bluuebunny/crossref_metadata_2025 huggingface dataset:
Four Planetary Landscapes That Scientists Can’t Explain
Authors: Wendel JoAnna
Published: December 2017

These are just a handful of the hundreds of mysterious features across our solar neighborhood that beg to be studied closer.
Erratum: Telomere Length and Bipolar Disorder
Authors: Powell Timothy R , Dima Danai , Frangou Sophia , Breen Gerome
Published: December 2017

Correction to: Neuropsychopharmacology advance online publication, 26 July 2017; doi:10.1038/npp.2017.125 This article was originally published under NPG’s License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.
Effects of meal timing on changes in circulating epinephrine, norepinephrine, and acylated ghrelin concentrations: a pilot study
Authors: Bo Simona , Broglio Fabio , Settanni Fabio , Parasiliti Caprino Mirko , Ianniello Alice , Mengozzi Giulio , De Francesco Antonella , Fadda Maurizio , Fedele Debora , Guggino Alice , Ghigo Ezio , Maccario Mauro
Published: December 2017

Background

Timing of food intake impacts on metabolic diseases. Few data are available about post-meal changes in epinephrine (E), norepinephrine (NE), and acylated ghrelin (AG) at different times of the day.

Subjects and methods

This randomized cross-over trial investigated E/NE/AG concentrations after identical meals consumed at 0800 or 2000 hours in 20 healthy volunteers, by standardizing diet, exercise, duration of fast, and resting. Participants randomly received the test meal at 0800 or 2000 hours, and vice versa after 1 week. Blood samples were collected before and up to 180-min post-meal, every 30 min, with participants supine, motionless, but awake.

Results

Median E levels increased at 30–60 min, then declined and rose again at 150 min; values at 60 min (19.0 vs. 15.0 ng/l, p = 0.03) and 180 min (25.0 vs. 11.0 ng/l, p < 0.001) were higher after the morning meals. NE rose at 30–60 min and then progressively declined; median values at 60 min (235.3 vs. 206.3 ng/l, p = 0.02) and 120 min (208.8 vs. 142.0 ng/l, p = 0.04) increased more after morning meals. AG progressively declined to increase again at 90 min after meal; median AG area-under-the-curve (AUC) values were lower at morning (7206.8 vs. 8828.3 pg/mL×h). AG-AUC was inversely associated with diet-induced thermogenesis (β = −121.6; 95% CI −201.0 to 42.2; p = 0.009 for each unit increase), while log NE-AUC was inversely associated with log-triglyceride AUC (β = −0.57; 95% CI −0.98 to 0.16; p = 0.015) in a multiple regression model, after multiple adjustments.

Conclusions

In conclusion, E/NE concentrations were higher after the morning meal, while AG showed an opposite behavior. These data, although requiring confirmation in larger samples, suggest an adjunctive possible mechanism explaining the unfavorable effects of evening eating on metabolic risk
HRD1 prevents apoptosis in renal tubular epithelial cells by mediating eIF2α ubiquitylation and degradation
Authors: Huang Yujie , Sun Yifei , Cao Yizhi , Sun Hui , Li Min , You Hui , Su Dongming , Li Yanjiao , Liang Xiubin
Published: December 2017

Apoptosis of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. One factor that regulates important cellular processes like apoptosis and cell proliferation is HRD1, an E3 ubiquitin ligase that acts by promoting ubiquitylation and degradation of its target protein. However, the detailed mechanisms by which HRD1 acts as a regulator of apoptosis in renal tubular epithelial cells have not been established. In our previous liquid chromatography-tandem mass spectrometry (LC-MS/MS) study (Mol Endocrinol. 2016;30:600–613), we demonstrated that one substrate of HRD1 was eIF2α, a critical protein in the PERK-eIF2α-ATF4-CHOP signaling pathway of endoplasmic reticulum (ER) stress. Here, we show that eIF2α expression was increased and HRD1 expression decreased when apoptosis was induced in HKC-8 cells by palmitic acid (PA) or high glucose (HG). HRD1 expression was also lower in kidney tissues from mice with diabetic nephropathy (DN) than in control mice. Forced expression of HRD1 also inhibited apoptosis in HKC-8 cells, while HRD1 overexpression decreased the expression of phosphorylated eIF2α and eIF2α. Further analysis indicated that HRD1 interacted with eIF2α and promoted its ubiquitylation and degradation by the proteasome. Moreover, the HRD1 protection of PA-treated HKC-8 cells was blunted by transfection with Myc-eIF2α. Thus, eIF2α ubiquitylation by HRD1 protects tubular epithelial cells from apoptosis caused by HG and PA, indicating a novel upstream target for therapeutic prevention of renal tubulointerstitial injury.
CACUL1 reciprocally regulates SIRT1 and LSD1 to repress PPARγ and inhibit adipogenesis
Authors: Jang Min Jun , Park Ui-Hyun , Kim Jeong Woo , Choi Hanbyeul , Um Soo-Jong , Kim Eun-Joo
Published: December 2017

Peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation and is closely linked to the development of obesity. Despite great progress in elucidating the transcriptional network of PPARγ, epigenetic regulation of this pathway by histone modification remains elusive. Here, we found that CDK2-associated cullin 1 (CACUL1), identified as a novel SIRT1 interacting protein, directly bound to PPARγ through the co-repressor nuclear receptor (CoRNR) box 2 and repressed the transcriptional activity and adipogenic potential of PPARγ. Upon CACUL1 depletion, less SIRT1 and more LSD1 were recruited to the PPARγ-responsive gene promoter, leading to increased histone H3K9 acetylation, decreased H3K9 methylation, and PPARγ activation during adipogenesis in 3T3-L1 cells. These findings were reversed upon fasting or resveratrol treatment. Further, gene expression profiling using RNA sequencing supported the repressive role of CACUL1 in PPARγ activation and fat accumulation. Finally, we confirmed CACUL1 function in human adipose-derived stem cells. Overall, our data suggest that CACUL1 tightly regulates PPARγ signaling through the mutual opposition between SIRT1 and LSD1, providing insight into its potential use for anti-obesity treatment.
Longitudinal intravital imaging of the femoral bone marrow reveals plasticity within marrow vasculature
Authors: Reismann David , Stefanowski Jonathan , Günther Robert , Rakhymzhan Asylkhan , Matthys Romano , Nützi Reto , Zehentmeier Sandra , Schmidt-Bleek Katharina , Petkau Georg , Chang Hyun-Dong , Naundorf Sandra , Winter York , Melchers Fritz , Duda Georg , Hauser Anja E. , Niesner Raluca A.
Published: December 2017

The bone marrow is a central organ of the immune system, which hosts complex interactions of bone and immune compartments critical for hematopoiesis, immunological memory, and bone regeneration. Although these processes take place over months, most existing imaging techniques allow us to follow snapshots of only a few hours, at subcellular resolution. Here, we develop a microendoscopic multi-photon imaging approach called LIMB (longitudinal intravital imaging of the bone marrow) to analyze cellular dynamics within the deep marrow. The approach consists of a biocompatible plate surgically fixated to the mouse femur containing a gradient refractive index lens. This microendoscope allows highly resolved imaging, repeatedly at the same regions within marrow tissue, over months. LIMB reveals extensive vascular plasticity during bone healing and steady-state homeostasis. To our knowledge, this vascular plasticity is unique among mammalian tissues, and we expect this insight will decisively change our understanding of essential phenomena occurring within the bone marrow.
Frustration-driven C
4 symmetric order in a naturally-heterostructured superconductor Sr2VO3FeAs
Authors: Ok Jong Mok , Baek S.-H. , Hoch C. , Kremer R. K. , Park S. Y. , Ji Sungdae , Büchner B. , Park J.-H. , Hyun S. I. , Shim J. H. , Bang Yunkyu , Moon E. G. , Mazin I. I. , Kim Jun Sung
Published: December 2017

A subtle balance between competing interactions in iron-based superconductors (FeSCs) can be tipped by additional interfacial interactions in a heterostructure, often inducing exotic phases with unprecedented properties. Particularly when the proximity-coupled layer is magnetically active, rich phase diagrams are expected in FeSCs, but this has not been explored yet. Here, using high-accuracy 75As and 51V nuclear magnetic resonance measurements, we investigate an electronic phase that emerges in the FeAs layer below T0 ~ 155 K of Sr2VO3FeAs, a naturally assembled heterostructure of an FeSC and a Mott-insulating vanadium oxide. We find that frustration of the otherwise dominant Fe stripe and V Neel fluctuations via interfacial coupling induces a charge/orbital order in the FeAs layers, without either static magnetism or broken C4 symmetry, while suppressing the Neel antiferromagnetism in the SrVO3 layers. These findings demonstrate that the magnetic proximity coupling stabilizes a hidden order in FeSCs, which may also apply to other strongly correlated heterostructures.
Associations between self-rated health, sickness behaviour and inflammatory markers in primary care patients with allergic asthma: a longitudinal study
Authors: Lodin Karin , Lekander Mats , Syk Jörgen , Alving Kjell , Andreasson Anna
Published: December 2017

Allergic asthma is a chronic inflammatory disorder associated with elevated levels of immunoglobulin E (IgE), serum eosinophilic cationic protein (S-ECP), plasma eosinophil-derived neurotoxin (P-EDN) and fraction of exhaled nitric oxide (FENO). Poor self-rated health and sickness behaviour has repeatedly been associated with inflammatory markers, but the nature of this relationship in chronic inflammatory disease is not known. Likewise, such findings largely rely on cross-sectional investigations. Self-rated health (How would you rate your general state of health?), sickness behaviour (mean rating of satisfaction with energy, sleep, fitness, appetite and memory), IgE, S-ECP, P-EDN, and FENO were assessed in 181 non-smoking primary care patients with asthma in a 1-year longitudinal study. Associations between repeated measurements were calculated using mixed regression models and Spearman’s correlations for change scores. Poor self-rated health was associated with high levels of seasonal IgE (p = 0.05) and food IgE (p = 0.04), but not total IgE or inflammatory markers. An increase over 1 year in perennial IgE was associated with a worsening of self-rated health (ρ = 0.16, p = 0.04). Poor self-rated health was associated with more pronounced sickness behaviour (p < 0.001), and a worsening in sickness behaviour was associated with a worsening of self-rated health over time (ρ = 0.21, p = 0.007). The study corroborates the importance of sickness behaviour as a determinant of self-rated health by showing that these factors co-vary over a 1-year period in a group of patients with allergic asthma. The importance of specific IgE for perceived health in primary care patients with mild to moderate asthma needs further investigation.
Fresnel diffractograms from pure-phase wave fields under perfect spatio-temporal coherence: Non-linear/non-local aspects and far-field behavior
Authors: Trost F. , Hahn S. , Müller Y. , Gasilov S. , Hofmann R. , Baumbach T.
Published: December 2017

Recently, the diffractogram, that is, the Fourier transform of the intensity contrast induced by Fresnel free-space propagation of a given (exit) wave field, was investigated non-perturbatively in the phase-scaling factor S (controlling the strength of phase variation) for the special case of a Gaussian phase of width $$\sqrt{{\bf{w}}}$$

w

. Surprisingly, an additional low-frequency zero σ* = σ*(S, F) >0 emerges critically at small Fresnel number F (σ proportional to square of 2D spatial frequency). Here, we study the S-scaling behavior of the entire diffractogram. We identify a valley of maximum S-scaling linearity in the F − σ plane corresponding to a nearly universal physical frequency ξml = (0:143 ± 0.001)w−1/2. Large values of F (near field) are shown to imply S-scaling linearity for low σ but nowhere else (overdamped non-oscillatory). In contrast, small F values (far field) entail distinct, sizable s-bands of good S-scaling linearity (damped oscillatory). These bands also occur in simulated diffractograms induced by a complex phase map (Lena). The transition from damped oscillatory to overdamped non-oscillatory diffractograms is shown to be a critical phenomenon for the Gaussian case. We also give evidence for the occurrence of this transition in an X-ray imaging experiment. Finally, we show that the extreme far-field limit generates a σ-universal diffractogram under certain requirements on the phase map: information on phase shape then is solely encoded in S-scaling behavior.
Bouncing of an ellipsoidal drop on a superhydrophobic surface
Authors: Yun Sungchan
Published: December 2017

Drop impact on superhydrophobic surfaces has received significant attention because of the advantages of self-cleaning and anti-icing attained by minimum contact time with the surface. Drop hydrodynamics is generally assumed to be axisymmetric, and the contact time is still bounded below by a theoretical Rayleigh limit. In this study, we report an ellipsoidal drop impact on a superhydrophobic surface to demonstrate an efficient way to reduce the contact time and suppress the bounce magnitude by breaking the symmetry. The outcome of the bounce is characterized in terms of a geometric aspect ratio (AR) and Weber number of the drop by comparing the dynamics with a spherical drop. The experimental result shows that the bouncing of the ellipsoidal drop can reduce the contact time and maximum bounce height below the spherical one by at least 30% and 60%, respectively. The exceptional rim dynamics at high AR produces a liquid alignment along the principal direction, leading to the symmetry breaking in the mass and momentum distribution and the subsequent fast drop detachment, which is quantitatively rationalized by the numerical study. The distinct features of the ellipsoidal drop impact will provide an insight into shape-dependent dynamics and open up new opportunities for self-cleaning and anti-icing strategies.
Blueprint for Large-Scale Silicon Optical Phased Array Using Electro-Optical Micro-Ring Pixels
Authors: Zhao Che , Peng Chao , Hu Weiwei
Published: December 2017

We propose a modularized architecture of a large-scale optical phased array (OPA) on a silicon on insulator (SOI) platform, using electro-optical (EO) pixels. Each pixel contains a directional coupler, a micro-ring phase shifter, and a grating optical antenna, on a compact configuration of area 50 μm × 50 μm, with optical and electrical interconnections. Moreover, we present an exemplary blueprint of an OPA consisting of 32 × 32 EO pixels, which sets the width of the main lobe as 0.04° × 0.04° and the field of view as 1.78°. By applying an over-coupled condition, the modulation efficiency and the accompanying intensity modulation are balanced, thus, the OPA performance is not severely degraded. The discussion on the fabrication tolerance shows that the proposed architecture is robust and feasible regarding the state-of-the-art fabrication process, and the performance of the main lobe width and field of view can be further optimized by a larger system size and smaller pixel size. Furthermore, the complexity of interconnections linearly depends on the number of rows and columns, making it highly scalable.
Two-colour serial femtosecond crystallography dataset from gadoteridol-derivatized lysozyme for MAD phasing
Authors: Gorel Alexander , Motomura Koji , Fukuzawa Hironobu , Doak R. Bruce , Grünbein Marie Luise , Hilpert Mario , Inoue Ichiro , Kloos Marco , Nass Kovács Gabriela , Nango Eriko , Nass Karol , Roome Christopher M , Shoeman Robert L , Tanaka Rie , Tono Kensuke , Foucar Lutz , Joti Yasumasa , Yabashi Makina , Iwata So , Ueda Kiyoshi , Barends Thomas R. M , Schlichting Ilme
Published: December 2017

We provide a detailed description of a gadoteridol-derivatized lysozyme (gadolinium lysozyme) two-colour serial femtosecond crystallography (SFX) dataset for multiple wavelength anomalous dispersion (MAD) structure determination. The data was collected at the Spring-8 Angstrom Compact free-electron LAser (SACLA) facility using a two-colour double-pulse beam to record two diffraction patterns simultaneously in one diffraction image. Gadolinium lysozyme was chosen as a well-established model system that has a very strong anomalous signal. Diffraction patterns from gadolinium lysozyme microcrystals were recorded to a resolution of 1.9 Å in both colours. This dataset is publicly available through the Coherent X-ray Imaging Data Bank (CXIDB) as a resource for algorithm development.
The mineralocorticoid receptor knockout in medaka is further validated by glucocorticoid receptor compensation
Authors: Sakamoto Tatsuya , Yoshiki Madoka , Sakamoto Hirotaka
Published: December 2017

To study the critical role of mineralocorticoid signalling, we generated a constitutive mineralocorticoid receptor (MR)-knockout (KO) medaka as the first adult-viable MR-KO animal. This KO medaka displayed abnormal behaviours affected by visual stimuli. In contrast, the loss of MR did not result in overt phenotypic changes in osmoregulation, despite the well-known osmoregulatory functions of MR in mammals. Since glucocorticoid receptor (GR) has been suggested to compensate for loss of MR, we examined expression of duplicated GRs with markedly different ligand sensitivities, in various tissues. qRT-PCR results revealed that the absence of MR induced GR1 in the brain and eyes, but not in osmoregulatory organs. This reinforces the important functions of glucocorticoid signalling, but the minor role of mineralocorticoid signalling, in fish osmoregulation. Because both 11-deoxycorticosterone (DOC) and cortisol are ligands for MR, whereas GRs are specific to cortisol, GR1 signalling may compensate for the absence of cortisol-MR, rather than that of DOC-MR. Thus, this GR expression suggests that our MR-KO model can be used specifically to characterize DOC-MR signalling.
Molybdenum isotope fractionation in plants measured by MC-ICPMS
Authors: Malinovsky Dmitry , Kashulin Nikolay A.
Published: December 2017

A new method for determination of Mo isotope ratios in plants has been developed.
An aptamer-based electrochemical biosensor for simple and sensitive detection of staphylococcal enterotoxin B in milk
Authors: Xiong Xiaohui , Shi Xinping , Liu Yuanjian , Lu Lixia , You Jingjing
Published: December 2017

The relative percentage error between the proposed method and ELISA ranged from −8.38 to 8.33, which indicates that there is no significant difference between the results.
On-site monitoring of occupational exposure to volatile organic compounds by a portable comprehensive 2-dimensional gas chromatography device
Authors: Lee Jiwon , Sayler Stephanie K. , Zhou Menglian , Zhu Hongbo , Richardson Rudy J. , Neitzel Richard L. , Kurabayashi Katsuo , Fan Xudong
Published: December 2017

An automated portable comprehensive 2-dimensional gas chromatography device was used for rapid field analysis of occupational volatile organic compounds at a Spray and Finishing Shop.
Is secondary organic aerosol yield governed by kinetic factors rather than equilibrium partitioning?
Authors: Wang Chen , Wania Frank , Goss Kai-Uwe
Published: December 2017

The concept of differential SOA yield and a consideration of kinetic processes are important when modelling SOA formation under atmospherically relevant conditions.
Engineered silica nanoparticles interact differently with lipid monolayers compared to lipid bilayers
Authors: Asghari Adib Ali , Nazemidashtarjandi Saeed , Kelly Alexander , Kruse Adelaide , Cimatu Katherine , David Allan E. , Farnoud Amir M.
Published: December 2017

Engineered silica nanoparticles interact differently with lipid monolayers and bilayers.
Immunomodulating protein aggregates in soy and whey hydrolysates and their resistance to digestion in an in vitro infant gastrointestinal model: new insights in the mechanism of immunomodulatory hydrolysates
Authors: Kiewiet Mensiena B. G. , Dekkers Renske , Ulfman Laurien H. , Groeneveld Andre , de Vos Paul , Faas Marijke M.
Published: December 2017

A soy hydrolysate contains protein aggregates which possess TLR activating properties.
Phenolic profiles of eight olive cultivars from Algeria: effect ofBactrocera oleaeattack
Authors: Medjkouh Lynda , Tamendjari Abderezak , Alves Rita C. , Laribi Rahima , Oliveira M. Beatriz P. P.
Published: December 2017

Olive fly (Bactrocera oleaeR.) affects olive fruit development and olive oil production.
Copper-induced reduction in myocardial fibrosis is associated with increased matrix metalloproteins in a rat model of cardiac hypertrophy
Authors: Liu Yinjie , Xiao Ying , Liu Jiaming , Feng Li , Kang Y. James
Published: December 2017

AAC induces Cu loss from the heart and depressed MMP-2 in combination with increased TIMPs, leading to increased collagen deposition. TETA replenishes Cu in the heart, increases MMP-2, and decreases TIMP-1 and -2, collectively resulting in reduction in cardiac fibrosis.
Metal ion assisted interface re-engineering of a ferritin nanocage for enhanced biofunctions and cancer therapy
Authors: Wang Zhantong , Dai Yunlu , Wang Zhe , Jacobson Orit , Zhang Fuwu , Yung Bryant C. , Zhang Pengfei , Gao Haiyan , Niu Gang , Liu Gang , Chen Xiaoyuan
Published: December 2017

The bottom-up self-assembly of protein subunits into supramolecular nanoarchitectures is ubiquitously exploited to recapitulate and expand features of natural proteins to advance nanoscience in medicine.
DABCO-catalyzed silver-promoted direct thiolation of pyrazolones with diaryl disulfides
Authors: Thupyai Akkharaphong , Pimpasri Chaleena , Yotphan Sirilata
Published: December 2017

Efficient direct thiolation of N-substituted pyrazolones with diaryl disulfides was developed using a combination of DABCO and AgOAc to assist C–S bond formation.
Thermosensitive polynorbornene poly(ethylene oxide) nanoparticles loaded with oligoDNAs: an innovative approach for acting on cancer-associated pain
Authors: Pichavant L. , López-González M. J. , Favereaux A. , Héroguez V.
Published: December 2017

DNA oligonucleotides (oligoDNAs) have been recently identified as a novel class of therapeutic tools for acting on the cancer-associated pain.
Structure and excellent visible light catalysis of Prussian blue analogues BiFe(CN)6·4H2O
Authors: Gao Qilong , Chen Jun , Li Qiang , Zhang Ji , Zhai Zhao , Zhang Shantao , Yu Ranbo , Xing Xianran
Published: December 2017

BiFe(CN)6·4H2O, which exhibited a layered structure of FeC6 and BiN6 coordination polyhedra, was synthesised and exhibited excellent visible light catalytic activity.
Poly(lactic acid)/poly(ethylene glycol) stereocomplexed physical hydrogels showing thermally-induced gel–sol–gel multiple phase transitions
Authors: Mao Hailiang , Wang Chen , Chang Xiaohua , Cao Heqing , Shan Guorong , Bao Yongzhong , Pan Pengju
Published: December 2017

A novel thermogel exhibiting unique thermally-induced gel–sol–gel multiple phase transitions was obtained by controlling the compositions of PLA/PEG copolymers.
Highly diastereoselective C → N acyl rearrangement in polysubstituted pyrrolidine 2,2-dicarboxylates. Stereocontrolled synthesis of densely functionalized prolines
Authors: Reboredo Silvia , García-Marijuan Ainara , Uria Uxue , Reyes Efraím , Carrillo Luisa , Ugarriza Iratxe , Vicario Jose L.
Published: December 2017

A fully diastereoselective C–N acyl transfer reaction operates in enantiopure densely substituted pyrrolidine 2,2-dicarboxylates.
Insertion of sulfur dioxide via a radical process: an efficient route to sulfonyl compounds
Authors: Qiu Guanyinsheng , Zhou Kaida , Gao Liang , Wu Jie
Published: December 2017

This review is focused on the recent advances in the chemistry of sulfur dioxide fixation through a radical process. Diverse sulfonyl compounds can be obtained efficiently under mild conditions.
Unravelling vaginal microbial genetic diversity and abundance between Holstein and Fleckvieh cattle
Authors: Nesengani Lucky T. , Wang Jun , Yang Yujiang , Yang Lianyu , Lu Wenfa
Published: December 2017

The breed effect could determine the vaginal microbial genetic diversity and abundance between Holstein and Fleckvieh cattle.
A true cable assembly with a carbon nanotube sheath and nickel wire core: a fully flexible electrode integrating energy storage and electrical conduction
Authors: Ye Huating , Wang Kai , Zhou Juntao , Song Li , Gu Li , Cao Xuebo
Published: December 2017

Scalable production of fully flexible cables consisting of a carbon nanotube sheath and nickel wire core for wire-shaped supercapacitors is demonstrated.
Exploring unbalanced electrode configurations for electrochromic devices
Authors: Hassab Sofiane , Shen D. Eric , Österholm Anna M. , Reynolds John R. , Padilla Javier
Published: December 2017

A new unbalanced electrochromic configuration is demonstrated, allowing minimum energy consumption while maintaining optimum optoelectrochemical performance.
JMJD6 induces HOTAIR, an oncogenic lincRNA, by physically interacting with its proximal promoter
Authors: Biswas Antara , Shettar Abhijith , Mukherjee Geetashree , Kondaiah Paturu , Desai Kartiki V.
Published: December 2017

Using microarray analysis, we found that HOX transcript antisense intergenic RNA (HOTAIR) is up-regulated by Jumonji domain containing-6 (JMJD6), a bifunctional lysyl hydroxylase and arginine demethylase. In breast cancer, both JMJD6 and HOTAIR RNAs increase tumor growth and associate with poor prognosis but no molecular relationship between them is known. We show that overexpression of JMJD6 increased HOTAIR expression and JMJD6 siRNAs suppressed it in ER+ MCF-7, triple negative MDA-MB-231 and non-breast cancer HEK 293 cells. Therefore, JMJD6 regulates HOTAIR independent of ER status. Using various deletion constructs spanning (−1874 to +50) of the HOTAIR promoter, we identified pHP216 (−216 to +50 bp) as the smallest construct that retained maximal JMJD6 responsiveness. In ChIP assays, JMJD6 bound this region suggesting that JMJD6 may be directly recruited to the HOTAIR promoter. Mutant JMJD6H187A that is devoid of enzymatic activity could bind this site but failed to induce transcription. ChIP and electromobility shift assays identified a JMJD6 interaction region from (−123 to −103 bp) within the HOTAIR promoter. In tumor samples but not normal breast tissue, the expression of JMJD6 linearly correlated with HOTAIR suggesting that JMJD6-mediated up-regulation may occur specifically in tumors. Further, concurrent high expression of both genes correlated with poor survival when individual expression of either gene showed no significant association in TCGA datasets. We propose that high JMJD6 expression may achieve higher levels of HOTAIR in breast tumors. Further, since high levels of HOTAIR promote metastasis and death, blocking JMJD6 may be useful in preventing such events.
The mammalian ULK1 complex and autophagy initiation
Authors: Zachari Maria , Ganley Ian G.
Published: December 2017

Autophagy is a vital lysosomal degradation pathway that serves as a quality control mechanism. It rids the cell of damaged, toxic or excess cellular components, which if left to persist could be detrimental to the cell. It also serves as a recycling pathway to maintain protein synthesis under starvation conditions. A key initial event in autophagy is formation of the autophagosome, a unique double-membrane organelle that engulfs the cytosolic cargo destined for degradation. This step is mediated by the serine/threonine protein kinase ULK1 (unc-51-like kinase 1), which functions in a complex with at least three protein partners: FIP200 (focal adhesion kinase family interacting protein of 200 kDa), ATG (autophagy-related protein) 13 (ATG13), and ATG101. In this artcile, we focus on the regulation of the ULK1 complex during autophagy initiation. The complex pattern of upstream pathways that converge on ULK1 suggests that this complex acts as a node, converting multiple signals into autophagosome formation. Here, we review our current understanding of this regulation and in turn discuss what happens downstream, once the ULK1 complex becomes activated.
Exploiting cancer vulnerabilities: mTOR, autophagy, and homeostatic imbalance
Authors: Johnson Charlotte E. , Tee Andrew R.
Published: December 2017

Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) at lysosomes plays a pivotal role in cell growth control where an array of large multiprotein complexes relay nutrient, energy, and growth signal inputs through mTORC1. In cancer cells, such regulation often becomes disconnected, leading to uncontrolled cell growth and an elevation in cellular stress. Consequently, cancer cells often lose homeostatic balance as they grow in unfavorable conditions, i.e. when nutrients and energy are limited yet mTORC1 is still aberrantly activated. Cancer cells lose signaling flexibility because of hyperactive mTORC1 that leads to heightened cellular stress and loss of nutrient and energy homeostasis, all of which are potential avenues for cancer therapy. Cancer cells often enhance mTORC1 to drive cell growth and proliferation, while also maintaining their survival. Autophagy regulation by mTORC1 is critically involved in nutrient and energy homeostasis, cell growth control, and survival. Studying mTORC1 and autophagy as a potential therapeutic target for cancer treatment has been the focus of a wide range of research over the past few decades. This review will explore the signaling pathways central to mTORC1 and autophagy regulation, and cancer vulnerabilities while considering anticancer therapies.
Cancer immune resistance: can theories converge?
Authors: Lu Rongze , Turan Tolga , Samayoa Josue , Marincola Francesco M.
Published: December 2017

Immune oncology (IO) is challenged to expand its usefulness to a broader range of cancers. A second generation of IO agents acting beyond the realm of Checkpoint Inhibitor Therapy (CIT) is sought with the intent of turning immune-resistant cancers into appealing IO targets. The published literature proposes a profusion of models to explain cancer immune resistance to CIT that largely outnumber the immune landscapes and corresponding resistance mechanisms. In spite of the complex and contradicting models suggested to explain refractoriness to CIT, the identification of prevailing mechanisms and their targeting may not be as daunting as it at first appears. Here, we suggest that cancer cells go through a conserved evolutionary bottleneck facing a Two-Option Choice to evade recognition by the immune competent host: they can either adopt a clean oncogenic process devoid of immunogenic stimuli (immune-silent tumors) or display an entropic biology prone to immune recognition (immune-active tumors) but resilient to rejection thanks to the recruitment of compensatory immune suppressive processes. Strategies aimed at enhancing the effectiveness of CIT will be different according to the immune landscape targeted.
TREX1 is a checkpoint for innate immune sensing of DNA damage that fosters cancer immune resistance
Authors: Demaria Sandra , Vanpouille-Box Claire
Published: December 2017

Genomic instability is a hallmark of neoplastic transformation that leads to the accumulation of mutations, and generates a state of replicative stress in neoplastic cells associated with dysregulated DNA damage repair (DDR) responses. The importance of increasing mutations in driving cancer progression is well established, whereas relatively little attention has been devoted to the DNA displaced to the cytosol of cancer cells, a byproduct of genomic instability and of the ensuing DDR response. The presence of DNA in the cytosol promotes the activation of viral defense pathways in all cells, leading to activation of innate and adaptive immune responses. In fact, the improper accumulation of cytosolic DNA in normal cells is known to drive severe autoimmune pathology. Thus, cancer cells must evade cytoplasmic DNA detection pathways to avoid immune-mediated destruction. The main sensor for cytoplasmic DNA is the cyclic GMP–AMP synthase, cGAS. Upon activation by cytosolic DNA, cGAS catalyzes the formation of the second messenger cGAMP, which activates STING (stimulator of IFN genes), leading to the production of type I interferon (IFN-I). IFN-I is a critical effector of cell-mediated antiviral and antitumor immunity, and its production by cancer cells can be subverted by several mechanisms. However, the key upstream regulator of cytosolic DNA-mediated immune stimulation is the DNA exonuclease 3′-repair exonuclease 1 (TREX1). Here, we will discuss evidence in support of a role of TREX1 as an immune checkpoint that, when up-regulated, hinders the development of antitumor immune responses.
Flat‐gain dual‐patch antenna with multi‐radiation nulls and low cross‐polarisation
Authors: Meng Chunmei , Shi Jin , Chen Jian‐Xin
Published: December 2017

A coupled‐fed dual‐patch antenna with vias, stubs and a metallic shield is proposed. The proposed design shows all the key features of multi‐radiation nulls, low cross‐polarisation, wide bandwidth, high and flat gain, while the reported single‐patch and multi‐patch antennas have part of the features. One prototype operated at 10.3 GHz has been fabricated and measured. The measured results show a 10‐dB fractional bandwidth of 12.1%, the gain at the centre frequency is 8.7 dBi, and three radiation nulls appear at 7.6, 8.15 and 12.25 GHz, respectively. The cross‐polarisation is less than −25 dB. The gain ripple is 0.36 dB.
Blood leakage detection during dialysis therapy based on fog computing with array photocell sensors and heteroassociative memory model
Authors: Wu Jian‐Xing , Huang Ping‐Tzan , Lin Chia‐Hung , Li Chien‐Ming
Published: December 2017

Blood leakage and blood loss are serious life‐threatening complications occurring during dialysis therapy. These events have been of concerns to both healthcare givers and patients. More than 40% of adult blood volume can be lost in just a few minutes, resulting in morbidities and mortality. The authors intend to propose the design of a warning tool for the detection of blood leakage/blood loss during dialysis therapy based on fog computing with an array of photocell sensors and heteroassociative memory (HAM) model. Photocell sensors are arranged in an array on a flexible substrate to detect blood leakage via the resistance changes with illumination in the visible spectrum of 500–700 nm. The HAM model is implemented to design a virtual alarm unit using electricity changes in an embedded system. The proposed warning tool can indicate the risk level in both end‐sensing units and remote monitor devices via a wireless network and fog/cloud computing. The animal experimental results (pig blood) will demonstrate the feasibility.
GA‐based optimisation of the interaction structure of an X‐band helix travelling wave tube
Authors: Narasimhan Purushothaman , Srivastava Vishnu , Ghosh Sanjay K.
Published: December 2017

Genetic algorithm (GA) has been adopted for the optimisation of the slow wave structure (SWS) of an X‐band helix travelling wave tube. To reduce the optimisation time and to achieve the desired performance, a software code based on GA has been developed to automate the optimisation process of the helix SWS. A two‐section SWS has been optimised. The pitches and the lengths of all the subsections have been considered with the objective of achieving the desired saturated output power and the saturated gain over the operating frequency range. The procedure for the implementation of the GA has been demonstrated. Multiple trials have been conducted for achieving the most optimal set of parameters. The cost over several generations for all the trials is presented and the optimised values of the saturated output power and the saturated gain are also shown.
High‐efficiency PV inverter with SiC technology
Authors: Wall Simon , Hong Xiao‐Cong , Sha Long , Xie Jing‐Ren
Published: December 2017

A high‐efficiency, three‐phase, solar photovoltaic (PV) inverter is presented that has low ground current and is suitable for direct connection to the low voltage (LV) grid. The proposed topology includes a three‐phase, two‐level (2L) voltage source inverter (VSI) and an active common‐mode (CM) filter. The VSI utilises silicon (Si) insulated‐gate bipolar transistors with silicon carbide (SiC) diodes to reduce switching losses and provide very high efficiency. The active CM filter reduces the high level of CM voltage associated with the three‐phase 2L VSI. The active CM filter is controlled so that the PV ground current is reduced to acceptable levels, even when the PV inverter is connected directly to a LV grid with low‐impedance grounding. 50 and 100 kW prototypes are presented that demonstrate high efficiency.
Rhythm‐based identification of alcohol EEG signals
Authors: Taran Sachin , Bajaj Varun
Published: December 2017

Alcohol is a severe intoxication substance that changes the functionality of brain by disturbing the neuronal process of the central nervous system, which causes mental and behavioural disorders. These disorders can be diagnosed by automatic classification of normal and alcohol electroencephalogram (EEG) signals, because it provides neurophysiology of alcoholic human brain. In this study, EEG rhythms based features are proposed for automatic identification and analysis of alcohol EEG signals. The instantaneous‐frequency computed by analytic representation of intrinsic mode functions (IMFs) is used for separation of different frequency ranges known as EEG rhythms. IMFs are obtained by applying empirical mode decomposition on an EEG signal. The variability and complexity of separated EEG rhythms are measured by features namely: mean absolute deviation, inter quartile range, coefficient of variation, entropy, and neg‐entropy. The p‐value analysis of these features shows that low‐frequency (LF)‐rhythms based features are statistically significant for identification and neurological analysis of alcohol EEG signals. The LF‐rhythms based features are applied as input to an extreme learning machine (ELM) and least squares support vector machine classifiers for classification of normal and alcohol EEG signals. The proposed method with an ELM classifier provides better classification accuracy (97.92%) as compared with other existing methods.
Performance of silver nanoparticle fixed on magnetic iron nanoparticles () in water disinfection
Authors: Sharifi Roya , Hassani Amir Hessam , Ahmad Panahi Homayon , Borghei Mehdi
Published: December 2017

Microbial contamination poses a serious threat to human health. The evaluation of alternative systems and their reliability for the treatment of water is essential. In this work, a new method for the deposit of more silver nanoparticles (AgNPs) on the external surface of nanoparticles is presented. nanoparticles were synthesised by chemical co‐precipitation and were modified in two stages using 3‐mercaptopropyl trimethoxysilane and grafting allyl glycidyl ether and N, N‐dimethylacrylamide. Then, AgNPs were loaded onto the modified to be used for water disinfection. The resulting nanoparticles were characterised by transmission electron microscopy, X‐ray powder diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometer and thermal gravimetric analysis. Batch experiments were performed to investigate the effects of parameters such as amount of , contact time, and initial concentrations of MPN (the most probable number) and pH. The kinetic data was analysed by pseudo‐first‐order and pseudo‐second‐order equations. Results showed that the optimum conditions were a contact time of 30 min (94%), 50 mg of , and a pH was 6.5 for the maximum MPN removal efficiency (99.76%) in 750 cfu/ml MPN. On the basis of the results of fitting data, the pseudo‐second‐order kinetic model was selected as suitable for the data.
Modified Schottky Barrier CNTFET with lightly doped drain
Authors: Raeini Amin Ghasemi Nejad , Kordrostami Zoheir
Published: December 2017

For the first time, a modified Schottky barrier carbon nanotube field‐effect transistor (SB‐CNTFET) with lightly doped drain (LDD) has been proposed. The newly designed CNTFET benefits from the advantages of both SB in source and the lightly doped ohmic drain contact. Simulations are based on two‐dimensional non‐equilibrium Green's function solved self‐consistently with Poisson's equation. To get to an improved electrical characteristic, comparisons have been made among four CNTFET structures which are conventional SB‐CNTFETs, triple LDD‐CNTFET (TLDD‐CNTFET), double LDD‐CNTFET and Schottky source and ohmic drain CNTFET. The results show that the TLDD‐CNTFET design decreases the leakage current significantly and increases on–off‐current ratio as well as the cut‐off frequency. It is also demonstrated that TLDD‐CNTFET structure possesses three perceivable steps in the potential profile of the channel, which leads to additional lateral electric field peaks inside the channel and thus improve the immunity against short‐channel effects. The important parameters such as transconductance, on–off ratio, subthreshold swing, cut‐off frequency, delay and drain‐induced barrier lowering of the CNTFETs have been calculated and discussed. Results show that by using lightly doped regions in the drain of SB‐CNTFETs, the dc and ac characteristics have been considerably improved compared with the conventional SB‐CNTFET.
Long-term evolution of the heliospheric magnetic field inferred from cosmogenic 44Ti activity in meteorites
Authors: Mancuso S. , Taricco C. , Colombetti P. , Rubinetti S. , Sinha N. , Bhandari N.
Published: December 2017

Typical reconstructions of historic heliospheric magnetic field (HMF) BHMF are based on the analysis of the sunspot activity, geomagnetic data or on measurement of cosmogenic isotopes stored in terrestrial reservoirs like trees (14C) and ice cores (10Be). The various reconstructions of BHMF are however discordant both in strength and trend. Cosmogenic isotopes, which are produced by galactic cosmic rays impacting on meteoroids and whose production rate is modulated by the varying HMF convected outward by the solar wind, may offer an alternative tool for the investigation of the HMF in the past centuries. In this work, we aim to evaluate the long-term evolution of BHMF over a period covering the past twenty-two solar cycles by using measurements of the cosmogenic 44Ti activity (τ1∕2 = 59.2 ± 0.6 yr) measured in 20 meteorites which fell between 1766 and 2001. Within the given uncertainties, our result is compatible with a HMF increase from 4.87-0.30+0.24 nT in 1766 to 6.83-0.11+0.13 nT in 2001, thus implying an overall average increment of 1.96-0.35+0.43 nT over 235 years since 1766 reflecting the modern Grand maximum. The BHMF trend thus obtained is then compared with the most recent reconstructions of the near-Earth HMF strength based on geomagnetic, sunspot number, and cosmogenic isotope data.
Stereoselective Ammonium-Directed Epoxidation in the Asymmetric Syntheses of Dihydroconduramines (–)-A-2, (–)-B-2, (–)-C-3 and (+)-F-3
Authors: Davies Stephen , Da Silva Pinto Solange , Fletcher Ai , Roberts Paul , Thomson James
Published: December 2017

Epoxidation of racemic trans-2-(N,N-dibenzylamino)cyclohex-3-en-1-ol, upon treatment with Cl3CCO2H then m-CPBA, proceeded with poor diastereoselectivity (ca. 60:40 dr), whilst epoxidation of racemic trans-2-(N-benzylamino)cyclohex-3-en-1-ol under the same conditions proceeded with high diastereoselectivity (>95:5 dr) and was followed by completely regioselective and stereospecific ring-opening in situ to give, after methanolysis of the intermediate trichloroacetate ester, (1RS,2SR,3SR,4SR)-2-(N-benzylamino)cyclohexane-1,3,4-triol. Use of aq HBF4 as the acid protecting agent gave the amino triol directly. The differing diastereoselectivities of these epoxidation reactions may be due to a predilection towards formation of an intramolecular hydrogen-bond in the former substrate disrupting the ability of the in situ formed ammonium moiety to act as a directing group for the incoming oxidant; the presence of two potential hydrogen-bond donors (i.e., two N–H bonds) in the latter substrate circumvents this limitation. With the criterion for a highly diastereoselective (ammonium-directed) epoxidation in this system established, a synthesis of enantiopure trans-2-(N-benzylamino)cyclohex-3-en-1-ol (>99% ee) was developed and the ammonium-directed epoxidation was then employed as a key synthetic step to facilitate the asymmetric syntheses of enantiopure dihydroconduramines (–)-A-2, (–)-B-2, (–)-C-3 and (+)-F-3 (>98% ee in each case) from 1,3-cyclohexadiene.
Thieme Chemistry Journals Awardees – Where Are They Now? ­Ribosylation of an Acid-Labile Glycosyl Acceptor as a Potential Key Step for the Synthesis of Nucleoside Antibiotics
Authors: Ducho Christian , Wiegmann Daniel , Spork Anatol , Niro Giuliana
Published: December 2017

Naturally occurring nucleoside antibiotics (e.g., muraymycins and caprazamycins) represent attractive lead structures for the development of urgently needed novel antibacterial agents. One major challenge in the total synthesis of muraymycins, caprazamycins, and their analogues is the efficient construction of the densely functionalized aminoribosylated uridine-derived core unit. In order to avoid tedious protecting-group manipulations, we have aimed to conduct the aminoribosylation step with an acid-labile glycosyl acceptor. Therefore, different glycosylation approaches have been studied, with pentenyl glycosides giving the best results.
Der kombinierte posteromediale und anterolaterale Zugang in der „floating“-Position zur operativen Versorgung der Zwei-Pfeiler-Tibiakopffraktur
Authors: Reul Maike , Hoekstra Harm
Published: December 2017

Hintergrund Intraartikuläre Tibiaplateaufrakturen involvieren häufig das posteriore Plateau, wobei die operative Versorgung und Stabilisierung der posterioren Frakturen als ein prognostisch wichtiger Faktor erkannt ist. Die offene Reposition und interne Fixation lateraler und posteriorer Zwei-Pfeiler-Tibiakopffrakturen kann mittels eines kombinierten umgekehrten posterioren L-förmigen Zugangs und eines anterolateralen Zugangs in der frei schwebenden („floating“) Halbseitenlagerung ohne Notwendigkeit der intraoperativen Umlagerung erfolgen.

Material und Methoden Mit dieser Operationsmethode wird zunächst dorsal begonnen und der hintere Pfeiler des Tibiaplateaus nach lateraler Retraktion des medialen Schenkels des M. gastrocnemius freigelegt. Danach erfolgt die Reposition und Fixation des posterioren Bruchfragments. Anschließend wird nach leichter Kippung des Patienten auf das Knie leichter Flexions- und Varusstress ausgeübt. Eine anterolaterale Hautinzision wird durchgeführt, die laterale Säule wird freigelegt, die lateralen Fragmente werden reponiert und fixiert.

Ergebnisse Seit Juni 2014 wurden 14 Patienten mit Zwei-Pfeiler-Tibiaplateaufrakturen mit Beteiligung des posterioren und lateralen Pfeilers nach der beschriebenen Methode operiert. Das mediane Follow-up betrug 306 Tage (IQR 194 – 438), 1 Patient ist aus dem Follow-up verloren gegangen. Bei der letzten klinischen Kontrolle gaben 7 Patienten noch Schmerzen an. Nach im Median 110 Tagen (IQR 96 – 181) bestand bei 10 Patienten ein vollständiges Bewegungsausmaß. Postoperativ trat 1 tiefe Infektion auf. Insgesamt zeigte sich bei 11 von 14 Patienten in der postoperativen CT-Kontrolle nach 3 – 4 Monaten ein gutes Repositionsergebnis mit Wiederherstellung des Alignments, bei 8 der 14 Patienten zeigte sich eine kongruente Gelenkfläche ohne signifikante (< 2 mm) intraartikuläre Stufenbildung.

Zusammenfassung Es konnte gezeigt werden, dass die operative Behandlung der posterolateralen Zwei-Pfeiler-Tibiakopffraktur mittels eines kombinierten posterioren umgekehrt L-förmigen Zugangs und eines anterolateralen Zugangs in einer frei schwebenden („floating“) Halbseitenlagerung technisch sehr gut möglich ist, ohne dabei den Patienten umlagern zu müssen.

Fazit Unserer Erfahrung nach zeigt dieses kombinierte Verfahren klinisch und radiologisch gute Ergebnisse bei Patienten mit posterolateralen Frakturen, obwohl es bisher nur bei einer kleinen Patientenzahl durchgeführt wurde.