bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal mechanisms of seismo-EM phenomena during the 1965–1967 Matsushiro earthquake swarm
Authors: Enomoto Yuji , Yamabe Tsuneaki , Okumura Nobuo
Published: March 2017

The 1965–1967 Matsushiro earthquake swarm in central Japan exhibited two unique characteristics. The first was a hydro-mechanical crust rupture resulting from degassing, volume expansion of CO2/water, and a crack opening within the critically stressed crust under a strike-slip stress. The other was, despite the lower total seismic energy, the occurrence of complexed seismo-electromagnetic (seismo-EM) phenomena of the geomagnetic intensity increase, unusual earthquake lights (EQLs) and atmospheric electric field (AEF) variations. Although the basic rupture process of this swarm of earthquakes is reasonably understood in terms of hydro-mechanical crust rupture, the associated seismo-EM processes remain largely unexplained. Here, we describe a series of seismo-EM mechanisms involved in the hydro-mechanical rupture process, as observed by coupling the electric interaction of rock rupture with CO2 gas and the dielectric-barrier discharge of the modelled fields in laboratory experiments. We found that CO2 gases passing through the newly created fracture surface of the rock were electrified to generate pressure-impressed current/electric dipoles, which could induce a magnetic field following Biot-Savart’s law, decrease the atmospheric electric field and generate dielectric-barrier discharge lightning affected by the coupling effect between the seismic and meteorological activities.
Mechanistic and structural basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity
Authors: Sahoo Bikash R. , Maruyama Kenta , Edula Jyotheeswara R. , Tougan Takahiro , Lin Yuxi , Lee Young-Ho , Horii Toshihiro , Fujiwara Toshimichi
Published: March 2017

Peptide-drug discovery using host-defense peptides becomes promising against antibiotic-resistant pathogens and cancer cells. Here, we customized the therapeutic activity of bovine cathelicidin-5 targeting to bacteria, protozoa, and tumor cells. The membrane dependent conformational adaptability and plasticity of cathelicidin-5 is revealed by biophysical analysis and atomistic simulations over 200 μs in thymocytes, leukemia, and E. coli cell-membranes. Our understanding of energy-dependent cathelicidin-5 intrusion in heterogeneous membranes aided in designing novel loss/gain-of-function analogues. In vitro findings identified leucine-zipper to phenylalanine substitution in cathelicidin-5 (1–18) significantly enhance the antimicrobial and anticancer activity with trivial hemolytic activity. Targeted mutants of cathelicidin-5 at kink region and N-terminal truncation revealed loss-of-function. We ensured the existence of a bimodal mechanism of peptide action (membranolytic and non-membranolytic) in vitro. The melanoma mouse model in vivo study further supports the in vitro findings. This is the first structural report on cathelicidin-5 and our findings revealed potent therapeutic application of designed cathelicidin-5 analogues.
A Ras GTPase associated protein is involved in the phototropic and circadian photobiology responses in fungi
Authors: Polaino Silvia , Villalobos-Escobedo José M. , Shakya Viplendra P. S. , Miralles-Durán Alejandro , Chaudhary Suman , Sanz Catalina , Shahriari Mahdi , Luque Eva M. , Eslava Arturo P. , Corrochano Luis M. , Herrera-Estrella Alfredo , Idnurm Alexander
Published: March 2017

Light is an environmental signal perceived by most eukaryotic organisms and that can have major impacts on their growth and development. The MadC protein in the fungusPhycomyces blakesleeanus(Mucoromycotina) has been postulated to form part of the photosensory input for phototropism of the fruiting body sporangiophores, but themadCgene has remained unidentified since the 1960s whenmadCmutants were first isolated. In this study themadCgene was identified by positional cloning. AllmadCmutant strains contain loss-of-function point mutations within a gene predicted to encode a GTPase activating protein (GAP) for Ras. ThemadCgene complements theSaccharomyces cerevisiaeRas-GAPira1mutant and the encoded MadC protein interacts withP. blakesleeanusRas homologs in yeast two-hybrid assays, indicating that MadC is a regulator of Ras signaling. Deletion of the homolog in the filamentous ascomyceteNeurospora crassaaffects the circadian clock output, yielding a pattern of asexual conidiation similar to aras-1mutant that is used in circadian studies inN. crassa. Thus, MadC is unlikely to be a photosensor, yet is a fundamental link in the photoresponses from blue light perceived by the conserved White Collar complex with Ras signaling in two distantly-related filamentous fungal species.
Exposure of pregnant mice to triclosan impairs placental development and nutrient transport
Authors: Cao Xinyuan , Hua Xu , Wang Xiaoli , Chen Ling
Published: March 2017

Triclosan (TCS) is associated with spontaneous abortions and fetal growth restriction. Here, we showed that when pregnant mice were treated with 8 mg/kg TCS (8-TCS mice) on gestational days (GD) 6–18 fetal body weights were lower than controls. Placental weights and volumes were reduced in 8-TCS mice. The placental proliferative cells and expression of PCNA and Cyclin D3 on GD13 were remarkably decreased in 8-TCS mice. The decreases in activities and expression of placental System A amino acid or glucose transporters on GD14 and GD17 were observed in 8-TCS mice. Levels of serum thyroxine (T4) and triiodothyronine (T3) were lower in 8-TCS mice than those in controls. Declines of placental Akt, mTOR and P70S6K phosphorylation in 8-TCS mice were corrected by L-thyroxinein (T4). Treating 8-TCS mice with T4 rescued the placental cell proliferation and recovered the activity and expression of amino acid and glucose transporters, which were sensitive to mTOR inhibition by rapamycin. Furthermore, the replacement of T4 could rescue the decrease in fetal body weight, which was blocked by rapamycin. These findings indicate that TCS-induced hypothyroxinemia in gestation mice through reducing Akt-mTOR signaling may impair placental development and nutrient transfer leading to decreases in fetal body weight.
Tea polyphenols inhibit the growth and virulence properties of Fusobacterium nucleatum
Authors: Ben Lagha Amel , Haas Bruno , Grenier Daniel
Published: March 2017

Fusobacterium nucleatum plays a key role in creating the pathogenic subgingival biofilm that initiates destructive periodontitis. It is also a common resident of the human gastrointestinal tract and has been associated with inflammatory bowel disease. The aim of the present study was to investigate the effects of green and black tea extracts as well as two of their bioactive components, EGCG and theaflavins, on the growth and virulence properties of F. nucleatum. The tea extracts and components displayed various degrees of antibacterial activity that may involve damage to the bacterial cell membrane and the chelation of iron. They also prevented biofilm formation by F. nucleatum at concentrations that did not interfere with bacterial growth. In addition, the treatment of a pre-formed F. nucleatum biofilm with the green tea extract and EGCG caused a time-dependent decrease in biofilm viability. The green and black tea extracts, EGCG, and theaflavins decreased the adherence of F. nucleatum to oral epithelial cells and matrix proteins. Moreover, these tea components also attenuated F. nucleatum-mediated hemolysis and hydrogen sulfide production, two other virulence factors expressed by this bacterium. In summary, this study showed that tea polyphenols may be of interest for treating F. nucleatum-associated disorders.
Tumour infiltrating lymphocytes correlate with improved survival in patients with esophageal squamous cell carcinoma
Authors: Jiang Dongxian , Liu Yalan , Wang Hao , Wang Haixing , Song Qi , Sujie Akesu , Huang Jie , Xu Yifan , Zeng Haiying , Tan Lijie , Hou Yingyong , Xu Chen
Published: March 2017

We undertook a study of tumour infiltrating lymphocytes (TILs) in a large and relatively homogeneous group of patients with completely resected esophageal squamous cell carcinoma (ESCC). Hematoxylin and eosin–stained sections of 235 ESCC tumours were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Foxp3+, CD4+, and CD8+ T cells in tumoural and stromal areas were evaluated by immunohistochemistry. Of the 235 tumours, high sTIL (>10%), and iTIL (>10%) were observed in 101 (43.0%) and 98 (41.7%), respectively. The median follow-up period was 36.0 months (95% CI 29.929–42.071). Univariate analysis revealed that sTIL (>10%), iTIL (>20%), vessels involvement, lymph node metastasis, and clinical stage were significantly associated with postoperative outcome. In multivariate analysis, high sTIL (HR: 0.664, P = 0.019 for Disease free survival; HR: 0.608, P = 0.005 for Overall survival) was identified as independent better prognostic factor. Further analysis, sTIL was identified as independently prognostic factor in Stage III-IVa disease, which was not found in Stage I-II disease. Our study demonstrated that sTIL was associated with better ESCC patients’ survival, especially in Stage III-IVa disease. Assessment of sTIL could be useful to discriminate biological behavior for ESCC patients.
Quantification of the impact of aerosol on broadband solar radiation in North China
Authors: Hu Bo , Zhao Xiujuan , Liu Hui , Liu Zirui , Song Tao , Wang Yuesi , Tang Liqin , Xia Xiangao , Tang Guiqian , Ji Dongsheng , Wen Tianxue , Wang Lili , Sun Yang , Xin Jinyuan
Published: March 2017

PM2.5 plays a key role in the solar radiation budget and air quality assessments, but observations and historical data are relatively rare for Beijing. Based on the synchronous monitoring of PM2.5 and broadband solar radiation (Rs), a logarithmic function was developed to describe the quantitative relationship between these parameters. This empirical parameterization was employed to calculate Rsn from PM2.5 with normalized mean bias (NMB) −0.09 and calculate PM2.5 concentration from Rsn with NMB −0.12. Our results indicate that this parameterization provides an efficient and straightforward method for estimating PM2.5 from Rs or Rs from PM2.5.
Influence of the Ag concentration on the medium-range order in a CuZrAlAg bulk metallic glass
Authors: Gammer C. , Escher B. , Ebner C. , Minor A. M. , Karnthaler H. P. , Eckert J. , Pauly S. , Rentenberger C.
Published: March 2017

Fluctuation electron microscopy of bulk metallic glasses of CuZrAl(Ag) demonstrates that medium-range order is sensitive to minor compositional changes. By analyzing nanodiffraction patterns medium-range order is detected with crystal-like motifs based on the B2 CuZr structure and its distorted structures resembling the martensitic ones. This result demonstrates some structural homology between the metallic glass and its high temperature crystalline phase. The amount of medium-range order seems slightly affected with increasing Ag concentration (0, 2, 5 at.%) but the structural motifs of the medium-range ordered clusters become more diverse at the highest Ag concentration. The decrease of dominant clusters is consistent with the destabilization of the B2 structure measured by calorimetry and accounts for the increased glass-forming ability.
Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2)
Authors: Xu Zheng , Li Weixin , Han Jibo , Zou Chunpeng , Huang Weijian , Yu Weihui , Shan Xiaoou , Lum Hazel , Li Xiaokun , Liang Guang
Published: March 2017

Growing evidence indicates that angiotensin II (Ang II), a potent biologically active product of RAS, is a key regulator of renal inflammation and fibrosis. In this study, we tested the hypothesis that Ang II induces renal inflammatory injury and fibrosis through interaction with myeloid differentiation protein-2 (MD2), the accessory protein of toll-like receptor 4 (TLR4) of the immune system. Results indicated that in MD2−/− mice, the Ang II-induced renal fibrosis, inflammation and kidney dysfunction were significantly reduced compared to control Ang II-infused wild-type mice. Similarly, in the presence of small molecule MD2 specific inhibitor L6H21 or siRNA-MD2, the Ang II-induced increases of pro-fibrotic and pro-inflammatory molecules were prevented in tubular NRK-52E cells. MD2 blockade also inhibited activation of NF-κB and ERK. Moreover, MD2 blockade prevented the Ang II-stimulated formation of the MD2/TLR4/MyD88 signaling complex, as well as the increased surface binding of Ang II in NRK-52E cells. In addition, Ang II directly bound recombinant MD2 protein, rather than TLR4 protein. We conclude that MD2 is a significant contributor in the Ang II-induced kidney inflammatory injury in chronic renal diseases. Furthermore, MD2 inhibition could be a new and important therapeutic strategy for preventing progression of chronic renal diseases.
A structure- and chemical genomics-based approach for repositioning of drugs against VCP/p97 ATPase
Authors: Segura-Cabrera Aldo , Tripathi Reshmi , Zhang Xiaoyi , Gui Lin , Chou Tsui-Fen , Komurov Kakajan
Published: March 2017

Valosin-containing protein (VCP/p97) ATPase (a.k.a. Cdc48) is a key member of the ER-associated protein degradation (ERAD) pathway. ERAD and VCP/p97 have been implicated in a multitude of human diseases, such as neurodegenerative diseases and cancer. Inhibition of VCP/p97 induces proteotoxic ER stress and cell death in cancer cells, making it an attractive target for cancer treatment. However, no drugs exist against this protein in the market. Repositioning of drugs towards new indications is an attractive alternative to the de novo drug development due to the potential for significantly shorter time to clinical translation. Here, we employed an integrative strategy for the repositioning of drugs as novel inhibitors of the VCP/p97 ATPase. We integrated structure-based virtual screening with the chemical genomics analysis of drug molecular signatures, and identified several candidate inhibitors of VCP/p97 ATPase. Importantly, experimental validation with cell-based and in vitro ATPase assays confirmed three (ebastine, astemizole and clotrimazole) out of seven tested candidates (~40% true hit rate) as direct inhibitors of VCP/p97 and ERAD. This study introduces an effective integrative strategy for drug repositioning, and identified new drugs against the VCP/p97/ERAD pathway in human diseases.
Global temperature change potential of nitrogen use in agriculture: A 50-year assessment
Authors: Fagodiya R. K. , Pathak H. , Kumar A. , Bhatia A. , Jain N.
Published: March 2017

Nitrogen (N) use in agriculture substantially alters global N cycle with the short- and long-term effects on global warming and climate change. It increases emission of nitrous oxide, which contributes 6.2%, while carbon dioxide and methane contribute 76% and 16%, respectively of the global warming. However, N causes cooling due to emission of NOx, which alters concentrations of tropospheric ozone and methane. NOx and NH3 also form aerosols with considerable cooling effects. We studied global temperature change potential (GTP) of N use in agriculture. The GTP due to N2O was 396.67 and 1168.32 Tg CO2e on a 20-year (GTP20) and 439.94 and 1295.78 Tg CO2e on 100-year scale (GTP100) during years 1961 and 2010, respectively. Cooling effects due to N use were 92.14 and 271.39 Tg CO2e (GTP20) and 15.21 and 44.80 Tg CO2e (GTP100) during 1961 and 2010, respectively. Net GTP20 was 369.44 and 1088.15 Tg CO2e and net GTP100 was 429.17 and 1264.06 Tg CO2e during 1961 and 2010, respectively. Thus net GTP20 is lower by 6.9% and GTP100 by 2.4% compared to the GTP considering N2O emission alone. The study shows that both warming and cooling effects should be considered to estimate the GTP of N use.
Alterations in Gastric Microbiota After H. Pylori Eradication and in Different Histological Stages of Gastric Carcinogenesis
Authors: Li Tung Hiu , Qin Youwen , Sham Pak Chung , Lau K.S. , Chu Kent-Man , Leung Wai K.
Published: March 2017

The role of bacteria other thanHelicobacter pylori(HP) in the stomach remains elusive. We characterized the gastric microbiota in individuals with different histological stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP negative controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominantH. pylori, we observed otherProteobacteriaincludingHaemophilus, Serratia, NeisseriaandStenotrophomonasas the major components of the human gastric microbiota. Although samples were largely converged according to the relative abundance of HP, a clear separation of GC and other samples was recovered. Whilst there was a strong inverse association between HP relative abundance and bacterial diversity, this association was weak in GC samples which tended to have lower bacterial diversity compared with other samples with similar HP levels. Eradication of HP resulted in an increase in bacterial diversity and restoration of the relative abundance of other bacteria to levels similar to individuals without HP. In conclusion, HP colonization results in alterations of gastric microbiota and reduction in bacterial diversity, which could be restored by antibiotic treatment.
12-O-Tetradecanoylphorbol-13-acetate (TPA) is anti-tumorigenic in liver cancer cells via inhibiting YAP through AMOT
Authors: Zhu Guoqing , Chen Yan , Zhang Xiao , Wu Qi , Zhao Yinghui , Chen Yuxin , Sun Fenyong , Qiao Yongxia , Wang Jiayi
Published: March 2017

TPA stimulates carcinogenesis in various types of cancers. However, we found that TPA inhibits transformative phenotypes in liver cancer cells via the translocation of YAP from the nucleus, where it functions as a transcriptional co-factor, to the cytoplasm. Such effects led to a separation of YAP from its dependent transcription factors. The inhibitory effects of TPA on YAP were AMOT dependent. Without AMOT, TPA was unable to alter YAP activity. Importantly, the depletion of YAP and AMOT blocked the TPA-reduced transformative phenotypes. In sum, TPA has been established as an anti-tumorigenic drug in liver cancer cells via YAP and AMOT.
The epidemic dynamics of hepatitis C virus subtypes 4a and 4d in Saudi Arabia
Authors: Al-Qahtani Ahmed A. , Baele Guy , Khalaf Nisreen , Suchard Marc A. , Al-Anazi Mashael R. , Abdo Ayman A. , Sanai Faisal M. , Al-Ashgar Hamad I. , Khan Mohammed Q. , Al-Ahdal Mohammed N. , Lemey Philippe , Vrancken Bram
Published: March 2017

The relatedness between viral variants sampled at different locations through time can provide information pertinent to public health that cannot readily be obtained through standard surveillance methods. Here, we use virus genetic data to identify the transmission dynamics that drive the hepatitis C virus subtypes 4a (HCV4a) and 4d (HCV4d) epidemics in Saudi Arabia. We use a comprehensive dataset of newly generated and publicly available sequence data to infer the HCV4a and HCV4d evolutionary histories in a Bayesian statistical framework. We also introduce a novel analytical method for an objective assessment of the migration intensity between locations. We find that international host mobility patterns dominate over within country spread in shaping the Saudi Arabia HCV4a epidemic, while this may be different for the HCV4d epidemic. This indicates that the subtypes 4a and 4d burden can be most effectively reduced by combining the prioritized screening and treatment of Egyptian immigrants with domestic prevention campaigns. Our results highlight that the joint investigation of evolutionary and epidemiological processes can provide valuable public health information, even in the absence of extensive metadata information.
Standardized Herbal Formula PM014 Inhibits Radiation-Induced Pulmonary Inflammation in Mice
Authors: Kim Jee-Youn , Shin Dasom , Lee Gihyun , Kim Jin-Mo , Kim Dongwook , An Yong-Min , Yoo Byung Rok , Chang Hanna , Kim Miran , Cho Jaeho , Bae Hyunsu
Published: March 2017

Radiation therapy is widely used for thoracic cancers. However, it occasionally causes radiation-induced lung injuries, including pneumonitis and fibrosis. Chung-Sang-Bo-Ha-Tang (CSBHT) has been traditionally used to treat chronic pulmonary disease in Korea. PM014, a modified herbal formula derived from CSBHT, contains medicinal herbs of seven species. In our previous studies, PM014 exhibited anti-inflammatory effects in a chronic obstructive pulmonary disease model. In this study, we have evaluated the effects of PM014 on radiation-induced lung inflammation. Mice in the treatment group were orally administered PM014 six times for 2 weeks. Effects of PM014 on radiation pneumonitis were evaluated based on histological findings and differential cell count in bronchoalveolar lavage fluid. PM014 treatment significantly inhibited immune cell recruitment and collagen deposition in lung tissue. Normal lung volume, evaluated by radiological analysis, in PM014-treated mice was higher compared to that in irradiated control mice. PM014-treated mice exhibited significant changes in inspiratory capacity, compliance and tissue damping and elastance. Additionally, PM014 treatment resulted in the downregulation of inflammatory cytokines, chemokines, and fibrosis-related genes and a reduction in the transforming growth factor-β1-positive cell population in lung tissue. Thus, PM014 is a potent therapeutic agent for radiation-induced lung fibrosis and inflammation.
Gene-based genome-wide association study identified 19p13.3 for lean body mass
Authors: Ran Shu , Zhang Lei , Liu Lu , Feng An-Ping , Pei Yu-Fang , Zhang Lei , Han Ying-Ying , Lin Yong , Li Xiao , Kong Wei-Wen , You Xin-Yi , Zhao Wen , Tian Qing , Shen Hui , Zhang Yong-Hong , Deng Hong-Wen
Published: March 2017

Lean body mass (LBM) is a complex trait for human health. To identify genomic loci underlying LBM, we performed a gene-based genome-wide association study of lean mass index (LMI) in 1000 unrelated Caucasian subjects, and replicated in 2283 unrelated Caucasians subjects. Gene-based association analyses highlighted the significant associations of three genes UQCR, TCF3 and MBD3 in one single locus 19p13.3 (discovery p = 6.10 × 10−5, 1.65 × 10−4 and 1.10 × 10−4; replication p = 2.21 × 10−3, 1.84 × 10−3 and 6.95 × 10−3; combined p = 2.26 × 10−6, 4.86 × 10−6 and 1.15 × 10−5, respectively). These results, together with the known functional relevance of the three genes to LMI, suggested that the 19p13.3 region containing UQCR, TCF3 and MBD3 genes was a novel locus underlying lean mass variation.
An aqueous electrolyte of the widest potential window and its superior capability for capacitors
Authors: Tomiyasu Hiroshi , Shikata Hirokazu , Takao Koichiro , Asanuma Noriko , Taruta Seiichi , Park Yoon-Yul
Published: March 2017

A saturated aqueous solution of sodium perchlorate (SSPAS) was found to be electrochemically superior, because the potential window is remarkably wide to be approximately 3.2 V in terms of a cyclic voltammetry. Such a wide potential window has never been reported in any aqueous solutions, and this finding would be of historical significance for aqueous electrolyte to overcome its weak point that the potential window is narrow. In proof of this fact, the capability of SSPAS was examined for the electrolyte of capacitors. Galvanostatic charge-discharge measurements showed that a graphite-based capacitor containing SSPAS as an electrolyte was stable within 5% deviation for the 10,000 times repetition at the operating voltage of 3.2 V without generating any gas. The SSPAS worked also as a functional electrolyte in the presence of an activated carbon and metal oxides in order to increase an energy density. Indeed, in an asymmetric capacitor containing MnO2 and Fe3O4 mixtures in the positive and negative electrodes, respectively, the energy density enlarged to be 36.3 Whkg−1, which belongs to the largest value in capacitors. Similar electrochemical behaviour was also confirmed in saturated aqueous solutions of other alkali and alkaline earth metal perchlorate salts.
Agonist-mediated assembly of the crustacean methyl farnesoate receptor
Authors: Kakaley Elizabeth K. Medlock , Wang Helen Y. , LeBlanc Gerald A.
Published: March 2017

The methyl farnesoate receptor (MfR) orchestrates aspects of reproduction and development such as male sex determination in branchiopod crustaceans. Phenotypic endpoints regulated by the receptor have been well-documented, but molecular interactions involved in receptor activation remain elusive. We hypothesized that the MfR subunits, methoprene-tolerant transcription factor (Met) and steroid receptor coactivator (SRC), would be expressed coincident with the timing of sex programming of developing oocytes by methyl farnesoate in daphnids. We also hypothesized that methyl farnesoate activates MfR assembly. Met mRNA was expressed rhythmically during the reproductive cycle, with peak mRNA accumulation just prior period of oocytes programming of sex. Further, we revealed evidence that Met proteins self-associate in the absence of methyl farnesoate, and that the presence of methyl farnesoate stimulates dissociation of Met multimers with subsequent association with SRC. Results demonstrated that the Met subunit is highly dynamic in controlling the action of methyl farnesoate through temporal variation in its expression and availability for receptor assembly.
Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development
Authors: Lee Hyunseung , Kim Mihwa , Baek Minwoo , Morales Liza D. , Jang Ik-Soon , Slaga Thomas J. , DiGiovanni John , Kim Dae Joon
Published: March 2017

Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2fl/fl) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP deficiency also resulted in a significant increase in epidermal thickness and hyperproliferation following exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis showed that both phosphorylated STAT3 and phosphorylated AKT expressions were significantly increased in epidermis of TC-PTP-deficient mice compared to control mice following TPA treatment. Inhibition of STAT3 or AKT reversed the effects of TC-PTP deficiency on apoptosis and proliferation. Finally, TC-PTP knockout mice showed a shortened latency of tumorigenesis and significantly increased numbers of tumors during two-stage skin carcinogenesis. Our findings reveal that TC-PTP has potential as a novel target for the prevention of skin cancer through its role in the regulation of STAT3 and AKT signaling.
Enhanced Transmissions Through Three-dimensional Cascade Sharp Waveguide Bends Using C-slit Diaphragms
Authors: Yang Rui , Hu Bowei , Zhang Aofang , Gao Dongxing , Wang Hui , Shi Ayuan , Lei Zhenya , Yang Pei
Published: March 2017

Transmission properties through sharp rectangular waveguide bends are investigated to determine the cut-off bending angles of the wave propagation. We show that a simple metallic diaphragm at the bending corner with properly devised sub-wavelength defect apertures of C-slits would be readily to turn on the transmissions with scarce reflections of the propagating modes, while preserving the integrity of the transmitting fields soon after the bends. In particularly, our design also demonstrates the capability of eliminating all the unwanted cavity resonant transmissions that exist in the three-dimensional cascade sharp waveguide bends, and solely let the desired signals travel along the whole passage of the waveguide. The present approach, using C-slit diaphragms to support the sharp bending behaviors of the guided waves with greatly enhanced transmissions, would be especially effective in constructing novel waveguides and pave the way for the development of more compact and miniaturized electromagnetic systems that exploit these waveguide bends.
A global reference model of Curie-point depths based on EMAG2
Authors: Li Chun-Feng , Lu Yu , Wang Jian
Published: March 2017

In this paper, we use a robust inversion algorithm, which we have tested in many regional studies, to obtain the first global model of Curie-point depth (GCDM) from magnetic anomaly inversion based on fractal magnetization. Statistically, the oceanic Curie depth mean is smaller than the continental one, but continental Curie depths are almost bimodal, showing shallow Curie points in some old cratons. Oceanic Curie depths show modifications by hydrothermal circulations in young oceanic lithosphere and thermal perturbations in old oceanic lithosphere. Oceanic Curie depths also show strong dependence on the spreading rate along active spreading centers. Curie depths and heat flow are correlated, following optimal theoretical curves of average thermal conductivities K = ~2.0 W(m°C)−1 for the ocean and K = ~2.5 W(m°C)−1 for the continent. The calculated heat flow from Curie depths and large-interval gridding of measured heat flow all indicate that the global heat flow average is about 70.0 mW/m2, leading to a global heat loss ranging from ~34.6 to 36.6 TW.
Identification of an RNase that preferentially cleaves A/G nucleotides
Authors: Xie Jumin , Chen Zhen , Zhang Xueyan , Chen Honghe , Guan Wuxiang
Published: March 2017

Ribonucleases play an important role in the RNA metabolism which is critical for the localization, stability and function of mature RNA transcripts. More and more ribonucleases were discovered in recent years with the progress of technology. In the present study, we found that the uncharacterized C19orf43, a novel interacting protein of human telomerase RNA (hTR), digested T7 transcribed RNA, total cellular RNA and RNA oligos but not DNA. Thus we named this new RNase as hTRIR (human telomerase RNA interacting RNase). Genetic analysis showed that hTRIR is conserved among eukaryotic species and widely expressed in different cell lines. The RNase activity of hTRIR works in a broad temperature and pH range while divalent cations are not required. The conserved C-terminus of C19orf43 is necessary for its activity. Finally, we found that hTRIR cleaves all four unpaired RNA nucleotides from 5′ end or 3′ end with higher efficiency for purine bases, which suggested that hTRIR is an exoribonuclease. Taken together, our study showed the first evidence of the novel function of hTRIR in vitro, which provides clue to study the regulatory mechanism of hTR homeostasis in vivo.
Treadmill exercise suppressed stress-induced dendritic spine elimination in mouse barrel cortex and improved working memory via BDNF/TrkB pathway
Authors: Chen K , Zhang L , Tan M , Lai C S W , Li A , Ren C , So K-F
Published: March 2017

Stress-related memory deficit is correlated with dendritic spine loss. Physical exercise improves memory function and promotes spinogenesis. However, no studies have been performed to directly observe exercise-related effects on spine dynamics, in association with memory function. This study utilized transcranial two-photon in vivo microscopy to investigate dendritic spine formation and elimination in barrel cortex of mice under physical constrain or naive conditions, followed by memory performance in a whisker-dependent novel texture discrimination task. We found that stressed mice had elevated spine elimination rate in mouse barrel cortex plus deficits in memory retrieval, both of which can be rescued by chronic exercise on treadmill. Exercise also elevated brain-derived neurotrophic factor (BDNF) expression in barrel cortex. The above-mentioned rescuing effects for both spinognesis and memory function were abolished after inhibiting BDNF/tyrosine kinase B (TrkB) pathway. In summary, this study demonstrated the improvement of stress-associated memory function by exercise via facilitating spine retention in a BDNF/TrkB-dependent manner.
Magnetic iron oxide nanoparticles for the collection and direct measurement of adsorbed alpha-emitting radionuclides from environmental waters by liquid scintillation analysis
Authors: O'Hara Matthew J. , Addleman R. Shane
Published: March 2017

Radioactive contamination, be it from accidental or intentional release, can create an urgent need to assess water and food supplies and the environment, and monitor human health.
An EC-QCL based N2O sensor at 5.2 μm using cavity ring-down spectroscopy for environmental applications
Authors: Banik Gourab Dutta , Som Suman , Maity Abhijit , Pal Mithun , Maithani Sanchi , Mandal Santanu , Pradhan Manik
Published: March 2017

A laser based N2O sensor for atmospheric measurement.
Protecting patches in colloidal synthesis of Au semishells
Authors: Mann Daniel , Voogt Stefanie , van Zandvoort Ryan , Keul Helmut , Möller Martin , Verheijen Marcel , Nascimento-Duplat Daniel , Xu Man , Urbach H. Paul , Adam Aurèle J. L. , Buskens Pascal
Published: March 2017

Extending the concept of protecting group chemistry from molecular to colloidal synthesis: three-step colloidal synthesis of Au semishells as a prototypical example.
Simple synthesis of multiple length-scale structured Nb2O5with functional macrodomain-integrated mesoporous frameworks
Authors: Kim Seongseop , Jeong Inyoung , Hwang Jongkook , Ko Min Jae , Lee Jinwoo
Published: March 2017

Multiple length-scale structured Nb2O5was synthesized by the interplay of macro- and microphase separation and macro-/mesostructures exhibit light-scattering capability and high surface areas.
Enantiomeric two-fold interpenetrated 3D zinc(ii) coordination networks as a catalytic platform: significant difference between water within the cage and trace water in transesterification
Authors: Choi Eunkyung , Ryu Minjoo , Lee Haeri , Jung Ok-Sang
Published: March 2017

The steric hindrance of reactants and trace water effects on transesterification catalysis using the cage coordination network have been scrutinized.
Selective C–C coupling at a Pt(iv) centre: 100% preference for sp2–sp3 over sp3–sp3
Authors: Shaw Paul A. , Rourke Jonathan P.
Published: March 2017

Oxidative addition of alkyl halides to platinum(ii) gives six-coordinate platinum(iv) complexes that spontaneously reductively couple with complete selectivity.
Photophysical properties of a series of cycloplatinated(ii) complexes featuring allyldiphenylphosphane
Authors: Shahsavari Hamid R. , Babadi Aghakhanpour Reza , Babaghasabha Mojgan , Golbon Haghighi Mohsen , Nabavizadeh S. Masoud , Notash Behrouz
Published: March 2017

Cycloplatinated(ii) complexes 1–4 were synthesized and characterized. All complexes exhibit strong luminescence except 3.
Hot off the press
Authors: Hill Robert A. , Sutherland Andrew
Published: March 2017

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as furanmonogone A from Hypericum monogynum.
Efficient synthesis of polymethoxyselenoflavones via regioselective direct C–H arylation of selenochromones
Authors: Yang Woo-Ram , Choi Yong-Sung , Jeong Jin-Hyun
Published: March 2017

A simple direct C–H arylation of two difficult coupling partners, selenochromones and electron-rich aryl bromide, has been developed, affording diverse polymethoxyselenoflavones with great efficiency and high selectivity.
Tunable design of yolk–shell ZnFe2O4@RGO@TiO2 microspheres for enhanced high-frequency microwave absorption
Authors: Feng Jiantao , Wang Yechen , Hou Yanhui , Li Liangchao
Published: March 2017

Yolk–shell ZnFe2O4@RGO@TiO2 microspheres with a tunable void size and TiO2 shell thickness possess enhanced high-frequency microwave absorption properties.
N-annulated perylene diimide dimers: the effect of thiophene bridges on physical, electronic, optical, and photovoltaic properties
Authors: Hendsbee Arthur D. , Dayneko Sergey V. , Pells Jefferson A. , Cann Jonathan R. , Welch Gregory C.
Published: March 2017

In this work, we report on the synthesis, characterization, and photovoltaic properties of two new N-annulated PDI derivatives connected with one (M1) or two (M2) thiophene bridging units and directly compare to a twisted PDI dimer with no thiophene units (tPDI-Hex).
Cobalt–borate nanowire array as a high-performance catalyst for oxygen evolution reaction in near-neutral media
Authors: Ren Xiang , Ge Ruixiang , Zhang Yong , Liu Danni , Wu Dan , Sun Xu , Du Bin , Wei Qin
Published: March 2017

As a durable catalyst, cobalt–borate nanowire array on Ti mesh exhibits high activity for water oxidation in near-neutral media, thereby achieving a geometrical catalytic current density of 10 mA cm−2 at an overpotential of 420 mV.
Design of coherent anode materials with 0D Ni3S2nanoparticles self-assembled on 3D interconnected carbon networks for fast and reversible sodium storage
Authors: Zhao Xu , Wang Hong-En , Massé Robert C. , Cao Jian , Sui Jiehe , Li Jiangyu , Cai Wei , Cao Guozhong
Published: March 2017

Coherent Ni3S2/carbon nanocomposites were designed and successfully synthesized. Outstanding Na-ion-storage performances are attributed to effectively alleviated volume changes and confined poly-sulfides.
Analysis and implementation of high‐gain non‐isolated DC–DC boost converter
Authors: Muhammad Musbahu , Armstrong Matthew , Elgendy Mohammed A.
Published: March 2017

High step‐up DC–DC converters are increasingly required in many industrial applications. Conventional topologies operate at extreme duty cycle, high‐semiconductor voltage stress, switching loss, and diode reverse recovery problems. This study presents a new non‐isolated high gain, boost converter operating with a modest duty cycle by integrating a coupled inductor and switched capacitor technique. Importantly, the structure of the high‐voltage side, together with the switched capacitor, reduces the voltage stress of the power switch to less than one third of the output voltage, which in turn helps to reduce the conduction loss by using a low on‐resistance (Rds‐on) switch. The diode voltage stress is less than the output voltage which facilitates faster recovery. Furthermore, the converter employs a passive clamp circuit to recycle the leakage energy. The main switch achieves zero current switching (ZCS) turn‐on performance and all diodes achieve (ZCS) turn off reducing reverse recovery related losses. As a result, the circuit exhibits high efficiency performance; which is essential for most modern power electronic applications. In this study, the operational principle and performance characteristics of the proposed converter is presented and validated experimentally with a 250 W, 20V input voltage/190V output voltage prototype circuit.
Design guidelines for MPC‐based frequency regulation for islanded microgrids with storage, voltage, and ramping constraints
Authors: Liang Liang , Hou Yunhe , Hill David John
Published: March 2017

This study addresses the frequency regulation for a microgrid under islanded mode with variable renewables. Due to the structure and parameters of microgrids, the frequency of the system and the voltages on the buses are coupled. Furthermore, to smooth out the fast fluctuations of renewables, the controllability of components are quantified accurately. In this study, some critical and realistic considerations are identified and modelled, and the guidelines for battery energy storage system (BESS) sizing are thus obtained. First, the frequency and voltage regulation loops are coordinated by a non‐linear model predictive control (MPC) controller, and the controllable resources are sequentially dispatched. Second, the dynamic model for evaluating the state of charge (SOC) of BESS under a fast response is introduced. Finally, general guidelines of the required energy capacity of BESS and the length of MPC control horizons are quantified by deriving the process of the responding disturbances. Ramping rates and response time delays of controllable resources are involved in the mathematical analysis. The simulation results show that the effectiveness of the proposed MPC controller and design guidelines can be generalised for microgrids in islanded mode with two kinds of controllable operating resources, which are represented by diesel generators and BESS.
Expected signatures from hadronic emission processes in the TeV spectra of BL Lacertae objects
Authors: Zech A. , Cerruti M. , Mazin D.
Published: March 2017

Context. The wealth of recent data from Imaging Air Cherenkov telescopes (IACTs), ultra-high energy cosmic-ray experiments and neutrino telescopes have fuelled a renewed interest in hadronic emission models for γ-loud blazars.

Aims. We explore physically plausible solutions for a lepto-hadronic interpretation of the stationary emission from high-frequency peaked BL Lac objects (HBLs). The modelled spectral energy distributions are then searched for specific signatures at very high energies that could help to distinguish the hadronic origin of the emission from a standard leptonic scenario.

Methods. By introducing a few basic constraints on parameters of the model, such as assuming the co-acceleration of electrons and protons, we significantly reduced the number of free parameters. We then systematically explored the parameter space of the size of the emission region and its magnetic field for two bright γ-loud HBLs, PKS 2155-304 and Mrk 421. For all solutions close to equipartition between the energy densities of protons and of the magnetic field, and with acceptable jet power and light-crossing timescales, we inspected the spectral hardening in the multi-TeV domain from proton-photon induced cascades and muon-synchrotron emission inside the source. Very-high-energy spectra simulated with the available instrument functions from the future Cherenkov Telescope Array (CTA) were evaluated for detectable features as a function of exposure time, source redshift, and flux level.

Results. A range of hadronic scenarios are found to provide satisfactory solutions for the broad band emission of the sources under study. The TeV spectrum can be dominated either by proton-synchrotron emission or by muon-synchrotron emission. The solutions for HBLs cover a parameter space that is distinct from the one found for the most extreme BL Lac objects in an earlier study. Over a large range of model parameters, the spectral hardening due to internal synchrotron-pair cascades, the “cascade bump”, should be detectable for acceptable exposure times with the future CTA for a few nearby and bright HBLs.
Supplier-retailer production and inventory models with defective items and inspection errors in non-cooperative and cooperative environments
Authors: Yang Chih-Te , Ho Chia-Huei , Lee Hsiu-Mei , Ouyang Liang-Yuh
Published: March 2017

This paper proposes single-supplier single-retailer production and inventory models for maximizing the supplier and retailer’s profits in non-cooperative and cooperative environments. The effect of defective items and inspection errors are considered in the proposed models. In addition, we consider that the supplier offers the retailer a quantity threshold to absorb transportation costs for promoting the economies of scale of transport. Mathematical analyses are conducted, and optimal equilibrium production and replenishment strategies for the supplier and retailer are derived under non-cooperative and cooperative situations. Subsequently, we establish two algorithms to explain the optimal equilibrium solutions for these cases. Finally, several numerical examples and a sensitivity analysis with respect to major parameters are presented to demonstrate the theoretical results, compare the distinct solutions, and derive managerial insights.
Multiscale simulations of anisotropic particles combining molecular dynamics and Green’s function reaction dynamics
Authors: Vijaykumar Adithya , Ouldridge Thomas E. , ten Wolde Pieter Rein , Bolhuis Peter G.
Published: March 2017

The modeling of complex reaction-diffusion processes in, for instance, cellular biochemical networks or self-assembling soft matter can be tremendously sped up by employing a multiscale algorithm which combines the mesoscopic Green’s Function Reaction Dynamics (GFRD) method with explicit stochastic Brownian, Langevin, or deterministic molecular dynamics to treat reactants at the microscopic scale [A. Vijaykumar, P. G. Bolhuis, and P. R. ten Wolde, J. Chem. Phys. 143, 214102 (2015)]. Here we extend this multiscale MD-GFRD approach to include the orientational dynamics that is crucial to describe the anisotropic interactions often prevalent in biomolecular systems. We present the novel algorithm focusing on Brownian dynamics only, although the methodology is generic. We illustrate the novel algorithm using a simple patchy particle model. After validation of the algorithm, we discuss its performance. The rotational Brownian dynamics MD-GFRD multiscale method will open up the possibility for large scale simulations of protein signalling networks.
The glass transition temperature of thin films: A molecular dynamics study for a bead-spring model
Authors: Stevenson Craig S. , Curro John G. , McCoy John D.
Published: March 2017

Molecular dynamics simulations were carried out on free-standing liquid films of different thicknesses h using a bead-spring model of 10 beads per chain. The glass transition temperatures, Tg, of the various films were determined from plots of the internal energy versus temperature. We used these simulations to test the validity of our earlier conjecture that the glass transition of a confined liquid could be approximated by pre-averaging over the non-uniform density profile of the film. Using the density profiles from our simulations, we computed the average density of the free-standing films as a function of temperature. In all our film simulations we found, within the error of the simulation, that Tg of the film occurred at the same density (or packing fraction) as the bulk system at the bulk glass transition temperature TgB. By equating these densities at their respective glass transition temperatures, as suggested by the simulations, we deduced that Tg/TgB is proportional to h0/h. This is consistent with previous simulations and experimental data. Moreover, the parameter h0 is determinable in our model from the density profile of the films.
Formation of coffee-stain patterns at the nanoscale: The role of nanoparticle solubility and solvent evaporation rate
Authors: Zhang Jianguo , Milzetti Jasmin , Leroy Frédéric , Müller-Plathe Florian
Published: March 2017

When droplets of nanoparticle suspension evaporate from surfaces, they leave behind a deposit of nanoparticles. The mechanism of evaporation-induced pattern formation in the deposit is studied by molecular dynamics simulations for sessile nanodroplets. The influence of the interaction between nanoparticles and liquid molecules and the influence of the evaporation rate on the final deposition pattern are addressed. When the nanoparticle-liquid interaction is weaker than the liquid-liquid interaction, an interaction-driven or evaporation-induced layer of nanoparticles appears at the liquid-vapor interface and eventually collapses onto the solid surface to form a uniform deposit independently of the evaporation rate. When the nanoparticle-liquid and liquid-liquid interactions are comparable, the nanoparticles are dispersed inside the droplet and evaporation takes place with the contact line pinned at a surface defect. In such a case, a pattern with an approximate ring-like shape is found with fast evaporation, while a more uniform distribution is observed with slower evaporation. When the liquid-nanoparticle interaction is stronger than the liquid-liquid interaction, evaporation always occurs with receding contact line. The final deposition pattern changes from volcano-like to pancake-like with decreasing evaporation rate. These findings might help to design nanoscale structures like nanopatterns or nanowires on surface through controlled solvent evaporation.