bluuebunny/crossref_metadata_2025_split huggingface dataset:
μ Opioid receptor: novel antagonists and structural modeling
Authors: Kaserer Teresa , Lantero Aquilino , Schmidhammer Helmut , Spetea Mariana , Schuster Daniela 
Published: February 2016

AbstractThe μ opioid receptor (MOR) is a prominent member of the G protein-coupled receptor family and the molecular target of morphine and other opioid drugs. Despite the long tradition of MOR-targeting drugs, still little is known about the ligand-receptor interactions and structure-function relationships underlying the distinct biological effects upon receptor activation or inhibition. With the resolved crystal structure of the β-funaltrexamine-MOR complex, we aimed at the discovery of novel agonists and antagonists using virtual screening tools, i.e. docking, pharmacophore- and shape-based modeling. We suggest important molecular interactions, which active molecules share and distinguish agonists and antagonists. These results allowed for the generation of theoretically validated in silico workflows that were employed for prospective virtual screening. Out of 18 virtual hits evaluated in in vitro pharmacological assays, three displayed antagonist activity and the most active compound significantly inhibited morphine-induced antinociception. The new identified chemotypes hold promise for further development into neurochemical tools for studying the MOR or as potential therapeutic lead candidates.
Chronic consumption of a western diet induces robust glial activation in aging mice and in a mouse model of Alzheimer’s disease
Authors: Graham Leah C. , Harder Jeffrey M. , Soto Ileana , de Vries Wilhelmine N. , John Simon W. M. , Howell Gareth R. 
Published: February 2016

AbstractStudies have assessed individual components of a western diet, but no study has assessed the long-term, cumulative effects of a western diet on aging and Alzheimer’s disease (AD). Therefore, we have formulated the first western-style diet that mimics the fat, carbohydrate, protein, vitamin and mineral levels of western diets. This diet was fed to aging C57BL/6J (B6) mice to identify phenotypes that may increase susceptibility to AD, and to APP/PS1 mice, a mouse model of AD, to determine the effects of the diet in AD. Astrocytosis and microglia/monocyte activation were dramatically increased in response to diet and was further increased in APP/PS1 mice fed the western diet. This increase in glial responses was associated with increased plaque burden in the hippocampus. Interestingly, given recent studies highlighting the importance of TREM2 in microglia/monocytes in AD susceptibility and progression, B6 and APP/PS1 mice fed the western diet showed significant increases TREM2+ microglia/monocytes. Therefore, an increase in TREM2+ microglia/monocytes may underlie the increased risk from a western diet to age-related neurodegenerative diseases such as Alzheimer’s disease. This study lays the foundation to fully investigate the impact of a western diet on glial responses in aging and Alzheimer’s disease.
Human Vascular Microphysiological System for in vitro Drug Screening
Authors: Fernandez C. E. , Yen R. W. , Perez S. M. , Bedell H. W. , Povsic T. J. , Reichert W. M. , Truskey G. A. 
Published: February 2016

AbstractIn vitro human tissue engineered human blood vessels (TEBV) that exhibit vasoactivity can be used to test human toxicity of pharmaceutical drug candidates prior to pre-clinical animal studies. TEBVs with 400–800 μM diameters were made by embedding human neonatal dermal fibroblasts or human bone marrow-derived mesenchymal stem cells in dense collagen gel. TEBVs were mechanically strong enough to allow endothelialization and perfusion at physiological shear stresses within 3 hours after fabrication. After 1 week of perfusion, TEBVs exhibited endothelial release of nitric oxide, phenylephrine-induced vasoconstriction and acetylcholine-induced vasodilation, all of which were maintained up to 5 weeks in culture. Vasodilation was blocked with the addition of the nitric oxide synthase inhibitor L-NG-Nitroarginine methyl ester (L-NAME). TEBVs elicited reversible activation to acute inflammatory stimulation by TNF-α which had a transient effect upon acetylcholine-induced relaxation and exhibited dose-dependent vasodilation in response to caffeine and theophylline. Treatment of TEBVs with 1 μM lovastatin for three days prior to addition of Tumor necrosis factor – α (TNF-α) blocked the injury response and maintained vasodilation. These results indicate the potential to develop a rapidly-producible, endothelialized TEBV for microphysiological systems capable of producing physiological responses to both pharmaceutical and immunological stimuli.
Long Noncoding RNA LOC100129973 Suppresses Apoptosis by Targeting miR-4707-5p and miR-4767 in Vascular Endothelial Cells
Authors: Lu Wei , Huang Shu Ya , Su Le , Zhao Bao Xiang , Miao Jun Ying 
Published: February 2016

AbstractAccumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are key regulators of multiple biological processes by altering gene expression at various levels. Apoptosis in vascular endothelial cells (VECs) is closely linked to numerous cardiovascular diseases, such as arteriosclerosis, thrombus formation and plaque erosion. However, studies on lncRNAs in the cardiovascular system are just beginning. And thus far, no anti-apoptosis lncRNAs have been identified in VECs. Here, we focused on the anti-apoptosis roles of lncRNAs in the serum and FGF-2 starvation-induced apoptosis of VECs. Using microarray analysis, we found a novel lncRNA LOC100129973 which acted as an apoptosis inhibitor in VECs. Through sponging miR-4707-5p and miR-4767, lncRNA LOC100129973 upregulated the expression of two apoptosis repressors gene, Apoptosis Inhibitor 5 (API5) and BCL2 like 12 (BCL2L12) and thus alleviated the serum and FGF-2 starvation-induced apoptosis in VECs. This evidence suggests that lncRNA LOC100129973 is an attractive target to improve endothelial function and for therapy of apoptosis related cardiovascular diseases.
BIRC3 is a novel driver of therapeutic resistance in Glioblastoma
Authors: Wang Dapeng , Berglund Anders , Kenchappa Rajappa S. , Forsyth Peter A. , Mulé James J. , Etame Arnold B. 
Published: February 2016

AbstractGenome-wide analysis of glioblastoma (GBM) reveals pervasive aberrations in apoptotic signaling pathways that collectively contribute to therapeutic resistance. Inhibitors of apoptosis proteins (IAP) exert critical control on the terminal segment of apoptosis leading to apoptosis evasion. In this study, we uncover a unique role for BIRC3, as an IAP that is critical in GBM in response to therapy. Using the TCGA dataset of 524 unique samples, we identify BIRC3 is the only IAP whose differential expression is associated with long-term survival in GBM patients. Using patient tissue samples we further show that BIRC3 expression increases with recurrence. When extrapolated to a preclinical model of a human GBM cell line, we find an increase in BIRC3 expression in response to irradiation (RT) and temozolomide (TMZ) treatment. More importantly, we mechanistically implicate STAT3 and PI3K signaling pathways as drivers of RT-induced up-regulation of BIRC3 expression. Lastly, we demonstrate that both in-vivo and in-vitro BIRC3 up-regulation results in apoptosis evasion and therapeutic resistance in GBM. Collectively, our study identifies a novel translational and targetable role for BIRC3 expression as a predictor of aggressiveness and therapeutic resistance to TMZ and RT mediated by STAT3 and PI3K signaling in GBM.
Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways
Authors: Yu Yingli , Sun Guibo , Luo Yun , Wang Min , Chen Rongchang , Zhang Jingyi , Ai Qidi , Xing Na , Sun Xiaobo 
Published: February 2016

AbstractBackground: Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases. Objective: We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro. Methods: H9c2 cadiomyocytes were incubated with NGR1 for 24 h and exposed to hypoxia/reoxygenation. Isolated rat hearts were perfused by NGR1 for 15 min and then subjected to global ischemia/reperfusion. Hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase and decrease of left ventricular pressure (±dP/dt max/min). Results: NGR1 pretreatment prevents cell apoptosis and delays the onset of ERS by decreasing the protein expression levels of ERS-responsive proteins GRP78, P-PERK, ATF6, IRE, and inhibiting the expression of pro-apoptosis proteins CHOP, Caspase-12, and P-JNK. Besides, NGR1 scavenges free radical, and increases the activity of antioxidase. NGR1 inhibits Tunicamycin-induced cell death and cardic dysfunction. Conclusion: We elucidated the significant cardioprotective effects of NGR1 against I/R injuries, and demonstrated the involvement of oxidative stress and ERS in the protective effects of NGR1.
Extremely Low Frequency Electromagnetic Fields Facilitate Vesicle Endocytosis by Increasing Presynaptic Calcium Channel Expression at a Central Synapse
Authors: Sun Zhi-cheng , Ge Jian-long , Guo Bin , Guo Jun , Hao Mei , Wu Yi-chen , Lin Yi-an , La Ting , Yao Pan-tong , Mei Yan-ai , Feng Yi , Xue Lei 
Published: February 2016

AbstractAccumulating evidence suggests significant biological effects caused by extremely low frequency electromagnetic fields (ELF-EMF). Although exo-endocytosis plays crucial physical and biological roles in neuronal communication, studies on how ELF-EMF regulates this process are scarce. By directly measuring calcium currents and membrane capacitance at a large mammalian central nervous synapse, the calyx of Held, we report for the first time that ELF-EMF critically affects synaptic transmission and plasticity. Exposure to ELF-EMF for 8 to 10 days dramatically increases the calcium influx upon stimulation and facilitates all forms of vesicle endocytosis, including slow and rapid endocytosis, endocytosis overshoot and bulk endocytosis, but does not affect the RRP size and exocytosis. Exposure to ELF-EMF also potentiates PTP, a form of short-term plasticity, increasing its peak amplitude without impacting its time course. We further investigated the underlying mechanisms and found that calcium channel expression, including the P/Q, N, and R subtypes, at the presynaptic nerve terminal was enhanced, accounting for the increased calcium influx upon stimulation. Thus, we conclude that exposure to ELF-EMF facilitates vesicle endocytosis and synaptic plasticity in a calcium-dependent manner by increasing calcium channel expression at the nerve terminal.
Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis
Authors: Liśkiewicz Arkadiusz D. , Kasprowska Daniela , Wojakowska Anna , Polański Krzysztof , Lewin–Kowalik Joanna , Kotulska Katarzyna , Jędrzejowska–Szypułka Halina 
Published: February 2016

AbstractNutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/−) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.
Compact all‐metallic cavity‐cascaded antenna
Authors: Chang Le , Li Yue , Zhang Zhijun , Feng Zhenghe 
Published: February 2016

A compact all‐metallic cavity‐cascaded antenna is presented. A two‐end‐shorted metallic plate is shorted and divided averagely by five identical shorting walls alternatively, forming five alternatively cascaded open cavities. By selecting proper width of the metallic plate and length of the shorting walls, all the five open cavities operate in the TM1n0 (n = 0.5) mode, generating five fringing fields with the same phase. Thus, effective radiation is achieved. The proposed antenna is operated in the 5‐order mode, e.g. five standing waves are distributed along the proposed antenna. It only occupies a volume of 0.43λ0 × 2.83λ0 (λ0 is the wavelength of the centre frequency). Moreover, the proposed antenna is fabricated by all metal, resulting in low cost, light weight, wide bandwidth, high gain and high efficiency. A prototype that can provide an overlapped impedance bandwidth and 3 dB gain bandwidth of 7.72% from 8.10 to 8.75 GHz and a peak gain of 13.37 dBi at 8.5 GHz is built and measured.
Design considerations on wideband envelope termination for high efficiency RF power amplifiers
Authors: Chung S. , Ma R. , Teo K.H. 
Published: February 2016

Design approach of wideband envelope termination (ET) for high efficiency RF power amplifiers (PAs) is discussed, considering power loss subject to design constraints including envelope bandwidth, inductor quality factor, and transistor output impedance. Analysis shows that the optimum ET topology depends on the design constraints. For LTE‐advanced transmission with 80 MHz channel bandwidth, a novel wideband ET is designed using an AC‐terminated third‐order LC filter (LCF‐ET), providing 3 dB envelope impedance bandwidth of 150 MHz. Measured results demonstrate 1.75 dB envelope power loss and −39.2 dB normalised root‐mean‐square error with the LTE envelope signals. For the LTE signal with 10.3 dB peak‐to‐average power ratio, the average power efficiency of an ideal Class‐A RF PA with the LCF‐ET prototype is calculated as 33.4% from the measured 1.75 dB envelope power loss, which exceeds 4.7% and 24.0% average power efficiency of conventional Class‐A and Class‐B PAs without ET.
High‐efficiency duty‐cycle controlled full‐bridge converter for ultracapacitor chargers
Authors: Woo‐Young Choi 
Published: February 2016

This study proposes a high‐efficiency duty‐cycle controlled full‐bridge dc–dc converter for ultracapacitor chargers. By the asymmetric duty‐cycle control, the proposed converter achieves zero‐voltage switching of power switches without circulating currents. It reduces the output current ripple by the current‐doubler rectifier. A control strategy is suggested for charging ultracapacitors. A constant current and constant voltage charging is performed. The proposed converter achieves a higher efficiency compared with the conventional phase‐shift controlled full‐bridge converter. The performance of the proposed converter is evaluated by experimental results for a 30 F ultracapacitor bank.
Output power stabilisation of wireless power transfer system with multiple transmitters
Authors: Tan Linlin , Guo Jinpeng , Huang Xueliang , Wen Feng 
Published: February 2016

Wireless power transfer via strongly coupled magnetic resonance is an effective and convenient technology to transfer energy. The output power splitting in close distances and monotonic decay of the output power in longer distances exist when it comes to single‐transmitter case. For the sake of more stable output power in a broader space, the authors proposed a novel wireless power system with multiple transmitters. Further analysis of features of both single‐transmitter and multiple‐transmitter systems was presented with the adoption of MATLAB and High‐Frequency Structure Simulator. The authors demonstrated the superiority of the multiple‐transmitter system and then investigated the impact of transmitter spacing on output power. To stabilise the output power as much as possible, an optimisation strategy is designed by setting transmitter spacing as decision variables and the minimum power variance as the target. The measurement shows that for a load demand of 5 W, a stable area with a standard deviation of 0.32 can be achieved when transmitters are placed 0.33 m apart. Both theoretical and simulation results make it possible to power the movable devices more stably.
Classification and separation of partial discharge ultra‐high‐frequency signals in a 252 kV gas insulated substation by using cumulative energy technique
Authors: Zhu Ming‐Xiao , Xue Jian‐Yi , Zhang Jia‐Ning , Li Yuan , Deng Jun‐Bo , Mu Hai‐Bao , Zhang Guan‐Jun , Shao Xian‐Jun , Liu Xiao‐Wei 
Published: February 2016

Ultra‐high‐frequency (UHF) method is regarded as an effective approach for partial discharge (PD) detection in gas insulated substation (GIS). The feature parameters representing UHF signal characteristics can be extracted from its waveform, and applied to PD source classification and mixed signals separation. In this study, an UHF signal feature extraction algorithm based on cumulative energy (CE) technique is proposed. The CE functions in time domain (TCE) and frequency domain (FCE) are calculated from UHF waveforms and their fast Fourier transform spectrums, respectively. The mathematical morphology gradient (MMG) operation is applied to TCE and FCE to characterise their rising behavior. The feature parameters including width, area and sharpness are extracted from CEs and MMGs in both time and frequency domain. Moreover, the extracted features are applied to UHF signals classification and mixed signals separation. First, experiments on four kinds of typical defects in a 252 kV GIS are performed, and the classification performance of the extracted features is examined with the acquired signals. Second, by clustering the extracted features with fuzzy maximum‐likelihood algorithm, mixed UHF signals originated from multiple PD sources are successfully separated. The results indicate that the proposed features are effective for representing UHF signal characteristics.
Quadrature identities for interlacing and orthogonal polynomials
Authors: Lubinsky D. 
Published: February 2016

Let

S
S

be a real polynomial of degree

n
n

with real simple zeros

{

x

j

}

j
=
1

n

\left \{ x_{j}\right \} _{j=1}^{n}

. Let

R
R

be a real polynomial of degree

n
−
1

n-1

whose zeros interlace those of

S
S

. We prove the quadrature identity

∫

−
∞

∞

P
(
t
)

S

2

(
t
)

h

(

R
S

(
t
)

)

d
t
=

(

∫

−
∞

∞

h

(
t
)

d
t
)

∑

j
=
1

n

P

(

x

j

)

(
R

S

′

)

(

x

j

)

,

\begin{equation*} \int _{-\infty }^{\infty }\frac {P(t)}{S^{2}\left ( t\right ) }h\left ( \frac {R}{S }\left ( t\right ) \right ) dt=\left ( \int _{-\infty }^{\infty }h\left ( t\right ) dt\right ) \sum _{j=1}^{n}\frac {P\left ( x_{j}\right ) }{\left ( RS^{\prime }\right ) \left ( x_{j}\right ) }, \end{equation*}

valid for all polynomials

P
P

of degree

≤
2
n
−
2

\leq 2n-2

and any

h
∈

L

1

(

R

)

h\in L_{1}\left ( \mathbb {R}\right )

. We deduce identities involving orthogonal polynomials and weak convergence results involving orthogonal polynomials.
A ring-like concentration of mm-sized particles in Sz 91
Authors: Canovas H. , Caceres C. , Schreiber M. R. , Hardy A. , Cieza L. , Ménard F. , Hales A. 
Published: February 2016

Abstract
Models of planet formation and disc evolution predict a variety of observables in the dust structure of protoplanetary discs. Here, we present Atacama Large Millimeter/submillimeter Array (ALMA) Band-6 and Band-7 observations of the transition disc Sz 91 showing that the continuum emission at 870 μm, which is dominated by emission from large dust grains, is localized in an optically thin narrow ring. We find that most of the emission (∼95 per cent) is concentrated in a ring located at 110 au from the central star that is only about 44 au wide. In contrast, the 12CO (2–1) emission peaks closer to the star and is detected up to ∼488 au from the star. The concentration of large grains in a ring-like structure while the gas disc extends much further in and further out is in qualitative agreement with predictions of hydrodynamical models of planet–disc interactions including radial drift and gas drag.
Does Magnesium Sulfate as an Adjuvant of Local Anesthetics Facilitate Better Effect of Perineural Nerve Blocks?
Authors: Li Mengzhu , Jin Shuqing , Zhao Xiang , Xu Zhendong , Ni Xiu , Zhang Lingling , Liu Zhiqiang 
Published: February 2016

Objectives:
To investigate the efficacy and safety of magnesium sulfate as an adjuvant of local anesthetics in perineural nerve blocks.

Materials and Methods:
Randomized controlled trials studying the effect and safety of magnesium sulfate in perineural nerve blocks were retrieved from online databases. The mean difference (MD), risk ratio, and their corresponding 95% confidence intervals (CIs) were calculated using RevMan 5.3 statistical software.

Results:
Seven trials evaluating 493 patients were included. The pooled results from our meta-analysis showed that a combination of magnesium sulfate and local anesthetics in nerve blocks could result in longer postoperative duration time of analgesia (MD=124.66; 95% CI, 65.09-184.23; P<0.0001), longer duration time of sensory (MD=106.69; 95% CI, 60.93-152.45; P<0.00001) and motor block (MD=89.95; 95% CI, 50.89-129.00; P<0.0001). In addition, magnesium sulfate in nerve blocks was also associated with significantly quick onset of motor block (MD=−1.17; 95% CI, −1.73 to −0.60; P<0.0001). For onset time of sensory block, number of patients requiring supplementary analgesics, and incidence of postoperative nausea and vomiting, no statistically differences were observed between the 2 groups.

Discussion:
The present study suggests that combined magnesium sulfate and local anesthetics in perineural nerve blocks provided better analgesic efficacy. For it prolongs the postoperative duration time of analgesia, sensory and motor block without increasing the short-term side effects. Magnesium sulfate may be a promising analgesic for perineural nerve blocks, but further studies are required to validate our results.