bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic transcanal modified canal‐wall‐down mastoidectomy for cholesteatoma
Authors: Sajjadi Hamed
Published: October 2017

Attic cholesteatoma with antral extension in tight sclerotic mastoid cavities is a common presentation that creates difficult decision‐making intraoperatively. Drilling through a sclerotic and small mastoid cavity, keeping the canal wall intactis often difficult and increases the risk of serious injury. Consequently, a canal‐wall‐down mastoidectomy is often performed. The endoscopic transcanal modified canal‐wall‐down mastoidectomy approach allows the benefits of an open cavity for cholesteatoma resection and the benefits of a closed cavity for better long‐term care and a more normal ear canal and middle ear reconstruction.
Towards a New Horizon in Investor–State Dispute Settlement? Reflections on the Investment Tribunal System in the Comprehensive Economic Trade Agreement (CETA)
Authors: SARDINHA ELSA
Published: October 2017

The Comprehensive Economic Trade Agreement (CETA) between Canada and the European Union is the first treaty to specify new rules governing the identity and tenure of arbitral members and provide a more extensive review function through a two-tiered investment tribunal system (ITS). CETA signals a shift towards a more public and judicialized system, akin to that of many national legal systems and the World Trade Organization. The ITS creates a permanent first instance tribunal and an appeal tribunal (featuring a pre-elected roster of tribunal members), which is competent to review the tribunal’s decisions for errors of law and fact, as well as on the grounds of Article 52 of the Convention on the Settlement of Investment Disputes between States and Nationals of Other States (ICSID Convention) — making it a novel one-stop-appellate-shop. This treaty comment assesses the operation of, and reasons for, key provisions of CETA’s Investment Chapter and examines the extent to which it addresses points of criticism and lessons learned from the experience of arbitrating under the North American Free Trade Agreement and other open-textured treaties. The analysis draws analogies to, and distinctions from, other treaties and relevant jurisprudence that have influenced the negotiators. Among CETA’s most striking features are its purported modification of existing arbitral rules (ICSID Convention, ICSID Additional Facility Rules, and UNCITRAL Arbitration Rules) and its removal of disputing party involvement in the selection of the tribunal in favour of a roster appointed ex ante by the state parties, which results in a considerable amount of the investor’s autonomy being stripped away. While these and other issues must be further analyzed and balanced in the context of present discussions regarding the creation of a multilateral investment tribunal, CETA nevertheless contains significant procedural and substantive innovations and stands as a guide for future treaty negotiations and reforms of investor–state dispute settlement.
Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women
Authors: Takagi Sahoko , Naito Mariko , Kawai Sayo , Okada Rieko , Nagata Chisato , Hosono Satoyo , Nishida Yuichiro , Takashima Naoyuki , Suzuki Sadao , Shimoshikiryo Ippei , Mikami Haruo , Uemura Hirokazu , Kuriyama Nagato , Ohnaka Keizo , Kubo Michiaki , Hamajima Nobuyuki , Tanaka Hideo , Wakai Kenji
Published: October 2017

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47–69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2–Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.
Learner language morphology as a window to crosslinguistic influences: A key structure analysis
Authors: Ivaska Ilmari , Siitonen Kirsti
Published: October 2017

The study of crosslinguistic influences (CLI) has proven that morphosyntactic features exhibit CLI. Technical development and novel resources have enabled detection-based approaches, where potential CLI are revealed based on their observed frequencies and on differences between learners with different language backgrounds. The two research questions are as follows: (i) How construction-specific typological (dis)similarities between L1 and L2 affect the frequencies of linguistic features? (ii) Can such (dis)similarities be detected by comparing feature frequency data of L2? The data come from the International Corpus of Learner Finnish, and the methodology applied is the key structure analysis. The results support the applicability of the method: they show that constructional similarities may trigger CLI construction by construction, irrespective of the general similarities or genealogical categorizations. The results further imply the importance of controlling the genre-related and topical variation to account for skewed nature of the data when dealing with naturally occurring learner language data.
Comparison of Treatment Outcomes Between Lesbian, Gay, Bisexual and Heterosexual Individuals Receiving a Primary Care Psychological Intervention
Authors: Rimes Katharine A. , Broadbent Matthew , Holden Rachel , Rahman Qazi , Hambrook David , Hatch Stephani L. , Wingrove Janet
Published: October 2017

Background: Lesbian, gay and bisexual individuals experience more anxiety and depression than heterosexual people. Little is known about their comparative treatment response to psychological interventions. Aims: To compare sociodemographic/clinical characteristics and treatment outcomes across sexual orientation groups, for adults receiving primary care psychological interventions from Improving Access to Psychological Therapies (IAPT) services in London, adjusting for possible confounders. Method: Data from 188 lesbian women, 222 bisexual women, 6637 heterosexual women, 645 gay men, 75 bisexual men and 3024 heterosexual men were analysed from pre-treatment and last treatment sessions. Males and females were analysed separately. Results: Before treatment, lesbian and bisexual women were more likely to report clinical levels of impairment (Work and Social Adjustment Scale) than heterosexual women; there were no significant differences in depression (PHQ-9) or anxiety (GAD-7). Bisexual men were more likely to meet depression caseness than gay men but less likely to meet anxiety caseness than gay or heterosexual men. Compared with heterosexual women, lesbian and bisexual individuals showed smaller reductions in depression and impairment, controlling for age, ethnicity, employment, baseline symptoms, number of sessions and intervention type. Bisexual women experienced significantly smaller reductions in anxiety than heterosexual women and were less likely to show recovery or reliable recovery. There were no significant differences in treatment outcomes between gay, bisexual and heterosexual men. Conclusions: Reasons for poorer outcomes in lesbian and bisexual women require investigation, for example lifetime trauma or stigma/discrimination regarding gender or sexual orientation in everyday life or within therapy services.
Reliability and Utility of Manual and Automated Estimates of Total Intracranial Volume
Authors: Crowley Samuel J. , Tanner Jared J. , Ramon Daniel , Schwab Nadine A. , Hizel Loren P. , Price Catherine C.
Published: October 2017

Objectives: Total intracranial volume (TICV) is an important control variable in brain–behavior research, yet its calculation has challenges. Manual TICV (Manual) is labor intensive, and automatic methods vary in reliability. To identify an accurate automatic approach we assessed the reliability of two FreeSurfer TICV metrics (eTIV and Brainmask) relative to manual TICV. We then assessed how these metrics alter associations between left entorhinal cortex (ERC) volume and story retention. Methods: Forty individuals with Parkinson’s disease (PD) and 40 non-PD peers completed a brain MRI and memory testing. Manual metrics were compared to FreeSurfer’s Brainmask (a skull strip mask with total volume of gray, white, and most cerebrospinal fluid) and eTIV (calculated using the transformation matrix into Talairach space). Volumes were compared with two-way interclass correlations and dice similarity indices. Associations between ERC volume and Wechsler Memory Scale-Third Edition Logical Memory retention were examined with and without correction using each TICV method. Results: Brainmask volumes were larger and eTIV volumes smaller than Manual. Both automated metrics correlated highly with Manual. All TICV metrics explained additional variance in the ERC-Memory relationship, although none were significant. Brainmask explained slightly more variance than other methods. Conclusions: Our findings suggest Brainmask is more reliable than eTIV for TICV correction in brain-behavioral research. (JINS, 2018, 24, 206–211)
The Changing Role of European Documentation Centres and How ‘Brexit’ Might Affect the Network
Authors: Watson Margaret
Published: October 2017

European Documentation Centres (EDCs) are neutral collections of official publications of the European Union, open to the public and normally housed in academic institutions throughout the European Union (EU). EDC status entitles the host organisation to receive one copy of the most significant publications and documents of the EU. The EDC network goes back to 1963, and its primary purpose has always been the support of academic research into European integration. The decision to trigger Article 50 of the Treaty on European Union clearly raises questions about role of the EDCs in the United Kingdom after ‘Brexit’. This article is written by Margaret Watson.
Legal Research Training at Middle Temple Library
Authors: Woellhaf Adam
Published: October 2017

This article, written by Adam Woellhaf, describes the legal research training offered by Middle Temple Library to Inns of Court members. It examines the challenges of designing and delivering legal research training to practitioners, as well as offering guidance and advice to others in their own legal research training efforts. It also looks at the potential for using mobile technology in legal research instruction.
miR-23a/b promote tumor growth and suppress apoptosis by targeting PDCD4 in gastric cancer
Authors: Hu Xiuting , Wang Yanbo , Liang Hongwei , Fan Qian , Zhu Ruichi , Cui Jiayi , Zhang Weijie , Zen Ke , Zhang Chen-Yu , Hou Dongxia , Zhou Zhen , Chen Xi
Published: October 2017

MicroRNAs (miRNAs) are short non-coding RNAs of 21–23 nucleotides that play important roles in virtually all biological pathways in mammals and in other multicellular organisms. miR-23a and miR-23b (miR-23a/b) are critical oncomiRs (miRNAs that are associated with human cancers) of gastric cancer, but their detailed roles in the initiation and progression of gastric cancer remain to be elucidated. In this study, we found that miR-23a/b were consistently upregulated in gastric cancer tissues. We then investigated the molecular mechanisms through which miR-23a/b contribute to gastric cancer and identified programmed cell death 4 (PDCD4) as a direct target gene of miR-23a/b. In contrast to the upregulated expression levels of miR-23a/b, PDCD4 protein levels were dramatically downregulated and inversely correlated with miR-23a/b in gastric cancer tissues. Moreover, we observed that cell apoptosis was increased by miR-23a/b inhibitors and decreased by miR-23a/b mimics in gastric cancer cells and that the restoration of PDCD4 expression attenuated the anti-apoptotic effects of miR-23a/b in gastric cancer cells, indicating that PDCD4 is a direct mediator of miR-23a/b functions. Finally, we showed that miR-23a/b significantly suppressed PDCD4 expression and enhanced tumor growth in a gastric cancer xenograft mouse model. Taken together, this study highlights an important role for miR-23a/b as oncomiRs in gastric cancer through the inhibition of PDCD4 translation. These findings may shed new light on the molecular mechanism of gastric carcinogenesis and provide a new avenue for gastric cancer treatment.
Trehalose ameliorates oxidative stress-mediated mitochondrial dysfunction and ER stress via selective autophagy stimulation and autophagic flux restoration in osteoarthritis development
Authors: Tang Qian , Zheng Gang , Feng Zhenhua , Chen Yu , Lou Yiting , Wang Chenggui , Zhang Xiaolei , Zhang Yu , Xu Huazi , Shang Ping , Liu Haixiao
Published: October 2017

Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model. We found aberrant p62 accumulation and increased apoptosis in human OA cartilage and chondrocytes. Consistently, p62 and cleaved caspase-3 levels increased in mouse chondrocytes under oxidative stress. Furthermore, trehalose restored oxidative stress-induced autophagic flux disruption and targeted autophagy selectively by activating BCL2 interacting protein 3 (BNIP3) and Phosphoglycerate mutase family member 5 (PGAM5). Trehalose could ameliorate oxidative stress-mediated mitochondrial membrane potential collapse, ATP level decrease, dynamin-related protein 1 (drp-1) translocation into the mitochondria, and the upregulation of proteins involved in mitochondria and endoplasmic reticulum (ER) stress-related apoptosis pathway. In addition, trehalose suppressed the cleavage of caspase 3 and poly(ADP-ribose) polymerase (PARP) and prevented DNA damage under oxidative stress. However, the anti-apoptotic effects of trehalose in TBHP-treated chondrocytes were partially abolished by autophagic flux inhibitor chloroquine and BNIP3- siRNA. The protective effect of trehalose was also found in mouse OA model. Taken together, these results indicate that trehalose has anti-apoptotic effects through the suppression of oxidative stress-induced mitochondrial injury and ER stress which is dependent on the promotion of autophagic flux and the induction of selective autophagy. Thus, trehalose is a promising therapeutic agent for OA.
Dexamethasone mediates pancreatic cancer progression by glucocorticoid receptor, TGFβ and JNK/AP-1
Authors: Liu Li , Aleksandrowicz Ewa , Schönsiegel Frank , Gröner Daniel , Bauer Nathalie , Nwaeburu Clifford C , Zhao Zhefu , Gladkich Jury , Hoppe-Tichy Torsten , Yefenof Eitan , Hackert Thilo , Strobel Oliver , Herr Ingrid
Published: October 2017

Glucocorticoids such as dexamethasone are widely co-prescribed with cytotoxic therapy because of their proapoptotic effects in lymphoid cancer, reduction of inflammation and edema and additional benefits. Concerns about glucocorticoid-induced therapy resistance, enhanced metastasis and reduced survival of patients are largely not considered. We analyzed dexamethasone-induced tumor progression in three established and one primary human pancreatic ductal adenocarcinoma (PDA) cell lines and in PDA tissue from patients and xenografts by FACS and western blot analysis, immunohistochemistry, MTT and wound assay, colony and spheroid formation, EMSA and in vivo tumor growth and metastasis of tumor xenografts on chicken eggs and mice. Dexamethasone in concentrations observed in plasma of patients favored epithelial–mesenchymal transition, self-renewal potential and cancer progression. Ras/JNK signaling, enhanced expression of TGFβ, vimentin, Notch-1 and SOX-2 and the inhibition of E-cadherin occurred. This was confirmed in patient and xenograft tissue, where dexamethasone induced tumor proliferation, gemcitabine resistance and metastasis. Inhibition of each TGFβ receptor-I, glucocorticoid receptor or JNK signaling partially reversed the dexamethasone-mediated effects, suggesting a complex signaling network. These data reveal that dexamethasone mediates progression by membrane effects and binding to glucocorticoid receptor.
Berberine induces oxidative DNA damage and impairs homologous recombination repair in ovarian cancer cells to confer increased sensitivity to PARP inhibition
Authors: Hou Dong , Xu Guangwei , Zhang Caibo , Li Boxuan , Qin Junchao , Hao Xiaohe , Liu Qiao , Zhang Xiyu , Liu Jinsong , Wei Jianjun , Gong Yaoqin , Liu Zhaojian , Shao Changshun
Published: October 2017

Many cancer drugs exert their therapeutic effect by inducing oxidative stress in the cancer cells. Oxidative stress compromises cell survival by inflicting lesions in macromolecules like DNA. Cancer cells rely on enhanced antioxidant metabolism and increased DNA repair function to survive oxidative assault. PARP1, a protein that senses DNA-strand breaks and orchestrates their repair, has an important role in the repair of oxidative DNA damage. Berberine, an alkaloid compound present in many herbal plants, is capable of inducing oxidative DNA damage and downregulating homologous recombination repair (HRR) in cancer cells. In this study, we demonstrated that berberine and PARP inhibitor niraparib have a synthetic lethal effect on ovarian cancer cells. Oxidative DNA damage was greatly induced by berberine in ovarian cancer cells. In addition, the level of RAD51 and the capacity of HRR were also reduced by berberine. Correspondingly, PARP became hyperactivated in response to berberine treatment. Cancer cells treated with berberine and niraparib in combination exhibited greatly increased apoptosis and remarkably reduced tumor growth in vivo. Together, the results indicate that by inducing oxidative DNA damage and downregulating HRR in cancer cells berberine is able to further sensitize cancer cells to PARP inhibition. Our findings demonstrate a potential therapeutic value of combined application of berberine and PARP inhibitors in ovarian cancer treatment.
Tat-protein disulfide-isomerase A3: a possible candidate for preventing ischemic damage in the spinal cord
Authors: Yoo Dae Young , Cho Su Bin , Jung Hyo Young , Kim Woosuk , Choi Goang-Min , Won Moo-Ho , Kim Dae Won , Hwang In Koo , Choi Soo Young , Moon Seung Myung
Published: October 2017

In the present study, we searched for possible candidates that can prevent ischemic damage in the rabbit spinal cord. For this study, we used two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, in sham- and ischemia-operated animals. As the level of protein disulfide-isomerase A3 (PDIA3) significantly decreased 3 h after ischemia/reperfusion, we further investigated its possible role against ischemic damage using an in vitro spinal cord cell line and in vivo spinal cord ischemic model. The administration of Tat-PDIA3 significantly reduced the hydrogen peroxide-induced formation of reactive oxygen species and cell death, based on terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling and a colorimetric WST-1 assay. Further, Tat-PDIA3 significantly ameliorated the ischemia-induced deficits in motor function, based on Tarlov’s criteria, 24–72 h after ischemia/reperfusion, as well as the degeneration of motor neurons in the ventral horn 72 h after ischemia/reperfusion. Tat-PDIA3 administration also reduced the ischemia-induced activation of microglia and lipid peroxidation in the motor neurons 72 h after ischemia/reperfusion. PDIA3 also potentially ameliorated the ischemia-induced increase in oxidative markers in serum and decreased the activity of Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase in spinal cord homogenates, 24 h and 72 h after ischemia/reperfusion. These results suggest that Tat-PDIA3 could be used to protect spinal cord neurons from ischemic damage, due to its modulatory action on the oxidative/anti-oxidative balance. Tat-PDIA3 could be applicable to protects neurons from the ischemic damage induced by thoracoabdominal aorta obstruction.
HSF4 regulates lens fiber cell differentiation by activating p53 and its downstream regulators
Authors: Gao Meng , Huang Yuwen , Wang Ling , Huang Mi , Liu Fei , Liao Shengjie , Yu Shanshan , Lu Zhaojing , Han Shanshan , Hu Xuebin , Qu Zhen , Liu Xiliang , Assefa Yimer Tinsae , Yang Lifang , Tang Zhaohui , Li David Wan-Cheng , Liu Mugen
Published: October 2017

Cataract refers to opacities of the lens that impede the passage of light. Mutations in heat shock transcription factor 4 (HSF4) have been associated with cataract; however, the mechanisms regarding how mutations in HSF4 cause cataract are still obscure. In this study, we generated an hsf4 knockout zebrafish model using TALEN technology. The mutant zebrafish developed an early-onset cataract with multiple developmental defects in lens. The epithelial cells of the lens were overproliferated, resulting in the overabundance of lens fiber cells in hsf4null zebrafish lens. Consequently, the arrangement of the lens fiber cells became more disordered and irregular with age. More importantly, the terminal differentiation of the lens fiber cell was interrupted as the organelles cannot be cleaved in due time. In the cultured human lens epithelial cells, HSF4 could stabilize and retain p53 in the nucleus to activate its target genes such as fas cell surface death receptor (Fas) and Bcl-2-associated X apoptosis regulator (Bax). In the hsf4null fish, both p53 and activated-caspase3 were significantly decreased. Combined with the finding that the denucleation defect could be partially rescued through microinjection of p53, fas and bax mRNA into the mutant embryos, we directly proved that HSF4 promotes lens fiber cell differentiation by activating p53 and its downstream regulators. The data we presented suggest that apoptosis-related genes are involved in the lens fiber cell differentiation. Our finding that HSF4 functions in the upstream to activate these genes highlighted the new regulatory modes of HSF4 in the terminal differentiation of lens fiber cell.
Neuron and microglia/macrophage-derived FGF10 activate neuronal FGFR2/PI3K/Akt signaling and inhibit microglia/macrophages TLR4/NF-κB-dependent neuroinflammation to improve functional recovery after spinal cord injury
Authors: Chen Jian , Wang Zhouguang , Zheng ZengMing , Chen Yu , Khor Sinan , Shi KeSi , He ZiLi , Wang Qingqing , Zhao Yingzheng , Zhang Hongyu , Li Xiaokun , Li Jiawei , Yin Jiayu , Wang Xiangyang , Xiao Jian
Published: October 2017

Therapeutics used to treat central nervous system (CNS) injury were designed to repair neurites and inhibit cell apoptosis. Previous studies have shown that neuron-derived FGF10 exerts potential neuroprotective effects after cerebral ischemia injury. However, little is known about the role of endogenous FGF10 in the recovery process after spinal cord injury (SCI). In this study, we found that FGF10 is mainly produced by neuron and microglia/macrophages, and its expression is increased after SCI. Exogenous treatment of FGF10 improved functional recovery after injury by reducing apoptosis, as well as repairing neurites via FGFR2/PI3K/Akt pathway. On another hand, inhibiting the PI3K/Akt pathway with LY294002 partially reversed the therapeutic effects of FGF10. In addition, small interfering RNA knockdown of FGFR2 suppressed PI3K/Akt pathway activation by FGF10 and abolished its anti-apoptotic and neurite repair effects in vitro. Furthermore, FGF10 treatment inhibited the activation and proliferation of microglia/macrophages through regulation of TLR4/NF-κB pathway, and attenuated the release of pro-inflammatory cytokines after SCI. Thus, the increased expression of FGF10 after acute SCI is an endogenous self-protective response, suggesting that FGF10 could be a potential treatment for CNS injury.
Tristetraprolin inhibits macrophage IL-27-induced activation of antitumour cytotoxic T cell responses
Authors: Wang Qinghong , Ning Huan , Peng Hui , Wei Lin , Hou Rong , Hoft Daniel F. , Liu Jianguo
Published: October 2017

IFN-γ-producing cytotoxic T lymphocytes are essential for host defense against viral infection and cancer. Here we show that the RNA-binding tristetraprolin, encoded by Zfp36, is needed for CD8+ T-cell production of IFN-γ in vivo. When activated in vitro, however, IFN-γ production by naive wild type and tristetraprolin-deficient CD8+ T-cells is comparable. IL-27 is overproduced by tristetraprolin-deficient macrophages and increased systemically in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by promoting p28 mRNA degradation. Importantly, deletion of IL-27 receptor WSX-1 in tristetraprolin-deficient mice (WSX-1/tristetraprolin double knockout) leads to a reduction in cytotoxic T lymphocyte numbers. Moreover, tumor growth is accelerated, not only in tristetraprolin-deficient mice after cytotoxic T lymphocyte depletion, but also in WSX-1/tristetraprolin double knockout mice, with substantial reduction in the number of tumor cytotoxic T lymphocytes. This study describes a regulatory pathway for IL-27 expression and cytotoxic T lymphocyte function mediated by tristetraprolin, contributing to regulation of antitumour immunity.
Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes
Authors: Riaz Nadeem , Blecua Pedro , Lim Raymond S. , Shen Ronglai , Higginson Daniel S. , Weinhold Nils , Norton Larry , Weigelt Britta , Powell Simon N. , Reis-Filho Jorge S.
Published: October 2017

BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair and are germ-line cancer pre-disposition genes that result in a syndrome of hereditary breast and ovarian cancer (HBOC). Whether germ-line or somatic alterations in these genes or other members of the HR pathway and if mono- or bi-allelic alterations of HR-related genes have a phenotypic impact on other cancers remains to be fully elucidated. Here, we perform a pan-cancer analysis of The Cancer Genome Atlas (TCGA) data set and observe that bi-allelic pathogenic alterations in homologous recombination (HR) DNA repair-related genes are prevalent across many malignancies. These bi-allelic alterations often associate with genomic features of HR deficiency. Further, in ovarian, breast and prostate cancers, bi-allelic alterations are mutually exclusive of each other. The combination of these two properties facilitates reclassification of variants of unknown significance affecting DNA repair genes, and may help personalize HR directed therapies in the clinic.
A cdk1 gradient guides surface contraction waves in oocytes
Authors: Bischof Johanna , Brand Christoph A. , Somogyi Kálmán , Májer Imre , Thome Sarah , Mori Masashi , Schwarz Ulrich S. , Lénárt Péter
Published: October 2017

Surface contraction waves (SCWs) in oocytes and embryos lead to large-scale shape changes coupled to cell cycle transitions and are spatially coordinated with the cell axis. Here, we show that SCWs in the starfish oocyte are generated by a traveling band of myosin II-driven cortical contractility. At the front of the band, contractility is activated by removal of cdk1 inhibition of the RhoA/RhoA kinase/myosin II signaling module, while at the rear, contractility is switched off by negative feedback originating downstream of RhoA kinase. The SCW’s directionality and speed are controlled by a spatiotemporal gradient of cdk1-cyclinB. This gradient is formed by the release of cdk1-cyclinB from the asymmetrically located nucleus, and progressive degradation of cyclinB. By combining quantitative imaging, biochemical and mechanical perturbations with mathematical modeling, we demonstrate that the SCWs result from the spatiotemporal integration of two conserved regulatory modules, cdk1-cyclinB for cell cycle regulation and RhoA/Rok/NMYII for actomyosin contractility.
Ecogenomics of virophages and their giant virus hosts assessed through time series metagenomics
Authors: Roux Simon , Chan Leong-Keat , Egan Rob , Malmstrom Rex R. , McMahon Katherine D. , Sullivan Matthew B.
Published: October 2017

Virophages are small viruses that co-infect eukaryotic cells alongside giant viruses (Mimiviridae) and hijack their machinery to replicate. While two types of virophages have been isolated, their genomic diversity and ecology remain largely unknown. Here we use time series metagenomics to identify and study the dynamics of 25 uncultivated virophage populations, 17 of which represented by complete or near-complete genomes, in two North American freshwater lakes. Taxonomic analysis suggests that these freshwater virophages represent at least three new candidate genera. Ecologically, virophage populations are repeatedly detected over years and evolutionary stable, yet their distinct abundance profiles and gene content suggest that virophage genera occupy different ecological niches. Co-occurrence analyses reveal 11 virophages strongly associated with uncultivated Mimiviridae, and three associated with eukaryotes among the Dinophyceae, Rhizaria, Alveolata, and Cryptophyceae groups. Together, these findings significantly augment virophage databases, help refine virophage taxonomy, and establish baseline ecological hypotheses and tools to study virophages in nature.
A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone
Authors: Castrignanò Erika , Mardal Marie , Rydevik Axel , Miserez Bram , Ramsey John , Shine Trevor , Pantoș G. Dan , Meyer Markus R. , Kasprzyk-Hordern Barbara
Published: October 2017

Wastewater-based epidemiology is an innovative approach to estimate public health status using biomarker analysis in wastewater. A new compound detected in wastewater can be a potential biomarker of an emerging trend in public health. However, it is currently difficult to select new biomarkers mainly due to limited human metabolism data. This manuscript presents a new framework, which enables the identification and selection of new biomarkers of human exposure to drugs with scarce or unknown human metabolism data. Mephedrone was targeted to elucidate the assessment of biomarkers for emerging drugs of abuse using a four-step analytical procedure. This framework consists of: (i) identification of possible metabolic biomarkers present in wastewater using an in-vivo study; (ii) verification of chiral signature of the target compound; (iii) confirmation of human metabolic residues in in-vivo/vitro studies and (iv) verification of stability of biomarkers in wastewater. Mephedrone was selected as a suitable biomarker due to its high stability profile in wastewater. Its enantiomeric profiling was studied for the first time in biological and environmental matrices, showing stereoselective metabolism of mephedrone in humans. Further biomarker candidates were also proposed for future investigation: 4′-carboxy-mephedrone, 4′-carboxy-normephedrone, 1-dihydro-mephedrone, 1-dihydro-normephedrone and 4′-hydroxy-normephedrone.
Enhanced cell attachment and hemocompatibility of titanium by nanoscale surface modification through severe plastic integration of magnesium-rich islands and porosification
Authors: Rezaei Masoud , Tamjid Elnaz , Dinari Ali
Published: October 2017

Besides the wide applications of titanium and its alloys for orthopedic and biomedical implants, the biocompatible nature of titanium has emerged various surface modification techniques to enhance its bioactivity and osteointegration with living tissues. In this work, we present a new procedure for nanoscale surface modification of titanium implants by integration of magnesium-rich islands combined with controlled formation of pores and refinement of the surface grain structure. Through severe plastic deformation of the titanium surface with fine magnesium hydride powder, Mg-rich islands with varying sizes ranging from 100 nm to 1000 nm can be integrated inside a thin surface layer (100–500 µm) of the implant. Selective etching of the surface forms a fine structure of surface pores which their average size varies in the range of 200–500 nm depending on the processing condition. In vitro biocompatibility and hemocompatibility assays show that the Mg-rich islands and the induced surface pores significantly enhance cell attachment and biocompatibility without an adverse effect on the cell viability. Therefore, severe plastic integration of Mg-rich islands on titanium surface accompanying with porosification is a new and promising procedure with high potential for nanoscale modification of biomedical implants.
Robust Fusion of Diffusion MRI Data for Template Construction
Authors: Yang Zhanlong , Chen Geng , Shen Dinggang , Yap Pew-Thian
Published: October 2017

Construction of brain templates is generally carried out using a two-step procedure involving registering a population of images to a common space and then fusing the aligned images to form a template. In practice, image registration is not perfect and simple averaging of the images will blur structures and cause artifacts. In diffusion MRI, this is further complicated by intra-voxel inter-subject differences in fiber orientation, fiber configuration, anisotropy, and diffusivity. In this paper, we propose a method to improve the construction of diffusion MRI templates in light of inter-subject differences. Our method involves a novel q-space (i.e., wavevector space) patch matching mechanism that is incorporated in a mean shift algorithm to seek the most probable signal at each point in q-space. Our method relies on the fact that the mean shift algorithm is a mode seeking algorithm that converges to the mode of a distribution and is hence robust to outliers. Our method is therefore in effect seeking the most probable signal profile at each voxel given a distribution of signal profiles. Experimental results show that our method yields diffusion MRI templates with cleaner fiber orientations and less artifacts caused by inter-subject differences in fiber orientation.
Highly sensitive, self-powered and wearable electronic skin based on pressure-sensitive nanofiber woven fabric sensor
Authors: Zhou Yuman , He Jianxin , Wang Hongbo , Qi Kun , Nan Nan , You Xiaolu , Shao Weili , Wang Lidan , Ding Bin , Cui Shizhong
Published: October 2017

The wearable electronic skin with high sensitivity and self-power has shown increasing prospects for applications such as human health monitoring, robotic skin, and intelligent electronic products. In this work, we introduced and demonstrated a design of highly sensitive, self-powered, and wearable electronic skin based on a pressure-sensitive nanofiber woven fabric sensor fabricated by weaving PVDF electrospun yarns of nanofibers coated with PEDOT. Particularly, the nanofiber woven fabric sensor with multi-leveled hierarchical structure, which significantly induced the change in contact area under ultra-low load, showed combined superiority of high sensitivity (18.376 kPa−1, at ~100 Pa), wide pressure range (0.002–10 kPa), fast response time (15 ms) and better durability (7500 cycles). More importantly, an open-circuit voltage signal of the PPNWF pressure sensor was obtained through applying periodic pressure of 10 kPa, and the output open-circuit voltage exhibited a distinct switching behavior to the applied pressure, indicating the wearable nanofiber woven fabric sensor could be self-powered under an applied pressure. Furthermore, we demonstrated the potential application of this wearable nanofiber woven fabric sensor in electronic skin for health monitoring, human motion detection, and muscle tremor detection.
Unexpected 3+ valence of iron in FeO2, a geologically important material lying “in between” oxides and peroxides
Authors: Streltsov Sergey S. , Shorikov Alexey O. , Skornyakov Sergey L. , Poteryaev Alexander I. , Khomskii Daniel I.
Published: October 2017

Recent discovery of the pyrite FeO2, which can be an important ingredient of the Earth’s lower mantle and which in particular may serve as an extra source of water in the Earth’s interior, opens new perspectives for geophysics and geochemistry, but this is also an extremely interesting material from physical point of view. We found that in contrast to naive expectations Fe is nearly 3+ in this material, which strongly affects its magnetic properties and makes it qualitatively different from well known sulfide analogue - FeS2. Doping, which is most likely to occur in the Earth’s mantle, makes FeO2 much more magnetic. In addition we show that unique electronic structure places FeO2 “in between” the usual dioxides and peroxides making this system interesting both for physics and solid state chemistry.
An integrated microfluidic system using a micro-fluxgate and micro spiral coil for magnetic microbeads trapping and detecting
Authors: Sun Xuecheng , Feng Zhu , Zhi Shaotao , Lei Chong , Zhang Di , Zhou Yong
Published: October 2017

We report an innovative integrated microfluidic platform based on micro-fluxgate and micro-coils for trapping and detecting magnetic beads. A micro-spiral coil fabricated by microfabrication technology is used to trap the magnetic beads, and the micro-fluxgate is employed to detect the weak magnetic field induced by the trapped magnetic beads. The fabrication process of the magnetic bead trapping system using a micro-coil is highly compatible with that of the micro-fluxgate sensor, making fabrication of this integrated microfluidic system convenient and efficient. It is observed that the magnetic bead trapping ratio increases as the number of magnetic beads is increased with a flow rate of 5 to 16.5 μL·min−1. Samples spiked with different concentrations of magnetic beads can be distinguished clearly using the micro-fluxgate sensor in this microfluidic system. In this study, the results demonstrate that the microfluidic system traps and detects magnetic beads efficiently and is a promising candidate for biomarker capture and detection.
Trade routes and plague transmission in pre-industrial Europe
Authors: Yue Ricci P. H. , Lee Harry F. , Wu Connor Y. H.
Published: October 2017

Numerous historical works have mentioned that trade routes were to blame for the spread of plague in European history, yet this relationship has never been tested by quantitative evidence. Here, we resolve the hypothetical role of trade routes through statistical analysis on the geo-referenced major trade routes in the early modern period and the 6,656 geo-referenced plague outbreak records in AD1347–1760. Ordinary Least Square (OLS) estimation results show that major trade routes played a dominant role in spreading plague in pre-industrial Europe. Furthermore, the negative correlation between plague outbreaks and their distance from major trade ports indicates the absence of a permanent plague focus in the inland areas of Europe. Major trade routes decided the major plague outbreak hotspots, while navigable rivers determined the geographic pattern of sporadic plague cases. A case study in Germany indicates that plague penetrated further into Europe through the local trade route network. Based on our findings, we propose the mechanism of plague transmission in historical Europe, which is imperative in demonstrating how pandemics were spread in recent human history.
Optimizing extraction and analysis of pharmaceuticals in human urine, struvite, food crops, soil, and lysimeter water by liquid chromatography-tandem mass spectrometry
Authors: Mullen Rachel A. , Wigginton Krista R. , Noe-Hays Abraham , Nace Kim , Love Nancy G. , Bott Charles B. , Aga Diana S.
Published: October 2017

Matrix-specific methods were developed and validated for the analysis of pharmaceuticals in human urine, struvite, soil, and vegetables.
Heterogeneous mesoporous manganese/cobalt oxide catalysts for selective oxidation of 5-hydroxymethylfurfural to 2,5-diformylfuran
Authors: Biswas Sourav , Dutta Biswanath , Mannodi-Kanakkithodi Arun , Clarke Ryan , Song Wenqiao , Ramprasad Ramamurthy , Suib Steven L.
Published: October 2017

We report a heterogeneous catalytic protocol for the oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-diformylfuran (DFF) using a mesoporous manganese doped cobalt oxide material.
Synthesis of novel hierarchical SiC–SiO2heterostructures via a catalyst free method
Authors: Dai Jixiang , Sha Jianjun , Zhang Zhaofu , Shao Junqi , Zu Yufei , Lei Mingkai
Published: October 2017

Novel hierarchical SiC–SiO2heterostructures were synthesized on a graphite paper substrateviaa catalyst free method.
Synthesis of variously shaped magnetic FeCo nanoparticles and the growth mechanism of FeCo nanocubes
Authors: Yuan Jie , Li Cai-Fu , Liu Zhi-Quan , Wu Di , Cao Lihua
Published: October 2017

TEM characterization of FeCo nanosheets and FeCo cubes.
Catechol–cation adhesion on silica surfaces: molecular dynamics simulations
Authors: Li Yingtu , Liao Mingrui , Zhou Jian
Published: October 2017

Understanding the interaction mechanism between catechol–cation and inorganic surfaces is vital for controlling the interfacial adhesion behavior.
The effect of dietary factors on strawberry anthocyanins oral bioavailability
Authors: Xiao Di , Sandhu Amandeep , Huang Yancui , Park Eunyoung , Edirisinghe Indika , Burton-Freeman Britt M.
Published: October 2017

Strawberries are a dietary source of anthocyanins, particularly pelargonidin glycosides.
Neuroprotective action of tea polyphenols on oxidative stress-induced apoptosis through the activation of the TrkB/CREB/BDNF pathway and Keap1/Nrf2 signaling pathway in SH-SY5Y cells and mice brain
Authors: Qi Guoyuan , Mi Yashi , Wang Yiwen , Li Runnan , Huang Shuxian , Li Xingyu , Liu Xuebo
Published: October 2017

Neuroprotective effects of tea polyphenols on apoptosis and oxidative stress induced by constant darkness and H2O2in vivoandin vitro.
Axially chiral amino acid scaffolds as efficient fluorescent discriminators of methanol–ethanol
Authors: Bag Subhendu Sekhar , Jana Subhashis
Published: October 2017

Differential solvation guided H-bonding interaction allows novel axially chiral amino acid scaffolds for efficient discrimination of ethanol–methanolviaa switch-on fluorescence response.
Correction: A simple one-pot synthesis of a Zn(O,S)/Ga2O3 nanocomposite photocatalyst for hydrogen production and 4-nitrophenol reduction
Authors: Abdullah Hairus , Susanto Gultom Noto , Kuo Dong-Hau
Published: October 2017

Correction for ‘A simple one-pot synthesis of a Zn(O,S)/Ga2O3 nanocomposite photocatalyst for hydrogen production and 4-nitrophenol reduction’ by Hairus Abdullah et al., New J. Chem., 2017, DOI: 10.1039/c7nj02505j.
From electroburning to sublimation: substrate and environmental effects in the electrical breakdown process of monolayer graphene
Authors: El Abbassi Maria , Pósa László , Makk Péter , Nef Cornelia , Thodkar Kishan , Halbritter András , Calame Michel
Published: October 2017

We have identified two distinct electrical breakdown mechanisms yielding few nanometer wide graphene nanogaps.
CoSex nanocrystalline-dotted CoCo layered double hydroxide nanosheets: a synergetic engineering process for enhanced electrocatalytic water oxidation
Authors: Xue Yuzhu , Ren Zhiyu , Xie Ying , Du Shichao , Wu Jun , Meng Huiyuan , Fu Honggang
Published: October 2017

The synergistic manipulation of CoSex nanocrystalline-dotted porous CoCo LDH nanosheets in their structure, component, and electron configuration leads to enhanced OER activity.
Rigid blocks matching method based on contour curves and feature regions
Authors: Zhao Fuqun , Zhou Mingquan , Geng Guohua , Zhu Lipin
Published: October 2017

This study proposes a blocks matching method based on contour curves and feature regions that improve the matching precision and speed with which rigid blocks with a specified thickness in point clouds are matched. The method comprises two steps: coarse matching and fine matching. In the coarse matching step, the rigid blocks are first segmented into a series of surfaces and the fracture surfaces are distinguished. Then, the contour curves of the fracture surfaces are extracted using an improved boundary growth method and the rigid blocks are coarsely matched with them. In the fine matching step, feature regions are first extracted from the fracture surfaces. Then, the centroid of each feature region is calculated and the fine matching of rigid blocks with the centroid sets is completed using an improved iterative closest point (ICP) algorithm. The improved ICP algorithm integrates the rotation angle constraint and dynamic iteration coefficient into a probability ICP algorithm, which significantly improves matching precision and speed. Experiments conducted using public blocks and Terracotta Warriors blocks indicate that the proposed method carries out rigid blocks matching more accurately and rapidly than various conventional methods.
Fault location approach for distribution systems based on modern monitoring infrastructure
Authors: Cavalcante Paulo A.H. , de Almeida Madson C.
Published: October 2017

This study presents an approach based on short‐circuit theory and on modern monitoring infrastructure for locating permanent and temporary faults in power distribution systems. The main innovative aspects of the proposed approach are: (i) no fault classification is required if phasor measurements are adopted, (ii) both current and voltage measurements may be included in the problem, (iii) in the fault location criterion the measurements are weighted according to their proximity to the fault location, (iv) a refinement scheme allows finding the fault on branches and not only at buses. The proposed approach can cope with magnitude measurements, synchronised phasors obtained via micro phasor measurement unit and unsynchronised phasors, which are being used for the first time for fault location purposes. Case studies are carried out considering a real 134‐bus feeder. Initially, the performance of the proposed approach is assessed with respect to fault location, fault type and fault resistance. Next, studies regarding the influence of the number, position and type of measurements are presented. Statistical simulations are performed for assessing the influence of the random errors inherent to measurements, load forecasting and distribution system parameters. The results indicate that the proposed approach is accurate and very promising.