bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing the quantum critical fan of strongly correlated systems using quantum correlations
Authors: Frérot Irénée , Roscilde Tommaso
Published: February 2019

Albeit occurring at zero temperature, quantum critical phenomena have a huge impact on the finite-temperature phase diagram of strongly correlated systems, giving experimental access to their observation. Indeed, the existence of a gapless, zero-temperature quantum critical point induces the existence of an extended region in parameter space—the quantum critical fan (QCF)—characterized by power-law temperature dependences of all observables. Identifying experimentally the QCF and its crossovers to other regimes (renormalized classical, quantum disordered) remains nonetheless challenging. Focusing on paradigmatic models of quantum phase transitions, here we show that quantum correlations—captured by the quantum variance of the order parameter—exhibit the temperature scaling associated with the QCF over a parameter region much broader than that revealed by ordinary correlations. The link existing between the quantum variance and the dynamical susceptibility paves the way to an experimental reconstruction of the QCF using spectroscopic techniques.
Label-free Quantitative Analysis of Protein Expression Alterations in miR-26a-Knockout HeLa Cells using SWATH-MS Technology
Authors: Shen Hexiao , Li Li , Teng Zhaowei , Meng Tianqing , Kong Xiangbin , Hu Yan , Zhu Yun , Ma Lixin
Published: February 2019

MicroRNAs (miRNAs) bind to the 3ʹ-untranslated region of target mRNAs in a sequence-specific manner and subsequently repress gene translation. Human miR-26a has been studied extensively, but the target transcripts are far from complete. We first employed the CRISPR-Cas9 system to generate an miR-26a-knockout line in human cervical cancer HeLa cells. The miR26a-knockout line showed increased cell growth and altered proliferation. Proteomics technology of sequential window acquisition of all theoretical mass spectra (SWATH-MS) was utilized to compare the protein abundance between the wild-type and the knockout lines, with an attempt to identify transcripts whose translation was influenced by miR-26a. Functional classification of the proteins with significant changes revealed their function in stress response, proliferation, localization, development, signaling, etc. Several proteins in the cell cycle/proliferation signaling pathway were chosen to be validated by western blot and parallel reaction monitoring (PRM). The satisfactory consistency among the three approaches indicated the reliability of the SWATH-MS quantification. Among the computationally predicted targets, a subset of the targets was directly regulated by miR-26a, as demonstrated by luciferase assays and Western blotting. This study creates an inventory of miR-26a-targeted transcripts in HeLa cells and provides fundamental knowledge to further explore the functions of miR-26a in human cancer.
Quantum-like decreased embryogenesis time with increased cold exposure time
Authors: Vasanthan Tarushika , Nederveen Joshua P. , Stone Jonathon
Published: February 2019

Three theoretical models have been proposed to explain lifespan extension resulting from exposure to extreme conditions in microscopic animals: individuals become completely dormant and stop aging, continue to age or age but at a diminished rate. Here we show that the earliest life history stages, embryonic cell divisions, in the tardigrade species Hypsibius dujardini are retarded when eggs are reared at 0 °C. Compared to control specimens reared at 22 °C, juveniles that hatched from eggs exposed to 0 °C for 4 days and returned to 22 °C experienced a three-day lag, indicating that their biological age was less than their chronological age. As cold exposure duration increased (days = 10, 20, 40), incubation period at 22 °C decreased incrementally (days = 3, 2, 1), suggesting that tardigrades involve a threshold-determined, quantum-like, energetic-based system for controlling embryogenesis.
Biofilm Formation of Staphylococcus aureus under Food Heat Processing Conditions: First Report on CML Production within Biofilm
Authors: Miao Jian , Lin Shiqi , Soteyome Thanapop , Peters Brian M. , Li Yanmei , Chen Huishan , Su Jianyu , Li Lin , Li Bing , Xu Zhenbo , Shirtliff Mark E. , harro Janette M.
Published: February 2019

This study aimed to evaluate the Staphylococcus aureus biofilm formation and Nε-carboxymethyl-lysine generation ability under food heat processing conditions including pH (5.0–9.0), temperature (25 °C, 31 °C, 37 °C, 42 °C and 65 °C), NaCl concentration (10%, 15% and 20%, w/v) and glucose concentration (0.5%, 1%, 2%, 3%, 5%, 10%, w/v). S. aureus biofilm genetic character was obtained by PCR detecting atl, ica operon, sasG and agr. Biofilm biomass and metabolic activity were quantified with crystal violet and methyl thiazolyl tetrazolium staining methods. S. aureus biofilm was sensitive to food heat processing conditions with 37 °C, pH 7.0, 2% glucose concentration (w/v) and 10% NaCl concentration (w/v) were favorable conditions. Besides, free and bound Nε-carboxymethyl-lysine level in weak, moderate and strong biofilm were detected by optimized high performance liquid chromatography tandem mass spectrometry. Nε-carboxymethyl-lysine level in S. aureus biofilm possessed a significant gap between strong, moderate and weak biofilm strains. This investigation revealed the biological and chemical hazard of Staphylococcus aureus biofilm to food processing environment.
Structural and biochemical insight into mode of action and subsite specificity of a chitosan degrading enzyme from Bacillus spec. MN
Authors: Singh Ratna , Weikert Tobias , Basa Sven , Moerschbacher Bruno M.
Published: February 2019

Chitosans, partially de-N-acetylated derivatives of chitin, are multifunctional biopolymers. In nature, biological activities of partially acetylated chitosan polymers are mediated in part by their oligomeric breakdown products, which are generated in situ by the action of chitosanolytic enzymes. Understanding chitosanolytic enzymes, therefore, can lead to the production of chitosan oligomers with fully defined structures that may confer specific bioactivities. To address whether defined oligomer products can be produced via chitosanolytic enzymes, we here characterized a GH8 family chitosanase from Bacillus spec. MN, determining its mode of action and product profiles. We found that the enzyme has higher activity towards polymers with lower degree of acetylation. Oligomeric products were dominated by GlcN3, GlcN3GlcNAc1, and GlcN4GlcNAc1. The product distribution from oligomers were GlcN3 > GlcN2. Modeling and simulations show that the binding site comprises subsites ranging from (−3) to (+3), and a putative (+4) subsite, with defined preferences for GlcN or GlcNAc at each subsite. Flexible loops at the binding site facilitate enzyme-substrate interactions and form a cleft at the active site which can open and close. The detailed insight gained here will help to engineer enzyme variants to produce tailored chitosan oligomers with defined structures that can then be used to probe their specific biological activities.
Diagnostic Value of Circulating microRNAs for In-Stent Restenosis in Patients with Lower Extremity Arterial Occlusive Disease
Authors: Yuan Liangxi , Dong Jian , Zhu Guanglang , Bao Junmin , Lu Qingsheng , Zhou Jian , Jing Zaiping
Published: February 2019

In-stent restenosis (ISR) is still a major cause of failure of endovascular stenting treatment in patients with lower extremity arterial occlusive disease (LEAOD). Sensitive and reliable biomarkers for early diagnosis to predict ISR should be considered. This study was conducted to explore the diagnostic value of microRNA in predicting ISR in patients with LEAOD after endovascular stenting treatment. From March 2014 to July 2016, 208 patients (170 males and 38 females) with LEAOD undergoing interventional treatment were enrolled in this research. Patients were divided into the restenosis and non-restenosis groups according to routine postoperative angiography. Circulating microRNAs expression were detected in 208 participants, including 78 ISR patients, 68 non-ISR patients and 62 healthy volunteers. We selected 6 microRNAs from microarray screening as candidates for further testing via qRT-PCR. A receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of circulating microRNAs in predicting ISR for LEAOD patients. The results showed that circulating microRNA-320a and microRNA-572 in patients with ISR (n = 78) had significantly higher expression levels than it from non-ISR and healthy volunteers. By receiver operating characteristic curve analysis, the sensitivity was 82.1% and the specificity was 63.8% for microRNA-320a; the sensitivity was 69.2% and the specificity was 68.9% for microRNA-572, and the AUC was 0.766 and 0.690 for detection of ISR, respectively. Furthermore, 78 patients with ISR had significantly higher circulating expression levels of microRNA-3937 and microRNA-642a-3p and lower circulating expression levels of microRNA-4669 and microRNA-3138 compared with 68 non-ISR patients and 62 healthy volunteers, but they have no significant difference. We found that differential circulating microRNA expression in patients after stenting with ISR, and the data indicate that circulating microRNA-320a and microRNA-572 have promising value in diagnosing ISR in patients with LEAOD.
Entanglement criterion independent on observables for multipartite Gaussian states based on uncertainty principle
Authors: He Kan , Huang Miaomiao , Hou Jinchuan
Published: February 2019

Quantum entanglement is one of important resources for quantum communication. Entanglement criteria help us detect entangled states. One of important criteria is the local uncertainty relation (LUR) entanglement criteria, which is studied extensively. However, all existent LUR criteria are dependent on the chosen observables. In the paper, applying the uncertainty principle, we improve the LUR criteria to obtain entanglement criteria for multipartite Gaussian states, which are independent on observalbes.
Anaerobic degradation of hexadecane and phenanthrene coupled to sulfate reduction by enriched consortia from northern Gulf of Mexico seafloor sediment
Authors: Shin Boryoung , Kim Minjae , Zengler Karsten , Chin Kuk-Jeong , Overholt Will A. , Gieg Lisa M. , Konstantinidis Konstantinos T. , Kostka Joel E.
Published: February 2019

To advance understanding of the fate of hydrocarbons released from the Deepwater Horizon oil spill and deposited in marine sediments, this study characterized the microbial populations capable of anaerobic hydrocarbon degradation coupled with sulfate reduction in non-seep sediments of the northern Gulf of Mexico. Anaerobic, sediment-free enrichment cultures were obtained with either hexadecane or phenanthrene as sole carbon source and sulfate as a terminal electron acceptor. Phylogenetic analysis revealed that enriched microbial populations differed by hydrocarbon substrate, with abundant SSU rRNA gene amplicon sequences from hexadecane cultures showing high sequence identity (up to 98%) to Desulfatibacillum alkenivorans (family Desulfobacteraceae), while phenanthrene-enriched populations were most closely related to Desulfatiglans spp. (up to 95% sequence identity; family Desulfarculaceae). Assuming complete oxidation to CO2, observed stoichiometric ratios closely resembled the theoretical ratios of 12.25:1 for hexadecane and 8.25:1 for phenanthrene degradation coupled to sulfate reduction. Phenanthrene carboxylic acid was detected in the phenanthrene-degrading enrichment cultures, providing evidence to indicate carboxylation as an activation mechanism for phenanthrene degradation. Metagenome-assembled genomes (MAGs) revealed that phenanthrene degradation is likely mediated by novel genera or families of sulfate-reducing bacteria along with their fermentative syntrophic partners, and candidate genes linked to the degradation of aromatic hydrocarbons were detected for future study.
INITIAL – An observational study of disease severity in newly diagnosed asthma patients and initial response following 12 weeks’ treatment
Authors: Lin Jiangtao , Fu Xiuhua , Jiang Ping , Song Weidong , Hu Xiaoyun , Jie Zhijun , Liu Chuntao , He Zhengguang , Zhou Xiangdong , Tang Huaping
Published: February 2019

In China, there are an estimated 30 million people with asthma, a condition that remains poorly controlled in many patients. The INITIAL study (NCT02143739) was a 12-week, multicentre, prospective, observational study comprising 45 centres across Northern and Southern China that aimed to assess asthma severity among newly diagnosed patients as well as their prescribed medications and response to treatment. The primary objective was to evaluate asthma severity using Global Initiative for Asthma (GINA) 2006 research criteria. Secondary objectives included the distribution of asthma medication by GINA severity category and evaluation of GINA 2012-defined control levels. Medications were prescribed as per usual clinical practice. At baseline, among 4491 patients, 3.9%, 12.0%, 22.6% and 61.6% had intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Inhaled corticosteroid/long-acting β2agonist was the most common initial therapy in 90.2% of patients. GINA 2012-defined controlled asthma levels increased in all groups, rising from 6.1% at baseline to 43.0%, 53.8% and 67.8% at Weeks 4, 8 and 12, respectively. Most patients presented with severe persistent asthma. Newly diagnosed patients with asthma could benefit from at least 3 months of regular treatment followed by long-term pharmacological management.
The Distribution of Standard Deviations Applied to High Throughput Screening
Authors: Hanley Quentin S.
Published: February 2019

High throughput screening (HTS) assesses compound libraries for “activity” using target assays. A subset of HTS data contains a large number of sample measurements replicated a small number of times providing an opportunity to introduce the distribution of standard deviations (DSD). Applying the DSD to some HTS data sets revealed signs of bias in some of the data and discovered a sub-population of compounds exhibiting high variability which may be difficult to screen. In the data examined, 21% of 1189 such compounds were pan-assay interference compounds. This proportion reached 57% for the most closely related compounds within the sub-population. Using the DSD, large HTS data sets can be modelled in many cases as two distributions: a large group of nearly normally distributed “inactive” compounds and a residual distribution of “active” compounds. The latter were not normally distributed, overlapped inactive distributions – on both sides –, and were larger than typically assumed. As such, a large number of compounds are being misclassified as “inactive” or are invisible to current methods which could become the next generation of drugs. Although applied here to HTS, it is applicable to data sets with a large number of samples measured a small number of times.
Imaging the Galápagos mantle plume with an unconventional application of floating seismometers
Authors: Nolet Guust , Hello Yann , Lee Suzan van der , Bonnieux Sébastien , Ruiz Mario C. , Pazmino Nelson A. , Deschamps Anne , Regnier Marc M. , Font Yvonne , Chen Yongshun J. , Simons Frederik J.
Published: February 2019

We launched an array of nine freely floating submarine seismometers near the Galápagos islands, which remained operational for about two years. P and PKP waves from regional and teleseismic earthquakes were observed for a range of magnitudes. The signal-to-noise ratio is strongly influenced by the weather conditions and this determines the lowest magnitudes that can be observed. Waves from deep earthquakes are easier to pick, but the S/N ratio can be enhanced through filtering and the data cover earthquakes from all depths. We measured 580 arrival times for different raypaths. We show that even such a limited number of data gives a significant increase in resolution for the oceanic upper mantle. This is the first time an array of floating seismometers is used in seismic tomography to improve the resolution significantly where otherwise no seismic information is available. We show that the Galápagos Archipelago is underlain by a deep (about 1900 km) 200–300 km wide plume of high temperature, with a heat flux very much larger than predicted from its swell bathymetry. The decrease of the plume temperature anomaly towards the surface indicates that the Earth’s mantle has a subadiabatic temperature gradient.
The evolution of the axial skeleton intercentrum system in snakes revealed by new data from the Cretaceous snakes Dinilysia and Najash
Authors: Garberoglio Fernando F. , Gómez Raúl O. , Simões Tiago R. , Caldwell Michael W. , Apesteguía Sebastián
Published: February 2019

Snakes are an extremely modified and long-lived clade of lizards that have either lost or highly altered many of the synapomorphies that would clearly link them to their closest sister-group among squamates. We focus here on one postcranial morphological complex, the intercentrum system which in most non-ophidian squamates is limited to the cervical and caudal regions. The Cervical Intercentrum System (CeIS) is composed of a single intercentral element that sometimes articulates with a ventral projection (hypapophyses) of the centrum; the Caudal Intercentrum System (CaIS) is formed by an intercentral element, the haemal arch/chevron bone, and paired ventral projections of the centrum, the haemapophyses. In modern snakes, the intercentrum element of the CeIS is considered lost or fused to the hypaphophysis, and the chevron bone in CaIS is considered lost. Here, we describe new specimens of the early snake Dinilysia patagonica, and reinterpret previously known specimens of Dinilysia and Najash rionegrina, that do not show the expected snake morphology. The anatomy of these fossil taxa unambiguously shows that free cervical and caudal intercentra attached to distinct downgrowths (hypapophyses and haemapophyses) of the centra, are present in basal fossil snakes, and agrees with the proposed loss of post atlas-axis intercentra in later evolving snakes.
Efficacy of High-intensity Statin Use for Transient Ischemic Attack Patients with Positive Diffusion-weighted Imaging
Authors: Song Bo , Cao Yuan , Pei Lulu , Fang Hui , Zhao Lu , Chen Pei , Si Pan , Liu Xinjing , Liu Kai , Gao Yuan , Wu Jun , Sun Shilei , Wang Xiaoying , Lo Eng H. , Buonanno Ferdinando S. , Ning Mingming , Xu Yuming
Published: February 2019

To determine whether positive or negative DWI TIA patients could get benefits from HST we conducted a cohort study which data from the prospective, hospital-based, TIA database of the First Affiliated Hospital of Zhengzhou University. The end-point was 7-day and 90-day incidence of stroke. Cox proportional hazard regression models were used to analyze the association between end-points and high-intensity statin treatment in TIA patients with positive and negative DWI. A total of 987 eligible TIA patients were analyzed. The stroke risk of patients with positive DWI was about a four-fold increase compared to that with negative DWI (7 d, 10.9 versus 1.8, p < 0.001 and 90 d, 18.3 versus 4.2, p < 0.001). After adjusting confounding factors, HST significantly improved both 7-day (HR 0.331, 95% CI 0.165–0.663; p = 0.002) and 90-day (HR 0.480, 95% CI 0.288–0.799; p = 0.005) outcomes in positive DWI patients. As a conclusion, high-intensity statin use reduces the 90 days’ recurrent stroke risk in DWI-positive TIA patients but not in DWI-negative patients.
Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer’s Disease
Authors: Stimmell Alina C. , Baglietto-Vargas David , Moseley Shawn C. , Lapointe Valérie , Thompson Lauren M. , LaFerla Frank M. , McNaughton Bruce L. , Wilber Aaron A.
Published: February 2019

In early Alzheimer’s disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost is one of the first impairments to emerge in AD. It is possible that getting lost represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not 3-month female, 6-month male, or 12-month male, 3xTg-AD mice were impaired. 6-month male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks.
Autofluorescence lifetime augmented reality as a means for real-time robotic surgery guidance in human patients
Authors: Gorpas D. , Phipps J. , Bec J. , Ma D. , Dochow S. , Yankelevich D. , Sorger J. , Popp J. , Bewley A. , Gandour-Edwards R. , Marcu L. , Farwell D. G.
Published: February 2019

Due to loss of tactile feedback the assessment of tumor margins during robotic surgery is based only on visual inspection, which is neither significantly sensitive nor specific. Here we demonstrate time-resolved fluorescence spectroscopy (TRFS) as a novel technique to complement the visual inspection of oral cancers during transoral robotic surgery (TORS) in real-time and without the need for exogenous contrast agents. TRFS enables identification of cancerous tissue by its distinct autofluorescence signature that is associated with the alteration of tissue structure and biochemical profile. A prototype TRFS instrument was integrated synergistically with the da Vinci Surgical robot and the combined system was validated in swine and human patients. Label-free and real-time assessment and visualization of tissue biochemical features during robotic surgery procedure, as demonstrated here, not only has the potential to improve the intraoperative decision making during TORS but also other robotic procedures without modification of conventional clinical protocols.
Ligand-induced conformational switch in an artificial bidomain protein scaffold
Authors: Léger Corentin , Di Meo Thibault , Aumont-Nicaise Magali , Velours Christophe , Durand Dominique , Li de la Sierra-Gallay Ines , van Tilbeurgh Herman , Hildebrandt Niko , Desmadril Michel , Urvoas Agathe , Valerio-Lepiniec Marie , Minard Philippe
Published: February 2019

Artificial proteins binding any predefined “target” protein can now be efficiently generated using combinatorial libraries based on robust protein scaffolds. αRep is such a family of artificial proteins, based on an α-solenoid protein repeat scaffold. The low aggregation propensity of the specific “binders” generated from this library opens new protein engineering opportunities such as the creation of biosensors within multidomain constructions. Here, we have explored the properties of two new types of artificial bidomain proteins based on αRep structures. Their structural and functional properties are characterized in detail using biophysical methods. The results clearly show that both bidomain proteins adopt a closed bivalve shell-like conformation, in the ligand free form. However, the presence of ligands induces a conformational transition, and the proteins adopt an open form in which each domain can bind its cognate protein partner. The open/closed equilibria alter the affinities of each domain and induce new cooperative effects. The binding-induced relative domain motion was monitored by FRET. Crystal structures of the chimeric proteins indicate that the conformation of each constituting domain is conserved but that their mutual interactions explain the emergent properties of these artificial bidomain proteins. The ligand-induced structural transition observed in these bidomain proteins should be transferable to other αRep proteins with different specificity and could provide the basis of a new generic biosensor design.
Uncovering regional variability in disturbance trends between parks and greater park ecosystems across Canada (1985–2015)
Authors: Bolton Douglas K. , Coops Nicholas C. , Hermosilla Txomin , Wulder Michael A. , White Joanne C. , Ferster Colin J.
Published: February 2019

We assess the protective function of Canada’s parks and protected areas (PPAs) by analyzing three decades of stand-replacing disturbance derived from Landsat time series data (1985–2015). Specifically, we compared rates of wildfire and harvest within 1,415 PPAs against rates of disturbance in surrounding greater park ecosystems (GPEs). We found that disturbance rates in GPEs were significantly higher (p < 0.05) than in corresponding PPAs in southern managed forests (six of Canada’s 12 forested ecozones). Higher disturbance rates in GPEs were attributed to harvesting activities, as the area impacted by wildfire was not significantly different between GPEs and PPAs in any ecozone. The area burned within PPAs and corresponding GPEs was highly correlated (r = 0.90), whereas the area harvested was weakly correlated (r = 0.19). The average area burned in PPAs/GPEs below 55° N was low (0.05% yr−1) largely due to fire suppression aimed at protecting communities, timber, and recreational values, while the average burn rate was higher in northern PPAs/GPEs where fire suppression is uncommon (0.40% yr−1 in PPAs/GPEs above 55° N). Assessing regional variability in disturbance patterns and the pressures faced by PPAs can better inform policy and protection goals across Canada and the globe.
High PKD2 predicts poor prognosis in lung adenocarcinoma via promoting Epithelial–mesenchymal Transition
Authors: Pang Zhaofei , Wang Yu , Ding Nan , Chen Xiaowei , Yang Yufan , Wang Guanghui , Liu Qi , Du Jiajun
Published: February 2019

Protein kinase D2 (PKD2) has been reported to be related with progression and invasion in various cancers. However, its prognostic value and the underlying mechanism in lung cancer remains unclear. Herein we evaluated the expression of PKD2 in lung adenocarcinoma and investigated its relationship with EMT. GSEA, TCGA and K-M plotter database were applied and revealed that high PKD2 expression predicted poor outcome and related with lymph nodes metastasis in lung cancer. IHC and qRT-PCR were performed and found PKD2 was elevated in lung adenocarcinoma and negatively related with OS (p = 0.015), PFS (p = 0.006) and the level of E-cadherin (p = 0.021). Experiment in lung adenocarcinoma cell lines demonstrated up-regulation of PKD2 led to high expression of mesenchymal markers (N-cadherin, vim, mmp9 et al.) and EMT transcription factors(zeb1, twist, snail), and the results were reversed when PKD2 was knocked down. Further investigation showed that abrogation of PKD2 inhibited A549 cell migration, invasion, proliferation and induced cell arrest in G2/M phase. We concluded that high expression of PKD2 was associated with poor prognosis and cancer progression in lung adenocarcinoma patients by promoting EMT.
Endogenous Neurosteroid (3α,5α)3-Hydroxypregnan-20-one Inhibits Toll-like-4 Receptor Activation and Pro-inflammatory Signaling in Macrophages and Brain
Authors: Balan Irina , Beattie Matthew C. , O’Buckley Todd K. , Aurelian Laure , Morrow A. Leslie
Published: February 2019

The endogenous neurosteroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) has protective activity in animal models of alcoholism, depression, traumatic brain injury, schizophrenia, multiple sclerosis, and Alzheimer’s disease that is poorly understood. Because these conditions involve proinflammatory signaling through toll-like receptors (TLRs), we examined the effects of 3α,5α-THP, and pregnenolone on TLR4 activation in both the periphery and the central nervous system (CNS). We used monocytes/macrophages (RAW264.7) as a model of peripheral immune signaling and studied innately activated TLR4 in the ventral tegmental area (VTA) of selectively bred alcohol-preferring (P) rats. LPS activated the TLR4 pathway in RAW264.7 cells as evidenced by increased levels of p-TAK1, TRAF6, NF-κB p50, phospho-NF-κB- p65, pCREB, HMGB1, and inflammatory mediators, including MCP-1 and TNFα. Both 3α,5α-THP and pregnenolone (0.5–1.0μM) substantially (~80%) inhibited these effects, indicating pronounced inhibition of TLR4 signaling. The mechanism of inhibition appears to involve blockade of TLR4/MD-2 protein interactions in RAW246.7 cells. In VTA, 3α,5α-THP (15 mg/kg, IP) administration reduced TRAF6 (~20%), CRF (~30%), and MCP-1 (~20%) levels, as well as TLR4 binding to GABAA receptor α2 subunits (~60%) and MyD88 (~40%). The data suggest that inhibition of proinflammatory neuroimmune signaling underlies protective effects of 3α,5α-THP in immune cells and brain, apparently involving blocking of protein-protein interactions that initiate TLR4-dependent signaling. Inhibition of pro-inflammatory TLR4 activation represents a new mechanism of 3α,5α-THP action in the periphery and the brain.
High percentages and activity of synovial fluid NK cells present in patients with advanced stage active Rheumatoid Arthritis
Authors: Yamin Rachel , Berhani Orit , Peleg Hagit , Aamar Suhail , Stein Natan , Gamliel Moriya , Hindi Issam , Scheiman-Elazary Anat , Gur Chamutal
Published: February 2019

Rheumatoid Arthritis (RA) causes chronic inflammation of joints. The cytokines TNFα and IFNγ are central players in RA, however their source has not been fully elucidated. Natural Killer (NK) cells are best known for their role in elimination of viral-infected and transformed cells, and they secrete pro-inflammatory cytokines. NK cells are present in the synovial fluids (SFs) of RA patients and are considered to be important in bone destruction. However, the phenotype and function of NK cells in the SFs of patients with erosive deformative RA (DRA) versus non-deformative RA (NDRA) is poorly characterized. Here we characterize the NK cell populations present in the blood and SFs of DRA and NDRA patients. We demonstrate that a distinct population of activated synovial fluid NK (sfNK) cells constitutes a large proportion of immune cells found in the SFs of DRA patients. We discovered that although sfNK cells in both DRA and NDRA patients have similar phenotypes, they function differently. The DRA sfNK secrete more TNFα and IFNγ upon exposure to IL-2 and IL-15. Consequently, we suggest that sfNK cells may be a marker for more severely destructive RA disease.
Critical comparison of methods for fault diagnosis in metabolomics data
Authors: Koeman M. , Engel J. , Jansen J. , Buydens L.
Published: February 2019

Platforms like metabolomics provide an unprecedented view on the chemical versatility in biomedical samples. Many diseases reflect themselves as perturbations in specific metabolite combinations. Multivariate analyses are essential to detect such combinations and associate them to specific diseases. For this, usually targeted discriminations of samples associated to a specific disease from non-diseased control samples are used. Such targeted data interpretation may not respect the heterogeneity of metabolic responses, both between diseases and within diseases. Here we show that multivariate methods that find any set of perturbed metabolites in a single patient, may be employed in combination with data collected with a single metabolomics technology to simultaneously investigate a large array of diseases. Several such untargeted data analysis approaches have been already proposed in other fields to find both expected and unexpected perturbations, e.g. in Statistical Process Control. We have critically compared several of these approaches for their sensitivity and their correct identification of the specifically perturbed metabolites. Also a new approach is introduced for this purpose. The newly introduced Sparse Mean approach, which we find here as most sensitive and best able to identify the specifically perturbed metabolites, turns metabolomics into an untargeted diagnostic platform. Aside from metabolomics, the proposed approach may greatly benefit fault diagnosis with untargeted analyses in many other fields, such as Industrial Process Control, food Adulteration Detection, and Intrusion Detection.
Revealing Solid Properties of High-energy-density Molecular Cocrystals from the Cooperation of Hydrogen Bonding and Molecular Polarizability
Authors: Zhang Lei , Jiang Sheng-Li , Yu Yi , Chen Jun
Published: February 2019

In the domain of high-energy-density materials, the understanding to physico-chemical properties has long been primarily based on molecular structures whereas the crystal packing effect that significantly affects solid properties has been seldom involved. Herewith we predict the solid properties of six novel energetic cocrystals by taking into account of the crystal packing effect using a quantum chemistry method. We discover that the hydrogen bonding causes an increase in the molecular polarizability and their cooperation significantly changes the solid-state nature of the cocrystals compared to the pristine crystal and the gas counterparts. For example, stabilizing the multi-component molecular association by increasing the binding energy by 19–41% over the pristine crystals, improving the detonation performance by 5–10% and reducing the sensitivity to external stimuli compared to their pure crystal or gas counterparts. Therefore, the solid nature of the cocrystal is not a simple combination of the pure crystalline properties of its components and the heterogeneous molecular coupling effects must be considered to design improved functional cocrystals.
Theoretical requirements and inverse design for broadband perfect absorption of low-frequency waterborne sound by ultrathin metasurface
Authors: Zhong Jie , Zhao Honggang , Yang Haibin , Wang Yang , Yin Jianfei , Wen Jihong
Published: February 2019

Effective absorption of low-frequency waterborne sound with subwavelength absorbers has always been a challenging work. In this paper, we derive two theoretical requirements for broadband perfect absorption of low-frequency waterborne sound by ultrathin acoustic metasurface under a finite-thickness steel plate followed by semi-infinite air. Based on the theoretical requirements, an acoustic metasurface, a rubber layer embedded periodically with cavities, is inversely designed to achieve perfect absorption at 500 Hz. The metasurface is as thin as 1% of the working wavelength and maintains a substantially high absorptance over a relatively broad bandwidth. The perfect absorption peak is attributed to the overall resonance mode of the metasurface/steel plate system. Besides, high absorption can still be achieved even if the loss factor of the given rubber material cannot meet the ideal requirement. Finally, a strategy to utilize the inherent frequency-dependent characteristics of dynamic parameters of rubber material is suggested to achieve an ultra-broadband perfect absorption. When the frequency-dependent characteristics of the given rubber matrix cannot meet the theoretical requirements, a broadband super-absorption can still be realized by properly designing the frequency position of perfect absorption of the cavity-based metasurface.
Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells
Authors: Mahendrasingam Shanthini , Furness David N.
Published: February 2019

Transmembrane channel like protein 1 (TMC1) is likely to be a pore-forming subunit of the transduction channel of cochlear hair cells that is mechanically gated by tension on tip links in the stereocilia bundle. To localise TMC1 precisely, we labelled mice cochleae of different ages using custom-made polyclonal antibodies to TMC1 for light and transmission electron microscopy (TEM). Immunofluorescence revealed stereocilia labelling at P9 but not at P3 in apical hair cells. Immunogold labelling for TEM confirmed that labelling was absent at P3, and showed weak labelling at P6 with no stereocilia tip labelling, increasing at P9, with specific tip labelling on shorter stereocilia and some throughout the bundle. At P12 and P21, labelling was refined mostly to stereocilia tips. Quantification showed that labelling overall reached maximum by P12, labelling per tip was relatively constant from P9 to P21, but percent tips labelled was reduced from 16% to 8%. Tmc1−/− showed no labelling. Thus TMC1 occurs at the lower end of the tip link, supporting its presence in the MET complex and likely the channel. Tip localisation from P9 onwards coincides with lipoma HMGIC fusion partner-like 5 (LHFPL5), a protein that may be involved in acquiring/maintaining TMC1 localisation.
Selection for background matching drives sympatric speciation in Wall Gecko
Authors: Fulgione Domenico , Buglione Maria , Rippa Daniela , Trapanese Martina , Petrelli Simona , Monti Daria Maria , Aria Massimo , Del Giudice Rita , Maselli Valeria
Published: February 2019

The Wall Gecko shows heterogeneous colour pattern, which may vary among individuals, depending on the time of day and on the habitat segregation. Nocturnal pale geckos live exclusively on walls. Diurnal dark geckos preferentially live on olive tree trunks, demonstrating an ability to change skin colour that is superior to that of the pale gecko and allows diurnal geckos becoming camouflaged on the diverse substrates occupied during the day. In our study, the nocturnal/pale/wall and diurnal/dark/trunk geckos could be considered the extremes of an ecological cline of morphological variation on which divergent selection may be acting. Combining the effect of balancing selection on nocturnal geckos and disruptive selection between two sympatric populations could lead to speciation. All geckos analysed here belong to the same species, as confirmed by genetic characterization, however diurnal and nocturnal gecko populations seem to be in an early stage of incipient speciation. These two different morphs still combine genes, as revealed by neutral genetic markers, yet they show complete separation according to the analyses of mtDNA coding genes. Experimental results show that diurnal and nocturnal geckos do not swap their niches, likely because the predation pressure causes severe selection for background matching. Genomic analysis of complete mtDNA suggests that nocturnal geckos seem to be under balancing selection perhaps due to the narrow niche in which they live, whereas the daytime population has more opportunity in fitting into the multiple available niches, and they experience positive selection. Here we hypothesize that the ecological segregation that we are witnessing between the nocturnal and diurnal geckos, can lead to a ecological speciation.
Flexible Printed Monolithic-Structured Solid-State Dye Sensitized Solar Cells on Woven Glass Fibre Textile for Wearable Energy Harvesting Applications
Authors: Liu Jingqi , Li Yi , Yong Sheng , Arumugam Sasikumar , Beeby Steve
Published: February 2019

Previously, textile dye sensitised solar cells (DSSCs) woven using photovoltaic (PV) yarns have been demonstrated but there are challenges in their implementation arising from the mechanical forces in the weaving process, evaporation of the liquid electrolyte and partially shaded cells area, which all reduce the performance of the cell. To overcome these problems, this paper proposes a novel fabrication process for a monolithic-structured solid-state dye sensitized solar cell (ssDSSC) on textile using all solution based processes. A glass fibre textile substrate was used as the target substrate for the printed ssDSSC that contain multiple layers of electrodes and active materials. The printed ssDSSC on textile have been successfully demonstrated and compared with a reference device made with the same processes on a glass substrate. All PV textile devices were characterized under simulated AM 1.5 conditions and a peak efficiency of 0.4% was achieved. This approach is potentially suitable for the low cost integration of PV devices onto high temperature textiles, but to widen the range of applications future research is required to reduce the processing temperature to enable the device to be fabricated on the standard fabric substrates.
Associations of maternal vitamin D, PTH and calcium with hypertensive disorders of pregnancy and associated adverse perinatal outcomes: Findings from the Born in Bradford cohort study
Authors: Santorelli Gillian , Whitelaw Donald , Farrar Diane , West Jane , Lawlor Debbie A.
Published: February 2019

Vitamin D and parathyroid hormone (PTH) regulate mineral metabolism and are required to maintain calcium levels. Vitamin D deficiency is common, particularly during pregnancy, and has been associated with hypertensive disorders of pregnancy. We sought to determine whether maternal 25(OH)D, PTH and calcium concentrations at 26 weeks gestation are associated with adverse outcomes of pregnancy and establish whether these differ by ethnicity. This study included 476 White British and 534 Pakistani origin mother-offspring pairs from the Born in Bradford cohort study. We used multinomial or logistic regression to explore the association between vitamin D, PTH and calcium with gestational hypertension (GH), pre-eclampsia (PE), caesarean section (CS), preterm birth (PTB) and small for gestational age (SGA). Pakistani women had lower 25(OH)D (median 13.0 vs 36.0 nmol/L), higher PTH (median 7.7 vs 3.3 pmol/L) and similar calcium concentrations compared to White British women. In Pakistani women, higher concentrations of 25(OH)D were associated with a 60% increased odds of GH, and a 37% reduced odds of SGA; PTH was associated with a 45% reduction in the odds of GH. In White British women, each 1 SD increase in calcium concentration was associated with a 34% increase in developing GH but a 33% reduction in the odds of PTB. Associations with PE and CS were consistent with the null. In conclusion, there are ethnic differences in the associations of 25(OH)D, PTH and calcium with important perinatal outcomes. Future research would benefit from examining the associations of 25(OH)D, PTH and calcium together with a range of perinatal outcomes in order to assess the risk-benefit action of each.
Acoustic Emission from Porous Collapse and Moving Dislocations in Granular Mg-Ho Alloys under Compression and Tension
Authors: Chen Yan , Ding Xiangdong , Fang Daqing , Sun Jun , Salje Ekhard K. H.
Published: February 2019

We identified heterogeneous Mg-Ho alloys as an ideal material to measure the most extensive acoustic emission spectra available. Mg-Ho alloys are porous and show a high density of dislocations, which slide under external tension and compression. These dislocations nucleate near numerous heterogeneities. Two mechanisms compete under external forcing in the structural collapse, namely collapsing holes and the movements of dislocations. Their respective fingerprints in acoustic emission (AE) measurements are very different and relate to their individual signal strengths. Porous collapse generates very strong AE signals while dislocation movements create more but weaker AE signals. This allows the separation of the two processes even though they almost always coincide temporarily. The porous collapse follows approximately mean-field behavior (ε = 1.4, τ’ = 1.82, α = 2.56,x = 1.93, χ = 1.95) with mean field scaling fulfilled. The exponents for dislocation movement are greater (ε = 1.92, τ’ = 2.44, α = 3.0,x = 1.7, χ = 1.42) and follows approximately the force integrated mean-field predictions. The Omori scaling is similar for both mechanisms. The Bath’s law is well fulfilled for the porous collapse but not for the dislocation movements. We suggest that such ‘complex’ mixing behavior is dominant in many other complex materials such as (multi-) ferroics, entropic alloys and porous ferroelastics, and, potentially, homogeneous materials with the simultaneous appearance of different collapse mechanisms.
Diversity and environmental distribution of the cosmopolitan endosymbiont “Candidatus Megaira”
Authors: Lanzoni Olivia , Sabaneyeva Elena , Modeo Letizia , Castelli Michele , Lebedeva Natalia , Verni Franco , Schrallhammer Martina , Potekhin Alexey , Petroni Giulio
Published: February 2019

Members of the order Rickettsiales are often found in association with ciliated protists. An interesting case is the bacterial endosymbiont “Candidatus Megaira”, which is phylogenetically closely related to the pathogen Rickettsia. “Candidatus Megaira” was first described as an intracellular bacterium in several ciliate species. Since then it has been found in association with diverse evolutionary distantly-related hosts, among them other unicellular eukaryotes, and also algae, and metazoa, such as cnidarians. We provide the characterization of several new strains of the type species “Candidatus Megaira polyxenophila”, and the multidisciplinary description of a novel species, “Candidatus Megaira venefica”, presenting peculiar features, which highlight the diversity and variability of these widespread bacterial endosymbionts. Screening of the 16S rRNA gene short amplicon database and phylogenetic analysis of 16S rRNA gene hypervariable regions revealed the presence of further hidden lineages, and provided hints on the possibility that these bacteria may be horizontally transmitted among aquatic protists and metazoa. The phylogenetic reconstruction supports the existence of at least five different separate species-level clades of “Candidatus Megaira”, and we designed a set of specific probes allowing easy recognition of the four major clades of the genus.
In-Situ observation of local atomic structure of Al-Cu-Fe quasicrystal formation
Authors: Parsamehr Hadi , Lu Ying-Jiu , Lin Tzu-Ying , Tsai An-Pang , Lai Chih-Huang
Published: February 2019

The phase and local environment, neighbouring atoms and coordination numbers (CN), for an Al-Cu-Fe multilayer were studied during heating (to 800 °C) and cooling (to room temperature) processes using in-situ X-Ray diffraction (XRD) and in-situ X-ray absorption spectroscopy (XAS) techniques to investigate the formation of Al-Cu-Fe quasicrystals (QCs). In-situ XRD clarified the transition of the ω-Al7Cu2Fe phase to a liquid state at the high temperature which transformed into the QC phase during cooling. The in-situ XAS showed a relatively small shift in distance between Cu-Al and Fe-Al during the phase evolution from RT to 700 °C. The distance between Cu-Cu, however, showed a significant increase from ω-phase at 700 °C to the liquid state at 800 °C, and this distance was maintained after QC formation. Furthermore, the CN of Fe-Al was changed to N = 9 during cooling. Through our observations of changes in CN, atomic distances and the atomic environment, we propose the local structural ordering of the quasicrystalline phase originated from a liquid state via ω-phase. In this study, we give a clear picture of the atomic environment from the crystalline to the quasicrystalline phase during the phase transitions, which provides a better understanding of the synthesis of functional QC nanomaterials.
Interplay between Josephson and Aharonov-Bohm effects in Andreev interferometers
Authors: Dolgirev Pavel E. , Kalenkov Mikhail S. , Zaikin Andrei D.
Published: February 2019

Proximity induced quantum coherence of electrons in multi-terminal voltage-driven hybrid normal-superconducting nanostructures may result in a non-trivial interplay between topology-dependent Josephson and Aharonov-Bohm effects. We elucidate a trade-off between stimulation of the voltage-dependent Josephson current due to non-equilibrium effects and quantum dephasing of quasiparticles causing reduction of both Josephson and Aharonov-Bohm currents. We also predict phase-shifted quantum coherent oscillations of the induced electrostatic potential as a function of the externally applied magnetic flux. Our results may be employed for engineering superconducting nanocircuits with controlled quantum properties.