bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying redox-induced Schottky barrier variations in memristive devices via in operando spectromicroscopy with graphene electrodes
Authors: Baeumer Christoph , Schmitz Christoph , Marchewka Astrid , Mueller David N. , Valenta Richard , Hackl Johanna , Raab Nicolas , Rogers Steven P. , Khan M. Imtiaz , Nemsak Slavomir , Shim Moonsub , Menzel Stephan , Schneider Claus Michael , Waser Rainer , Dittmann Regina
Published: August 2016

The continuing revolutionary success of mobile computing and smart devices calls for the development of novel, cost- and energy-efficient memories. Resistive switching is attractive because of, inter alia, increased switching speed and device density. On electrical stimulus, complex nanoscale redox processes are suspected to induce a resistance change in memristive devices. Quantitative information about these processes, which has been experimentally inaccessible so far, is essential for further advances. Here we use in operando spectromicroscopy to verify that redox reactions drive the resistance change. A remarkable agreement between experimental quantification of the redox state and device simulation reveals that changes in donor concentration by a factor of 2–3 at electrode-oxide interfaces cause a modulation of the effective Schottky barrier and lead to >2 orders of magnitude change in device resistance. These findings allow realistic device simulations, opening a route to less empirical and more predictive design of future memory cells.
Blocking transport resonances via Kondo many-body entanglement in quantum dots
Authors: Niklas Michael , Smirnov Sergey , Mantelli Davide , Margańska Magdalena , Nguyen Ngoc-Viet , Wernsdorfer Wolfgang , Cleuziou Jean-Pierre , Grifoni Milena
Published: August 2016

Many-body entanglement is at the heart of the Kondo effect, which has its hallmark in quantum dots as a zero-bias conductance peak at low temperatures. It signals the emergence of a conducting singlet state formed by a localized dot degree of freedom and conduction electrons. Carbon nanotubes offer the possibility to study the emergence of the Kondo entanglement by tuning many-body correlations with a gate voltage. Here we show another side of Kondo correlations, which counterintuitively tend to block conduction channels: inelastic co-tunnelling lines in the magnetospectrum of a carbon nanotube strikingly disappear when tuning the gate voltage. Considering the global SU(2) ⊗ SU(2) symmetry of a nanotube coupled to leads, we find that only resonances involving flips of the Kramers pseudospins, associated to this symmetry, are observed at temperatures and voltages below the corresponding Kondo scale. Our results demonstrate the robust formation of entangled many-body states with no net pseudospin.
Identification of carbon-encapsulated iron nanoparticles as active species in non-precious metal oxygen reduction catalysts
Authors: Varnell Jason A. , Tse Edmund C. M. , Schulz Charles E. , Fister Tim T. , Haasch Richard T. , Timoshenko Janis , Frenkel Anatoly I. , Gewirth Andrew A.
Published: August 2016

The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction. Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts. However, the identity of the active species in non-precious metal catalysts remains elusive, impeding the development of new catalysts. Here we demonstrate the reversible deactivation and reactivation of an iron-based non-precious metal oxygen reduction catalyst achieved using high-temperature gas-phase chlorine and hydrogen treatments. In addition, we observe a decrease in catalyst heterogeneity following treatment with chlorine and hydrogen, using Mössbauer and X-ray absorption spectroscopy. Our study reveals that protected sites adjacent to iron nanoparticles are responsible for the observed activity and stability of the catalyst. These findings may allow for the design and synthesis of enhanced non-precious metal oxygen reduction catalysts with a higher density of active sites.
Schizophrenia patient-derived olfactory neurosphere-derived cells do not respond to extracellular reelin
Authors: Tee Jing Yang , Sutharsan Ratneswary , Fan Yongjun , Mackay-Sim Alan
Published: August 2016

Reelin expression is reduced in various regions in the post-mortem brain of schizophrenia patients but the exact role of reelin function in the neurobiology of schizophrenia remains elusive. Absence of reelin in knockout mouse causes inverted lamination of the neocortex due to aberrant neuronal migration. The aim of this study was to utilize patient-derived olfactory neurosphere-derived (ONS) cells to investigate whether extracellular reelin alters cell motility in schizophrenia patient-derived cells. ONS cells from nine patients were compared with cells from nine matched healthy controls. Automated high-throughput imaging and analysis were used to track motility of individual living cells on reelin-coated surfaces produced from reelin secreted into the medium by HEK293FT cells transfected with the full-length reelin plasmid pCrl. Automated assays were used to quantify intracellular cytoskeleton composition, cell morphology, and focal adhesions. Expression of reelin and components of the reelin signaling pathway were measured by western blot and flow cytometry. Reelin inhibited the motility of control cells but not patient cells, and increased the number and size of focal adhesions in control cells but not patient cells. Patient and control cells expressed similar levels of the reelin receptors and the reelin signaling protein, Dab1, but patient cells expressed less reelin. Patient cells were smaller than control cells and had less actin and acetylated α-tubulin, components of the cytoskeleton. These findings are the first direct evidence that cellular responses to reelin are impaired in schizophrenia and are consistent with the role of reelin in cytoarchitectural deficits observed in schizophrenia patient brains.
Urinary π-glutathione S-transferase Predicts Advanced Acute Kidney Injury Following Cardiovascular Surgery
Authors: Shu Kai-Hsiang , Wang Chih-Hsien , Wu Che-Hsiung , Huang Tao-Min , Wu Pei-Chen , Lai Chien-Heng , Tseng Li-Jung , Tsai Pi-Ru , Connolly Rory , Wu Vin-Cent
Published: August 2016

Urinary biomarkers augment the diagnosis of acute kidney injury (AKI), with AKI after cardiovascular surgeries being a prototype of prognosis scenario. Glutathione S-transferases (GST) were evaluated as biomarkers of AKI. Urine samples were collected in 141 cardiovascular surgical patients and analyzed for urinary alpha-(α-) and pi-(π-) GSTs. The outcomes of advanced AKI (KDIGO stage 2, 3) and all-cause in-patient mortality, as composite outcome, were recorded. Areas under the receiver operator characteristic (ROC) curves and multivariate generalized additive model (GAM) were applied to predict outcomes. Thirty-eight (26.9%) patients had AKI, while 12 (8.5%) were with advanced AKI. Urinary π-GST differentiated patients with/without advanced AKI or composite outcome after surgery (p < 0.05 by generalized estimating equation). Urinary π-GST predicted advanced AKI at 3 hrs post-surgery (p = 0.033) and composite outcome (p = 0.009), while the corresponding ROC curve had AUC of 0.784 and 0.783. Using GAM, the cutoff value of 14.7 μg/L for π-GST showed the best performance to predict composite outcome. The addition of π-GST to the SOFA score improved risk stratification (total net reclassification index = 0.47). Thus, urinary π-GST levels predict advanced AKI or hospital mortality after cardiovascular surgery and improve in SOFA outcome assessment specific to AKI.
Toxicology Study of Single-walled Carbon Nanotubes and Reduced Graphene Oxide in Human Sperm
Authors: Asghar Waseem , Shafiee Hadi , Velasco Vanessa , Sah Vasu R. , Guo Shirui , El Assal Rami , Inci Fatih , Rajagopalan Adhithi , Jahangir Muntasir , Anchan Raymond M. , Mutter George L. , Ozkan Mihrimah , Ozkan Cengiz S. , Demirci Utkan
Published: August 2016

Carbon-based nanomaterials such as single-walled carbon nanotubes and reduced graphene oxide are currently being evaluated for biomedical applications includingin vivodrug delivery and tumor imaging. Several reports have studied the toxicity of carbon nanomaterials, but their effects on human male reproduction have not been fully examined. Additionally, it is not clear whether the nanomaterial exposure has any effect on sperm sorting procedures used in clinical settings. Here, we show that the presence of functionalized single walled carbon nanotubes (SWCNT-COOH) and reduced graphene oxide at concentrations of 1–25 μg/mL do not affect sperm viability. However, SWCNT-COOH generate significant reactive superoxide species at a higher concentration (25 μg/mL), while reduced graphene oxide does not initiate reactive species in human sperm. Further, we demonstrate that exposure to these nanomaterials does not hinder the sperm sorting process, and microfluidic sorting systems can select the sperm that show low oxidative stress post-exposure.
Climate extremes can drive biological assemblages to early successional stages compared to several mild disturbances
Authors: Sanz-Lázaro Carlos
Published: August 2016

Extreme climatic events have a major role in the structuring of biological communities, and their occurrence is expected to increase due to climate change. Here I use a manipulative approach to test the effects of extreme storm events on rocky mid-shore assemblages. This study shows that an extreme storm can cause more negative effects than several mild storms, primarily by bringing the biological assemblages towards early stages of succession. This finding contrasts with the effects of clustering of climatic events due to climate change, which are expected to mitigate its ecological impacts. Thus, the ecological consequences of climatic events that are influenced by climate change may have contrasting effects depending on the features that are considered. These results have relevant implications in the forecasting of the ecological consequences of climate change and should be considered when designing measures to mitigate its effects.
Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China
Authors: Yang Feiling , Hu Jinming , Wu Ruidong
Published: August 2016

Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan’s protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan.
Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists
Authors: Liu Shenping , Dakin Leslie A. , Xing Li , Withka Jane M. , Sahasrabudhe Parag V. , Li Wei , Banker Mary Ellen , Balbo Paul , Shanker Suman , Chrunyk Boris A. , Guo Zuojun , Chen Jinshan M. , Young Jennifer A. , Bai Guoyun , Starr Jeremy T. , Wright Stephen W. , Bussenius Joerg , Tan Sheng , Gopalsamy Ariamala , Lefker Bruce A. , Vincent Fabien , Jones Lyn H. , Xu Hua , Hoth Lise R. , Geoghegan Kieran F. , Qiu Xiayang , Bunnage Mark E. , Thorarensen Atli
Published: August 2016

Interleukin-17A (IL-17A) is a principal driver of multiple inflammatory and immune disorders. Antibodies that neutralize IL-17A or its receptor (IL-17RA) deliver efficacy in autoimmune diseases, but no small-molecule IL-17A antagonists have yet progressed into clinical trials. Investigation of a series of linear peptide ligands to IL-17A and characterization of their binding site has enabled the design of novel macrocyclic ligands that are themselves potent IL-17A antagonists.
Ammonia intercalated flower-like MoS2 nanosheet film as electrocatalyst for high efficient and stable hydrogen evolution
Authors: Wang F. Z. , Zheng M. J. , Zhang B. , Zhu C. Q. , Li Q. , Ma L. , Shen W. Z.
Published: August 2016

Ammonia intercalated flower-like MoS2 electrocatalyst film assembled by vertical orientated ultrathin nanosheet on graphite sheethas been successfully synthesized using one-step hydrothermal method. In this strategy, ammonia can effectively insert into the parallel plane of the MoS2 nanosheets, leading to the expansion of lattice and phase transfer from 2H to 1T, generating more active unsaturated sulfur atoms. The flower-like ammoniated MoS2 electrocatalysts with more active sites and large surface area exhibited excellent HER activity with a small Tafel slope and low onset overpotential, resulting a great enhancement in hydrogen evolution. The high efficient activity and recyclable utilization, as well as large-scale, indicate that it is a very promising electrocatalyst to replace Pt in industry application.
Nematicidal spore-forming Bacilli share similar virulence factors and mechanisms
Authors: Zheng Ziqiang , Zheng Jinshui , Zhang Zhengming , Peng Donghai , Sun Ming
Published: August 2016

In the soil environment, Bacilli can affect nematode development, fecundity and survival. However, although many Bacillus species can kill nematodes, the virulence mechanisms Bacilli utilize remain unknown. In this study, we collected 120 strains comprising 30 species across the Bacillaceae and Paenibacillaceae families of the Bacillales order and measured their nematicidal activities in vitro. Comparison of these strains’ nematicidal capacities revealed that nine species, including Bacillus thuringiensis, B. cereus, B. subtilis, B. pumilus, B. firmus, B. toyonensis, Lysinibacillus sphaericus, Brevibacillus laterosporus and B. brevis, were highly nematicidal, the first of which showed the highest activity. Genome sequencing and analysis identified many potential virulence factors, which grouped into five types. At least four possible mechanisms were deduced on the basis of the combination of these factors and the bacterial nematicidal activity, including a pore-forming mechanism of crystal proteins, an inhibition-like mechanism of thuringiensin and a degradation mechanism of proteases and/or chitinases. Our results demonstrate that 120 spore-forming Bacilli across different families share virulence factors that may contribute to their nematicidal capacity.
Metal-electrode-free Window-like Organic Solar Cells with p-Doped Carbon Nanotube Thin-film Electrodes
Authors: Jeon Il , Delacou Clement , Kaskela Antti , Kauppinen Esko I. , Maruyama Shigeo , Matsuo Yutaka
Published: August 2016

Organic solar cells are flexible and inexpensive, and expected to have a wide range of applications. Many transparent organic solar cells have been reported and their success hinges on full transparency and high power conversion efficiency. Recently, carbon nanotubes and graphene, which meet these criteria, have been used in transparent conductive electrodes. However, their use in top electrodes has been limited by mechanical difficulties in fabrication and doping. Here, expensive metal top electrodes were replaced with high-performance, easy-to-transfer, aerosol-synthesized carbon nanotubes to produce transparent organic solar cells. The carbon nanotubes were p-doped by two new methods: HNO3 doping via ‘sandwich transfer’, and MoOx thermal doping via ‘bridge transfer’. Although both of the doping methods improved the performance of the carbon nanotubes and the photovoltaic performance of devices, sandwich transfer, which gave a 4.1% power conversion efficiency, was slightly more effective than bridge transfer, which produced a power conversion efficiency of 3.4%. Applying a thinner carbon nanotube film with 90% transparency decreased the efficiency to 3.7%, which was still high. Overall, the transparent solar cells had an efficiency of around 50% that of non-transparent metal-based solar cells (7.8%).
Genome-wide Expression Analysis and Metabolite Profiling Elucidate Transcriptional Regulation of Flavonoid Biosynthesis and Modulation under Abiotic Stresses in Banana
Authors: Pandey Ashutosh , Alok Anshu , Lakhwani Deepika , Singh Jagdeep , Asif Mehar H. , Trivedi Prabodh K.
Published: August 2016

Flavonoid biosynthesis is largely regulated at the transcriptional level due to the modulated expression of genes related to the phenylpropanoid pathway in plants. Although accumulation of different flavonoids has been reported in banana, a staple fruit crop, no detailed information is available on regulation of the biosynthesis in this important plant. We carried out genome-wide analysis of banana (Musa acuminata, AAA genome) and identified 28 genes belonging to 9 gene families associated with flavonoid biosynthesis. Expression analysis suggested spatial and temporal regulation of the identified genes in different tissues of banana. Analysis revealed enhanced expression of genes related to flavonol and proanthocyanidin (PA) biosynthesis in peel and pulp at the early developmental stages of fruit. Genes involved in anthocyanin biosynthesis were highly expressed during banana fruit ripening. In general, higher accumulation of metabolites was observed in the peel as compared to pulp tissue. A correlation between expression of genes and metabolite content was observed at the early stage of fruit development. Furthermore, this study also suggests regulation of flavonoid biosynthesis, at transcriptional level, under light and dark exposures as well as methyl jasmonate (MJ) treatment in banana.
Model-based action planning involves cortico-cerebellar and basal ganglia networks
Authors: Fermin Alan S. R. , Yoshida Takehiko , Yoshimoto Junichiro , Ito Makoto , Tanaka Saori C. , Doya Kenji
Published: August 2016

Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future states reached by hypothetical actions and motor-memory RL selects past successful state-action mapping. In order to investigate the neural substrates that implement these strategies, we conducted a functional magnetic resonance imaging (fMRI) experiment while humans performed a sequential action selection task under conditions that promoted the use of a specific RL strategy. The ventromedial prefrontal cortex and ventral striatum increased activity in the exploratory condition; the dorsolateral prefrontal cortex, dorsomedial striatum and lateral cerebellum in the model-based condition; and the supplementary motor area, putamen and anterior cerebellum in the motor-memory condition. These findings suggest that a distinct prefrontal-basal ganglia and cerebellar network implements the model-based RL action selection strategy.
Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models
Authors: Sanchez-Martinez Alvaro , Beavan Michelle , Gegg Matthew E. , Chau Kai-Yin , Whitworth Alexander J. , Schapira Anthony H. V.
Published: August 2016

GBA gene mutations are the greatest cause of Parkinson disease (PD). GBA encodes the lysosomal enzyme glucocerebrosidase (GCase) but the mechanisms by which loss of GCase contributes to PD remain unclear. Inhibition of autophagy and the generation of endoplasmic reticulum (ER) stress are both implicated. Mutant GCase can unfold in the ER and be degraded via the unfolded protein response, activating ER stress and reducing lysosomal GCase. Small molecule chaperones that cross the blood brain barrier help mutant GCase refold and traffic correctly to lysosomes are putative treatments for PD. We treated fibroblast cells from PD patients with heterozygous GBA mutations and Drosophila expressing human wild-type, N370S and L444P GBA with the molecular chaperones ambroxol and isofagomine. Both chaperones increased GCase levels and activity, but also GBA mRNA, in control and mutant GBA fibroblasts. Expression of mutated GBA in Drosophila resulted in dopaminergic neuronal loss, a progressive locomotor defect, abnormal aggregates in the ER and increased levels of the ER stress reporter Xbp1-EGFP. Treatment with both chaperones lowered ER stress and prevented the loss of motor function, providing proof of principle that small molecule chaperones can reverse mutant GBA-mediated ER stress in vivo and might prove effective for treating PD.
Three-dimensional fluorescent microscopy via simultaneous illumination and detection at multiple planes
Authors: Ma Qian , Khademhosseinieh Bahar , Huang Eric , Qian Haoliang , Bakowski Malina A. , Troemel Emily R. , Liu Zhaowei
Published: August 2016

The conventional optical microscope is an inherently two-dimensional (2D) imaging tool. The objective lens, eyepiece and image sensor are all designed to capture light emitted from a 2D ‘object plane’. Existing technologies, such as confocal or light sheet fluorescence microscopy have to utilize mechanical scanning, a time-multiplexing process, to capture a 3D image. In this paper, we present a 3D optical microscopy method based upon simultaneously illuminating and detecting multiple focal planes. This is implemented by adding two diffractive optical elements to modify the illumination and detection optics. We demonstrate that the image quality of this technique is comparable to conventional light sheet fluorescent microscopy with the advantage of the simultaneous imaging of multiple axial planes and reduced number of scans required to image the whole sample volume.
Simulated leakage of high pCO2 water negatively impacts bivalve dominated infaunal communities from the Western Baltic Sea
Authors: Schade Hanna , Mevenkamp Lisa , Guilini Katja , Meyer Stefanie , Gorb Stanislav N. , Abele Doris , Vanreusel Ann , Melzner Frank
Published: August 2016

Carbon capture and storage is promoted as a mitigation method counteracting the increase of atmospheric CO2levels. However, at this stage, environmental consequences of potential CO2leakage from sub-seabed storage sites are still largely unknown. In a 3-month-long mesocosm experiment, this study assessed the impact of elevatedpCO2levels (1,500 to 24,400 μatm) onCerastoderma eduledominated benthic communities from the Baltic Sea. Mortality ofC. edulewas significantly increased in the highest treatment (24,400 μatm) and exceeded 50%. Furthermore, mortality of small size classes (0–1 cm) was significantly increased in treatment levels ≥6,600 μatm. First signs of external shell dissolution became visible at ≥1,500 μatm, holes were observed at >6,600 μatm.C. edulebody condition decreased significantly at all treatment levels (1,500–24,400 μatm). Dominant meiofauna taxa remained unaffected in abundance. Densities of calcifying meiofauna taxa (i.e. Gastropoda and Ostracoda) decreased in high CO2treatments (>6,600 μatm), while the non - calcifying Gastrotricha significantly increased in abundance at 24,400 μatm. In addition, microbial community composition was altered at the highestpCO2level. We conclude that strong CO2leakage can alter benthic infauna community composition at multiple trophic levels, likely due to high mortality of the dominant macrofauna speciesC. edule.
Insights into the transmission of respiratory infectious diseases through empirical human contact networks
Authors: Huang Chunlin , Liu Xingwu , Sun Shiwei , Li Shuai Cheng , Deng Minghua , He Guangxue , Zhang Haicang , Wang Chao , Zhou Yang , Zhao Yanlin , Bu Dongbo
Published: August 2016

In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology. Furthermore, the special contact pattern within Chinese colleges results in disease spreading patterns distinct from those of the US schools. Remarkably, class cancelation, though simple, shows a mitigating power equal to quarantine/vaccination applied on ~25% of college students, which quantitatively explains its success in Chinese colleges during the SARS period. Our findings greatly facilitate reliable prediction of epidemic prevalence and thus should help establishing effective strategies for respiratory infectious diseases control.
Microbial and diagenetic steps leading to the mineralisation of Great Salt Lake microbialites
Authors: Pace Aurélie , Bourillot Raphaël , Bouton Anthony , Vennin Emmanuelle , Galaup Serge , Bundeleva Irina , Patrier Patricia , Dupraz Christophe , Thomazo Christophe , Sansjofre Pierre , Yokoyama Yusuke , Franceschi Michel , Anguy Yannick , Pigot Léa , Virgone Aurélien , Visscher Pieter T.
Published: August 2016

Microbialites are widespread in modern and fossil hypersaline environments, where they provide a unique sedimentary archive. Authigenic mineral precipitation in modern microbialites results from a complex interplay between microbial metabolisms, organic matrices and environmental parameters. Here, we combined mineralogical and microscopic analyses with measurements of metabolic activity in order to characterise the mineralisation of microbial mats forming microbialites in the Great Salt Lake (Utah, USA). Our results show that the mineralisation process takes place in three steps progressing along geochemical gradients produced through microbial activity. First, a poorly crystallized Mg-Si phase precipitates on alveolar extracellular organic matrix due to a rise of the pH in the zone of active oxygenic photosynthesis. Second, aragonite patches nucleate in close proximity to sulfate reduction hotspots, as a result of the degradation of cyanobacteria and extracellular organic matrix mediated by, among others, sulfate reducing bacteria. A final step consists of partial replacement of aragonite by dolomite, possibly in neutral to slightly acidic porewater. This might occur due to dissolution-precipitation reactions when the most recalcitrant part of the organic matrix is degraded. The mineralisation pathways proposed here provide pivotal insight for the interpretation of microbial processes in past hypersaline environments.
Mechanical properties and failure behaviors of the interface of hybrid graphene/hexagonal boron nitride sheets
Authors: Ding Ning , Chen Xiangfeng , Wu Chi-Man Lawrence
Published: August 2016

Hybrid graphene/h-BN sheet has been fabricated recently and verified to possess unusual physical properties. During the growth process, defects such as vacancies are unavoidably present at the interface between graphene and h-BN. In the present work, typical vacancy defects, which were located at the interface between graphene and h-BN, were studied by density functional theory. The interface structure, mechanical and electronic properties, and failure behavior of the hybrid graphene/h-BN sheet were investigated and compared. The results showed that the formation energy of the defective graphene/h-BN interface basically increased with increasing inflection angles. However, Young’s modulus for all graphene/h-BN systems studied decreased with the increase in inflection angles. The intrinsic strength of the hybrid graphene/h-BN sheets was affected not only by the inflection angles, but also by the type of interface connection and the type of defects. The energy band structure of the hybrid interface could be tuned by applying mechanical strain to the systems. These results demonstrated that vacancies introduced significant effects on the mechanical and electronic properties of the hybrid graphene/h-BN sheet.
The Switch in a Genetic Toggle System with Lévy Noise
Authors: Xu Yong , Li Yongge , Zhang Hao , Li Xiaofan , Kurths Jürgen
Published: August 2016

A bistable toggle switch is a paradigmatic model in the field of biology. The dynamics of the system induced by Gaussian noise has been intensively investigated, but Gaussian noise cannot incorporate large bursts typically occurring in real experiments. This paper aims to examine effects of variations from one protein imposed by a non-Gaussian Lévy noise, which is able to describe even large jumps, on the coherent switch and the on/off switch via the steady-state probability density, the joint steady-state probability density and the mean first passage time. We find that a large burst of one protein due to the Lévy noises can induce coherent switches even with small noise intensities in contrast to the Gaussian case which requires large intensities for this. The influences of the stability index, skewness parameter and noise intensity on the on/off switch are analyzed, leading to an adjustment of the concentrations of both proteins and a decision which stable point to stay most. The mean first passage times show complex effects under Lévy noise, especially the stability index and skewness parameter. Our results also imply that the presence of non-Gaussian Lévy noises has fundamentally changed the escape mechanism in such a system compared with Gaussian noise.
Identification of salivary metabolomic biomarkers for oral cancer screening
Authors: Ishikawa Shigeo , Sugimoto Masahiro , Kitabatake Kenichiro , Sugano Ayako , Nakamura Marina , Kaneko Miku , Ota Sana , Hiwatari Kana , Enomoto Ayame , Soga Tomoyoshi , Tomita Masaru , Iino Mitsuyoshi
Published: August 2016

The objective of this study was to explore salivary metabolite biomarkers by profiling both saliva and tumor tissue samples for oral cancer screening. Paired tumor and control tissues were obtained from oral cancer patients and whole unstimulated saliva samples were collected from patients and healthy controls. The comprehensive metabolomic analysis for profiling hydrophilic metabolites was conducted using capillary electrophoresis time-of-flight mass spectrometry. In total, 85 and 45 metabolites showed significant differences between tumor and matched control samples and between salivary samples from oral cancer and controls, respectively (P < 0.05 correlated by false discovery rate); 17 metabolites showed consistent differences in both saliva and tissue-based comparisons. Of these, a combination of only two biomarkers yielded a high area under receiver operating characteristic curves (0.827; 95% confidence interval, 0.726–0.928,P < 0.0001) for discriminating oral cancers from controls. Various validation tests confirmed its high generalization ability. The demonstrated approach, integrating both saliva and tumor tissue metabolomics, helps eliminate pseudo-molecules that are coincidentally different between oral cancers and controls. These combined salivary metabolites could be the basis of a clinically feasible method of non-invasive oral cancer screening.
Negative Feedback Regulation of HIV-1 by Gene Editing Strategy
Authors: Kaminski Rafal , Chen Yilan , Salkind Julian , Bella Ramona , Young Won-bin , Ferrante Pasquale , Karn Jonathan , Malcolm Thomas , Hu Wenhui , Khalili Kamel
Published: August 2016

The CRISPR/Cas9 gene editing method is comprised of the guide RNA (gRNA) to target a specific DNA sequence for cleavage and the Cas9 endonuclease for introducing breaks in the double-stranded DNA identified by the gRNA. Co-expression of both a multiplex of HIV-1-specific gRNAs and Cas9 in cells results in the modification and/or excision of the segment of viral DNA, leading to replication-defective virus. In this study, we have personalized the activity of CRISPR/Cas9 by placing the gene encoding Cas9 under the control of a minimal promoter of HIV-1 that is activated by the HIV-1 Tat protein. We demonstrate that functional activation of CRISPR/Cas9 by Tat during the course of viral infection excises the designated segment of the integrated viral DNA and consequently suppresses viral expression. This strategy was also used in a latently infected CD4+ T-cell model after treatment with a variety of HIV-1 stimulating agents including PMA and TSA. Controlled expression of Cas9 by Tat offers a new strategy for safe implementation of the Cas9 technology for ablation of HIV-1 at a very early stage of HIV-1 replication during the course of the acute phase of infection and the reactivation of silent proviral DNA in latently infected cells.
Differences among lesions with exon 19, exon 21 EGFR mutations and wild types in surgically resected non-small cell lung cancer
Authors: Jin Ying , Chen Ming , Yu Xinmin
Published: August 2016

The clinical behavior of patients with advanced non-small cell lung cancer (NSCLC) differ between epidermal growth factor receptor (EGFR) exon 19 deletion (Ex19) and EGFR exon 21 L858R mutation (Ex21). This study aimed to evaluate whether these differences exist in surgically resected NSCLC. A total of 198 patients with surgically resected NSCLC harbouring Ex19 (n = 53), Ex21 (n = 51), and EGFR wild-type (Wt) (n = 94) were analyzed. The clinicopathological features, laboratory parameters, recurrent sites and disease-free survival (DFS) were compared according to mutational EGFR status. Ex21 occurred more frequently in female (p < 0.001), never-smokers (p < 0.001), adenocarcinoma (p < 0.001), low grade (p = 0.013) than Wt lesions. Ex19 occurred more frequently in female (p = 0.016), never-smokers (p = 0.008), adenocarcinoma (p < 0.001), low grade (p = 0.025) than Wt lesions. Ex 21 lesions (p = 0.026) had larger lepidic components than Wt lesions. Wt lesions had larger mucinous variant components than Ex21 lesions (p = 0.045) and Ex19 lesions (p = 0.015). Ex21 lesions were associated with lower pretreatment neutrophil: lymphocyte ratio (NLR) than Wt lesions (p = 0.017). The recurrent sites and DFS were similar among patients with Wt, Ex19 and Ex21.
Super-focusing of center-covered engineered microsphere
Authors: Wu Mengxue , Chen Rui , Soh Jiahao , Shen Yue , Jiao Lishi , Wu Jianfeng , Chen Xudong , Ji Rong , Hong Minghui
Published: August 2016

Engineered microsphere possesses the advantage of strong light manipulation at sub-wavelength scale and emerges as a promising candidate to shrink the focal spot size. Here we demonstrated a center-covered engineered microsphere which can adjust the transverse component of the incident beam and achieve a sharp photonic nanojet. Modification of the beam width and working distance of the photonic nanojet were achieved by tuning the cover ratio of the engineered microsphere, leading to a sharp spot size which exceeded the optical diffraction limit. At a wavelength of 633 nm, a focal spot of 245 nm (0.387 λ) was achieved experimentally under plane wave illumination. Strong localized field with Bessel-like distribution was demonstrated by employing the linearly polarized beam and a center-covered mask being engineered on the microsphere.
Microbial Cryptotopes are Prominent Targets of B-cell Immunity
Authors: Rieder Franz J. J. , Biebl Julia , Kastner Marie-Theres , Schneider Martina , Jungbauer Christof , Redlberger-Fritz Monika , Britt William J. , Kundi Michael , Steininger Christoph
Published: August 2016

B-cell recognition of microbial antigens may be limited by masking of epitopes within three-dimensional structures (cryptotopes). Here we report that unmasking of cryptotopes by unfolding whole cytomegalovirus (CMV) antigen preparations with the chaotropic reagent Urea and probing with immune sera from healthy individuals (n = 109) increased ELISA signals by 36% in comparison to folded CMV antigens (P < 0.001). ELISA signals increased also significantly upon unfolding of S. aureus or E. coli antigens, whereas unfolded influenza H1N1 or respiratory syncitial virus antigens yielded reduced or unchanged reactivity in comparison to folded ones, respectively. Blocking of CMV cryptotope-specific Abs by incubation of an immunoglobuline preparation and three sera with unfolded CMV antigens enhanced clearly the neutralizing capacity of this immunoglobuline preparation against CMV infection. Thus, B-cell immunity frequently targets cryptotopes on CMV but these Abs are non-neutralizing, may reduce the neutralizing effectiveness of pathogen-specific Abs and increase during immune maturation following primary CMV infection. The observation of functional consequences of Abs specific for cryptotopes may open whole new avenues to a better understanding of the humoral immune response to CMV and development of more effective vaccines and immunoglobuline preparations.
Nanoscopic characterization of the water vapor-salt interfacial layer reveals a unique biphasic adsorption process
Authors: Yang Liu , He Jianfeng , Shen Yi , Li Xiaowei , Sun Jielin , Czajkowsky Daniel M. , Shao Zhifeng
Published: August 2016

Our quantitative understanding of water adsorption onto salt surfaces under ambient conditions is presently quite poor owing to the difficulties in directly characterizing this interfacial layer under these conditions. Here we determine the thickness of the interfacial layer on NaCl at different relative humidities (RH) based on a novel application of atomic force spectroscopy and capillary condensation theory. In particular, we take advantage of the microsecond-timescale of the capillary condensation process to directly resolve the magnitude of its contribution in the tip-sample interaction, from which the interfacial water thickness is determined. Further, to correlate this thickness with salt dissolution, we also measure surface conductance under similar conditions. We find that below 30% RH, there is essentially only the deposition of water molecules onto this surface, typical of conventional adsorption onto solid surfaces. However, above 30% RH, adsorption is simultaneous with the dissolution of ions, unlike conventional adsorption, leading to a rapid increase of surface conductance. Thus, water adsorption on NaCl is an unconventional biphasic process in which the interfacial layer not only exhibits quantitative differences in thickness but also qualitative differences in composition.
Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment
Authors: Lizotte Patrick H. , Jones Robert E. , Keogh Lauren , Ivanova Elena , Liu Hongye , Awad Mark M. , Hammerman Peter S. , Gill Ritu R. , Richards William G. , Barbie David A. , Bass Adam J. , Bueno Raphael , English Jessie M. , Bittinger Mark , Wong Kwok-Kin
Published: August 2016

With the emergence of checkpoint blockade and other immunotherapeutic drugs, and the growing adoption of smaller, more flexible adaptive clinical trial designs, there is an unmet need to develop diagnostics that can rapidly immunophenotype patient tumors. The ability to longitudinally profile the tumor immune infiltrate in response to immunotherapy also presents a window of opportunity to illuminate mechanisms of resistance. We have developed a fine needle aspirate biopsy (FNA) platform to perform immune profiling on thoracic malignancies. Matching peripheral blood, bulk resected tumor, and FNA were analyzed from 13 mesothelioma patients. FNA samples yielded greater numbers of viable cells when compared to core needle biopsies. Cell numbers were adequate to perform flow cytometric analyses on T cell lineage, T cell activation and inhibitory receptor expression, and myeloid immunosuppressive checkpoint markers. FNA samples were representative of the tumor as a whole as assessed by head-to-head comparison to single cell suspensions of dissociated whole tumor. Parallel analysis of matched patient blood enabled us to establish quality assurance criteria to determine the accuracy of FNA procedures to sample tumor tissue. FNA biopsies provide a diagnostic to rapidly phenotype the tumor immune microenvironment that may be of great relevance to clinical trials.
Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression
Authors: Wei Y B , Liu J J , Villaescusa J C , Åberg E , Brené S , Wegener G , Mathé A A , Lavebratt C
Published: August 2016

Elevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated with an overexpression of LIN28B and downregulation of let-7 miRNAs, the former an RNA-binding protein that selectively represses let-7 synthesis. Also DROSHA, a key enzyme in miRNA biogenesis was downregulated in FSL. Running was previously shown to have an antidepressant-like effect in the FSL rat. We found that running reduced Il6 levels and selectively increased let-7i and miR-98 expression in the PFC of FSL, although there were no differences in LIN28B and DROSHA expression. Pri-let-7i was upregulated in the running FSL group, which associated with increased histone H4 acetylation. In conclusion, the disturbance of let-7 family biogenesis may underlie increased proinflammatory markers in the depressed FSL rats while physical activity could reduce their expression, possibly through regulating primary miRNA expression via epigenetic mechanisms.
Dual design spaces for micro-extraction together with the core–shell chromatographic determination of dorzolamide and timolol in rabbit plasma: an example of quality by design method development
Authors: Mohamed Abdel-Maaboud Ismail , Abdel-Wadood Hanaa Mohammed , Mousa Heba Salah
Published: August 2016

An innovative quality by design-integrated VA-SALLME-core–shell chromatographic method was developed for the simultaneous determination of DOR and TIM in plasma.
A long wavelength fluorescent probe for biothiols and its application in cell imaging
Authors: Li Jiawei , Yin Caixia , Zhang Yongbin , Chao Jianbin , Huo Fangjun
Published: August 2016

A long wavelength and turn-on fluorescent probe (1) containing the maleimide group as a reactive site was designed and synthesized.
Azobenzene photocontrol of peptides and proteins
Authors: Mart Robert J. , Allemann Rudolf K.
Published: August 2016

Significant advances have been made in the use of light as a stimulus to control biomolecular interactions in biological systems. This article places recent developments in context, illustrating their importance.
MOF–aminoclay composites for superior CO2capture, separation and enhanced catalytic activity in chemical fixation of CO2
Authors: Chakraborty Anindita , Achari Amritroop , Eswaramoorthy Muthusamy , Maji Tapas Kumar
Published: August 2016

A novel composite with ultra-small (2–3 nm) MOF nanoparticles stabilized on an aminoclay template shows high CO2capture, separation and chemical fixation efficacy.
Membrane-disrupting iridium(iii) oligocationic organometallopeptides
Authors: Salvadó Iria , Gamba Ilaria , Montenegro Javier , Martínez-Costas José , Brea Jose Manuel , Loza María Isabel , Vázquez López Miguel , Vázquez M. Eugenio
Published: August 2016

A series of oligoarginine peptide derivatives containing cyclometallated iridium(iii) units display remarkable cytotoxicity, comparable to that of cisplatin.
Nitrite reduction by a pyridinediimine complex with a proton-responsive secondary coordination sphere
Authors: Kwon Yubin M. , Delgado Mayra , Zakharov Lev N. , Seda Takele , Gilbertson John D.
Published: August 2016

The reduction of NO2− to NO is achieved with a FePDI complex containing a proton-responsive secondary coordination sphere coupled with redox-active sites.
Intramolecular H⋯S interactions in metal di-(isopropyl)dithiocarbamate complexes
Authors: Angeloski Alexander , Hook James M. , Bhadbhade Mohan , Baker Anthony T. , McDonagh Andrew M.
Published: August 2016

Intramolecular C–H⋯S interactions create restricted rotation of groups within di(isopropyl)dithiocarbate complexes.
Understanding the effect of an in situ generated and integrated spinel phase on a layered Li-rich cathode material using a non-stoichiometric strategy
Authors: Zhang Jicheng , Gao Rui , Sun Limei , Li Zhengyao , Zhang Heng , Hu Zhongbo , Liu Xiangfeng
Published: August 2016

The effect of an in situ generated and integrated spinel phase on a layered Li-rich cathode material is revealed using a non-stoichiometric strategy.
Water dissociation on MnO(1 × 1)/Ag(100)
Authors: Arble Chris , Tong Xiao , Giordano Livia , Ferrari Anna Maria , Newberg John T.
Published: August 2016

MnO(1 × 1)/Ag(100) hydroxylation occurs at terrace sites for water monomers.
New solvatochromic probes: performance enhancement via regulation of excited state structures
Authors: Liu Huijing , Xu Xiaojie , Peng Haonan , Chang Xingmao , Fu Xuwei , Li Qianshu , Yin Shiwei , Blanchard Gary J. , Fang Yu
Published: August 2016

Regulation of excited state structures resulted in new fluorophores with much enhanced solvatochromic properties.
How do random superficial defects influence the electro-oxidation of glycerol on Pt(111) surfaces?
Authors: Fernández Pablo S. , Tereshchuk Polina , Angelucci Camilo A. , Gomes Janaina F. , Garcia Amanda C. , Martins Cauê A. , Camara Giuseppe A. , Martins María E. , Da Silva Juarez L. F. , Tremiliosi-Filho Germano
Published: August 2016

The glycerol electrooxidation reaction (GEOR) has attracted huge interest in the last decade due to the very low price and availability of this polyol.
EPR characterization of Mn(ii) complexes for distance determination with pulsed dipolar spectroscopy
Authors: Keller Katharina , Zalibera Michal , Qi Mian , Koch Vanessa , Wegner Julia , Hintz Henrik , Godt Adelheid , Jeschke Gunnar , Savitsky Anton , Yulikov Maxim
Published: August 2016

EPR properties of four Mn(ii) complexes and Tikhonov regularization-based analysis of RIDME data containing dipolar overtones are presented.
Computational insights into the destabilization of α-helical conformations formed by leucine zipper peptides in response to temperature
Authors: Xu Xiejun , Xiao Xingqing , Xu Shouhong , Liu Honglai
Published: August 2016

The computed transition temperature of leucine zipper peptides is 319.1 K, which is in quantitative agreement with the experimental measurement, 321.1 K.
1,2,4,5-Dioxadiazine-functionalized [N–NO2]− furazan energetic salts
Authors: Huang Haifeng , Shi Yameng , Liu Yanfang , Yang Jun
Published: August 2016

1,2,4,5-Dioxadiazine is identified as a key bridge to improve the density and detonation performance of energetic materials.
Exceptional long-life performance of lithium-ion batteries using ionic liquid-based electrolytes
Authors: Elia Giuseppe Antonio , Ulissi Ulderico , Jeong Sangsik , Passerini Stefano , Hassoun Jusef
Published: August 2016

A lithium ion battery using an ionic liquid electrolyte reveals enhanced safety and exceptionally long life, extended to thousands of cycles.
Structurally stable Mg-doped P2-Na2/3Mn1−yMgyO2 sodium-ion battery cathodes with high rate performance: insights from electrochemical, NMR and diffraction studies
Authors: Clément Raphaële J. , Billaud Juliette , Robert Armstrong A. , Singh Gurpreet , Rojo Teófilo , Bruce Peter G. , Grey Clare P.
Published: August 2016

Mg substitution of a (sustainable) sodium-ion battery positive electrode material results in faster Na-ion motion and fewer structural changes on cycling.