bluuebunny/crossref_metadata_2025 huggingface dataset:
Two SNPs Associated With Spontaneous Dizygotic Twinning: Effect Sizes and How We Communicate Them
Authors: Mbarek Hamdi , Dolan Conor V. , Boomsma Dorret I.
Published: July 2016

In a recent GWAS of spontaneous dizygotic twinning, Mbarek et al. (The American Journal of Human Genetics, 2016, Vol 98, pp. 898–908) identified two SNPs, rs11031006 (near FSHB) and rs17293443 (in SMAD3). In the present note, we address the question how to present the results in terms of effect sizes in a manner that is comprehensible to the general audience (e.g., mothers of twins, readership of newspapers). We propose to avoid the standard effect sizes such as odds ratios and relative risk as these require some knowledge of probability theory. Rather, we convey the results in terms of the conditional probabilities, but expressed in natural language.
The FANCD2–FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2
Authors: Liang Chih-Chao , Li Zhuolun , Lopez-Martinez David , Nicholson William V. , Vénien-Bryan Catherine , Cohn Martin A.
Published: July 2016

The Fanconi anaemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2–FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination. It has remained elusive whether the complex is recruited before or after the critical monoubiquitination. Here, we report the first structural insight into the human FANCD2–FANCI complex by obtaining the cryo-EM structure. The complex contains an inner cavity, large enough to accommodate a double-stranded DNA helix, as well as a protruding Tower domain. Disease-causing mutations in the Tower domain are observed in several FA patients. Our work reveals that recruitment of the complex to a stalled replication fork serves as the trigger for the activating monoubiquitination event. Taken together, our results uncover the mechanism of how the FANCD2–FANCI complex activates the FA pathway, and explains the underlying molecular defect in FA patients with mutations in the Tower domain.
Human serum-derived protein removes the need for coating in defined human pluripotent stem cell culture
Authors: Pijuan-Galitó Sara , Tamm Christoffer , Schuster Jens , Sobol Maria , Forsberg Lars , Merry Catherine L. R. , Annerén Cecilia
Published: July 2016

Reliable, scalable and time-efficient culture methods are required to fully realize the clinical and industrial applications of human pluripotent stem (hPS) cells. Here we present a completely defined, xeno-free medium that supports long-term propagation of hPS cells on uncoated tissue culture plastic. The medium consists of the Essential 8 (E8) formulation supplemented with inter-α-inhibitor (IαI), a human serum-derived protein, recently demonstrated to activate key pluripotency pathways in mouse PS cells. IαI efficiently induces attachment and long-term growth of both embryonic and induced hPS cell lines when added as a soluble protein to the medium at seeding. IαI supplementation efficiently supports adaptation of feeder-dependent hPS cells to xeno-free conditions, clonal growth as well as single-cell survival in the absence of Rho-associated kinase inhibitor (ROCKi). This time-efficient and simplified culture method paves the way for large-scale, high-throughput hPS cell culture, and will be valuable for both basic research and commercial applications.
Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
Authors: Sánchez-Huertas Carlos , Freixo Francisco , Viais Ricardo , Lacasa Cristina , Soriano Eduardo , Lüders Jens
Published: July 2016

Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function. In newborn migrating neurons, the microtubule network is organized by the centrosome. During neuron maturation, however, the centrosome gradually loses this activity, and how microtubules are organized in more mature neurons remains poorly understood. Here, we demonstrate that microtubule organization in post-mitotic neurons strongly depends on non-centrosomal nucleation mediated by augmin and by the nucleator γTuRC. Disruption of either complex not only reduces microtubule density but also microtubule bundling. These microtubule defects impair neurite formation, interfere with axon specification and growth, and disrupt axonal trafficking. In axons augmin does not merely mediate nucleation of microtubules but ensures their uniform plus end-out orientation. Thus, the augmin-γTuRC module, initially identified in mitotic cells, may be commonly used to generate and maintain microtubule configurations with specific polarity.
Atomic scale observation of oxygen delivery during silver–oxygen nanoparticle catalysed oxidation of carbon nanotubes
Authors: Yue Yonghai , Yuchi Datong , Guan Pengfei , Xu Jia , Guo Lin , Liu Jingyue
Published: July 2016

To probe the nature of metal-catalysed processes and to design better metal-based catalysts, atomic scale understanding of catalytic processes is highly desirable. Here we use aberration-corrected environmental transmission electron microscopy to investigate the atomic scale processes of silver-based nanoparticles, which catalyse the oxidation of multi-wall carbon nanotubes. A direct semi-quantitative estimate of the oxidized carbon atoms by silver-based nanoparticles is achieved. A mechanism similar to the Mars–van Krevelen process is invoked to explain the catalytic oxidation process. Theoretical calculations, together with the experimental data, suggest that the oxygen molecules dissociate on the surface of silver nanoparticles and diffuse through the silver nanoparticles to reach the silver/carbon interfaces and subsequently oxidize the carbon. The lattice distortion caused by oxygen concentration gradient within the silver nanoparticles provides the direct evidence for oxygen diffusion. Such direct observation of atomic scale dynamics provides an important general methodology for investigations of catalytic processes.
Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models
Authors: Bottos Alessia , Gotthardt Dagmar , Gill Jason W. , Gattelli Albana , Frei Anna , Tzankov Alexandar , Sexl Veronika , Wodnar-Filipowicz Aleksandra , Hynes Nancy E.
Published: July 2016

The JAK/STAT pathway is an attractive target for breast cancer therapy due to its frequent activation, and clinical trials evaluating JAK inhibitors (JAKi) in advanced breast cancer are ongoing. Using patient biopsies and preclinical models of breast cancer, we demonstrate that the JAK/STAT pathway is active in metastasis. Unexpectedly, blocking the pathway with JAKi enhances the metastatic burden in experimental and orthotopic models of breast cancer metastasis. We demonstrate that this prometastatic effect is due to the immunosuppressive activity of JAKi with ensuing impairment of NK-cell-mediated anti-tumour immunity. Furthermore, we show that immunostimulation with IL-15 overcomes the enhancing effect of JAKi on metastasis formation. Our findings highlight the importance of evaluating the effect of targeted therapy on the tumour environment. The impact of JAKi on NK cells and the potential value of immunostimulators to overcome the weakened tumour immunosurveillance, are worthwhile considering in the clinical setting of breast cancer.
Dual band metamaterial perfect absorber based on artificial dielectric “molecules”
Authors: Liu Xiaoming , Lan Chuwen , Li Bo , Zhao Qian , Zhou Ji
Published: July 2016

Dual band metamaterial perfect absorbers with two absorption bands are highly desirable because of their potential application areas such as detectors, transceiver system and spectroscopic imagers. However, most of these dual band metamaterial absorbers proposed were based on resonances of metal patterns. Here, we numerically and experimentally demonstrate a dual band metamaterial perfect absorber composed of artificial dielectric “molecules” with high symmetry. The artificial dielectric “molecule” consists of four “atoms” of two different sizes corresponding to two absorption bands with near unity absorptivity. Numerical and experimental absorptivity verify that the dual-band metamaterial absorber is polarization insensitive and can operate in wide-angle incidence.
Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population
Authors: Lee I. Russel , Molton James S. , Wyres Kelly L. , Gorrie Claire , Wong Jocelyn , Hoh Chu Han , Teo Jeanette , Kalimuddin Shirin , Lye David C. , Archuleta Sophia , Holt Kathryn E. , Gan Yunn-Hwen
Published: July 2016

Hypervirulent Klebsiella pneumoniae is an emerging cause of community-acquired pyogenic liver abscess. First described in Asia, it is now increasingly recognized in Western countries, commonly afflicting those with Asian descent. This raises the question of genetic predisposition versus geospecific strain acquisition. We leveraged on the Antibiotics for Klebsiella Liver Abscess Syndrome Study (A-KLASS) clinical trial ongoing in ethnically diverse Singapore, to prospectively examine the profiles of 70 patients together with their isolates’ genotypic and phenotypic characteristics. The majority of isolates belonged to capsule type K1, a genetically homogenous group corresponding to sequence-type 23. The remaining K2, K5, K16, K28, K57 and K63 isolates as well as two novel cps isolates were genetically heterogeneous. K1 isolates carried higher frequencies of virulence-associated genes including rmpA (regulator of mucoid phenotype A), kfu (Klebsiella ferric uptake transporter), iuc (aerobactin), iro (salmochelin) and irp (yersiniabactin) than non-K1 isolates. The Chinese in our patient cohort, mostly non-diabetic, had higher prevalence of K1 infection than the predominantly diabetic non-Chinese (Malays, Indian and Caucasian). This differential susceptibility to different capsule types among the various ethnic groups suggests patterns of transmission (e.g. environmental source, familial transmission) and/or genetic predisposition unique to each race despite being in the same geographical location.
Evaluation of physiological risk factors, oxidant-antioxidant imbalance, proteolytic and genetic variations of matrix metalloproteinase-9 in patients with pressure ulcer
Authors: Latifa Khlifi , Sondess Sahli , Hajer Graiet , Manel Ben-Hadj-Mohamed , Souhir Khelil , Nadia Bouzidi , Abir Jaballah , Salima Ferchichi , Abdelhedi Miled
Published: July 2016

Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant–antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers. In this study, we aimed to evaluate the major clinical elements and biological scars in Tunisian patients suffering from PU. Consistently, non-healing wound remains a challenging clinical problem. The complex challenges of the wound environment, involving nutrient deficiencies, bacterial infection, as well as the critical role played by inflammatory cells, should be considered because of their negative impact on wound healing. In addition, an imbalance between pro-oxidants and antioxidant systems seems to be more aggravated in patients with PU compared to healthy subjects. Of interest, this study provides further evidence to support a core role of the biological activity of MMP-9 in the pathogenesis of PU and indicates that the MMP9-1562 C/T (rs 3918242) functional polymorphism is associated with protection against this disease.
Spin texture of time-reversal symmetry invariant surface states on W(110)
Authors: Kutnyakhov D. , Chernov S. , Medjanik K. , Wallauer R. , Tusche C. , Ellguth M. , Nepijko S. A. , Krivenkov M. , Braun J. , Borek S. , Minár J. , Ebert H. , Elmers H. J. , Schönhense G.
Published: July 2016

We find in the case of W(110) previously overlooked anomalous surface states having their spin locked at right angle to their momentum using spin-resolved momentum microscopy. In addition to the well known Dirac-like surface state with Rashba spin texture near the "Equation missing"-point, we observe a tilted Dirac cone with circularly shaped cross section and a Dirac crossing at 0.28 × "Equation missing" "Equation missing" within the projected bulk band gap of tungsten. This state has eye-catching similarities to the spin-locked surface state of a topological insulator. The experiments are fortified by a one-step photoemission calculation in its density-matrix formulation.
A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis
Authors: Saintigny Yannick , Chevalier François , Bravard Anne , Dardillac Elodie , Laurent David , Hem Sonia , Dépagne Jordane , Radicella J. Pablo , Lopez Bernard S.
Published: July 2016

Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [3H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [3H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses.
Nutritional and non-nutritional food components modulate phenotypic variation but not physiological trade-offs in an insect
Authors: Pascacio-Villafán Carlos , Williams Trevor , Birke Andrea , Aluja Martín
Published: July 2016

Our understanding of how food modulates animal phenotypes and mediate trade-offs between life-history traits has benefited greatly from the study of combinations of nutritional and non-nutritional food components, such as plant secondary metabolites. We used a fruit fly pest,Anastrepha ludens, to examine phenotypic variation across larval, pupal and adult stages as a function of larval food with varying nutrient balance and content of chlorogenic acid, a secondary metabolite. Larval insects that fed on carbohydrate-biased diets relative to protein exhibited longer larval and pupal developmental periods, were often heavier as pupae and resisted desiccation and starvation for longer periods in the adult stage than insects fed on highly protein-biased diets. Except for a potential conflict between pupal development time and adult desiccation and starvation resistance, we did not detect physiological trade-offs mediated by the nutritional balance in larval food. Chlorogenic acid affectedA. ludensdevelopment in a concentration and nutrient-dependent manner. Nutrients and host plant secondary metabolites in the larval diet induced changes inA. ludensphenotype and could influence fruit fly ecological interactions. We provide a unique experimental and modelling approach useful in generating predictive models of life history traits in a variety of organisms.
Hypothalamic TLR2 triggers sickness behavior via a microglia-neuronal axis
Authors: Jin Sungho , Kim Jae Geun , Park Jeong Woo , Koch Marco , Horvath Tamas L. , Lee Byung Ju
Published: July 2016

Various pathophysiologic mechanisms leading to sickness behaviors have been proposed. For example, an inflammatory process in the hypothalamus has been implicated, but the signaling modalities that involve inflammatory mechanisms and neuronal circuit functions are ill-defined. Here, we show that toll-like receptor 2 (TLR2) activation by intracerebroventricular injection of its ligand, Pam3CSK4, triggered hypothalamic inflammation and activation of arcuate nucleus microglia, resulting in altered input organization and increased activity of proopiomelanocortin (POMC) neurons. These animals developed sickness behavior symptoms, including anorexia, hypoactivity, and hyperthermia. Antagonists of nuclear factor kappa B (NF-κB), cyclooxygenase pathway and melanocortin receptors 3/4 reversed the anorexia and body weight loss induced by TLR2 activation. These results unmask an important role of TLR2 in the development of sickness behaviors via stimulation of hypothalamic microglia to promote POMC neuronal activation in association with hypothalamic inflammation.
Linear dependence of surface expansion speed on initial plasma temperature in warm dense matter
Authors: Bang W. , Albright B. J. , Bradley P. A. , Vold E. L. , Boettger J. C. , Fernández J. C.
Published: July 2016

Recent progress in laser-driven quasi-monoenergetic ion beams enabled the production of uniformly heated warm dense matter. Matter heated rapidly with this technique is under extreme temperatures and pressures, and promptly expands outward. While the expansion speed of an ideal plasma is known to have a square-root dependence on temperature, computer simulations presented here show a linear dependence of expansion speed on initial plasma temperature in the warm dense matter regime. The expansion of uniformly heated 1–100 eV solid density gold foils was modeled with the RAGE radiation-hydrodynamics code, and the average surface expansion speed was found to increase linearly with temperature. The origin of this linear dependence is explained by comparing predictions from the SESAME equation-of-state tables with those from the ideal gas equation-of-state. These simulations offer useful insight into the expansion of warm dense matter and motivate the application of optical shadowgraphy for temperature measurement.
Exciton Relaxation Dynamics in Photo-Excited CsPbI3 Perovskite Nanocrystals
Authors: Liu Qinghui , Wang Yinghui , Sui Ning , Wang Yanting , Chi Xiaochun , Wang Qianqian , Chen Ying , Ji Wenyu , Zou Lu , Zhang Hanzhuang
Published: July 2016

The exciton relaxation process of CsPbI3 perovskite nanocrystals (NCs) has been investigated by using transient absorption (TA) spectroscopy. The hot exciton relaxation process is confirmed to exist in the CsPbI3 NCs, through comparing the TA data of CsPbI3 NCs in low and high energy excitonic states. In addition, the Auger recombination and intrinsic decay paths also participate in the relaxation process of CsPbI3 NCs, even the number of exciton per NC is estimated to be less than 1. Excitation intensity-dependent TA data further confirms the existence of Auger recombination. Meanwhile, the spectral data also confirms that the weight of hot exciton also increase together with that of Auger recombination at high excitation intensity when CsPbI3 NCs in high energy excitonic states.
Investigating poultry trade patterns to guide avian influenza surveillance and control: a case study in Vietnam
Authors: Fournié Guillaume , Tripodi Astrid , Nguyen Thi Thanh Thuy , Nguyen Van Trong , Tran Trong Tung , Bisson Andrew , Pfeiffer Dirk U. , Newman Scott H.
Published: July 2016

Live bird markets are often the focus of surveillance activities monitoring avian influenza viruses (AIV) circulating in poultry. However, in order to ensure a high sensitivity of virus detection and effectiveness of management actions, poultry management practices features influencing AIV dynamics need to be accounted for in the design of surveillance programmes. In order to address this knowledge gap, a cross-sectional survey was conducted through interviews with 791 traders in 18 Vietnamese live bird markets. Markets greatly differed according to the sources from which poultry was obtained, and their connections to other markets through the movements of their traders. These features, which could be informed based on indicators that are easy to measure, suggest that markets could be used as sentinels for monitoring virus strains circulating in specific segments of the poultry production sector. AIV spread within markets was modelled. Due to the high turn-over of poultry, viral amplification was likely to be minimal in most of the largest markets. However, due to the large number of birds being introduced each day, and challenges related to cleaning and disinfection, environmental accumulation of viruses at markets may take place, posing a threat to the poultry production sector and to public health.
Bilayer Membrane Modulation of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Structure and Proteolytic Activity
Authors: Cerofolini Linda , Amar Sabrina , Lauer Janelle L. , Martelli Tommaso , Fragai Marco , Luchinat Claudio , Fields Gregg B.
Published: July 2016

Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple-helices occurs within blades I and II of this domain. Examination of simultaneous membrane interaction and triple-helix binding revealed a possible regulation of proteolysis due to steric effects of the membrane. At bicelle concentrations of 1%, enzymatic activity towards triple-helices was increased 1.5-fold. A single mutation in the putative membrane interaction region of MT1-MMP (Ser466Pro) resulted in lower enzyme activation by bicelles. An initial structural framework has thus been developed to define the role(s) of cell membranes in modulating proteolysis.
Ultrahigh brilliance quasi-monochromatic MeV γ-rays based on self-synchronized all-optical Compton scattering
Authors: Yu Changhai , Qi Rong , Wang Wentao , Liu Jiansheng , Li Wentao , Wang Cheng , Zhang Zhijun , Liu Jiaqi , Qin Zhiyong , Fang Ming , Feng Ke , Wu Ying , Tian Ye , Xu Yi , Wu Fenxiang , Leng Yuxin , Weng Xiufeng , Wang Jihu , Wei Fuli , Yi Yicheng , Song Zhaohui , Li Ruxin , Xu Zhizhan
Published: July 2016

Inverse Compton scattering between ultra-relativistic electrons and an intense laser field has been proposed as a major route to generate compact high-brightness and high-energy γ-rays. Attributed to the inherent synchronization mechanism, an all-optical Compton scattering γ-ray source, using one laser to both accelerate electrons and scatter via the reflection of a plasma mirror, has been demonstrated in proof-of-principle experiments to produce a x-ray source near 100 keV. Here, by designing a cascaded laser wakefield accelerator to generate high-quality monoenergetic e-beams, which are bound to head-on collide with the intense driving laser pulse via the reflection of a 20-um-thick Ti foil, we produce tunable quasi-monochromatic MeV γ-rays (33% full-width at half-maximum) with a peak brilliance of ~3 × 1022 photons s−1 mm−2 mrad−2 0.1% BW at 1 MeV. To the best of our knowledge, it is one order of magnitude higher than ever reported value of its kinds in MeV regime. This compact ultrahigh brilliance γ-ray source may provide applications in nuclear resonance fluorescence, x-ray radiology and ultrafast pump-probe nondestructive inspection.
Magnetic Tunnel Junction Based Long-Term Short-Term Stochastic Synapse for a Spiking Neural Network with On-Chip STDP Learning
Authors: Srinivasan Gopalakrishnan , Sengupta Abhronil , Roy Kaushik
Published: July 2016

Spiking Neural Networks (SNNs) have emerged as a powerful neuromorphic computing paradigm to carry out classification and recognition tasks. Nevertheless, the general purpose computing platforms and the custom hardware architectures implemented using standard CMOS technology, have been unable to rival the power efficiency of the human brain. Hence, there is a need for novel nanoelectronic devices that can efficiently model the neurons and synapses constituting an SNN. In this work, we propose a heterostructure composed of a Magnetic Tunnel Junction (MTJ) and a heavy metal as a stochastic binary synapse. Synaptic plasticity is achieved by the stochastic switching of the MTJ conductance states, based on the temporal correlation between the spiking activities of the interconnecting neurons. Additionally, we present a significance driven long-term short-term stochastic synapse comprising two unique binary synaptic elements, in order to improve the synaptic learning efficiency. We demonstrate the efficacy of the proposed synaptic configurations and the stochastic learning algorithm on an SNN trained to classify handwritten digits from the MNIST dataset, using a device to system-level simulation framework. The power efficiency of the proposed neuromorphic system stems from the ultra-low programming energy of the spintronic synapses.
The discovery of the Amazonian tree flora with an updated checklist of all known tree taxa
Authors: ter Steege Hans , Vaessen Rens W. , Cárdenas-López Dairon , Sabatier Daniel , Antonelli Alexandre , de Oliveira Sylvia Mota , Pitman Nigel C. A. , Jørgensen Peter Møller , Salomão Rafael P.
Published: July 2016

Amazonia is the most biodiverse rainforest on Earth, and the debate over how many tree species grow there remains contentious. Here we provide a checklist of all tree species collected to date, and describe spatial and temporal trends in data accumulation. We report 530,025 unique collections of trees in Amazonia, dating between 1707 and 2015, for a total of 11,676 species in 1225 genera and 140 families. These figures support recent estimates of 16,000 total Amazonian tree species based on ecological plot data from the Amazonian Tree Diversity Network. Botanical collection in Amazonia is characterized by three major peaks, centred around 1840, 1920, and 1980, which are associated with flora projects and the establishment of inventory plots. Most collections were made in the 20th century. The number of collections has increased exponentially, but shows a slowdown in the last two decades. We find that a species’ range size is a better predictor of the number of times it has been collected than the species’ estimated basin-wide population size. Finding, describing, and documenting the distribution of the remaining species will require coordinated efforts at under-collected sites.
Optimizing the Dopant and Carrier Concentration of Ca5Al2Sb6 for High Thermoelectric Efficiency
Authors: Yan Yuli , Zhang Guangbiao , Wang Chao , Peng Chengxiao , Zhang Peihong , Wang Yuanxu , Ren Wei
Published: July 2016

The effects of doping on the transport properties of Ca5Al2Sb6 are investigated using first-principles electronic structure methods and Boltzmann transport theory. The calculated results show that a maximum ZT value of 1.45 is achieved with an optimum carrier concentration at 1000 K. However, experimental studies have shown that the maximum ZT value is no more than 1 at 1000 K. By comparing the calculated Seebeck coefficient with experimental values, we find that the low dopant solubility in this material is not conductive to achieve the optimum carrier concentration, leading a smaller experimental value of the maximum ZT. Interestingly, the calculated dopant formation energies suggest that optimum carrier concentrations can be achieved when the dopants and Sb atoms have similar electronic configurations. Therefore, it might be possible to achieve a maximum ZT value of 1.45 at 1000 K with suitable dopants. These results provide a valuable theoretical guidance for the synthesis of high-performance bulk thermoelectric materials through dopants optimization.
Profiling of Host Cell Response to Successive Canine Parvovirus Infection Based on Kinetic Proteomic Change Identification
Authors: Zhao Hang , Cheng Yuening , Wang Jianke , Lin Peng , Yi Li , Sun Yaru , Ren Jingqiang , Tong Mingwei , Cao Zhigang , Li Jiawei , Deng Jinliang , Cheng Shipeng
Published: July 2016

Canine parvovirus (CPV) reproduces by co-opting the resources of host cells, inevitably causing cytotoxic effects to the host cells. Feline kidney F81 cells are sensitive to CPV infection and show disparate growing statuses at different time points post-infection. This study analysed the response of F81 cells to CPV infection at successive infection time points by iTRAQ-based quantitative proteomics. Differentially expressed proteins (DEPs) during 60 h of infection and at selected time points post-infection were identified by an analysis of variance test and a two-tailed unpaired t test, respectively. DEPs with similar quantitative changes were clustered by hierarchical clustering and analysed by gene ontology enrichment, revealing that 12 h and 60 h post-infection were the optimal times to analyse the autonomous parvovirus replication and apoptosis processes, respectively. Using the MetacoreTM database, 29 DEPs were enriched in a network involved in p53 regulation. Besides, a significantly enriched pathway suggests that the CPV-induced cytopathic effect was probably due to the deficiency of functional CFTR caused by CPV infection. This study uncovered the systemic changes in key cellular factors involved in CPV infection and help to understand the molecular mechanisms of the anti-cancer activity of CPV and the cytopathic effects induced by CPV infection.
Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound
Authors: Fatehullah A. , Sharma S. , Newton I. P. , Langlands A. J. , Lay H. , Nelson S. A. , McMahon R. K. , McIlvenny N. , Appleton P. L. , Cochran S. , Näthke I. S.
Published: July 2016

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.
The reactive element effect of ceria particle dispersion on alumina growth: A model based on microstructural observations
Authors: Wang X. , Peng X. , Tan X. , Wang F.
Published: July 2016

The oxidation kinetics of alumina-forming metals can be affected by adding a small amount of a reactive (normally rare earth) element oxide (RExOy) and the segregation of the reactive element (RE) ions to the growing alumina grain boundaries (GBs) has been considered as a responsible reason. However, this interpretation remains a controversial issue as to how RE ions are produced by RExOy which is thermodynamically and chemically stable in metals. The question is answered by a model that is based on transmission electron microscopy (TEM) investigation of a CeO2-dispersed nickel aluminide oxidized in air at 1100 °C. The CeO2 dispersion is incorporated into the alumina scale by the inward growth of inner α-Al2O3, where it partially dissolves producing tetravalent Ce cations which then transform to trivalent cations by trapping electrons. The trivalent cations segregate to the α-Al2O3 GBs and diffuse outward along first the GBs and later the twin boundaries (TBs) in the outer γ-Al2O3 layer, being precipitated as Ce2O3 particles near surface.
Multimodal Imaging of Nanocomposite Microspheres for Transcatheter Intra-Arterial Drug Delivery to Liver Tumors
Authors: Kim Dong-Hyun , Li Weiguo , Chen Jeane , Zhang Zhuoli , Green Richard M. , Huang Sui , Larson Andrew C.
Published: July 2016

A modern multi-functional drug carrier is critically needed to improve the efficacy of image-guided catheter-directed approaches for the treatment of hepatic malignancies. For this purpose, a nanocomposite microsphere platform was developed for selective intra-arterial transcatheter drug delivery to liver tumors. In our study, continuous microfluidic methods were used to fabricate drug-loaded multimodal MRI/CT visible microspheres that included both gold nanorods and magnetic clusters. The resulting hydrophilic, deformable and non-aggregated microspheres were mono-disperse and roughly 25 um in size. Sustained drug release and strong MRI T2 and CT contrast effects were achieved with the embedded magnetic nano-clusters and radiopaque gold nanorods. The microspheres were successfully infused through catheters selectively placed within the hepatic artery in rodent models and subsequent distribution in the targeted liver tissues and hepatic tumors confirmed with MRI and CT imaging. These multimodal nanocomposite drug carriers should be ideal for selective intra-arterial catheter-directed administration to liver tumors while permitting MRI/CT visualization for patient-specific confirmation of tumor-targeted delivery.
Survivability of Deterministic Dynamical Systems
Authors: Hellmann Frank , Schultz Paul , Grabow Carsten , Heitzig Jobst , Kurths Jürgen
Published: July 2016

The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures.
Development of near-zero water consumption cement materials via the geopolymerization of tektites and its implication for lunar construction
Authors: Wang Kai-tuo , Tang Qing , Cui Xue-min , He Yan , Liu Le-ping
Published: July 2016

The environment on the lunar surface poses some difficult challenges to building long-term lunar bases; therefore, scientists and engineers have proposed the creation of habitats using lunar building materials. These materials must meet the following conditions: be resistant to severe lunar temperature cycles, be stable in a vacuum environment, have minimal water requirements and be sourced from local Moon materials. Therefore, the preparation of lunar building materials that use lunar resources is preferred. Here, we present a potential lunar cement material that was fabricated using tektite powder and a sodium hydroxide activator and is based on geopolymer technology. Geopolymer materials have the following properties: approximately zero water consumption, resistance to high- and low-temperature cycling, vacuum stability and good mechanical properties. Although the tektite powder is not equivalent to lunar soil, we speculate that the alkali activated activity of lunar soil will be higher than that of tektite because of its low Si/Al composition ratio. This assumption is based on the tektite geopolymerization research and associated references. In summary, this study provides a feasible approach for developing lunar cement materials using a possible water recycling system based on geopolymer technology.
A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer
Authors: Auslander Noam , Yizhak Keren , Weinstock Adam , Budhu Anuradha , Tang Wei , Wang Xin Wei , Ambs Stefan , Ruppin Eytan
Published: July 2016

Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured.
Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus
Authors: Mohamed Mohamed F. , Abdelkhalek Ahmed , Seleem Mohamed N.
Published: July 2016

Methicillin-resistant Staphylococcus aureus (MRSA) infections present a serious challenge because of the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, antimicrobial peptides are novel alternatives to traditional antibiotics for tackling the issue of bacterial multidrug resistance. Herein, we investigated the antibacterial activity of two short novel peptides (WR12, a 12 residue peptide composed exclusively of arginine and tryptophan, and D-IK8, an eight residue β-sheet peptide) against multidrug resistant staphylococci. In vitro, both peptides exhibited good antibacterial activity against MRSA, vancomycin-resistant S. aureus, linezolid-resistant S. aureus, and methicillin-resistant S. epidermidis. WR12 and D-IK8 were able to eradicate persisters, MRSA in stationary growth phase, and showed significant clearance of intracellular MRSA in comparison to both vancomycin and linezolid. In vivo, topical WR12 and D-IK8 significantly reduced both the bacterial load and the levels of the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in MRSA-infected skin lesions. Moreover, both peptides disrupted established in vitro biofilms of S. aureus and S. epidermidis significantly more so than traditional antimicrobials tested. Taken together, these results support the potential of WR12 and D-IK8 to be used as a topical antimicrobial agent for the treatment of staphylococcal skin infections.
Gene expression in term placentas is regulated more by spinal or epidural anesthesia than by late-onset preeclampsia or gestational diabetes mellitus
Authors: Lekva Tove , Lyle Robert , Roland Marie Cecilie Paasche , Friis Camilla , Bianchi Diana W. , Jaffe Iris Z. , Norwitz Errol R. , Bollerslev Jens , Henriksen Tore , Ueland Thor
Published: July 2016

Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are common complications of pregnancy, but the mechanisms underlying these disorders remain unclear. The aim was to identify the extent of altered gene expression in term placentas from pregnant women with late-onset PE and GDM compared to controls. RNAseq identified few significantly differentially regulated genes in placental biopsies between PE, GDM, or uncomplicated pregnancy (n = 10 each group). Five genes were altered in placentas from PE including 4 non-coding genes and Angiopoietin 2 (ANGPT2). No genes were significantly regulated by GDM. In contrast, many genes were significantly regulated by fetal, maternal and delivery-specific variables, particularly spinal and epidural anesthesia. We selected ANGPT2 and Chemokine (C-X-C motif) ligand 14 (CXCL14) to test with qPCR in a larger set of placentas (n = 475) and found no differences between the groups. However, regression analysis revealed a stronger association between placental ANGPT2 and CXCL14 mRNA expression and fetal, maternal and delivery-specific variables than diagnostic group. To conclude, the gene expression in term placentas are highly affected by fetal, maternal and delivery specific variables. Few regulated genes were found in late-onset PE and GDM placentas, which may suggest that these conditions could be more affected by maternal factors.
Involucratusins A–H: Unusual Cadinane Dimers from Stahlianthus involucratus with Multidrug Resistance Reversal Activity
Authors: Li Qiang-Ming , Luo Jian-Guang , Wang Rui-Zhi , Wang Xiao-Bing , Yang Ming-Hua , Luo Jun , Kong Ling-Yi
Published: July 2016

Three novel cadinane dimers, involucratusins A–C (1–3), five unique nor-cadinane-dimers, involucratusins D–H (4–8), together with a known compound (9) were isolated from the rhizomes of Stahlianthus involucratus. Their challenging structures and absolute configurations were determined by spectroscopic data, CD experimentation, chemical conversions and single-crystal X-ray diffraction. Compounds 1–3 are unusual cadinane dimers with new connection and novel cores. Compound 4 is a unique nor-cadinane-dimer and 5 and 6 are two pairs of hemiketal racemates with novel dinor-cadinane-dimer backbone. Compounds 7 and 8 represent unusual dodecanor-cadinane-dimer and tetradecanor-cadinane-dimer carbon skeletons, respectively. The possible biogenetic pathways of 1–8 were proposed, involving nucleophilic addition, SN2 nucleophilic displacement, [3 + 3] benzannulation, oxidative cleavage, decarboxylation and oxidative phenol coupling reactions. Multidrug resistance (MDR) reversal activity assay of the isolates were evaluated in doxorubicin-resistant human breast cancer cells (MCF-7/DOX). The combined use of these novel cadinane dimers at a concentration of 10 μM increased the cytotoxicity of doxorubicin by 2.2–5.8-fold. It is the first report about the MDR reversal activity of cadinane dimers.
Tunable switch mediated shikimate biosynthesis in an engineered non-auxotrophic Escherichia coli
Authors: Gu Pengfei , Su Tianyuan , Wang Qian , Liang Quanfeng , Qi Qingsheng
Published: July 2016

Shikimate is a key intermediate in the synthesis of neuraminidase inhibitors. Compared with traditional methods, microbial production of shikimate has the advantages of environmental friendliness, low cost, feed stock renewability and product selectivity and diversity. Despite these advantages, shikimate kinase I and II respectively encoded by aroK and aroL are inactivated in most shikimate microbial producers, thus requiring the addition of aromatic compounds during the fermentation process. To overcome this problem, we constructed a non-auxotrophic, shikimate-synthesising strain of Escherichia coli. By inactivation of repressor proteins, blocking of competitive pathways and overexpression of key enzymes, we increased the shikimate production of wild-type E. coli BW25113 to 1.73 g/L. We then designed a tunable switch that can conditionally decrease gene expression and substituted it for the original aroK promoters. Expression of aroK in the resulting P-9 strain was maintained at a high level during the growth phase and then reduced at a suitable time by addition of an optimal concentration of inducer. In 5-L fed-batch fermentation, strain P-9 produced 13.15 g/L shikimate without the addition of any aromatic compounds. The tunable switch developed in this study is an efficient tool for regulating indispensable genes involved in critical metabolic pathways.
Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice
Authors: Guo Chuanlong , Li Mengshuang , Qi Xia , Lin Guiming , Cui Fenghua , Li Fengjie , Wu Xianggen
Published: July 2016

Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy.
Subtractive Color Filters Based on a Silicon-Aluminum Hybrid-Nanodisk Metasurface Enabling Enhanced Color Purity
Authors: Yue Wenjing , Gao Song , Lee Sang-Shin , Kim Eun-Soo , Choi Duk-Yong
Published: July 2016

Highly efficient subtractive tri-color filters of cyan, magenta and yellow with enhanced color purity and robustness have been proposed and realized, by exploiting a silicon-aluminum (Si-Al) hybrid-nanodisk (ND) metasurface atop a Si substrate. The aspect ratio of the Si-Al hybrid ND is much lower than that of the conventional Si nanowire, which is disadvantageous due to its fragility and low color purity. In response to incident light impinging upon the metasurface, the hybrid-NDs individually play the role in exciting a magnetic dipole (MD) resonance through the mediation of Mie-scattering between the hybrid ND and air. The light stored in the resonance is coupled to the substrate, giving rise to a suppressed reflection. By virtue of the top Al ND, the excited MD resonance is strongly confined by the Si ND. As a consequence, a near-zero resonant dip that exhibits high off-resonance reflection and narrow bandwidth is produced for embodying highly efficient tri-color filters with enhanced color purity. The spectral position can be tuned by a simple adjustment of the hybrid-ND diameter. A full-color palette was successfully created with a high color purity and large color gamut. The proposed devices may be applied for photorealistic high-resolution color printing and holographic displays.