bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B virus genome replication triggers toll-like receptor 3-dependent interferon responses in the absence of hepatitis B surface antigen
Authors: Real Catherine Isabell , Lu Mengji , Liu Jia , Huang Xuan , Trippler Martin , Hossbach Markus , Deckert Jochen , Jahn-Hofmann Kerstin , Ickenstein Ludger Markus , John Matthias Johannes , Gibbert Kathrin , Dittmer Ulf , Vornlocher Hans-Peter , Schirmbeck Reinhold , Gerken Guido , Schlaak Joerg Friedrich , Broering Ruth 
Published: April 2016

AbstractThe hepatitis B virus (HBV) has been described as stealth virus subverting immune responses initially upon infection. Impaired toll-like receptor signaling by the HBV surface antigen (HBsAg) attenuates immune responses to facilitate chronic infection. This implies that HBV replication may trigger host innate immune responses in the absence of HBsAg. Here we tested this hypothesis, using highly replicative transgenic mouse models. An HBV replication-dependent expression of antiviral genes was exclusively induced in HBsAg-deficient mice. These interferon responses attributed to toll-like receptor 3 (TLR3)-activated Kupffer and liver sinusoidal endothelial cells and further controlled the HBV genome replication. However, activation of TLR3 with exogenous ligands indicated additional HBs-independent immune evasion events. Our data demonstrate that in the absence of HBsAg, hepatic HBV replication leads to Tlr3-dependent interferon responses in non-parenchymal liver cells. We hypothesize that HBsAg is a major HBV-mediated evasion mechanism controlling endogenous antiviral responses in the liver. Eradication of HBsAg as a therapeutic goal might facilitate the induction of endogenous antiviral immune responses in patients chronically infected with HBV.
MicroRNA-223 Attenuates Hypoxia-induced Vascular Remodeling by Targeting RhoB/MLC2 in Pulmonary Arterial Smooth Muscle Cells
Authors: Zeng Yan , Zhang Xiaoying , Kang Kang , Chen Jidong , Wu Zhiqin , Huang Jinyong , Lu Wenju , Chen Yuqin , Zhang Jie , Wang Zhiwei , Zhai Yujia , Qu Junle , Ramchandran Ramaswamy , Raj J. Usha , Wang Jian , Gou Deming 
Published: April 2016

AbstractThere is growing evidence that microRNAs are implicated in pulmonary arterial hypertension (PAH), but underlying mechanisms remain elusive. Here, we identified that miR-223 was significantly downregulated in chronically hypoxic mouse and rat lungs, as well as in pulmonary artery and pulmonary artery smooth muscle cells (PASMC) exposed to hypoxia. Knockdown of miR-223 increased PASMC proliferation. In contrast, miR-223 overexpression abrogated cell proliferation, migration and stress fiber formation. Administering miR-223 agomir in vivo antagonized hypoxia-induced increase in pulmonary artery pressure and distal arteriole muscularization. RhoB, which was increased by hypoxia, was identified as one of the targets of miR-223. Overexpressed miR-223 suppressed RhoB and inhibited the consequent phosphorylation of myosin phosphatase target subunit (MYPT1) and the expression of myosin light chain of myosin II (MLC2), which was identified as another target of miR-223. Furthermore, serum miR-223 levels were decreased in female patients with PAH associated with congenital heart disease. Our study provides the first evidence that miR-223 can regulate PASMC proliferation, migration and actomyosin reorganization through its novel targets, RhoB and MLC2, resulting in vascular remodeling and the development of PAH. It also highlights miR-223 as a potential circulating biomarker and a small molecule drug for diagnosis and treatment of PAH.
A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process
Authors: An Fan , Qu Yueyang , Luo Yong , Fang Ning , Liu Yang , Gao Zhigang , Zhao Weijie , Lin Bingcheng 
Published: April 2016

AbstractNew techniques are urgently needed to replace conventional long and costly pre-clinical testing in the new drug administration process. In this study, a laminated microfluidic device was fabricated to mimic the drug ADME response test in vivo. This proposed device was loaded and cultured with functional cells for drug response investigation and organ tissues that are involved in ADME testing. The drug was introduced from the top of the device and first absorbed by the Caco-2 cell layer and then metabolized by the primary hepatocyte layer. It subsequently interacted with the MCF-7 cell layer, distributed in the lung, heart and fat tissues and was finally eliminated through the dialysis membrane. Throughout this on-chip ADME process, the proposed device can be used as a reliable tool to simultaneously evaluate the drug anti-tumor activity, hepatotoxicity and pharmacokinetics. Furthermore, this device was proven to be able to reflect the hepatic metabolism of a drug, drug distribution in the target tissues and the administration method of a drug. Furthermore, this microdevice is expected to reduce the number of drug candidates and accelerate the pre-clinical testing process subject to animal testing upon adaptation in new drug discovery.
Whispering galleries and the control of artificial atoms
Authors: Forrester Derek Michael , Kusmartsev Feodor V. 
Published: April 2016

AbstractQuantum computation using artificial-atoms, such as novel superconducting circuits, can be sensitively controlled by external electromagnetic fields. These fields and the self-fields attributable to the coupled artificial-atoms influence the amount of quantum correlation in the system. However, control elements that can operate without complete destruction of the entanglement of the quantum-bits are difficult to engineer. Here we investigate the possibility of using closely-spaced-linear arrays of metallic-elliptical discs as whispering gallery waveguides to control artificial-atoms. The discs confine and guide radiation through the array with small notches etched into their sides that act as scatterers. We focus on π-ring artificial-atoms, which can generate their own spontaneous fluxes. We find that the micro-discs of the waveguides can be excited by terahertz frequency fields to exhibit whispering-modes and that a quantum-phase-gate composed of π-rings can be operated under their influence. Furthermore, we gauge the level of entanglement through the concurrence measure and show that under certain magnetic conditions a series of entanglement sudden-deaths and revivals occur between the two qubits. This is important for understanding the stability and life-time of qubit operations using, for example, a phase gate in a hybrid of quantum technologies composed of control elements and artificial-atoms.
Dynamics of histone H2A, H4 and HS1ph during spermatogenesis with a focus on chromatin condensation and maturity of spermatozoa
Authors: Zhang Zhao-Hui , Mu Shu-Mei , Guo Ming-Shen , Wu Jiang-li , Li Yan-qin , Zhang Han , Wang Ying , Kang Xian-Jiang 
Published: April 2016

AbstractHistones and histone phosphorylation play vital roles during animal spermatogenesis and spermatozoa maturation. The dynamic distribution of histones H2A and H4 and phosphorylated H2A and H4 at serine 1 (HS1ph) was explored in mammalian and Decapoda germ cells, with a special focus on the distribution of H2A, H4 and HS1ph between mouse condensed spermatozoa chromatin and crab non-condensed spermatozoa chromatin. The distribution of histone marks was also analysed in mature spermatozoa with different chromatin structures. Histone H2A and H4 marks were closely associated with the relatively loose chromatin structure in crab spermatozoa. The significant decrease in the HS1ph signal during spermatogenesis suggests that eliminating most of these epigenetic marks in the nucleusis closely associated with spermatozoa maturity.
The orphan nuclear receptor NR4A2 is part of a p53–microRNA-34 network
Authors: Beard Jordan A. , Tenga Alexa , Hills Justin , Hoyer Jessica D. , Cherian Milu T. , Wang Yong-Dong , Chen Taosheng 
Published: April 2016

AbstractNuclear receptor subfamily 4 group A member 2 (NR4A2) is an orphan nuclear receptor that is over-expressed in cancer and promotes cell proliferation, migration, transformation and chemoresistance. Increased expression and function of NR4A2 have been attributed to various signaling pathways, but little is known about microRNA (miRNA) regulation of NR4A2 in cancer. To investigate the posttranscriptional regulation of NR4A2, we used a 3′ untranslated region (UTR) reporter screen and identified miR-34 as a putative regulator of NR4A2. By using computer predictions, we identified and confirmed an miRNA recognition element in the 3′ UTR of NR4A2 that was responsible for miR-34–mediated suppression. We next demonstrated that overexpression of exogenous miR-34 or activation of the p53 pathway, which regulates endogenous miR-34 expression, decreased NR4A2 expression. Consistent with previous reports, overexpression of NR4A2 blocked the induction of p53 target genes, including mir-34a. This was a phenotypic effect, as NR4A2 overexpression could rescue cells from p53-induced inhibition of proliferation. In summary, our results are the first characterization of a cancer-related miRNA capable of regulating NR4A2 and suggest a network and possible feedback mechanism involving p53, miR-34 and NR4A2.
Detection and quantification of water-based aerosols using active open-path FTIR
Authors: Kira Oz , Linker Raphael , Dubowski Yael 
Published: April 2016

AbstractAerosols have a leading role in many eco-systems and knowledge of their properties is critical for many applications. This study suggests using active Open-Path Fourier Transform Infra-Red (OP-FTIR) spectroscopy for quantifying water droplets and solutes load in the atmosphere. The OP-FTIR was used to measure water droplets, with and without solutes, in a 20 m spray tunnel. Three sets of spraying experiments generated different hydrosols clouds: (1) tap water only, (2) aqueous ammonium sulfate (0.25–3.6%wt) and (3) aqueous ethylene glycol (0.47–2.38%wt). Experiment (1) yielded a linear relationship between the shift of the extinction spectrum baseline and the water load in the line-of-sight (LOS) (R2 = 0.984). Experiment (2) also yielded a linear relationship between the integrated extinction in the range of 880–1150 cm−1 and the ammonium sulfate load in the LOS (R2 = 0.972). For the semi-volatile ethylene glycol (experiment 3), present in the gas and condense phases, quantification was much more complex and two spectral approaches were developed: (1) according to the linear relationship from the first experiment (determination error of 8%) and (2) inverse modeling (determination error of 57%). This work demonstrates the potential of the OP-FTIR for detecting clouds of water-based aerosols and for quantifying water droplets and solutes at relatively low concentrations.
Low protein diets produce divergent effects on energy balance
Authors: Pezeshki Adel , Zapata Rizaldy C. , Singh Arashdeep , Yee Nicholas J. , Chelikani Prasanth K. 
Published: April 2016

AbstractDiets deficient in protein often increase food consumption, body weight and fat mass; however, the underlying mechanisms remain poorly understood. We compared the effects of diets varying in protein concentrations on energy balance in obesity-prone rats. We demonstrate that protein-free (0% protein calories) diets decreased energy intake and increased energy expenditure, very low protein (5% protein) diets increased energy intake and expenditure, whereas moderately low protein (10% protein) diets increased energy intake without altering expenditure, relative to control diet (15% protein). These diet-induced alterations in energy expenditure are in part mediated through enhanced serotonergic and β-adrenergic signaling coupled with upregulation of key thermogenic markers in brown fat and skeletal muscle. The protein-free and very low protein diets decreased plasma concentrations of multiple essential amino acids, anorexigenic and metabolic hormones, but these diets increased the tissue expression and plasma concentrations of fibroblast growth factor-21. Protein-free and very low protein diets induced fatty liver, reduced energy digestibility, and decreased lean mass and body weight that persisted beyond the restriction period. In contrast, moderately low protein diets promoted gain in body weight and adiposity following the period of protein restriction. Together, our findings demonstrate that low protein diets produce divergent effects on energy balance.
Extending the duration of hypothermia does not further improve white matter protection after ischemia in term-equivalent fetal sheep
Authors: Davidson Joanne O. , Yuill Caroline A. , Zhang Frank G. , Wassink Guido , Bennet Laura , Gunn Alistair J. 
Published: April 2016

AbstractA major challenge in modern neonatal care is to further improve outcomes after therapeutic hypothermia for hypoxic ischemic encephalopathy. In this study we tested whether extending the duration of cooling might reduce white matter damage. Term-equivalent fetal sheep (0.85 gestation) received either sham ischemia followed by normothermia (n = 8) or 30 minutes of bilateral carotid artery occlusion followed by three days of normothermia (n = 8), three days of hypothermia (n = 8) or five days of hypothermia (n = 8) started three hours after ischemia. Histology was assessed 7 days after ischemia. Ischemia was associated with loss of myelin basic protein (MBP) and Olig-2 positive oligodendrocytes and increased Iba-1-positive microglia compared to sham controls (p < 0.05). Three days and five days of hypothermia were associated with a similar, partial improvement in MBP and numbers of oligodendrocytes compared to ischemia-normothermia (p < 0.05). Both hypothermia groups had reduced microglial activation compared to ischemia-normothermia (p < 0.05). In the ischemia-five-day hypothermia group, but not ischemia-three-day, numbers of microglia remained higher than in sham controls (p < 0.05). In conclusion, delayed cerebral hypothermia partially protected white matter after global cerebral ischemia in fetal sheep. Extending cooling from 3 to 5 days did not further improve outcomes, and may be associated with greater numbers of residual microglia.
Sustainable Sulfur-rich Copolymer/Graphene Composite as Lithium-Sulfur Battery Cathode with Excellent Electrochemical Performance
Authors: Ghosh Arnab , Shukla Swapnil , Khosla Gaganpreet Singh , Lochab Bimlesh , Mitra Sagar 
Published: April 2016

AbstractA sulfur-rich copolymer, poly(S-r-C-a) has been synthesized via a sustainable route, showing the utility of two major industrial wastes- elemental sulfur (petroleum waste) and cardanol (agro waste), to explore its potential as cathode material for Li-S batteries. The sulfur-rich copolymer exhibited a reduction in the active material dissolution into the electrolyte and a low self-discharge rate behavior during the rest time compared to an elemental sulfur cathode, indicating the chemical confinement of sulfur units. The presence of organosulfur moieties in copolymer suppress the irreversible deposition of end-discharge products on electrode surfaces and thus improve the electrochemical performances of Li-S batteries. This sulfur copolymer offered a reversible capacity of 892 mA h g−1 at 2nd cycle and maintained the capacity of 528 mA h g−1 after 50 cycles at 200 mA g−1. Reduced graphene oxide (rGO) prepared via a sustainable route was used as a conductive filler to extract the better electrochemical performances from this sulfur copolymer. Such sustainable origin batteries prepared via economically viable showed an improved specific capacity of ~975 mA h g−1 after 100 cycles at 200 mA g−1 current rate with capacity fading of 0.15% per cycle and maintained a stable performance over 500 cycles at 2000 mA g−1.
Barrier Modification of Metal-contact on Silicon by Sub-2 nm Platinum Nanoparticles and Thin Dielectrics
Authors: Zheng Haisheng , Mahajan Bikram K. , Su Sheng C. , Mukherjee Somik , Gangopadhyay Keshab , Gangopadhyay Shubhra 
Published: April 2016

AbstractWe report metal/p-Si contact barrier modification through the introduction of either “isolated” or “nonisolated” tilted-target-sputtered sub-2 nm platinum nanoparticles (Pt NPs) in combination with either a 0.98 nm Atomic Layer Deposited Al2O3 or a 1.6 nm chemically grown SiO2 dielectric layer, or both. Here, we study the role of these Pt NP’s size dependent properties, i.e., the Pt NP-metal surface dipole, the Coulomb blockade and quantum confinement effect in determining the degree of Fermi level depinning observed at the studied metal/p-Si interfaces. By varying only the embedded Pt NP size and its areal density, the nature of the contact can also be modulated to be either Schottky or Ohmic upon utilizing the same gate metal. 0.74 nm Pt NPs with an areal density of 1.1 × 1013 cm−2 show ~382 times higher current densities compared to the control sample embedded with similarly sized Pt NPs with ~1.6 times lower areal densities. We further demonstrate that both Schottky (Ti/p-Si) and poor Ohmic (Au/p-Si) contact can be modulated into a good Ohmic contact with current density of 18.7 ± 0.6 A/cm2 and 10.4 ± 0.4 A/cm2, respectively, showing ~18 and ~30 times improvement. A perfect forward/reverse current ratio of 1.041 is achieved for these low doped p-Si samples.
A new hand-held optical reflectometer to measure enamel erosion: correlation with surface hardness and calcium release
Authors: Carvalho Thiago Saads , Baumann Tommy , Lussi Adrian 
Published: April 2016

AbstractIn the present study, the surface reflection intensity (SRI) was measured from enamel with different induced erosion degrees using a hand-held pen-size reflectometer (Hand-Held) and a Table-Top reflectometer. To validate the Hand-Held reflectometer, we correlated its optical signals with the change of surface microhardness (SMH) and amount of calcium released from the enamel samples during erosion. We used 124 tooth enamel specimens that were exposed to an erosive challenge of either 1, 2, 4, 6, 8, or 10 minutes. SRI and SMH were measured before and after the erosive challenge and we also measured the amount of calcium released to the citric acid. Relative SRI loss (rSRIloss) and relative SMH loss (rSMHloss) were calculated. rSRIloss from the Hand-Held and the Table-Top reflectometers were similar and significantly correlated to rSMHloss and calcium release. The regression analyses showed a significant association between rSRIloss from both reflectometers and rSMHloss and calcium, showing that both reflectometers can be used to measure erosive demineralization of enamel. The Hand-Held reflectometer is capable of assessing in vitro erosion, correlating to other commonly used methods. It is small, easy to handle and provides fast measurement, being a possible candidate to measure erosion in clinical studies.
Factors associated with graft survival and endothelial cell density after Descemet’s stripping automated endothelial keratoplasty
Authors: Ishii Nobuhito , Yamaguchi Takefumi , Yazu Hiroyuki , Satake Yoshiyuki , Yoshida Akitoshi , Shimazaki Jun 
Published: April 2016

AbstractPostoperative endothelial cell loss leads to graft failure after corneal transplantation, and is one of the important issues for long-term prognosis. The objective of this study was to identify clinical factors affecting graft survival and postoperative endothelial cell density (ECD) after Descemet’s stripping automated endothelial keratoplasty (DSAEK). A total of 198 consecutive Japanese patients (225 eyes) who underwent DSAEK were analysed using Cox proportional hazard regression and multiple linear regression models. The candidate factors included recipient age; gender; diagnosis; pre-existing iris damage state, scored based on its severity; the number of previous intraocular surgeries; graft ECD; graft diameter; simultaneous cataract surgery; surgeons experience; intraoperative iris damage; postoperative rebubbling; and graft rejection. Eyes with higher pre-existing iris damage score and more number of previous intraocular surgery had a significantly higher risk of graft failure (HR = 8.53; P < 0.0001, and HR = 2.66; P = 0.026, respectively). Higher pre-existing iris damage score, lower graft ECD, and smaller graft diameter were identified as significant predisposing factors for lower postoperative ECD. The results show that iris damage status before DSAEK may be clinically useful in predicting the postoperative course. Avoiding intraoperative iris damage, especially in eyes with low ECD can change the prognosis of future DSAEK.
Monolithic nanoporous copper fabricated through decomposition and sintering of oxalate
Authors: Li Bing , Li Mingyu , Zeng Qingxuan , Wu Xingyu 
Published: April 2016

Two more simple methods were used for preparation of the monolithic nanoporous copper. One was that through decomposition and sintering of copper oxalate precipitate directly. The other was that through decomposition and sintering of copper oxalate and manganese oxalate. The effects of sintered temperature and holding time on the morphology of the monolithic nanoporous copper were investigated. Thermal decomposition, composition and morphology of copper oxalate precipitate, as well as microscopic morphology and specific surface area of the monolithic nanoporous copper were analysed by thermogravimetric analysis, X‐ray diffraction, scanning electron microscope and nitrogen adsorption–desorption. The preferable nanoporous copper can be prepared by decomposition and sintering of copper oxalate directly at 400°C for 30 min. The prepared monolithic nanoporous copper is of open and interconnected pores and is made up of copper grains with the size of about 100 nm, which is as high as 69.9 m2 g−1 in specific surface area.
The reversal test, status quo bias, and opposition to human cognitive enhancement
Authors: Clarke Steve 
Published: April 2016

AbstractBostrom and Ord’s reversal test has been appealed to by many philosophers to substantiate the charge that preferences for status quo options are motivated by status quo bias. I argue that their characterization of the reversal test needs to be modified, and that their description of the burden of proof it imposes needs to be clarified. I then argue that there is a way to meet that burden of proof which Bostrom and Ord fail to recognize. I also argue that the range of circumstances in which the reversal test can be usefully applied is narrower than they recognize.
Coordinated process of polarized growth in filamentous fungi
Authors: Takeshita Norio 
Published: April 2016

AbstractFilamentous fungi are extremely polarized organisms, exhibiting continuous growth at their hyphal tips. The hyphal form is related to their pathogenicity in animals and plants, and their high secretion ability for biotechnology. Polarized growth requires a sequential supply of proteins and lipids to the hyphal tip. This transport is managed by vesicle trafficking via the actin and microtubule cytoskeleton. Therefore, the arrangement of the cytoskeleton is a crucial step to establish and maintain the cell polarity. This review summarizes recent findings unraveling the mechanism of polarized growth with special emphasis on the role of actin and microtubule cytoskeleton and polarity marker proteins. Rapid insertions of membranes via highly active exocytosis at hyphal tips could quickly dilute the accumulated polarity marker proteins. Recent findings by a super-resolution microscopy indicate that filamentous fungal cells maintain their polarity at the tips by repeating transient assembly and disassembly of polarity sites.
Cutaneous malignancy
Authors: Fowell Christopher , Rehman Khaleeq-Ur 
Published: April 2016

Abstract
Cutaneous malignancy is on the rise in the UK with over 100,000 new cases per year. Currently there are very clear guidelines for the multidisciplinary team to manage this group of diseases. We present three case histories covering morphoeic basal cell carcinoma, lentigo maligna melanoma, and a squamous cell carcinoma of the scalp. The management of all these cases involves surgery at some point but the non-surgical management of cutaneous malignancy is comprehensively covered. The current British Association of Dermatologists Guidelines on the management of skin cancer are discussed in reference to these cases.