bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic Deuterium Evolution and H/D Exchange in DNA
Authors: Dorčák Vlastimil , Paleček Emil
Published: November 2018

Recently, it has been shown that DNA catalyzes the hydrogen evolution reaction (HER) at mercury‐containing electrodes, which provide voltammetric and chronopotentiometric stripping (CPS) peaks
, allowing label‐free DNA determination at very low concentrations. Here, we compared DNA catalytic HER in H2O with catalytic deuterium evolution reaction (DER) in D2O. We show that in D2O single‐stranded (ss) and double‐stranded (ds) DNAs produced CPS peaks
due to DER. Compared to peaks
obtained in H2O, peaks
were smaller and appeared at more negative potentials. Under conditions where dsDNA did not produce any peak
in D2O, this DNA produced in H2O peak
. These results suggested a lack of accessible bases in the D2O surface‐attached dsDNA. This might be attributed to the greater stability of deuterated dsDNA, better resisting the electric field effects at the negatively charged interface. The process of protonation of deuterated ssDNA was very fast in contrast to that of dsDNA, which was much slower and could be followed by CPS in a time range of tens of minutes.
Insights into the Electrocatalytic Hydrogen Evolution Reaction Mechanism on Two‐Dimensional Transition‐Metal Carbonitrides (MXene)
Authors: Huang Bin , Zhou Naigen , Chen Xingzhu , Ong Wee‐Jun , Li Neng
Published: November 2018

Developing highly active, non‐noble‐metal H2‐evolution catalysts is appealing yet still remains a great challenge in the field of electrocatalytic and photocatalytic H2 production. In this work, high quality transition‐metal carbonitrides M3CN (MXene) are investigated using well‐defined density functional theory (DFT) calculations. The structural configurations, H‐adsorption free energy (ΔGH) and charge transfer for bare, surface‐terminated and transition‐metal (TM)‐modified M3CNO2 are systematically studied. The calculated results indicate that all bare transition metal carbonitrides exhibit strong binding between H atom and catalysts. In addition, only Ti3CNO2 and Nb3CNO2 have the potential to be HER active catalysts based on the ΔGH results. In an attempt to overcome poor HER activity limitations, we apply O as well as OH mixed groups and TMs modification on the Ti3CNO2 surface for tuning HER activity, and a significant improvement of HER activity is observed. Overall, this work presents in‐depth investigations for transition‐metal carbonitrides (MXene) and opens up new designs for robust metal carbonitrides as noble‐metal‐free cocatalysts for highly efficient and low‐cost MXene‐based nanocomposites for water splitting applications.
In vitro Anti‐atherogenic Properties of N‐Heterocyclic Carbene Aurate(I) Compounds
Authors: Sioriki Eleni , Lordan Ronan , Nahra Fady , Van Hecke Kristof , Zabetakis Ioannis , Nolan Steven P.
Published: November 2018

The anti‐atherogenic (anti‐inflammatory) properties of various aurate(I) salts, of the general formula [NHC⋅H][AuCl2] (NHC=N‐heterocyclic carbene) were investigated. The aurates were easily synthesized and obtained in analytically pure form. In addition, the biological activity of these compounds against atheromatosis via in vitro inhibition of platelet‐activating factor (PAF)‐induced platelet aggregation was probed. All complexes were found to possess anti‐aggregatory properties in vitro with [IPr*⋅H][AuCl2] (6) being the most potent inhibitor of PAF at micromolar concentration. Based on our findings, we conclude that these simply assembled aurates are a very promising class of PAF inhibitors and anti‐inflammatory drugs.
Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients with BRAF‐mutated melanoma and other advanced malignancies
Authors: Bhatty Minny , Kato Shumei , Piha‐Paul Sarina A. , Naing Aung , Subbiah Vivek , Huang Helen J. , Karp Daniel D. , Tsimberidou Apostolia M. , Zinner Ralph G. , Hwu Wen‐Jen , Javle Milind , Patel Sapna P. , Hu Mimi I. , Varadhachary Gauri R. , Conley Anthony P. , Ramzanali Nishma M. , Holley Veronica R. , Kurzrock Razelle , Meric‐Bernstam Funda , Kwang Chae Young , Kim Kevin B. , Falchook Gerald S. , Janku Filip
Published: November 2018

Background

BRAF inhibitors are effective against selected BRAFV600‐mutated tumors. Preclinical data suggest that BRAF inhibition in conjunction with chemotherapy has increased therapeutic activity.

Methods

Patients with advanced cancers and BRAF mutations were enrolled into a dose‐escalation study (3+3 design) to determine the maximum tolerated dose (MTD) and dose‐limiting toxicities (DLTs).

Results

Nineteen patients with advanced cancers and BRAF mutations were enrolled and received vemurafenib (480‐720 mg orally twice a day), carboplatin (area under the curve [AUC] 5‐6 intravenously every 3 weeks), and paclitaxel (100‐135 mg/m2 intravenously every 3 weeks). The MTD was not reached, and vemurafenib at 720 mg twice a day, carboplatin at AUC 5, and paclitaxel at 135 mg/m2 were the last safe dose levels. DLTs included a persistent grade 2 creatinine elevation (n = 1), grade 3 transaminitis (n = 1), and grade 4 thrombocytopenia (n = 1). Non–dose‐limiting toxicities that were grade 3 or higher and occurred in more than 2 patients included grade 3/4 neutropenia (n = 5), grade 3/4 thrombocytopenia (n = 5), grade 3 fatigue (n = 4), and grade 3 anemia (n = 3). Of the 19 patients, 5 (26%; all with melanoma) had a partial response (PR; n = 4) or complete response (CR; n = 1); these responses were mostly durable and lasted 3.1 to 54.1 months. Of the 13 patients previously treated with BRAF and/or mitogen‐activated protein kinase kinase (MEK) inhibitors, 4 (31%) had a CR (n = 1) or PR (n = 3). Patients not treated with prior platinum therapy had a higher response rate than those who did (45% vs 0%; P = .045).

Conclusions

The combination of vemurafenib, carboplatin, and paclitaxel is well tolerated and demonstrates encouraging activity, predominantly in patients with advanced melanoma and BRAFV600 mutations, regardless of prior treatment with BRAF and/or MEK inhibitors.
A logical relationship for schizophrenia, bipolar, and major depressive disorder. Part 4: Evidence from chromosome 4 high‐density association screen
Authors: Tang Jian , Chen Xing , Cai Bin , Chen Gang
Published: November 2018

Convergent evidence from genetics, symptomatology, and psychopharmacology imply that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD). Familial clustering of SCZ, BPD, and MDD was systematically investigated [Aukes et al. (2012); Genetics in Medicine 14(3): 338–341], and any two or even three of these disorders could co‐exist in some families. A total of 56,134 SNPs on chromosome 4 were genotyped by Affymetrix Genome‐Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (Type‐I), 177 MDD patients, and 1,000 controls in a relative homogenous population in China. Susceptibility genes on chromosome 4 for the three major psychiatric disorders were systematically identified including outstanding genes (CXCL13, FSTL5, GLRB, KCNIP4, LPHN3, MAPK10, NPFFR2, NSUN7, PCDH10, PCDH7, PPA2, PPARGC1A, SCD5, SCFD2, and UNC5C). Unexpectedly, flanking genes for up to 93.67% of the associated SNPs were also confirmed in an enlarged cohort of 986 SCZ patients. Taken all relevant evidence together, our chromosome 4 results implicate that both of bipolar and major depressive disorders might be subtypes of SCZ rather than independent disease entity. Furthermore, similar evidence was also observed on chromosome 3, 5, 6, 7, and 8 [2018; The Journal of Comparative Neurology 526(1):59–79; Chen et al. (2017); American Journal of Translational Research 9(5):2473–2491; Chen et al. (2016); Current Molecular Medicine, 16(9):840–854; Chen et al. (2015); Behavioural Brain Research, 293:241–51; Chen et al. (2016); Molecular Neurobiology, 54(8):5868–5882].
Design, Synthesis and Computational Study of Fluorinated Quinoxaline‐Oligothiophene‐based Conjugated Polymers with Broad Spectral Coverage
Authors: Gedefaw Desta , Hedström Svante , Xia Yuxin , Persson Petter , Andersson Mats R.
Published: November 2018

Donor‐acceptor (D‐A) copolymers typically show two absorption peaks in the visible region, flanking a valley region of limited absorptivity. One strategy for more panchromatic light harvesting is to incorporate side‐groups orthogonal to the polymer backbone, which enable 2D π conjugation and can give rise to additional absorption peaks. Here we design and synthesize two D‐A polymers which both carry a fluorinated quinoxaline acceptor unit, but while P1 includes a benzodithiophene donor moiety with thiophene side‐groups (2D‐BDT), the P2 polymer lacks 2D conjugation in its simpler pentathiophene donor segment. The P1 polymer consequently shows an atypical absorption profile with more panchromatic absorption with no apparent valley in the spectrum. In order to understand the structure‐electronic relations, the optical and electrochemical properties were predicted using a previously developed computational approach. The predicted optical properties show very good agreement with the experimental results. Solar cells made from P1 show a short‐circuit current more than twice as large as P2, attributed to its enhanced spectral coverage. However, poor fill factors limit the preliminary power conversion efficiencies to 3.3 % for P1 and 1.0 % for P2 as blended with PCBM[70] in a 1 : 1.5 (w/w) ratio.
Preparation of a Hierarchically Porous Lead/Carbon Composite and Its Application in Lead‐Carbon Batteries
Authors: Gao Yunfang , Wan Huojun , Xia Yunchuan , Xu Xin , Wu BaoLiang
Published: November 2018

A novel and scalable lead‐modified phenolic resin‐based carbon material (Pb/PRC) has been successfully prepared by using lead‐modified phenolic resin (Pb/PR) as a precursor, toluene as a pore‐forming agent, and KOH as an activating agent. The Pb/PRC composite presents a hierarchically porous nanosphere structure, and this structure contributes to prolong its cycling life under high‐rate partial state‐of‐charge (HRPSoC) operation. Pb/PRC with nano‐lead can effectively inhibit hydrogen evolution and provide pseudocapacitance. Compared with a blank negative plate, a lead‐carbon battery with Pb/PRC displays 18 000 cycles under HRPSoC operation and exhibits a capacity of 100 mA h g−1 at 2 C discharge rate.
IRMS delta values (13C) of nandrolone and testosterone products available in the UK: Implications for anti‐doping
Authors: Brailsford Alan D. , Majidin Wan Noor Mahirah , Wojek Nick , Cowan David A. , Walker Christopher
Published: November 2018

Anabolic androgenic steroids (AAS) are the most widely abused class of drugs by athletes and thus represent a significant problem to the anti‐doping community. Confirmation of a doping violation for AAS cannot always be based on their presence alone due to the endogenous production of some steroids. Both testosterone (and its metabolites) and the major diagnostic metabolite of nandrolone (19‐norandrosterone) are produced endogenously. Gas chromatography–combustion–isotope ratio mass spectrometry (GC–C–IRMS) is used in such cases to differentiate between the administration of a synthetic preparation and endogenous steroid production by measurement of their differing carbon isotope (13C/12C) ratio. The purpose of this study was to investigate the availability of steroid preparations in the UK with a 13C content analytically indistinguishable from that of endogenous steroids. Fourteen preparations containing nandrolone (n = 9) and testosterone (n = 5) were analyzed. The δ13C values were determined using GC–C–IRMS and the identity of the steroid preparations was confirmed using gas chromatography–mass spectrometry (GC–MS). Ten steroid preparations displayed δ13C values within the range expected for synthetic steroids (less than −27‰). However, four nandrolone preparations displayed δ13C values that overlap with the values considered to be endogenous in origin (range: −26 to −16‰). Misuse of these preparations could prevent the confirmation of nandrolone administration using GC–C–IRMS in anti‐doping cases.
Generation and characterization of Megf6 null and Cre knock‐in alleles
Authors: Wang Ye , Song Hejie , Wang Wenfeng , Zhang Zhen
Published: November 2018

Megf6, a member of MEGF (multiple EGF‐like domains) protein family, is a conserved high molecular weight protein with 30 EGF‐like domains. Although many members of the MEGF protein family are essential for embryonic development and homeostasis, the role of Megf6 in development and physiology is still unknown. Here, we generated Megf6‐deficient mice using CRISPR‐Cas9 technique and showed that Megf6 is dispensable for embryonic development. We also constructed the Megf6Cre allele to study Megf6‐expressing cell lineages. Our results showed that Megf6‐expressing cells contribute to the periotic mesenchyme and its derivatives, skin epidermis, certain cells in brain and ribs. Therefore, the Megf6Cre allele can be a useful tool for conditional deletion in these tissues, in particular for periotic mesenchyme deletion.
A Sequential One‐Pot Synthesis of Functionalized Esters and Thioesters through a Ring‐Opening Acylation of Cyclic Ethers and Thioethers
Authors: Gopinath Purushothaman , Chandrasekaran Srinivasan
Published: November 2018

A one‐pot protocol for the synthesis of functionalized esters and thioesters is reported from cyclic ethers/thioethers and carboxylic acids via acyloxyphosphonium salts as key intermediates. The reaction of styrene oxide with acyloxyphosphonium salts gave complete regioselectivity and good yields of the resulting functionalized ester, whereas cyclohexene oxide gave moderate yields. Styrene episulfide, on the other hand, gave good yields with moderate regioselectivity whereas cyclohexene sulfide gave quantitative yields of the corresponding thioesters. We have also shown an alternate procedure for the ring opening of THF to form 4‐bromo butyl esters. All these reactions were carried out in the absence of a catalyst, showing the synthetic versatility of our method.
3D Multilayered paper‐ and thread/paper‐based microfluidic devices for bioassays
Authors: Neris Natalia M. , Guevara Ricardo D. , Gonzalez Ariana , Gomez Frank A.
Published: November 2018

In this paper we describe the fabrication of novel 3D microfluidic paper‐based analytical devices (3D‐μPADs) and a 3D microfluidic thread/paper‐based analytical device (3D‐μTPAD) to detect glucose and BSA through colorimetric assays. The 3D‐μPAD and 3D‐μTPAD consisted of three (wax, heat pressed wax‐printed paper, single‐sided tape) and four (hole‐punched single‐sided tape, blank chromatography circles, heat‐pressed wax‐printed paper, hole‐punched single‐sided tape containing trifurcated thread) layers, respectively. The saturation curves for each assay were generated for all platforms. For the glucose assay, a solution of glucose oxidase (GOx), horseradish peroxidase, and potassium iodide was flowed through each platform and, upon contact with glucose, generated a yellow‐brown color indicative of the oxidation of iodide to iodine. For the protein assay, BSA was flowed through each device and, upon contact with citrate buffer and tetrabromophenol blue, resulted in a color change from yellow to blue. The devices were dried, scanned, and analyzed yielding a correlation between either yellow intensity and glucose concentration or cyan intensity and BSA concentration. A similar glucose assay, using unknown concentrations of glucose in artificial urine, was conducted and, when compared to the saturation curve, showed good correlation between the theoretical and actual concentrations (percent differences <10%). The development of 3D‐μPADs and 3D‐μTPADs can further facilitate the use of these platforms for colorimetric bioassays.
Epigenetic Clocks
Authors: Guevara Elaine E. , Lawler Richard R.
Published: November 2018

Recent research has revealed clock‐like patterns of epigenetic change across the life span in humans. Models describing these epigenetic changes have been dubbed “epigenetic clocks,” and they can not only predict chronological age but also reveal biological age, which measures physiological homeostasis and deterioration over the life span. Comparative studies of the epigenetic clocks of different primate species are likely to provide insights into the evolution of life history schedules, as well as shed light on the physiological and genetic bases of aging and aging‐related diseases. Chronological age estimation using clock‐based calculators may also offer biological anthropologists a useful tool for applying to forensic and demographic studies.
Robust upper bounds for American put options
Authors: Du Ye , Xue Shan , Liu Yanchu
Published: November 2018

In this paper, we develop robust and model‐free upper bounds for American put option prices. Our bounds have all of those appealing features of the upper bounds for European options provided in DeMarzo et al. (2016, Robust option pricing: Hannan and Blackwell meet Black and Scholes, Journal of Economic Theory, 410‐434) but cover more popular derivatives in practice. Numerical and empirical investigations illustrate the performance of our method.
Price discovery among SSE 50 Index‐based spot, futures, and options markets
Authors: Ahn Kwangwon , Bi Yingyao , Sohn Sungbin
Published: November 2018

This paper studies the contribution of newly launched SSE 50 Index‐based options and futures to price discovery. We find that the derivatives markets quickly begin exhibiting price leadership over the corresponding spot market, despite their short history; the information share from both derivatives markets rose from 59.84% in mid‐2015 to 84.6% in mid‐2017. Using substantial regulation changes during the sample period, we test the trading cost hypothesis. The increases in derivatives transaction costs do not immediately impede their roles in price discovery. Findings suggest that in nascent and immature markets, investors’ trading experience matters more than trading costs.
Indian equity options: Smile, risk premiums, and efficiency
Authors: Jain Sonali , Varma Jayanth R. , Agarwalla Sobhesh Kumar
Published: November 2018

We study the pricing of equity options in India which is one of the world's largest options markets. Our findings are supportive of market efficiency: A parsimonious smile‐adjusted Black model fits option prices well, and the implied volatility (IV) has incremental predictive power for future volatility. However, the risk premium embedded in IV for Single Stock Options appears to be higher than in other markets. The study suggests that even a very liquid market with substantial participation of global institutional investors can have structural features that lead to systematic departures from the behavior of a fully rational market while being “microefficient.”
Effective feature learning and fusion of multimodality data using stage‐wise deep neural network for dementia diagnosis
Authors: Zhou Tao , Thung Kim‐Han , Zhu Xiaofeng , Shen Dinggang
Published: November 2018

In this article, the authors aim to maximally utilize multimodality neuroimaging and genetic data for identifying Alzheimer's disease (AD) and its prodromal status, Mild Cognitive Impairment (MCI), from normal aging subjects. Multimodality neuroimaging data such as MRI and PET provide valuable insights into brain abnormalities, while genetic data such as single nucleotide polymorphism (SNP) provide information about a patient's AD risk factors. When these data are used together, the accuracy of AD diagnosis may be improved. However, these data are heterogeneous (e.g., with different data distributions), and have different number of samples (e.g., with far less number of PET samples than the number of MRI or SNPs). Thus, learning an effective model using these data is challenging. To this end, we present a novel three‐stage deep feature learning and fusion framework, where deep neural network is trained stage‐wise. Each stage of the network learns feature representations for different combinations of modalities, via effective training using the maximum number of available samples. Specifically, in the first stage, we learn latent representations (i.e., high‐level features) for each modality independently, so that the heterogeneity among modalities can be partially addressed, and high‐level features from different modalities can be combined in the next stage. In the second stage, we learn joint latent features for each pair of modality combination by using the high‐level features learned from the first stage. In the third stage, we learn the diagnostic labels by fusing the learned joint latent features from the second stage. To further increase the number of samples during training, we also use data at multiple scanning time points for each training subject in the dataset. We evaluate the proposed framework using Alzheimer's disease neuroimaging initiative (ADNI) dataset for AD diagnosis, and the experimental results show that the proposed framework outperforms other state‐of‐the‐art methods.
A multi‐layered nerve guidance conduit design adapted to facilitate surgical implantation
Authors: Belanger Kayla , Schlatter Guy , Hébraud Anne , Marin Frédéric , Testelin Sylvie , Dakpé Stéphanie , Devauchelle Bernard , Egles Christophe
Published: November 2018

Background and Aims

The gold standard procedure after a severe nerve injury is the nerve autograft, yet this technique has drawbacks. In recent years, progress has been made in the development of artificial nerve guides to replace the autograft, but no device has been able to demonstrate superiority. The present study introduces an adaptable foundation design for peripheral nerve regeneration.

Methods

Silk fibroin was electrospun, creating a tri‐layered material with aligned fiber surfaces and a randomly deposited fiber interior. This material was rolled into a micro‐channeled conduit, which was then enveloped by a jacket layer of the same tri‐layered material.

Results

The proposed implant design succeeds in incorporating various desirable aspects of synthetic nerve guides, while facilitating the surgical implantation process for medical application. The aligned fiber surfaces of the conduit support axon guidance, while the tri‐layered architecture improves its structural integrity compared with a fully aligned fiber material. Moreover, the jacket layer creates a small niche on each end which facilitates surgical implantation. An in vivo study in rats showed that nerve regeneration using this device was comparable to results after direct suture.

Conclusion

This proof‐of‐principle study, therefore, advances the development of tissue engineered nerve grafts by creating an optimized guidance conduit design capable of successful nerve regeneration.
Bldesin, the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities
Authors: Luo Xudong , Zhu Wen , Ding Li , Ye Xiangdong , Gao Huanhuan , Tai Xuejiao , Wu Zheng , Qian Yi , Ruan Xuzhi , Li Jian , Li Shan , Chen Zongyun
Published: November 2018

Fungus defensin is a kind of important natural peptide resource, such as plectasin from the soil fungus Pseudoplectania nigrella with potential application in the antimicrobial peptide lead drug discovery. Here, a fungus defensin named Bldesin with Kv1.3 channel and serine protease inhibitory activities was first explored. By GST‐Bldesin fusion expression and enterokinase cleaving strategy, recombinant Bldesin was obtained successfully. Antimicrobial assays showed that Bldesin had potent activity against Gram‐positive
Staphylococcus aureus, but had no effect on Gram‐negative
Escherichia coli. Electrophysiological experiments showed that Bldesin had Kv1.3 channel inhibitory activity. Serine protease inhibitory associated experiments showed that Bldesin had unique chymotrypsin protease inhibitory, elastase protease inhibitory, and serine protease‐associated coagulation inhibitory activities. To the best of our knowledge, Bldesin is the first functionally characterized pathogenic fungus defensin with Kv1.3 channel and chymotrypsin inhibitory activities and highlighted novel pharmacological effects of fungus‐derived defensin peptides.
Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR‐625 and miR‐892b
Authors: Hao Liguo , Rong Wei , Bai Lianjie , Cui Hongsheng , Zhang Shuli , Li Yuanchun , Chen Datong , Meng Xin
Published: November 2018

Circular RNAs (circRNAs) have been regarded as critical regulators of human diseases and biological markers in some types of malignancies, including pancreatic ductal adenocarcinoma (PDAC). Recently, circ_0007534 has been identified as a novel cancer‐related circRNA. Nevertheless, its clinical relevance, functional roles, and mechanism have not been studied in PDAC. In the current study, real‐time quantitative polymerase chain reaction (RT‐qPCR) was used to detect the expression of circ_0007534 in 60‐paired PDAC tissue samples and different cell lines. Loss‐of‐function and gain‐of‐function assays were performed to detect cell proliferation, apoptosis, and metastatic properties affected by circ_0007534. An animal study was also carried out. The luciferase reporter assay was performed to uncover the underlying mechanism of circ_0007534. As a result, circ_0007534 was overexpressed not only in PDAC tissues but also in a panel of PDAC cell lines, and this overexpression is closely associated with advanced tumor stage and positive lymph node invasion. In addition, circ_0007534 may be regarded as an independent prognostic factor for patients with PDAC. For the part of functional assays, circ_0007534 significantly increased cell proliferation, migratory, and invasive potential of PDAC cells. Circ_0007534 could inhibit cell apoptosis partly via a Bcl‐2/caspase‐3 pathway. The xenograft study further confirmed the cell growth promoting the role of circ_0007534. Mechanistically, miR‐625 and miR‐892b were sponged by circ_0007534. The oncogenic functions of circ_0007534 is partly dependent on its regulation of miR‐625 and miR‐892b. In conclusion, our study illuminates a novel circRNA that confers an oncogenic function in PDAC.
The long noncoding RNA TPTE2P1 promotes the viability of colorectal cancer cells
Authors: Dai Xiaoyu , Xie Yangyang , Dong Mingjun , Zhao Jianpei , Yu Hua , Zhou Baofeng , Xu Yidong , Yu Yongming , Cao Yisheng , Zhang Youping
Published: November 2018

Long noncoding RNAs (lncRNAs) have important functions in tumor development and progression, including colorectal cancer (CRC), but their roles are not completely understood. In this study, the roles of the lncRNA transmembrane phosphoinositide 3‐phosphatase and tensin homolog 2 pseudogene 1 (TPTE2P1), previously implicated in gallbladder cancer cell migration and invasion, were evaluated in CRC. In particular, quantitative polymerase chain reaction was used to quantify TPTE2P1 levels in tumor tissues and cell lines. The association between TPTE2P1 and survival was analyzed using the online tool OncoLnc. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays, colony formation assays, and flow cytometry were used to evaluate the effects of TPTE2P1 on viability, cell cycle progression, and apoptosis. Signaling pathway proteins were quantitated by Western blot analysis. Finally, the role of TPTE2P1 was analyzed in vivo using mouse models. TPTE2P1 levels were significantly higher in CRC tissues than in adjacent normal tissues. Higher expression was associated with a poor survival rate. The silencing of TPTE2P1 led to cell cycle arrest at the S phase and thereby inhibited cell viability. TPTE2P1 knockdown also caused cancer cell apoptosis via the activation of the apoptosis regulator (BCL2)/caspase 3 signaling cascade. In addition, the inhibition of TPTE2P1 had suppressive effects on tumors in vivo. TPTE2P1 is upregulated in CRC and plays essential roles in the regulation of cell viability in vitro and tumor formation in vivo.
The impact of interferon‐free direct‐acting antivirals on clinical outcome after curative treatment for hepatitis C virus–associated hepatocellular carcinoma: Comparison with interferon‐based therapy
Authors: Nagaoki Yuko , Imamura Michio , Nishida Yuno , Daijo Kana , Teraoka Yuji , Honda Fumi , Nakamura Yuki , Morio Kei , Fujino Hatsue , Nakahara Takashi , Kawaoka Tomokazu , Tsuge Masataka , Hiramatsu Akira , Kawakami Yoshiiku , Miki Daiki , Hiyama Yuichi , Ochi Hidenori , Chayama Kazuaki , Aikata Hiroshi
Published: November 2018

Background and Aim

To examine the effect on recurrence and survival of treatment by interferon (IFN)‐free direct‐acting antivirals (DAA) for patients with hepatitis C virus (HCV)‐associated hepatocellular carcinoma (HCC) who underwent primary curative treatment.

Methods

This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti‐HCV treatment after HCC treatment, 38 patients received IFN‐free DAA therapy (DAA patients) and 94 received IFN‐based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case‐control study.

Results

The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237;
P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively (
P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742;
P < 0.001) as independent predictors of overall survival. Propensity score matching analysis showed no significant difference in HCC development rates and overall survival rates in the two groups.

Conclusions

We found that SVR obtained after curative treatment for primary HCC suppressed recurrence and improved overall survival. And, IFN‐free DAA therapy after curative treatment for primary HCC could predict improving overall survival and suppressed HCC recurrence.
Hepatitis C virus genotypes in hemodialysis patients in Angola
Authors: da Costa Marques Borges Luis Filipe , Zalis Mariano Gustavo , Santoro‐Lopes Guilherme , Varella Rafael Brandão
Published: November 2018

To our knowledge, there are no published data on hepatitis C virus (HCV) genotypes in Angola. This study aimed at assessing the distribution of HCV genotypes in seropositive hemodialysis patients in Luanda. Among 51 HCV‐positive subjects included, viremia was detected in 27 (53%). HCV genotyping was performed by bidirectional sequencing of the 5'‐untranslated region by the Sanger method. HCV genotype 4 was largely predominant (20 cases; 74%), followed by genotypes 1b (5 cases; 18.5%), 1a and 2 (one case each; 3.7%). These results suggest that the distribution of HCV genotypes in Angola is similar to that reported from other Central African countries.
p107 Deficiency Increases Energy Expenditure by Inducing Brown‐Fat Thermogenesis and Browning of White Adipose Tissue
Authors: Cunarro Juan , Buque Xabier , Casado Sabela , Lugilde Javier , Vidal Anxo , Mora Alfonso , Sabio Guadalupe , Nogueiras Rubén , Aspichueta Patricia , Diéguez Carlos , Tovar Sulay
Published: November 2018

Scope

The tumor suppressor p107, a pocket protein member of the retinoblastoma susceptibility protein family, plays an important role in the cell cycle and cellular adipocyte differentiation. Nonetheless, the mechanism by which it influences whole body Energy homeostasis is unknown.

Methods and Results

The phenotype of p107 knockout (KO) mixed‐background C57BL6/129 mice phenotype is studied by focusing on the involvement of white and brown adipose tissue (WAT and BAT) in energy metabolism. It is shown that p107 KO mice are leaner and have high‐fat diet resistence. This phenomenon is explained by an increase of energy expenditure. The higher energy expenditure is caused by the activation of thermogenesis and may be mediated by both BAT and the browning of WAT. Consequently, it leads to the resistance of p107 KO mice to high‐fat diet effects, prevention of liver steatosis, and improvement of the lipid profile and glucose homeostasis.

Conclusion

These data allowed the unmasking of a mechanism by which a KO of p107 prevents diet‐induced obesity by increasing energy expenditure via increased thermogenesis in BAT and browning of WAT, indicating the relevance of p107 as a modulator of metabolic activity of both brown and white adipocytes. Therefore, it can be targeted for the development of new therapies to ameliorate the metabolic syndrome.
Degenerative chain‐transfer process: Controlling all chain‐growth polymerizations and enabling novel monomer sequences
Authors: Kamigaito Masami , Satoh Kotaro , Uchiyama Mineto
Published: November 2018

The use of dormant species has opened a new era in precision polymerization and has changed the concept of living polymerization. The dormant species can be exchanged into the active species via reversible termination or via reversible chain transfer. Professor Mitsuo Sawamoto has greatly contributed to the establishment of the concepts of living cationic and radical polymerizations based on the reversible activation of dormant species. This highlight, dedicated to Professor Sawamoto on his retirement from Kyoto University, provides an overview of reversible or degenerative chain‐transfer (DT) processes, which are effective in controlling all chain‐growth polymerizations, including radical, cationic, anionic, coordination, ring‐opening metathesis, and ring‐opening polymerizations. In addition, structures with novel sequences accessible only by a combination of different propagating species with a common DT agent are reviewed. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 243–254
Cross‐strand disulfides in the hydrogen bonding site of antiparallel β‐sheet (aCSDhs): Forbidden disulfides that are highly strained, easily broken
Authors: Haworth Naomi L. , Wouters Michael J. , Hunter Morgan O. , Ma Lixia , Wouters Merridee A.
Published: November 2018

Some disulfide bonds perform important structural roles in proteins, but another group has functional roles via redox reactions. Forbidden disulfides are stressed disulfides found in recognizable protein contexts, which currently constitute more than 10% of all disulfides in the PDB. They likely have functional redox roles and constitute a major subset of all redox‐active disulfides. The torsional strain of forbidden disulfides is typically higher than for structural disulfides, but not so high as to render them immediately susceptible to reduction under physionormal conditions. Previously we characterized the most abundant forbidden disulfide in the Protein Data Bank, the aCSDn: a canonical motif in which disulfide‐bonded cysteine residues are positioned directly opposite each other on adjacent anti‐parallel β‐strands such that the backbone hydrogen‐bonded moieties are directed away from each other. Here we perform a similar analysis for the aCSDh, a less common motif in which the opposed cysteine residues are backbone hydrogen bonded. Oxidation of two Cys in this context places significant strain on the protein system, with the β‐chains tilting toward each other to allow disulfide formation. Only left‐handed aCSDh conformations are compatible with the inherent right‐handed twist of β‐sheets. aCSDhs tend to be more highly strained than aCSDns, particularly when both hydrogen bonds are formed. We discuss characterized roles of aCSDh motifs in proteins of the dataset, which include catalytic disulfides in ribonucleotide reductase and ahpC peroxidase as well as a redox‐active disulfide in P1 lysozyme, involved in a major conformation change. The dataset also includes many binding proteins.
Residence Life, Men, and Masculinities: Recruitment, Training, and Administrative Processes
Authors: Wagner Rachel , Tillapaugh Daniel
Published: November 2018

Authors examine how interrogating hegemonic gender roles can enhance recruitment, training, and engagement practices for residence life staff in leadership positions. Under specific focus are issues of gendered expectations of the men as paraprofessional role, dynamics in supervision, recruitment and training of staff, and bystander intervention in the residential community.
Treatment of fetal circular shunt with non‐steroidal anti‐inflammatory drugs
Authors: Torigoe T. , Mawad W. , Seed M. , Ryan G. , Marini D. , Golding F. , VAN Mieghem T. , Jaeggi E.
Published: November 2018

A circular shunt (CS) is a life‐threatening condition involving massive shunting of systemic arterial blood via the ductus arteriosus to the left ventricle without traversing the lungs. In the prenatal setting, it occurs mainly in fetuses with severe forms of Ebstein's anomaly (EA) owing to unrestricted ductal flow and significant pulmonary and tricuspid regurgitation. We aimed to improve the fetal hemodynamics and chances of survival of affected fetuses by inducing ductal constriction using transplacental non‐steroidal anti‐inflammatory drugs (NSAIDs). Following initiation of treatment between 26 and 34 weeks' gestation, three (75%) of four fetuses with EA/CS responded with sustained ductal constriction and improved hemodynamic function, which allowed continuation of pregnancy for 3–7 weeks and elective delivery. All successfully treated cases underwent neonatal surgery immediately after birth to eliminate the CS and survived. This included two neonates that underwent single‐ventricle palliation surgery that required postoperative extracorporeal membrane oxygenation and hemofiltration for transient respiratory and renal failure. The one case that did not respond to treatment with NSAIDs was delivered prematurely for progressive fetal compromise and died shortly after birth. Transplacental treatment with NSAIDs represents a novel approach to controlling fetal CS, avoiding in‐utero death and prolonging the pregnancy to a more advanced gestational age, thereby potentially increasing the chances of neonatal survival. This treatment should be considered and initiated at an early stage of systemic steal to prevent brain injury due to hypoperfusion. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Increased Sylvian fissure angle as early sonographic sign of malformation of cortical development
Authors: Pooh R. K. , Machida M. , Nakamura T. , Uenishi K. , Chiyo H. , Itoh K. , Yoshimatsu J. , Ueda H. , Ogo K. , Chaemsaithong P. , Poon L. C.
Published: November 2018

Objective

To evaluate Sylvian fissure development by assessing Sylvian fissure angles in fetuses with malformation of cortical development (MCD).

Methods

This was a retrospective study of 22 fetuses with MCD. Cases with a stored three‐dimensional (3D) brain volume acquired at 18 + 0 to 30 + 6 weeks of gestation at an ultrasound‐based research clinic between January 2010 and December 2017 were identified through a database. Of the 22 fetuses, seven had an extracranial abnormality, such as cardiac, renal, gastrointestinal and/or digital anomalies, and five had a minor abnormality such as micrognathia, low‐set ears and/or single umbilical artery. To confirm the final clinical diagnosis of brain abnormality, postmortem histological findings or prenatal or postnatal magnetic resonance images were used. For measurement of Sylvian fissure angle, an anterior coronal plane of the fetal brain on transvaginal 3D volume multiplanar imaging was visualized as a single image from the three orthogonal views. The right and left Sylvian fissure angles were measured between a horizontal reference line (0°) and a line drawn along the upper side of the respective Sylvian fissure. The Sylvian fissure angle on both sides was plotted on the graphs of the reference ranges for gestational age in weeks.

Results

In 21 (95.5%; 95% CI, 86.8–100.0%) of 22 fetuses with MCD, the Sylvian fissure angle on one or both sides was larger than the 90th percentile of the normal reference. There was one case with apparent focal MCD in the parietal lobe, but the Sylvian fissure angles were normal. A case with apparent unilateral cortical dysplasia and one with apparent unilateral schizencephaly had conspicuous discrepancies between the left and right Sylvian fissure angles. Abnormal genetic test results were obtained in six cases, including four cases with a mutation in a single gene.

Conclusions

This study has shown that the Sylvian fissures, as defined by the Sylvian fissure angle, have delayed development in most MCD cases prior to the diagnosis of the condition. The Sylvian fissure angle may potentially be a strong indicator for the subsequent development of cortical malformation, before the time point at which the gyri and sulci become obvious on the fetal brain surface. Further research is required to validate these findings. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
The relationships between precipitation amounts, number of rain days, and relative vorticity in the mid‐troposphere over Iran
Authors: Darand Mohammad , Mirzaei Nabi
Published: November 2018

Precipitation is one of the most studied atmospheric parameters, and its occurrence has a direct relationship with the atmospheric circulation pattern. This study investigates the relationship between relative vorticity in the mid‐troposphere (at 500 hPa), and precipitation amounts and the number of rain days over the period 1979–2013 in Iran. Relative vorticity was calculated using the u and v components of the wind data from the European Centre for Medium‐Range Weather Forecasts (ECMWF) interim reanalysis (ERA‐Interim) over Iran, with 0.125° spatial resolution. Gridded daily precipitation data from the Asfazari National Dataset with a spatial resolution of 15 × 15 km, covering the same period, were also used. Pearson's correlation coefficient was used to investigate, at the 90% confidence level, the relationship between relative vorticity, and monthly precipitation amount and number of rain days. The significance of the trend for relative vorticity for different months, at the 90% confidence level, was evaluated using the nonparametric modified Mann–Kendall test. The results showed a significant relationship between relative vorticity and the number of rain days and precipitation amounts over Iran. In temporal terms, the correlations between relative vorticity and the number of rain days and precipitation amounts are strongest during the months of high precipitation over Iran, especially in November and December. In spatial terms, eastern Iran exhibits the strongest relationship between precipitation and relative vorticity at the 500 hPa level. Examination of the time series data showed that the monthly precipitation amounts and numbers of rain days fluctuate in line with changes in relative vorticity during the period of study. Analysis of trends in the relative vorticity data also showed, at the 90% confidence level, that the maximum variations in relative vorticity occurred in autumn and winter, respectively. Trend analysis also showed a decreasing trend in relative vorticity in March and an increasing trend in November.
Our World: International, Urbanizing, and Driven By Connectedness
Authors: Roberts Dennis C.
Published: November 2018

In order to thrive in a connected and interdependent world, those who engage in leadership and acts of citizenship will need to be literate across cultures, welcoming of different views, and see mutual survival and prosperity as the most compelling tasks ahead.
Clockwork axions in cosmology. Is chromonatural inflation chrononatural?
Authors: Agrawal Prateek , Fan JiJi , Reece Matthew
Published: November 2018

Abstract

Many cosmological models rely on large couplings of axions to gauge fields. Examples include theories of magnetogenesis, inflation on a steep potential, chiral gravitational waves, and chromonatural inflation. Such theories require a mismatch between the axion field range and the mass scale appearing in the

$$ aF\tilde{F} $$

a
F

F
˜

coupling. This mismatch suggests an underlying monodromy, with the axion winding around its fundamental period a large number of times. We investigate the extent to which this integer can be explained as a product of smaller integers in a UV completion: in the parlance of our times, can the theory be “clockworked”? We argue that a clockwork construction producing a potential

$$ {\mu}^4 \cos \left(\frac{a}{j{F}_a}\right) $$

μ
4

cos

a

j

F
a

for an axion of fundamental period F

a
will obey the constraint μ < F

a
. For a some applications, including chromonatural inflation with sub-Planckian field range, this constraint obstructs a clockwork UV completion. Alternative routes to a large coupling include fields of large charge (an approach limited by strong coupling) or kinetic mixing (requiring a lighter axion). Our results suggest that completions of axion cosmologies that explain the large parameter in the theory potentially alter the phenomenological predictions of the model.
Correlators of mixed symmetry operators in defect CFTs
Authors: Guha Sunny , Nagaraj Balakrishnan
Published: November 2018

Abstract

We use the embedding formalism technique to study correlation functions of a d-dimensional Euclidean CFT in the presence of a q co-dimensional defect. The defect breaks the global conformal group SO(d + 1, 1) into SO(d − q + 1, 1) × SO(q). We calculate all possible invariant structures that can appear in one-point, two-point and three-point correlation functions of bulk and defect operators in mixed symmetry representation. Their generalization to n-point correlation functions are also worked out. Correlation functions in the presence of a defect, in arbitrary representation of SO(q), are also calculated.
Sbottoms as probes to MSSM with nonholomorphic soft interactions
Authors: Chattopadhyay Utpal , Datta AseshKrishna , Mukherjee Samadrita , Swain Abhaya Kumar
Published: November 2018

Abstract

Presence of nonholomorphic soft SUSY breaking terms is known to be a possibility in the popular setup of the Minimal Supersymmetric Standard Model (MSSM). It has been shown that such a scenario known as NonHolomorphic Supersymmetric Standard Model (NHSSM) could remain ‘natural’ (i.e., not fine-tuned) even in the presence of a rather heavy higgsino-like LSP. However, it turns out that distinguishing such a scenario from the MSSM is unlikely to be an easy task, in particular at the Large Hadron Collider (LHC). In a first study of such a scenario at colliders (LHC), we explore a possible way that focuses on the sbottom phenomenology. This exploits the usual tan β-dependence (enhancement) of the bottom Yukawa coupling but reinforced/altered in the presence of non-vanishing nonholomorphic soft trilinear parameter A

b

′
. For a given set of masses of the sbottom(s) and the light electroweakinos (LSP, lighter chargino etc.) which are known from experiments, the difference between the two scenarios could manifest itself via event rate in the 2b-jets + "Image missing" final state, which could be characteristically different from its MSSM expectation. Impact on the phenomenology of the stops at the LHC is also touched upon.
Higher order fluctuations and correlations of conserved charges from lattice QCD
Authors: Borsanyi Szabolcs , Fodor Zoltan , Guenther Jana N. , Katz Sandor K. , Pasztor Attila , Portillo Israel , Ratti Claudia , Szabó K. K.
Published: November 2018

Abstract

We calculate several diagonal and non-diagonal fluctuations of conserved charges in a system of 2+1+1 quark flavors with physical masses, on a lattice with size 483 × 12. Higher order fluctuations at μ

B
= 0 are obtained as derivatives of the lower order ones, simulated at imaginary chemical potential. From these correlations and fluctuations we construct ratios of net-baryon number cumulants as functions of temperature and chemical potential, which satisfy the experimental conditions of strangeness neutrality and proton/baryon ratio. Our results qualitatively explain the behavior of the measured cumulant ratios by the STAR collaboration.