bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of Basic, Amphoteric, and Acidic Catalysts in the Oxidative Coupling of Methanol and Ethanol for Acrolein Production
Authors: Lilić Aleksandra , Wei Tiantian , Bennici Simona , Devaux Jean‐François , Dubois Jean‐Luc , Auroux Aline
Published: July 2017

The impact of acid/base properties (determined by adsorption microcalorimetry) of various catalysts on the cross‐aldolization of acetaldehyde and formaldehyde leading to acrolein was methodically studied in oxidizing conditions starting from a mixture of methanol and ethanol. The aldol condensation and further dehydration to acrolein were carried out on catalysts presenting various acid/base properties (MgO, Mg–Al oxides, Mg/SiO2, NbP, and heteropolyanions on silica, HPA/SiO2). Thermodynamic calculations revealed that cross‐aldolization is always favored compared with self‐aldolization of acetaldehyde, which leads to crotonaldehyde formation. The presence of strong basic sites is shown to be necessary, but a too high amount drastically increases COx production. On strong acid sites, production of acrolein and carbon oxides (COx) does not increase with temperature. The optimal catalyst for this process should be amphoteric with a balanced acid/base cooperation of medium strength sites and a small amount (<100 μmol g−1) of very strong basic sites (Qdiff>150 kJ mol−1).
Generation of electromagnetic waves in the terahertz frequency range by optical rectification of a Gaussian laser pulse in a plasma in presence of an externally applied static electric field
Authors: Singh Ram Kishor , Kumar Subodh , Sharma R.P.
Published: July 2017

We propose a theoretical model for the generation of electromagnetic waves in the terahertz (THz) frequency range by the optical rectification of a Gaussian laser pulse in a plasma with an applied static electric field transverse to the direction of propagation. A Gaussian laser pulse can exert a transverse component of the quasi‐static ponderomotive force on the electrons at a frequency in the THz range by a suitable choice of the laser pulse width. This nonlinear force is responsible for the density oscillation. The coupling of this oscillation with the drift velocity acquired by electrons due to the applied static electric field leads to the generation of a nonlinear current density. A spatial Gaussian intensity profile of the laser beam enhances the generated THz yield by many folds as compared to a uniform spatial intensity profile.
An energy‐efficient clustering approach for collaborative data forwarding in heterogeneous MANET
Authors: Mohindra Anubhuti Roda , Gandhi Charu
Published: July 2017

Mobile ad hoc network consists of a group of mobile nodes that can communicate with each other without any infrastructure. Clustering of the mobile nodes ensures efficient use of available bandwidth and high network throughput. Various clustering schemes are developed to improve the energy efficiency and lifetime of the network. However, there is an increase in the energy consumption with the increase in the number of clusters for forwarding data. This paper presents an energy‐efficient clustering approach for collaborative data forwarding in mobile ad hoc network. The cluster head (CH) is selected based on the processing capability of the nodes and link connection metrics. The CH receives the data from the server and forwards the data to the member nodes at a corresponding data rate of the nodes. Data offloading technique manages the data traffic in the network. The CH rejoining approach enables load balancing in the network. The proposed clustering approach achieves a significant reduction in the energy consumption and data traffic and improvement in the throughput rate through stable routing.
Specification of neurotransmitter identity by Tal1 in thalamic nuclei
Authors: Lee Bumwhee , Lee Myungsin , Song Somang , Loi Linh Duc , Lam Duc Tri , Yoon Jaeseung , Baek Kwanghee , Curtis David J. , Jeong Yongsu
Published: July 2017

Background: The neurons contributing to thalamic nuclei are derived from at least two distinct progenitor domains: the caudal (cTH) and rostral (rTH) populations of thalamic progenitors. These neural compartments exhibit unique neurogenic patterns, and the molecular mechanisms underlying the acquisition of neurotransmitter identity remain largely unclear. Results: T‐cell acute lymphocytic leukemia protein 1 (Tal1) was expressed in the early postmitotic cells in the rTH domain, and its expression was maintained in mature thalamic neurons in the ventrolateral geniculate nucleus (vLG) and the intergeniculate leaflet (IGL). To investigate a role of Tal1 in thalamic development, we used a newly generated mouse line driving Cre‐mediated recombination in the rTH domain. Conditional deletion of Tal1 did not alter regional patterning in the developing diencephalon. However, in the absence of Tal1, rTH‐derived thalamic neurons failed to maintain their postmitotic neuronal features, including neurotransmitter profile. Tal1‐deficient thalamic neurons lost their GABAergic markers such as Gad1, Npy, and Penk in IGL/vLG. These defects may be associated at least in part with down‐regulation of Nkx2.2, which is known as a critical regulator of rTH‐derived GABAergic neurons. Conclusions: Our results demonstrate that Tal1 plays an essential role in regulating neurotransmitter phenotype in the developing thalamic nuclei. Developmental Dynamics 246:749–758, 2017. © 2017 Wiley Periodicals, Inc.
Effects of parasitic infection and reproduction on corticosterone plasma levels in Galápagos land iguanas,Conolophus marthaeandC. subcristatus
Authors: Onorati Michela , Sancesario Giulia , Pastore Donatella , Bernardini Sergio , Cruz Marilyn , Carrión Jorge E. , Carosi Monica , Vignoli Leonardo , Lauro Davide , Gentile Gabriele
Published: July 2017

In vertebrates, one main feature of stress response is the release of glucocorticoids (corticosterone in reptiles), steroid hormones whose synthesis is regulated by the hypothalamic–pituitary–adrenal axis (HPA). In the Galápagos Islands, populations of land iguanas are differentially impacted by a tick‐transmitted apicomplexan hemoparasite of genusHepatozoon, which could cause diseases and ultimately reduce fitness. Using competitive enzyme‐linked immunosorbent assays (ELISA), we examined baseline plasma corticosterone levels of two syntopic and highly parasitized populations of the land iguana speciesConolophus marthaeandC. subcristatusin Wolf volcano (Isabela Island). We also used a poorly parasitized population ofC. subcristatusfrom the same island (Bahia Urbina) as a reference. To better interpret the observed glucocorticoids patterns, we simultaneously performed the count of white blood cells (WBCs) in all individuals and investigated the reproductive status of females. We did not find evidence in support of either a positive or negative relationship between the tick load, hemoparasite infection, and glucocorticoid plasma concentration inC. marthaeandC. subcristatusat Wolf volcano. The comparison between parasitized and non‐parasitized sites (V. Wolf and Bahia Urbina) would instead suggest an inverse relationship between corticosterone and parasites. Our findings support association between corticosterone plasma levels and reproduction.
BJ‐2266 ameliorates experimental autoimmune encephalomyelitis through down‐regulation of the JAK/STAT signaling pathway
Authors: You Zhiwei , Timilshina Maheshwor , Jeong Byeong‐Seon , Chang Jae‐Hoon
Published: July 2017

CD4+ T cells differentiate into distinct effector subsets upon antigenic stimulation. Cytokines, and micro‐environmental factors present during T‐cell priming, direct differentiation of naïve CD4+ T cells into pro‐inflammatory Th1 and Th17 cells. From extensive screening of 2,4,5‐trimethylpyridin‐3‐ol derivatives with various functional groups at C(6)‐position, BJ‐2266, a 6‐thioureido‐derivative, showed potent inhibitory activity on in vitro T helper (Th)‐cell differentiation. This compound inhibited IFN‐γ and IL‐17 production from polyclonal CD4+ T cells and ovalbumin (OVA)‐specific CD4+ T cells that were activated by T‐cell receptor (TCR) engagement. We assessed the inhibitory effect of BJ‐2266 in experimental autoimmune encephalomyelitis (EAE). Our results suggest that BJ‐2266 treatment significantly suppresses EAE disease progression with reduced generation of Th1 and Th17 cells. Notably, Th‐cell differentiation was significantly suppressed by BJ‐2266 treatment with no effect on apoptosis, activation and proliferation of activated T cells. Furthermore, adoptive transfer of BJ‐2266 treated MOG‐reactive Th1 and Th17 cells led to a lower EAE disease score and better clinical recovery from EAE. The underlying mechanism of BJ‐2266 effect involved the inhibition of JAK/STAT phosphorylation that is critical for Th‐cell differentiation. We conclude that BJ‐2266 regulates the JAK/STAT pathway in response to cytokine signals and subsequently suppresses the differentiation of Th‐cell responses.
Ruthenium‐Catalyzed Alkynylation of Benzoic Acids Mediated by a Weakly Coordination‐Directing Auxiliary
Authors: Chen Changpeng , Zeng Xiaoming
Published: July 2017

A method for the ruthenium‐catalyzed ortho‐alkynylation of benzoic acids was developed. The reaction was found to be directed by a weakly coordinating carboxyl group and offers a facile route for the synthesis of ortho‐alkynylated derivatives. A rare example of a bis(alkynylation) reaction of C–H bonds was described.
Synthesis of Mepivacaine and Its Analogues by a Continuous‐Flow Tandem Hydrogenation/Reductive Amination Strategy
Authors: Suveges Nícolas S. , de Souza Rodrigo O. M. A. , Gutmann Bernhard , Kappe C. Oliver
Published: July 2017

Herein we report a convenient, fast, and high‐yielding method for the generation of the racemic amide anaesthetics mepivacaine, ropivacaine, and bupivacaine. Coupling of α‐picolinic acid and 2,6‐xylidine under sealed‐vessel microwave conditions generates the intermediate amide after a reaction time of only 5 min at 150 °C. Subsequent reaction in a continuous‐flow high‐pressure hydrogenator (H‐Cube ProTM) in the presence of the respective aldehyde directly converts the intermediate to the final amide anaesthetics in a continuous, integrated, multi‐step ring‐hydrogenation/reductive amination protocol. Merits and limitations of the protocol are discussed.
Possible cleavage sites of glutelin partial degradation confirmed by immunological analysis in globulin‐less mutants of rice (Oryza sativa L.)
Authors: Khan Nadar , Yamaguchi Satoru , Katsube‐Tanaka Tomoyuki
Published: July 2017

Proteolytic cleavage or partial degradation of proteins is one of the important post‐translational modifications for various biological processes, but it is difficult to analyze. Previously, we demonstrated that some subunits of the major rice (Oryza sativa L.) seed storage protein glutelin are partially degraded to produce newly identified polypeptides X1‐X5 in mutants in which another major seed storage protein globulin is absent. In this study, the new polypeptides X3 and X4/X5 were immunologically confirmed to be derived from GluA3 and GluA1/GluA2 subunits, respectively. Additionally, the new polypeptides X1 and X2 were at least in part the α polypeptides of the GluB4 subunit partially degraded at the C‐terminus. Simulated 2D‐PAGE migration patterns of intact and partially degraded α polypeptides based on the calculation of their MWs and pIs enabled us to narrow or predict the possible locations of cleavage sites. The predicted cleavage sites were also verified by the comparison of 2D‐PAGE patterns between seed‐extracted and E. coli‐expressed proteins of the intact and truncated α polypeptides. The results and methodologies demonstrated here would be useful for analyses of partial degradation of proteins and the structure–function relationships of rice seed protein bodies.
Improved risk‐targeted performance‐based seismic design of reinforced concrete frame structures
Authors: Franchin Paolo , Petrini Francesco , Mollaioli Fabrizio
Published: July 2017

This paper presents a procedure for seismic design of reinforced concrete structures, in which performance objectives are formulated in terms of maximum accepted mean annual frequency (MAF) of exceedance, for multiple limit states. The procedure is explicitly probabilistic and uses Cornell's like closed‐form equations for the MAFs. A gradient‐based constrained optimization technique is used for obtaining values of structural design variables (members' section size and reinforcement) satisfying multiple objectives in terms of risk levels. The method is practically feasible even for real‐sized structures thanks to the adoption of adaptive equivalent linear models where element‐by‐element stiffness reduction is performed (2 linear analyses per intensity level). General geometric and capacity design constraints are duly accounted for. The procedure is applied to a 15‐storey plane frame building, and validation is conducted against results in terms of drift profiles and MAF of exceedance, obtained by multiple‐stripe analysis with records selected to match conditional spectra. Results show that the method is suitable for performance‐based seismic design of RC structures with explicit targets in terms of desired risk levels.
Choice between series and parallel connections of hysteretic system and viscous damper for seismic protection of structures
Authors: Bougteb Youness , Ray Tathagata
Published: July 2017

Supplemental viscous damping devices are generally envisioned to be connected in parallel to the inelastic parent structure or hysteretic damping devices. This gives rise to higher base shear, and often greater ductility demand of the hysteretic system. The series connection of the viscous and hysteretic system (the inelastic structure or a damper) is an alternative approach. In this paper, comparisons between the series and parallel connections of the hysteretic system and viscous dampers are done through response spectra analyses of single degree of freedom structures. Ductility demand of the hysteretic system and the total base shear are chosen as the response quantities. For the series model, a semi‐implicit solution scheme for classical Maxwell model is modified to include the inelasticity of the time‐independent hysteretic spring. It is observed that the series connection of the 2 dampers gives lower base shear than does the parallel connection. For long‐period and low‐damping structures, the ductility demand of the hysteretic system in series connection is higher than that in parallel connection. Increasing the viscous damping in series connection reduces the ductility demand substantially, lower than that obtained in parallel connection. Practical methods for implementing the series and parallel connections, in line with roof isolation, are also suggested.
Identification of isobutyl angelate, isoamyl angelate and 2‐methylbutyl isobutyrate as active constituents in Roman chamomile essential oil that promotes mouse ambulation
Authors: Umezu Toyoshi , Sano Tomoharu , Hayashi Junko , Yoshikawa Yasuko , Shibata Yasuyuki
Published: July 2017

Roman chamomile (Chamaemelum nobile or Anthemis nobilis) has traditionally been used for health care, health maintenance and medicinal purposes, and the essential oil obtained from the flowers is used as a basic ingredient for aromatherapy. Roman chamomile essential oil (CHA) produces psychostimulant‐like effects, such as the ambulation‐promoting effect, on mouse behaviour. However, mechanisms underlying the effects of CHA remain unclear. The present study aimed to identify the constituents responsible for the ambulation‐promoting effect of CHA and to elucidate a possible neuronal mechanism. GC/MS analysis revealed that isobutyl angelate, isoamyl angelate and 2‐methylbutyl isobutyrate were the major constituents of CHA. These compounds significantly promoted mouse ambulation, and were thus identified as the major active constituents for the ambulatory effect of CHA. The ambulatory effects were attenuated by chlorpromazine and haloperidol, suggesting that the neurotransmitter dopamine is involved in the ambulation‐promoting effects of these constituents similar to already‐known psychostimulants. The results suggest that CHA can change a mental condition, at least in part, through the CNS effects of the constituents identified in the current study. The results also suggest that mental effects of CHA are largely different from those of other Roman chamomile preparations due to the composition difference.
Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study)
Authors: Nakasone Hideki , Terasako‐Saito Kiriko , Hirano Teiichi , Wake Atsushi , Shimizu Seiichi , Kurita Naoki , Yamazaki Etsuko , Usuki Kensuke , Akazawa Kohei , Kanda Junya , Minauchi Koichiro , Yamamoto Go , Tanimoto Shiori , Kamoshita Masaharu , Yokoyama Yasuhisa , Miyaoka Etsuo , Ota Shuichi , Kako Shinichi , Izutsu Koji , Kanda Yoshinobu
Published: July 2017

Complete response (CR) after treatment for multiple myeloma is associated with superior progression‐free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto‐HCT) between 2010 and 2012. If patients did not achieve CR after auto‐HCT, BD consolidation therapy was added to target CR.

After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%). After auto‐HCT (n = 34), greater than or equal to CR was achieved in 9 patients (20%) and very good partial response (VGPR) was achieved in 11 (24%). Of the 24 patients who received auto‐HCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses. Finally, the maximum response with or without BD consolidation was greater than or equal to CR in 19 (41%), VGPR in 7 (15%), and PR in 6 (13%). Through BD consolidation, CR was achieved in 8 of 11 patients with post‐HCT VGPR and in 2 of 12 patients with post‐HCT PR.

In total, 4 year PFS and overall survival were 43 and 80%, respectively. After adjusting for clinical factors, there was no difference in PFS between CR patients after auto‐HCT and BD consolidation, while patients with less than or equal to VGPR after consolidation had a significantly lower PFS.

Patients with post‐HCT CR showed good PFS, and targeting CR through BD consolidation could improve the CR rate. It would be worthwhile to prospectively compare the efficacy of consolidation only for patients who failed to achieve CR to a universal consolidation strategy.
Vegetation impacts soil water content patterns by shaping canopy water fluxes and soil properties
Authors: Metzger Johanna Clara , Wutzler Thomas , Dalla Valle Nicolas , Filipzik Janett , Grauer Christoph , Lehmann Robert , Roggenbuck Martin , Schelhorn Danny , Weckmüller Josef , Küsel Kirsten , Totsche Kai Uwe , Trumbore Susan , Hildebrandt Anke
Published: July 2017

Soil water content is a key variable for biogeochemical and atmospheric coupled processes. Its small‐scale heterogeneity impacts the partitioning of precipitation (e.g., deep percolation or transpiration) by triggering threshold processes and connecting flow paths. Forest hydrologists frequently hypothesized that throughfall and stemflow patterns induce soil water content heterogeneity, yet experimental validation is limited. Here, we pursued a pattern‐oriented approach to explore the relationship between net precipitation and soil water content. Both were measured in independent high‐resolution stratified random designs on a 1‐ha temperate mixed beech forest plot in Germany. We recorded throughfall (350 locations) and stemflow (65 trees) for 16 precipitation events in 2015. Soil water content was measured continuously in topsoil and subsoil (210 profiles). Soil wetting was only weakly related to net precipitation patterns. The precipitation‐induced pattern quickly dissipates and returns to a basic pattern, which is temporally stable. Instead, soil hydraulic properties (by the proxy of field capacity) were significantly correlated with this stable soil water content pattern, indicating that soil structure more than net precipitation drives soil water content heterogeneity. Also, both field capacity and soil water content were lower in the immediate vicinity of tree stems compared to further away at all times, including winter, despite stemflow occurrence. Thus, soil structure varies systematically according to vegetation in our site. We conclude that enhanced macroporosity increases gravity‐driven flow in stem proximal areas. Therefore, although soil water content patterns are little affected by net precipitation, the resulting soil water fluxes may strongly be affected. Specifically, this may further enhance the channelling of stemflow to greater depth and beyond the rooting zone.
Group 9 Transition Metal‐Catalyzed C−H Halogenations
Authors: Lied Fabian , Patra Tuhin , Glorius Frank
Published: July 2017

The high importance of organic halides as synthetic precursors has led to the development of milder and environmentally benign methods for their synthesis. In this regard, transition metal catalyzed C−H activation has emerged as one of the most promising methods for the synthesis of organic halides with high atom economy and excellent stereo‐ and regio‐control. Despite the dominance of palladium and copper catalysts in the field of C−H halogenation reactions, iridium‐, rhodium‐ and cobalt‐complexes have also recently been employed as highly efficient catalysts for the formation of carbon‐halogen bonds. This review describes the current state of the art in the field of C−H halogenation reactions using group nine transition metal (Co, Rh, Ir) catalysts.
Untargeted metabolomics of neuronal cell culture: A model system for the toxicity testing of insecticide chemical exposure
Authors: Hayton Sarah , Maker Garth L. , Mullaney Ian , Trengove Robert D.
Published: July 2017

Toxicity testing is essential for the protection of human health from exposure to toxic environmental chemicals. As traditional toxicity testing is carried out using animal models, mammalian cell culture models are becoming an increasingly attractive alternative to animal testing. Combining the use of mammalian cell culture models with screening‐style molecular profiling technologies, such as metabolomics, can uncover previously unknown biochemical bases of toxicity. We have used a mass spectrometry‐based untargeted metabolomics approach to characterize for the first time the changes in the metabolome of the B50 cell line, an immortalised rat neuronal cell line, following acute exposure to two known neurotoxic chemicals that are common environmental contaminants; the pyrethroid insecticide permethrin and the organophosphate insecticide malathion. B50 cells were exposed to either the dosing vehicle (methanol) or an acute dose of either permethrin or malathion for 6 and 24 hours. Intracellular metabolites were profiled by gas chromatography–mass spectrometry. Using principal components analysis, we selected the key metabolites whose abundance was altered by chemical exposure. By considering the major fold changes in abundance (>2.0 or <0.5 from control) across these metabolites, we were able to elucidate important cellular events associated with toxic exposure including disrupted energy metabolism and attempted protective mechanisms from excitotoxicity. Our findings illustrate the ability of mammalian cell culture metabolomics to detect finer metabolic effects of acute exposure to known toxic chemicals, and validate the need for further development of this process in the application of trace‐level dose and chronic toxicity studies, and toxicity testing of unknown chemicals.
Restorative effects of Chrysin pretreatment on oxidant–antioxidant status, inflammatory cytokine production, and apoptotic and autophagic markers in acute paracetamol‐induced hepatotoxicity in rats: An experimental and biochemical study
Authors: Eldutar Eyup , Kandemir Fatih Mehmet , Kucukler Sefa , Caglayan Cuneyt
Published: July 2017

Paracetamol (PC) is a widely used analgesic and antipyretic drug, but it leads to acute hepatotoxicity at high doses intakes. This study was aimed to investigate the effects of Chrysin (CR) on hepatotoxicity constituted at high doses of PC in rats. Rats were subjected to oral pretreatment of CR (25 and 50 mg/kg b.w.) via feeding needle for 6 days against hepatotoxicity induced by a single dose of PC (500 mg/kg b.w.) administered orally via feeding needles. Although PC increases lipid peroxidation and liver enzyme activities, it has led to reduction of antioxidant enzyme activities. PC induced inflammatory responses by increasing the levels of TNF‐α and IL‐1β. Furthermore, PC caused apoptosis and autophagy by increasing activity of Caspase‐3 and LC3B level. On the other hand, CR therapy significantly regulated these values in rats. This study demonstrated that CR possesses restorative effect against PC‐induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptotic and autophagic tissue damage.
Eribulin regresses a doxorubicin‐resistant Ewing's sarcoma with a FUS‐ERG fusion and CDKN2A‐deletion in a patient‐derived orthotopic xenograft (PDOX) nude mouse model
Authors: Miyake Kentaro , Murakami Takashi , Kiyuna Tasuku , Igarashi Kentaro , Kawaguchi Kei , Li Yunfeng , Singh Arun S. , Dry Sarah M. , Eckardt Mark A. , Hiroshima Yukihiko , Momiyama Masashi , Matsuyama Ryusei , Chishima Takashi , Endo Itaru , Eilber Fritz C. , Hoffman Robert M.
Published: July 2017

Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)‐resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from tumor resected form the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to doxorubicin (DOX) and sensitive to palbociclib and linsitinib. In the present study, the PDOX models were randomized into three groups when the tumor volume reached 60 mm3: G1, untreated control (n = 6); G2, DOX treated (n = 6), intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, Eribulin treated (n = 6, intravenous (i.v.) injection, weekly for 2 weeks). All mice were sacrificed on day 15. Changes in body weight and tumor volume were assessed two times per week. Tumor weight was measured after sacrifice. DOX did not suppress tumor growth compared to the control group (P = 0.589), consistent with the previous results in the patient and PDOX. Eribulin regressed tumor size significantly compared to G1 and G2 (P = 0.006, P = 0.017) respectively. No significant difference was observed in body weight among any group. Our results demonstrate that eribulin is a promising novel therapeutic agent for Ewing's sarcoma.
Toxicity of chemotherapy regimens in advanced and metastatic pancreatic cancer therapy: A network meta‐analysis
Authors: Wang Xiao‐Fang , Huang Wen‐Feng , Nie Jian , Zhou Yong , Tan Ding‐Wu , Jiang Ji‐Hao
Published: July 2017

This network meta‐analysis is adopted in order to compare the toxicity of different chemotherapy regimens in the treatment of advanced/metastatic pancreatic cancer (PC). Randomized controlled trials (RCTs) about different chemotherapy regimens for advanced/metastatic PC were included in this network meta‐analysis using Cochrane Library and PubMed electronic databases. The network meta‐analysis was performed to combine direct and indirect evidence in order to calculate the odd ratios (OR) and draw a surface under the cumulative ranking (SUCRA) curve. A total of 19 RCTs were enrolled in this network meta‐analysis including 12 chemotherapy regimens (Gemcitabine, Gemcitabine + S‐1 [tegafur], Gemcitabine + nab‐paclitaxel, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, FOLFIRINOX [oxaliplatin + irinotecan + fluorouracil + leucovorin], Gemcitabine + oxaliplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, Gemcitabine + pemetrexed, Gemcitabine + 5‐FU, S‐1). The incidence of anemia of Gemcitabine + Capecitabine regimen was higher compared with Gemcitabine regimen, Gemcitabine + pemetrexed regimen exhibited the highest incidence rates of anemia and neutropenia; while Gemcitabine + S‐1, Gemcitabine + Cisplatin and FOLFIRINOX regimens exhibited the highest incidence rates of neutropenia. However, S‐1 regimen exhibited lower incidence rates of leukopenia and thrombocytopenia. Moreover, the incidence rates of nausea/vomiting and rash of Gemcitabine + S‐1 regimen were higher compared with Gemcitabine regimen, while Gemcitabine + Cisplatin regimen had the highest incidence rate of nausea/vomiting. This study demonstrated that the hematologic toxicity of S‐1 regimen was the lowest, while Gemcitabine regimen exhibited the lowest incidence rate of non‐hematologic toxicity, providing guidance for the treatment of advanced/metastatic PC.
ω‐hydroxyundec‐9‐enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines
Authors: Ahn Joungjwa , Chung Youn Wook , Park Jin‐Byung , Yang Kyung Mi
Published: July 2017

ω‐Hydroxyundec‐9‐enoic acid (ω‐HUA), a plant secondary metabolite, exhibits anti‐fungal activity. However, its effect on breast cancer cells is unknown. Here, we investigated the anti‐ breast cancer activity of ω‐HUA and its underlying mechanism. Treatment of human breast cancer cell lines, MDA‐MB‐231 and MDA‐MB‐435, with ω‐HUA induced apoptotic cell death with increased cleaved caspase‐3 and poly (ADP‐ribose) polymerase (PARP) levels, and p38 and JNK phosphorylation. Inhibition of these mitogen‐activated protein kinase (MAPK) pathways using specific inhibitors or siRNA, for p38 and JNK, respectively, blocked the ω‐HUA‐induced apoptosis in a dose‐dependent manner. Moreover, pretreatment of the cells with antioxidant N‐acetyl cysteine (NAC) inhibited ω‐HUA‐induced increased reactive oxygen species (ROS) levels, cleaved caspase‐3 and cleaved PARP, and phosphorylated JNK, phosphorylated p38, and increased cell viability and colony‐forming ability. MDA‐MB‐231 xenograft model showed that the ω‐HUA‐treated group exhibited greater tumor regression and significantly reduced tumor weight compared to that exhibited by the vehicle‐administered group. Collectively, ω‐HUA‐induced intracellular ROS generation induced breast cancer cell apoptosis through JNK and p38 signaling pathway activation, resulting in tumor regression. The results suggested that ω‐HUA is an effective supplement for inhibiting human breast cancer growth.
EPO modified MSCs can inhibit asthmatic airway remodeling in an animal model
Authors: Han Xin‐peng , Zhang Fang‐qi , Tan Xiang‐shu , Liu Liang , Ma Wen‐xian , Ou‐Yang Hai‐Feng , Wu Chang‐Gui
Published: July 2017

There was no effective measures can be obtained at present to reverse or prevent airway remodeling. We investigated the therapeutic effect of Erythropoietin (EPO) gene modified mesenchymal stem cells (MSCs) on asthmatic airway remodeling and the possible underlied molecular mechanisms. EPO gene was transfected into MSCs via lentivirus vector. The transfected cells (EPO‐MSCs) were identified by flow cytometry and the EPO secreting function was detected by PCR and Western blot. MSCs or EPO‐MSCs were administrated to albumin (OVA)‐induced chronic asthmatic mouse model via tail veins. The asthmatic phenotype was analyzed. Number of cells in bronchoalveolar lavage fluid (BALF) was counted using a hemocytometer. Histological findings of airways were evaluated by microscopic examination. The concentrations of interleukin 4(IL‐4), interleukin 5(IL‐5), and interleukin 13(IL‐13) in lung homogenate were determined by ELISA. The activation state of transforming growth factor‐β 1 (TGF‐β1), Transforming growth factor beta‐activated kinase 1 (TAK1), and p38 Mitogen Activated Protein Kinase (p38MAPK) signaling was detected by Real‐Time PCR and Western blotting. EPO‐MSCs were successfully constructed. EPO‐MSCs showed a more potently suppressive effect on local asthmatic airway inflammation and the level of IL‐4, IL‐5, and IL‐13 in lung tissue than MSCs. Moreover, the numbers of goblet cells, the thicknesses of smooth muscle layer, collagen density, percentage of proliferating cell nuclear antigen positive (PCNA+) mesenchymal cells, and von Willebrand factor positive(vWF+) vessels were also significantly inhibited by EPO‐MSCs. Furthermore, EPO‐MSCs could downregulate the expression of TGF‐β1, TAK1, and p38MAPK in lung tissue both in mRNA level and in protein level. EPO gene modified MSCs may more efficiently attenuate asthmatic airway remodeling, which maybe related with the downregulation of TGF‐β1‐TAK1‐p38MAPK pathway activity.
Luteoloside prevents lipopolysaccharide‐induced osteolysis and suppresses RANKL‐induced osteoclastogenesis through attenuating RANKL signaling cascades
Authors: Song Fangming , Wei Chengming , Zhou Lin , Qin An , Yang Mingli , Tickner Jennifer , Huang Yuanjiao , Zhao Jinmin , Xu Jiake
Published: July 2017

Bone destruction or osteolysis marked by excessive osteoclastic bone resorption is a very common medical condition. Identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for prevention and treatment of osteolytic conditions such as periprosthetic joint infection and periprosthetic loosening. Luteoloside, a flavonoid, is a natural bioactive compound with anti‐inflammation and anti‐tumor properties. However, the effect of Luteoloside on inflammation‐induced osteolysis is unknown. Here, we found that Luteoloside exhibited a strong inhibitory effect on lipopolysaccharide (LPS)‐induced osteolysis in vivo. In addition, Luteoloside suppressed RANKL‐induced osteoclast differentiation and abrogated bone resorption in a dose‐dependent manner. Further, we found that the anti‐osteoclastic and anti‐resorptive actions of Luteoloside are mediated via blocking NFATc1 activity and the attenuation of RANKL‐mediated Ca2+ signaling as well as NF‐κB and MAPK pathways. Taken together, this study shows that Luteoloside may be a potential therapeutic agent for osteolytic bone diseases associated with abnormal osteoclast formation and function in inflammatory conditions.
Political Settlements and the Politics of Transformation: Where Do ‘Inclusive Institutions’ Come From?
Authors: Rocha Menocal Alina
Published: July 2017

This article analyses how political settlements can help deepen our understanding of how underlying rules of the game and power relations shape patterns of inclusion and exclusion, and prospects for political, social and economic transformation. Drawing on insights from a growing body of research in the area of the politics of development, the paper explores what kinds of factors have helped to foster more inclusive institutions across the developing world. By way of conclusion, it offers reflections on how a political settlement approach can enable donors to engage more effectively in efforts to foster progressive change. Copyright © 2017 John Wiley & Sons, Ltd.
Burning the Tent Down: Violent Political Settlements in the Democratic Republic of the Congo
Authors: Perera Suda
Published: July 2017

There is a growing consensus amongst those working in conflict‐affected states that political settlements—the formal and informal negotiations, bargains, pacts and agreements made between elite actors—are central to peace and development. Indeed, many now subscribe to the idea that inclusive political settlements are required for positive developmental change. This is based on a notion that political settlements ‘tame’ politics by creating consensus around the rules of political competition and eliminate the need for political violence. However, especially in conflict‐affected states, a focus on political settlements often ignores the (violent) processes by which elites come to power and the extent to which elites may have incentives to maintain violence, even if a political settlement is reached. Through a case study of the Democratic Republic of the Congo, this article shows that political settlements are not always alternatives to violence and that even relatively stable and inclusive political settlements may be heavily underpinned by violence. A political settlement alone is therefore not a sufficient condition to ensure peace and development in a country. If the political settlement is based on an understanding of the rules of the game which incentivises violence and coercion by elites, then the outcome will necessarily be a violent one. As the Democratic Republic of the Congo shows, unless a political settlement directly addresses these predatory incentives, the settlement itself may be a driver of conflict, violence and underdevelopment. Copyright © 2017 John Wiley & Sons, Ltd.
Malawi's Political Settlement: Crafting Poverty and Peace, 1994–2014
Authors: Cammack Diana
Published: July 2017

Since 1994, Malawi's elite have constructed their political settlement in a way that has generally benefited them as a whole and individually. They have established a social contract with the population that mostly maintains enough services to sustain social conciliation, have created a workable though less‐than‐democratic governance arrangement and have done all of this while not establishing a policy environment conducive to national economic development. The paper analyses four ‘critical junctures’ between 1994 and 2014, which are key to Malawi's current political settlement. At each of these, institutions were laid down that have affected political and economic governance. Copyright © 2017 John Wiley & Sons, Ltd.
‘Without Sultan Qaboos, We Would Be Yemen’: The Renaissance Narrative and the Political Settlement in Oman
Authors: Phillips Sarah G. , Hunt Jennifer S.
Published: July 2017

Oman's developmental trajectory is a ‘positive outlier’ to most post‐colonial states, particularly those with significant natural resource reserves. Its trajectory confounds many of the usual expectations surrounding the impact of rentier incomes on conflict and inclusive development. This piece attempts to disentangle the threads of Oman's apparent good fortune to reveal characteristics of its political settlement that may (and may not) have salience elsewhere. This paper spotlights the influence of narrative and the non‐domestic factors that played pivotal roles in the formation and evolution of the political settlement, suggesting that both have generally been understated within the literature to date. © 2017 The Authors Journal of International Development Published by John Wiley & Sons Ltd
Ovarian nests in cultured females of the Siberian sturgeon Acipenser baerii (Chondrostei, Acipenseriformes)
Authors: Żelazowska Monika , Fopp‐Bayat Dorota
Published: July 2017

Ovaries of Acipenser baerii are of an alimentary type and probably are meroistic. They contain ovarian nests, individual follicles, inner germinal ovarian epithelium, and fat tissue. Nests comprise cystoblasts, germline cysts, numerous early previtellogenic oocytes, and somatic cells. Cysts are composed of cystocytes, which are connected by intercellular bridges and are in the pachytene stage of the first meiotic prophase. They contain bivalents, finely granular, medium electron dense material, and nucleoli in the nucleoplasm. Many cystocytes degenerate. Oocytes differ in size and structure. Most oocytes are in the pachytene and early diplotene stages and are referred to as the PACH oocytes. Oocytes in more advanced diplotene stage are referred to as the DIP oocytes. Nuclei in the PACH oocytes contain bivalents and irregularly shaped accumulation of DNA (DNA‐body), most probably corresponding to the rDNA‐body. The DNA‐body is composed of loose, fine granular material, and comprises multiple nucleoli. At peripheries, it is fragmented into blocks that remain in contact with the inner nuclear membrane. In the ooplasm, there is the rough endoplasmic reticulum, Golgi complexes, free ribosomes, complexes of mitochondria with cement, fine fibrillar material containing granules, and lipid droplets. The organelles and material of nuclear origin form a distinct accumulation (a granular ooplasm) in the vicinity of the nucleus. Some of the PACH oocytes are surrounded by flat somatic cells. There are lampbrush chromosomes and multiple nucleoli present (early diplotene stage) in the nucleoplasm. These PACH oocytes and neighboring somatic cells have initiated the formation of ovarian follicles. The remaining PACH oocytes transform to the DIP oocytes. The DIP oocytes contain lampbrush chromosomes and a DNA‐body is absent in nuclei. Multiple nucleoli are numerous in the nucleoplasm and granular ooplasm is present at the vegetal region of the oocyte.
Rapid characterization of chemical constituents of Platycodon grandiflorum and its adulterant Adenophora stricta by UPLC‐QTOF‐MS/MS
Authors: Wang Cuizhu , Zhang Nanqi , Wang Zhenzhou , Qi Zeng , Zheng Bingzhen , Li Pingya , Liu Jinping
Published: July 2017

Platycodon grandiflorum (PG) is extensively used for treating cough, excessive phlegm, sore throat, bronchitis and asthma, whereas Adenophora stricta (AS) is commonly used to reduce phlegm, clear lung and tonify stomach. Due to similar appearances, PG is sometimes adulterated with cheap AS so as to gain profits. And this will inevitably result in different pharmacological property. In order to further clarify the differences in the chemical composition of these two Chinese herbs, the ultra‐high performance liquid chromatography combined with quadrupole time‐of‐flight tandem mass spectrometry coupled with UNIFI platform was used to establish a reliable, simple, sensitive and rapid analytical method. Seventy‐five compounds, including triterpenoid saponins, organic acids, flavonoids, steroids, phenols, etc., were identified from PG based on MSE data and retention time under the optimized conditions. Meanwhile, 57 compounds including triterpenoid saponins, organic acids, steroids, phenols, alkaloids, etc. were identified from AS. Among all the identified compounds, there were only 14 common components (mainly organic acids) existing in two herbs, and most of the other chemical compositions are totally different between the two herbs. Based on the results, AS cannot substitute for PG. In addition, PG adulterated with AS will lead a poor efficacy in clinical application. In addition, the systematic comparison of similarities and differences between two Chinese herbs will provide reliable characterization profiles to clarify the pharmacological fundamental substances.
The WCS‐FDTD method for simulating graphene
Authors: Chen Juan , Mai Huanxiao , Tian Chunming
Published: July 2017

A weakly conditionally stable‐finite difference time‐domain (WCS‐FDTD) scheme to simulate graphene is developed. The Pade fit method is used to approximate the interband conductivity of graphene and introduced into the WCS‐FDTD method directly by using the auxiliary differential equation. The accuracy of the Pade method is verified, and the effect of chemical potential on the accuracy is discussed. The time step size in proposed method is only determined by one spatial cell size, so the computational efficiency of this method is considerably larger than those of the conventional FDTD method and implicit explicit‐finite (HIE)‐FDTD method. An infinite graphene sheet and a graphene‐based metal sheet are simulated by using presented method, and the results are compared with theoretical value and the numerical results of the conventional FDTD method and HIE‐FDTD method. Simulated results show that proposed WCS‐FDTD method has high accuracy, and compared with the FDTD method and HIE‐FDTD method, its computational time is largely shorted. Besides, the numerical example presents that the interband conductivity has important effect on the performance of the graphene at high‐frequency range, especially when the chemical potential is small.
Impact insertion of osteochondral grafts: Interference fit and central graft reduction affect biomechanics and cartilage damage
Authors: Su Alvin W. , Chen Yunchan , Wailes Dustin H. , Wong Van W. , Cai Shengqiang , Chen Albert C. , Bugbee William D. , Sah Robert L.
Published: July 2017

An osteochondral graft (OCG) is an effective treatment for articular cartilage and osteochondral defects. Impact of an OCG during insertion into the osteochondral recipient site (OCR) can cause chondrocyte death and matrix damage. The aim of the present study was to analyze the effects of graft‐host interference fit and a modified OCG geometry on OCG insertion biomechanics and cartilage damage. The effects of interference fit (radius of OCG ‐ radius of OCR), loose (0.00 mm), moderate (0.05 mm), tight (0.10 mm), and of a tight fit with OCG geometry modification (central region of decreased radius), were analyzed for OCG cylinders and OCR blocks from adult bovine knee joints with an instrumented drop tower apparatus. An increasingly tight (OCG ‐ OCR) interference fit led to increased taps for insertion, peak axial force, graft cartilage axial compression, cumulative and total energy delivery to cartilage, lower time of peak axial force, lesser graft advancement during each tap, higher total crack length in the cartilage surface, and lower chondrocyte viability. The modified OCG, with reduction of diameter in the central area, altered the biomechanical insertion variables and biological consequences to be similar to those of the moderate interference fit scenario. Micro‐computed tomography confirmed structural interference between the OCR bone and both the proximal and distal bone segments of the OCGs, with the central regions being slightly separated for the modified OCGs. These results clarify OCG insertion biomechanics and mechanobiology, and introduce a simple modification of OCGs that facilitates insertion with reduced energy while maintaining a structural interference fit. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:377–386, 2018.
High Average Power Near‐Infrared Few‐Cycle Lasers
Authors: Rothhardt J , Hädrich S , Delagnes JC , Cormier E , Limpert J
Published: July 2017

Ultra‐short laser pulses with only a few optical cycles duration have gained increasing importance during the recent decade and are currently employed in many laboratories worldwide. In addition, modern laser technology nowadays can provide few‐cycle pulses at very high average power which advances established studies and opens exciting novel research opportunities. In this paper, the two complementary approaches for providing few‐cycle pulses at high average power, namely optical parametric amplification and nonlinear pulse compression, are reviewed and compared. In addition, their limitations and future scaling potential are discussed. Furthermore, selected applications particularly taking advantage of the high average power and high repetition rate are presented.
Enzyme‐Induced Matrix Softening Regulates Hepatocarcinoma Cancer Cell Phenotypes
Authors: Liang Youyun , Clay Nicholas Edwin , Sullivan Kathryn M. , Leong Jiayu , Ozcelikkale Altug , Rich Max H. , Lee Min Kyung , Lai Mei‐Hsiu , Jeon Hojeong , Han Bumsoo , Tong Yen Wah , Kong Hyunjoon
Published: July 2017

The progression of cancer is often accompanied by changes in the mechanical properties of an extracellular matrix. However, limited efforts have been made to reproduce these biological events in vitro. To this end, this study demonstrates that matrix remodeling caused by matrix metalloproteinase (MMP)‐1 regulates phenotypic activities and modulates radiosensitivity of cancer cells exclusively in a 3D matrix. In this study, hepatocarcinoma cells are cultured in a collagen‐based gel tailored to present an elastic modulus of ≈4.0 kPa. The subsequent exposure of the gel to MMP‐1 decreases the elastic modulus from 4.0 to 0.5 kPa. In response to MMP‐1, liver cancer cells undergo active proliferation, downregulation of E‐cadherin, and the loss of detoxification capacity. The resulting spheroids are more sensitive to radiation than the spheroids cultured in the stiffer gel not exposed to MMP‐1. Overall, this study serves to better understand and control the effects of MMP‐induced matrix remodeling.