bluuebunny/crossref_metadata_2025 huggingface dataset:
Was the Milky Way Bulge Formed from the Buckling Disk Instability, Hierarchical Collapse, Accretion of Clumps, or All of the Above?
Authors: Nataf David M.
Published: September 2017

The assembly of the Milky Way bulge is an old topic in astronomy, one now in a period of renewed and rapid development. That is due to tremendous advances in observations of bulge stars, motivating observations of both local and high-redshift galaxies, and increasingly sophisticated simulations. The dominant scenario for bulge formation is that of the Milky Way as a nearly pure disk galaxy, with the inner disk having formed a bar and buckled. This can potentially explain virtually all bulge stars with [Fe/H] ≳ −1.0, which comprise 95% of the stellar population. The evidence is the incredible success in N-body models of this type in making non-trivial, non-generic predictions, such as the rotation curve and velocity dispersion measured from radial velocities, and the spatial morphologies of the peanut/X-shape and the long bar. The classical bulge scenario, whereby the bulge formed from early dissipative collapse and mergers, remains viable for stars with [Fe/H] ≲ −1.0 and potentially a minority of the other stars. A classical bulge is expected from Λ-CDM cosmological simulations, can accentuate the properties of an existing bar in a hybrid system, and is most consistent with the bulge abundance trends such as [Mg/Fe], which are elevated relative to both the thin and thick disks. Finally, the clumpy-galaxy scenario is considered, as it is the correct description of most Milky Way precursors given observations of high-redshift galaxies. Simulations predict that these star-forming clumps will sometimes migrate to the centres of galaxies where they may form a bulge, and galaxies often include a bulge clump as well. They will possibly form a bar with properties consistent with those of the Milky Way, such as the exponential profile and metallicity gradient. Given the relative successes of these scenarios, the Milky Way bulge is plausibly of composite origin, with a classical bulge and/or inner halo numerically dominant for stars with [Fe/H] ≲ −1.0, a buckling thick disk for stars with − 1.0 ≲ [Fe/H]] ≲ -0.50 perhaps descended from the clumpy-galaxy phase, and a buckling thin disk for stars with [Fe/H] ≳ −0.50. Overlaps from these scenarios are uncertain throughout.
Scraping Public Co-Occurrences for Statistical Network Analysis of Political Elites
Authors: Mahdavi Paasha
Published: September 2017

Collecting network information on political elites using conventional methods such as surveys and text records is challenging in authoritarian and/or conflict-ridden states. I introduce a data collection method for elite networks using scraping algorithms to capture public co-appearances at political and social events. Validity checks using existing data show the method effectively replicates interaction-based networks but not networks based on behavioral similarities; in both cases, measurement error remains a concern. Applying the method to Nigeria illustrates that patronage—measured in terms of public connectivity—does not drive national oil companies appointments. Given that theories of elite behavior aim to understand individual-level interactions, the applicability of data using this technique is well-suited to situations where intrusive data collection is costly or prohibitive.
Cold–temperate transition surface and permafrost base (CTS-PB) as an environmental axis in glacier–permafrost relationship, based on research carried out on the Storglaciären and its forefield, northern Sweden
Authors: Dobiński Wojciech , Grabiec Mariusz , Glazer Michał
Published: September 2017

Here, we present empirical ground penetrating radar (GPR) and electroresistivity tomography data (ERT) to verify the cold-temperate transition surface-permafrost base (CTS-PB) axis theoretical model. The data were collected from Storglaciären, in Tarfala, Northern Sweden, and its forefield. The GPR results show a material relation between the glacial ice and the sediments incorporated in the glacier, and a geophysical relation between the “cold ice” and the “temperate ice” layers. Clearly identifying lateral glacier margins is difficult, as periglacial and glacial environments frequently overlap. In this case, we identified areas showing permafrost aggradation already under the glacier, particularly where the CTS is replaced by the PB surface. This structure appears as a result of the influence of a cold climate over both the glacial and periglacial environments. The results show how these surfaces form a specific continuous environmental axis; thus, both glacial and periglacial areas can be treated uniformly as a specific continuum in the geophysical sense. Similarly, other examples previously described also allow identifying a continuation of permafrost from the periglacial environment onto the glacial base. In addition, the ERT results show the presence of double-layered periglacial permafrost, possibly suggesting a past climatic fluctuation in the study area.
Lithological control on fracture cementation in the Keuper Marl (Triassic), north Somerset, UK
Authors: MENG QINGFENG , HOOKER JOHN , CARTWRIGHT JOE
Published: September 2017

The spatial arrangement of gypsum veins as preserved natural hydraulic fractures have been characterized in the Triassic Keuper Marl Formation (UK), a caprock for hydrocarbon reservoirs and CO2sequestration. The marls cropping out are subdivided into five discrete fracture units based on the presence and abundance of gypsum veins. The nodular gypsum in evaporite horizons provides excess gypsum for nodule-rooted horizontal gypsum veins. Our petrographic observations demonstrate that the development of gypsum veins in beds lacking macroscopic evaporites is closely associated with disseminated gypsum cement in the marls. We interpret that the gypsum veins in marl are sourced from disseminated gypsum cements in the host rocks, based on stratigraphic correlations, and much lower Sr concentrations than gypsum nodules. Gypsum was transported to adjacent veins mainly through diffusion in the low-permeability marls. The localization of gypsum veins and varied Sr concentrations of veins and nodules indicate that the diagenetic fluids are a mix of connate water with meteoric water rather than brines transported from evaporite beds along faults to non-evaporite beds. This results in the absence of gypsum fillings in fractures in rocks without primary gypsum cements. The study implies that the cementation of natural fractures in low-permeability rocks can highly depend on the presence of cement minerals in the host rock.
The Haitong Project: Exploring a collaborative approach to implement TBLT in primary classrooms in China
Authors: Zhu Yan , Shu Dingfang
Published: September 2017

As one of the two ‘educational special zones’ in China, Shanghai is launching a new round of curriculum reforms centring on lide shuren, viz. ‘fostering integrity and promoting rounded development of people’ (Hu 2012). Apart from piloting a new plan for Gaokao, the national college entrance examination in 2014, a ground-breaking endeavour by the Shanghai Municipal Education Commission was to establish 17 key research centres at higher institutions for 16 basic education subjects in an effort to push forward city-wide curriculum innovations through in-depth university-school collaborations. Founded in 2016, the Shanghai Centre for Research in English Language Education (SCRELE) is one of these key research platforms.
The integrated function modeling framework and its relation to function structures
Authors: Gericke Kilian , Eisenbart Boris
Published: September 2017

Research and industrial practice have produced a host of function models and modeling approaches over the last decades. Each of these is meant to support designers in their design endeavors. Industrial practice is excessively diversified in terms of contextual requirements, aims, and adopted processes; this automatically begs the question which of the existing models should be selected for application in a specific situation. This paper sets out to contribute to this discourse. It strives to benchmark the fairly novel integrated function modeling (IFM) framework against the well-established function structures modeling approach. The paper comparatively investigates the respective capabilities of the approaches, following the benchmarking protocol used earlier in relation to this Special Issue. Function structures are used as reference as they represent one of the most widespread function modeling approaches in research and practice. Both function structures and the IFM framework are exemplarily applied for modeling a glue gun. The gradual generation and refinement of the models is used to showcase their respective benefits and shortcomings. Eventually, the IFM framework is found to excel over function structures in terms of comprehensiveness and support for different types of function analyses. Finally, future research directions are proposed.
Comparing function structures and pruned function structures for market price prediction: An approach to benchmarking representation inferencing value
Authors: Gill Amaninder Singh , Summers Joshua D. , Turner Cameron J.
Published: September 2017

Benchmarking function modeling and representation approaches requires a direct comparison, including the inferencing support by the different approaches. To this end, this paper explores the value of a representation by comparing the ability of a representation to support reasoning based on varying amounts of information stored in the representational components of a function structure: vocabulary, grammar, and topology. This is done by classifying the previously developed functional pruning rules into vocabulary, grammatical, and topological classes and applying them to function structures available from an external design repository. The original and pruned function structures of electromechanical devices are then evaluated for how accurately market values can be predicted using the graph complexity connectivity method. The accuracy is found to be inversely related to the amount of information and level of detail. Applying the topological rule does not significantly impact the predictive power of the models, while applying the vocabulary rules and the grammar rules reduces the accuracy of the predictions. Finally, the least predictive model set is that which had all rules applied. In this manner, the value of a representation to predict or answer questions is quantified.
The Relationship between Competence and Patient Outcome with Low-Intensity Cognitive Behavioural Interventions
Authors: Branson Amanda , Myles Pamela , Mahdi Mishka , Shafran Roz
Published: September 2017

Background: Little is understood about the relationship between therapist competence and the outcomes of patients treated for common mental health disorders. Furthermore, the evidence is yet to extend to competence in the delivery of low-intensity cognitive behavioural interventions. Understanding this relationship is essential to the dissemination and implementation of low-intensity cognitive behavioural interventions. Aims: The aim of this study was to explore the relationship between Psychological Well-being Practitioner (PWP) competence and patient outcome within the framework of the British government's Improving Access to Psychological Therapies (IAPT) initiative. Method: Forty-seven PWPs treating 3688 patients participated. Relationships between PWP scores on three observed standardized clinical examinations and reliable change in patients’ symptoms of anxiety and depression were explored at two time points: during the year-long training phase, and over a 12-month follow-up. Results: Results indicated that patients treated by qualified PWPs achieved superior outcomes than those treated by trainees. Little support was found for a general association between practitioner competence in delivering low-intensity cognitive behavioural interventions and patient outcome, either during or post-training; however, significantly more patients of the most competent PWPs demonstrated reliable improvement in their symptoms of anxiety and depression than would be expected by chance alone and fewer deteriorated compared with those treated by the least competent PWPs. Conclusion: Results were indicative of a complex, non-linear relationship, with patient outcome affected by PWP status (trainee or qualified) and by competence at its extremes. The implications of these results for the dissemination and implementation of low-intensity cognitive behavioural interventions are discussed.
A Preliminary Investigation of Metacognitive Therapy and Habit Reversal as a Treatment for Trichotillomania
Authors: Shareh Hossein
Published: September 2017

Background: Not all patients suffering from trichotillomania (TTM) recover completely using CBT and of those that do, only a few maintain their recovery over time. Aims: The purpose of the present study was to investigate the effectiveness of metacognitive methods combined with habit reversal (MCT/HRT) in trichotillomania with a relatively long-term follow-up. Method: A case series (n = 8) and a randomized wait-list controlled trial (n = 34) design were conducted in this study. In the case series, three of the eight patients dropped out of the study. Therefore, TTM-related symptoms were evaluated in five patients suffering from TTM before and after brief metacognitive plus habit reversal therapy during 1-month, 6-month, and 12-month follow-ups. The treatment consisted of detached mindfulness (DM) techniques, ritual postponement and habit reversal training (HRT) in eight sessions. Results: All patients were responders at post-treatment in case series. After the 12-month follow-up, the results were associated with higher pre-treatment levels of self-esteem and global functioning and lower pre-treatment levels of depression and anxiety with nearly complete abstinence from hair pulling immediately after treatment. A randomized wait-list controlled trial with experimental (n = 17) and waiting list group (n = 17) was then conducted to confirm the case series results. There were significant differences between the two groups regarding changes in MGH-HPS, Y-BOCS-TM, RSES, GAF, BDI, BAI and self-monitoring. Therefore, the MCT/HRT treatment was found to be more effective than the waiting list group. Conclusions: A combined treatment including metacognitive and habit reversal techniques is remarkably effective in patients with TTM.
Niche for high abundant extremophilic microbial communities in an ancient crater
Authors: Albokari Majed , Al-Najjar Mohammad A. A. , Mashhour Ibrahim , Huraysi Abdulaziz
Published: September 2017

Al Wahbah Crater, located in a remote area in western Saudi Arabia as part of The Harrat extinct volcanic chain, is 2 km wide with a depth of 250 m. It is registered by the General Commission for Tourism and National Heritage as an ancient and archaeological site. The crater is subjected to extreme environmental conditions as its bottom is rarely subjected to rainfall and mudflows. Because of high temperature, high evaporation rates and extremely limited rainfall, the crater leaves behind dried thick white sodium phosphate crystals. Here, we studied the chemical composition and the microbial community composition using 16S rRNA pyrosequencing in different vertical layers (2, 20, 40, 60, 80 and 100 cm) of the crater sediment. Total sodium concentrations were 28 000– 46 700 ppm and calcium levels were 31 400– 56 500 ppm. In addition, samples were very sulphuric, with sulphate and sulphite levels exceeding 2157 ppm and 5.54 ppm, respectively. Ferric ions concentrations were <0.2 ppm, while nitrate, ammonium and nitrite levels were <2 ppm, 1.5 ppm and 0.05 ppm, respectively. Archaea dominated the surface and the bottom, while bacteria were most common at 20–60 cm. Extremely halophilic archaea and bacteria includingHalorhabdusspp.Halorubrumspp.,Salinibacter iranicusandHalorhodospira halophilawere identified in all samples. Moreover, the relative abundance ofHalanaerobiaceaeaccounted for 22% of the species in the top of the crater.S. iranicusand species belonging toHalorhabdusandHalorubrumthat were identified between 60 and 100 cm could be considered as extreme organisms.
Umsetzung problemloser als angenommen
Authors: Hahn Sabine
Published: September 2017

Zusammenfassung. Brigitte Wüthrich arbeitet seit 1985 als diplomierte Pflegefachfrau Psychiatrie. Heute ist sie Leiterin Pflege im Domicil Mon Bijou in Bern, einer Pflegeeinrichtung für betagte Menschen, die beim eigenständigen Leben und Wohnen Unterstützung brauchen.
Power and Persuasion: Processes by Which Perceived Power Can Influence Evaluative Judgments
Authors: Briñol Pablo , Petty Richard E. , Durso Geoffrey R. O. , Rucker Derek D.
Published: September 2017

The present review focuses on how power—as a perception regarding the self, the source of the message, or the message itself—affects persuasion. Contemporary findings suggest that perceived power can increase or decrease persuasion depending on the circumstances and thus might result in both short-term and long-term consequences for behavior. Given that perceptions of power can produce different, and even opposite, effects on persuasion, it might seem that any relationship is possible and thus prediction is elusive or impossible. In contrast, the present review provides a unified perspective to understand and organize the psychological literature on the relationship between perceived power and persuasion. To accomplish this objective, present review identifies distinct mechanisms by which perceptions of power can influence persuasion and discusses when these mechanisms are likely to operate. In doing so, this article provides a structured approach for studying power and persuasion via antecedents, consequences, underlying psychological processes, and moderators. Finally, the article also discusses how power can affect evaluative judgments more broadly.
Emotional Oddball: A Review on Variants, Results, and Mechanisms
Authors: Schlüter Helge , Bermeitinger Christina
Published: September 2017

It is of the utmost importance for an organism to rapidly detect and react to changes in its environment. The oddball paradigm has repeatedly been used to explore the underlying cognitive and neurophysiological components of change detection. It is also used to investigate the special role of emotional content in perception and attention (emotional oddball paradigm; EOP). In this article, the EOP is systematically reviewed. The EOP is, for instance, used as a tool to address questions as to what degree emotional deviant stimuli trigger orientation reactions, which role the emotional context plays in the processing of deviant information, and how the processing of emotional deviant information differs interindividually (including clinical populations). Two main variants with regard to the emotionality of standards and deviants are defined. Most of the identified EOP studies report EEG data but an overview of behavioral data is also provided in this review. We integrate evidence from 99 EOP experiments and shape the EOP's theoretical background under the consideration of other paradigms’ mechanisms and theories.
Proximal and Distal Intent: Toward a New Folk Theory of Intentional Action
Authors: Plaks Jason E. , Robinson Jeffrey S.
Published: September 2017

Inferences regarding actors’ intentions play an important role in social and moral cognition. Numerous studies have operationalized intentionality in a binary fashion (i.e., an act is either “intentional” or “unintentional”). The authors suggest, however, that when determining the degree to which an act was intentional, lay observers consider two independent dimensions: proximal intent (the actor's focus on the means) and distal intent (the actor's focus on the end). They describe how the proximal intent/distal intent (PIDI) approach allows researchers to understand observers’ intent-related judgments with greater precision. The authors review studies highlighting a range of variables that lead perceivers to prioritize either proximal intent or distal intent in their social and moral judgment. They describe how previous findings in the literature may be reinterpreted in light of the PIDI framework. Finally, they suggest ways in which the PIDI framework implies novel directions for future research on moral cognition.
Disrupting CCT-β : β-tubulin selectively kills CCT-β overexpressed cancer cells through MAPKs activation
Authors: Liu Yan-Jin , Kumar Vathan , Lin Yuan-Feng , Liang Po-Huang
Published: September 2017

We have previously demonstrated the ability of I-Trp to disrupt the protein–protein interaction of β-tubulin with chaperonin-containing TCP-1β (CCT-β). This caused more severe apoptosis in multidrug-resistant MES-SA/Dx5, compared to MES-SA, due to its higher CCT-β overexpression. In this study, we screened a panel of cancer cell lines, finding CCT-β overexpression in the triple-negative breast cancer cell line MDA-MB-231, colorectal cancer cell lines Colo205 and HCT116, and a gastric cancer cell line MKN-45. Thus, I-Trp killed these cancers with sub- to low-μM EC50, whereas it was non-toxic to MCF-10A. We then synthesized analogs of I-Trp and evaluated their cytotoxicity. Furthermore, apoptotic mechanism investigations revealed the activation of both protein ubiquitination/degradation and ER-associated protein degradation pathways. These pathways proceeded through activation of MAPKs at the onset of CCT-β : β-tubulin complex disruption. We thus establish an effective strategy to treat CCT-β overexpressed cancers by disrupting the CCT-β : β-tubulin complex.
Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
Authors: Xiao Xinhua , Li Huiliang , Jin Huizi , Jin Jin , Yu Miao , Ma Chunmin , Tong Yin , Zhou Li , Lei Hu , Xu Hanzhang , Zhang Weidong , Liu Wei , Wu Yingli
Published: September 2017

Despite great advancements in the treatment of non-Hodgkin lymphoma (NHL), sensitivity of different subtypes to therapy varies. Targeting the aberrant activation NF-κB signaling pathways in lymphoid malignancies is a promising strategy. Here, we report that 11(13)-dehydroivaxillin (DHI), a natural compound isolated from the Carpesium genus, induces growth inhibition and apoptosis of NHL cells. Multiple signaling cascades are influenced by DHI in NHL cells. PI3K/AKT and ERK are activated or inhibited in a cell type dependent manner, whereas NF-κB signaling pathway was inhibited in all the NHL cells tested. Applying the cellular thermal shift assay, we further demonstrated that DHI directly interacts with IKKα/IKKβ in NHL cells. Interestingly, DHI treatment also reduced the IKKα/IKKβ protein level in NHL cells. Consistent with this finding, knockdown of IKKα/IKKβ inhibits cell proliferation and enhances DHI-induced proliferation inhibition. Overexpression of p65, p52 or RelB partially reverses DHI-induced cell growth inhibition. Furthermore, DHI treatment significantly inhibits the growth of NHL cell xenografts. In conclusion, we demonstrate that DHI exerts anti-NHL effect in vitro and in vivo, through a cumulative effect on NF-κB and other pathways. DHI may serve as a promising lead compound for the therapy of NHL.
Lithium titanate hydrates with superfast and stable cycling in lithium ion batteries
Authors: Wang Shitong , Quan Wei , Zhu Zhi , Yang Yong , Liu Qi , Ren Yang , Zhang Xiaoyi , Xu Rui , Hong Ye , Zhang Zhongtai , Amine Khalil , Tang Zilong , Lu Jun , Li Ju
Published: September 2017

Lithium titanate and titanium dioxide are two best-known high-performance electrodes that can cycle around 10,000 times in aprotic lithium ion electrolytes. Here we show there exists more lithium titanate hydrates with superfast and stable cycling. That is, water promotes structural diversity and nanostructuring of compounds, but does not necessarily degrade electrochemical cycling stability or performance in aprotic electrolytes. As a lithium ion battery anode, our multi-phase lithium titanate hydrates show a specific capacity of about 130 mA h g−1 at ~35 C (fully charged within ~100 s) and sustain more than 10,000 cycles with capacity fade of only 0.001% per cycle. In situ synchrotron diffraction reveals no 2-phase transformations, but a single solid-solution behavior during battery cycling. So instead of just a nanostructured intermediate to be calcined, lithium titanate hydrates can be the desirable final destination.
Potential for natural evaporation as a reliable renewable energy resource
Authors: Cavusoglu Ahmet-Hamdi , Chen Xi , Gentine Pierre , Sahin Ozgur
Published: September 2017

About 50% of the solar energy absorbed at the Earth’s surface drives evaporation, fueling the water cycle that affects various renewable energy resources, such as wind and hydropower. Recent advances demonstrate our nascent ability to convert evaporation energy into work, yet there is little understanding about the potential of this resource. Here we study the energy available from natural evaporation to predict the potential of this ubiquitous resource. We find that natural evaporation from open water surfaces could provide power densities comparable to current wind and solar technologies while cutting evaporative water losses by nearly half. We estimate up to 325 GW of power is potentially available in the United States. Strikingly, water’s large heat capacity is sufficient to control power output by storing excess energy when demand is low, thus reducing intermittency and improving reliability. Our findings motivate the improvement of materials and devices that convert energy from evaporation.
TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine
Authors: Bain C. C. , Montgomery J. , Scott C. L. , Kel J. M. , Girard-Madoux M. J. H. , Martens L. , Zangerle-Murray T. F. P. , Ober-Blöbaum J. , Lindenbergh-Kortleve D. , Samsom J. N. , Henri S. , Lawrence T. , Saeys Y. , Malissen B. , Dalod M. , Clausen B. E. , Mowat A. McI.
Published: September 2017

CD103+CD11b+dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFβR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion ofTgfbr1results in markedly fewer intestinal CD103+CD11b+DCs and a reciprocal increase in the CD103−CD11b+dendritic cell subset. Transcriptional profiling identifies markers that define the CD103+CD11b+DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+DCs in CD11c-Cre.Tgfbr1fl/flmice reflects defective differentiation from CD103−CD11b+intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+regulatory T cells in vitro and in vivo, and by reduced numbers of endogenous Th17 cells in the intestinal mucosa. Thus, TGFβR1-mediated signalling may explain the tissue-specific development of these unique DCs.
A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis
Authors: Wang Jing-Rong , Gao Wei-Na , Grimm Rudolf , Jiang Shibo , Liang Yong , Ye Hua , Li Zhan-Guo , Yau Lee-Fong , Huang Hao , Liu Ju , Jiang Min , Meng Qiong , Tong Tian-Tian , Huang Hai-Hui , Lee Stephanie , Zeng Xing , Liu Liang , Jiang Zhi-Hong
Published: September 2017

N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect. Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip. We discover 20 sulfated and 4 acetylated N-glycans on IgGs. Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans. From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients. This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.
Bioenergetic state regulates innate inflammatory responses through the transcriptional co-repressor CtBP
Authors: Shen Yiguo , Kapfhamer David , Minnella Angela M. , Kim Ji-Eun , Won Seok Joon , Chen Yanting , Huang Yong , Low Ley Hian , Massa Stephen M. , Swanson Raymond A.
Published: September 2017

The innate inflammatory response contributes to secondary injury in brain trauma and other disorders. Metabolic factors such as caloric restriction, ketogenic diet, and hyperglycemia influence the inflammatory response, but how this occurs is unclear. Here, we show that glucose metabolism regulates pro-inflammatory NF-κB transcriptional activity through effects on the cytosolic NADH:NAD+ ratio and the NAD(H) sensitive transcriptional co-repressor CtBP. Reduced glucose availability reduces the NADH:NAD+ ratio, NF-κB transcriptional activity, and pro-inflammatory gene expression in macrophages and microglia. These effects are inhibited by forced elevation of NADH, reduced expression of CtBP, or transfection with an NAD(H) insensitive CtBP, and are replicated by a synthetic peptide that inhibits CtBP dimerization. Changes in the NADH:NAD+ ratio regulate CtBP binding to the acetyltransferase p300, and regulate binding of p300 and the transcription factor NF-κB to pro-inflammatory gene promoters. These findings identify a mechanism by which alterations in cellular glucose metabolism can influence cellular inflammatory responses.
Evidence for percolation diffusion of cations and reordering in disordered pyrochlore from accelerated molecular dynamics
Authors: Perriot Romain , Uberuaga Blas P. , Zamora Richard J. , Perez Danny , Voter Arthur F.
Published: September 2017

Diffusion in complex oxides is critical to ionic transport, radiation damage evolution, sintering, and aging. In complex oxides such as pyrochlores, anionic diffusion is dramatically affected by cation disorder. However, little is known about how disorder influences cation transport. Here, we report results from classical and accelerated molecular dynamics simulations of vacancy-mediated cation diffusion in Gd2Ti2O7 pyrochlore, on the microsecond timescale. We find that diffusion is slow at low levels of disorder, while higher disorder allows for fast diffusion, which is then accompanied by antisite annihilation and reordering, and thus a slowing of cation transport. Cation diffusivity is therefore not constant, but decreases as the material reorders. We also show that fast cation diffusion is triggered by the formation of a percolation network of antisites. This is in contrast with observations from other complex oxides and disordered media models, suggesting a fundamentally different relation between disorder and mass transport.
Dual-comb spectroscopic ellipsometry
Authors: Minamikawa Takeo , Hsieh Yi-Da , Shibuya Kyuki , Hase Eiji , Kaneoka Yoshiki , Okubo Sho , Inaba Hajime , Mizutani Yasuhiro , Yamamoto Hirotsugu , Iwata Tetsuo , Yasui Takeshi
Published: September 2017

Spectroscopic ellipsometry is a means of investigating optical and dielectric material responses. Conventional spectroscopic ellipsometry is subject to trade-offs between spectral accuracy, resolution, and measurement time. Polarization modulation has afforded poor performance because of its sensitivity to mechanical vibrational noise, thermal instability, and polarization-wavelength dependency. We combine spectroscopic ellipsometry with dual-comb spectroscopy, namely, dual-comb spectroscopic ellipsometry. Dual-comb spectroscopic ellipsometry (DCSE). DCSE directly and simultaneously obtains the ellipsometric parameters of the amplitude ratio and phase difference between s-polarized and p-polarized light signals with ultra-high spectral resolution and no polarization modulation, beyond the conventional limit. Ellipsometric evaluation without polarization modulation also enhances the stability and robustness of the system. In this study, we construct a polarization-modulation-free DCSE system with a spectral resolution of up to 1.2 × 10−5 nm throughout the spectral range of 1514–1595 nm and achieved an accuracy of 38.4 nm and a precision of 3.3 nm in the measurement of thin-film samples.
Controlled manipulation of oxygen vacancies using nanoscale flexoelectricity
Authors: Das Saikat , Wang Bo , Cao Ye , Rae Cho Myung , Jae Shin Yeong , Mo Yang Sang , Wang Lingfei , Kim Minu , Kalinin Sergei V. , Chen Long-Qing , Noh Tae Won
Published: September 2017

Oxygen vacancies, especially their distribution, are directly coupled to the electromagnetic properties of oxides and related emergent functionalities that have implications for device applications. Here using a homoepitaxial strontium titanate thin film, we demonstrate a controlled manipulation of the oxygen vacancy distribution using the mechanical force from a scanning probe microscope tip. By combining Kelvin probe force microscopy imaging and phase-field simulations, we show that oxygen vacancies can move under a stress-gradient-induced depolarisation field. When tailored, this nanoscale flexoelectric effect enables a controlled spatial modulation. In motion, the scanning probe tip thereby deterministically reconfigures the spatial distribution of vacancies. The ability to locally manipulate oxygen vacancies on-demand provides a tool for the exploration of mesoscale quantum phenomena and engineering multifunctional oxide devices.
Bacterial outer membrane vesicles suppress tumor by interferon-γ-mediated antitumor response
Authors: Kim Oh Youn , Park Hyun Taek , Dinh Nhung Thi Hong , Choi Seng Jin , Lee Jaewook , Kim Ji Hyun , Lee Seung-Woo , Gho Yong Song
Published: September 2017

Gram-negative bacteria actively secrete outer membrane vesicles, spherical nano-meter-sized proteolipids enriched with outer membrane proteins, to the surroundings. Outer membrane vesicles have gained wide interests as non-living complex vaccines or delivery vehicles. However, no study has used outer membrane vesicles in treating cancer thus far. Here we investigate the potential of bacterial outer membrane vesicles as therapeutic agents to treat cancer via immunotherapy. Our results show remarkable capability of bacterial outer membrane vesicles to effectively induce long-term antitumor immune responses that can fully eradicate established tumors without notable adverse effects. Moreover, systematically administered bacterial outer membrane vesicles specifically target and accumulate in the tumor tissue, and subsequently induce the production of antitumor cytokines CXCL10 and interferon-γ. This antitumor effect is interferon-γ dependent, as interferon-γ-deficient mice could not induce such outer membrane vesicle-mediated immune response. Together, our results herein demonstrate the potential of bacterial outer membrane vesicles as effective immunotherapeutic agent that can treat various cancers without apparent adverse effects.
Value of Measuring Anti-Carbamylated Protein Antibodies for Classification on Early Arthritis Patients
Authors: Regueiro Cristina , Nuño Laura , Ortiz Ana M. , Peiteado Diana , Villalba Alejandro , Pascual-Salcedo Dora , Martínez-Feito Ana , González-Alvaro Isidoro , Balsa Alejandro , González Antonio
Published: September 2017

Classification of patients with rheumatoid arthritis (RA) as quickly as possible improves their prognosis. This reason motivates specially dedicated early arthritis (EA) clinics. Here, we have used 1062 EA patients with two years of follow-up to explore the value of anti-carbamylated protein (anti-CarP) antibodies, a new type of RA specific autoantibodies, for classification. Specifically, we aimed to determine whether the addition of anti-CarP antibodies to IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are helpful in RA classification, improves it or not. Our analysis showed that incorporation of the anti-CarP antibodies to combinations of the other two antibodies (all joint by the OR Boolean operator) produces a modest increase in sensitivity (2.2% higher), at the cost of decreased specificity (8.1% lower). The cost-benefit ratio was more favorable in the patients lacking the other autoantibodies. However, it did not improve by considering different titer levels of the anti-CarP antibodies, or after exhaustively exploring other antibody combinations. Therefore, the place in RA classification of these antibodies is questionable in the context of current treatments and biomarkers. This conclusion does not exclude their potential value for stratifying patients in joint damage, disease activity, disability, or mortality categories.
A Dual-Specific Targeting Approach Based on the Simultaneous Recognition of Duplex and Quadruplex Motifs
Authors: Nguyen Thi Quynh Ngoc , Lim Kah Wai , Phan Anh Tuân
Published: September 2017

Small-molecule ligands targeting nucleic acids have been explored as potential therapeutic agents. Duplex groove-binding ligands have been shown to recognize DNA in a sequence-specific manner. On the other hand, quadruplex-binding ligands exhibit high selectivity between quadruplex and duplex, but show limited discrimination between different quadruplex structures. Here we propose a dual-specific approach through the simultaneous application of duplex- and quadruplex-binders. We demonstrated that a quadruplex-specific ligand and a duplex-specific ligand can simultaneously interact at two separate binding sites of a quadruplex-duplex hybrid harbouring both quadruplex and duplex structural elements. Such a dual-specific targeting strategy would combine the sequence specificity of duplex-binders and the strong binding affinity of quadruplex-binders, potentially allowing the specific targeting of unique quadruplex structures. Future research can be directed towards the development of conjugated compounds targeting specific genomic quadruplex-duplex sites, for which the linker would be highly context-dependent in terms of length and flexibility, as well as the attachment points onto both ligands.
Circulating Mycobacterium tuberculosis DosR latency antigen-specific, polyfunctional, regulatory IL10+ Th17 CD4 T-cells differentiate latent from active tuberculosis
Authors: Rakshit Srabanti , Adiga Vasista , Nayak Soumya , Sahoo Pravat Nalini , Sharma Prabhat Kumar , van Meijgaarden Krista E. , UK J. Anto Jesuraj , Dhar Chirag , Souza George D. , Finak Greg , De Rosa Stephen C. , Ottenhoff Tom H. M. , Vyakarnam Annapurna
Published: September 2017

The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB. The polyfunctionality score integrating up to 31 DosR-specific CD4 T-cell functional profiles was significantly higher in LTBI than EPTB or PTB subjects. Further analysis of 256 DosR-specific T-cell functional profiles identified regulatory IL10 + Th17 cells (IL10+IL17A+IL17F+IL22+) to be significantly enriched in LTBI; in contrast to pro-inflammatory Th17 cells (IFNγ+IL17A+/IL10−) in the blood and lung of EPTB and PTB subjects respectively. A blood polyfunctional, Mtb DosR latency antigen specific, regulatory, central memory response is therefore a novel functional component of T-cell immunity in latent TB and potential correlate of protection.
Energetics and mechanism of anion permeation across formate-nitrite transporters
Authors: Atkovska Kalina , Hub Jochen S.
Published: September 2017

Formate-nitrite transporters (FNTs) facilitate the translocation of monovalent polyatomic anions, such as formate and nitrite, across biological membranes. FNTs are widely distributed among pathogenic bacteria and eukaryotic parasites, but they lack human homologues, making them attractive drug targets. The mechanisms and energetics involved in anion permeation across the FNTs have remained largely unclear. Both, channel and transporter mode of function have been proposed, with strong indication of proton coupling to the permeation process. We combine molecular dynamics simulations, quantum mechanical calculations, and pKa calculations, to compute the energetics of the complete permeation cycle of an FNT. We find that anions as such, are not able to traverse the FNT pore. Instead, anion binding into the pore is energetically coupled to protonation of a centrally located histidine. In turn, the histidine can protonate the permeating anion, thereby enabling its release. Such mechanism can accommodate the functional diversity among the FNTs, as it may facilitate both, export and import of substrates, with or without proton co-transport. The mechanism excludes proton leakage via the Grotthuss mechanism, and it rationalises the selectivity for weak acids.
Clinical and radiological diversity in genetically confirmed primary familial brain calcification
Authors: Koyama Shingo , Sato Hidenori , Kobayashi Ryota , Kawakatsu Shinobu , Kurimura Masayuki , Wada Manabu , Kawanami Toru , Kato Takeo
Published: September 2017

Primary familial brain calcification (PFBC) is a rare neuropsychiatric disorder with characteristic symmetrical brain calcifications. Patients with PFBC may have a variety of symptoms, although they also may be clinically asymptomatic. Parkinsonism is one of the most common movement disorders; however, the underlying mechanism remains unclear. This condition is typically transmitted in an autosomal dominant fashion. To date, mutations in SLC20A2, PDGFRB, PDGFB, and XPR1 have been reported to cause PFBC. The aim of the study was to identify the genetic cause of brain calcification in probands from three PFBC families and in 8 sporadic patients and to perform clinical and radiological assessments focusing on parkinsonism in mutation carriers. Three familial PFBC probands and their relatives and eight sporadic patients affected with brain calcifications were enrolled in this study. Whole-exome sequencing identified three novel mutations: c.269G > T, p.(Gly90Val) and c.516+1G > A in SLC20A2 in familial cases, and c.602-1G > T in PDGFB in a sporadic patient. The c.516+1G > A mutation resulted in exon 4 skipping in SLC20A2 (p.Val144Glyfs*85). Dopamine transporter single photon emission computed tomography using 123I-ioflupane and 123I-metaiodobenzylguanidine cardiac scintigraphy revealed pre-synaptic dopaminergic deficit and cardiac sympathetic nerve dysfunction in two SLC20A2-related PFBC patients with parkinsonism.
Identification of Genes Involved in Chemoreception in Plutella xyllostella by Antennal Transcriptome Analysis
Authors: Yang Shiyong , Cao Depan , Wang Guirong , Liu Yang
Published: September 2017

Perception of environmental and habitat cues is of significance for insect survival and reproduction. Odor detection in insects is mediated by a number of proteins in antennae such as odorant receptors (ORs), ionotropic receptors (IRs), odorant binding proteins (OBPs), chemosensory proteins (CSPs), sensory neuron membrane proteins (SNMPs) and odorant degrading enzymes. In this study, we sequenced and assembled the adult male and female antennal transcriptomes of a destructive agricultural pest, the diamondback moth Plutella xyllostella. In these transcriptomes, we identified transcripts belonging to 6 chemoreception gene families related to ordor detection, including 54 ORs, 16 IRs, 7 gustatory receptors (GRs), 15 CSPs, 24 OBPs and 2 SNMPs. Semi-quantitative reverse transcription PCR analysis of expression patterns indicated that some of these ORs and IRs have clear sex-biased and tissue-specific expression patterns. Our results lay the foundation for future characterization of the functions of these P. xyllostella chemosensory receptors at the molecular level and development of novel semiochemicals for integrated control of this agricultural pest.
Mllt10 knockout mouse model reveals critical role of Af10-dependent H3K79 methylation in midfacial development
Authors: Ogoh Honami , Yamagata Kazutsune , Nakao Tomomi , Sandell Lisa L. , Yamamoto Ayaka , Yamashita Aiko , Tanga Naomi , Suzuki Mai , Abe Takaya , Kitabayashi Issay , Watanabe Toshio , Sakai Daisuke
Published: September 2017

Epigenetic regulation is required to ensure the precise spatial and temporal pattern of gene expression that is necessary for embryonic development. Although the roles of some epigenetic modifications in embryonic development have been investigated in depth, the role of methylation at lysine 79 (H3K79me) is poorly understood. Dot1L, a unique methyltransferase for H3K79, forms complexes with distinct sets of co-factors. To further understand the role of H3K79me in embryogenesis, we generated a mouse knockout of Mllt10, the gene encoding Af10, one Dot1L complex co-factor. We find homozygous Mllt10 knockout mutants (Mllt10-KO) exhibit midline facial cleft. The midfacial defects of Mllt10-KO embryos correspond to hyperterolism and are associated with reduced proliferation of mesenchyme in developing nasal processes and adjacent tissue. We demonstrate that H3K79me level is significantly decreased in nasal processes of Mllt10-KO embryos. Importantly, we find that expression of AP2α, a gene critical for midfacial development, is directly regulated by Af10-dependent H3K79me, and expression AP2α is reduced specifically in nasal processes of Mllt10-KO embryos. Suppression of H3K79me completely mimicked the Mllt10-KO phenotype. Together these data are the first to demonstrate that Af10-dependent H3K79me is essential for development of nasal processes and adjacent tissues, and consequent midfacial formation.
Improvement of a fermentation process for the production of two PfAMA1-DiCo-based malaria vaccine candidates in Pichia pastoris
Authors: Kastilan Robin , Boes Alexander , Spiegel Holger , Voepel Nadja , Chudobová Ivana , Hellwig Stephan , Buyel Johannes Felix , Reimann Andreas , Fischer Rainer
Published: September 2017

Pichia pastorisis a simple and powerful expression platform that has the ability to produce a wide variety of recombinant proteins, ranging from simple peptides to complex membrane proteins. A well-established fermentation strategy is available comprising three main phases: a batch phase, followed by a glycerol fed-batch phase that increases cell density, and finally an induction phase for product expression using methanol as the inducer. We previously used this three-phase strategy at the 15-L scale to express three different AMA1-DiCo-based malaria vaccine candidates to develop a vaccine cocktail. For two candidates, we switched to a two-phase strategy lacking the intermediate glycerol fed-batch phase. The new strategy not only provided a more convenient process flow but also achieved 1.5-fold and 2.5-fold higher space-time yields for the two candidates, respectively, and simultaneously reduced the final cell mass by a factor of 1.3, thus simplifying solid–liquid separation. This strategy also reduced the quantity of host cell proteins that remained to be separated from the two vaccine candidates (by 34% and 13%, respectively), thus reducing the effort required in the subsequent purification steps. Taken together, our new fermentation strategy increased the overall fermentation performance for the production of two different AMA1-DiCo-based vaccine candidates.