bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanoelectrical Conversion in Highly Ionic Conductive Solid‐State Polymer Electrolyte Membranes
Authors: Cao Jinwei , Piedrahita Camilo , Kyu Thein
Published: February 2019

A novel phenomenon of mechanoelectrical conversion in a flexible solid‐state polymer electrolyte membrane (PEM) is presented, hereafter denoted as flexoelectric effect. The flexoelectric coefficient (≈323 µC m−1), that is, a measure of the converted mechanoelectrical energy, is the highest among all flexoelectric materials hitherto reported. It is proposed in this work that the flexoelectricity in PEMs operates based on electrical energy generation driven by ion polarization/depolarization across the PEM subjected to a pressure gradient during bending. Of particular interest is the phenomenon of polarity switching during bending, that is, reversal of the polarization direction with increasing succinonitrile (SCN) concentration (i.e., 10–20 wt%). The size disparity between the solvated cations and anions is attributed as the key factor in determining the polarization direction, which is responsible for the polarity switching. Of particular importance is that the present flexoelectric PEM itself is a key component of the solid‐state lithium ion battery and thus their integration opens up a new avenue for energy harvesting and storage devices.
Stiffness‐Changing of Polymer Nanocomposites with Cellulose Nanocrystals and Polymeric Dispersant
Authors: Meesorn Worarin , Zoppe Justin O. , Weder Christoph
Published: February 2019

Bio‐inspired, water‐responsive, mechanically adaptive nanocomposites are reported based on cellulose nanocrystals (CNCs), poly(ethylene oxide‐co‐epichlorohydrin) (EO‐EPI), and a small amount of poly(vinyl alcohol) (PVA), which is added to aid the dispersion of the CNCs. In the dry state, the CNCs form a reinforcing network within the polymer matrix, and the substantial stiffness increase relative to the neat polymer is thought to be the result of hydrogen‐bonding interactions between the nanocrystals. Exposure to water, however, causes a large stiffness reduction, due to competitive hydrogen bonding of water molecules and the CNCs. It is shown here that the addition of PVA to the EO‐EPI/CNC nanocomposite increases the modulus difference between the dry and the wet state by a factor of up to four compared to the nanocomposites without the PVA. The main reason is that the PVA leads to a substantial increase of the stiffness in the dry state; for example, the storage modulus E
′ increased from 2.7 MPa (neat EO‐EPI) to 50 MPa upon introduction of 10% CNCs, and to 200 MPa when additionally 5% of PVA was added. By contrast, the incorporation of PVA only led to moderate increases of the equilibrium water swelling and the E
′ in the wet state.
Inhibition of the hexosamine biosynthesis pathway potentiates cisplatin cytotoxicity by decreasing BiP expression in non–small‐cell lung cancer cells
Authors: Chen Wenshu , Do Kieu C. , Saxton Bryanna , Leng Shuguang , Filipczak Piotr , Tessema Mathewos , Belinsky Steven A. , Lin Yong
Published: February 2019

Platinum anticancer agents are essential components in chemotherapeutic regimens for non–small‐cell lung cancer (NSCLC) patients ineligible for targeted therapy. However, platinum‐based regimens have reached a plateau of therapeutic efficacy; therefore, it is critical to implement novel approaches for improvement. The hexosamine biosynthesis pathway (HBP), which produces amino‐sugar N‐acetyl‐glucosamine for protein glycosylation, is important for protein function and cell survival. Here we show a beneficial effect by the combination of cisplatin with HBP inhibition. Expression of glutamine:fructose‐6‐phosphate amidotransferase (GFAT), the rate‐limiting enzyme of HBP, was increased in NSCLC cell lines and tissues. Pharmacological inhibition of GFAT activity or knockdown of GFATimpaired cell proliferation and exerted synergistic or additive cytotoxicity to the cells treated with cisplatin. Mechanistically, GFAT positively regulated the expression of binding immunoglobulin protein (BiP; also known as glucose‐regulated protein 78, GRP78), an endoplasmic reticulum chaperone involved in unfolded protein response (UPR). Suppressing GFAT activity resulted in downregulation of BiP that activated inositol‐requiring enzyme 1α, a sensor protein of UPR, and exacerbated cisplatin‐induced cell apoptosis. These data identify GFAT‐mediated HBP as a target for improving platinum‐based chemotherapy for NSCLC.
Aurora B kinase as a novel molecular target for inhibition the growth of osteosarcoma
Authors: Zhao Zhenjiang , Jin Guoguo , Yao Ke , Liu Kangdong , Liu Fangfang , Chen Hanyong , Wang Keke , Gorja Dhilli Rao , Reddy Kanamata , Bode Ann M. , Guo Zhiping , Dong Zigang
Published: February 2019

Osteosarcoma is the primary human malignant tumor affecting bone. This cancer most frequently arises in children and adolescents, with a second peak in those over the age of 50. Currently, surgery followed by radiotherapy and chemotherapy are the main treatments, but long‐term positive effects are very poor. Aurora B kinase is a serine/threonine kinase that is a key regulator of cell cycle and mitosis. Tissue array analysis revealed that Aurora B kinase is overexpressed in osteosarcoma compared with normal bone tissue. We developed a compound, HOI‐07 (i.e., (E)‐3‐((E)‐4‐(benzo[d] [1,3]dioxol‐5‐yl)‐2‐oxobut‐3‐en‐1‐ylidene)indolin‐2‐one), as a specific Aurora B kinase inhibitor and examined its effectiveness against osteosarcoma cell growth in this study. This compound inhibited Aurora B kinase activity in osteosarcoma and induced apoptosis, caused G2‐M phase arrest, and attenuated osteosarcoma anchorage‐independent cell growth. Moreover, knocking down the expression of Aurora B effectively reduced the sensitivity of osteosarcoma to HOI‐07. Results of a xenograft mouse study indicated that HOI‐07 treatment effectively suppressed the growth of 143B and KHOS xenografts, without affecting the body weight of mice. The expression of phosphorylated histone H3 (Ser10) was reduced in mice treated with HOI‐07. Overall, we identified HOI‐07 as a specific Aurora B kinase inhibitor for osteosarcoma treatment and this compound warrants further investigation.
ETS1 is coexpressed with ZEB2 and mediates ZEB2‐induced epithelial‐mesenchymal transition in human tumors
Authors: Yalim‐Camci Irem , Balcik‐Ercin Pelin , Cetin Metin , Odabas Gorkem , Tokay Nurettin , Sayan A. Emre , Yagci Tamer
Published: February 2019

Epithelial‐mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E‐box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Recently, expression of MMPs was associated to the activation of ETS1 transcription factor; however, a link between ZEB2 and ETS proto‐oncogene 1, transcription factor (ETS1) remains to be elucidated. Hence, we investigated the transcriptional regulation of ETS1 by ZEB2 after our initial observation that ZEB2 and ETS1 are coexpressed in hepatocellular carcinoma cells (HCCs). Chromatin immunoprecipitation and luciferase reporter assays clearly showed that ZEB2 binds to E‐box sequences on the promoter of ETS1. Elevated expression of ETS1 was found in DLD‐ZEB2 and A431‐ZEB2 inducible systems, and knockdown of ZEB2 caused an explicit downregulation of ETS1 in shZEB2‐SNU398 and shZEB2‐SK‐HEP‐1 cells. Repression of ETS1 expression in ZEB2‐induced conditions substantially impaired the migration and invasive capacities of DLD1 cells. Mechanistically, knockdown of ETS1 in ZEB2‐expressing cells resulted in the downregulation of established ZEB2 targets TWIST and MMP9. Correlation analyses in HCC lines, cancer complementary DNA arrays, and The Cancer Genome Atlas RNA‐sequencing data set revealed that ZEB2 and ETS1 are coexpressed, and their expressions in human tumors show a highly significant positive correlation. Our results demonstrated that ZEB2 acts as an upstream regulator of ETS1 and, in turn, ETS1 maintains ZEB2‐induced EMT. These findings add another level of complexity to the understanding of ZEB2 in the invasion and metastasis of cancer cells, and put ZEB2/ETS1 axis as a novel therapeutic target in human malignancies.
Me or information technology? Adoption of artificial intelligence in the delegation of personal strategic decisions
Authors: Schneider Sabrina , Leyer Michael
Published: February 2019

Artificial intelligence is revolutionizing the way we do business. Whereas both the adoption of technological innovations and strategic decision making have been subject to prior research, this experimental study is first to combine both. To understand the impact of choice complexity and cognitive perceptions on the willingness to delegate a strategic decision to an algorithm, we conducted an experiment with 310 participants. We find that although choice complexity has no effect, participants with low levels of situational awareness are more likely to delegate. The findings augment research on choice complexity in decision making by emphasizing the relevance of cognitive perceptions.
Bifurcation behaviors generated by Panda‐ring control circuit
Authors: Bahadoran Mahdi , Jalil Muhammad Arif , Ali Jalil , Amiri Iraj Sadegh , Yupapin Preecha
Published: February 2019

We have demonstrated that the bifurcation patterns can generate by the double Panda‐ring resonator system, where the first system is configured as the input source, while the second system is the feedback control systems. The key concept of the proposal is the two nonlinear side ring resonators that can induce the nonlinear Kerr effect into the center ring. The feedback signals generated from the second ring will induce into the first Panda‐ring, from which the required bifurcation behaviors are obtained. By adjusting the suitable parameters, the simulation results obtained have shown that there are the various exciting bifurcation behaviors in both systems that can be used for the applications such as textile pattern design, information security, and biosensors.
Robust water–fat separation for multi‐echo gradient‐recalled echo sequence using convolutional neural network
Authors: Cho JaeJin , Park HyunWook
Published: February 2019

Purpose

To accurately separate water and fat signals for bipolar multi‐echo gradient‐recalled echo sequence using a convolutional neural network (CNN).

Methods

A CNN architecture was designed and trained using the relationship between multi‐echo images from the bipolar multi‐echo gradient‐recalled echo sequence and artifact‐free water–fat‐separated images. The artifact‐free water–fat‐separated images for training the CNN were obtained from multiple signals with different TEs by using iterative decomposition of water and fat with echo asymmetry and the least‐squares estimation method, in which multiple signals at different TEs were acquired using a single‐echo gradient‐recalled echo sequence. We also proposed a data augmentation method using a synthetic field inhomogeneity to generate multi‐echo signals, including various bipolar multi‐echo gradient‐recalled echo artifacts so that the CNN could prevent overfitting and increase the separation accuracy. We trained the CNN using in vivo knee images and tested it using in vivo knee, head, and ankle images.

Results

In vivo imaging results showed that the proposed CNN could separate water–fat images accurately. Although the proposed CNN was trained using only in vivo knee images, the proposed CNN could also separate water–fat images of different imaging regions. The proposed data augmentation method could prevent overfitting even with a limited number of training data sets and make the method robust to magnetic field inhomogeneities.

Conclusion

The proposed CNN could obtain water–fat‐separated images from the multi‐echo images acquired from the bipolar multi‐echo gradient‐recalled echo sequence, which included artifacts from the bipolar gradients.
The Coulomb Hole of the Ne Atom
Authors: Rodríguez‐Mayorga Mauricio , Ramos‐Cordoba Eloy , Lopez Xabier , Solà Miquel , Ugalde Jesus M. , Matito Eduard
Published: February 2019

We analyze the Coulomb hole of Ne from highly‐accurate CISD wave functions obtained from optimized even‐tempered basis sets. Using a two‐fold extrapolation procedure we obtain highly accurate results that recover 97 % of the correlation energy. We confirm the existence of a shoulder in the short‐range region of the Coulomb hole of the Ne atom, which is due to an internal reorganization of the K‐shell caused by electron correlation of the core electrons. The feature is very sensitive to the quality of the basis set in the core region and it is not exclusive to Ne, being also present in most of second‐row atoms, thus confirming that it is due to K‐shell correlation effects.
Mechanistic Insights into a Stibene Cleavage Oxygenase NOV1 from Quantum Mechanical/Molecular Mechanical Calculations
Authors: Lu Jiarui , Lai Wenzhen
Published: February 2019

NOV1, a stilbene cleavage oxygenase, catalyzes the cleavage of the central double bond of stilbenes to two phenolic aldehydes, using a 4‐His Fe(II) center and dioxygen. Herein, we use in‐protein quantum mechanical/molecular mechanical (QM/MM) calculations to elucidate the reaction mechanism of the central double bond cleavage of phytoalexin resveratrol by NOV1. Our results showed that the oxygen molecule prefers to bind to the iron center in a side‐on fashion, as suggested from the experiment. The quintet Fe−O2 complex with the side‐on superoxo antiferromagnetic coupled to the resveratrol radical is identified as the reactive oxygen species. The QM/MM results support the dioxygenase mechanism involving a dioxetane intermediate with a rate‐limiting barrier of 10.0 kcal mol−1. The alternative pathway through an epoxide intermediate is ruled out due to a larger rate‐limiting barrier (26.8 kcal mol−1). These findings provide important insight into the catalytic mechanism of carotenoid cleavage oxygenases and also the dioxygen activation of non‐heme enzymes.
Electron Delocalization in Planar Metallacycles: Hückel or Möbius Aromatic?
Authors: Szczepanik Dariusz W. , Solà Miquel
Published: February 2019

In this work the relationship between the formal number of π‐electrons, d‐orbital conjugation topology, π‐electron delocalization and aromaticity in d‐block metallacycles is investigated in the context of recent findings concerning the correlation of π‐HOMO topology and the magnetic aromaticity indices in these species. It is demonstrated that for π‐electron rich d‐metallacycles the direct link between aromaticity, the number of π‐electrons and the frontier π‐orbital topology does not strictly hold and for such systems it is very difficult to unambiguously associate their aromaticity with the “4n+2” (Hückel) and “4n” (Möbius) rules. It is also shown that the recently proposed electron density of delocalized bonds (EDDB) method can successfully be used not only to quantify and visualize aromaticity in such difficult cases, but also – in contrast to magnetic aromaticity descriptors – to provide a great deal of information on the real role of d‐orbitals in metallacycles without the ambiguity of bookkeeping of electrons in the π‐subsystem of the molecular ring. Interestingly, some of the metallacycles studied cannot be classified exclusively as Hückel or Möbius because they have a hybrid Hückel‐Möbius or even quasi‐aromatic nature.
A mirror of the ethnic divide: Interest group pillarization and elite dominance in Bosnia and Herzegovina
Authors: Kapidžić Damir
Published: February 2019

To date, there is no comprehensive treatment of interests and interest groups in Bosnia and Herzegovina (BiH). This article seeks to fill that gap. It does so by explaining that interest groups reflect the country's complex political system with multiple levels of power sharing along societal cleavages. Political parties are the major power centers, and the link between ethnicity and party allegiance is most significant in defining the role of interest groups. The result is a pillarized (separate, intragroup) and bifurcated group system with 3 separate interest group subsystems with little interchange between them. This fragmentation has been challenged by international institutional organizations promoting multiethnic interests. Nevertheless, with the persistence of many informal interests, the group system is stymied in moving toward an integrated system, a development that is key to strengthening BiH's consociational democracy.
Propensity score methods and regression adjustment for analysis of nonrandomized studies with health‐related quality of life outcomes
Authors: Cottone Francesco , Anota Amelie , Bonnetain Franck , Collins Gary S. , Efficace Fabio
Published: February 2019

Purpose

The aim of this study was to investigate the potential added value of combining propensity score (PS) methods with multivariable linear regression (MLR) in estimating the average treatment effect on the treated (ATT) in nonrandomized studies with health‐related quality of life (HRQoL) outcomes.

Methods

We first used simulations to compare the performances of different PS‐based methods, either alone or in combination with further MLR adjustment, in estimating ATT. PS methods were, respectively, optimal pair (OPM) and full (OFM) PS matching, subclassification on the PS (SBC), and the inverse probability of treatment weighting (IPTW). We simulated several scenarios, according to different sample sizes, proportions of treated vs untreated subjects, and types of HRQoL outcomes. We also applied the same methods to a real clinical data set.

Results

OPM and IPTW provided the closest Type I error to the nominal threshold α = 0.05 across all scenarios. Overall, both methods showed also lower variability in estimates than SBC and OFM. SBC performed worst, generally providing the highest levels of bias. Further MLR adjustment lessened bias for all methods, however providing higher Type I error for SBC and OFM. In the real case, all methods provided similar ATT estimates except for one outcome.

Conclusions

Our findings suggest that for sample sizes up to n = 200, OPM and IPTW are to be preferred to OFM and SBC in estimating ATT on HRQoL outcomes. Specifically, OPM performed best in sample sizes of n ≥ 80, IPTW for smaller sample sizes. Additional MLR adjustment can further improve ATT estimates.
R‐E‐S‐P‐E‐C‐T: How Royal Botanic Gardens Victoria is responding to climate change
Authors: Entwisle Timothy J.
Published: February 2019

Societal Impact Statement

Botanic gardens have a responsibility to lead, encourage, and contribute to research into climate change, particularly relating to plants and their habitats. We must educate, in the broadest sense of that word, and safeguard plants through seedbanking and other ex situ collections, and contribute to restoration. Good planning is essential to prepare for the succession of our living landscapes. We can engage on many levels, but most importantly with policy, politicians, and public opinion. Partnerships are essential and we should collaborate within regional networks. Finally, we must show tenacity. In short, R‐E‐S‐P‐E‐C‐T, respect.

Summary

Climate change is our “biggest challenge,” “most pressing issue” or simply, and starkly, “a crisis.” As expressed in The Xishuangbanna Declaration on Botanical Gardens and Climate Change, there is much we can do as botanic gardens to help the world mitigate and adapt to global warming. We have a responsibility to lead, encourage, and contribute to research into the causes, consequences, and controls of climate change, particularly relating to plants and their habitats. Our core function, I think, is to educate, in the broadest sense of that word. We must safeguard plants through seedbanking and other ex situ collections, and contribute to restoration. Good planning is essential and we need to prepare for the succession of our living landscapes. We can engage on many levels, but most importantly perhaps with policy, politicians and public opinion. Partnerships are essential and I would encourage botanic gardens to participate actively in peak bodies such as the International Association of Botanic Gardens and Botanic Gardens Conservation International, and to collaborate within regional networks. Finally, show tenacity—hold firm and true to our purpose, to safeguard plants and to care for people and our planet. In short, R‐E‐S‐P‐E‐C‐T, respect.
Influence of Reaction Conditions and Promoting Role of Ammonia Produced at Higher Temperature Conditions in Its Synthesis Process over Cs‐Ru/MgO Catalyst
Authors: Javaid Rahat , Matsumoto Hideyuki , Nanba Tetsuya
Published: February 2019

Cs promoted Ru/MgO catalyst was prepared by an impregnation method using Ru(NO3)3 and Cs(NO3)2 as precursor compounds. The activity measurements for ammonia (NH3) synthesis were carried out in a fixed‐bed flow reactor. A reactant stream of H2 and N2 was used for NH3 synthesis. The influences of reaction temperature, pressure and H2/N2 ratio on the performance of the catalyst were investigated in detail. The relative concentration of H2 and N2 in the reactant stream highly influenced the catalytic activity. The remarkably higher rate of NH3 synthesis was observed for the higher H2/N2 ratio at 400 °C and lower H2 concentration in the reactant stream improved the catalytic activity at lower temperature conditions. A sharp increase in the catalytic activity of Cs−Ru/MgO with an increase in pressure was observed at 400 °C for a reactant stream with higher H2 concentration. Relatively less interaction of H2 with the surface of the catalyst is suggested in the presence of NH3 produced during the reaction conducted at elevated temperature conditions. This less susceptibility for H2 adsorption on the active sites of the catalyst is a plausible reason for a higher rate of NH3 synthesis at higher temperature conditions. We modified the Temkin equation model by considering the adsorbed species on the surface of the catalyst affecting NH3 synthesis.
Ultrathin SiC Nanosheets with High Reduction Potential for Improved CH4 Generation from Photocatalytic Reduction of CO2
Authors: Han Cheng , Wang Bing , Wu Chunzhi , Shen Shujin , Zhang Xiaoshan , Sun Lian , Tian Qiong , Lei Yongpeng , Wang Yingde
Published: February 2019

Exploitation of low‐cost and efficient photocatalysts for selective reduction of CO2 into fuels such as methane or methanol is highly desired in the field of solar‐to‐fuel conversion. Herein, ultrathin SiC nanosheets (NSs) with high crystallinity are prepared using two‐dimensional reduced graphene oxide as sacrificial template. The ultrathin feature of SiC NSs readily shortens the migration distance of photoexcited carriers, thereby reducing the recombination probability and providing more energetic electrons to participate in CO2 reduction. Consequently, both the yield (3.11 μmol h−1 g−1) and selectivity (90.6%) of CH4 over SiC NSs demonstrate dramatic improvements in comparison with that of micro‐size SiC (0.76 μmol h−1 g−1, 77.9%) and commercial TiO2 (1.46 μmol h−1 g−1, 61.0%). The initial absorption and activation of CO2 molecules on the surface of SiC NSs is confirmed by the in situ diffuse reflectance infrared Fourier transform spectroscopy. The SiC NSs can promote the deep reduction of carbon intermediate into CH4 thanks to the strong reduction potential of photoexcited electrons. This work not only proves ultrathin SiC NSs to be a promising photocatalyst for CO2 reduction, but also provides novel insights into deep photoreduction of CO2 to CH4.
Structural health monitoring for delamination detection and location in wind turbine blades employing guided waves
Authors: Gómez Muñoz Carlos Quiterio , García Marquez Fausto Pedro , Hernandez Crespo Borja , Makaya Kena
Published: February 2019

Wind power is becoming one of the most important renewable energies in the world. The reduction in operating and maintenance costs of the wind turbines has been identified as one of the biggest challenges to establish this energy as an alternative to fossil fuels. Predictive maintenance can detect a potential failure at an early stage reducing operating costs. Structural health monitoring together with non‐destructive techniques are an effective method to detect incipient delamination in wind turbine blades. Ultrasonic guided waves offer possibilities to inspect delamination and disunion between layers in composite structures. Delamination results in a concentration of tensions in certain areas near the fault, which can propagate and create the total break of the blade. This paper presents a new approach for disunity detection between layers comparing two real blades, also new in the literature, one of them built with three disbonds introduced in its manufacturing process. The signals are denoised by Daubechies wavelet transform. The threshold for the denoising is obtained by a wavelet coefficients selection rule using the Birgé‐Massart penalization method. The signals were normalized and their envelopes were obtained by Hilbert transform. Finally, a pattern recognition based on correlations was applied.
Supersymmetric V-systems
Authors: Antoniou Georgios , Feigin Misha
Published: February 2019

Abstract

We construct

$$ \mathcal{N}=4D\left(2,1;\ \alpha \right) $$

N
=
4
D

2
,
1
;

α

superconformal quantum mechanical system for any configuration of vectors forming a ∨-system. In the case of a Coxeter root system the bosonic potential of the supersymmetric Hamiltonian is the corresponding generalised Calogero-Moser potential. We also construct supersymmetric generalised trigonometric Calogero-Moser-Sutherland Hamiltonians for some root systems including BC

N
.
Identification of steroid C27 monooxygenase isoenzymes involved in sterol catabolism and stepwise pathway engineering of Mycobacterium neoaurum for improved androst-1,4-diene-3,17-dione production
Authors: Shao Minglong , Zhang Xian , Rao Zhiming , Xu Meijuan , Yang Taowei , Xu Zhenghong , Yang Shangtian
Published: February 2019

Cholesterol oxidase, steroid C27 monooxygenase and 3-ketosteroid-Δ1-dehydrogenase are key enzymes involved in microbial catabolism of sterols. Here, three isoenzymes of steroid C27 monooxygenase were firstly characterized from Mycobacterium neoaurum as the key enzyme in sterol C27-hydroxylation. Among these three isoenzymes, steroid C27 monooxygenase 2 exhibits the strongest function in sterol catabolism. To improve androst-1,4-diene-3,17-dione production, cholesterol oxidase, steroid C27 monooxygenase 2 and 3-ketosteroid-Δ1-dehydrogenase were coexpressed to strengthen the metabolic flux to androst-1,4-diene-3,17-dione, and 3-ketosteroid 9α-hydroxylase, which catalyzes the androst-1,4-diene-3,17-dione catabolism, was disrupted to block the androst-1,4-diene-3,17-dione degradation pathway in M. neoaurum JC-12. Finally, the recombinant strain JC-12S2-choM-ksdd/ΔkshA produced 20.1 g/L androst-1,4-diene-3,17-dione, which is the highest reported production with sterols as substrate. Therefore, this work is hopes to pave the way for efficient androst-1,4-diene-3,17-dione production through metabolic engineering.
The 2018 ter Brugge Lecture: Problems with the Introduction of Innovations in Neurovascular Care
Authors: Raymond Jean , Fahed Robert , Roy Daniel , Darsaut Tim E.
Published: February 2019

Most endovascular innovations have been introduced into clinical care by showing good outcomes in small enthusiastic case series of selected patients. Randomized clinical trials (RCTs) have rarely been performed, except for acute ischemic stroke, but even then most trial designs were too explanatory to inform clinical decisions. In this article, we review 2 × 2 tables and forest plots that summarize RCT results to examine methodological issues in the design and interpretation of clinical studies. Research results can apply in practice when RCTs are all-inclusive, pragmatic trials. Common problems include the following: (i) using restrictive eligibility criteria in explanatory trials, instead of including the diversity of patients in need of care, which hampers future generalizability of results; (ii) ignoring an entire line of the 2 × 2 table and excluding patients who do not meet the proposed criteria of a diagnostic test in its evaluation (perfusion studies) which renders clinical inferences misleading; (iii) ignoring an entire column of the 2 × 2 table and comparing different patients treated using the same treatment instead of different treatments in the same patients (the “wrong axis” comparisons of prognostic studies and clinical experience) which leads to unjustified treatment decisions and actions; or (iv) combining all aforementioned problems (case series and epidemiological studies). The most efficient and reliable way to improve patient outcomes, after as well as long before research results are available, is to change the way we practice: to use care trials to guide care in the presence of uncertainty.
A screening strategy for latent tuberculosis in healthcare workers: Cost-effectiveness and budget impact of universal versus targeted screening
Authors: Png May Ee , Yoong Joanne , Ong Catherine Wei Min , Fisher Dale , Bagdasarian Natasha
Published: February 2019

Objective:

To evaluate the clinical, cost-efficiency, and budgetary implications of universal versus targeted latent tuberculosis infection (LTBI) screening strategies among healthcare workers (HCWs) in an intermediate tuberculosis (TB)-burden country.

Design:

Pragmatic cost-effectiveness and budget impact analysis using decision-analytic modeling.

Setting:

A tertiary-care hospital in Singapore.

Methods:

We compared 7 potentially implementable LTBI screening programs including universal and targeted strategies with different screening frequencies. Feasible targeting methods included stratification by country of origin (a proxy for risk of prior TB exposure) and by high-risk occupation. The clinical and financial consequences of each strategy were estimated relative to “no screening” (current practice) and compared to locally appropriate cost-effectiveness thresholds. All analyses were conducted from the hospital’s perspective over a 3-year time horizon, based on the typical hospital planning period. Parameter uncertainties were accounted for using sensitivity analyses.

Results:

In our model, relative to current practice, screening new international hires and triennial screening of existing high-risk workers is most cost-effective (US$58 per quality adjusted life year [QALY]) and decreases active TB cases from 19 to 14. Screening all new hires combined with triennial universal screening, with or without annual high-risk screening or annual universal screening, reduced active TB to a range of 19 to 6 cases, but these strategies are less cost-effective and require substantially higher expenditures.

Conclusions:

Targeted LTBI screening for HCWs can be highly cost-effective for hospitals in settings similar to Singapore. More inclusive screening strategies (including regular universal screening) can yield better outcomes but are less efficient and may even be unaffordable.
Generalized helical vortex pairs
Authors: Durán Venegas E. , Le Dizès S.
Published: February 2019

New solutions describing the interaction of helical pairs of counter-rotating vortices are obtained using a vortex filament approach. The vortices are assumed to have a small core size allowing the calculation of the self-induced velocities from the Biot–Savart law using the cutoff theory. These new vortex structures do not possess any helical symmetry but they exhibit a spatial periodicity and are stationary in a rotating and translating frame. Their properties, such as radial deformation, frame velocity and induced flow, are provided as a function of the four geometric parameters characterizing each solution. Approximate solutions are also obtained when the mutual interaction is weak. This allows us to provide explicit expressions for the rotation and translation velocities of the structure in this limit. First-order corrections describing helix deformation are also calculated and used for comparison with the numerical results. The variation of the vortex core size induced by the helix deformation is also analysed. We show that these variations have a weak effect on the shape and characteristics of the solutions, for the range of parameters that we have considered. The results are finally applied to rotor wakes. It is explained how these solutions could possibly describe the far wake of an helicopter rotor in vertical flight.
The mid-frequency Square Kilometre Array phase synchronisation system
Authors: Schediwy S. W. , Gozzard D. R. , Gravestock C. , Stobie S. , Whitaker R. , Malan J. A. , Boven P. , Grainge K.
Published: February 2019

This paper describes the technical details and practical implementation of the phase synchronisation system selected for use by the Mid-Frequency Square Kilometre Array. Over a four-year period, the system has been tested on metropolitan fibre-optic networks, on long-haul overhead fibre at the South African Square Kilometre Array site, and on existing telescopes in Australia to verify its functional performance. The tests have shown that the system exceeds the 1-s Square Kilometre Array coherence loss requirement by a factor of 2 560, the 60-s coherence loss requirement by a factor of 239, and the 10-min phase drift requirement by almost five orders-of-magnitude. The paper also reports on tests showing that the system can operate within specification over all the required operating conditions, including maximum fibre link distance, temperature range, temperature gradient, relative humidity, wind speed, seismic resilience, electromagnetic compliance, frequency offset, and other operational requirements.
Lichenicolous ascomycetes onSiphula-like lichens, with a key to the species
Authors: MOTIEJŪNAITĖ Jurga , ZHURBENKO Mikhail P. , SUIJA Ave , KANTVILAS Gintaras
Published: February 2019

Sixteen species of lichenicolous fungi are documented fromSiphula-like lichens. Two new genera based on new species are introduced.AmylogallaSuija, Motiej. & Kantvilas, characterized by I+ blue, K/I+ violet vegetative hyphae and ascomatal wall, immersed, cleistohymenial, yellowish to orange ascomata, unitunicate, non-amyloid, 8-spored asci and hyaline, ellipsoid, aseptate ascospores, is described fromParasiphulain Tasmania.SaaniaZhurb., characterized by superficial, stromatic, multilocular ascomata, non-amyloid hymenial gel, persistent periphysoids, bitunicate, non-amyloid, 4(–8)-spored asci and narrowly obovate to ellipsoid, 1(–3)-septate, initially hyaline and smooth-walled, later sometimes brown and verruculose ascospores, is described fromSiphulain South Africa. Four additional species are described as new: two fromSiphula(Cercidospora santessoniiMotiej., Zhurb., Suija & Kantvilas andStigmidium kashiwadaniiZhurb.) and two fromParasiphula(Endococcus hafellnerianusMotiej., Suija & Kantvilas andPyrenidium macrosporumMotiej., Zhurb., Suija & Kantvilas). Additional hosts and/or expanded geographical ranges are reported forAabaarnia siphulicola,Epigloea soleiformis, Plectocarpon gayanumandPyrenidium actinellum. The Southern Hemisphere is the centre of species richness for siphulicolous fungi, with 12 species restricted to this region. Taxa recorded for the Northern Hemisphere areSphaerellothecium siphulae(arctic and boreal) and the subcosmopolitanEpigloea soleiformisandPyrenidium actinellum, both of which are also known from various lichen hosts. The distribution of siphulicolous fungi strongly underpins the current generic classification ofSiphula-like lichens, with five species being confined exclusively toParasiphulaand nine toSiphula. A key to the taxa occurring onSiphulaandParasiphulais provided.
The return of truth: defending the correspondence theory after the liberal/postliberal divide
Authors: KNIGHT JOHN ALLAN
Published: February 2019

This article defends the correspondence theory of truth against criticisms of three theologians: Stephen Long, Kevin Hector, and Bruce Marshall. Long's criticisms arise from his metaphysical commitments, Hector's from his anti-metaphysical commitments, and Marshall's from his methodological commitments. I treat Long and Hector briefly, before giving a more extended treatment of Bruce Marshall's attack on the correspondence theory using the slingshot argument of Donald Davidson. I argue that correspondence theories withstand their criticisms. They therefore pose no obstacle to using them in theology.
OPTIMIZING POLICYMAKERS’ LOSS FUNCTIONS IN CRISIS PREDICTION: BEFORE, WITHIN OR AFTER?
Authors: Sarlin Peter , von Schweinitz Gregor
Published: February 2019

Recurring financial instabilities have led policymakers to rely on early-warning models to signal financial vulnerabilities. These models rely on ex-post optimization of signaling thresholds on crisis probabilities accounting for preferences between forecast errors, but come with the crucial drawback of unstable thresholds in recursive estimations. We propose two alternatives for threshold setting with similar or better out-of-sample performance: (i) including preferences in the estimation itself and (ii) setting thresholds ex-ante according to preferences only. Given probabilistic model output, it is intuitive that a decision rule is independent of the data or model specification, as thresholds on probabilities represent a willingness to issue a false alarm vis-à-vis missing a crisis. We provide real-world and simulation evidence that this simplification results in stable thresholds, while keeping or improving on out-of-sample performance. Our solution is not restricted to binary-choice models, but directly transferable to the signaling approach and all probabilistic early-warning models.
Vitamin C improves liver and renal functions in hypothyroid rats by reducing tissue oxidative injury
Authors: Esmaeilizadeh Mahdi , Hosseini Mahmoud , Beheshti Farimah , Alikhani Vajihe , Keshavarzi Zakieh , Shoja Mohsen , Mansoorian Mozhgan , Sadeghnia Hamid Reza
Published: February 2019

Abstract. Background: The effects of Vit C on liver and renal function and the tissues oxidative damage was investigated in hypothyroid rats. Materials and methods: The pregnant rats were divided into 5 groups (n=6): (1) Control; (2) Propylthiouracil (PTU; 0.005%), (3–5) PTU plus 10, 100 or 500 mg/kg b.w. Vit C. The drugs were added to the drinking water of the dams and their pups during lactation period and then continued for the offspring through the ﬁrst 8 weeks of their life. Finally, 7 male offspring from each group were randomly selected. Results: Thyroxine, protein and albumin concentrations in the serum and thiol content and superoxide dismutase (SOD) and catalase (CAT) activities in renal and liver tissues of hypothyroid group was lower (all P<0.001) while, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALK-P), creatinine and blood urea nitrogen (BUN) concentrations in the serum and malondialdehyde (MDA) in the liver and renal tissues were higher than the control (all P<0.001). All doses of Vit C increased thyroxine, protein and albumin and thiol content in in renal and liver tissues while, decreased AST, ALT and ALK-P concentration and MDA in liver and renal tissues compared to PTU group (P<0.05–P<0.001). Creatinine, BUN and SOD and CAT were improved by both 100 and 500 mg/kg of Vit C in the renal (P<0.05–P<0.001) and by 100 mg/kg in the liver (P<0.05–P<0.001). Conclusion: Vit C improved liver and renal function of hypothyroid rats which might be due to its protective effects against tissues oxidative damage.
Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis
Authors: Park Seong-Hoon , Han A Lum , Kim Na-Hyung , Shin Sae-Ron
Published: February 2019

Abstract. Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.
A New Definition of the South‐East Madagascar Bloom and Analysis of Its Variability
Authors: Dilmahamod A. F. , Penven P. , Aguiar‐González B. , Reason C. J. C. , Hermes J. C.
Published: February 2019

The South‐East Madagascar Bloom occurs in an oligotrophic region of the southwest Indian Ocean. Phase locked to austral summer, this sporadic feature exhibits substantial temporal and spatial variability. Several studies, with different hypotheses, have focused on the initiation mechanism triggering the bloom, but none has been as yet clearly substantiated. With 19 years of ocean color data set available as well as in situ measurements (Argo profiles), the time is ripe to review this feature. The bloom is characterized in a novel manner, and a new bloom index is suggested, yielding 11 bloom years, including 3 major bloom years (1999, 2006, and 2008). Spatially, the bloom varies from a mean structure (22–32°S; 50–70°E) both zonally and meridionally. A colocation analysis of Argo profiles and chlorophyll‐a data revealed a bloom occurrence in a shallow‐stratified layer, with low‐salinity water in the surface layers. Additionally, a quantitative assessment of the previous hypotheses is performed and bloom occurrence is found to coincide with La Niña events and reduced upwelling intensity south of Madagascar. A stronger South‐East Madagascar Current during La Niña may support a detachment of the current from the coasts, dampening the upwelling south of Madagascar, and feeding low‐salinity waters into the Madagascar Basin, hence increasing stratification. Along with abundance of light, these provide the right conditions for a nitrogen‐fixing cyanobacterial phytoplankton bloom onset.
Temporal and Spatial Hydrodynamic Variability in the Mallorca Channel (Western Mediterranean Sea) From 8 Years of Underwater Glider Data
Authors: Barceló‐Llull Bàrbara , Pascual Ananda , Ruiz Simón , Escudier Romain , Torner Marc , Tintoré Joaquín
Published: February 2019

Eight years of glider data are used to characterize the temporal and spatial variability of a region in the western Mediterranean that will constitute one of the targets for the calibration phase of the Surface Water and Ocean Topography (SWOT) satellite mission. The characteristic horizontal dimension of mesoscale instabilities in the Mallorca channel is 6.0 km. The temporal evolution of intermediate water masses is dominated by an increase over time of the characteristic temperature values. Western Mediterranean and Levantine Intermediate waters display an increase of the temperature extrema of 0.064 ± 0.002 and 0.044 ± 0.002 °C/year between 2011 and 2018, respectively. At the layer of Levantine Intermediate water the salinity temporal regression reveals a mean trend of 0.010 year−1. Temperature annual cycle shows an averaged temperature gradient of ∼6 °C in 6 months at the upper layer, with a disconnection with the annual cycle at 100‐m depth. The circulation across the channel is dominated by high‐frequency variability. The signature of eddies with radius ranging from 5 to 18 km is apparent in 16% of the transects analyzed and mainly in spring and summer, with a dominance of subsurface cyclonic eddies. Two‐way flow controls the annual cycle of the water transport through the channel with prevalence of the inflow of Atlantic water. Variations of water transport over timescales of weeks to months can be similar to those identifiable as seasonal changes.
New Tiny Moon of Neptune Discovered
Authors: Cartier Kimberly
Published: February 2019

The moon’s size and orbit point to it being the remnant of a collision with Neptune’s moon Proteus.
Modulation of Economic Losses From European Floods by the North Atlantic Oscillation
Authors: Zanardo Stefano , Nicotina Ludovico , Hilberts Arno G. J. , Jewson Stephen P.
Published: February 2019

The space‐time structure of flood losses is arguably related to large‐scale climatic patterns; however, this interconnection is not always well understood. Here we show that the North Atlantic Oscillation (NAO) correlates with the occurrence of catastrophic floods across Europe and the associated economic losses. The analysis reveals that in Northern Europe the majority of historic winter floods occurred during a positive NAO state, whereas the majority of summer floods occurred during a negative state. Analogous, but stronger, patterns can be observed in individual Atlantic countries. Through the application of a state‐of‐the‐art catastrophe model, we find that there is a statistically significant relationship between the NAO and flood losses. Critically, we observe that the average flood loss during opposite NAO states can differ by up to 50%. These results can inform financial preparedness and disaster fund allocation, as stakeholders, such as governments and insurance companies, can distribute resources more effectively.
Downregulation of Npas4 in parvalbumin interneurons and cognitive deficits after neonatal NMDA receptor blockade: relevance for schizophrenia
Authors: Shepard Ryan , Heslin Kelsey , Hagerdorn Payton , Coutellier Laurence
Published: February 2019

Dysfunction of prefrontal parvalbumin (PV+) interneurons has been linked with severe cognitive deficits as observed in several neurodevelopmental disorders including schizophrenia. However, whether a specific aspect of PV+ neurons deregulation, or a specific molecular mechanism within PV+ neurons is responsible for cognitive deficits and other behavioral impairments remain to be determined. Here, we induced cognitive deficits and altered the prefrontal PV system in mice by exposing them neonatally to the NMDA receptor antagonist ketamine. We observed that the cognitive deficits and hyperactivity induced by neonatal ketamine were associated with a downregulation of Npas4 expression specifically in PV+ neurons. To determine whether Npas4 downregulation-induced dysfunction of PV+ neurons could be a molecular contributor to the cognitive and behavioral impairments reported after neonatal ketamine, we used a transgenic Cre-Lox approach. Reduced Npas4 expression within PV+ neurons replicates deficits in short-term memory observed after neonatal ketamine, but does not reproduce disturbances in general activity. Our data show for the first time that the brain-specific transcription factor Npas4 may be an important contributor to PV+ neurons dysfunction in neurodevelopmental disorders, and thereby could contribute to the cognitive deficits observed in diseases characterized by abnormal functioning of PV+ neurons such as schizophrenia. These findings provide a potential novel therapeutic target to rescue the cognitive impairments of schizophrenia that remain to date unresponsive to treatments.