bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastroprotective activity ofLoranthus acaciaeflower extract in a rodent model of ethanol-induced ulcer
Authors: Abbas Manal A. , Kandil Yasser I. , Disi Ahmad M. , Jaffal Sahar M. 
Published: April 2019

Loranthus acaciae (Loranthaceae) is a perennial green semi-parasitic plant used in ethnopharmacological medicine for healing wounds. The protective effect of L. acaciae on gastric ulcer induced by ethanol was investigated in a rat model. Ulcer index and total glutathione level were measured and histological and immunohistochemical studies for the expression of cyclooxygenase-2 were performed. Furthermore, chemical constituents of the flower extract were analyzed. Ulcer index was significantly lowered in L. acaciae-treated groups. Protection ratios were 75.9%, 98.9%, and 70.7% for 250 mg/kg and 500 mg/kg of L. acaciae and 40 mg/kg of esomeprazole, respectively. Histological examination revealed fewer hemorrhage in mucosa and less edema in submucosa of L. acaciae-treated groups compared with control. In the esomeprazole-treated group, there was mild disruption in the surface epithelium and mild hemorrhage. However, edema and leucocytes infiltration in the submucosa layer were present. Immunohistochemical staining of stomach sections for cyclooxygenase-2 (COX-2) was negative in the control group as well as in the L. acaciae-treated groups. Total glutathione level in mucosa layer of the stomach was higher in L. acaciae-treated groups compared with control. Liquid chromatography-mass spectrometric analysis revealed the presence of loranthin and rutin as the major constituents. It can be concluded that L. acaciae imparted a gastroprotective action against ethanol-induced ulcer in rats.Novelty 500 mg/kg L. acaciae protected the stomach by 98.9% from ulcerogenic effect of ethanol. L. acaciae increased total glutathione level but not COX-2 expression in gastric mucosa. Loranthin and rutin were the major constituents in L. acaciae flower extract.
Nanosecond level passively Q-switched Nd:YAG and Nd:YVO4 laser using black phosphorus as a saturable absorber
Authors: Sun Zhe , Li Guangying , Cheng Guanghua , Wang Yonggang 
Published: April 2019

Black phosphorus (BP) saturable absorber (SA) solution is fabricated by liquid-phase exfoliation method. By using the BP-SA solution, a compact diode-pumped passively [Formula: see text]-switched Nd:YAG and [Formula: see text] laser has been demonstrated. 100 Hz and 1 kHz repetition rate pulse lasers are achieved, respectively. The minimum pulse duration is 3.56 ns. In the [Formula: see text]-switched [Formula: see text] laser with wideband absorbers, the lowest repetition rate and the shortest pulse duration are obtained for the first time to the best of our knowledge. The maximum single pulse energy is as much as 0.1 mJ. Our results show that BP-SA solution can be developed as an effective SA to achieve nanosecond pulse laser.
New Voltage-Mode Sinusoidal Oscillators Using VDIBAs
Authors: Wang San-Fu , Chen Hua-Pin 
Published: April 2019

This paper presents two new voltage-mode sinusoidal oscillators based on voltage differencing inverting buffered amplifier (VDIBA). The first proposed circuit exhibits independent and electronic control of oscillation condition by using the bias current of the VDIBA. The proposed configuration contains only single VDIBA, two grounded capacitors and two resistors, which are the least number of active components and the minimum number of passive components necessary for realizing voltage-mode oscillator topology. The second proposed circuit exhibits independent and electronic control on the condition of oscillation without affecting the oscillation frequency by adjusting the separate bias currents of the VDIBAs. The proposed configuration contains two VDIBAs, two grounded capacitors and one resistor, which can provide four quadrature voltage outputs simultaneously. Both proposed circuits enjoy only two grounded capacitors, which are suitable for monolithic integration. HSpice simulations and experimental results are included to confirm the theoretical analysis.
Robust Loop Closure Detection Using Bayes Filters and CNN Features
Authors: Liu Qiang , Duan Fuhai 
Published: April 2019

This paper focuses on loop-closure detection (LCD) for a visual simultaneous localization and mapping (SLAM) system. We present a strategy that combines a Bayes filter and features from a pre-trained convolution neural network (CNN) to perform LCD. Rather than using features from only one layer, we fuse features from multiple layers based on spatial pyramid pooling. A flexible Bayes model is then formulated to integrate the sequential information and similarities that are computed by features at different scales. The introduction of a penalty factor and bidirectional propagation enables our approach to handle complex trajectories. We present extensive experiments on challenging datasets, and we compare our approach to state-of-the-art methods, to evaluate it. The results show that our approach can ensure remarkable performance under severe condition changes and handle trajectories that have different characteristics. We also show the advantages of Bayes filters over sequence matching in the experiments, and we analyze our feature fusion strategy by visualizing the activations of the CNN.
A Novel Orally Active Inverse Agonist of Estrogen-related Receptor Gamma (ERRγ), DN200434, A Booster of NIS in Anaplastic Thyroid Cancer
Authors: Singh Thoudam Debraj , Song Jaeyoung , Kim Jina , Chin Jungwook , Ji Hyun Dong , Lee Jae-Eon , Lee Sang Bong , Yoon Heeseok , Yu Ji Hoon , Kim Sang Kyoon , Yoon Ghil Suk , Hwang Hayoung , Lee Ho Won , Oh Ji Min , Lee Sang-Woo , Lee Jaetae , Choi Hueng-Sik , Na Soon-Young , Choi Won-Il , Park Young Joo , Song Young Shin , Kim Young A. , Lee In-Kyu , Cho Sung Jin , Jeon Yong Hyun 
Published: April 2019

Abstract

Purpose:
New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy–refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERRγ) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC50 = 0.006 μmol/L), selective, and orally available ERRγ inverse agonist for NIS enhancement in ATC.

Experimental Design:
We sought to identify better ERRγ-targeting ligands and explored the crystal structure of ERRγ in complex with DN200434. After treating ATC cells with DN200434, the change in iodide-handling gene expression, as well as radioiodine avidity was examined. ATC tumor–bearing mice were orally administered with DN200434, followed by 124I-positron emission tomography/CT (PET/CT). For radioiodine therapy, ATC tumor–bearing mice treated with DN200434 were administered 131I (beta ray–emitting therapeutic radioiodine) and then bioluminescent imaging was performed to monitor the therapeutic effects. Histologic analysis was performed to evaluate ERRγ expression status in normal tissue and ATC tissue, respectively.

Results:
DN200434–ERRγ complex crystallographic studies revealed that DN200434 binds to key ERRγ binding pocket residues through four-way interactions. DN200434 effectively upregulated iodide-handling genes and restored radioiodine avidity in ATC tumor lesions, as confirmed by 124I-PET/CT. DN200434 enhanced ATC tumor radioiodine therapy susceptibility, markedly inhibiting tumor growth. Histologic findings of patients with ATC showed higher ERRγ expression in tumors than in normal tissue, supporting ERRγ as a therapeutic target for ATC.

Conclusions:
DN200434 shows potential clinical applicability for diagnosis and treatment of ATC or other poorly differentiated thyroid cancers.
Single-Cell Lymphocyte Heterogeneity in Advanced Cutaneous T-cell Lymphoma Skin Tumors
Authors: Gaydosik Alyxzandria M. , Tabib Tracy , Geskin Larisa J. , Bayan Claire-Audrey , Conway James F. , Lafyatis Robert , Fuschiotti Patrizia 
Published: April 2019

Abstract

Purpose:
The heterogeneity of tumor cells presents a major challenge to cancer diagnosis and therapy. Cutaneous T-cell lymphomas (CTCL) are a group of T lymphocyte malignancies that primarily affect skin. Lack of highly specific markers for malignant lymphocytes prevents early diagnosis, while only limited treatment options are available for patients with advanced stage CTCL. Droplet-based single-cell transcriptome analysis of CTCL skin biopsies opens avenues for dissecting patient-specific T lymphocyte heterogeneity, providing a basis for identifying specific markers for diagnosis and cure of CTCL.

Experimental Design:
Single-cell RNA-sequencing was performed by Droplet-based sequencing (10X Genomics), focusing on 14,056 CD3+ lymphocytes (448 cells from normal and 13,608 cells from CTCL skin samples) from skin biopsies of 5 patients with advanced-stage CTCL and 4 healthy donors. Protein expression of identified genes was validated in advanced stage CTCL skin tumors by immunohistochemistry and confocal immunofluorescence microscopy.

Results:
Our analysis revealed a large inter- and intratumor gene expression heterogeneity in the T lymphocyte subset, as well as a common gene expression signature in highly proliferating lymphocytes that was validated in multiple advanced-stage skin tumors. In addition, we established the immunologic state of reactive lymphocytes and found heterogeneity in effector and exhaustion programs across patient samples.

Conclusions:
Single-cell analysis of CTCL skin tumor samples reveals patient-specific landscapes of malignant and reactive lymphocytes within the local microenvironment of each tumor, giving an unprecedented view of lymphocyte heterogeneity and identifying tumor-specific molecular signatures, with important implications for diagnosis and personalized disease treatment.
Novel RB1-Loss Transcriptomic Signature Is Associated with Poor Clinical Outcomes across Cancer Types
Authors: Chen William S. , Alshalalfa Mohammed , Zhao Shuang G. , Liu Yang , Mahal Brandon A. , Quigley David A. , Wei Ting , Davicioni Elai , Rebbeck Timothy R. , Kantoff Philip W. , Maher Christopher A. , Knudsen Karen E. , Small Eric J. , Nguyen Paul L. , Feng Felix Y. 
Published: April 2019

Abstract

Purpose:
Rb-pathway disruption is of great clinical interest, as it has been shown to predict outcomes in multiple cancers. We sought to develop a transcriptomic signature for detecting biallelic RB1 loss (RBS) that could be used to assess the clinical implications of RB1 loss on a pan-cancer scale.

Experimental Design:
We utilized data from the Cancer Cell Line Encyclopedia (N = 995) to develop the first pan-cancer transcriptomic signature for predicting biallelic RB1 loss (RBS). Model accuracy was validated using The Cancer Genome Atlas (TCGA) Pan-Cancer dataset (N = 11,007). RBS was then used to assess the clinical relevance of biallelic RB1 loss in TCGA Pan-Cancer and in an additional metastatic castration-resistant prostate cancer (mCRPC) cohort.

Results:
RBS outperformed the leading existing signature for detecting RB1 biallelic loss across all cancer types in TCGA Pan-Cancer (AUC, 0.89 vs. 0.66). High RBS (RB1 biallelic loss) was associated with promoter hypermethylation (P = 0.008) and gene body hypomethylation (P = 0.002), suggesting RBS could detect epigenetic gene silencing. TCGA Pan-Cancer clinical analyses revealed that high RBS was associated with short progression-free (P &lt; 0.00001), overall (P = 0.0004), and disease-specific (P &lt; 0.00001) survival. On multivariable analyses, high RBS was predictive of shorter progression-free survival in TCGA Pan-Cancer (P = 0.03) and of shorter overall survival in mCRPC (P = 0.004) independently of the number of DNA alterations in RB1.

Conclusions:
Our study provides the first validated tool to assess RB1 biallelic loss across cancer types based on gene expression. RBS can be useful for analyzing datasets with or without DNA-sequencing results to investigate the emerging prognostic and treatment implications of Rb-pathway disruption.
See related commentary by Choudhury and Beltran, p. 4199
Yield of Clinical Screening for Hypertrophic Cardiomyopathy in Child First-Degree Relatives
Authors: Norrish Gabrielle , Jager Joanna , Field Ella , Quinn Ellie , Fell Hannah , Lord Emma , Cicerchia Marcos N. , Ochoa Juan Pablo , Cervi Elena , Elliott Perry M. , Kaski Juan Pablo 
Published: April 2019

Background:
Hypertrophic cardiomyopathy (HCM) is a heritable myocardial disease with age-related penetrance. Current guidelines recommend clinical screening of relatives beginning at 10 years of age, but the clinical value of this approach has not been systematically evaluated.

Methods:
Anonymized clinical data were collected from children referred for family screening between 1994 and 2017 after diagnosis of HCM in a first-degree relative.

Results:

Of 1198 consecutive children (≤18 years of age) from 594 families who underwent serial evaluation (median, 3.5 years; interquartile range, 1.2–7), 32 individuals met diagnostic criteria at baseline (median maximal left ventricular wall thickness, 13 mm; interquartile range, 8-21 mm), and 25 additional patients developed HCM during follow-up. Median age at diagnosis was 10 years (interquartile range, 4–13 years); 44 (72%) were ≤12 years of age. Median age of affected patients at the last follow-up was 14 years (interquartile range, 9.5–18.2 years). A family history of childhood HCM was more common in those patients diagnosed with HCM (n=32 [56%] versus n=257 [23%];
P
<0.001). Eighteen patients (32%) were started on medication for symptoms; 2 (4%) underwent a septal myectomy; 14 (25%) received an implantable cardioverter-defibrillator; 1 underwent cardiac transplantation; 2 had a resuscitated cardiac arrest; and 1 died after a cerebrovascular accident.

Conclusions:
Almost 5% of first-degree child relatives undergoing screening meet diagnostic criteria for HCM at first or subsequent evaluations, with the majority presenting as preadolescents; a diagnosis in a child first-degree relative is made in 8% of families screened. The phenotype of familial HCM in childhood is varied and includes severe disease, suggesting that clinical screening should begin at a younger age.
The Second Wind Forecast Improvement Project (WFIP2): General Overview
Authors: Shaw William J. , Berg Larry K. , Cline Joel , Draxl Caroline , Djalalova Irina , Grimit Eric P. , Lundquist Julie K. , Marquis Melinda , McCaa Jim , Olson Joseph B. , Sivaraman Chitra , Sharp Justin , Wilczak James M. 
Published: April 2019

AbstractIn 2015 the U.S. Department of Energy (DOE) initiated a 4-yr study, the Second Wind Forecast Improvement Project (WFIP2), to improve the representation of boundary layer physics and related processes in mesoscale models for better treatment of scales applicable to wind and wind power forecasts. This goal challenges numerical weather prediction (NWP) models in complex terrain in large part because of inherent assumptions underlying their boundary layer parameterizations. The WFIP2 effort involved the wind industry, universities, the National Oceanographic and Atmospheric Administration (NOAA), and the DOE’s national laboratories in an integrated observational and modeling study. Observations spanned 18 months to assure a full annual cycle of continuously recorded observations from remote sensing and in situ measurement systems. The study area comprised the Columbia basin of eastern Washington and Oregon, containing more than 6 GW of installed wind capacity. Nests of observational systems captured important atmospheric scales from mesoscale to NWP subgrid scale. Model improvements targeted NOAA’s High-Resolution Rapid Refresh (HRRR) model to facilitate transfer of improvements to National Weather Service (NWS) operational forecast models, and these modifications have already yielded quantitative improvements for the short-term operational forecasts. This paper describes the general WFIP2 scope and objectives, the particular scientific challenges of improving wind forecasts in complex terrain, early successes of the project, and an integrated approach to archiving observations and model output. It provides an introduction for a set of more detailedBAMSpapers addressing WFIP2 observational science, modeling challenges and solutions, incorporation of forecasting uncertainty into decision support tools for the wind industry, and advances in coupling improved mesoscale models to microscale models that can represent interactions between wind plants and the atmosphere.
Parameter Sweep Experiments on a Spectrum of Cyclones with Diabatic and Baroclinic Processes
Authors: Yanase Wataru , Niino Hiroshi 
Published: April 2019

Abstract
A wide range of environments that prevail over the globe generate various types of cyclones such as tropical, extratropical, and hybrid cyclones. In this paper, idealized numerical experiments are used to explore a spectrum of cyclones ranging from the diabatic type to the baroclinic type in a parameter space consisting of three environmental factors: temperature, vertical shear, and planetary vorticity. The experiments reproduce not only typical dynamics of tropical and extratropical cyclones but also their modified dynamics, which are consistent with theoretical studies; tropical cyclones are suppressed by vertical shear, while extratropical cyclones are intensified by condensational heating. The experiments also reproduce hybrid cyclones in environments with high temperature and large baroclinicity. The hybrid cyclones show multiscale dynamics in which synoptic-scale baroclinic systems spawn smaller-scale tropical cyclone–like convective cores. The spectrum of cyclones is found to be nonmonotonic in the parameter space because of a two-sided effect of the vertical shear: moderate shear weakens a tropical cyclone by tilting the small-scale vortex to the downshear, while strong shear develops a large-scale vortex of an extratropical cyclone or a hybrid cyclone through warm-air advection from the south. The indices based on the energetics and the symmetric and asymmetric structures overview the different types of cyclones in the parameter space. These parameter sweep experiments provide useful information on what environment is favorable for cyclones, particularly for intermediate environments where cyclone mechanisms are yet to be fully defined.
Entrainment and Mixing in Stratocumulus: Effects of a New Explicit Subgrid-Scale Scheme for Large-Eddy Simulations with Particle-Based Microphysics
Authors: Hoffmann Fabian , Feingold Graham 
Published: April 2019

Abstract
The entrainment and mixing of free-tropospheric air is an essential component of the observed microphysical structure of stratocumulus clouds. Since the relevant scales involved in this process are usually smaller than the grid spacing of typical large-eddy simulations (LESs), their correct representation is difficult. To adequately accommodate these small-scale processes, we apply a recently developed approach that explicitly simulates LES subgrid-scale (SGS) turbulence fluctuation of supersaturation using the one-dimensional linear eddy model. As a result of reduced numerical diffusion and the ability to explicitly represent the SGS distribution of liquid water and supersaturation, entrainment rates tend to be lower in the new approach compared to simulations without it. Furthermore, cloud holes comprising free-tropospheric air with negligible liquid water are shown to persist longer in the stratocumulus deck. Their mixing with the cloud is shown to be more sensitive to the microphysical composition of the cloud as a result of the explicitly resolved inhomogeneous mixing, which is also confirmed analytically. Moreover, inhomogeneous mixing is shown to decrease the droplet concentration and to increase droplet growth significantly, in contrast to previous studies. All in all, the simulations presented can be seen as a first step to bridge the gap between ultra-high-resolution direct numerical simulation and LES, allowing an appropriate representation of small-scale mixing processes, together with the large-scale dynamics of a stratocumulus system.
The Variation of the Intensity, Height, and Size of Precipitation Systems with El Niño–Southern Oscillation in the Tropics and Subtropics
Authors: Liu Nana , Liu Chuntao , Lavigne Thomas 
Published: April 2019

AbstractA 16-yr (1998–2013) Tropical Rainfall Measuring Mission (TRMM) Precipitation Feature (PF) database is used to examine the impacts of El Niño–Southern Oscillation (ENSO) on the characteristics of precipitation systems in the tropics and subtropics. Noticeable differences in the fractions of deep systems (20-dBZ radar echo tops greater than 10 km) and mesoscale convective systems (MCSs) (an area greater than 2000 km2) between different phases of ENSO are found over specific regions, including the central Pacific (CPACI), the western Maritime Continent (WMC), the eastern Maritime Continent (EMC), Gulf of Mexico (GM), Argentina (ARGEN), and Australia (AUS). The coefficients of determination R2 between the multivariate ENSO index (MEI) and the population fractions of deep convection and MCSs are analyzed seasonally over these regions. The responses from these precipitation systems to ENSO are found to be more pronounced in the winter half-year than in the summer half-year. An increase of rainfall during El Niño periods over the CPACI, GM, and ARGEN is found to be associated with more precipitation events and a higher fraction of intense, deep, and large precipitation systems. AUS has fewer precipitation events and a higher fraction of shallow and small precipitation systems during El Niño conditions. Both EMC and WMC have a higher fraction of MCSs during La Niña than El Niño conditions. The EMC observes a higher fraction of deep convection during La Niña conditions. However, the WMC has a higher fraction of deep convection during El Niño conditions, possibly related to the effect of the Indian Ocean dipole.
Nonuniform Contribution of Internal Variability to Recent Arctic Sea Ice Loss
Authors: England Mark , Jahn Alexandra , Polvani Lorenzo 
Published: April 2019

Abstract
Over the last half century, the Arctic sea ice cover has declined dramatically. Current estimates suggest that, for the Arctic as a whole, nearly one-half of the observed loss of summer sea ice cover is not due to anthropogenic forcing but rather is due to internal variability. Using the 40 members of the Community Earth System Model Large Ensemble (CESM-LE), our analysis provides the first regional assessment of the role of internal variability on the observed sea ice loss. The CESM-LE is one of the best available models for such an analysis, because it performs better than other CMIP5 models for many metrics of importance. Our study reveals that the local contribution of internal variability has a large range and strongly depends on the month and region in question. We find that the pattern of internal variability is highly nonuniform over the Arctic, with internal variability accounting for less than 10% of late summer (August–September) East Siberian Sea sea ice loss but more than 60% of the Kara Sea sea ice loss. In contrast, spring (April–May) sea ice loss, notably in the Barents Sea, has so far been dominated by internal variability.