bluuebunny/crossref_metadata_2025 huggingface dataset:
MD001, a Novel Peroxisome Proliferator-activated Receptor α/γ Agonist, Improves Glucose and Lipid Metabolism
Authors: Kim Seok-Ho , Hong Shin Hee , Park Young-Joon , Sung Jong-Hyuk , Suh Wonhee , Lee Kyeong Won , Jung Kiwon , Lim Changjin , Kim Jin-Hee , Kim Hyoungsu , Park Kyong Soo , Park Sang Gyu
Published: February 2019

Peroxisome proliferator-activated receptor (PPAR)-α/γ dual agonists have been developed to treat metabolic diseases; however, most of them exhibit side effects such as body weight gain and oedema. Therefore, we developed a novel PPARα/γ dual agonist that modulates glucose and lipid metabolism without adverse effects. We synthesised novel compounds composed of coumarine and chalcone, determined their crystal structures, and then examined their binding affinity toward PPARα/γ. We investigated the expression of PPARα and PPARγ target genes by chemicals in HepG2, differentiated 3T3-L1, and C2C12 cells. We examined the effect of chemicals on glucose and lipid metabolism in db/db mice. Only MD001 functions as a PPARα/γ dual agonist in vitro. MD001 increased the transcriptional activity of PPARα and PPARγ, resulting in enhanced expression of genes related to β-oxidation and fatty acid and glucose uptake. MD001 significantly improved blood metabolic parameters, including triglycerides, free fatty acids, and glucose, in db/db mice. In addition, MD001 ameliorated hepatic steatosis by stimulating β-oxidation in vitro and in vivo. Our results demonstrated the beneficial effects of the novel compound MD001 on glucose and lipid metabolism as a PPARα/γ dual agonist. Consequently, MD001 may show potential as a novel drug candidate for the treatment of metabolic disorders.
Satellite-based soil moisture provides missing link between summertime precipitation and surface temperature biases in CMIP5 simulations over conterminous United States
Authors: Al-Yaari A. , Ducharne A. , Cheruy F. , Crow W. T. , Wigneron J.-P.
Published: February 2019

Past studies have shown that climate simulations have substantial warm and dry biases during the summer in the conterminous United States (CONUS), particularly in the central Great Plains (CGP). These biases have critical implications for the interpretation of climate change projections, but the complex overlap of multiple land-atmosphere feedback processes make them difficult to explain (and therefore correct). Even though surface soil moisture (SM) is often cited as a key control variable in these processes, there are still knowledge gaps about its specific role. Here, we use recently developed remotely sensed SM products to analyse the link between spatial patterns of summertime SM, precipitation and air temperature biases over CONUS in 20 different CMIP5 simulations. We identify three main types of bias combinations: (i) a dry/warm bias over the CGP region, with a significant inter-model correlation between SM and air temperature biases (R = −0.65), (ii) a wet/cold bias in NW CONUS, and (iii) a dry/cold bias in SW CONUS. Combined with irrigation patterns, these results suggest that land-atmosphere feedbacks over the CGP are not only local but have a regional dimension, and demonstrate the added-value of large-scale SM observations for resolving the full feed-back loop between precipitation and temperature.
The major allergen Der p 2 is a cholesterol binding protein
Authors: Reginald Kavita , Chew Fook Tim
Published: February 2019

Der p 2 is a major dust mite allergen and >80% of mite allergic individuals have specific IgE to this allergen. Although it is well characterized in terms of allergenicity, there is still some ambiguity in terms of its biological function. Three-dimensional structural analysis of Der p 2 and its close homologues indicate the presence of a hydrophobic cavity which can potentially bind to lipid molecules. In this study, we aimed to identify the potential ligand of Der p 2. Using a liposome pulldown assay, we show that recombinant Der p 2 binds to liposomes prepared with exogenous cholesterol in a dose dependent fashion. Next, an ELISA based assay using immobilized lipids was used to study binding specificities of other lipid molecules. Cholesterol was the preferred ligand of Der p 2 among 11 different lipids tested. Two homologues of Der p 2, Der f 2 and Der f 22 also bound to cholesterol. Further, using liquid chromatography-mass spectrometry (LC-MS), we confirmed that cholesterol is the natural ligand of Der p 2. Three amino acid residues of Der p 2, V104, V106 and V110 are possible cholesterol binding sites, as alanine mutations of these residues showed a significant decrease in binding (p < 0.05) compared to wild-type Der p 2. These results provide the first direct experimental evidence that Der p 2 binds to cholesterol.
Heritability and genetic and environmental correlations of heart rate variability and baroreceptor reflex sensitivity with ambulatory and beat-to-beat blood pressure
Authors: Man Tengfei , Riese Harriëtte , Jaju Deepali , Muñoz M. Loretto , Hassan Mohammed O. , Al-Yahyaee Said , Bayoumi Riad A. , Comuzzie Anthony G. , Floras John S. , van Roon Arie M. , Nolte Ilja M. , Albarwani Sulayma , Snieder Harold
Published: February 2019

This family study from Oman (n = 1231) explored the heritability and genetic and environmental correlations of heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS) with ambulatory and beat-to-beat blood pressure (BP). Ambulatory BP was measured for 24 hours to calculate mean values for daytime and sleep separately. Time and frequency domain HRV indices, BRS, office beat-to-beat BP, and heart rate (HR) were measured for 10 minutes at rest. SOLAR software was used to perform univariate and bivariate quantitative genetic analyses adjusting for age, age2, sex, their interactions and BMI. Heritability of SBP and DBP ranged from 16.8% to 40.4% for daytime, sleeping, 24-hour and office beat-to-beat measurements. HR and BRS showed a heritability of 31.9% and 20.6%, respectively, and for HRV indices heritability ranged from 11.1% to 20.5%. All HRV measurements and BRS were found to be negatively correlated with BP, but phenotypic correlation coefficients were relatively weak; HR was positively correlated with BP. None of the genetic correlations were statistically significant while environmental factors explained most of the correlations for all HRV indices with BP. Our study found consistent but weak correlations among HRV, HR, BRS and ambulatory/office beat-to-beat BP. However, environmental rather than genetic factors contributed most to those correlations.
Implementation of digital optical phase conjugation with embedded calibration and phase rectification
Authors: Yu Zhipeng , Xia Meiyun , Li Huanhao , Zhong Tianting , Zhao Fangyuan , Deng Hao , Li Zihao , Li Deyu , Wang Daifa , Lai Puxiang
Published: February 2019

Focused and controllable optical delivery beyond the optical diffusion limit in biological tissue has been desired for long yet considered challenging. Digital optical phase conjugation (DOPC) has been proven promising to tackle this challenge. Its broad applications, however, have been hindered by the system’s complexity and rigorous requirements, such as the optical beam quality, the pixel match between the wavefront sensor and wavefront modulator, as well as the flatness of the modulator’s active region. In this paper, we present a plain yet reliable DOPC setup with an embedded four-phase, non-iterative approach that can rapidly compensate for the wavefront modulator’s surface curvature, together with a non-phase-shifting in-line holography method for optical phase conjugation in the absence of an electro-optic modulator (EOM). In experiment, with the proposed setup the peak-to-background ratio (PBR) of optical focusing through a standard ground glass in experiment can be improved from 460 up to 23,000, while the full width at half maximum (FWHM) of the focal spot can be reduced from 50 down to 10 μm. The focusing efficiency, as measured by the value of PBR, reaches nearly 56.5% of the theoretical value. Such a plain yet efficient implementation, if further engineered, may potentially boost DOPC suitable for broader applications.
eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes
Authors: Imam Shahnawaz , Prathibha R. , Dar Pervaiz , Almotah Khalil , Al-Khudhair Ahmed , Hasan Syed Abdul-Moiz , Salim Nancy , Jilani Talha Naser , Mirmira Raghavendra G. , Jaume Juan Carlos
Published: February 2019

We have developed a transgenic mouse model of Type 1 Diabetes (T1D) in which human GAD65 is expressed in pancreatic β-cells, and human MHC-II is expressed on antigen presenting cells. Induced GAD65 antigen presentation activates T-cells, which initiates the downstream events leading to diabetes. In our humanized mice, we have shown downregulation of eukaryotic translation initiation factor 5 A (elF5A), expressed only in actively dividing mammalian cells. In-vivo inhibition of elF5A hypusination by deoxyhypusine synthase (DHS) inhibitor “GC7” was studied; DHS inhibitor alters the pathophysiology in our mouse model by catalyzing the crucial hypusination and the rate-limiting step of elF5A activation. In our mouse model, we have shown that inhibition of eIF5A resets the pro-inflammatory bias in the pancreatic microenvironment. There was: (a) reduction of Th1/Th17 response, (b) an increase in Treg numbers, (c) debase in IL17 and IL21 cytokines levels in serum, (d) lowering of anti-GAD65 antibodies, and (e) ablation of the ER stress that improved functionality of the β-cells, but minimal effect on the cytotoxic CD8 T-cell (CTL) mediated response. Conclusively, immune modulation, in the case of T1D, may help to manipulate inflammatory responses, decreasing disease severity, and may help manage T1D in early stages of disease. Our study also demonstrates that without manipulating the CTLs mediated response extensively, it is difficult to treat T1D.
A novel approach to triple-negative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses
Authors: Prado-Vázquez Guillermo , Gámez-Pozo Angelo , Trilla-Fuertes Lucía , Arevalillo Jorge M. , Zapater-Moros Andrea , Ferrer-Gómez María , Díaz-Almirón Mariana , López-Vacas Rocío , Navarro Hilario , Maín Paloma , Feliú Jaime , Zamora Pilar , Espinosa Enrique , Fresno Vara Juan Ángel
Published: February 2019

Triple-negative breast cancer is a heterogeneous disease characterized by a lack of hormonal receptors and HER2 overexpression. It is the only breast cancer subgroup that does not benefit from targeted therapies, and its prognosis is poor. Several studies have developed specific molecular classifications for triple-negative breast cancer. However, these molecular subtypes have had little impact in the clinical setting. Gene expression data and clinical information from 494 triple-negative breast tumors were obtained from public databases. First, a probabilistic graphical model approach to associate gene expression profiles was performed. Then, sparse k-means was used to establish a new molecular classification. Results were then verified in a second database including 153 triple-negative breast tumors treated with neoadjuvant chemotherapy. Clinical and gene expression data from 494 triple-negative breast tumors were analyzed. Tumors in the dataset were divided into four subgroups (luminal-androgen receptor expressing, basal, claudin-low and claudin-high), using the cancer stem cell hypothesis as reference. These four subgroups were defined and characterized through hierarchical clustering and probabilistic graphical models and compared with previously defined classifications. In addition, two subgroups related to immune activity were defined. This immune activity showed prognostic value in the whole cohort and in the luminal subgroup. The claudin-high subgroup showed poor response to neoadjuvant chemotherapy. Through a novel analytical approach we proved that there are at least two independent sources of biological information: cellular and immune. Thus, we developed two different and overlapping triple-negative breast cancer classifications and showed that the luminal immune-positive subgroup had better prognoses than the luminal immune-negative. Finally, this work paves the way for using the defined classifications as predictive features in the neoadjuvant scenario.
Structure modulated charge transfer in carbon atomic wires
Authors: Milani A. , Barbieri V. , Facibeni A. , Russo V. , Li Bassi A. , Lucotti A. , Tommasini M. , Tzirakis M. D. , Diederich F. , Casari C. S.
Published: February 2019

sp-Hybridized carbon atomic wires are appealing systems with large property tunability. In particular, their electronic properties are intimately related to length, structure, and type of functional end-groups as well as to other effects such as the intermolecular charge transfer with metal nanoparticles. Here, by a combined Raman, Surface Enhanced Raman Scattering (SERS) investigation and first principles calculations of different N,N-dimethylanilino-terminated polyynes, we suggest that, upon charge transfer interaction with silver nanoparticles, the function of sp-carbon atomic wire can change from electron donor to electron acceptor by increasing the wire length. In addition, the insertion into the wire of a strong electrophilic group (1,1,4,4-tetracyanobuta-1,3-diene-2,3-diyl) changes the electron-accepting molecular regions involved in this intermolecular charge transfer. Our results indicate that carbon atomic wires could display a tunable charge transfer between the sp-wire and the metal, and hold promise as active materials in organic optoelectronics and photovoltaics.
Imaging of nanoparticle dynamics in live and apoptotic cells using temporally-modulated polarization
Authors: Wagner Omer , Schultz Moty , Edri Eitan , Meir Rinat , Barnoy Eran , Meiri Amihai , Shpaisman Hagay , Sloutskin Eli , Zalevsky Zeev
Published: February 2019

Gold nanoparticles are widely exploited in phototherapy. Owing to their biocompatibility and their strong visible-light surface plasmonic resonance, these particles also serve as contrast agents for cell image enhancement and super-resolved imaging. Yet, their optical signal is still insufficiently strong for many important real-life applications. Also, the differentiation between adjacent nanoparticles is usually limited by the optical resolution and the orientations of non-spherical particles are unknown. These limitations hamper the progress in cell research by direct optical microscopy and narrow the range of phototherapy applications. Here we demonstrate exploiting the optical anisotropy of non-spherical nanoparticles to achieve super-resolution in live cell imaging and to resolve the intracellular nanoparticle orientations. In particular, by modulating the light polarization and taking advantage of the polarization-dependence of gold nanorod optical properties, we realize the ‘lock-in amplification’, widely-used in electronic engineering, to achieve image enhancement in live cells and in cells that undergo apoptotic changes.
Transcriptome profiling of zebrafish optic fissure fusion
Authors: Richardson R. , Owen N. , Toms M. , Young Rodrigo M. , Tracey-White D. , Moosajee M.
Published: February 2019

Incomplete fusion of the optic fissure leads to ocular coloboma, a congenital eye defect that affects up to 7.5 per 10,000 births and accounts for up to 10 percent of childhood blindness. The molecular and cellular mechanisms that facilitate optic fissure fusion remain elusive. We have profiled global gene expression during optic fissure morphogenesis by transcriptome analysis of tissue dissected from the margins of the zebrafish optic fissure and the opposing dorsal retina before (32 hours post fertilisation, hpf), during (48 hpf) and after (56 hpf) optic fissure fusion. Differential expression analysis between optic fissure and dorsal retinal tissue resulted in the detection of several known and novel developmental genes. The expression of selected genes was validated by qRT-PCR analysis and localisation investigated using in situ hybridisation. We discuss significantly overrepresented functional ontology categories in the context of optic fissure morphogenesis and highlight interesting transcripts from hierarchical clustering for subsequent analysis. We have identified netrin1a (ntn1a) as highly differentially expressed across optic fissure fusion, with a resultant ocular coloboma phenotype following morpholino antisense translation-blocking knockdown and downstream disruption of atoh7 expression. To support the identification of candidate genes in human studies, we have generated an online open-access resource for fast and simple quantitative querying of the gene expression data. Our study represents the first comprehensive analysis of the zebrafish optic fissure transcriptome and provides a valuable resource to facilitate our understanding of the complex aetiology of ocular coloboma.
Objective risk stratification of prostate cancer using machine learning and radiomics applied to multiparametric magnetic resonance images
Authors: Varghese Bino , Chen Frank , Hwang Darryl , Palmer Suzanne L , De Castro Abreu Andre Luis , Ukimura Osamu , Aron Monish , Aron Manju , Gill Inderbir , Duddalwar Vinay , Pandey Gaurav
Published: February 2019

Multiparametric magnetic resonance imaging (mpMRI) has become increasingly important for the clinical assessment of prostate cancer (PCa), but its interpretation is generally variable due to its relatively subjective nature. Radiomics and classification methods have shown potential for improving the accuracy and objectivity of mpMRI-based PCa assessment. However, these studies are limited to a small number of classification methods, evaluation using the AUC score only, and a non-rigorous assessment of all possible combinations of radiomics and classification methods. This paper presents a systematic and rigorous framework comprised of classification, cross-validation and statistical analyses that was developed to identify the best performing classifier for PCa risk stratification based on mpMRI-derived radiomic features derived from a sizeable cohort. This classifier performed well in an independent validation set, including performing better than PI-RADS v2 in some aspects, indicating the value of objectively interpreting mpMRI images using radiomics and classification methods for PCa risk assessment.
Effect of sexual transmission on the West Africa Ebola outbreak in 2014: a mathematical modelling study
Authors: Luo Dongmei , Zheng Rongjiong , Wang Duolao , Zhang Xueliang , Yin Yi , Wang Kai , Wang Weiming
Published: February 2019

The outbreak of the Ebola virus has resulted in significant morbidity and mortality in the affected areas, and Ebola virus RNA has been found in the semen of the survivors after 9 months of symptom onset. However, the role that sexual transmission played in the transmission is not very clear. In this paper, we developed a compartmental model for Ebola virus disease (EVD) dynamics, which includes three different infectious routes: contact with the infectious, contact with dead bodies, and transmission by sexual behaviour with convalescent survivors. We fitted the model to daily cumulative cases from the first reported infected case to October 25, 2014 for the epidemic in Sierra Leone, Liberia and Guinea. The basic reproduction numbers in these countries were estimated as 1.6726 (95%CI:1.5922–1.7573), 1.8162 (95%CI:1.7660–1.8329) and 1.4873 (95%CI:1.4770–1.4990), respectively. We calculated the contribution of sexual transmission to the basic reproduction number R0 as 0.1155 (6.9%), 0.0236 (2.8%) and 0.0546 (3.7%) in Sierra Leone, Liberia and Guinea, respectively. Sensitivity analysis shows that the transmission rates caused by contacts with alive patients and sexual activities with convalescent patients have stronger impacts on the R0. These results suggest that isolating the infectious individuals and advising the recovery men to avoid sexual intercourse are efficient ways for the eradication of endemic EVD.
Thermal Decomposition and Nonisothermal Kinetics of Monoethanolamine Mixed with Various Metal Ions
Authors: Wei Mengning , Huang An-Chi , Shu Chi-Min , Zhang Lijing
Published: February 2019

Ethanolamine is a critical chemical for petrochemical enterprises. When corrosion occurs in pipelines, equipment, and containers in petrochemical enterprises, minute amounts of metal ions are released. In this study, the thermal decomposition and nonisothermal kinetics of monoethanolamine (MEA) and MEA mixed with copper and zinc ions were analyzed using thermogravimetry (TG) and differential scanning calorimetry (DSC). The TG tests revealed that MEA mixed with copper (II) and zinc (II) began thermal decomposition at 75.2 and 60.3 °C, respectively, whereas pure MEA began thermal decomposition at 89.7 °C. Two exothermic peaks were observed in the DSC curves for MEA mixed with copper (II) and zinc (II), and thermokinetic parameters were obtained from DSC data. The apparent activation energy (Ea) of each stage was calculated using several nonisothermal kinetic methods, namely the ASTM E698, Kissinger–Akahira–Sunose, Starink, and Flynn–Wall–Ozawa methods. The Ea of pure MEA was 28.7 ± 2.5 kJ/mol, whereas that of the copper and zinc mixtures were 80.5 ± 1.1 and 46.8 ±1.7 kJ/mol, respectively. The results can be used to improve the intrinsic safety of storage tanks and petrochemical plants.
Optically Guided Epidural Needle Placement Using 405-nm Wavelength for Accurate Puncture
Authors: Lin Su-Man , Gong Cihun-Siyong Alex , Chiang Tai-An , Tsou Mei-Yung , Ting Chien-Kun
Published: February 2019

Several approaches of locating the epidural space have been proposed. However, loss of Resistance method (LOR) remains the most common method for epidural anesthesia. Different optical signals were received from the ligamentum flavum and the epidural space allows operator to pinpoint position of the needle and determine whether the needle tip has entered the epidural space. Optical signals throughout the penetration process was recorded and position of needle tip was confirmed with a C-arm fluoroscopy. 60 lumbar punctures were performed in 20 vivo porcine models, and success rate of locating the epidural space with the optical auxiliary is calculated statistically. The data are expressed in mean ± SD. During all the lumber puncture processes, the strength of optical signals received decreased significantly while the needle tip penetrates the ligamentum flavum and entered the epidural space. The strength of optical signal received when needle tip was in the ligamentum flavum was 1.38 ± 0.57. The signal strength at epidural space was 0.46 ± 0.35. Strength of signal decreased by 67% when entered epidural space, and there is no significant differences in decrease of strength from data obtained from thevertebrae (lumbar segments)L2-L3, L3-L4, and L4-L5. Finally, we calculated with assistance of the proposed optical auxiliary, the success rate for guiding the needle tip to the epidural space using was as high as 87%. It is evidently believed that the optical auxiliary equipped is visualized to assist operators inserting needle accurately and efficiently into epidural space during epidural anesthesia operation.
Fluid Containing Structures in the tips of the fingers and toes delineated by Ultrasound Imaging before and after Induced Skin Wrinkling
Authors: Gechev Antonin
Published: February 2019

This Ultrasound study identified spaces within the pulp of distal phalanx of the fingers and toes that halve in area after Water Induced Skin Wrinkling. These spaces appeared as fluid filled sacculi between connective tissue compartments accountable for distending digital pulp under normal circumstances and skin wrinkling after water immersion. Whilst studying conditions related to sympathetic nerve function with WISW ultrasound imaging is a valuable adjunct to the visual assessment.
Normalization strategies differently affect circulating miRNA profile associated with the training status
Authors: Faraldi Martina , Gomarasca Marta , Sansoni Veronica , Perego Silvia , Banfi Giuseppe , Lombardi Giovanni
Published: February 2019

MicroRNAs are fine regulators of the whole-body adaptive response but their use as biomarkers is limited by the lack of standardized pre- and post-analytical procedures. This work aimed to compare different normalization approaches for RT-qPCR data analyses, in order to identify the most reliable and reproducible method to analyze circulating miRNA expression profiles in sedentary and highly-trained subjects. As the physically active status is known to affect miRNA expression, they could be effective biomarkers of the homeostatic response. Following RNA extraction from plasma, a panel of 179 miRNAs was assayed by RT-qPCR and quantified by applying different normalization strategies based on endogenous miRNAs and exogenous oligonucleotides. hsa-miR-320d was found as the most appropriate reference miRNA in reducing the technical variability among the experimental replicates and, hence, in highlighting the inter-cohorts differences. Our data showed an association between the physically active status and specific skeletal muscle- and bone-associated circulating miRNAs profiles, revealing that established epigenetic modifications affect the baseline physiological status of these tissues. Since different normalization strategies led to different outputs, in order to avoid misleading interpretation of data, we remark the importance of the accurate choice of the most reliable normalization method in every experimental setting.
Optimal birth weight and term mortality risk differ among different ethnic groups in the U.S.
Authors: Jeon Jihyun , Kim Do-Hyun , Park Min Soo , Park Chang-Gi , Sriram Sudhir , Lee Kwang-Sun
Published: February 2019

Among European countries, optimal birth weight at which the mortality is minimal is shown to be different by country. We investigated this difference examining one geopolitical population, the U.S. term live births, born to the five groups of the same ethnic parents; White, Black, Hispanic, North Asian, and South Asian. North Asians and South Asians had more favorable maternal factors for birth weight. Yet, Whites had the highest mean birth weight and South Asians, the lowest. However, neonatal mortality rate in Whites was 0.78 per 1,000 live births, significantly higher than 0.36 and 0.72 per 1,000 live births in North Asians and South Asians, respectively. Other maternal factors hardly explained this ethnic disparity in birth weight or mortality. Optimal birth weight was greatest in Whites (3,890 g), and least in South Asians (3,491 g). However, neonatal mortality at optimal birth weight was significantly lower in North Asians. Adjustment of maternal factors except parental ethnicity changed little of this difference. Optimal birth weight and its mortality differ by ethnicity. On planning the best birth outcome in a population, one should consider the variable mortality risks by ethnicity.
Perceptual learning of task-irrelevant features depends on the sensory context
Authors: Bruns Patrick , Watanabe Takeo
Published: February 2019

The brain has evolved to extract behaviourally meaningful information from the environment. For example, it has been shown that visual perceptual learning (VPL) can occur for task-irrelevant stimulus features when those features are consistently paired with internal or external reinforcement signals. It is, however, unclear whether or not task-irrelevant VPL is influenced by stimulus features that are unrelated to reinforcement in a given sensory context. To address this question, we exposed participants to task-irrelevant and subliminal coherent motion stimuli in the background while they performed a central character identification task. A specific motion direction was consistently paired with the task-targets, while two other directions occurred only with distractors and, thus, were unrelated to reinforcement. We found that the magnitude of VPL of the target-paired direction was significantly greater when the distractor-paired directions were close to the target-paired direction, compared to when they were farther. Thus, even very weak signals that are both subliminal and unrelated to reinforcement are processed and exert an influence on VPL. This finding suggests that the outcome of VPL depends on the sensory context in which learning takes place and calls for a refinement of VPL theories to incorporate exposure-based influences on learning.
Plasmid DNA contaminant in molecular reagents
Authors: Wally N. , Schneider M. , Thannesberger J. , Kastner M. T. , Bakonyi T. , Indik S. , Rattei T. , Bedarf J. , Hildebrand F. , Law J. , Jovel J. , Steininger C.
Published: February 2019

Background noise in metagenomic studies is often of high importance and its removal requires extensive post-analytic, bioinformatics filtering. This is relevant as significant signals may be lost due to a low signal-to-noise ratio. The presence of plasmid residues, that are frequently present in reagents as contaminants, has not been investigated so far, but may pose a substantial bias. Here we show that plasmid sequences from different sources are omnipresent in molecular biology reagents. Using a metagenomic approach, we identified the presence of the (pol) of equine infectious anemia virus in human samples and traced it back to the expression plasmid used for generation of a commercial reverse transcriptase. We found fragments of multiple other expression plasmids in human samples as well as commercial polymerase preparations. Plasmid contamination sources included production chain of molecular biology reagents as well as contamination of reagents from environment or human handling of samples and reagents. Retrospective analyses of published metagenomic studies revealed an inaccurate signal-to-noise differentiation. Hence, the plasmid sequences that seem to be omnipresent in molecular biology reagents may misguide conclusions derived from genomic/metagenomics datasets and thus also clinical interpretations. Critical appraisal of metagenomic data sets for the possibility of plasmid background noise is required to identify reliable and significant signals.
Megathrust earthquake drives drastic organic carbon supply to the hadal trench
Authors: Kioka A. , Schwestermann T. , Moernaut J. , Ikehara K. , Kanamatsu T. , McHugh C. M. , dos Santos Ferreira C. , Wiemer G. , Haghipour N. , Kopf A. J. , Eglinton T. I. , Strasser M.
Published: February 2019

The giant 2011 Tohoku-oki earthquake has been inferred to remobilise fine-grained, young surface sediment enriched in organic matter from the slope into the >7 km deep Japan Trench. Yet, this hypothesis and assessment of its significance for the carbon cycle has been hindered by limited data density and resolution in the hadal zone. Here we combine new high-resolution bathymetry data with sub-bottom profiler images and sediment cores taken during 2012–2016 in order to map for the first time the spatial extent of the earthquake-triggered event deposit along the hadal Japan Trench. We quantify a sediment volume of ~0.2 km3 deposited from spatially-widespread remobilisation of young surficial seafloor slope sediments triggered by the 2011 earthquake and its aftershock sequence. The mapped volume and organic carbon content in sediment cores encompassing the 2011 event reveals that this single tectonic event delivered >1 Tg of organic carbon to the hadal trench. This carbon supply is comparable to high carbon fluxes described for other Earth system processes, shedding new light on the impact of large earthquakes on long-term carbon cycling in the deep-sea.
Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1
Authors: Vousden Katherine A. , Lundqvist Tomas , Popovic Bojana , Naiman Brian , Carruthers Alan M. , Newton Philip , Johnson Daniel J. D. , Pomowski Anja , Wilkinson Trevor , Dufner Patrick , de Mendez Isabelle , Mallinder Philip R. , Murray Clare , Strain Martin , Connor Jane , Murray Lynne A. , Sleeman Matthew A. , Lowe David C. , Huntington James A. , Vaughan Tristan J.
Published: February 2019

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (serpin) that regulates fibrinolysis, cell adhesion and cell motility via its interactions with plasminogen activators and vitronectin. PAI-1 has been shown to play a role in a number of diverse pathologies including cardiovascular diseases, obesity and cancer and is therefore an attractive therapeutic target. However the multiple patho-physiological roles of PAI-1, and understanding the relative contributions of these in any one disease setting, make the development of therapeutically relevant molecules challenging. Here we describe the identification and characterisation of fully human antibody MEDI-579, which binds with high affinity and specificity to the active form of human PAI-1. MEDI-579 specifically inhibits serine protease interactions with PAI-1 while conserving vitronectin binding. Crystallographic analysis reveals that this specificity is achieved through direct binding of MEDI-579 Fab to the reactive centre loop (RCL) of PAI-1 and at the same exosite used by both tissue and urokinase plasminogen activators (tPA and uPA). We propose that MEDI-579 acts by directly competing with proteases for RCL binding and as such is able to modulate the interaction of PAI-1 with tPA and uPA in a way not previously described for a human PAI-1 inhibitor.
A convenient method for the generation of {Rh(PNP)}+ and {Rh(PONOP)}+ fragments: reversible formation of vinylidene derivatives
Authors: Gyton Matthew R. , Hood Thomas M. , Chaplin Adrian B.
Published: February 2019

A new entry point into the organometallic chemistry of reactive rhodium(i) pincer complexes.
Dietary methionine restriction ameliorates the impairment of learning and memory function induced by obesity in mice
Authors: Xu Yuncong , Yang Yuhui , Sun Jin , Zhang Yuanyuan , Luo Tingyu , Li Bowen , Jiang Yuge , Shi Yonghui , Le Guowei
Published: February 2019

Dietary methionine restriction improves impairment of learning and memory function induced by obesity, likely by increasing H2S production.
Ru(ii)-Catalysed synthesis of (1H)-isothiochromenes by oxidative coupling of benzylthioethers with internal alkynes
Authors: Urriolabeitia Esteban P. , Ruiz Sara
Published: February 2019

(1H)-Isothiochromenes have been prepared by Ru-catalysed oxidative coupling of benzylthioethers with internal alkynes.
Yttrium and europium separation by solvent extraction with undiluted thiocyanate ionic liquids
Authors: Banda Raju , Forte Federica , Onghena Bieke , Binnemans Koen
Published: February 2019

Yttrium and europium are separated from a mixed oxide through solvent extraction with undiluted thiocyanate ionic liquids.
Photoswitchable probe with distinctive characteristics for selective fluorescence imaging and long-term tracing
Authors: Tu Zhenzhen , Zhang Qian , Xu Xiuxia , Wang Lianhui , Qian Yan , Huang Wei
Published: February 2019

In this work, a photoswitchable probe was synthesized by integrating a photochromophore with an excited-state intramolecular proton transfer (ESIPT) moiety. It was explored to be a favorable fluorophore for selective fluorescence imaging and long-term tracing.
Fe-doped H3PMo12O40 immobilized on covalent organic frameworks (Fe/PMA@COFs): a heterogeneous catalyst for the epoxidation of cyclooctene with H2O2
Authors: Yu Dandan , Gao Wenxiu , Xing Shuyu , Lian Lili , Zhang Hao , Wang Xiyue , lou Dawei
Published: February 2019

Fe/PMA@COF composites for the epoxidation of cyclooctene: the spatial configuration and nitrogen content of the COF support significantly influence the catalytic activity and stability.
Chiral phosphoric acid-catalyzed enantioselective construction of structurally diverse benzothiazolopyrimidines
Authors: Jarrige Lucie , Glavač Danijel , Levitre Guillaume , Retailleau Pascal , Bernadat Guillaume , Neuville Luc , Masson Géraldine
Published: February 2019

Chiral phosphoric acid catalyzed the formal [4+2]-cycloaddition of 2-benzothiazolimines with enecarbamates to provide benzothiazolopyrimidines with up to 99% yield and >99% ee.
Synthesis of acyl(chloro)phosphines enabled by phosphinidene transfer
Authors: Szkop Kevin M. , Geeson Michael B. , Stephan Douglas W. , Cummins Christopher C.
Published: February 2019

Acyl(chloro)phosphines RC(O)P(Cl)(t-Bu) have been prepared by formal insertion of tert-butyl phosphinidene (t-Bu–P) from t-BuPA (A = C14H10 or anthracene) into the C–Cl bond of acyl chlorides.
All-dielectric metasurfaces for simultaneously realizing polarization rotation and wavefront shaping of visible light
Authors: Gao Song , Park Chul-Soon , Lee Sang-Shin , Choi Duk-Yong
Published: February 2019

It has been proposed that monolayer all-dielectric metasurfaces efficiently manipulate the wavefront of transmitted visible light exhibiting controllable linear polarization angles.
Chemoselective syntheses of spirodihydrofuryl and spirocyclopropyl barbiturates via cascade reactions of barbiturate-based olefins and acetylacetone
Authors: Yan Xuebin , Shao Pei , Song Xixi , Zhang Chaofei , Lu Chang , Liu Songtao , Li Yanli
Published: February 2019

Spirodihydrofuryl and spirocyclopropyl barbiturates were chemoselectively synthesized from barbiturate-based olefins and acetylacetone in the presence of different bases and NBS.
Ammonium chloride–metal hydride based reaction cycle for vehicular applications
Authors: Stewart Helen G. , Humphries Terry D. , Sheppard Drew A. , Tortoza Mariana S. , Sofianos M. Veronica , Liu Shaomin , Buckley Craig E.
Published: February 2019

A cost effective stationary fuel has been developed using mixtures of ammonium chloride and metal hydrides.
A novel molecular design employing a backbone freezing linker for improved efficiency, sharpened emission and long lifetime in thermally activated delayed fluorescence emitters
Authors: Yu Ji Gwang , Han Si Hyun , Lee Ha Lim , Hong Wan Pyo , Lee Jun Yeob
Published: February 2019

A novel molecular design employing a backbone structure freezing linker was developed to improve the external quantum efficiency, lifetime and emission profile of thermally activated delayed fluorescence (TADF) emitters.
1.2 MHz relaxation oscillator with 16.8 ppm/°C temperature coefficient using resistive self‐bias current
Authors: Choi J. , Kim J. , Lee Y. , Chun J.‐H.
Published: February 2019

In this research, the authors propose a self‐biased relaxation oscillator that outputs a constant 1.2 MHz clock over a wide temperature range. Excluding any external bias, the proposed oscillator embodies a self‐bias circuit that generates a bias current from a precisely trimmed resistor. To minimise the power consumption, a switched‐bias technique was applied to the two comparators in the oscillator. The proposed circuit was fabricated in a 180 nm CMOS process. It consumes 17.9 µW from a 1.5 V supply, and its temperature coefficient is 16.8 ppm/°C in the range of −20–80°C.
3D local directional patterns for early diagnosis of Alzheimer's disease
Authors: Yan Shiju , Song Chengli , Zheng Bin
Published: February 2019

We propose a three‐dimensional‐local directional pattern (3D‐LDP) computation method in this study for early diagnosis of Alzheimer's disease. The proposed 3D‐LDP is defined as a 1‐bit decimal pattern which is calculated by computing and comparing edge response values in 18 directions. By concatenating three individual histograms extracted from three segmented sub‐regions of grey matter, the accuracy, sensitivity, and specificity of the proposed 3D‐LDP method were obtained as 81, 84, and 79%, respectively, comparable or even better than those of the existing 3D‐LTP method (80, 85, and 78%).
Regular and linear permutation languages
Authors: Madejski Grzegorz
Published: February 2019

A permutation rule is a non-context-free rule whose both sides contain the same multiset of symbols with at least one non-terminal. This rule does not add or substitute any symbols in the sentential form, but can be used to change the order of neighbouring symbols. In this paper, we consider regular and linear grammars extended with permutation rules. It is established that the generative power of these grammars relies not only on the length of the permutation rules, but also whether we allow or forbid the usage of erasing rules. This is quite surprising, since there is only one non-terminal in sentential forms of derivations for regular or linear grammars. Some decidability problems and closure properties of the generated families of languages are investigated. We also show a link to a similar model which mixes the symbols: grammars with jumping derivation mode.
Update Uroonkologie – was gibt‘s Neues 2018?
Authors: Heers Hendrik , Boegemann Martin , Hegele Axel
Published: February 2019

Es bleibt spannend in der Uroonkologie. Immer zahlreicher werden die Studien, immer neue Substanzen zur Tumortherapie erobern den Markt. Da es immer schwieriger wird, als Kliniker den Überblick zu behalten, soll dieser Artikel die wichtigsten Neuigkeiten in Bezug auf die 3 bedeutendsten urologischen Tumorentitäten zusammenfassen. Aktuelle Daten der wichtigsten urologischen und onkologischen Kongresse 2018 zum Prostatakarzinom, Nierenzellkarzinom und Urothelkarzinom werden vorgestellt und ihre Relevanz für die Praxis diskutiert.
Urologie der Frau – Rückblick auf die Entwicklung in den letzten 5 Jahrzehnten
Authors: Neymeyer Joerg , Moldovan Diana , Miller Kurt , Weinberger Sarah
Published: February 2019

Die Urogynäkologie ist ein hochspezialisierter interdisziplinärer Fachbereich vom Charakter einer Subspezialisierung. Sie verfolgt das Ziel der Untersuchung und nachhaltigen ganzheitlichen Behandlung funktioneller, statischer, endokriner und sexueller Störungen bzw. Erkrankungen im Bereich des Urogenitalsystems und des kleinen Beckens.

Der Arbeitskreis „Urologische Funktionsdiagnostik und Urologie der Frau“ der Akademie der Deutschen Urologen wurde 1977 gegründet und fokussiert die Urogynäkologie auf die Aktualisierung und Fortentwicklung der Diagnostik und klinischen Therapieverfahren, auf die Weiterbildung sowie auf die Mitgestaltung der urogynäkologischen Leitlinien.

Harninkontinenz und Beckenbodensenkungen nehmen demografisch bedingt zu. Steigende soziokulturelle Ansprüche der Frauen erfordern effektivere Behandlungen mit erfolgssicheren und komplikationsarmen Methoden.

Meilensteine in der Urogynäkologie waren die Einführung und Weiterentwicklung minimalinvasiver Operationsverfahren wie unter anderem TVT („tension-free vaginal tape“) -Systeme, laparoskopische und roboterassistierte Techniken, die Entwicklung eines Komplikationsmanagements, gezieltere medikamentöse Therapien sowie die Möglichkeiten der modernen Funktionsdiagnostik mit Beckenbodensonografie und MRT-Untersuchungen.

Klassische Operationstechniken wie Kolposuspensionen oder Kolposakropexien und vaginale Plastiken ohne Fremdmaterial haben weiterhin einen hohen Stellenwert. In speziellen Fällen sowie Rezidivsenkungen haben sich netzbasierte pelvine Plastiken den konventionellen Verfahren wegen guter Langzeiterfolge und nur geringen Rezidivraten als überlegen erwiesen, sofern eine anatomisch korrekte Operationstechnik, kritische Auswahl textiler Implantate sowie eine angemessene Aufklärung erfolgt. Instrumentelle Nahttechniken und Operationsroboter sind aufgrund der beengten Zugänge und Aktionsräume vorteilhaft. Bei apikalen direkten Fixationen ist die therapeutisch relevante Zielgröße der Elevationswinkel der Scheide. Bewährte anatomische Fixationspunkte sind vorzuziehen.

Die Aus- und Weiterbildung auf dem Fachgebiet der Urogynäkologie und die Harmonisierung mit europäischen Vorgaben (European Board & College of Obstetrics and Gynaecology) sollten umgesetzt werden. Fähigkeiten und Fertigkeiten zu hochspezialisierten netzbasierten Eingriffen und effektiven Techniken zum Komplikationsmanagement sollten genauso interdisziplinär vermittelt werden, wie einfach zu erlernende und zu nutzende diagnostische Verfahren, besonders aber die Beckenbodensonografie.

Nur eine Fächerübergreifende urogynäkologische Subspezialisierung kann die Entwicklung erforderlicher Fachkompetenzen garantieren. Interdisziplinäre Weiterbildungen sollten durch die beteiligten Fachgesellschaften (Urologie, Chirurgie und Gynäkologie) inhaltlich festgelegt und deren Umsetzung vereinbart werden.
Die Rolle Der Psychotherapie Beim Reizdarmsyndrom
Authors: Weibert Elena , Stengel Andreas
Published: February 2019

Das Reizdarmsyndrom ist eine häufige funktionelle gastrointestinale Störung, die aufgrund wiederkehrender gastrointestinaler Beschwerden wie Bauchschmerzen oder Stuhlveränderungen die Lebensqualität erheblich beeinträchtigen kann. Basierend auf dem biopsychosozialen Krankheitsmodell wird die Ausprägung des Reizdarmsyndroms durch die Kombination von veränderten physiologischen Prozessen, sozialen Aspekten und psychischen Faktoren beeinflusst. Während der Fokus bisher auf der Linderung der Darmbeschwerden mittels Diät sowie medikamentöser Therapie lag, stellen Psychotherapieverfahren angesichts der starken Assoziation mit psychischen Komorbiditäten (u. a. Depression, Angststörung) zunehmend alternative oder ergänzende Behandlungsmethoden mit mittlerweile sehr guter Evidenz dar. Grundsätzlich können zusätzliche psychische Begleitsymptome die Wahrscheinlichkeit komplizierter Krankheitsverläufe erhöhen, wobei sich psychische Symptome und Darmbeschwerden maßgeblich gegenseitig beeinflussen. Mithilfe von kognitiver Verhaltenstherapie, psychodynamischer Psychotherapie, Hypnotherapie, achtsamkeitsbasierter Therapie und anderen psychotherapeutischen Verfahren sollen die Krankheitsbewältigung und -kontrolle gesteigert und fehlregulierte kognitive Prozesse umstrukturiert werden. In dieser Übersichtsarbeit fokussieren wir uns auf den psychosozialen Aspekt des Reizdarmsyndroms und diskutieren den Nutzen der psychotherapeutischen Verfahren.
Interrater Reliability of Ultrasound in the Diagnosis of Sialolithiasis
Authors: Goncalves Miguel , Mantsopoulos Konstantinos , Schapher Mirco Lothar , Zenk Johannes , Bozzato Alessandro , Kuenzel Julian , Zengel Pamela , Iro Heinrich , Koch Michael
Published: February 2019

Purpose The aim of this study was to assess the interrater reliability of ultrasound for diagnosing sialolithiasis.

Materials and Methods A total of 100 consecutive patients with signs of obstructive sialadenopathy were evaluated. The patients all underwent ultrasound examinations in a standardized manner conducted by one specialist with extensive experience in the management of salivary gland disorders and proficiency in head and neck ultrasonography. The video recordings were sent to six colleagues with comparable experience without providing any further information about the patients’ medical history and physical examination.

Results The overall agreement between the seven observers was substantial, with a κ of 0.765 for the 100 cases and a percentage agreement level of 88.29 ± 3.01 % (range: 83–94 %). The range of agreement on this video set for observer pairs varied from substantial to almost perfect agreement (0.663 to 0.878). Among the few false-negative findings (5.4 %), 71.8 % were due to distal sialolithiasis. Two-thirds of the false-positive findings (3.7 %) were due to fibrotic stenosis.

Conclusion The study confirmed the diagnostic value of ultrasound in sialolithiasis and demonstrated a very high level of interrater agreement, even in the absence of additional clinical patient information, thus further underscoring the importance of ultrasound as the examination of first choice in sialolithiasis.
A One-Pot Approach to 2-(N-Substituted Amino)-1,4-naphthoquinones with Use of Nitro Compounds and 1,4-Naphthoquinones in Water
Authors: Wang Ji-Yu , Chen Xu-Ling , Dong Yu , He Shuai , Zhang Rui , Zhang Hua , Tang Lei , Zhang Xiao-Mei
Published: February 2019

A one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones from 1,4-naphthoquinones and nitro compounds in water has been developed. This method features mild reaction conditions and provides aromatic nitro compounds with various functional groups such as halogens, methylthio, ester, amide, even allyl, propargyl, and heterocycles, as well as aliphatic nitro compounds that are well tolerated. This method can be scaled up and we conducted further transformation of the obtained 2-(N-substituted amino)-1,4-naphthoquinones to synthesize carbazolequinone derivatives.