, the resistance instead varies in a manner consistent with the influence of scattering from acoustic and optical phonons. The crossover from phonon-, to charged-impurity, limited conduction occurs once the concentration of gate-induced carriers is reduced below that of the residual carriers. In bilayer graphene, the resistance exhibits a monotonic decrease with increasing temperature for all densities, with the importance of short-range impurity scattering resulting in a “universal” density-independent (scaled) conductivity at high densities. At lower densities, the conductivity deviates from this universal curve, pointing to the importance of thermal activation of carriers out of charge puddles. These various assignments, in both systems, are made possible by an approach of “differential-conductance mapping”, which allows us to suppress quantum corrections to reveal the underlying mechanisms governing the resistivity.
The immunologic advantage of recurrent nasopharyngeal carcinoma from the viewpoint of Galectin-9/Tim-3-related changes in the tumour microenvironment
Authors: Chen Tseng-Cheng , Chen Chao-Hsien , Wang Cheng-Ping , Lin Pei-Hsuan , Yang Tsung-Lin , Lou Pei-Jen , Ko Jenq-Yuh , Wu Chen-Tu , Chang Yih-Leong
Published: August 2017

Given salvage treatment for recurrent nasopharyngeal carcinoma (NPC) remains a clinical dilemma, immunotherapy targeting NPC-specific immunosuppression may bring new hope. We analyzed the expression of CD8, CD4, Foxp3 and Tim-3 in lymphocytes, and of Galectin-9 in tumour cells between paired primary and recurrent NPC from 95 patients and we noted that there was significant increase in the expression of Galectin-9+ tumour cells (p < 0.001) and Foxp3+ lymphocytes (p < 0.001) but a significant decrease in the expression of CD8+ lymphocytes (p = 0.01) between paired primary and recurrent NPC. Of all patients, 53 patients (55.79%) and 57 patients (60%) had increased percentages of Galectin-9+ tumour cells and of Foxp3+ lymphocytes, respectively. Conversely, 42 patients (44.21%) had decreased percentages of CD8+ lymphocytes. The patients with high Galectin-9 expression in recurrent NPC frequently also had high Tim-3 (p = 0.04) and Foxp3 (p = 0.01), and low CD8 (p = 0.04) expression in lymphocytes. After multivariate analyses, low CD8 expression in lymphocytes was an independent risk factor for relapse-free survival (p = 0.002) and overall survival (p = 0.02). Our data suggests that recurrent NPC may had more immunologic advantage than primary NPC, especially the Galectin-9/Tim-3 pathway. The immunotherapies targeting Galectin-9/Tim-3/Foxp3 interaction may serve as a potential salvage treatment for recurrent NPC.
Cervical nodal volume for prognostication and risk stratification of patients with nasopharyngeal carcinoma, and implications on the TNM-staging system
Authors: Yuan Hui , Ai Qi-Yong , Kwong Dora Lai-Wan , Fong Daniel Yee-Tak , King Ann D. , Vardhanabhuti Varut , Lee Victor Ho-Fun , Khong Pek-Lan
Published: August 2017

We aim to evaluate the quantitative parameters of 18F-FDG PET/CT (metabolic parameters) and MRI (morphologic parameters) for prognostication and risk stratification in nasopharyngeal carcinoma (NPC). 200 (147 males, aged 50 ± 13 years-old, mean ± S.D.) newly diagnosed patients with NPC (TxNxM0) were prospectively recruited. Primary tumor and nodal lesions were identified and segmented for both morphologic (volume, VOL) and metabolic (SUV and MTV) quantification. Independent predictive factors for recurrence free survival (RFS) and overall survival (OS) were morphologic nodal volume (VOL_N, p < 0.001), TNM-stage (p = 0.022), N-Stage (p = 0.024) for RFS, and VOL_N (p = 0.014) for OS. Using Classification and Regression Tree (CART) analysis, three risk-layers were identified for RFS: Stage I/II with VOL_N < 18cc (HR = 1), stage III /IV with VOL_N < 18cc (HR = 2.93), VOL_N ≥ 18cc (HR = 7.84) regardless of disease stage (p < 0.001). For OS, two risk layers were identified: VOL_N < 18cc (HR = 1), VOL_N ≥ 18cc (HR = 4.23) (p = 0.001). The 18cc threshold for morphologic nodal volume was validated by an independent cohort (n = 105). Based on the above risk-classification, 35 patients (17.5%) would have a higher risk than suggested by the TNM-staging system. Thus, morphologic nodal volume is an important factor in prognostication and risk stratification in NPC, and should be incorporated into the staging system, while PET parameters have no advantage for this purpose in our cohort.
Estradiol Regulates Txnip and Prevents Intermittent Hypoxia-Induced Vascular Injury
Authors: Lan Xiao Fei , Zhang Xiu Juan , Lin Ying Ni , Wang Qiong , Xu Hua Jun , Zhou Li Na , Chen Pei Li , Li Qing Yun
Published: August 2017

Chronic intermittent hypoxia (IH) contributes to obstructive sleep apnea (OSA)-related cardiovascular diseases through increasing oxidative stress. It has been widely recognized that estradiol decreases the risk for cardiovascular disease, but the estrogen replacement therapy is limited for its side effects. Thioredoxin (Trx) and its endogenous inhibitor, thioredoxin-interacting protein (Txnip), are associated with the protective effect of estradiol in some conditions. In this study, we aimed to explore whether estradiol could protect against IH-induced vascular injury, and the possible effect of Trx-1/Txnip in this process. Forty-eight adult female C57/BL6J mice were randomly divided into 4 groups, ovariectomy combined with IH group, sham operation combined with IH group, IH group and the control group. The mice treated with IH for 8 hrs/day, and 28 days. IH induced the injury of aorta, and ovariectomized mice were more prone to the IH-induced aortic injury, with higher level of oxidative stress. In vitro, estradiol increased Trx-1 level, but decreased the level of Txnip and oxidative stress in human umbilical vein endothelial cells (HUVECs) treated with IH for 16 hrs. Knock-down of Txnip by specific siRNA rescued oxidative stress and apoptosis. In conclusion, estradiol protects against IH-induced vascular injury, partially through the regulation of Trx-1/Txnip pathway.
Molecular characterization of 20 small supernumerary marker chromosome cases using array comparative genomic hybridization and fluorescence in situ hybridization
Authors: Sun Mingran , Zhang Han , Li Guiying , Guy Carrie J. , Wang Xianfu , Lu Xianglan , Gong Fangchao , Lee Jiyun , Hassed Susan , Li Shibo
Published: August 2017

The variability of a small supernumerary marker chromosome (sSMC)-related phenotype is determined by the molecular component, the size, and shape of the marker chromosome. As fluorescence in situ hybridization has limitations regarding the resolution, efficiency, and accuracy. Recently, array comparative genomic hybridization (aCGH) was used for sSMC characterization. In this study, twenty cases with sSMCs were characterized by aCGH and FISH. Chromosomal origin of the marker chromosomes were successfully identified in seventeen of them. For the three cases with negative aCGH results, two of them were more likely due to that the sSMCs only contained centromere heterochromatin, whereas the reason for the remaining case with negative aCGH finding was uncertain. In order to establish a stronger genotype-phenotype correlation for clinical service in the future and avoid miss characterization, more sSMC cases were needed to be detailed characterized. This will help to clarify the variable clinical characteristics of sSMCs and provide additional information to aid clinical service and future research.
Time-Resolved Pharmacological Studies using Automated, On-line Monitoring of Five Parallel Suspension Cultures
Authors: Alhusban Ala A. , Breadmore Michael C. , Gueven Nuri , Guijt Rosanne M.
Published: August 2017

Early stage pharmacological studies rely on in vitro methodologies for screening and testing compounds. Conventional assays based on endpoint measurements provide limited information because the lack in temporal resolution may not determine the pharmacological effect at its maximum. We developed an on-line, automated system for near real-time monitoring of extracellular content from five parallel suspension cultures, combining cell density measurements with a high-resolution separations every 12 minutes for 4 days. Selector and switching valves provide the fluidic control required to sample from one culture during the analysis of the previous sample from another culture, a time-saving measure that is fundamental to the throughput of the presented system. The system was applied to study the metabolic effects of the drugs rotenone, β-lapachone and clioquinol using lactate as metabolic indicator. For each drug, 96 assays were executed on the extracellular matrix at three concentrations with two controls in parallel, consuming only 5.78 mL of media from each culture over four days, less than 60 μL per analysis. The automated system provides high sample throughput, good temporal resolution and low sample consumption combined with a rugged analytical method with adequate sensitivity, providing a promising new platform for pharmacological and biotechnological studies.
Activation of liver stromal cells is associated with male-biased liver tumor initiation in xmrk and Myc transgenic zebrafish
Authors: Yang Qiqi , Yan Chuan , Gong Zhiyuan
Published: August 2017

Hepatocellular carcinoma (HCC) is more prevalent in men than in women. Previously we have found that some stromal cells, including hepatic stellate cells (HSCs), neutrophils and macrophages, play crucial roles in promoting sex disparity in krasV12-induced zebrafish HCC. The activation of HSCs is mediated by serotonin while activation of neutrophils and macrophages is mediated by cortisol. To ensure that these findings are also applicable to other oncogene induced tumors, stromal cell activation was compared between male and female fish during liver tumorigenesis initiated by xmrk or Myc oncogene. Consistently, we observed male-biased liver tumorigenesis in the xmrk and Myc models. In both models, there was a higher rate of HSC activation accompanied with a higher level of serotonin in male liver tumors. For tumor-infiltrated neutrophils and macrophages, significantly higher densities in male liver tumors were observed in both xmrk and Myc models. However, the male-biased increase of cortisol was observed only in xmrk- but not apparently in Myc expressing liver tumors. Overall, these observations are consistent with the observations in the kras liver tumor model, indicating that the serotonin- and cortisol-mediated pathways also play roles in sex disparity of liver tumors caused by other molecular pathways.
3D imaging of the brain morphology and connectivity defects in a model of psychiatric disorders: MAP6-KO mice
Authors: Gimenez Ulysse , Boulan Benoit , Mauconduit Franck , Taurel Fanny , Leclercq Maxime , Denarier Eric , Brocard Jacques , Gory-Fauré Sylvie , Andrieux Annie , Lahrech Hana , Deloulme Jean Christophe
Published: August 2017

In the central nervous system, microtubule-associated protein 6 (MAP6) is expressed at high levels and is crucial for cognitive abilities. The large spectrum of social and cognitive impairments observed in MAP6-KO mice are reminiscent of the symptoms observed in psychiatric diseases, such as schizophrenia, and respond positively to long-term treatment with antipsychotics. MAP6-KO mice have therefore been proposed to be a useful animal model for these diseases. Here, we explored the brain anatomy in MAP6-KO mice using high spatial resolution 3D MRI, including a volumetric T1w method to image brain structures, and Diffusion Tensor Imaging (DTI) for white matter fiber tractography. 3D DTI imaging of neuronal tracts was validated by comparing results to optical images of cleared brains. Changes to brain architecture included reduced volume of the cerebellum and the thalamus and altered size, integrity and spatial orientation of some neuronal tracks such as the anterior commissure, the mammillary tract, the corpus callosum, the corticospinal tract, the fasciculus retroflexus and the fornix. Our results provide information on the neuroanatomical defects behind the neurological phenotype displayed in the MAP6-KO mice model and especially highlight a severe damage of the corticospinal tract with defasciculation at the location of the pontine nuclei.
Magnetite nanoparticles enhance the performance of a combined bioelectrode-UASB reactor for reductive transformation of 2,4-dichloronitrobenzene
Authors: Wang Caiqin , Ye Lu , Jin Jie , Chen Hui , Xu Xiangyang , Zhu Liang
Published: August 2017

Direct interspecies electron transfer (DIET) among the cometabolism microbes plays a key role in the anaerobic degradation of persistent organic pollutants and stability of anaerobic bioreactor. In this study, the COD removal efficiency increased to 99.0% during the start-up stage in the combined bioelectrode-UASB system (R1) with magnetite nanoparticles addition, which was higher than those in the coupled bioelectrode-UASB (R2; 83.2%) and regular UASB (R3; 71.0%). During the stable stage, the increase of 2,4-dichloronitrobenzene (2,4-DClNB) concentration from 25 mg L−1 to 200 mg L−1 did not affect the COD removal efficiencies in R1 and R2, whereas the performance of R3 was deteriorated obviously. Further intermediates analysis indicated that magnetite nanoparticles enhanced the reductive dechlorination of 2,4-DClNB. High-throughput sequencing results showed that the functional microbes like Syntrophobacter and Syntrophomonas which have been reported to favor the DIET, were predominant on the cathode surface of R1 reactor. It is speculated that the addition of magnetite nanoparticles favors the cooperative metabolism of dechlorinating microbes and electricigens during 2,4-DClNB degradation process in the combined bioelectrode-UASB reactor. This study may provide a new strategy to improve the performance of microbial electrolysis cells and enhance the pollutant removal efficiency.
Functional expression of the entire adhesiome of Salmonella enterica serotype Typhimurium
Authors: Hansmeier Nicole , Miskiewicz Katarzyna , Elpers Laura , Liss Viktoria , Hensel Michael , Sterzenbach Torsten
Published: August 2017

Adhesins are crucial virulence factors of pathogenic bacteria involved in colonization, transmission and pathogenesis. Many bacterial genomes contain the information for a surprisingly large number of diverse adhesive structures. One prominent example is the invasive and facultative intracellular pathogen Salmonella enterica with an adhesiome of up to 20 adhesins. Such large repertoire of adhesins contributes to colonization of a broad range of host species and may allow adaptation to various environments within the host, as well as in non-host environments. For S. enterica, only few members of the adhesiome are functionally expressed under laboratory conditions, and accordingly the structural and functional understanding of the majority of adhesins is sparse. We have devised a simple and versatile approach to functionally express all adhesins of S. enterica serotype Typhimurium, either within Salmonella or within heterologous hosts such as Escherichia coli. We demonstrate the surface expression of various so far cryptic adhesins and show ultrastructural features using atomic force microscopy and transmission electron microscopy. In summary, we report for the first time the expression of the entire adhesiome of S. enterica serotype Typhimurium.
Central Nervous System Responses of the Oriental migratory, Locusta migratoria manilensis, to Fungal Infection
Authors: Zhang Wei , Chen Jianhong , Keyhani Nemat O. , Jin Kai , Wei Qinlv , Xia Yuxian
Published: August 2017

Responses of the central nervous system (CNS) to microbial challenge and the interplay between the CNS and the immune system are important for defending against pathogen attack. We have examined the CNS transcriptional response of Locusta migratoria manilensis to infection by the locust-specific fungal pathogen, Metarhizium acridum. CNS responses were examined during spore attachment, fungal germination and pre-penetration of the cuticle, and cuticle penetration/hemocoel ingress and proliferation. Effects were seen at the earliest time points (4 h post-infection) and the number of differentially expressed genes (DEGs) was highest during late mycosis (72 h post-infection). Significantly affected neurological pathways included genes involved in serotonergic, cholinergic, dopaminergic, GABAergic, and glutamergic synapse responses, as well as pathways responsible for synaptic vesicle cycle, long-term potentiation and depression, and neurotrophin and retrograde endocannabinoid signaling. In addition, a significant number of immune related DEGs were identified. These included components of the Toll, Imd and JAK/STAT pathways, consistent with interactions between the CNS and immune systems. The activation of immune response related CNS genes during early stage infection highlights the rapid detection of microbial pathogens and suggests an important role for the CNS in modulating immunity potentially via initiating behavioral adaptations along with innate immune responses.
Monitoring the electron dynamics of the excited state via higher-order spectral minimum
Authors: Zhang Cai-Ping , Xia Chang-Long , Jia Xiang-Fu , Miao Xiang-Yang
Published: August 2017

A pump-probe scheme for monitoring the electron dynamics of the excited state has been investigated by numerically solving the two-state time-dependent Schrödinger equation based on the non-Born-Oppenheimer approximation. By adjusting the delay time between a mid-infrared probe pulse and an ultra violet pump pulse, an obvious minimum can be seen in the higher-order harmonic region. With electron probability density distribution, ionization rate and classical simulation, the minimum can be ascribed to the electron localization around one nucleus at larger delay time and represents the electron dynamics of the excited state at the time of ionization. Moreover, the position of the minimum is much more sensitive to the nuclear motion.
Late-onset hypersensitivity after a lesion in the ventral posterolateral nucleus of the thalamus: A macaque model of central post-stroke pain
Authors: Nagasaka Kazuaki , Takashima Ichiro , Matsuda Keiji , Higo Noriyuki
Published: August 2017

Central post-stroke pain (CPSP) can occur as a result of a cerebrovascular accident in the ventral posterolateral nucleus (VPL) of the thalamus. Developing therapeutic interventions for CPSP is difficult because its pathophysiology is unclear. Here we developed and characterized a macaque model of CPSP. The location of the VPL was determined by magnetic resonance imaging (MRI) and extracellular recording of neuronal activity during tactile stimulation, after which a hemorrhagic lesion was induced by injecting collagenase type IV. Histological analysis revealed that most of the lesion was localized within the VPL. Several weeks after the injection, the macaques displayed behavioral changes that were interpreted as reflecting the development of both mechanical allodynia and thermal hyperalgesia. Immunohistochemistry revealed that microglial and astrocytic activation in the perilesional areas lasted at least 3 months after injection. The present model reproduced the symptoms of patients suffering from CPSP, in which both mechanical allodynia and thermal hyperalgesia often develop several weeks after cerebrovascular accident. Further, the long-lasting glial activation revealed here may be characteristic of primate brains following injury. The present model will be useful not only for examining the neurological changes underlying CPSP, but also for testing therapeutic interventions for CPSP.
The role of Hfq in regulation of lipA expression in Pseudomonas protegens Pf-5
Authors: Liu Wu , Li Menggang , Yan Jinyong , Yan Yunjun
Published: August 2017

Pseudomonas lipase is a well-studied lipase. However, few studies have been conducted to examine the mechanisms underlying the regulation of the lipase expression. Hfq is a global regulatory protein that, among others, controls the expression of multiple genes, regulate bacterial peristalsis, and participates in the regulation of quorum-sensing (QS) system. In this study, the effects of Hfq on lipase expression were investigated by knocking out the hfq and rsmY genes or overexpressing of hfq and rsmY genes. We found that Hfq regulates the expression of lipA at both transcriptional and translational levels. The translational level was the main regulatory level of lipA. Hfq also regulates the expression and stability of rsmY. Additionally, using hfq/rsmY double gene knock-out, we showed that Hfq can directly bind to the rsmY to regulate lipA activity. In conclusion, our results indicate that Hfq regulates the expression of rsmY mainly at the translational level to influence the expression of lipA in Pseudomonas protegens Pf-5.
Disorder versus two transport lifetimes in a strongly correlated electron liquid
Authors: Marshall Patrick B. , Kim Honggyu , Stemmer Susanne
Published: August 2017

We report on angle-dependent measurements of the sheet resistances and Hall coefficients of electron liquids in SmTiO3/SrTiO3/SmTiO3 quantum well structures, which were grown by molecular beam epitaxy on (001) DyScO3. We compare their transport properties with those of similar structures grown on LSAT [(La0.3Sr0.7)(Al0.65Ta0.35)O3]. On DyScO3, planar defects normal to the quantum wells lead to a strong in-plane anisotropy in the transport properties. This allows for quantifying the role of defects in transport. In particular, we investigate differences in the longitudinal and Hall scattering rates, which is a non-Fermi liquid phenomenon known as lifetime separation. The residuals in both the longitudinal resistance and Hall angle were found to depend on the relative orientations of the transport direction to the planar defects. The Hall angle exhibited a robust T2 temperature dependence along all directions, whereas no simple power law could describe the temperature dependence of the longitudinal resistances. Remarkably, the degree of the carrier lifetime separation, as manifested in the distinctly different temperature dependences and diverging residuals near a critical quantum well thickness, was completely insensitive to disorder. The results allow for a clear distinction between disorder-induced contributions to the transport and intrinsic, non-Fermi liquid phenomena, which includes the lifetime separation.
Predicting irreversible electroporation-induced tissue damage by means of magnetic resonance electrical impedance tomography
Authors: Kranjc Matej , Kranjc Simona , Bajd Franci , Serša Gregor , Serša Igor , Miklavčič Damijan
Published: August 2017

Irreversible electroporation (IRE) is gaining importance in routine clinical practice for nonthermal ablation of solid tumors. For its success, it is extremely important that the coverage and exposure time of the treated tumor to the electric field is within the specified range. Measurement of electric field distribution during the electroporation treatment can be achieved using magnetic resonance electrical impedance tomography (MREIT). Here, we show improved MREIT-enabled electroporation monitoring of IRE-treated tumors by predicting IRE-ablated tumor areas during IRE of mouse tumors in vivo. The in situ prediction is enabled by coupling MREIT with a corresponding Peleg-Fermi mathematical model to obtain more informative monitoring of IRE tissue ablation by providing cell death probability in the IRE-treated tumors. This technique can potentially be used in electroporation-based clinical applications, such as IRE tissue ablation and electrochemotherapy, to improve and assure the desired treatment outcome.