bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Classification of Benign and Malignant Proliferative Breast Lesions
Authors: Radiya-Dixit Evani , Zhu David , Beck Andrew H. 
Published: August 2017

AbstractMisclassification of breast lesions can result in either cancer progression or unnecessary chemotherapy. Automated classification tools are seen as promising second opinion providers in reducing such errors. We have developed predictive algorithms that automate the categorization of breast lesions as either benign usual ductal hyperplasia (UDH) or malignant ductal carcinoma in situ (DCIS). From diagnosed breast biopsy images from two hospitals, we obtained 392 biomarkers using Dong et al.’s (2014) computational tools for nuclei identification and feature extraction. We implemented six machine learning models and enhanced them by reducing prediction variance, extracting active features, and combining multiple algorithms. We used the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for performance evaluation. Our top-performing model, a Combined model with Active Feature Extraction (CAFE) consisting of two logistic regression algorithms, obtained an AUC of 0.918 when trained on data from one hospital and tested on samples of the other, a statistically significant improvement over Dong et al.’s AUC of 0.858. Pathologists can substantially improve their diagnoses by using it as an unbiased validator. In the future, our work can also serve as a valuable methodology for differentiating between low-grade and high-grade DCIS.
A functional approach to the structural complexity of coral assemblages based on colony morphological features
Authors: Denis Vianney , Ribas-Deulofeu Lauriane , Sturaro Nicolas , Kuo Chao-Yang , Chen Chaolun Allen 
Published: August 2017

AbstractColony morphological features is among the best predictor of the scleractinian coral’s function in reef ecosystems. However, morphological traits are categorical and to convert this information into a quantitative value as well as estimate their influence on ecosystem process remain a challenge. Here, we propose a trait-based approach to quantify morphological diversity and assess the structural complexity of the habitat provided by corals. We used a previously published dataset that is related to a bleaching event that affected the coral reef off Tikus Island in Indonesia in 1983. We found clear signs of recovery of the coral assemblage’s complexity toward pre El Niño conditions five years after the event. Independent of the change observed in species richness, this return in structural complexity was accompanied by a global decrease in species number associated with each particular morphological entity (Functional Redundancy) and an increase in the number of single-species entities (Functional Vulnerability). Together with species loss, we show an overall functional erosion of the coral assemblage and suggest that the role of the coral reef habitat could be strongly imperiled under repeated or synergistic disturbances. This approach offers an opportunity for a better understanding of coral responses to natural and anthropogenic disturbances.
IRF2BP2-deficient microglia block the anxiolytic effect of enhanced postnatal care
Authors: Hari Aswin , Cruz Shelly A. , Qin Zhaohong , Couture Pascal , Vilmundarson Ragnar O. , Huang Hua , Stewart Alexandre F. R. , Chen Hsiao-Huei 
Published: August 2017

AbstractEnhanced postnatal care (EPC) increases resilience to adversity in adulthood. Since microglia participate in shaping neural circuits, we asked how ablation of an inflammation-suppressing factor IRF2BP2 (Interferon Regulatory Factor 2 Binding Protein 2) in microglia would affect the responses to EPC. Mice lacking IRF2BP2 in microglia (KO) and littermate controls (WT) were subjected to EPC during the first 3 weeks after birth. EPC reduced anxiety in WT but not KO mice. This was associated with reduced inflammatory cytokine expression in the hypothalamus. Whole genome RNAseq profiling of the hypothalamus identified 101 genes whose expression was altered by EPC: 95 in WT, 11 in KO, with 5 in common that changed in opposite directions. Proteoglycan 4 (Prg4), prostaglandin D2 synthase (Ptgds) and extracellular matrix protease inhibitor Itih2 were suppressed by EPC in WT but elevated in KO mice. On the other hand, the glutamate transporter VGLUT1 (Slc17a7) was increased by EPC in WT but not KO mice. Prostaglandin D2 (PGD2) is known to enhance microglial inflammation and promote Gfap expression. ELISA confirmed reduced PGD2 in the hypothalamus of WT mice after EPC, associated with reduced Gfap expression. Our study suggests that the anxiety-reducing effect of EPC operates by suppressing microglial inflammation, likely by reducing neuronal prostaglandin D2 production.
Identification of the protective mechanisms of Lactoferrin in the irradiated salivary gland
Authors: Sakai Manabu , Matsushita Takumi , Hoshino Ryoko , Ono Hitomi , Ikai Kazuki , Sakai Takayoshi 
Published: August 2017

AbstractRadiotherapy is commonly used in patients with head and neck cancer, and usually results in irreversible salivary glands damage and hypofunction. It is therefore important to manage such irradiation to prevent damage to the salivary glands. A previous study showed that Lactoferrin (LF) has a radioprotective effect, but the mechanism was not determined in salivary glands. In the present study, we investigated the detailed radioprotective effect of LF using bothex vivosubmandibular salivary gland organ culture and ICR male micein vivo. We found that LF had effects on both cell proliferation and CyclinD1-mediated cell-cycle progression which were regulated via the ERK1/2 and AKT signal transduction pathways. In addition, LF affected acinar cell structure and function after irradiation. These findings suggest that LF may be a useful agent to prevent irradiation effects in salivary glands.
Water-assisted and controllable synthesis of core/shell/shell structured carbon-based nanohybrids, and their magnetic and microwave absorption properties
Authors: Qi Xiaosi , Yang Erqi , Cai Hongbo , Xie Ren , Bai Zhongchen , Jiang Yang , Qin Shuijie , Zhong Wei , Du Youwei 
Published: August 2017

AbstractBy controlling the pyrolysis temperature, core/shell/shell structured Fe/Fe5C2/carbon nanotube bundles (Fe/Fe5C2/CNTBs), Fe/Fe3C/helical carbon nanotubes (Fe/Fe3C/HCNTs) and Fe/Fe3C/chain-like carbon nanospheres (Fe/Fe3C/CCNSs) with high encapsulation efficiency could be selectively synthesized in large-scale by water-assisted chemical vapor deposition method. Water vapor was proved to play an important role in the growth process. Because of α-Fe nanoparticles tightly wrapped by two layers, the obtained core/shell/shell structured nanohybrids showed high stabilities and good magnetic properties. The minimum reflection loss values of the as-prepared nanohybrids reached approximately −15.0, −46.3 and −37.1 dB, respectively. The excellent microwave absorption properties of the as-prepared core/shell/shell structured nanohybrids were considered to the quarter-wavelength matching model. Moreover, the possible enhanced microwave absorption mechanism of the as-prepared Fe/Fe3C/HCNTs and Fe/Fe3C/CCNSs were discussed in details. Therefore, we proposed a simple, inexpensive and environment-benign strategy for the synthesis of core/shell/shell structured carbon-based nanohybrids, exhibiting a promising prospect as high performance microwave absorbing materials.
Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing
Authors: Numata Tomohiro , Tsumoto Kunichika , Yamada Kazunori , Kurokawa Tatsuki , Hirose Shinichi , Nomura Hideki , Kawano Mitsuhiro , Kurachi Yoshihisa , Inoue Ryuji , Mori Yasuo 
Published: August 2017

AbstractNumerical model-based simulations provide important insights into ion channel gating when experimental limitations exist. Here, a novel strategy combining numerical simulations with patch clamp experiments was used to investigate the net positive charges in the putative transmembrane segment 4 (S4) of the atypical, positively-shifted voltage-dependence of polycystic kidney disease 2-like 1 (PKD2L1) channel. Charge-neutralising mutations (K452Q, K455Q and K461Q) in S4 reduced gating charges, positively shifted the Boltzmann-type activation curve [i.e., open probability (Popen)-V curve] and altered the time-courses of activation/deactivation of PKD2L1, indicating that this region constitutes part of a voltage sensor. Numerical reconstruction of wild-type (WT) and mutant PKD2L1-mediated currents necessitated, besides their voltage-dependent gating parameters, a scaling factor that describes the voltage-dependence of maximal conductance, Gmax. Subsequent single-channel conductance (γ) measurements revealed that voltage-dependence of Gmax in WT can be explained by the inward-rectifying property of γ, which is greatly changed in PKD2L1 mutants. Homology modelling based on PKD2 and NaVAb structures suggest that such voltage dependence of Popen and γ in PKD2L1 could both reflect the charged state of the S4 domain. The present conjunctive experimental and theoretical approaches provide a framework to explore the undetermined mechanism(s) regulating TRP channels that possess non-classical voltage-dependent properties.
High predictive values of RBC membrane-based diagnostics by biophotonics in an integrated approach for Autism Spectrum Disorders
Authors: Giacometti Giorgia , Ferreri Carla , Sansone Anna , Chatgilialoglu Chryssostomos , Marzetti Carla , Spyratou Ellas , Georgakilas Alexandros G. , Marini Marina , Abruzzo Provvidenza M. , Bolotta Alessandra , Ghezzo Alessandro , Minguzzi Renato , Posar Annio , Visconti Paola 
Published: August 2017

AbstractMembranes attract attention in medicine, concerning lipidome composition and fatty acid correlation with neurological diseases. Hyperspectral dark field microscopy (HDFM), a biophotonic imaging using reflectance spectra, provides accurate characterization of healthy adult RBC identifying a library of 8 spectral end-members. Here we report hyperspectral RBC imaging in children affected by Autism Spectrum Disorder (ASD) (n = 21) compared to healthy age-matched subjects (n = 20), investigating if statistically significant differences in their HDFM spectra exist, that can comprehensively map a membrane impairment involved in disease. A significant difference concerning one end-member (spectrum 4) was found (P value = 0.0021). A thorough statistical treatment evidenced: i) diagnostic performance by the receiving operators curve (ROC) analysis, with cut-offs and very high predictive values (P value = 0.0008) of spectrum 4 for identifying disease; ii) significant correlations of spectrum 4 with clinical parameters and with the RBC membrane deficit of the omega-3 docosahexaenoic acid (DHA) in ASD patients; iii) by principal component analysis, very high affinity values of spectrum 4 to the factor that combines behavioural parameters and the variable “cc” discriminating cases and controls. These results foresee the use of biophotonic methodologies in ASD diagnostic panels combining with molecular elements for a correct neuronal growth.
An Orbital Angular Momentum (OAM) Mode Reconfigurable Antenna for Channel Capacity Improvement and Digital Data Encoding
Authors: Liu Baiyang , Lin Guoying , Cui Yuehui , Li RongLin 
Published: August 2017

AbstractFor purpose of utilizing orbital angular momentum (OAM) mode diversity, multiple OAM beams should be generated preferably by a single antenna. In this paper, an OAM mode reconfigurable antenna is proposed. Different from the existed OAM antennas with multiple ports for multiple OAM modes transmitting, the proposed antenna with only a single port, but it can be used to transmit mode 1 or mode −1 OAM beams arbitrary by controlling the PIN diodes on the feeding network through a programmable microcontroller which control by a remote controller. Simulation and measurement results such as return loss, near-field and far-field radiation patterns of two operating states for mode 1 and mode −1, and OAM mode orthogonality are given. The proposed antenna can serve as a candidate for utilizing OAM diversity, namely phase diversity to increase channel capacity at 2.4 GHz. Moreover, an OAM-mode based encoding method is experimentally carried out by the proposed OAM mode reconfigurable antenna, the digital data are encoded and decoded by different OAM modes. At the transmitter, the proposed OAM mode reconfigurable antenna is used to encode the digital data, data symbol 0 and 1 are mapped to OAM mode 1 and mode −1, respectively. At the receiver, the data symbols are decoded by phase gradient method.
Decrease of FSTL1-BMP4-Smad signaling predicts poor prognosis in lung adenocarcinoma but not in squamous cell carcinoma
Authors: Chiou Jean , Su Chia-Yi , Jan Yi-Hua , Yang Chih-Jen , Huang Ming-Shyan , Yu Yung-Luen , Hsiao Michael 
Published: August 2017

AbstractFollistatin-related protein 1 (FSTL1) plays a critical role in lung development through regulating BMP4-p-Smad1/5/8-Smad4 pathway. Regarding that many developmental pathways in embryogenesis are dysregulated in cancer, we aim to unravel the role of FSTL1-BMP4-Smad pathway in lung cancer. Our results showed low FSTL1 immunoexpression was significantly correlated with poor prognosis while patients with low BMP4 or low Smad4 immunoexpression showed a trend toward poor prognosis. When stratified by different histological types, low FSTL1, BMP4, and Smad4 expression retained their trends in predicting poor prognosis in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma (SCC). Low FSTL1, BMP4, and Smad4 expression were more frequently observed in LUAD patients with smoking history. To determine smoking effect on FSTL1, normal cell BEAS2B and lung cancer cell lines was treated with nicotine and the results showed nicotine increased the proliferation of these cells. Interestingly, FSTL1 attenuated nicotine-induced BEAS2B and lung cancer cell line proliferation. Altogether, low FSTL1, BMP4, and Smad4 expression significantly correlated with poor prognosis in LUAD but not in SCC. Frequent decrease of FSTL1 expression in smokers LUAD further indicates its importance and therapeutic potential for lung cancer patients with specific subtypes. FSTL1 may prevent nicotine-induced lung cancer cell proliferation.
The Role of Na+/Ca2+ Exchanger 1 in Maintaining Ductus Arteriosus Patency
Authors: Li Minghui , Jiang Chuan , Ye Lincai , Wang Shoubao , Zhang Haibo , Liu Jinfen , Hong Haifa 
Published: August 2017

AbstractPatency of the ductus arteriosus (DA) is crucial for both fetal circulation and patients with DA-dependent congenital heart diseases (CHD). The Na+/Ca2+ exchanger 1 (NCX1) protein has been shown to play a key role in the regulation of vascular tone and is elevated in DA-dependent CHD. This current study was conducted to investigate the mechanisms underpinning the role of NCX1 in DA patency. Our data showed NCX1 expression was up-regulated in the DA of fetal mice. Up-regulation of NCX1 expression resulted in a concomitant decrease in cytosolic Ca2+ levels in human DA smooth muscle cells (DASMCs) and an inhibition of the proliferation and migration capacities of human DASMCs. Furthermore, treatment of DASMCs with KB-R7943, which can reduce Ca2+ influx, resulted in the inhibition of both cell proliferation and migration. These findings indicate that NCX1 may play a role in maintaining patent DA not only by preventing DA functional closure through reducing cytosolic Ca2+ level in DASMC but also by delaying the anatomical closure process. The latter delay is facilitated by the down-regulation of human DASMC proliferation and migration. It is also likely that a reduction in cytosolic Ca2+ levels inhibits the proliferation and migration capacities of human DASMCs in vitro.
Early gestational maternal low-protein diet diminishes hepatic response to fasting in young adult male mice
Authors: Sato Noriko , Sudo Katsuko , Mori Masayo , Imai Chihiro , Muramatsu Masaaki , Sugimoto Masahiro 
Published: August 2017

AbstractMaternal low-protein (MLP) diet can lead to hepatic steatosis, which only develops with ageing. It is still unclear whether the young offspring show any signs of past exposure to prenatal adverse conditions. We hypothesized that early nutritional insult would first affect the dynamic responsiveness to nutritional challenges rather than the static state. We analyzed the transcriptome and metabolome profiles of the hepatic response to fasting/refeeding in young male mice offspring to identify changes induced by early gestational MLP diet. Restricted MLP exposure strictly to early gestation was achieved by the embryo transfer method. As a result, the fasting-induced upregulation of genes related to long-chain fatty acid metabolism and of stress response genes related to protein folding were significantly diminished in MLP pups. Lipid profiling after fasting showed that the hepatic signature of triacylglycerols was shifted to longer acyl-chains and higher saturation by the MLP diet. Bioinformatic analyses suggested that these phenomenological changes may be partially linked to the peroxisome proliferator activated receptor α (PPARα) pathway. Taken together, early gestational MLP diet affected the hepatic dynamic response to nutritional stress in seemingly healthy young offspring, accompanied with partial deterioration of PPARα action.
Production of Monoclonal Antibodies to Pathologic β-sheet Oligomeric Conformers in Neurodegenerative Diseases
Authors: Goñi Fernando , Martá-Ariza Mitchell , Peyser Daniel , Herline Krystal , Wisniewski Thomas 
Published: August 2017

AbstractWe describe a novel approach to produce conformational monoclonal antibodies selected to specifically react with the β-sheet secondary structure of pathological oligomeric conformers, characteristic of many neurodegenerative diseases. Contrary to past and current efforts, we utilize a mammalian non-self-antigen as an immunogen. The small, non-self peptide selected was covalently polymerized with glutaraldehyde until it reached a high β-sheet secondary structure content, and species between 10–100kDa that are immunogenic, stable and soluble (p13Bri). Inoculation of p13Bri in mice elicited antibodies to the peptide and the β-sheet secondary structure conformation. Hybridomas were produced and clones selected for their reactivity with at least two different oligomeric conformers from Alzheimer’s, Parkinson and/or Prion diseases. The resulting conformational monoclonals are able to detect pathological oligomeric forms in different human neurodegenerative diseases by ELISA, immunohistochemistry and immunoblots. This technological approach may be useful to develop tools for detection, monitoring and treatment of multiple misfolding disorders.
Expression and Purification of the Pain Receptor TRPV1 for Spectroscopic Analysis
Authors: Velisetty Phanindra , Stein Richard A. , Sierra-Valdez Francisco J. , Vásquez Valeria , Cordero-Morales Julio F. 
Published: August 2017

AbstractThe transient receptor potential vanilloid 1 (TRPV1) channel is an essential component of the cellular mechanism through which noxious stimuli evoke pain. Functional and structural characterizations of TRPV1 shed light on vanilloid activation, yet the mechanisms for temperature and proton gating remain largely unknown. Spectroscopic approaches are needed to understand the mechanisms by which TRPV1 translates diverse stimuli into channel opening. Here, we have engineered a minimal cysteine-less rat TRPV1 construct (eTRPV1) that can be stably purified and reconstituted for spectroscopic studies. Biophysical analyses of TRPV1 constructs reveal that the S5-pore helix loop influences protein stability and vanilloid and proton responses, but not thermal sensitivity. Cysteine mutants retain function and stability for double electron-electron resonance (DEER) and electron paramagnetic resonance (EPR) spectroscopies. DEER measurements in the closed state demonstrate that eTRPV1 reports distances in the extracellular vestibule, equivalent to those observed in the apo TRPV1 structure. EPR measurements show a distinct pattern of mobilities and spectral features, in detergent and liposomes, for residues at the pore domain that agree with their location in the TRPV1 structure. Our results set the stage for a systematic characterization of TRPV1 using spectroscopic approaches to reveal conformational changes compatible with thermal- and ligand-dependent gating.
Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury
Authors: Zhou Han , Tian Xuefei , Tufro Alda , Moeckel Gilbert , Ishibe Shuta , Goodwin Julie 
Published: August 2017

AbstractNephrotic syndrome is a common disorder in adults and children whose etiology is largely unknown. Glucocorticoids remain the mainstay of therapy in most cases, though their mechanism of action remains poorly understood. Emerging evidence suggests that immunomodulatory therapies used in nephrotic syndrome directly target the podocytes. To study how steroids directly affect the podocytes in the treatment of proteinuria, we created a mouse model with podocyte-specific deletion of the glucocorticoid receptor. The podocyte-specific glucocorticoid receptor (GR) knockout mice had similar renal function and protein excretion compared to wild type. However, after glomerular injury induced by either LPS or nephrotoxic serum, the podocyte GR knockout mice demonstrated worsened proteinuria compared to wild type. Ultrastructural examination of podocytes confirmed more robust foot process effacement in the knockout animals. Expression of several key slit diaphragm protein was down regulated in pGR KO mice. Primary podocytes isolated from wild type and podocyte GR knockout mice showed similar actin stress fiber staining patterns in unstimulated conditions. Yet, when exposed to LPS, GR knockout podocytes demonstrated fewer stress fibers and impaired migration compared to wild type podocytes. We conclude that the podocyte glucocorticoid receptor is important for limiting proteinuria in settings of podocyte injury.
Highly tunable time-reversal-invariant topological superconductivity in topological insulator thin films
Authors: Parhizgar Fariborz , Black-Schaffer Annica M. 
Published: August 2017

AbstractWe study time-reversal-invariant topological superconductivity in topological insulator (TI) thin films including both intra- and inter-surface pairing. We find a nontrivial topology for multiple different configurations. For intra-surface pairing a π-phase difference between the intra-surface pairing states is required. We show that in this case the resulting topological phase is highly tunable by both an applied electric field and varied chemical potential. For spin-singlet inter-surface pairing, a sign-changing tunnel coupling present in many TI thin films is needed, and again, the topology can be tuned by electric field or doping. Notably, we find that the required inter-surface pairing strength for achieving nontrivial topology can still be subdominant compared to the intra-surface pairing. Finally, for spin-triplet inter-surface pairing we prove that the superconducting state is always topological nontrivial. We show that thin films of Cu-doped Bi2Se3 will likely host such spin-triplet inter-surface pairing. Taken together, these results show that time-reversal-invariant topological superconductivity is common in superconducting TI thin films and that the topological phase and its Kramers pair of Majorana edge modes is highly tunable with an applied electric field and varied chemical potential.