bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of Phase, Microstructure and ZrC Lattice Parameter in Solid-solution-treated W-ZrC Composite
Authors: Jia Peng , Chen Lei , Rao Jiancun , Wang Yujin , Meng Qingchang , Zhou Yu
Published: July 2017

Zirconium carbide (ZrC) reinforced tungsten (W) composite was hot-pressed at 2200 °C for 1 h in vacuum, which was subsequently heat treated in the temperature range of 2200 to 2500 °C for 1.5 or 2 h. The relative ratios of ZrC phase were 21.0, 23.3 and 25.9 mol.% for the mixture of starting powders, composites sintered for 1 h and solid-solution treated at 2500 °C for 1.5 h, respectively. The solid solubility of W in ZrC increased with the increment in heat-treating temperature and time to a maximum value of 18.9 mol.% at 2500 °C for 1.5 h. The lattice parameter of cubic ZrC phase diminished from 0.4682 nm in the starting powder to 0.4642 nm in the solid-solution composite treated at 2500 °C for 1.5 h. This work demonstrated that the relationship between the solid solubility of W in ZrC and the lattice parameter of ZrC is linear, with a slope of −1.93 × 10−4 nm/at.%. Overall, more W atoms diffused into ZrC lattice after heat treatment, meanwhile, the previous precipitated nano-sized W dissolved in the supersaturated (Zr,W)C solid-solution, as detected by SEM and TEM.
Comprehensive analysis of human protein N-termini enables assessment of various protein forms
Authors: Yeom Jeonghun , Ju Shinyeong , Choi YunJin , Paek Eunok , Lee Cheolju
Published: July 2017

Various forms of protein (proteoforms) are generated by genetic variations, alternative splicing, alternative translation initiation, co- or post-translational modification and proteolysis. Different proteoforms are in part discovered by characterizing their N-terminal sequences. Here, we introduce an N-terminal-peptide-enrichment method, Nrich. Filter-aided negative selection formed the basis for the use of two N-blocking reagents and two endoproteases in this method. We identified 6,525 acetylated (or partially acetylated) and 6,570 free protein N-termini arising from 5,727 proteins in HEK293T human cells. The protein N-termini included translation initiation sites annotated in the UniProtKB database, putative alternative translational initiation sites, and N-terminal sites exposed after signal/transit/pro-peptide removal or unknown processing, revealing various proteoforms in cells. In addition, 46 novel protein N-termini were identified in 5′ untranslated region (UTR) sequence with pseudo start codons. Our data showing the observation of N-terminal sequences of mature proteins constitutes a useful resource that may provide information for a better understanding of various proteoforms in cells.
The regulation of Hh/Gli1 signaling cascade involves Gsk3β- mediated mechanism in estrogen-derived endometrial hyperplasia
Authors: Kaushal Jyoti Bala , Sankhwar Pushplata , Kumari Suparna , Popli Pooja , Shukla Vinay , Hussain Mohd. Kamil , Hajela Kanchan , Dwivedi Anila
Published: July 2017

The present study was undertaken to explore the functional involvement of Hh signaling and its regulatory mechanism in endometrial hyperplasia. Differential expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3β was observed in endometrial hyperplasial (EH) cells as compared to normal endometrial cells. Estradiol induced the expression of Hh signaling molecules and attenuated the expression of Gsk3β whereas anti-estrogen (K1) or progestin (MPA) suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA knockdown suppressed the growth of EH cells and reduced the expression of proliferative markers. Estradiol also induced the nuclear translocation of Gli1 which was suppressed by both MPA and K1 in EH cells. While exploring non-canonical mechanism, LY-294002 (Gsk3β activator) caused a decrease in Gli1 expression indicating the involvement of Gsk3β in Gli1 regulation. Further, Gsk3β silencing promoted the expression and nuclear translocation of Gli1 demonstrating that Gsk3β serves as a negative kinase regulator of Gli1 in EH cells. Similar attenuation of Hh signaling molecules was observed in rats with uterine hyperplasia undergoing anti-estrogen treatment. The study suggested that Hh/Gli1 cascade (canonical pathway) as well as Gsk3β-Gli1 crosstalk (non-canonical pathway) play crucial role in estrogen-dependent cell proliferation in endometrial hyperplasia.
Structural and physical determinants of the proboscis–sucking pump complex in the evolution of fluid-feeding insects
Authors: Kornev Konstantin G. , Salamatin Arthur A. , Adler Peter H. , Beard Charles E.
Published: July 2017

Fluid-feeding insects have evolved a unique strategy to distribute the labor between a liquid-acquisition device (proboscis) and a sucking pump. We theoretically examined physical constraints associated with coupling of the proboscis and sucking pump into a united functional organ. Classification of fluid feeders with respect to the mechanism of energy dissipation is given by using only two dimensionless parameters that depend on the length and diameter of the proboscis food canal, maximum expansion of the sucking pump chamber, and chamber size. Five species of Lepidoptera — White-headed prominent moth (Symmerista albifrons), White-dotted prominent moth (Nadata gibosa), Monarch butterfly (Danaus plexippus), Carolina sphinx moth (Manduca sexta), and Death’s head sphinx moth (Acherontia atropos) — were used to illustrate this classification. The results provide a rationale for categorizing fluid-feeding insects into two groups, depending on whether muscular energy is spent on moving fluid through the proboscis or through the pump. These findings are relevant to understanding energetic costs of evolutionary elaboration and reduction of the mouthparts and insect diversification through development of new habits by fluid-feeding insects in general and by Lepidoptera in particular.
Hybrid High-order Functional Connectivity Networks Using Resting-state Functional MRI for Mild Cognitive Impairment Diagnosis
Authors: Zhang Yu , Zhang Han , Chen Xiaobo , Lee Seong-Whan , Shen Dinggang
Published: July 2017

Conventional functional connectivity (FC), referred to as low-order FC, estimates temporal correlation of the resting-state functional magnetic resonance imaging (rs-fMRI) time series between any pair of brain regions, simply ignoring the potentially high-level relationship among these brain regions. A high-order FC based on “correlation’s correlation” has emerged as a new approach for abnormality detection of brain disease. However, separate construction of the low- and high-order FC networks overlooks information exchange between the two FC levels. Such a higher-level relationship could be more important for brain diseases study. In this paper, we propose a novel framework, namely “hybrid high-order FC networks” by exploiting the higher-level dynamic interaction among brain regions for early mild cognitive impairment (eMCI) diagnosis. For each sliding window-based rs-fMRI sub-series, we construct a whole-brain associated high-order network, by estimating the correlations between the topographical information of the high-order FC sub-network from one brain region and that of the low-order FC sub-network from another brain region. With multi-kernel learning, complementary features from multiple time-varying FC networks constructed at different levels are fused for eMCI classification. Compared with other state-of-the-art methods, the proposed framework achieves superior diagnosis accuracy, and hence could be promising for understanding pathological changes of brain connectome.
The anti-cancer effects of itraconazole in epithelial ovarian cancer
Authors: Choi Chel Hun , Ryu Ji-Yoon , Cho Young-Jae , Jeon Hye-Kyung , Choi Jung-Joo , Ylaya Kris , Lee Yoo-Young , Kim Tae-Joong , Chung Joon-Yong , Hewitt Stephen M. , Kim Byoung-Gie , Bae Duk-Soo , Lee Jeong-Won
Published: July 2017

We assessed the anti-proliferative activity of itraconazole using an EOC cell line (SKOV3ip1) and endothelial cell lines (HUVEC & SVEC4-10). We also examined angiogenesis (VEGFR2, p-ERK, p-PLCr1/2), hedgehog (Gli1, Ptch1, SMO), and mTOR (pS6K1) signaling pathways to determine the mechanism of action of itraconazole. Furthermore, we evaluated the synergistic effects of itraconazole and paclitaxel using orthotopic mouse models with established EOC cells (SKOV3ip1 or HeyA8) as well as patient-derived xenografts (PDXs). Itraconazole treatment inhibited proliferation of endothelial cells in a dose-dependent manner, but had no effect on EOC cells. The endothelial cell antiproliferative effect was associated with inhibition of hedgehog, and mTOR pathways and angiogenesis. In xenograft models of EOC using SKOV3ip1 or HeyA8, mice treated with the combination of itraconazole and paclitaxel had significantly decreased tumor weight than the control, paclitaxel-alone, or itraconazole-alone groups. Tissue derived from these tumors had significantly lower microvessel density than tissue from the other groups as well as hedgehog and mTOR pathway inhibition. We confirmed those effects in two EOC PDX models. These results suggest that itraconazole selectively inhibits endothelial cells rather than cancer cells by targeting multiple pathways including hedgehog, and mTOR pathways and angiogenesis.
Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
Authors: Dakal Tikam Chand , Kala Deepak , Dhiman Gourav , Yadav Vinod , Krokhotin Andrey , Dokholyan Nikolay V.
Published: July 2017

Here we report anin-silicoapproach for identification, characterization and validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene using three steps. In first step, sequence homology-based genetic analysis of a set of 50 coding SNPs associated with 41 rsIDs using SIFT (Sorting Intolerant from Tolerant) and PROVEAN (Protein Variation Effect Analyzer) identified 23 nsSNPs to be putatively damaging/deleterious in at least one of the two tools used. Subsequently, structure-homology based PolyPhen-2 (Polymorphism Phenotyping) analysis predicted 9 of 23 nsSNPs (K4T, E31A, E31K, S41Y, I55N, P59L, P59S, L70P and V88D) to be damaging. According to the conditional hypothesis for the study, only nsSNPs that score damaging/deleterious prediction in both sequence and structural homology-based approach will be considered as ‘high-confidence’ nsSNPs. In step 2, based on conservation of amino acid residues, stability analysis, structural superimposition, RSMD and docking analysis, the possible structural-functional relationship was ascertained for high-confidence nsSNPs. Finally, in a separate analysis (step 3), the IL-8 deregulation has also appeared to be an important prognostic marker for detection of patients with gastric and lung cancer. This study, for the first time, provided in-depth insights on the effects of amino acid substitutions on IL-8 protein structure, function and disease association.
Mid-infrared femtosecond laser-induced damages in As2S3 and As2Se3 chalcogenide glasses
Authors: You Chenyang , Dai Shixun , Zhang Peiqing , Xu Yinsheng , Wang Yingying , Xu Dong , Wang Rongping
Published: July 2017

In this paper, we report the first measurements of mid-infrared (MIR) femtosecond laser-induced damage in two typical chalcogenide glasses, As2S3 and As2Se3. Damage mechanism is studied via optical microscopy, scanning electron microscopy and elemental analysis. By irradiating at 3, 4 and 5 μm with 150 fs ultrashort pulses, the evolution of crater features is presented with increasing laser fluence. The dependence of laser damage on the bandgap and wavelength is investigated and finally the laser-induced damage thresholds (LIDTs) of As2S3 and As2Se3 at 3 and 4 μm are calculated from the experimental data. The results may be a useful for chalcogenide glasses (ChGs) applied in large laser instruments to prevent optical damage.
Major histocompatibility complex genes partly explain early survival in house sparrows
Authors: Lukasch B. , Westerdahl H. , Strandh M. , Knauer F. , Winkler H. , Moodley Y. , Hoi H.
Published: July 2017

Environmental factors and genetic incompatibilities between parents have been suggested as important determinants for embryonic mortality and survival. The genetic set-up of the immune system, specifically the highly polymorphic major histocompatibility complex (MHC) may also influence individual resistance to infections. MHC proteins are important for an appropriate adaptive immune response and enable T-cells to separate ‘self’ from ‘non-self’. Here we investigate the importance of MHC functional diversity for early development in birds, more specifically, if offspring survival and body mass or size depends on number of different functional MHC alleles, specific functional MHC alleles or similarity of MHC alleles in the parents. Unhatched eggs are common in clutches of many bird species. In house sparrows (Passer domesticus), embryo and nestling mortality can exceed 50%. To control for environmental factors, our study was carried out on an aviary population. We found that one specific functional MHC allele was associated with reduced nestling survival, which was additionally supported by lower body mass and a smaller tarsus when nestlings have been 6 days old. Another allele was positively associated with tarsus length at a later nestling stage (nestlings 12 days old). These results indicate that MHC alleles might influence pathogen resistance or susceptibility.
Gambling-like behavior in pigeons: ‘jackpot’ signals promote maladaptive risky choice
Authors: Smith Aaron P. , Beckmann Joshua S. , Zentall Thomas R.
Published: July 2017

Individuals often face choices that have uncertain outcomes and have important consequences. As a model of this environment, laboratory experiments often offer a choice between an uncertain, large reward that varies in its probability of delivery against a certain but smaller reward as a measure of an individual’s risk aversion. An important factor generally lacking from these procedures are gambling related cues that may moderate risk preferences. The present experiment offered pigeons choices between unreliable and certain rewards but, for the Signaled group on winning choices, presented a ‘jackpot’ signal prior to reward delivery. The Unsignaled group received an ambiguous stimulus not informative of choice outcomes. For the Signaled group, presenting win signals effectively blocked value discounting for the large, uncertain outcome as the probability of a loss increased, whereas the Unsignaled group showed regular preference changes similar to previous research lacking gambling related cues. These maladaptive choices were further shown to be unaffected by more salient loss signals and resistant to response cost increases. The results suggest an important role of an individual’s sensitivity to outcome-correlated cues in influencing risky choices that may moderate gambling behaviors in humans, particularly in casino and other gambling-specific environments.
4-dimensional functional profiling in the convulsant-treated larval zebrafish brain
Authors: Winter Matthew J. , Windell Dylan , Metz Jeremy , Matthews Peter , Pinion Joe , Brown Jonathan T. , Hetheridge Malcolm J. , Ball Jonathan S. , Owen Stewart F. , Redfern Will S. , Moger Julian , Randall Andrew D. , Tyler Charles R.
Published: July 2017

Functional neuroimaging, using genetically-encoded Ca2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.
Resting-state brain connectivity changes in obese women after Roux-en-Y gastric bypass surgery: A longitudinal study
Authors: Olivo Gaia , Zhou Wei , Sundbom Magnus , Zhukovsky Christina , Hogenkamp Pleunie , Nikontovic Lamia , Stark Julia , Wiemerslage Lyle , Larsson Elna-Marie , Benedict Christian , Schiöth Helgi B.
Published: July 2017

Bariatric surgery is an effective method to rapidly induce weight loss in severely obese people, however its impact on brain functional connectivity after longer periods of follow-up is yet to be assessed. We investigated changes in connectivity in 16 severely obese women one month before, one month after and one year after Roux-en-Y gastric bypass surgery (RYGB). 12 lean controls were also enrolled. Resting-state fMRI was acquired for all participants following an overnight fast and after a 260 kcal load. Connectivity between regions involved in food-related saliency attribution and reward-driven eating behavior was stronger in presurgery patients compared to controls, but progressively weakened after follow-up. At one year, changes in networks related to cognitive control over eating and bodily perception also occurred. Connectivity between regions involved in emotional control and social cognition had a temporary reduction early after treatment but had increased again after one year of follow-up. Furthermore, we could predict the BMI loss by presurgery connectivity in areas linked to emotional control and social interaction. RYGBP seems to reshape brain functional connectivity, early affecting cognitive control over eating, and these changes could be an important part of the therapeutic effect of bariatric surgery.
Niches and Interspecific Associations of Dominant Populations in Three Changed Stages of Natural Secondary Forests on Loess Plateau, P.R. China
Authors: Gu Li , Gong Zhi-wen , Li Wei-zhong
Published: July 2017

Ecological niches remain central to explaining community structure, and niche-based studies have helped us to better understand species interactions, distributions, coexistence and associated mechanisms.Quercus wutaishanseapopulations on Loess Plateau are currently expanding their dominance in natural secondary forest types. In the present paper, we focused on the dynamic changes of niches and interspecific association among different changed stages. The overall interspecies association of the three communities exhibited positive association for Variance Ratio (VR) >1; the value of χ2significance test further revealed that the overall association had reached the level of significant association. Among the total of 45 species pairs composed of 10 dominant species, in thePinus tabulaeformisforest, the ratio of positive and negative associations was below 1, which 19 pairs showing positive association, 25 pairs showing negative association, and 1 pair showing no association; in contrast, in another forests, the ratios of positive and negative associations were above 1. The timing and consequences of these associations may illuminate how interaction mechanisms such as competition and alleopathy, structure changes. Then differences of species features in niches and associations should receive greater attention when planning forest management and developing restoration strategies.
Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness
Authors: Bhattacharya Soumyaroop , Rosenberg Alex F. , Peterson Derick R. , Grzesik Katherine , Baran Andrea M. , Ashton John M. , Gill Steven R. , Corbett Anthony M. , Holden-Wiltse Jeanne , Topham David J. , Walsh Edward E. , Mariani Thomas J. , Falsey Ann R.
Published: July 2017

Lower respiratory tract infection (LRTI) commonly causes hospitalization in adults. Because bacterial diagnostic tests are not accurate, antibiotics are frequently prescribed. Peripheral blood gene expression to identify subjects with bacterial infection is a promising strategy. We evaluated whole blood profiling using RNASeq to discriminate infectious agents in adults with microbiologically defined LRTI. Hospitalized adults with LRTI symptoms were recruited. Clinical data and blood was collected, and comprehensive microbiologic testing performed. Gene expression was measured using RNASeq and qPCR. Genes discriminatory for bacterial infection were identified using the Bonferroni-corrected Wilcoxon test. Constrained logistic models to predict bacterial infection were fit using screened LASSO. We enrolled 94 subjects who were microbiologically classified; 53 as “non-bacterial” and 41 as “bacterial”. RNAseq and qPCR confirmed significant differences in mean expression for 10 genes previously identified as discriminatory for bacterial LRTI. A novel dimension reduction strategy selected three pathways (lymphocyte, α-linoleic acid metabolism, IGF regulation) including eleven genes as optimal markers for discriminating bacterial infection (naïve AUC = 0.94; nested CV-AUC = 0.86). Using these genes, we constructed a classifier for bacterial LRTI with 90% (79% CV) sensitivity and 83% (76% CV) specificity. This novel, pathway-based gene set displays promise as a method to distinguish bacterial from nonbacterial LRTI.
Porcine familial adenomatous polyposis model enables systematic analysis of early events in adenoma progression
Authors: Flisikowska Tatiana , Stachowiak Monika , Xu Hongen , Wagner Alexandra , Hernandez-Caceres Alejandra , Wurmser Christine , Perleberg Carolin , Pausch Hubert , Perkowska Anna , Fischer Konrad , Frishman Dmitrij , Fries Ruedi , Switonski Marek , Kind Alexander , Saur Dieter , Schnieke Angelika , Flisikowski Krzysztof
Published: July 2017

We compared gene expression in low and high-grade intraepithelial dysplastic polyps from pigs carrying an APC
1311
truncating mutation orthologous to human APC
1309
, analysing whole samples and microdissected dysplastic epithelium. Gene set enrichment analysis revealed differential expression of gene sets similar to human normal mucosa versus T1 stage polyps. Transcriptome analysis of whole samples revealed many differentially-expressed genes reflecting immune infiltration. Analysis of microdissected dysplastic epithelium was markedly different and showed increased expression in high-grade intraepithelial neoplasia of several genes known to be involved in human CRC; and revealed possible new roles for GBP6 and PLXND1. The pig model thus facilitates analysis of CRC pathogenesis.
Next Generation Ceramic Substrate Fabricated at Room Temperature
Authors: Kim Yuna , Ahn Cheol-Woo , Choi Jong-Jin , Ryu Jungho , Kim Jong-Woo , Yoon Woon-Ha , Park Dong-Soo , Yoon Seog-Young , Ma Byungjin , Hahn Byung-Dong
Published: July 2017

A ceramic substrate must not only have an excellent thermal performance but also be thin, since the electronic devices have to become thin and small in the electronics industry of the next generation. In this manuscript, a thin ceramic substrate (thickness: 30–70 µm) is reported for the next generation ceramic substrate. It is fabricated by a new process [granule spray in vacuum (GSV)] which is a room temperature process. For the thin ceramic substrates, AlN GSV films are deposited on Al substrates and their electric/thermal properties are compared to those of the commercial ceramic substrates. The thermal resistance is significantly reduced by using AlN GSV films instead of AlN bulk-ceramics in thermal management systems. It is due to the removal of a thermal interface material which has low thermal conductivity. In particular, the dielectric strengths of AlN GSV films are much higher than those of AlN bulk-ceramics which are commercialized, approximately 5 times. Therefore, it can be expected that this GSV film is a next generation substrate in thermal management systems for the high power application.
Molecular mechanisms of Charcot-Marie-Tooth neuropathy linked to mutations in human myelin protein P2
Authors: Ruskamo Salla , Nieminen Tuomo , Kristiansen Cecilie K. , Vatne Guro H. , Baumann Anne , Hallin Erik I. , Raasakka Arne , Joensuu Päivi , Bergmann Ulrich , Vattulainen Ilpo , Kursula Petri
Published: July 2017

Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neuropathies. Recently, three CMT1-associated point mutations (I43N, T51P, and I52T) were discovered in the abundant peripheral myelin protein P2. These mutations trigger abnormal myelin structure, leading to reduced nerve conduction velocity, muscle weakness, and distal limb atrophy. P2 is a myelin-specific protein expressed by Schwann cells that binds to fatty acids and membranes, contributing to peripheral myelin lipid homeostasis. We studied the molecular basis of the P2 patient mutations. None of the CMT1-associated mutations alter the overall folding of P2 in the crystal state. P2 disease variants show increased aggregation tendency and remarkably reduced stability, T51P being most severe. In addition, P2 disease mutations affect protein dynamics. Both fatty acid binding by P2 and the kinetics of its membrane interactions are affected by the mutations. Experiments and simulations suggest opening of the β barrel in T51P, possibly representing a general mechanism in fatty acid-binding proteins. Our findings demonstrate that altered biophysical properties and functional dynamics of P2 may cause myelin defects in CMT1 patients. At the molecular level, a few malformed hydrogen bonds lead to structural instability and misregulation of conformational changes related to ligand exchange and membrane binding.
Engineering the geometrical shape of mesenchymal stromal cells through defined cyclic stretch regimens
Authors: Walters Brandan , Uynuk-Ool Tatiana , Rothdiener Miriam , Palm Julian , Hart Melanie L. , Stegemann Jan P. , Rolauffs Bernd
Published: July 2017

Stem cells have been predicted to improve disease outcomes and patient lives. Steering stem cell fate - through controlling cell shape - may substantially accelerate progress towards this goal. As mesenchymal stromal cells (MSCs) are continuously exposed in vivo to a dynamically changing biomechanical environment, we hypothesized that exogenous forces can be applied for engineering a variety of significantly different MSC shapes. We applied specific cyclic stretch regimens to human MSCs and quantitatively measured the resulting cell shape, alignment, and expression of smooth muscle (SMC) differentiation markers, as those have been associated with elongated morphology. As proof of principle, a range of different shapes, alignments, and correlating SMC marker levels were generated by varying strain, length, and repetition of stretch. However, the major determinant of biomechanically engineering cellular shape was the repetition of a chosen stretch regimen, indicating that the engineered shape and associated differentiation were complex non-linear processes relying on sustained biomechanical stimulation. Thus, forces are key regulators of stem cell shape and the targeted engineering of specific MSC shapes through biomechanical forces represents a novel mechanobiology concept that could exploit naturally occurring in vivo forces for improving stem cell fate in clinical regenerative therapies.
Quantum optical measurements with undetected photons through vacuum field indistinguishability
Authors: Lee Sun Kyung , Yoon Tai Hyun , Cho Minhaeng
Published: July 2017

Quantum spectroscopy and imaging with undetected idler photons have been demonstrated by measuring one-photon interference between the corresponding entangled signal fields from two spontaneous parametric down conversion (SPDC) crystals. In this Report, we present a new quantum optical measurement scheme utilizing three SPDC crystals in a cascading arrangement; here, neither the detection of the idler photons which interact with materials of interest nor their conjugate signal photons which do not interact with the sample is required. The coherence of signal beams in a single photon W-type path-entangled state is induced and modulated by indistinguishabilities of the idler beams and crucially the quantum vacuum fields. As a result, the optical properties of materials or objects interacting with the idler beam from the first SPDC crystal can be measured by detecting second-order interference between the signal beams generated by the other two SPDC crystals further down the set-up. This gedankenexperiment illustrates the fundamental importance of vacuum fields in generating an optical tripartite entangled state and thus its crucial role in quantum optical measurements.
Mutations targeting the coagulation pathway are enriched in brain metastases
Authors: Richichi Cristina , Fornasari Lorenzo , Melloni Giorgio E. M. , Brescia Paola , Patanè Monica , Del Bene Massimiliano , Mustafa Dana A. M. , Kros Johan M. , Pollo Bianca , Pruneri Giancarlo , Sciandivasci Angela , Munzone Elisabetta , DiMeco Francesco , Pelicci Pier Giuseppe , Riva Laura , Pelicci Giuliana
Published: July 2017

Brain metastases (BMs) are the most common malignancy of the central nervous system. Recently it has been demonstrated that plasminogen activator inhibitor serpins promote brain metastatic colonization, suggesting that mutations in serpins or other members of the coagulation cascade can provide critical advantages during BM formation. We performed whole-exome sequencing on matched samples of breast cancer and BMs and found mutations in the coagulation pathway genes in 5 out of 10 BM samples. We then investigated the mutational status of 33 genes belonging to the coagulation cascade in a panel of 29 BMs and we identified 56 Single Nucleotide Variants (SNVs). The frequency of gene mutations of the pathway was significantly higher in BMs than in primary tumours, and SERPINI1 was the most frequently mutated gene in BMs. These findings provide direction in the development of new strategies for the treatment of BMs.
Rashba spin-orbit coupling in graphene monolayer coated by periodic magnetic stripes
Authors: Li Xiaojing , Wu Zhenhua , Liu Jiangtao
Published: July 2017

We investigate theoretically the effects of a modulated periodic perpendicular magnetic fields and the Rashba spin-orbit coupling (RSOC) on the electronic states and optical absorption spectrum in a graphene monolayer. The magnetic fields and supperlattice geometry give rise to distinct Dirac cone shift and open a finite bandgap at the Dirac point. In contrast to the energy spectrum without the RSOC interaction, we find that the RSOC term will develop a spin-splitting energy-momentum dispersion relation in this graphene magnetic supperlattice. Anisotropic and spin-split group velocities, effective masses and the momentum-dependent carrier distributions along the magnetic strips are demonstrated. And the manipulations of these exotic properties by tuning the magnetic fields and the RSOC are addressed systematically. Accordingly, we find bright-to-dark transitions in the electron-hole pairs transition rate spectrum and absorption peak splitting in the optical absorption spectrum tuned by the RSOC interaction. This feature offers us a practical way to detect these band engineering effects especially the exotic spin splitting states by using the conductance and optical technique.
Changes of corneal tomography in patients with congenital blepharoptosis
Authors: Zhu Tiepei , Ye Xin , Xu Peifang , Wang Jingyi , Zhang Huina , Ni Hailong , Su Zhaoan , Ye Juan
Published: July 2017

The study aimed to evaluate the effect of drooped eyelid on corneal tomography in congenital blepharoptosis patients. Sixty-four patients with congenital blepharoptosis and 64 age- and sex- matched healthy subjects were included. According to the eyelid margin to corneal light reflex distance (MRD), eyes with congenital blepharoptosis were categorized as mild, moderate, or severe. The eyes were scanned using the rotating Scheimpflug camera. Increased topometric parameters were observed in moderate and severe blepharoptosis. Back corneal elevations at the thinnest point were significant higher for mild (P = 0.009), moderate (P < 0.001), and severe (P < 0.001) congenital blepharoptosis compared with controls. Maximum Ambrósio’s relational thickness (ART) was decreased in eyes with severe blepharoptosis (P < 0.001). Fnal D values were significantly higher in moderate (P < 0.001) and severe blepharoptosis (P < 0.001) groups than that of controls. There were significant correlations between MRD and most corneal tomographic parameters. Our findings indicated there was a trend toward subclinical keratoconus-like changes in the corneas of congenital blepharoptosis, with the increase of ptosis severity.
Tailoring seed oil composition in the real world: optimising omega-3 long chain polyunsaturated fatty acid accumulation in transgenic Camelina sativa
Authors: Usher Sarah , Han Lihua , Haslam Richard P. , Michaelson Louise V. , Sturtevant Drew , Aziz Mina , Chapman Kent D. , Sayanova Olga , Napier Johnathan A.
Published: July 2017

There is considerable interest in the de novo production of omega-3 long chain polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), not least of all given the importance of these fatty acids in both aquaculture and human nutrition. Previously we have demonstrated the feasibility of using metabolic engineering in transgenic plants (Camelina sativa) to modify the seed oil composition to now include EPA and/or DHA. In this study, we further tailored the seed oil profile to reduce the omega-6 content, and evaluated the performance of such GM plants under field conditions (i.e. environmental releases), in terms of agronomic performance and also the lipidomic profile of seed oil. We used MALDI- mass spectrometry imaging to identify discrete tissue-types in the seed in which these non-native fatty acids preferentially accumulated. Collectively, these data provide new insights into the complexity of plant lipid metabolism and the challenges associated with predictive manipulation of these pathways. However, this study identified the likely dispensable nature of a Δ12-desturase activity in our omega-3 metabolic engineering rationales for Camelina.
Association of pre-operative estimated GFR on post-operative pulmonary complications in laparoscopic surgeries
Authors: Shimomura Akihiro , Obi Yoshitsugu , Fazl Alizadeh Reza , Li Shiri , Nguyen Ninh T. , Stamos Michael J. , Kalantar-Zadeh Kamyar , Ichii Hirohito
Published: July 2017

Despite a large body of evidence showing the pandemic of chronic kidney disease, the impact of pre-operative kidney function on the risk of post-operative pulmonary complications (PPCs) is not well known. We used multivariable logistic regression analyses with 3-level hierarchical adjustments to identify the association of pre-operative estimated glomerular filtration rate (eGFR) with PPCs in laparoscopic surgeries. Among 452,213 patients between 2005 and 2013 in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Database, a total of 3,727 patients (0.9%) experienced PPCs. We found a gradient association between lower eGFR and higher likelihood of PPCs in the unadjusted model. In the case-mix adjusted model, a reverse-J-shaped association was observed; a small albeit significant association with the highest eGFR category emerged. Further adjustment slightly attenuated these associations, but the PPCs risk in the eGFR groups of <30, 30–60, and ≥120 mL/min/1.73 m2 remained significant: odds ratios (95% confidence intervals) of 1.82 (1.54–2.16), 1.38 (1.24–1.54), and 1.28 (1.07–1.53), respectively (reference: 90–120 mL/min/1.73 m2). Our findings propose a need for careful pre-operative evaluation of cardiovascular and pulmonary functions and post-operative fluid management among patients with not only lower but also very high eGFR.
Ring-like N-fold Models of Aβ42 fibrils
Authors: Xi Wenhui , Hansmann Ulrich H. E.
Published: July 2017

When assembling as fibrils Aβ40 peptides can only assume U-shaped conformations while Aβ42 can also arrange as S-shaped three-stranded chains. We show that this allows Aβ42 peptides to assemble pore-like structures that may explain their higher toxicity. For this purpose, we develop a scalable model of ring-like assemblies of S-shaped Aβ1–42 chains and study the stability and structural properties of these assemblies through atomistic molecular dynamics simulations. We find that the proposed arrangements are in size and symmetry compatible with experimentally observed Aβ assemblies. We further show that the interior pore in our models allows for water leakage as a possible mechanism of cell toxicity of Aβ42 amyloids.
Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1
Authors: Muguruma Naoki , Okamoto Koichi , Nakagawa Tadahiko , Sannomiya Katsutaka , Fujimoto Shota , Mitsui Yasuhiro , Kimura Tetsuo , Miyamoto Hiroshi , Higashijima Jun , Shimada Mitsuo , Horino Yoko , Matsumoto Shinya , Hanaoka Kenjiro , Nagano Tetsuo , Shibutani Makoto , Takayama Tetsuji
Published: July 2017

Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.
A systems approach to a spatio-temporal understanding of the drought stress response in maize
Authors: Miao Zhenyan , Han Zhaoxue , Zhang Ting , Chen Siyuan , Ma Chuang
Published: July 2017

Crops are often subjected to periods of drought stress during their life cycle. However, how stress response mechanisms contribute to the crosstalk between stress signaling pathways and developmental signaling pathways is still unknown. We built a gene co-expression network from a spatio-temporal transcriptomic map of the drought stress response in maize (Zea mays), profiled from three tissues and four developmental stages and characterized hub genes associated with duplication events, selection, and regulatory networks. Co-expression analysis grouped drought-response genes into ten modules, covering 844 highly connected genes (hub genes). Of these, 15.4% hub genes had diverged by whole-genome duplication events and 2.5% might then have been selected during natural domestication and artificial improvement processes, successively. We identified key transcription factor hubs in a transcriptional regulatory network, which may function as a crosstalk mechanism between drought stress and developmental signalling pathways in maize. Understanding the evolutionary biases that have evolved to enhance drought adaptation lays the foundation for further dissection of crosstalk between stress signalling pathways and developmental signalling pathways in maize, towards molecular design of new cultivars with desirable yield and greater stress tolerance.
Super-strong dislocation-structured high-carbon martensite steel
Authors: Sun Jun-jie , Liu Yong-ning , Zhu Yun-tian , Lian Fu-liang , Liu Hong-ji , Jiang Tao , Guo Sheng-wu , Liu Wen-qing , Ren Xiao-bing
Published: July 2017

High-carbon martensite steels (with C > 0.5 wt.%) are very hard but at the same time as brittle as glass in as-quenched or low-temperature-tempered state. Such extreme brittleness, originating from a twin microstructure, has rendered these steels almost useless in martensite state. Therefore, for more than a century it has been a common knowledge that high-carbon martensitic steels are intrinsically brittle and thus are not expected to find any application in harsh loading conditions. Here we report that these brittle steels can be transformed into super-strong ones exhibiting a combination of ultrahigh strength and significant toughness, through a simple grain-refinement treatment, which refines the grain size to ~4 μm. As a result, an ultra-high tensile strength of 2.4~2.6 GPa, a significant elongation of 4~10% and a good fracture toughness (K1C) of 23.5~29.6 MPa m1/2 were obtained in high-carbon martensitic steels with 0.61–0.65 wt.% C. These properties are comparable with those of “the king of super-high-strength steels”—maraging steels, but achieved at merely 1/30~1/50 of the price. The drastic enhancement in mechanical properties is found to arise from a transition from the conventional twin microstructure to a dislocation one by grain refinement. Our finding may provide a new route to manufacturing super-strong steels in a simple and economic way.
Novel strategies to mimic transmembrane tumor necrosis factor-dependent activation of tumor necrosis factor receptor 2
Authors: Fischer Roman , Marsal Jessica , Guttà Cristiano , Eisler Stephan A. , Peters Nathalie , Bethea John R. , Pfizenmaier Klaus , Kontermann Roland E.
Published: July 2017

Tumor necrosis factor receptor 2 (TNFR2) is known to mediate immune suppression and tissue regeneration. Interestingly, the transmembrane form of tumor necrosis factor (tmTNF) is necessary to robustly activate TNFR2. To characterize the stoichiometry and composition of tmTNF during TNFR2 activation, we constructed differently oligomerized single chain TNF ligands (scTNF) comprised of three TNF homology domain (THD) protomers that mimic tmTNF. Using a variety of cellular andin vivoassays, we can show that higher oligomerization of the scTNF trimers results in more efficient TNF/TNFR2 clustering and subsequent signal transduction. Importantly, the three-dimensional orientation of the scTNF trimers impacts the bioactivity of the oligomerized scTNF ligands. Our data unravel the organization of tmTNF-mimetic scTNF ligands capable of robustly activating TNFR2 and introduce novel TNFR2 agonists that hold promise as therapeutics to treat a variety of diseases.
An atomic carbon source for high temperature molecular beam epitaxy of graphene
Authors: Albar J. D. , Summerfield A. , Cheng T. S. , Davies A. , Smith E. F. , Khlobystov A. N. , Mellor C. J. , Taniguchi T. , Watanabe K. , Foxon C. T. , Eaves L. , Beton P. H. , Novikov S. V.
Published: July 2017

We report the use of a novel atomic carbon source for the molecular beam epitaxy (MBE) of graphene layers on hBN flakes and on sapphire wafers at substrate growth temperatures of ~1400 °C. The source produces a flux of predominantly atomic carbon, which diffuses through the walls of a Joule-heated tantalum tube filled with graphite powder. We demonstrate deposition of carbon on sapphire with carbon deposition rates up to 12 nm/h. Atomic force microscopy measurements reveal the formation of hexagonal moiré patterns when graphene monolayers are grown on hBN flakes. The Raman spectra of the graphene layers grown on hBN and sapphire with the sublimation carbon source and the atomic carbon source are similar, whilst the nature of the carbon aggregates is different - graphitic with the sublimation carbon source and amorphous with the atomic carbon source. At MBE growth temperatures we observe etching of the sapphire wafer surface by the flux from the atomic carbon source, which we have not observed in the MBE growth of graphene with the sublimation carbon source.
Failure in Cognitive Suppression of Negative Affect in Adolescents with Generalized Anxiety Disorder
Authors: Yin Dazhi , Liu Wenjing , Zeljic Kristina , Lv Qian , Wang Zhiwei , You Meina , Men Weiwei , Fan Mingxia , Cheng Wenhong , Wang Zheng
Published: July 2017

Hyperactivity of limbic (e.g., amygdalar) responses to negative stimuli has been implicated in the pathophysiology of generalized anxiety disorder (GAD). Evidence has also suggested that even a simple cognitive task involving emotionally salient stimuli can modulate limbic and prefrontal neural activation. However, whether neural modulation of emotional stimulus processing in a cognitive task is defective in adolescents with GAD has not yet been investigated. In this study, 20 adolescents with GAD and 14 comparable healthy controls underwent event-related functional magnetic resonance imaging (fMRI) coupled with an emotional valence evaluation task. During the evaluation of negative versus neutral stimuli, we found significant activation of the right inferior frontal gyrus (IFG) in healthy controls, while the bilateral amygdala was activated in GAD patients. Between-group analyses showed dramatically reduced task-activation of the right IFG in GAD patients, and the magnitude of IFG activity negatively correlated with symptom severity. Psychophysiological interaction analysis further revealed significantly decreased functional interaction between right IFG and anterior cingulate cortex and ventromedial prefrontal cortex in GAD patients compared with healthy controls. Taken together, our findings show failure to suppress negative affect by recruiting a cognitive distraction in adolescents with GAD, providing new insights into the pathophysiology of GAD.
Quantitative assessment of energy transfer in upconverting nanoparticles grafted with organic dyes
Authors: Dukhno Oleksii , Przybilla Frédéric , Collot Mayeul , Klymchenko Andrey , Pivovarenko Vasyl , Buchner Markus , Muhr Verena , Hirsch Thomas , Mély Yves
Published: July 2017

Energy transfer efficiencies of UCNP-based RET systems are quantified through comparison of spectra, decay lifetimes, and semiempirical simulations.
Development of an indirect competitive enzyme-linked immunosorbent assay for screening ethopabate residue in chicken muscle and liver
Authors: Li Zhaozhou , Wang Yao , Li Daomin , Chen Xiujin , Li Zhili , Gao Hongli , Cao Li , Li Songbiao , Hou Yuze
Published: July 2017

Development of an indirect competitive enzyme-linked immunosorbent assay for screening ethopabate residue in chicken muscle and liver.
Understanding water structure from Raman spectra of isotopic substitution H2O/D2O up to 573 K
Authors: Hu Qingcheng , Zhao Haiwen , Ouyang Shunli
Published: July 2017

The OH/OD stretch band features on Raman spectra of isotopic substitution H2O/D2O at temperatures up to 573 K are correlated with a multi-structure model that water has five dominant hydrogen bonding configurations: tetrahedral, deformed tetrahedral, single donor, single hydrogen bonded water and free water.
On the use of the Cu2+–iminodiacetic acid complex for double histidine based distance measurements by pulsed ESR
Authors: Lawless M. J. , Ghosh S. , Cunningham T. F. , Shimshi A. , Saxena S.
Published: July 2017

The Cu2+-based DEER signal of the double histidine motif was increased by a factor of two by understanding optimal loading conditions.