bluuebunny/crossref_metadata_2025 huggingface dataset:
A simplified multi‐objective optimization‐based direct finite‐control‐set model predictive control for active front‐end rectifiers with fast dynamic response
Authors: Liu Xing , Wang Dan , Peng Zhouhua
Published: August 2017

In this paper, a simplified, multi‐objective, optimization‐based, direct finite‐control‐set model predictive control method is proposed for active front‐end rectifiers. Specifically, the proposed method replaces a cost function to combine a simplified computational method and multi‐objective optimization strategy based on average ranking. The process of selection of the desired voltage vector is optimized by using a sector distribution method. Meanwhile, the proposed method can achieve flexible control of powers without overshoot by applying dynamic references through mathematical deduction. The advantages of the proposed method can be summarized as follows: First, the proposed algorithm avoids the tuning of the weighting factors without affecting the control performance. Second, due to the fact that the proposed strategy avoids the use of an external proportional‐integral controller, fast dynamic response can be obtained. Third, since the proposed strategy avoids exhaustive explorations for testing all feasible voltage vectors, the optimizing efficiency can be improved. Simulation results are presented to demonstrate the efficacy of the proposed method. © 2017 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Implementation of a Localized Task‐Based Course in an EFL Context: A Study of Students’ Evolving Perceptions
Authors: Kim Youjin , Jung Yeonjoo , Tracy‐Ventura Nicole
Published: August 2017

Despite a strong pedagogical orientation, the majority of research examining the effectiveness of task‐based language teaching (TBLT) and perceptions toward TBLT has been investigated in isolation rather than embedded in larger curricular contexts (McDonough, ). The current study examines the process of developing a TBLT curriculum in South Korea and evolving perceptions toward this particular semester‐long task‐based course of students from one intact university class. Dynamic systems theory is used to investigate students’ evolving perceptions of the new task‐based course using two longitudinal data sources, surveys and portfolios. End‐of‐task unit surveys from 27 students and one focal participant's portfolio entries were analyzed both quantitatively and qualitatively. Findings demonstrate that students’ perceptions toward TBLT changed over time and that diverse factors affected how learners feel about task‐based instruction. Findings are discussed in light of developing localized TBLT curricula.
Contingent Needs Analysis for Task Implementation: An Activity Systems Analysis of Group Writing Conferences
Authors: Mochizuki Naoko
Published: August 2017

Needs analysis (NA) plays a significant role in developing tasks that create opportunities for natural language use in classrooms. Preemptive NA, however, does not necessarily predict the contingently emerging interpersonal and social variables which influence learners and teachers’ behaviours. These unpredictable variables often lead to a gap between what has been planned for a task to achieve and what learners actually get from a task in classrooms. To narrow this gap, this study proposes an analysis of needs at the task implementation stage adopting activity systems analysis (Engeström, ). The study investigates needs in group writing conferences for PhD students, where a task, giving and receiving oral feedback on one another's writing, is implemented. The participants were seven PhD students in two groups of writing conferences led by different facilitators in a thesis writing support program at an Australian university. Data were collected through observation and audiorecordings of writing conference sessions, interviews with the students and the facilitators, and students’ written drafts. The collected data were analysed for the relationships between students’ motives, participation patterns, and rules/division of labour in the groups. The identified aspects of this activity that require pedagogical innovation concern discursive practice during the sessions, students’ motives and interests in engaging the task, the rules of writing manifested through discussion, and ascribed and self‐ascribed roles of the students. The study highlights the potential of activity systems analysis for NA in classroom task implementation and proposes a new path to investigating tasks in classroom realities.
The Reaction of Cs2[Tc(NO)F5] with BF3 in Acetonitrile: Formation and Structure of [{Tc(NO)(CH3CN)4}2(μ‐F)](BF4)3
Authors: Balasekaran Samundeeswari Mariappan , Hagenbach Adelheid , Spandl Johann , Abram Ulrich
Published: August 2017

The deep blue, paramagnetic Cs2[TcII(NO)F5] is formed during reactions of pertechnetate, acetohydroxamic acid, and CsF in aqueous HF. A reaction of Cs2[Tc(NO)F5] with BF3·MeOH in acetonitrile gives yellow blocks of the fluorido‐bridged dimer [{TcI(NO)(CH3CN)4}2F](BF4)3. The compound is stable as solid and in acetonitrile solutions. The complex cation contains a bent μ‐F– ligand and two linear nitrosyl groups.
Determining an optimal clinical dose of elobixibat, a novel inhibitor of the ileal bile acid transporter, in Japanese patients with chronic constipation: a phase II, multicenter, double-blind, placebo-controlled randomized clinical trial
Authors: Nakajima Atsushi , Seki Mitsunori , Taniguchi Shinya
Published: August 2017

Background

Elobixibat is an oral treatment candidate for chronic constipation with a novel mechanism of action via inhibition of the ileal bile acid transporter. We performed this randomized, double-blind, placebo-controlled, dose-finding phase IIb study in Japanese patients with chronic constipation to determine the optimal clinical dose of elobixibat.

Methods

Japanese patients with chronic constipation were randomized to receive elobixibat (5, 10, or 15 mg) or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline in frequency of spontaneous bowel movements at Week 1 of treatment. Secondary endpoints and adverse events were also examined.

Results

Among 226 patients who provided informed consent, 163 patients were randomized and included in the full analysis set. In the 10- and 15-mg groups, frequency of spontaneous bowel movements (±standard deviation) were significantly higher than baseline (5.7 ± 4.2 and 5.6 ± 3.5 times per week, respectively, compared with 2.6 ± 2.9 times per week in the placebo group [P = 0.0005, P = 0.0001, respectively]). Subgroup analysis indicated that elobixibat was equally effective in patients with or without constipation-predominant irritable bowel syndrome. Common adverse events included mild abdominal pain and diarrhea in the elobixibat groups; no serious or severe adverse events occurred. Elobixibat was well tolerated at once-daily oral doses up to 15 mg for 2 weeks.

Conclusions

Our study results suggest that 10 mg of elobixibat is a clinically optimal dose for Japanese patients with chronic constipation.

Clinical trial registration number

JapicCTI-142608.
AMPK Prevents Palmitic Acid‐Induced Apoptosis and Lipid Accumulation in Cardiomyocytes
Authors: Adrian Lucas , Lenski Matthias , Tödter Klaus , Heeren Jörg , Böhm Michael , Laufs Ulrich
Published: August 2017

Palmitic acid, a main fatty acid (FA) in human nutrition, can induce apoptosis of cardiomyocytes. However, a specific combination of palmitic, myristic and palmitoleic acid (CoFA) has been reported to promote beneficial cardiac growth. The aim of this study was to investigate the relevance of CoFA for cardiac growth and to delineate the underlying signaling pathways of CoFA and palmitic acid treatment. CoFA treatment of C57Bl/6 mice increased FA serum concentrations. However, morphologic and echocardiographic analysis did not show myocardial hypertrophy. Cell culture studies using rat ventricular cardiomyocytes revealed an increased phosphorylation of AMP activated protein kinase α (AMPKα) to 155 ± 19% and its target acetyl‐CoA‐carboxylase to 177 ± 23% by CoFA. Treatment with myristic acid also increased AMPKα phosphorylation to 189 ± 32%. Palmitic acid did not activate AMPKα but increased expression of the FA translocase CD36 (FAT/CD36) to 163 ± 23% and adipose‐differentiation‐related‐protein (ADRP), a sensitive marker of lipid accumulation, to 168 ± 42%. This was associated with an increased phosphorylation of the stress‐activated‐protein‐kinase/Jun‐amino‐terminal‐kinase (SAPK/JNK) to 173 ± 27%. In CoFA‐treated cells, phosphorylation of SAPK/JNK was unaltered. FACS analysis revealed increased apoptosis to 159 ± 5% by palmitic acid but not by CoFA. AMPK activator AICAR (5‐aminoimidazole‐4‐carboxamide ribonucleotide) prevented up‐regulation of ADRP and increased apoptosis by palmitic acid. Confirming these findings, inhibition of AMPK by compound C in CoFA‐treated cardiomyocytes resulted in an increased expression of ADRP to 154 ± 27%, FAT/CD36 to 167 ± 28% and apoptosis to 183 ± 12%. These data reveal that AMPK activation plays an important role in prevention of palmitic acid‐induced apoptosis and lipid accumulation in cardiomyocytes.
MatriDerm Decreases Donor Site Morbidity After Radial Forearm Free Flap Harvest in Transgender Surgery
Authors: Watfa William , di Summa Pietro G. , Meuli Joaquim , Raffoul Wassim , Bauquis Olivier
Published: August 2017

Background

Phalloplasty with the radial forearm free flap is associated with a large donor site defect.

Aim

To compare two methods of donor site closure for functional and cosmetic long-term results: full-thickness skin grafting vs split-thickness skin grafting with MatriDerm.

Methods

Thirty-seven transgender patients had a neophallus created from a radial forearm free flap, and all were operated on by the same senior surgeon. Eight patients had their donor site defect closed by total skin grafting and 29 patients, operated on after 2009, received a split-thickness skin graft with MatriDerm closure. All 37 patients were evaluated by questionnaire and by careful clinical examination. Pressure perception was assessed with the Semmes-Weinstein monofilament test. Sensory recovery, skin quality, and cosmetic result also were compared. The contralateral arm was used as the control.

Outcomes

Pressure perception values showed better sensory return in the MatriDerm group. Split-thickness skin grafting with MatriDerm achieved superior results in skin sensibility, superficial radial nerve recovery, and cosmetic aspect.

Results

Our findings support the hypothesis that MatriDerm can be used to preserve sensory function and decrease morbidity of the donor site.

Clinical Implications

The use of a dermal substitute decreases the morbidity of the forearm free flap donor site.

Strengths and Limitations

The strength of this study is its retrospective nature conducted of a prospectively maintained database of 37 consecutive radial forearm free flaps with superimposable dimensions and location performed by the same surgeon, thus limiting biases. A limitation is its small sample (particularly for the control group).

Conclusion

Our experience showed that the combination of a split-thickness skin graft with MatriDerm substantially decreases postoperative complications at the donor site defect on the forearm of transgender patients.
Targeting cytokines for treatment of neuropathic pain
Authors: Hung Alice L. , Lim Michael , Doshi Tina L.
Published: August 2017

Background

Neuropathic pain is a challenging condition often refractory to existing therapies. An increasing number of studies have indicated that the immune system plays a crucial role in the mediation of neuropathic pain. Exploration of the various functions of individual cytokines in neuropathic pain will provide greater insight into the mechanisms of neuropathic pain and suggest potential opportunities to expand the repertoire of treatment options.

Methods

A literature review was performed to assess the role of pro-inflammatory and antiinflammatory cytokines in the development of neuropathic pain. Both direct and indirect therapeutic approaches that target various cytokines for pain were reviewed. The current understanding based on preclinical and clinical studies is summarized.

Results and conclusions

In both human and animal studies, neuropathic pain has been associated with a pro-inflammatory state. Analgesic therapies involving direct manipulation of various cytokines and indirect methods to alter the balance of the immune system have been explored, although there have been few large-scale clinical trials evaluating the efficacy of immune modulators in the treatment of neuropathic pain. TNF-α is perhaps the widely studied pro-inflammatory cytokine in the context of neuropathic pain, but other pro-inflammatory (IL-1β, IL-6, and IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β) signaling molecules are garnering increased interest. With better appreciation and understanding of the interaction between the immune system and neuropathic pain, novel therapies may be developed to target this condition.
UN Peacekeeping Operations and the Protection of Civilians
Authors: Foley Conor
Published: August 2017

This book is based on the author´s experience of working for more than two decades in over thirty conflict and post-conflict zones. It is written for those involved in UN peacekeeping and the protection of civilians. It is intended to be accessible to non- lawyers working in the field who may need to know the applicable legal standards relating to issues such as the use of force and arrest and detention powers on the one hand and the delivery of life-saving assistance according to humanitarian principles on the other. It will also be of interest to scholars and students of peacekeeping, international law and international relations on the practical dilemmas facing those trying to operationalise the various conceptions of 'protection' during humanitarian crises in recent years.
The Sacrificial Laws of Leviticus and the Joseph Story
Authors: Carmichael Calum
Published: August 2017

In this study, Calum Carmichael offers a new assessment of the Joseph story from the perspective of the biblical laws in Leviticus 1-10. These sacrificial laws, he argues, respond to the many problems in the first Israelite family. Understanding how ancient lawgivers thought about Joseph's and his brothers' troubling behavior leads to a greater appreciation of this complicated tale. The study of the laws in Leviticus 1-10 in relation to the Joseph story provides evidence that all biblical laws, over 400, constitute commentary on issues in the biblical narratives. They do not, as commonly thought, directly reflect the societal concerns in ancient Israelite times. Through close reading and analysis, Carmichael reveals how biblical narrators and lawgivers found distinctive and subtle ways of evaluating a single development in a narrative from multiple perspectives. Thus, the sacrificial laws addressing idolatry, keeping silent about a known offense, confessing wrongdoing, and seeking forgiveness become readily understandable when reviewed as responses to the events in the Joseph story.
Cannabinoid hyperemesis syndrome presentation to the emergency department: A two-year multicentre retrospective chart review in a major urban area
Authors: Hernandez Jeremy M. , Paty Jared , Price Ira M.
Published: August 2017

Objective

Cannabinoid hyperemesis syndrome (CHS) is a paradoxical side effect of cannabis use. Patients with CHS often present multiple times to the emergency department (ED) with cyclical nausea, vomiting, and abdominal pain, and are discharged with various misdiagnoses. CHS studies to date are limited to case series. The objective was to examine the epidemiology of CHS cases presenting to two major urban tertiary care centre EDs and one urgent care centre over a 2-year period.

Methods

Using explicit variables, trained abstractors, and standardized abstraction forms, we abstracted data for all adults (ages 18 to 55 years) with a presenting complaint of vomiting and/or a discharge diagnosis of vomiting and/or cyclical vomiting, during a 2-year period. The inter-rater agreement was measured using a kappa statistic.

Results

We identified 494 cases: mean age 31 (+/-11) years; 36% male; and 19.4% of charts specifically reported cannabis use. Among the regular cannabis users (>three times per week), 43% had repeat ED visits for similar complaints. Moreover, of these patients, 92% had bloodwork done in the ED, 92% received intravenous fluids, 89% received antiemetics, 27% received opiates, 19% underwent imaging, 8% were admitted to hospital, and 8% were referred to the gastroenterology service. The inter-rater reliability for data abstraction was kappa=1.

Conclusions

This study suggests that CHS may be an overlooked diagnosis for nausea and vomiting, a factor that can possibly contribute to unnecessary investigations and treatment in the ED. Additionally, this indicates a lack of screening for CHS on ED history, especially in quantifying cannabis use and eliciting associated symptoms of CHS.
THE EU–US UNEMPLOYMENT PUZZLE REVISITED: INSTITUTIONS, DEMOGRAPHY, AND CAPITAL FLOWS
Authors: Marchiori Luca , Pierrard Olivier , Sneessens Henri R.
Published: August 2017

The historical evolution of the EU–US unemployment-rate gap is often explained in the literature in terms of asymmetric changes in labor-market institutions. There may well also be asymmetries in population aging, which may generate international capital flows and have substantial impacts on relative unemployment rates. In this paper, we ask whether the combination of institutions, aging, and capital flows explains the rise in the unemployment gap between 1960 and 2010. To this end, we set up a two-region OLG model with search unemployment in which we introduce the historical and projected changes in labor-market institutions and demographics. We show that asymmetric institutional changes alone can reproduce a large part of the historical rise in the unemployment gap. However, this result no longer holds once we add asymmetric aging in closed economies. We find this initial result again, and in an even stronger form, when we allow for international capital mobility.
Geospatial Distribution of Local Health Department Tweets and Online Searches About Ebola During the 2014 Ebola Outbreak
Authors: Wong Roger , Harris Jenine K.
Published: August 2017

Objective

This study compared the geospatial distribution of Ebola tweets from local health departments (LHDs) to online searches about Ebola across the United States during the 2014 Ebola outbreak.

Methods

Between September and November 2014, we collected all tweets sent by 287 LHDs known to be using Twitter. Coordinates for each Ebola tweet were imported into ArcGIS 10.2.2 to display the distribution of tweets. Online searches with the search term “Ebola” were obtained from Google Trends. A Pearson’s correlation test was performed to assess the relationship between online search activity and per capita number of LHD Ebola tweets by state.

Results

Ebola tweets from LHDs were concentrated in cities across the northeast states, including Philadelphia and New York City. In contrast, states with the highest online search queries for Ebola were primarily in the south, particularly Oklahoma and Texas. A weak, negative, non-significant correlation (r=−0.03, P=0.83, 95% CI: −0.30, 0.25) was observed between online search activity and per capita number of LHD Ebola tweets by state.

Conclusions

We recommend that LHDs consider using social media to communicate possible disease outbreaks in a timely manner, and that they consider using online search data to tailor their messages to align with the public health interests of their constituents. (Disaster Med Public Health Preparedness. 2018; 12: 287–290)
Mineral dissolution and wormholing from a pore-scale perspective
Authors: Soulaine Cyprien , Roman Sophie , Kovscek Anthony , Tchelepi Hamdi A.
Published: August 2017

A micro-continuum approach is proposed to simulate the dissolution of solid minerals at the pore scale under single-phase flow conditions. The approach employs a Darcy–Brinkman–Stokes formulation and locally averaged conservation laws combined with immersed boundary conditions for the chemical reaction at the solid surface. The methodology compares well with the arbitrary-Lagrangian–Eulerian technique. The simulation framework is validated using an experimental microfluidic device to image the dissolution of a single calcite crystal. The evolution of the calcite crystal during the acidizing process is analysed and related to the flow conditions. Macroscopic laws for the dissolution rate are proposed by upscaling the pore-scale simulations. Finally, the emergence of wormholes during the injection of acid in a two-dimensional domain of calcite grains is discussed based on pore-scale simulations.
Reproduction biotechnologies in germplasm banking of livestock species: a review
Authors: Morrell J.M. , Mayer I.
Published: August 2017

Many biotechnologies are currently used in livestock breeding with the aim of improving reproductive efficiency and increasing the rate of genetic progress in production animals. Semen cryopreservation is the most widely used cryobiotechnology, although vitrification techniques now allow embryos and oocytes to be banked in ever-increasing numbers. Cryopreservation of other types of germplasm (reproductive tissue in general) is also possible, although the techniques are still in the early stages of development for use in livestock species. Although still in their infancy, these techniques are increasingly being used in aquaculture. Germplasm conservation enables reproductive tissues from both animals and fish to be preserved to generate offspring in the future without having to maintain large numbers of living populations of these species. However, such measures need careful planning and coordination. This review explains why the preservation of genetic diversity is needed for livestock and fish, and describes some of the issues involved in germplasm banking. Furthermore, some recent developments in semen handling leading to improved semen cryopreservation and biosecurity measures are also discussed.
Finite model reasoning over existential rules
Authors: AMENDOLA GIOVANNI , LEONE NICOLA , MANNA MARCO
Published: August 2017

Ontology-based query answering asks whether a Boolean conjunctive query is satisfied by all models of a logical theory consisting of a relational database paired with an ontology. The introduction of existential rules (i.e., Datalog rules extended with existential quantifiers in rule heads) as a means to specify the ontology gave birth to Datalog+/-, a framework that has received increasing attention in the last decade, with focus also on decidability and finite controllability to support effective reasoning. Five basic decidable fragments have been singled out: linear, weakly acyclic, guarded, sticky, and shy. Moreover, for all these fragments, except shy, the important property of finite controllability has been proved, ensuring that a query is satisfied by all models of the theory iff it is satisfied by all its finite models. In this paper, we complete the picture by demonstrating that finite controllability of ontology-based query answering holds also for shy ontologies, and it therefore applies to all basic decidable Datalog+/- classes. To make the demonstration, we devise a general technique to facilitate the process of (dis)proving finite controllability of an arbitrary ontological fragment.
Role of PD-L1 expression as a biomarker for GEP neuroendocrine neoplasm grading
Authors: Cavalcanti Elisabetta , Armentano Raffaele , Valentini Anna Maria , Chieppa Marcello , Caruso Maria Lucia
Published: August 2017

Neuroendocrine neoplasms (NENs) are rare, heterogeneous and ubiquitous tumors commonly localized in the gastrointestinal tract, lung, and pancreas. The clinical behavior of NEN is highly unpredictable; in fact, low-grade cases can unexpectedly be associated with metastases. Currently, the 2010 WHO NEN classification employs histological differentiation and the proliferation index for grading tumors but fails to provide reliable prognostic and therapeutic indications. Therefore, there is an urgent need for a better characterization of G2/G3 NENs. Similar to several other tumors, NENs possess immune-escape mechanisms, but very little has yet been done to characterize this crucial aspect. There are no available data describing PD-L1 expression in these tumors. Here we provide, for the first time, evidence of PD-L1 tissue expression in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). PD-L1 expression was significantly associated with a high-grade WHO classification (G3) (P<0.001) but not with gender, primary site, or lymph node status. The PD-L1 positivity rate and signal intensity are directly correlated (P<0.001) with a grade increase from G1 to G3. In particular in G3 cases, we observed a dichotomy between the morphology (WD- and PD-NENs) and Ki67. Moreover, our study demonstrated a significant association with the grade and PD-L1 expression levels in immune-infiltrating cells (P<0.001). In particular, G3 tumors are characterized by strong PD-L1 expression in both the tumor and infiltrating immune cells (P<0.001), reflecting an unfavorable environment for T-cell-mediated tumor aggression. These findings suggest that NENs might acquire resistance to immune surveillance by upregulating PD-L1 and inhibiting peritumoral and intratumoral infiltrating lymphocytes. Here we demonstrate that PD-L1 is currently the best-known biomarker for G3 NENs, becoming the new gold standard for G3 NEN discrimination. Furthermore, pharmacological approaches using anti-PD-1 antibodies may become the logical choice for the treatment of G3 cases with a poor prognosis.
Cardioprotective effects of fibroblast growth factor 21 against doxorubicin-induced toxicity via the SIRT1/LKB1/AMPK pathway
Authors: Wang Shudong , Wang Yonggang , Zhang Zhiguo , Liu Quan , Gu Junlian
Published: August 2017

Doxorubicin (DOX) is a highly effective antineoplastic anthracycline drug; however, the adverse effect of the cardiotoxicity has limited its widespread application. Fibroblast growth factor 21 (FGF21), as a well-known regulator of glucose and lipid metabolism, was recently shown to exert cardioprotective effects. The aim of this study was to investigate the possible protective effects of FGF21 against DOX-induced cardiomyopathy. We preliminarily established DOX-induced cardiotoxicity models in H9c2 cells, adult mouse cardiomyocytes, and 129S1/SyImJ mice, which clearly showed cardiac dysfunction and myocardial collagen accumulation accompanying by inflammatory, oxidative stress, and apoptotic damage. Treatment with FGF21 obviously attenuated the DOX-induced cardiac dysfunction and pathological changes. Its effective anti-inflammatory activity was revealed by downregulation of inflammatory factors (tumor necrosis factor-α and interleukin-6) via the IKK/IκBα/nuclear factor-κB pathway. The anti-oxidative stress activity of FGF21 was achieved via reduced generation of reactive oxygen species through regulation of nuclear transcription factor erythroid 2-related factor 2 transcription. Its anti-apoptotic activity was shown by reductions in the number of TUNEL-positive cells and DNA fragments along with a decreased ratio of Bax/Bcl-2 expression. In a further mechanistic study, FGF21 enhanced sirtuin 1 (SIRT1) binding to liver kinase B1 (LKB1) and then decreased LKB1 acetylation, subsequently inducing AMP-activated protein kinase (AMPK) activation, which improved the cardiac inflammation, oxidative stress, and apoptosis. These alterations were significantly prohibited by SIRT1 RNAi. The present work demonstrates for the first time that FGF21 obviously prevented DOX-induced cardiotoxicity via the suppression of oxidative stress, inflammation, and apoptosis through the SIRT1/LKB1/AMPK signaling pathway.
Lysosomotropism depends on glucose: a chloroquine resistance mechanism
Authors: Gallagher Laura E , Radhi Ohood A , Abdullah Mahmud O , McCluskey Anthony G , Boyd Marie , Chan Edmond Y W
Published: August 2017

There has been long-standing interest in targeting pro-survival autophagy as a combinational cancer therapeutic strategy. Clinical trials are in progress testing chloroquine (CQ) or its derivatives in combination with chemo- or radiotherapy for solid and haematological cancers. Although CQ has shown efficacy in preclinical models, its mechanism of action remains equivocal. Here, we tested how effectively CQ sensitises metastatic breast cancer cells to further stress conditions such as ionising irradiation, doxorubicin, PI3K-Akt inhibition and serum withdrawal. Contrary to the conventional model, the cytotoxic effects of CQ were found to be autophagy-independent, as genetic targeting of ATG7 or the ULK1/2 complex could not sensitise cells, like CQ, to serum depletion. Interestingly, although CQ combined with serum starvation was robustly cytotoxic, further glucose starvation under these conditions led to a full rescue of cell viability. Inhibition of hexokinase using 2-deoxyglucose (2DG) similarly led to CQ resistance. As this form of cell death did not resemble classical caspase-dependent apoptosis, we hypothesised that CQ-mediated cytotoxicity was primarily via a lysosome-dependent mechanism. Indeed, CQ treatment led to marked lysosomal swelling and recruitment of Galectin3 to sites of membrane damage. Strikingly, glucose starvation or 2DG prevented CQ from inducing lysosomal damage and subsequent cell death. Importantly, we found that the related compound, amodiaquine, was more potent than CQ for cell killing and not susceptible to interference from glucose starvation. Taken together, our data indicate that CQ effectively targets the lysosome to sensitise towards cell death but is prone to a glucose-dependent resistance mechanism, thus providing rationale for the related compound amodiaquine (currently used in humans) as a better therapeutic option for cancer.
Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma
Authors: Liu Kuisheng , Ren Tingting , Huang Yi , Sun Kunkun , Bao Xing , Wang Shidong , Zheng Bingxin , Guo Wei
Published: August 2017

The cure rate of osteosarcoma has not improved in the past 30 years. The search for new treatments and drugs is urgently needed. Apatinib is a high selectivity inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2) tyrosine kinase, exerting promising antitumoral effect in various tumors. The antitumor effect of Apatinib in human osteosarcoma has never been reported. We investigated the effects of Apatinib in osteosarcoma in vitro and in vivo. Osteosarcoma patients with high levels of VEGFR2 have poor prognosis. Apatinib can inhibit cell growth of osteosarcoma cells. In addition to cycle arrest and apoptosis, Apatinib induces autophagy. Interestingly, inhibition of autophagy increased Apatinib-induced apoptosis in osteosarcoma cells. Immunoprecipitation confirmed direct binding between VEGFR2 and signal transducer and activator of transcription 3 (STAT3). Downregulation of VEGFR2 by siRNA resulted in STAT3 inhibition in KHOS cells. VEGFR2 and STAT3 are inhibited by Apatinib in KHOS cells, and STAT3 act downstream of VEGFR2. STAT3 and BCL-2 were downregulated by Apatinib. STAT3 knockdown by siRNA reinforced autophagy and apoptosis induced by Apatinib. BCL-2 inhibits autophagy and was apoptosis restrained by Apatinib too. Overexpression of BCL-2 decreased Apatinib-induced apoptosis and autophagy. Apatinib repressed the expression of STAT3 and BCL-2 and suppressed the growth of osteosarcoma in vivo. To sum up, deactivation of VEGFR2/STAT3/BCL-2 signal pathway leads to Apatinib-induced growth inhibition of osteosarcoma.
SMARCD1 regulates senescence-associated lipid accumulation in hepatocytes
Authors: Inoue Chisato , Zhao Chong , Tsuduki Yumi , Udono Miyako , Wang Lixiang , Nomura Masatoshi , Katakura Yoshinori
Published: August 2017

Previously, we have identified 16 senescence-associated genes by a subtractive proteomic analysis using presenescent and senescent human fibroblast cells, TIG-1. The aim of this study was to clarify the role of SMARCD1, one of the identified genes, also known as BAF60a, in hepatic senescence. SMARCD1 is a member of the SWI/SNF chromatin remodeling complex family, and regulates the transcription of target genes through the alterations of chromatin structure. We demonstrated that the reduced expression of SMARCD1 triggers cellular senescence and induces the accumulation of lipids, suggesting that SMARCD1 acts as a mediator in these processes. Furthermore, palmitic acid treatment and high-fat diet led to a significant reduction of SMARCD1 expression, and consequently induced cellular senescence and lipid accumulation in HepG2 cells and mouse liver, respectively. The results obtained here suggest that dietary nutrient-associated impaired expression of SMARCD1 triggers cellular senescence and lipid accumulation, indicating a potential application of SMARCD1 in the prevention of lifestyle-related diseases.
A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies
Authors: Nachbagauer Raffael , Liu Wen-Chun , Choi Angela , Wohlbold Teddy John , Atlas Talia , Rajendran Madhusudan , Solórzano Alicia , Berlanda-Scorza Francesco , García-Sastre Adolfo , Palese Peter , Albrecht Randy A. , Krammer Florian
Published: August 2017

Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary to re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts to redirect antibody responses from the variable, immuno-dominant hemagglutinin head towards the conserved—but immuno-subdominant—hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based vaccines expressing exotic head domains, and a conserved hemagglutinin stalk. We compared a live-attenuated influenza virus prime followed by an inactivated split-virus boost to two doses of split-virus vaccines and assessed the impact of adjuvant on protection against challenge with pandemic H1N1 virus in ferrets. All tested immunization regimens successfully induced broadly cross-reactive antibody responses. The combined live-attenuated/split virus vaccination conferred superior protection against pandemic H1N1 infection compared to two doses of split-virus vaccination. Our data support advancement of this chimeric hemagglutinin-based vaccine approach to clinical trials in humans.
Intertidal marine sediment harbours Actinobacteria with promising bioactive and biosynthetic potential
Authors: Jose Polpass Arul , Jha Bhavanath
Published: August 2017

Actinobacteria are the major source of bioactive natural products that find their value in research and drug discovery programmes. Antimicrobial resistance and the resulting high demand for novel antibiotics underscore the need for exploring novel sources of these bacteria endowed with biosynthetic potential. Intertidal ecosystems endure regular periods of immersion and emersion, and represent an untapped source of Actinobacteria. In this study, we studied the diversity and biosynthetic potential of cultivable Actinobacteria from intertidal sediments of Diu Island in the Arabian Sea. A total of 148 Actinobacteria were selectively isolated using a stamping method with eight isolation media. Isolates were grouped into OTUs based on their 16S rRNA gene sequence, and categorized within actinobacterial families such as Glycomycetaceae, Micromonosporaceae, Nocardiaceae, Nocardiopsaceae, Pseudonocardiaceae, Streptomycetaceae, and Thermomonosporaceae. The biosynthetic potential of the Actinobacteria, necessary for secondary metabolite biosynthesis, was screened and confirmed by extensive fingerprinting approaches based on genes coding for polyketide synthases and nonribosomal peptide synthetases. The observed biosynthetic potential was correlated with the antibacterial activity exhibited by these isolates in laboratory conditions. Ultimately, the results demonstrate that intertidal sediment is a rich source of diverse cultivable Actinobacteria with high potential to synthesize novel bioactive compounds in their genomes.
Tribochemistry of adaptive integrated interfaces at boundary lubricated contacts
Authors: Wan Shanhong , Tieu Anh Kiet , Xia Yana , Wang Liping , Li Dongshan , Zhang Guangan , Zhu Hongtao , Tran Bach H. , Mitchell David R. G.
Published: August 2017

Understanding how an adaptive integrated interface between lubricant additives and solid contacts works will enable improving the wear and friction of moving engine components. This work represents the comprehensive characterization of compositional and structural orientation at the sliding interface from the perspective of surface/interface tribochemistry. The integrated interface of a lubricant additive-solid resulting from the friction testing of Graphite-like carbon (GLC) and PVD-CrN coated rings sliding against cast iron under boundary lubrication was studied. The results indicate that in the case of the CrN/cast iron pair the antiwear and friction behavior were very strongly dependent upon lubricant. In contrast, the tribology of the GLC surface showed a much lower dependence on lubrication. In order to identify the compounds and their distribution across the interface, x-ray microanalysis phase mapping was innovatively applied and the principle of hard and soft acids and bases (HSAB) to understand the behaviour. Phase mapping clearly showed the hierarchical interface of the zinc-iron polyphosphate tribofilm for various sliding pairs and different sliding durations. This interface structure formed between lubricant additives and the sliding surfaces adapts to the sliding conditions – the term adaptive interface. The current results help explain the tribology of these sliding components in engine.
MTOPVIB interacts with AtPRD1 and plays important roles in formation of meiotic DNA double-strand breaks in Arabidopsis
Authors: Tang Yu , Yin Zhongnan , Zeng Yuejuan , Zhang Qinxin , Chen Liqun , He Yan , Lu Pingli , Ye De , Zhang Xueqin
Published: August 2017

Meiotic recombination is initiated from the formation of DNA double-strand breaks (DSBs). In Arabidopsis, several proteins, such as AtPRD1, AtPRD2, AtPRD3, AtDFO and topoisomerase (Topo) VI-like complex, have been identified as playing important roles in DSB formation. Topo VI-like complex in Arabidopsis may consist of subunit A (Topo VIA: AtSPO11-1 and AtSPO11-2) and subunit B (Topo VIB: MTOPVIB). Little is known about their roles in Arabidopsis DSB formation. Here, we report on the characterization of the MTOPVIB gene using the Arabidopsis mutant alleles mtopVIB-2 and mtopVIB-3, which were defective in DSB formation. mtopVIB-3 exhibited abortion in embryo sac and pollen development, leading to a significant reduction in fertility. The mtopVIB mutations affected the homologous chromosome synapsis and recombination. MTOPVIB could interact with Topo VIA proteins AtSPO11-1 and AtSPO11-2. AtPRD1 interacted directly with Topo VI–like proteins. AtPRD1 also could interact with AtPRD3 and AtDFO. The results indicated that AtPRD1 may act as a bridge protein to interact with AtPRD3 and AtDFO, and interact directly with the Topo VI-like proteins MTOPVIB, AtSPO11-1 and AtSPO11-2 to take part in DSB formation in Arabidopsis.
Highly wear-resistant and low-friction Si3N4 composites by addition of graphene nanoplatelets approaching the 2D limit
Authors: Tapasztó Orsolya , Balko Ján , Puchy Viktor , Kun Péter , Dobrik Gergely , Fogarassy Zsolt , Horváth Zsolt Endre , Dusza Ján , Balázsi Katalin , Balázsi Csaba , Tapasztó Levente
Published: August 2017

Graphene nanoplatelets (GNPs) have emerged as one of the most promising filler materials for improving the tribological performance of ceramic composites due to their outstanding solid lubricant properties as well as mechanical and thermal stability. Yet, the addition of GNPs has so far enabled only a very limited improvement in the tribological properties of ceramics, particularly concerning the reduction of their friction coefficient. This is most likely due to the challenges of achieving a continuous lubricating and protecting tribo-film through a high GNP coverage of the exposed surfaces. Here we demonstrate that this can be achieved by efficiently increasing the exfoliation degree of GNPs down to the few-layer (FL) range. By employing FL-GNPs as filler material, the wear resistance of Si3N4 composites can be increased by more than twenty times, the friction coefficient reduced to nearly its half, while the other mechanical properties are also preserved or improved. Confocal Raman spectroscopy measurements revealed that at the origin of the spectacular improvement of the tribological properties is the formation of a continuous FL- GNP tribo-film, already at 5 wt% FL-GNP content.
How spontaneous brain activity and narcissistic features shape social interaction
Authors: Scalabrini Andrea , Huang Zirui , Mucci Clara , Perrucci Mauro Gianni , Ferretti Antonio , Fossati Andrea , Romani Gian Luca , Northoff Georg , Ebisch Sjoerd J. H.
Published: August 2017

There is an increasing interest in how ongoing spontaneous brain activity and personality provide a predisposition for the processing of environmental demands. It further has been suggested that the brain has an inherent sensitivity to the social environment. Here we tested in healthy volunteers if spontaneous brain activity contributes to a predisposition for social behavior and how this is modulated by narcissistic personality features associated with poor interpersonal functioning. Functional magnetic resonance imaging included a resting state and an experimental paradigm focusing on the anticipation of actively touching an animate (human hand) versus an inanimate target (mannequin hand). The experimental task induced a significant modulation of neural activity in left postcentral gyrus (PostCG), right culmen and, co-varying with narcissistic features, in right anterior insula (AI). Neural activity in anticipation of the animate target significantly correlated with spontaneous activity during the resting state indexed by the Power Law Exponent (PLE) in PostCG and AI. Finally, the correlation between spontaneous and task-induced activity in AI was mediated by narcissistic features. These findings provide novel evidence for a relationship between intrinsic brain activity and social behavior and show how personality could contribute to individual differences in our predisposition to approach the animate world.
Correction: Corrigendum: MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/β-catenin pathway
Authors: Zhang Jun-gang , Shi Ying , Hong De-fei , Song Mengqi , Huang Dongsheng , Wang Chun-you , Zhao Gang
Published: August 2017

Scientific Reports 5: Article number: 8087; published online: 28 January 2015; updated: 24 August 2017. In the original version of this Article, an additional affiliation for Ying Shi was omitted. The correct affiliations are listed below: Pancreatic Disease Institute, Union Hospital, Tongji MedicalCollege, Huazhong University of Science and Technology, Wuhan, 430022, China.
Determination of spectral markers of cytotoxicity and genotoxicity using in vitro Raman microspectroscopy: cellular responses to polyamidoamine dendrimer exposure
Authors: Efeoglu Esen , Casey Alan , Byrne Hugh J.
Published: August 2017

Raman microspectroscopy as anin vitrolabel-free, high content screening technique to determine spectral markers of cytogenotoxicity.
Facile cyclometallation of a mesitylsilylene: synthesis and preliminary catalytic activity of iridium(iii) and iridium(v) iridasilacyclopentenes
Authors: Cabeza Javier A. , García-Álvarez Pablo , González-Álvarez Laura
Published: August 2017

The cyclometallation of a monosilylene has been achieved in iridium(iii) and iridium(v) complexes; the former catalyse arene deuteriations and borylations.
Asymmetric conjugate addition of alkylzirconium reagents to α,β-unsaturated thioesters: access to fragrances and acyclic stereochemical arrays
Authors: Gao Zhenbo , Fletcher Stephen P.
Published: August 2017

An asymmetric iterative route for the synthesis of acyclic stereochemical arrays is obtained by addition to α,β-unsaturated thioesters.
3D hyperbranched heterostructures of Ag nanocrystals-decorated ZnO nanopillars: controlled growth and characterization of the optical properties
Authors: Daud S. N. H. , Haw C. Y. , Chiu W. S. , Aspanut Z. , Jani N. A. , Khiew P. S. , Lim Y. C. , Abd. Hamid M. A. , Ali A. M.
Published: August 2017

Mechanistic formation of 3D hierarchical structure of silver-decorated ZnO nanopillars grown on Zn foilviaa hydrothermal route.
Modelling oxygen defects in orthorhombic LaMnO3 and its low index surfaces
Authors: Gavin Ailbhe L. , Watson Graeme W.
Published: August 2017

The findings of this work represent the first comprehensive study of the formation of oxygen defects in bulk orthorhombic LaMnO3 and at its low index surfaces.
Role of intermolecular charge delocalization and its dimensionality in efficient band-like electron transport in crystalline 2,5-difluoro-7,7,8,8-tetracyanoquinodimethane (F2-TCNQ)
Authors: Sosorev Andrey Yu.
Published: August 2017

Theoretical investigation unravels the importance of multidimensional intermolecular charge delocalization for efficient band-like charge transport in small-molecule organic semiconductors.
Composition-tunable synthesis of “clean” syngas via a one-step synthesis of metal-free pyridinic-N-enriched self-supported CNTs: the synergy of electrocatalyst pyrolysis temperature and potential
Authors: Liu Kai-Hua , Zhong Hai-Xia , Yang Xiao-Yang , Bao Di , Meng Fan-Lu , Yan Jun-Min , Zhang Xin-Bo
Published: August 2017

Exploring efficient and environmentally friendly ways for producing clean syngas is of great significance for realizing an artificial carbon cycle associated with clean and renewable energy.
Enhancement of multiferroic properties and unusual magnetic phase transition in Eu doped bismuth ferrite nanoparticles
Authors: Banerjee Mahasweta , Mukherjee Ayan , Banerjee Amit , Das Debajyoti , Basu Soumen
Published: August 2017

Improvement of the multiferroic properties of bismuth ferrite is essential for its practical application and commercialization in the growing field of spintronics.
MxNi100−x (M = Ag, and Co) nanoparticles supported on CeO2 nanorods derived from Ce–metal organic frameworks as an effective catalyst for reduction of organic pollutants: Langmuir–Hinshelwood kinetics and mechanism
Authors: Kohantorabi Mona , Gholami Mohammad Reza
Published: August 2017

AgxNi100−x and CoxNi100−x bimetallic nanoparticles supported on CeO2 nanorods showed remarkable catalytic activity in a reduction reaction.
An enantioselective conjugate addition reaction of 3-substituted benzothiophen-2-ones and 2-phthalimidoacrylates
Authors: Li Shoulei , Zhang Enge , Feng Junjun , Li Xin
Published: August 2017

A highly enantioselective conjugate addition reaction of 3-substituted benzothiophen-2-ones to 2-phthalimidoacrylates has been developed using a bifunctional tertiary-amine thiourea catalyst.
Antipodal Vivaldi antenna with novel differentially fed structure for lowering cross‐polarisation level
Authors: Wang Ya‐wei
Published: August 2017

A novel differentially fed double‐slot structure with two metal layers is proposed for an antipodal Vivaldi antenna. When fed differentially, the slots can have their E‐field vectors summed to an E‐field vector parallel to the layers, which endows the antenna with a significantly lowered cross‐polarisation level by comparison with a typical antipodal Vivaldi antenna whose E‐field vectors in the slot are skewed to the layers. A wideband balun based on a double‐sided parallel stripline is used to realise the demanded differential feeding. The simulation and measurement are carried out to validate the remarkable characteristic of a two‐layer structure, which is simpler than a three‐layer structure of a balanced antipodal Vivaldi antenna.