bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Confucian Values Deter Chinese Citizens’ Support for Democracy?
Authors: Zhai Yida
Published: December 2016

The cultural prerequisites of democracy have been receiving considerable attention over the past decades. Confucian values are regarded as incompatible with liberal democracy and are considered to impede democratization. This article explores the effect of Confucian values on the commitment of ordinary Chinese people to democracy. Support for democracy is divided into attachment to democracy and adherence to liberal democratic values. Attachment to democracy indicates explicit support for democracy, while adherence to liberal democratic values reflects implicit support for democracy. This study examines the impacts of Confucian values on each of these areas. The results show that there was no evidence that Confucian values inhibit the Chinese public's support for democracy in a democratic transition, but they are negatively connected to liberal democratic values, which are fundamental to the resilience and consolidation of a fledgling democracy. However, liberal democratic values are prone to increase with the generational shift.
Kognitive Kompetenzen und kognitive Bewältigungsstrategien im Vor- und Grundschulalter
Authors: Piekny Jeanette , Thomsen Tamara , Schuchardt Kirsten , Lessing Nora , Greve Werner , Mähler Claudia
Published: December 2016

Zusammenfassung. Das Ziel dieser Studie bestand darin, Erkenntnisse zu Bedingungen und Wechselwirkungen in der Entwicklung kognitiver Kompetenzen und Bewältigungsstrategien im Vor- und Grundschulalter zu gewinnen. Anhand eines längsschnittlichen Designs im Altersbereich von 5 bis10 Jahren wurde an einer Stichprobe von 198 Kindern untersucht, welche kognitiven Kompetenzen (Theory of Mind, Exekutive Funktionen, Intelligenz, Flexibles Hypothesenbilden) die Nutzungshäufigkeit von Bewältigungsstrategien (Akzeptanz, Positive Neubewertung, Relativieren, Positive Refokussierung) vorhersagen, und ob Wechselwirkungen zwischen dem Flexiblen Hypothesenbilden und Bewältigungsstrategien im Grundschulalter bestehen. Pfadanalysen zeigten, dass kognitiv ausgerichtete Bewältigungsstrategien in Beziehung zum Flexiblen Hypothesenbilden stehen, während affektiv ausgerichtete Strategien keinen Zusammenhang zum Flexiblen Hypothesenbilden aufwiesen. Die Ergebnisse werden in Bezug auf Interventions- und Präventionsmöglichkeiten diskutiert.
Kognitive Fähigkeiten und Lesekompetenz
Authors: Tischler Tanja , Daseking Monika , Petermann Franz
Published: December 2016

Zusammenfassung. In der vorliegenden Studie wird der Zusammenhang zwischen kognitiven Fähigkeiten und der Lesefertigkeit bei Schulkindern untersucht. Anhand einer Stichprobe von 101 deutschsprachigen Kindern im Alter zwischen 7 und 16 Jahren wurden Zusammenhänge zwischen den verschiedenen Indizes der Wechsler Intelligence Scale for Children-4th Edition, WISC-IV ( Petermann & Petermann, 2011 ), und den Leistungen in zwei standardisierten Lesetests analysiert. Die Ergebnisse deuten auf einen umschriebenen Einfluss bestimmter Intelligenzbereiche auf die Qualität der Lesefertigkeit hin. Dies unterstützt die in den Leitlinien der Deutschen Gesellschaft für Kinder- und Jugendpsychiatrie und -psychotherapie et al. ( DGKJP; 2015 ) empfohlene Verwendung eines IQ-Diskrepanzkriteriums, auch unter der Verwendung differenzierter Intelligenztests, wie der aktuellen Version des Wechsler Intelligenztests für Kinder und Jugendliche, WISC-IV.
Stressverarbeitung, Lebensqualität und körperliche Beanspruchungssymptome bei Kindern und Jugendlichen
Authors: Hampel Petra , Petermann Franz
Published: December 2016

Zusammenfassung. In der vorliegenden Studie wurden hauptsächlich die Geschlechts- und Alterseffekte auf die Stressverarbeitung, gesundheitsbezogene Lebensqualität und körperliche Beanspruchungssymptomatik untersucht. Ferner sollte noch der Einfluss von Stressverarbeitungstypen auf die gesundheitsbezogene Lebensqualität und körperliche Beanspruchungssymptomatik überprüft werden. Hierfür wurden N = 577 Kinder und Jugendliche im Alter zwischen neun und 16 Jahren anhand des Stressverarbeitungsfragebogens für Kinder und Jugendliche, des KIDSCREEN-27 und dreier Items zur körperlichen Beanspruchungssymptomatik befragt. Die zweifaktoriellen multivariaten Varianzanalysen mit den unabhängigen Faktoren „Geschlecht“ und „Klassenstufe“ (4., 5., 7. vs. 9. Klasse) ergaben ein ungünstiges Stressverarbeitungsprofil, eine geringere Lebensqualität und eine erhöhte körperliche Beanspruchungssymptomatik bei den Älteren bzw. bei den Mädchen. Außerdem stellten Varianzanalysen eine höhere Lebensqualität und geringere körperliche Beanspruchungssymptomatik bei der Gruppe mit einem adaptiven Stressverarbeitungsstil im Vergleich zu der Gruppe mit einem maladaptiven Stil und der Gruppe mit insgesamt hohen Ausprägungen in der Stressverarbeitung fest. Die Befunde unterstützen die Bedeutung geschlechtssensibler, altersangepasster Gesundheitsförderprogramme im Grundschulalter.
N-Myc overexpression increases cisplatin resistance in neuroblastoma via deregulation of mitochondrial dynamics
Authors: Casinelli Gabriella , LaRosa Jeff , Sharma Manika , Cherok Edward , Banerjee Swati , Branca Maria , Edmunds Lia , Wang Yudong , Sims-Lucas Sunder , Churley Luke , Kelly Samantha , Sun Ming , Stolz Donna , Graves J Anthony
Published: December 2016

N-Myc is a global transcription factor that regulates the expression of genes involved in a number of essential cellular processes including: ribosome biogenesis, cell cycle and apoptosis. Upon deregulation, N-Myc can drive pathologic expression of many of these genes, which ultimately defines its oncogenic potential. Overexpression of N-Myc has been demonstrated to contribute to tumorigenesis, most notably for the pediatric tumor, neuroblastoma. Herein, we provide evidence that deregulated N-Myc alters the expression of proteins involved in mitochondrial dynamics. We found that N-Myc overexpression leads to increased fusion of the mitochondrial reticulum secondary to changes in protein expression due to aberrant transcriptional and post-translational regulation. We believe the structural changes in the mitochondrial network in response to N-Myc amplification in neuroblastoma contributes to two important aspects of tumor development and maintenance—bioenergetic alterations and apoptotic resistance. Specifically, we found that N-Myc overexpressing cells are resistant to programmed cell death in response to exposure to low doses of cisplatin, and demonstrated that this was dependent on increased mitochondrial fusion. We speculate that these changes in mitochondrial structure and function may contribute significantly to the aggressive clinical ph9enotype of N-Myc amplified neuroblastoma.
Role and regulation of Cdc25A phosphatase in neuron death induced by NGF deprivation or β-amyloid
Authors: Chatterjee Nandini , Sanphui Priyankar , Kemeny Stav , Greene Lloyd A , Biswas Subhas C
Published: December 2016

Neuron death during development and in Alzheimer’s disease (AD) is associated with aberrant regulation/induction of cell cycle proteins. However, the proximal events in this process are unknown. Cell cycle initiation requires dephosphorylation of cyclin-dependent kinases by cell division cycle 25A (Cdc25A). Here, we show that Cdc25A is essential for neuronal death in response to NGF deprivation or β-amyloid (Aβ) treatment and describe the mechanisms by which it is regulated in these paradigms. Cdc25A mRNA, protein and Cdc25A phosphatase activity were induced by NGF deprivation and Aβ treatment. Enhanced Cdc25A expression was also observed in rat brains infused with Aβ and in Aβ-overexpressing AβPPswe-PS1dE9 mice. In cultured neurons Cdc25A inhibition by chemical inhibitors or shRNA prevented cell death and neurite degeneration caused by NGF deprivation or Aβ. Additionally, Cdc25A inhibition diminished distal signaling events including Cdk-dependent elevation of phospho-pRb and subsequent caspase-3 activation. Mechanism studies revealed that Cdc25A induction by NGF deprivation and Aβ is mediated by activation of Forkhead transcription factors that in turn suppress miR-21, a negative regulator of Cdc25A. Our studies thus identify Cdc25A as a required upstream element of the apoptotic cell cycle pathway that is required for neuron death in response to trophic factor deprivation and to Aβ exposure and therefore as a potential target to suppress pathologic neuron death.
Regulation of VDAC trafficking modulates cell death
Authors: Dubey Ashvini K , Godbole Ashwini , Mathew M K
Published: December 2016

The voltage-dependent anion channel (VDAC) and mitochondria-associated hexokinase (HxK) have crucial roles in both cell survival and death. Both the individual abundances and their ratio seem to influence the balance of survival and death and are thus critical in scenarios, such as neurodegeneration and cancer. Elevated levels of both VDAC and HxK have been reported in cancerous cells. Physical interaction is surmised and specific residues or regions involved have been identified, but details of the interaction and the mechanism by which it modulates survival are yet to be elucidated. We and others have shown that heterologous expression of VDAC can induce cell death, which can be mitigated by concomitant overexpression of HxK. We have also observed that upon overexpression, fluorescently tagged VDAC is distributed between the cytosol and mitochondria. In this study, we show that cell death ensues only when the protein, which is synthesized on cytoplasmic ribosomes, migrates to the mitochondrion. Further, coexpression of rat HxK II (rHxKII) can delay the translocation of human VDAC1 (hVDAC1) protein to mitochondria and thereby inhibit VDAC-induced cell death. Variation in the level of HxK protein as seen endogenously in different cell lines, or as experimentally manipulated by silencing and overexpression, can lead to differential VDAC translocation kinetics and related cell death. The N-terminal region of HxK and the Glu73 residue of hVDAC1, which have previously been implicated in a physical interaction, are required for cytosolic retention of VDAC. Finally, we show that, in otherwise unperturbed cells in culture, there is a small but significant amount of soluble VDAC in the cytosol present in a complex with HxK. This complex could well determine how a cell is poised with respect to incoming thanatopic signals, thereby tilting the survival/death balance in pharmacologically interesting situations, such as neurodegeneration and cancer.
Role of syn-eruptive plagioclase disequilibrium crystallization in basaltic magma ascent dynamics
Authors: La Spina G. , Burton M. , de’ Michieli Vitturi M. , Arzilli F.
Published: December 2016

Timescales of magma ascent in conduit models are typically assumed to be much longer than crystallization and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallization and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Here we use observations from Mount Etna’s 2001 eruption and a magma ascent model to constrain timescales for crystallization and exsolution processes. Our results show that plagioclase reaches equilibrium in 1–2 h, whereas ascent times were <1 h. Using these new constraints on disequilibrium plagioclase crystallization we also reproduce observed crystal abundances for different basaltic eruptions. The strong relation between magma ascent rate and disequilibrium crystallization and exsolution plays a key role in controlling eruption dynamics in basaltic volcanism.
Superconductivity in the antiperovskite Dirac-metal oxide Sr3−xSnO
Authors: Oudah Mohamed , Ikeda Atsutoshi , Hausmann Jan Niklas , Yonezawa Shingo , Fukumoto Toshiyuki , Kobayashi Shingo , Sato Masatoshi , Maeno Yoshiteru
Published: December 2016

Investigations of perovskite oxides triggered by the discovery of high-temperature and unconventional superconductors have had crucial roles in stimulating and guiding the development of modern condensed-matter physics. Antiperovskite oxides are charge-inverted counterpart materials to perovskite oxides, with unusual negative ionic states of a constituent metal. No superconductivity was reported among the antiperovskite oxides so far. Here we present the first superconducting antiperovskite oxide Sr3−xSnO with the transition temperature of around 5 K. Sr3SnO possesses Dirac points in its electronic structure, and we propose from theoretical analysis a possibility of a topological odd-parity superconductivity analogous to the superfluid 3He-B in moderately hole-doped Sr3−xSnO. We envision that this discovery of a new class of oxide superconductors will lead to a rapid progress in physics and chemistry of antiperovskite oxides consisting of unusual metallic anions.
Conditional repair by locally switching the thermal healing capability of dynamic covalent polymers with light
Authors: Fuhrmann Anne , Göstl Robert , Wendt Robert , Kötteritzsch Julia , Hager Martin D. , Schubert Ulrich S. , Brademann-Jock Kerstin , Thünemann Andreas F. , Nöchel Ulrich , Behl Marc , Hecht Stefan
Published: December 2016

Healable materials could play an important role in reducing the environmental footprint of our modern technological society through extending the life cycles of consumer products and constructions. However, as most healing processes are carried out by heat alone, the ability to heal damage generally kills the parent material’s thermal and mechanical properties. Here we present a dynamic covalent polymer network whose thermal healing ability can be switched ‘on’ and ‘off’ on demand by light, thereby providing local control over repair while retaining the advantageous macroscopic properties of static polymer networks. We employ a photoswitchable furan-based crosslinker, which reacts with short and mobile maleimide-substituted poly(lauryl methacrylate) chains forming strong covalent bonds while simultaneously allowing the reversible, spatiotemporally resolved control over thermally induced de- and re-crosslinking. We reason that our system can be adapted to more complex materials and has the potential to impact applications in responsive coatings, photolithography and microfabrication.
Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence
Authors: Revandkar Ajinkya , Perciato Maria Luna , Toso Alberto , Alajati Abdullah , Chen Jingjing , Gerber Hermeto , Dimitrov Mitko , Rinaldi Andrea , Delaleu Nicolas , Pasquini Emiliano , D’Antuono Rocco , Pinton Sandra , Losa Marco , Gnetti Letizia , Arribas Alberto , Fraering Patrick , Bertoni Francesco , Nepveu Alain , Alimonti Andrea
Published: December 2016

Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression ofADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of bothPtenandNotch1along with preclinical trials carried out inPten-null prostate conditional mouse models, we demonstrate thatPten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in bothPten-null andPten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients.
Universal structural parameter to quantitatively predict metallic glass properties
Authors: Ding Jun , Cheng Yong-Qiang , Sheng Howard , Asta Mark , Ritchie Robert O. , Ma Evan
Published: December 2016

Quantitatively correlating the amorphous structure in metallic glasses (MGs) with their physical properties has been a long-sought goal. Here we introduce ‘flexibility volume’ as a universal indicator, to bridge the structural state the MG is in with its properties, on both atomic and macroscopic levels. The flexibility volume combines static atomic volume with dynamics information via atomic vibrations that probe local configurational space and interaction between neighbouring atoms. We demonstrate that flexibility volume is a physically appropriate parameter that can quantitatively predict the shear modulus, which is at the heart of many key properties of MGs. Moreover, the new parameter correlates strongly with atomic packing topology, and also with the activation energy for thermally activated relaxation and the propensity for stress-driven shear transformations. These correlations are expected to be robust across a very wide range of MG compositions, processing conditions and length scales.
Additional energy scale in SmB6 at low-temperature
Authors: Jiao L. , Rößler S. , Kim D. J. , Tjeng L. H. , Fisk Z. , Steglich F. , Wirth S.
Published: December 2016

Topological insulators give rise to exquisite electronic properties because of their spin-momentum locked Dirac-cone-like band structure. Recently, it has been suggested that the required opposite parities between valence and conduction band along with strong spin-orbit coupling can be realized in correlated materials. Particularly, SmB6 has been proposed as candidate material for a topological Kondo insulator. Here we observe, by utilizing scanning tunnelling microscopy and spectroscopy down to 0.35 K, several states within the hybridization gap of about ±20 meV on well characterized (001) surfaces of SmB6. The spectroscopic response to impurities and magnetic fields allows to distinguish between dominating bulk and surface contributions to these states. The surface contributions develop particularly strongly below about 7 K, which can be understood in terms of a suppressed Kondo effect at the surface. Our high-resolution data provide insight into the electronic structure of SmB6, which reconciles many current discrepancies on this compound.
Hall effect in charged conducting ferroelectric domain walls
Authors: Campbell M. P. , McConville J.P.V. , McQuaid R.G.P. , Prabhakaran D. , Kumar A. , Gregg J. M.
Published: December 2016

Enhanced conductivity at specific domain walls in ferroelectrics is now an established phenomenon. Surprisingly, however, little is known about the most fundamental aspects of conduction. Carrier types, densities and mobilities have not been determined and transport mechanisms are still a matter of guesswork. Here we demonstrate that intermittent-contact atomic force microscopy (AFM) can detect the Hall effect in conducting domain walls. Studying YbMnO3 single crystals, we have confirmed that p-type conduction occurs in tail-to-tail charged domain walls. By calibration of the AFM signal, an upper estimate of ∼1 × 1016 cm−3 is calculated for the mobile carrier density in the wall, around four orders of magnitude below that required for complete screening of the polar discontinuity. A carrier mobility of∼50 cm2V−1s−1 is calculated, about an order of magnitude below equivalent carrier mobilities in p-type silicon, but sufficiently high to preclude carrier-lattice coupling associated with small polarons.
Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway
Authors: Chen H L , Tsai T C , Tsai Y C , Liao J W , Yen C C , Chen C M
Published: December 2016

Objective:

In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides on high-fructose-induced hepatic steatosis and the possible molecular mechanism.

Results:

An animal model of 30% high-fructose-induced NAFLD in C57BL/6J mice was established. The experiment is divided into the following six groups: (1) normal: H2O drinking water; (2) mock: H2O+30% fructose; (3) KL: low-dose kefir peptides (50 mg kg−1)+30% fructose; (4) KM: medium-dose kefir peptides (100 mg kg−1)+30% fructose; (5) KH: high-dose kefir peptides (150 mg kg−1)+30% fructose; and (6) CFM: commercial fermented milk (100 mg kg−1)+30% fructose. The results show that kefir peptides improve fatty liver syndrome by decreasing body weight, serum alanine aminotransferase, triglycerides, insulin and hepatic triglycerides, cholesterol, and free fatty acids as well as the inflammatory cytokines (TNF-α, IL-6 and IL-1β) that had been elevated in fructose-induced NAFLD mice. In addition, kefir peptides markedly increased phosphorylation of AMPK to downregulate its targeted enzymes, ACC (acetyl-CoA carboxylase) and SREBP-1c (sterol regulatory element-binding protein 1), and inhibited de novo lipogenesis. Furthermore, kefir peptides activated JAK2 to stimulate STAT3 phosphorylation, which can translocate to the nucleus, and upregulated several genes, including the CPT1 (carnitine palmitoyltransferase-1) involved in fatty acid oxidation.

Conclusion:

Our data have demonstrated that kefir peptides can improve the symptoms of NAFLD, including body weight, energy intake, inflammatory reaction and the formation of fatty liver by activating JAK2 signal transduction through the JAK2/STAT3 and JAK2/AMPK pathways in the high-fructose-induced fatty liver animal model. Therefore, kefir peptides may have the potential for clinical application for the prevention or treatment of clinical metabolic syndrome.
ERK-mediated NF-κB activation through ASIC1 in response to acidosis
Authors: Chen B , Liu J , Ho T-T , Ding X , Mo Y-Y
Published: December 2016

Acidic microenvironment is a common feature of solid tumors. We have previously shown that neuron specific acid-sensing ion channel 1 (ASIC1) is expressed in breast cancer, and it is responsible for acidosis-induced cellular signaling through AKT, leading to nuclear factor-κB (NF-κB) activation, and cell invasion and metastasis. However, AKT is frequently activated in cancer. Thus, a key question is whether ASIC1-mediated cell signaling still takes place in the cancer cells carrying constitutively active AKT. In the present study, we show that among four prostate cancer cell lines tested, 22Rv1 cells express the highest level of phosphorylated AKT that is not impacted by acidosis. However, acidosis can still induce NF-κB activation during which extracellular signal-regulated kinase (ERK) serves as an alternative pathway for ASIC-mediated cell signaling. Inhibition of ERK by chemical inhibitors or small interfering RNAs suppresses the acidosis-induced NF-κB activity through regulation of the inhibitory subunit IκBα phosphorylation. Furthermore, suppression of ASIC1-mediated generation of reactive oxygen species (ROS) by ROS scavengers, such as glutathione or N-acetyl-cysteine causes a decrease in ERK phosphorylation and degradation of IκBα. Finally, ASIC1 is upregulated in a subset of prostate cancer cases and ASIC1 knockout by CRISPR/Cas9 significantly suppresses cell invasion, and castration resistance both in vitro and in vivo. Together, these results support the significance of ASIC1-ROS-ERK-IκBα-NF-κB axis in prostate tumorigenesis, especially in the constitutively active AKT background.
G-rich DNA-induced stress response blocks type-I-IFN but not CXCL10 secretion in monocytes
Authors: Herzner Anna-Maria , Wolter Steven , Zillinger Thomas , Schmitz Saskia , Barchet Winfried , Hartmann Gunther , Bartok Eva , Schlee Martin
Published: December 2016

Excessive inflammation can cause damage to host cells and tissues. Thus, the secretion of inflammatory cytokines is tightly regulated at transcriptional, post-transcriptional and post-translational levels and influenced by cellular stress responses, such as endoplasmic reticulum (ER) stress or apoptosis. Here, we describe a novel type of post-transcriptional regulation of the type-I-IFN response that was induced in monocytes by cytosolic transfection of a short immunomodulatory DNA (imDNA), a G-tetrad forming CpG-free derivative of the TLR9 agonist ODN2216. When co-transfected with cytosolic nucleic acid stimuli (DNA or 3P-dsRNA), imDNA induced caspase-3 activation, translational shutdown and upregulation of stress-induced genes. This stress response inhibited the type-I-IFN induction at the translational level. By contrast, the induction of most type-I-IFN-associated chemokines, including Chemokine (C-X-C Motif) Ligand (CXCL)10 was not affected, suggesting a differential translational regulation of chemokines and type-I-IFN. Pan-caspase inhibitors could restore IFN-β secretion, yet, strikingly, caspase inhibition did not restore global translation but instead induced a compensatory increase in the transcription of IFN-β but not CXCL10. Altogether, our data provide evidence for a differential regulation of cytokine release at both transcriptional and post-transcriptional levels which suppresses type-I-IFN induction yet allows for CXCL10 secretion during imDNA-induced cellular stress.
VRK3-mediated nuclear localization of HSP70 prevents glutamate excitotoxicity-induced apoptosis and Aβ accumulation via enhancement of ERK phosphatase VHR activity
Authors: Song Haengjin , Kim Wanil , Kim Sung-Hoon , Kim Kyong-Tai
Published: December 2016

Most of neurodegenerative disorders are associated with protein aggregation. Glutamate-induced excitotoxicity and persistent extracellular signal-regulated kinase (ERK) activation are also implicated in neurodegenerative diseases. Here, we found that vaccinia-related kinase 3 (VRK3) facilitates nuclear localization of glutamate-induced heat shock protein 70 (HSP70). Nuclear HSP70 leads to enhancement of vaccinia H1-related phosphatase (VHR) activity via protein-protein interaction rather than its molecular chaperone activity, thereby suppressing excessive ERK activation. Moreover, glutamate-induced ERK activation stimulates the expression of HSP70 and VRK3 at the transcriptional level. Downregulation of either VRK3 or HSP70 rendered cells vulnerable to glutamate-induced apoptosis. Overexpression of HSP70 fused to a nuclear localization signal attenuated apoptosis more than HSP70 alone. The importance of nuclear localization of HSP70 in the negative regulation of glutamate-induced ERK activation was further confirmed in VRK3-deficient neurons. Importantly, we showed a positive correlation between levels of VRK3 and HSP70 in the progression of Alzheimer’s and Parkinson’s diseases in humans, and neurons with HSP70 nuclear localization exhibited less Aβ accumulation in brains from patients with Alzheimer’s disease. Therefore, HSP70 and VRK3 could potentially serve as diagnostic and therapeutic targets in neurodegenerative diseases.
Meandering instability of air flow in a granular bed: self-similarity and fluid-solid duality
Authors: Yoshimura Yuki , Yagisawa Yui , Okumura Ko
Published: December 2016

Meandering instability is familiar to everyone through river meandering or small rivulets of rain flowing down a windshield. However, its physical understanding is still premature, although it could inspire researchers in various fields, such as nonlinear science, fluid mechanics and geophysics, to resolve their long-standing problems. Here, we perform a small-scale experiment in which air flow is created in a thin granular bed to successfully find a meandering regime, together with other remarkable fluidized regimes, such as a turbulent regime. We discover that phase diagrams of the flow regimes for different types of grains can be universally presented as functions of the flow rate and the granular-bed thickness when the two quantities are properly renormalized. We further reveal that the meandering shapes are self-similar as was shown for meandering rivers. The experimental findings are explained by theory, with elucidating the physics. The theory is based on force balance, a minimum-dissipation principle, and a linear-instability analysis of a continuum equation that takes into account the fluid-solid duality, i.e., the existence of fluidized and solidified regions of grains along the meandering path. The present results provide fruitful links to related issues in various fields, including fluidized bed reactors in industry.
Nanosomes carrying doxorubicin exhibit potent anticancer activity against human lung cancer cells
Authors: Srivastava Akhil , Amreddy Narsireddy , Babu Anish , Panneerselvam Janani , Mehta Meghna , Muralidharan Ranganayaki , Chen Allshine , Zhao Yan Daniel , Razaq Mohammad , Riedinger Natascha , Kim Hogyoung , Liu Shaorong , Wu Si , Abdel-Mageed Asim B. , Munshi Anupama , Ramesh Rajagopal
Published: December 2016

Successful chemotherapeutic intervention for management of lung cancer requires an efficient drug delivery system. Gold nanoparticles (GNPs) can incorporate various therapeutics; however, GNPs have limitations as drug carriers. Nano-sized cellular vesicles like exosomes (Exo) can ferry GNP-therapeutic complexes without causing any particle aggregation or immune response. In the present study, we describe the development and testing of a novel Exo-GNP-based therapeutic delivery system -‘nanosomes’- for lung cancer therapy. This system consists of GNPs conjugated to anticancer drug doxorubicin (Dox) by a pH-cleavable bond that is physically loaded onto the exosomes (Exo-GNP-Dox). The therapeutic efficacy of Dox in nanosomes was assessed in H1299 and A549 non-small cell lung cancer cells, normal MRC9 lung fibroblasts, and Dox-sensitive human coronary artery smooth muscle cells (HCASM). The enhanced rate of drug release under acidic conditions, successful uptake of the nanosomes by the recipient cells and the cell viability assays demonstrated that nanosomes exhibit preferential cytotoxicity towards cancer cells and have minimal activity on non-cancerous cells. Finally, the underlying mechanism of cytotoxicity involved ROS-mediated DNA damage. Results from this study mark the establishment of an amenable drug delivery vehicle and highlight the advantages of a natural drug carrier that demonstrates reduced cellular toxicity and efficient delivery of therapeutics to cancer cells.
Nuclear Factor Erythroid 2-related Factor 2 Deficiency Exacerbates Lupus Nephritis in B6/lpr mice by Regulating Th17 Cell Function
Authors: Zhao Mei , Chen Huanpeng , Ding Qingfeng , Xu Xiaoxie , Yu Bolan , Huang Zhaofeng
Published: December 2016

Lupus nephritis (LN) is the major clinical manifestation of systemic lupus erythematosus. LN is promoted by T helper 17 (Th17) cells, which are the major pro-inflammatory T cell subset contributing to autoimmunity regulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is critical for suppressing reactive oxygen species (ROS) and relieving oxidant stress by regulating antioxidant gene expression. Previous studies have demonstrated that Nrf2 deficiency promotes drug-induced or spontaneous LN. However, whether NRF2 regulates Th17 function during LN development is still unclear. In this study, we introduced Nrf2 deficiency into a well-known LN model, the B6/lpr mouse strain, and found that it promoted early-stage LN with altered Th17 activation. Th17 cells and their relevant cytokines were dramatically increased in these double-mutant mice. We also demonstrated that naïve T cells from the double-mutant mice showed significantly increased differentiation into Th17 cells in vitro, with decreased expression of the Th17 differentiation suppressor Socs3 and increased phosphorylation of STAT3. Our results demonstrated that Nrf2 deficiency promoted Th17 differentiation and function during LN development. Moreover, our results suggested that the regulation of Th17 differentiation via NRF2 could be a therapeutic target for the treatment of subclinical LN patients.
Development of an oxide-dispersion-strengthened steel by introducing oxygen carrier compound into the melt aided by a general thermodynamic model
Authors: Moghadasi Mohammad Amin , Nili-Ahmadabadi Mahmoud , Forghani Farsad , Kim Hyoung Seop
Published: December 2016

In general, melting process is not a common method for the production of oxide dispersion strengthened (ODS) alloys due to agglomeration and coarsening of oxide particles. However, vacuum casting process has recently been employed as a promising process to produce micro-scale oxide dispersed alloys. In this paper, we report the process and characterization of in situ formation and uniform dispersion of nano-scale Y-Ti oxide particles in Fe-10Ni-7Mn (wt.%) alloy. The processing route involves a solid-liquid reaction between the added TiO2 as an oxygen carrier and dissolved yttrium in liquid metal leading to an optimal microstructure with nano-sized dispersed oxide particles. The developed thermodynamic model shows the independence of the final phase constituents from experimental conditions such as melting temperature or vacuum system pressure which offers a general pathway for the manufacture of oxide dispersion strengthened materials.
Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT
Authors: Ma Kuo-Hsing , Liu Tsung-Ta , Weng Shao-Ju , Chen Chien-Fu F. , Huang Yuahn-Sieh , Chueh Sheau-Huei , Liao Mei-Hsiu , Chang Kang-Wei , Sung Chi-Chang , Hsu Te-Hung , Huang Wen-Sheng , Cheng Cheng-Yi
Published: December 2016

3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effectin vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.
Deterministic composite nanophotonic lattices in large area for broadband applications
Authors: Xavier Jolly , Probst Jürgen , Becker Christiane
Published: December 2016

Exotic manipulation of the flow of photons in nanoengineered materials with an aperiodic distribution of nanostructures plays a key role in efficiency-enhanced broadband photonic and plasmonic technologies for spectrally tailorable integrated biosensing, nanostructured thin film solarcells, white light emitting diodes, novel plasmonic ensembles etc. Through a generic deterministic nanotechnological route here we show subwavelength-scale silicon (Si) nanostructures on nanoimprinted glass substrate in large area (4 cm2) with advanced functional features of aperiodic composite nanophotonic lattices. These nanophotonic aperiodic lattices have easily tailorable supercell tiles with well-defined and discrete lattice basis elements and they show rich Fourier spectra. The presented nanophotonic lattices are designed functionally akin to two-dimensional aperiodic composite lattices with unconventional flexibility- comprising periodic photonic crystals and/or in-plane photonic quasicrystals as pattern design subsystems. The fabricated composite lattice-structured Si nanostructures are comparatively analyzed with a range of nanophotonic structures with conventional lattice geometries of periodic, disordered random as well as in-plane quasicrystalline photonic lattices with comparable lattice parameters. As a proof of concept of compatibility with advanced bottom-up liquid phase crystallized (LPC) Si thin film fabrication, the experimental structural analysis is further extended to double-side-textured deterministic aperiodic lattice-structured 10 μm thick large area LPC Si film on nanoimprinted substrates.
Theoretical analyses of resonant frequency shift in anomalous dispersion enhanced resonant optical gyroscopes
Authors: Lin Jian , Liu Jiaming , Zhang Hao , Li Wenxiu , Zhao Lu , Jin Junjie , Huang Anping , Zhang Xiaofu , Xiao Zhisong
Published: December 2016

Rigorous expressions of resonant frequency shift (RFS) in anomalous dispersion enhanced resonant optical gyroscopes (ADEROGs) are deduced without making approximation, which provides a precise theoretical guidance to achieve ultra-sensitive ADEROGs. A refractive index related modification factor "Equation missing" is introduced when considering special theory of relativity (STR). We demonstrate that the RFS will not be ”infinitely large” by using critical anomalous dispersion (CAD) and negative modification does not exist, which make the mechanism of anomalous dispersion enhancement clear and coherent. Although step change of RFS will happen when the anomalous dispersion condition varies, the amplification of RFS is limited by attainable variation of refractive index in practice. Moreover, it is shown that the properties of anomalous dispersion will influence not only the amplification of RFS, but also the detection range of ADEROGs.
Chemical ordering in substituted fluorite oxides: a computational investigation of Ho2Zr2O7 and RE2Th2O7 (RE=Ho, Y, Gd, Nd, La)
Authors: Solomon Jonathan M. , Shamblin Jacob , Lang Maik , Navrotsky Alexandra , Asta Mark
Published: December 2016

Fluorite-structured oxides find widespread use for applications spanning nuclear energy and waste containment, energy conversion, and sensing. In such applications the host tetravalent cation is often partially substituted by trivalent cations, with an associated formation of charge-compensating oxygen vacancies. The stability and properties of such materials are known to be influenced strongly by chemical ordering of the cations and vacancies, and the nature of such ordering and associated energetics are thus of considerable interest. Here we employ density-functional theory (DFT) calculations to study the structure and energetics of cation and oxygen-vacancy ordering in Ho2Zr2O7. In a recent neutron total scattering study, solid solutions in this system were reported to feature local chemical ordering based on the fluorite-derivative weberite structure. The calculations show a preferred chemical ordering qualitatively consistent with these findings, and yield values for the ordering energy of 9.5 kJ/mol-cation. Similar DFT calculations are applied to additional RE2Th2O7 fluorite compounds, spanning a range of values for the ratio of the tetravalent and trivalent (RE) cation radii. The results demonstrate that weberite-type order becomes destabilized with increasing values of this size ratio, consistent with an increasing energetic preference for the tetravalent cations to have higher oxygen coordination.
Neural Pathway of Renovative and Innovative Products Appreciation
Authors: Huang Furong , Chiu Chiyue , Luo Jing
Published: December 2016

According to the level of change an invention makes on existing things and how it overrides people’s mental schemas on established categories, new inventions can be classified into two groups: incremental inventions (i.e., renovations), which make minor improvements on existing designs, and radical inventions (i.e., innovations), which make major developments that enable people to do things they have never been able to do before. Although innovation and renovation are two fundamentally different types of creation that feature new changes ranging from those in product development to those in large scale social changes, and people tend to report higher subjective preferences for incremental inventions compared to radical inventions, the cognitive brain mechanisms underlying the mental representation of these two types of inventions remains unknown. Through the use of innovative and renovative designs as materials, we found that relative to non-creative designs, creative (renovative &innovative) designs enhanced memory or association-related activation in the right parahippocampus. In particular, innovations evoked more activation in the conceptual pathway for representing objects than did renovations, whereas renovations evoked more activation in the motor pathway than innovations. These results suggest that operating experiences may provide advantages for understanding and appreciating creative designs.
TiO2 nanotubes and mesoporous silica as containers in self-healing epoxy coatings
Authors: Vijayan P. Poornima , Al-Maadeed Mariam Ali S. A.
Published: December 2016

The potential of inorganic nanomaterials as reservoirs for healing agents is presented here. Mesoporous silica (SBA-15) and TiO2 nanotubes (TNTs) were synthesized. Both epoxy-encapsulated TiO2 nanotubes and amine-immobilized mesoporous silica were incorporated into epoxy and subsequently coated on a carbon steel substrate. The encapsulated TiO2 nanotubes was quantitatively estimated using a ‘dead pore ratio’ calculation. The morphology of the composite coating was studied in detail using transmission electron microscopic (TEM) analysis. The self-healing ability of the coating was monitored using electrochemical impedance spectroscopy (EIS); the coating recovered 57% of its anticorrosive property in 5 days. The self-healing of the scratch on the coating was monitored using Scanning Electron Microscopy (SEM). The results confirmed that the epoxy pre-polymer was slowly released into the crack. The released epoxy pre-polymer came into contact with the amine immobilized in mesoporous silica and cross-linked to heal the scratch.
Graphene nanoplatelets induced heterogeneous bimodal structural magnesium matrix composites with enhanced mechanical properties
Authors: Xiang Shulin , Wang Xiaojun , Gupta Manoj , Wu Kun , Hu Xiaoshi , Zheng Mingyi
Published: December 2016

In this work, graphene nanoplatelets (GNPs) reinforced magnesium (Mg) matrix composites were synthesised using the multi-step dispersion route. Well-dispersed but inhomogeneously distributed GNPs were obtained in the matrix. Compared with the monolithic alloy, the nanocomposites exhibited dramatically enhanced Young’s modulus, yield strength and ultimate tensile strength and relatively high plasticity, which mainly attributed to the significant heterogeneous laminated microstructure induced by the addition of GNPs. With increasing of the concentration of GNPs, mechanical properties of the composites were gradually improved. Especially, the strengthening efficiency of all the composites exceeded 100%, which was significantly higher than that of carbon nanotubes reinforced Mg matrix composites. The grain refinement and load transfer provided by the two-dimensional and wrinkled surface structure of GNPs were the dominated strengthening mechanisms of the composites. This investigation develops a new method for incorporating GNPs in metals for fabricating high-performance composites.
BLR1 and FCGR1A transcripts in peripheral blood associate with the extent of intrathoracic tuberculosis in children and predict treatment outcome
Authors: Jenum Synne , Bakken Rasmus , Dhanasekaran S. , Mukherjee Aparna , Lodha Rakesh , Singh Sarman , Singh Varinder , Haks Marielle C. , Ottenhoff Tom H. M. , Kabra S. K. , Doherty T. Mark , Ritz Christian , Grewal Harleen M. S.
Published: December 2016

Biomarkers reflecting the extent of Mycobacterium tuberculosis-induced pathology and normalization during anti-tuberculosis treatment (ATT) would considerably facilitate trials of new treatment regimens and the identification of patients with treatment failure. Therefore, in a cohort of 99 Indian children with intrathoracic tuberculosis (TB), we performed blood transcriptome kinetic analysis during ATT to explore 1) the association between transcriptional biomarkers in whole blood (WB) and the extent of TB disease at diagnosis and treatment outcomes at 2 and 6 months, and 2) the potential of the biomarkers to predict treatment response at 2 and 6 months. We present the first data on the association between transcriptional biomarkers and the extent of TB disease as well as outcome of ATT in children: Expression of three genes down-regulated on ATT (FCGR1A, FPR1 and MMP9) exhibited a positive correlation with the extent of TB disease, whereas expression of eight up-regulated genes (BCL, BLR1, CASP8, CD3E, CD4, CD19, IL7R and TGFBR2) exhibited a negative correlation with the extent of disease. Baseline levels of these transcripts displayed an individual capacity >70% to predict the six-month treatment outcome. In particular, BLR1 and FCGR1A seem to have a potential in monitoring and perhaps tailoring future antituberculosis therapy.
Self-preservation and structural transition of gas hydrates during dissociation below the ice point: an in situ study using Raman spectroscopy
Authors: Zhong Jin-Rong , Zeng Xin-Yang , Zhou Feng-He , Ran Qi-Dong , Sun Chang-Yu , Zhong Rui-Qin , Yang Lan-Ying , Chen Guang-Jin , Koh Carolyn A.
Published: December 2016

The hydrate structure type and dissociation behavior for pure methane and methane-ethane hydrates at temperatures below the ice point and atmospheric pressure were investigated usingin situRaman spectroscopic analysis. The self-preservation effect of sI methane hydrate is significant at lower temperatures (268.15 to 270.15 K), as determined by the stable C-H region Raman peaks andAL/ASvalue (Ratio of total peak area corresponding to occupancies of guest molecules in large cavities to small cavities) being around 3.0. However, it was reduced at higher temperatures (271.15 K and 272.15 K), as shown from the dramatic change in Raman spectra and fluctuations inAL/ASvalues. The self-preservation effect for methane-ethane double hydrate is observed at temperatures lower than 271.15 K. The structure transition from sI to sII occurred during the methane-ethane hydrate decomposition process, which was clearly identified by the shift in peak positions and the change in relative peak intensities at temperatures from 269.15 K to 271.15 K. Further investigation shows that the selectivity for self-preservation of methane over ethane leads to the structure transition; this kind of selectivity increases with decreasing temperature. This work provides new insight into the kinetic behavior of hydrate dissociation below the ice point.