bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro
and
In Vivo
Activities of DS-2969b, a Novel GyrB Inhibitor, and Its Water-Soluble Prodrug, DS11960558, against Methicillin-Resistant Staphylococcus aureus
Authors: Barman Tarani Kanta , Kumar Manoj , Mathur Tarun , Namba Eiko , Singh Diksha , Chaira Tridib , Kurosaka Yuichi , Yamada Makiko , Upadhyay Dilip Jatashankar , Masuda Nobuhisa
Published: April 2018

DS-2969b is a novel GyrB inhibitor under clinical development. In this study, the
in vitro
activity of DS-2969b and the
in vivo
activities of DS-2969b and its water-soluble prodrug, DS11960558, against methicillin-resistant
Staphylococcus aureus
(MRSA) were evaluated. DS-2969b inhibited the supercoiling activity of
S. aureus
DNA gyrase and the decatenation activity of its topoisomerase IV. DS-2969b showed antibacterial activity against Gram-positive aerobes but not against Gram-negative aerobes, except for
Moraxella catarrhalis
and
Haemophilus influenzae
. DS-2969b was active against MRSA with an MIC
90
of 0.25 μg/ml, which was 8-fold lower than that of linezolid. The presence of a pulmonary surfactant did not affect the MIC of DS-2969b. DS-2969b showed time-dependent slow killing against MRSA. The frequency of spontaneous resistance development was less than 6.2 × 10
−10
in all four
S. aureus
isolates at 4× MIC of DS-2969b. In a neutropenic MRSA-induced murine muscle infection model, DS-2969b was more efficacious than linezolid by both the subcutaneous and oral routes. DS-2969b and DS11960558 showed efficacy in a neutropenic murine MRSA lung infection model. The pharmacokinetics and pharmacodynamics of DS-2969b and DS11960558 against MRSA were characterized in a neutropenic murine thigh infection model; the percentage of time during the dosing period in which the free drug concentration exceeded the MIC (
fT
MIC
) correlated best with
in vivo
efficacy, and the static percent
fT
MIC
was 43 to 49%. A sufficient
fT
MIC
was observed in a phase 1 multiple-ascending-dose study of DS-2969b given orally at 400 mg once a day. These results suggest that DS11960558 and DS-2969b have potential for use as intravenous-to-oral step-down therapy for treating MRSA infections with a higher efficacy than linezolid.
High-Yield Production of Herbicidal Thaxtomins and Thaxtomin Analogs in a Nonpathogenic Streptomyces Strain
Authors: Jiang Guangde , Zhang Yucheng , Powell Magan M. , Zhang Peilan , Zuo Ran , Zhang Yi , Kallifidas Dimitris , Tieu Albert M. , Luesch Hendrik , Loria Rosemary , Ding Yousong
Published: April 2018

Thaxtomins are virulence factors of most plant-pathogenic
Streptomyces
strains. Due to their potent herbicidal activity, attractive environmental compatibility, and inherent biodegradability, thaxtomins are key active ingredients of bioherbicides approved by the U.S. Environmental Protection Agency. However, the low yield of thaxtomins in native
Streptomyces
producers limits their wide agricultural applications. Here, we describe the high-yield production of thaxtomins in a heterologous host. The thaxtomin gene cluster from
S. scabiei
87.22 was cloned and expressed in
S. albus
J1074 after chromosomal integration. The production of thaxtomins and nitrotryptophan analogs was observed using liquid chromatography-mass spectrometry (LC-MS) analysis. When the engineered
S. albus
J1074 was cultured in the minimal medium Thx defined medium supplemented with 1% cellobiose (TDMc), the yield of the most abundant and herbicidal analog, thaxtomin A, was 10 times higher than that in
S. scabiei
87.22, and optimization of the medium resulted in the highest yield of thaxtomin analogs at about 222 mg/liter. Further engineering of the thaxtomin biosynthetic gene cluster through gene deletion led to the production of multiple biosynthetic intermediates important to the chemical synthesis of new analogs. Additionally, the versatility of the thaxtomin biosynthetic system in
S. albus
J1074 was capitalized on to produce one unnatural fluorinated analog, 5-fluoro-thaxtomin A (5-F-thaxtomin A), whose structure was elucidated by a combination of MS and one-dimensional (1D) and 2D nuclear magnetic resonance (NMR) analyses. Natural and unnatural thaxtomins demonstrated potent herbicidal activity in radish seedling assays. These results indicated that
S. albus
J1074 has the potential to produce thaxtomins and analogs thereof with high yield, fostering their agricultural applications.

IMPORTANCE
Thaxtomins are agriculturally valuable herbicidal natural products, but the productivity of native producers is limiting. Heterologous expression of the thaxtomin gene cluster in
S. albus
J1074 resulted in the highest yield of thaxtomins ever reported, representing a significant leap forward in its wide agricultural use. Furthermore, current synthetic routes to thaxtomins and analogs are lengthy, and two thaxtomin biosynthetic intermediates produced at high yields in this work can provide precursors and building blocks to advanced synthetic routes. Importantly, the production of 5-F-thaxtomin A in engineered
S. albus
J1074 demonstrated a viable alternative to chemical methods in the synthesis of new thaxtomin analogs. Moreover, our work presents an attractive synthetic biology strategy to improve the supply of herbicidal thaxtomins, likely finding general applications in the discovery and production of many other bioactive natural products.
Cyclic di-GMP Positively Regulates DNA Repair in Vibrio cholerae
Authors: Fernandez Nicolas L. , Srivastava Disha , Ngouajio Amanda L. , Waters Christopher M.
Published: April 2018

Vibrio cholerae
is a prominent human pathogen that is currently causing a pandemic outbreak in Haiti, Yemen, and Ethiopia. The second messenger molecule cyclic di-GMP (c-di-GMP) mediates the transitions in
V. cholerae
between a sessile biofilm-forming state and a motile lifestyle, both of which are important during
V. cholerae
environmental persistence and human infections. Here, we report that in
V. cholerae
c-di-GMP also controls DNA repair. We elucidate the regulatory pathway by which c-di-GMP increases DNA repair, allowing this bacterium to tolerate high concentrations of mutagens at high intracellular levels of c-di-GMP. Our work suggests that DNA repair and biofilm formation may be linked in
V. cholerae
.
Using Preprints for Journal Clubs
Authors: Casadevall Arturo , Gow Neil
Published: April 2018

Journal clubs are important mechanisms for teaching how to approach the scientific literature critically and for disseminating findings. Papers from high-impact journals often dominate journal club selections, a practice that reinforces the unscientific emphasis of placing high value on publishing venue rather than scientific content and critical analysis of the publications. We suggest improving journal clubs by including preprints rather than focusing completely on published papers. This change in practice might benefit the scientific enterprise in numerous ways, including by providing direct criticisms to preprint authors before publication, deemphasizing publishing venue, teaching students the art of reviewing papers, and making journal clubs more current by discussing unpublished data.
Two-year follow-up of corneal cross-linking and refractive surface ablation in patients with asymmetric corneal topography
Authors: Malta João Baptista N S , Kaz Soong H , Moscovici Bernardo Kaplan , Campos Mauro
Published: April 2018

Aims

To evaluate the safety and efficacy of corneal cross-linking (CXL) followed by photorefractive keratectomy (PRK) for refractive correction in patients with bilateral asymmetric topography.

Methods

Forty-four patients (88 eyes) were enrolled in this prospective randomised clinical trial. CXL with subsequent PRK after 6 months was performed in one eye (study group), and PRK alone was performed in contralateral eyes (control group). Patients were followed for 24 months after PRK. Outcome measures investigated included visual acuity (VA), refraction, aberrometry, topography, pachymetry and endothelial cell count. Groups were compared with linear mixed regression and repeated measures logistic regression. Multiple comparison adjustment with the Holm procedure was performed.

Results

At baseline, the logMAR VA (best spectacle corrected) in study and control groups was 0.12±0.13 (mean±SD) and 0.08D±0.14, respectively, and axial inferior–superior index (IS) (topographic IS) in study and control groups were 0.59D±0.31D and 0.58D±0.32D, respectively. After 24 months, a mean under correction of −0.50D was observed in both groups. Change from baseline in logMAR VA in study and control groups was 0.00D±0.08D and −0.02D±0.10D, respectively. Frequency of haze at 30 months in study and control group eyes was, respectively, 18.2% and 4.6% (p=0.05). There was no statistical difference between groups in spherical aberration and coma after adjustment for multiple comparisons.

Conclusions

Non-simultaneous CXL followed by PRK may be performed safely, and refractive results over a 2-year follow-up are highly similar in virgin and previously cross-linked corneas. Despite using mitomycin C, corneal haze can be significantly higher in the first year after PRK in eyes pretreated with CXL.
Rise and fall of NT-proBNP in aortic valve intervention
Authors: Hultkvist Henrik , Holm Jonas , Svedjeholm Rolf , Vánky Farkas
Published: April 2018

Objectives

To describe the dynamics of N-terminal pro-B-type natriuretic peptide (NT-proBNP) from preoperative evaluation to 6-month follow-up in patients undergoing aortic valve intervention, and to evaluate NT-proBNP with regard to 1-year mortality.

Methods

At preoperative evaluation, we prospectively included 462 patients accepted for aortic valve intervention. The median time to surgical aortic valve replacement (SAVR; n=336) or transcatheter aortic valve implantation (TAVI; n=126) was 4 months. NT-proBNP was measured at enrolment for preoperative evaluation, on the day of surgery, postoperatively on day 1, day 3 and at the 6-month follow-up. Subgroups of patients undergoing SAVR with aortic regurgitation and aortic stenosis with and without coronary artery bypass were also analysed.

Results

NT-proBNP remained stable in all subgroups during the preoperative waiting period, but displayed a substantial transient early postoperative increase with a peak on day 3 except in the TAVI group, which peaked on day 1. At the 6-month follow-up, NT-proBNP had decreased to or below the preoperative level in all groups. In the SAVR group, NT-proBNP preoperatively and on postoperative days 1 and 3 revealed significant discriminatory power with regard to 1-year mortality (area under the curve (AUC)=0.79, P=0.0001; AUC=0.71, P=0.03; and AUC=0.79, P=0.002, respectively). This was not found in the TAVI group, which had higher levels of NT-proBNP both preoperatively and at the 6-month follow-up compared with the SAVR group.

Conclusions

The dynamic profile of NT-proBNP differed between patients undergoing TAVI and SAVR. NT-proBNP in the perioperative course was associated with increased risk of 1-year mortality in SAVR but not in TAVI.
The Half Cleaner Lemma: Constructing Efficient Interconnection Networks from Sorting Networks
Authors: Jain Tripti , Schneider Klaus
Published: April 2018

In general, efficient non-blocking interconnection networks can be derived from sorting networks, and to this end, one may either follow the merge-based or the radix-based sorting paradigm. Both paradigms require special modifications to handle partial permutations. In this article, we present a general lemma about half cleaner modules that were introduced as building blocks in Batcher’s bitonic sorting network. This lemma is the key to prove the correctness of many known optimizations of interconnection networks. In particular, we first show how to use any ternary sorter and a half cleaner for implementing an efficient split module as required for radix-based sorting networks for partial permutations. Second, our lemma formally proves the correctness of another known optimization of the Batcher-Banyan network.
Algorithmic Complexity and Reprogrammability of Chemical Structure Networks
Authors: Zenil Hector , Kiani Narsis A. , Shang Ming-mei , Tegnér Jesper
Published: April 2018

Here we address the challenge of profiling causal properties and tracking the transformation of chemical compounds from an algorithmic perspective. We explore the potential of applying a computational interventional calculus based on the principles of algorithmic probability to chemical structure networks. We profile the sensitivity of the elements and covalent bonds in a chemical structure network algorithmically, asking whether reprogrammability affords information about thermodynamic and chemical processes involved in the transformation of different compound classes. We arrive at numerical results suggesting a correspondence between some physical, structural and functional properties. Our methods are capable of separating chemical classes that reflect functional and natural differences without considering any information about atomic and molecular properties. We conclude that these methods, with their links to chemoinformatics via algorithmic, probability hold promise for future research.
Main features of detectors and isotopes to investigate double beta decay with increased sensitivity
Authors: Barabash A. S.
Published: April 2018

The current situation in double beta decay experiments, the characteristics of modern detectors and the possibility of increasing the sensitivity to neutrino mass in future experiments are discussed. The issue of the production and use of enriched isotopes in double beta decay experiments is discussed in addition.
Investigation of rare nuclear decays with the DAMA set-ups
Authors: Bernabei Rita , Cappella Fabio
Published: April 2018

The DAMA project has obtained many competitive or new results in the search for various rare nuclear processes. Most of them have been obtained with the help of many different high purity crystal scintillators which have been measured in the low-background DAMA set-ups located in the Gran Sasso underground laboratory of INFN In this paper, the main results will be summarized.
Sharp-pointed susceptibility of ferromagnetic films with magnetic anisotropy inhomogeneous in thickness
Authors: Dzhezherya Yu. I. , Khrebtov A. O. , Azarkh D. P. , Kruchinin S. P.
Published: April 2018

It is shown that in ferromagnetic films with anisotropy inhomogeneous in thickness, an interphase boundary can be formed for certain values and directions of the magnetic field. This boundary has a stable magnetic configuration. It is oriented parallel to the film plane and separates the regions with different orientations of the magnetization. In an alternating magnetic field, the interphase boundary oscillates, which may be accompanied by a resonance. The field and frequency dependences of the components of the magnetic susceptibility tensor are determined. It is shown that the susceptibility coefficients at a resonance are extremely sensitive to the direction of the external magnetic field which can underlie the development of a highly sensitive sensor.
Development of light irradiation calorimetry system for molecule-based compounds
Authors: Matsumura Y. , Kataoka S. , Imajo S. , Yamashita S. , Akutsu H. , Nakazawa Y.
Published: April 2018

Construction of a calorimetry system, by which the light irradiation to the surface area of molecular crystals at extremely low temperatures can be possible is reported. The development was performed based on the relaxation calorimetry technique to evaluate electronic structure using small amount of samples of molecular compounds where the electron correlation effects and electron–lattice coupling effects induce drastic change of the ground state. Detection of electronic structure changes occur as the light-induced phenomena becomes possible by this type of calorimetry apparatus. We report on the detailed structure of the small-sized calorimetry cells constructed for this purpose as well as the design of the calorimeter. The experimental results using organic superconductor and magnetic materials are given, which substantiate that the absolute value measurements under light irradiation are promising using the developed systems. Further possibility is also discussed.
First-principles investigations on structural, elastic and mechanical properties of BNxAs1−x ternary alloys
Authors: Zhang Junqin , Ma Huihui , Zhao Bin , Wei Qun , Yang Yintang
Published: April 2018

A systematic investigation of the structural optimization, elastic and mechanical properties of the BN[Formula: see text]As[Formula: see text] ternary alloys are reported in the present work using the density–functional theory with the generalized gradient approximation (GGA) of the exchange–correlation functional. Some of the constants which are used to analyze the properties including elastic constants and modulus, and some parameters describing the elastic anisotropy and Debye temperature are also calculated. Our calculations were performed to evaluate the equilibrium lattice constant and band structure compared with the available theoretical works. On the one hand, our results might be expected to provide a theoretical basis for future study of BN[Formula: see text]As[Formula: see text] alloys towards elastic or mechanical properties. On the other hand, we draw a conclusion that BN[Formula: see text]As[Formula: see text] alloys show direct bandgap when x equals 0.25, 0.5 or 0.75. We obtained the elastic modulus, Poisson’s ratio and universal anisotropic index which are used to demonstrate the elastic anisotropy of these alloys which is proved according to our calculations. Also, we calculated the Debye temperature to illustrate covalent interactions and obtained the lower limit of the thermal conductivity for further research.
Magnetization reversal in crossed double elliptic permalloy nanodisks studied by micromagnetic simulation
Authors: Mishra Amaresh Chandra , Giri R.
Published: April 2018

The remanent state of elliptical permalloy nanodisks depends on the orientation of the applied magnetic field with respect to the major and minor axes of the nanodisks [A. C. Mishra, Int. J. Mod. Phys. B 30, 1650192 (2016)]. The remanent state is usually an onion state if the external magnetic field is along the major axis, and is a vortex state if the external magnetic field is along the minor axis. In this work, we have analyzed the magnetization reversal of a crossed elliptic disk of permalloy using micromagnetic simulation. This is a new shape where two identical elliptic disks with semi-major axis of length a and semi-minor axis of length b intersect such that they are perpendicular to each other. If the value of b is very close to that of a, then the remanent state is a near saturation state. As the ratio a/b goes down, new complex remanent states are observed. The hysteresis loss is found to be decreased gradually with the increment of b for a given value of b.
Optical properties in GaAs/AlGaAs semiparabolic quantum wells by the finite difference method: Combined effects of electric field and magnetic field
Authors: Yan Ru-Yu , Tang Jian , Zhang Zhi-Hai , Yuan Jian-Hui
Published: April 2018

In the present work, the optical properties of GaAs/AlGaAs semiparabolic quantum wells (QWs) are studied under the effect of applied electric field and magnetic field by using the compact-density-matrix method. The energy eigenvalues and their corresponding eigenfunctions of the system are calculated by using the differential method. Simultaneously, the nonlinear optical rectification (OR) and optical absorption coefficients (OACs) are investigated, which are modulated by the applied electric field and magnetic field. It is found that the position and the magnitude of the resonant peaks of the nonlinear OR and OACs can depend strongly on the applied electric field, magnetic field and confined potential frequencies. This gives a new way to control the device applications based on the intersubband transitions of electrons in this system.
Single attosecond pulse generation by using plasmon-driven double optical gating technology in crossed metal nanostructures
Authors: Feng Liqiang , Liu Katheryn
Published: April 2018

An effective method to obtain the single attosecond pulses (SAPs) by using the multi-cycle plasmon-driven double optical gating (DOG) technology in the specifically designed metal nanostructures has been proposed and investigated. It is found that with the introduction of the crossed metal nanostructures along the driven and the gating polarization directions, not only the harmonic cutoff can be extended, but also the efficient high-order harmonic generation (HHG) at the very highest orders occurs only at one side of the region inside the nanostructure. As a result, a 93 eV supercontinuum with the near stable phase can be found. Further, by properly introducing an ultraviolet (UV) pulse into the driven laser polarization direction (which is defined as the DOG), the harmonic yield can be enhanced by two orders of magnitude in comparison with the singe polarization gating (PG) technology. However, as the polarized angle or the ellipticity of the UV pulse increase, the enhancement of the harmonic yield is slightly reduced. Finally, by superposing the selected harmonics from the DOG scheme, a 30 as SAP with intensity enhancement of two orders of magnitude can be obtained.
Non-thermal emission produced by the interaction of a jet with a supernova remnant
Authors: Vieyro F. L. , Bosch-Ramon V. , Torres-Albà N.
Published: April 2018

Core-collapse supernovae (SNe) are found in galaxies with ongoing star-formation. If a starburst galaxy hosts an active galactic nucleus (AGN) with a relativistic jet, the SN could take place inside the jet. The collision of the SN ejecta with the jet flow leads to the formation of a shock, where particles could be accelerated up to relativistic energies, and produce gamma-ray emission. In this work, we analyze the dynamical evolution of the SN within the jet, and compute the non-thermal radiation expected from the interaction. The evolution of the SN Lorentz factor and radius regulates the intensity of the non-thermal emission. The SN can achieve a relativistic regime for powerful jets, resulting in emission significantly enhanced by Doppler boosting for blazar sources. The interaction of SNe with jets of moderate luminosity can result in steady, unbeamed gamma-ray emission, that might be detectable for sources in the local universe.
FABRICATION OF SURFACE COMPOSITE BY FRICTION STIR PROCESSING USING A NOVEL DIRECT PARTICLE INJECTION TOOL
Authors: MUTHUKUMAR P. , JEROME S. , KUMAR R. JOHN FELIX , PRAKASH S.
Published: April 2018

In this work, aluminum/titanium carbide (Al/TiC) surface composite has been fabricated by friction stir processing using a novel modular Direct Particle Injection Tool (DPI–FSP). The tool has a unique feature wherein the TiC particles have been transferred from the tool itself by spring adjusted plunger movement into the matrix. The microstructural observations from optical and scanning electron microscope (SEM)-EDS results revealed the homogeneous distribution of particles in the stirred zone (SZ) and the thickness of the formed surface composite layer (SCL) is approximately 0.34[Formula: see text]mm. X-ray diffraction results confirmed that the particles are reinforced in the aluminum matrix, and no intermetallics have been formed in the composite. The microhardness of composite was increased from 68 to 135[Formula: see text]Hv, and the impact test results showed that the toughness was almost comparable to that of the base metal.
Domain formation on the nonpolar lithium niobate surfaces under electron-beam irradiation: A review
Authors: Volk T. R. , Kokhanchik L. S. , Gainutdinov R. V. , Bodnarchuk Y. V. , Lavrov S. D.
Published: April 2018

In this review, our recent results on the electron-beam domain writing (EBDW) on the nonpolar surfaces of LiNbO3 crystals of different compositions are presented. Under EB irradiation of the nonpolar surfaces, domains nucleated in irradiation points grow frontally along the polar [Formula: see text]-direction in a thin (of microns in thickness) surface layer; the driving force is the tangential component of space-charge fields induced by EB in irradiation points. This geometry of the experiment provides a possibility of three-dimensional (3D) characterization of domain patterns using the combination of atomic force microscopy (AFM) and second harmonic generation (SHG) confocal microscopy methods. The obtained results permitted us to relate the main characteristics of domain formation (the domain sizes and velocity [Formula: see text] of the frontal motion) to the irradiation conditions (the accelerating voltage [Formula: see text] of scanning electron microscopy (SEM), EB current [Formula: see text], the inserted charge [Formula: see text]). The domain depth [Formula: see text] is controlled by [Formula: see text] via the electron penetration depth; the domain length [Formula: see text] increases linearly with [Formula: see text] owing to the domain frontal growth by the viscous friction law. The electron emission coefficient [Formula: see text] affects the domain formation due to the fundamental dependence of [Formula: see text] on [Formula: see text]. In the framework of current approach to EB charging of insulators, the effect of an enhanced conductance on EBDW characteristics is analyzed. The difference between EBDW characteristics observed in varied LiNbO3 compositions is discussed in the framework of the intrinsic defect structure of LiNbO3. The obtained results extend the possibility of EBDW application to a wider range of crystals.
Implied volatility surfaces during the period of global financial crisis
Authors: Wirjanto Tony S. , Zhu Anyi
Published: April 2018

This paper adopts a parametric regression approach to model and calibrate implied volatility surface during the period of the global financial crisis. Due to its relatively low computational cost, it facilitates comparison across a great number of different competing models. The proposed regression models are backtested against historical S&P 500 prices during both volatile and non-volatile periods as proxied by the VIX index around the same time period, and the fits of the models are assessed. Furthermore both an equally weighted scheme and an alternative scheme based on observed implied volatilities as the weight are deployed and the results produced by these two schemes are contrasted and compared. Finally the concept of promptness, instead of the more traditional concept of time to maturity, is introduced as a covariate in the regression models to better capture the shape of the volatility surface during the period characterized by a prolonged low interest-rate environment.
Analytical pricing of discrete arithmetic Asian options under generalized CIR process with time change
Authors: Tong Zhigang , Liu Allen
Published: April 2018

Starting from CIR process, we build a new model for pricing discrete arithmetic Asian options with nonlinear transformation and stochastic time change. The new model introduces the nonlinearity in both drift and diffusion components of the underlying process and allows for flexible jump processes. We are able to derive the recursive formula for the moment generating function of average price by employing the eigenfunction expansion technique. The Asian option prices can then be implemented through a Fourier transform. We also investigate the sensitivities of option prices with respect to the parameters of the new model.
Does earnings management mediate the impact of financial policies on market value of firms? A comparative study of China and Pakistan
Authors: Kamran Muhammad Rizwan , Zhao Zheng , Ali Haji Suleman , Sabir Fiza
Published: April 2018

The study adds new mechanism of earnings management which explores the mediation between financial policies and market value of firms. A comparative study conducted on manufacturing sectors in which sample of 857 companies for China and 150 companies for Pakistanis taken from lists of Stock Exchanges during the period 2012 to 2016. Discretionary accruals have been calculated using the modified Jones Model (1995) and finally Panel analysis was used to analyze the data. Result discloses that in both countries, managers’ Earning Management practices could significantly mediate between these financial policies and firm’s value as measured by Tobin’s Q and stock return. This is the first empirical evidence that make available importance of financial policies which could efficiently influenced by earnings management and ultimately influences the firm’s performance.
A sauropod-dominated tracksite from Rubha nam Brathairean (Brothers’ Point), Isle of Skye, Scotland
Authors: dePolo Paige E. , Brusatte Stephen L. , Challands Thomas J. , Foffa Davide , Ross Dugald A. , Wilkinson Mark , Yi Hong-yu
Published: April 2018

Middle Jurassic dinosaur fossils are exceedingly rare, but new discoveries from the Isle of Skye, Scotland, are beginning to fill this gap. We here describe a new dinosaur tracksite found in the Lealt Shale Formation (Bathonian) of the Great Estuarine Group at Rubha nam Brathairean (Brothers' Point) on Skye. The site preserves an abundance of small sauropod manus and pes prints and several isolated and broken medium-to-large tridactyl footprints. The main site occurs on a single horizon of shaley limestone that formed in a lagoonal environment. The sauropod tracks are tentatively assigned to the ichnotaxon
Breviparopus
due to the narrow gauge of the trackways, the digital characteristics of the pes, and the ratio of heteropody observed between the manus and the pes. A theropod trackmaker is inferred for some of the tridactyl impressions with several indicative of the ichnotaxon
Eubrontes
. This new site strengthens the inference, originally based on a previously discovered locality near Duntulm Castle (Duntulm Formation) in northern Skye, that sauropods habitually spent time in lagoons during the Middle Jurassic.

Supplementary material
: The photogrammetric model of track BP2_40 and associated metadata and photographs are available at
https://doi.org/10.6084/m9.figshare.c.4046390
Hypersequents and Systems of Rules
Authors: Ciabattoni Agata , Genco Francesco A.
Published: April 2018

We define a bi-directional embedding between hypersequent calculi and a subclass of systems of rules (2-systems). In addition to showing that the two proof frameworks have the same expressive power, the embedding allows for the recovery of the benefits of locality for 2-systems, analyticity results for a large class of such systems, and a rewriting of hypersequent rules as natural deduction rules.
Effects of Transcutaneous Electrical Nerve Stimulation on Proinflammatory Cytokines: Systematic Review and Meta-Analysis
Authors: do Carmo Almeida Tábata Cristina , dos Santos Figueiredo Francisco Winter , Barbosa Filho Valter Cordeiro , de Abreu Luiz Carlos , Fonseca Fernando Luiz Affonso , Adami Fernando
Published: April 2018

The mechanism of pain reduction involves bidirectional processes of pain blocking (nociception) and reductions in the levels of proinflammatory cytokines in the blood. Does transcutaneous electrical nerve stimulation (TENS) reduce blood levels of proinflammatory cytokines? For this systematic review, we searched in six databases to identify randomized controlled trials with the criteria: humans older than 18 years (adults), use of TENS in the experimental group, and having at least one pre- and postintervention blood level of at least one proinflammatory cytokine. The risk of bias and the level of evidence were assessed. Five studies were included involving 240 participants. The heterogeneity of the studies was high (I2: 85%); therefore, we used a random-effects meta-analysis. It was observed through the meta-analysis synthesis measures that there were statistically significant differences following the use of TENS to reduce the general group of cytokines. When grouped by chronic disease, by postoperative settings, or by individual studies in the case of IL-6, it was observed that the significant reduction of cytokines related to the use of TENS was maintained. The use of TENS reduced the blood levels of proinflammatory cytokines (we observed a protective factor of TENS in relation to inflammation). The protocol of the systematic review was registered in PROSPERO, CRD42017060379.
IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model
Authors: Zhou Jun , Liang Tian , Wang Dejun , Li Liru , Cheng Yan , Guo Qiuyan , Zhang Guangmei
Published: April 2018

Background. Immunotherapy for cervical cancer with type I interferon (IFN) is limited because of the cytotoxicity that accompanies the high doses that are administered. In this study, we investigated the utilization of amniotic fluid-derived mesenchymal stem cells (AF-MSCs) as a means for delivering IFNα to local tumor sites for the suppression of cervical cancer in a mouse model using HeLa cell xenografts. Methods. The tumor tropism ability of AF-MSCs and AF-MSCs genetically modified to overexpress IFNα (IFNα-AF-MSCs) was examined through Transwell in vitro and through fluorescent images and immunohistochemistry in a mouse model. Tumor size and tumor apoptosis were observed to evaluate the efficacy of the targeting therapy. Mechanistically, tumor cell apoptosis was detected by cytometry and TUNEL, and oncogenic proteins c-Myc, p53, and Bcl-2 as well as microvessel density were detected by immunohistochemistry. Results. In this model, intravenously injected AF-MSCs selectively migrated to the tumor sites, participated in tumor construction, and promoted tumor growth. After being genetically modified to overexpress IFNα, the IFNα-AF-MSCs maintained their tumor tropism but could significantly suppress tumor growth. The restrictive efficacy of IFNα-AF-MSCs was associated with the suppression of angiogenesis, inhibition of tumor cell proliferation, and induction of apoptosis in tumor cells. Neither AF-MSCs nor IFNα-AF-MSCs trigger tumor formation. Conclusions. IFNα-AF-MSC-based therapy is feasible and shows potential for treating cervical cancer, suggesting that AF-MSCs may be promising vehicles for delivering targeted anticancer therapy.
Tetrahydroxystilbene Glucoside Effectively Prevents Apoptosis Induced Hair Loss
Authors: Chen Lulu , Duan Huichuan , Xie Feng , Gao Zhen , Wu Xiaoli , Chen Fanfan , Wu Wei
Published: April 2018

The effect of Polygonum multiflorum against hair loss has been widely recognized. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is the main component of Polygonum multiflorum; however, its role in hair regeneration has not been established. To evaluate the hair growth-promoting activity of TSG, depilated C57BL/6J mice were topically treated with normal saline, TSG, Pifithrin-α, Minoxidil for 2 weeks. In this study, we identified that p53, Caspase-3, Active Caspase-3, and Caspase-9 were obviously upregulated in the skin of human and mice with hair loss by western blot analysis. Depilated mice treated with TSG showed markedly hair regrowth. TUNEL+ cells were also reduced in mice with TSG. These changes were accompanied with inhibition of Fas, p53, Bax, Active Caspase-3, and Procaspase-9 activities. These results demonstrated that TSG exerts great hair regrowth effect on hair loss, which was probably mediated by inhibition of p53, Fas, and Bax induced apoptosis.
Nonylphenol and Octylphenol Differently Affect Cell Redox Balance by Modulating the Nitric Oxide Signaling
Authors: Magnifico Maria Chiara , Xhani Marla , Popov Milica , Saso Luciano , Sarti Paolo , Arese Marzia
Published: April 2018

Nonylphenol (NP) and octylphenol (OP) are pervasive environmental contaminants belonging to the broader class of compounds known as alkylphenols, with potential human toxic effects. Classified as “xenoestrogens,” NP and OP are able to interfere with the cell endocrine physiology via a direct interaction with the estrogen receptors. Here, using HepG2 cells in culture, the changes of the cell redox balance and mitochondrial activity induced by OP and NP have been investigated at μM concentrations, largely below those provoking acute toxicity, as those typical of environmental contaminants. Following 24 h cell exposure to both OP and NP, ROS production appeared significantly increased (p ≤ 0.01), together with the production of higher NO oxides (p = 0.003) and peroxynitrated protein‐derivatives (NP versus CTR, p = 0.003). The mitochondrial proton electrochemical potential gradient instead was decreased (p ≤ 0.05), as the oxygen consumption by complex IV, particularly following incubation with NP (NP versus CTR, p = 0.017). Consistently, the RT‐PCR and Western blot analyses proved that the OP and NP can modulate to a different extent the expression of the inducible NOS (NP versus CTR, p ≤ 0.01) and the endothelial NOS (OP versus CTR, p ≤ 0.05), with a significant variation of the coupling efficiency of the latter (NP versus CTR, p ≤ 0.05), a finding that may provide a novel clue to understand the specific xenoestrogenic properties of OP and NP.
Differential Movement Synchronous Tracking Control Strategy of Double‐Shaking Table System Loading with Specimen
Authors: Li Xiaojun , Wang Juke , Li Fangfang , Li Na , Huang Haohua
Published: April 2018

Multisupport, multidimension, and nonuniform excitation seismic experiments have new requirements for shaking table array system in synchronous tracking control. Therefore, this article proposed a novel synchronous tracking strategy, differential movement synchronous tracking control (DMSTC) strategy, for double‐shaking table system while taking the interaction between shaking tables and specimen into consideration. DMSTC Simulink model of the double‐shaking table with specimen was established and simulations were conducted in various conditions. The results demonstrate the viability of the proposed DMSTC in that the frequency bandwidth of the double‐shaking tables is expanded from 3.27 Hz to 64.57 Hz, the maximum value of differential movement synchronous error is decreased from 1.682 mm to 0.482 mm, and the maximum tracking errors of the two shaking tables decrease from 1.138 mm to 0.044 mm and from 1.030 mm to 0.497 mm, respectively.
Insight into the Effect of Adhesive Interface on the Ultimate Capacity of the Double‐Superposed Shear Wall
Authors: Zhang Wenying , Yang Lianping , Yu Shaole , Chen Xinxi , Zhang Xuewei
Published: April 2018

This paper presents the results of a numerical and analytical study to investigate the effect of adhesive interface on the ultimate capacity of a new composite sandwich shear wall: double‐superposed shear wall. The effect of adhesive interface on the ultimate capacity of two different wall configurations under different axial compression ratios was studied. The results indicate that, for the two different wall configurations, the bond strength of adhesive interface has a negligible effect on ultimate bearing capacity. As a result of the different intensity grades between cast‐in‐situ concrete wythe and precast concrete wythe, the double‐superposed shear wall with precast boundary elements (wall configuration W3) yields a higher ultimate bearing capacity than that with cast‐in‐place boundary elements (wall configuration W2), when the axial compression ratio exceeds 0.2, which is contrary to the results under 0.1 axial compression ratio. A new calculation method for ultimate bearing capacity is proposed to take into account the different intensity grades, and the calculation results show a very good agreement with the numerical simulation results.
Alkaline Ionic Liquid Modified Pd/C Catalyst as an Efficient Catalyst for Oxidation of 5-Hydroxymethylfurfural
Authors: Bin Zou , Xueshan Chen , Jiaojiao Xia , Cunshan Zhou
Published: April 2018

Conversion of HMF into FDCA was carried out by a simple and green process based on alkaline ionic liquid (IL) modified Pd/C catalyst (Pd/C-OH−). Alkaline ionic liquids were chosen to optimize Pd/C catalyst for special hydrophilicity and hydrophobicity, redox stability, and unique dissolving abilities for polar compounds. The Pd/C-OH− catalyst was successfully prepared and characterized by SEM, XRD, TG, FT-IR, and CO2-TPD technologies. Loading of alkaline ionic liquid on the surface of Pd/C was 2.54 mmol·g−1. The catalyst showed excellent catalytic activity in the HMF oxidation after optimization of reaction temperature, reaction time, catalyst amount, and solvent. Supported alkaline ionic liquid (IL) could be a substitute and promotion for homogeneous base (NaOH). Under optimal reaction conditions, high HMF conversion of 100% and FDCA yield of 82.39% were achieved over Pd/C-OH− catalyst in water at 373 K for 24 h.
Heart Protective Effects of Electroacupuncture in an Animal Experimental Study with Delayed Fluid Resuscitation after Hemorrhagic Shock
Authors: Wang Huan , Liu Zhen , Liu Yuanshi , Tong Zhanqi , Qian Yan , Chen Liping , Jiang Bin , Lin Mingxiong , Yang Tao , Gao Lu , Chen Mingjun , Litscher Daniela , Wang Lu , Litscher Gerhard
Published: April 2018

Fluid resuscitation could hardly be performed immediately after fatal hemorrhagic shock in outpatients. We investigated whether electroacupuncture (EA) at Zusanli (ST36) could prevent fatal hemorrhagic shock induced heart failure with delayed fluid resuscitation and whether the protective role of EA is related to the autonomic nervous system. Sixty Sprague Dawley rats were randomly divided into five groups (n = 12 each): group of sham hemorrhagic shock (SHAM), group of EA, group of sham EA (SEA), group of delayed fluid resuscitation with EA (EA + DR), and group of delayed fluid resuscitation with SEA (SEA + DR). After blood loss for 6 hours, caspase‐3 activity and positive rate of TUNEL in EA + DR group were significantly lower than in other hemorrhagic shock groups (e.g., versus SEA + DR: 0.156 ± 0.039 versus 0.301 ± 0.042; P < 0.05). Immediately EA treatment after the blood loss enhanced the protective effect of delayed resuscitation on the cardiac tissue of hemorrhagic shock rats. Considering the significant changes of epinephrine (137.8 ± 6.9 ng/L versus 98.6 ± 7.4 ng/L; P < 0.05) and acetylcholine (405 ± 8.6 pmol/L versus 341 ± 10.1 pmol/L; P < 0.05) after EA treatment (SEA + DR versus EA + DR), this cardiac protective effect may be related to regulation of the autonomic nervous system.
Researches on Damage Evolution and Acoustic Emission Characteristics of Rocks
Authors: Chen Yong , Yang Yugui , Gao Feng , Zhang Xiangxiang
Published: April 2018

Mechanical parameters of the rock are important for the design of geotechnical, mining engineering, and petroleum reservoir projects. Many researches have suggested that the mechanical variables of rock specimens, such as compressive strength and elastic modulus, do not have a single fixed value. Uncertainty in the basic mechanical variables of the rock material can significantly affect the structural performance and safety. In this study, a series of compression experiments with acoustic emission have been performed on rock specimens. The damage evolution characteristics of the rock in the process of loading were studied, and the macromechanical behaviors were obtained at the same time. Distribution characteristics of the strength and elastic modulus as random variables are illustrated, and the statistical damage model is presented by the authors to formulate analytical constitutive relations for deformation behavior. The comparisons between predicted results and experimental data show that the statistical damage constitutive model could well reproduce the deformation process of rock materials.
Establishment of a Model of Microencapsulated SGC7901 Human Gastric Carcinoma Cells Cocultured with Tumor-Associated Macrophages
Authors: Zhu Jin-Ming , Quan Xiu-Lian , Han Shi-Chao , Fan Xue-Jun , Li He-Ming , Liang Shan-Shan , Chen Xi , Wang Ruo-Yu , Ji Xue-Ning
Published: April 2018

The important factors of poor survival of gastric cancer (GC) are relapse and metastasis. For further elucidation of the mechanism, a culture system mimicking the microenvironment of the tumor in humans was needed. We established a model of microencapsulated SGC7901 human GC cells and evaluated the effects of coculturing spheres with tumor-associated macrophages (TAMs). SGC7901 cells were encapsulated in alginate-polylysine-sodium alginate (APA) microcapsules using an electrostatic droplet generator. MTT assays showed that the numbers of microencapsulated cells were the highest after culturing for 14 days. Metabolic curves showed consumption of glucose and production of lactic acid by day 20. Immunocytochemistry confirmed that Proliferating Cell Nuclear Antigen (PCNA) and Vascular Endothelial Growth Factor (VEGF) were expressed in microencapsulated SGC7901 cells on days 7 and 14. The expression of PCNA was observed outside spheroids; however, VEGF was found in the entire spheroids. PCNA and VEGF were increased after being cocultured with TAMs. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were detected in the supernatant of microencapsulated cells cocultured with TAMs but not in microencapsulated cells. Our study confirms the successful establishment of the microencapsulated GC cells. TAMs can promote PCNA, VEGF, MMP-2, and MMP-9 expressions of the GC cells.
Is Chemoprophylaxis for Child Contacts of Drug-Resistant TB Patients Beneficial? A Systematic Review
Authors: Padmapriyadarsini C. , Das Mrinalini , Burugina Nagaraja Sharath , Rajendran Mahalakshmi , Kirubakaran Richard , Chadha Sarabjit , Tharyan Prathap
Published: April 2018

Background. Preventive therapy for child contacts of multidrug-resistant tuberculosis (MDR-TB) patients is poorly studied, and no consensus about the role and the rationale of chemoprophylaxis has been reached. Objective. To conduct systematic review with an aim to determine the effectiveness of TB preventive therapy in reducing the incidence of TB disease in pediatric contacts of MDR-TB patients. Methods. We conducted a literature search for randomized control trials, cohort studies, and case reports of chemoprophylaxis for pediatric contacts of MDR-TB patients in PubMed, EMBASE, Cochrane Databases of Systematic Reviews, metaRegister of Controlled Trials, and other clinical registries through March 2017, using appropriate search strategy. In addition we searched abstracts from international conferences and references of published articles and reviews. Results. Of the 153 references assessed from various databases, seven studies were identified as relevant after adaption of eligibility criteria and assessed for systematic review. Of these, only two studies contributed data for the pooled meta-analysis. Conclusions. Though the available evidences suggest that the chemoprophylaxis for child contacts of MDR-TB patients is beneficial, data to support or reject preventive therapy is very limited. Further clinical research, in Tb endemic settings like India, needs to be performed to prove the beneficial effect of chemoprophylaxis for pediatric contacts of MDR-TB.