bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo imaging xenograft models for the evaluation of anti‐brain tumor efficacy of targeted drugs
Authors: Kita Kenji , Arai Sachiko , Nishiyama Akihiro , Taniguchi Hirokazu , Fukuda Koji , Wang Rong , Yamada Tadaaki , Takeuchi Shinji , Tange Shoichiro , Tajima Atsushi , Nakada Mitsutoshi , Yasumoto Kazuo , Motoo Yoshiharu , Murakami Takashi , Yano Seiji 
Published: November 2017

AbstractMolecular‐targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR, ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of brain metastases during treatment. Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR‐L858R/T790M‐positive H1975 lung adenocarcinoma cells, the NUGC4 hepatocyte growth factor (HGF)‐dependent gastric cancer cells, and the KM12SM colorectal cancer cells containing the TPM3‐NTRK1 gene fusion. We investigated the efficacy of targeted drugs by comparison with their effect in extracranial models. In vitro, H1975 cells were sensitive to the third‐generation epidermal growth factor receptor inhibitor osimertinib. Moreover, HGF stimulated the proliferation of NUGC4 cells, that was inhibited by crizotinib, which has anti‐MET activity. KM12SM cells were sensitive to the tropomyosin‐related kinase‐A inhibitors crizotinib and entrectinib. In in vivo H1975 cell models, osimertinib inhibited the progression of both brain and subcutaneous tumors. Furthermore, in in vivo NUGC4 cell models, crizotinib remarkably delayed the progression of brain tumors, and that of peritoneal carcinomatosis. Interestingly, in in vivo KM12SM cell models, treatment with crizotinib delayed the progression of liver metastases, but not that of brain tumors. Conversely, treatment with entrectinib discernibly delayed the progression of both tumor types. Thus, the effect of targeted drugs against brain tumors can differ from the one reported in extracranial tumors. Moreover, the same multikinase inhibitory drug can display different efficacies in brain tumor models containing different drivers. Therefore, our in vivo imaging model for brain tumors may prove useful for preclinical drug screening against brain metastases.
Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide
Authors: Supekar Nitin T. , Lakshminarayanan Vani , Capicciotti Chantelle J. , Sirohiwal Anju , Madsen Cathy S. , Wolfert Margreet A. , Cohen Peter A. , Gendler Sandra J. , Boons Geert‐Jan 
Published: November 2017

AbstractA fully synthetic MUC1‐based cancer vaccine was designed and chemically synthesized containing an endogenous helper T‐epitope (MHC class II epitope). The vaccine elicited robust IgG titers that could neutralize cancer cells by antibody‐dependent cell‐mediated cytotoxicity (ADCC). It also activated cytotoxic T‐lymphocytes. Collectively, the immunological data demonstrate engagement of helper T‐cells in immune activation. A synthetic methodology was developed for a penta‐glycosylated MUC1 glycopeptide, and antisera of mice immunized by the new vaccine recognized such a structure. Previously reported fully synthetic MUC1‐based cancer vaccines that elicited potent immune responses employed exogenous helper T‐epitopes derived from microbes. It is the expectation that the use of the newly identified endogenous helper T‐epitope will be more attractive, because it will activate cognate CD4+ T‐cells that will provide critical tumor‐specific help intratumorally during the effector stage of tumor rejection and will aid in the generation of sustained immunological memory.
A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding
Authors: Kost Lisa J. , Mootz Henning D. 
Published: November 2017

AbstractThe small ubiquitin‐like modifier (SUMO) can be assembled into polymeric chains as part of its diverse biochemical signal pattern upon conjugation to substrate proteins. SUMO chain recognition is facilitated by receptor proteins that contain at least two SUMO‐interacting motifs (SIMs). Little is known about the structure of SUMO chains, both in an unliganded form and upon complexation with multi‐SIM protein partners. A FRET sensor has been developed based on a linear dimer of human SUMO‐2 as a minimal SUMO chain analogue. The synthetic acceptor and donor dyes were conjugated by maleimide and copper‐catalyzed click chemistry to each of the two SUMO subunits. FRET changes were only observed in the presence of di‐ or multi‐SIM ligands. Alteration of the short linker sequence between SIMs 2 and 3 of RNF4 showed a great tolerance, and hence, structural flexibility, of the SUMO dimer for bivalent binding of adjacent SIMs. The di‐SUMO FRET sensor reports on the binding of SIM clusters of the proteins C5orf25 and SOBP; this suggest that these can bind to adjacent subunits of a SUMO chain. The developed FRET sensor will be a useful tool to study the importance of SIM and linker sequences, as well as biochemical and structural properties of SUMO chains and multi‐SIM proteins.
The hybrid of semisupervised manifold learning and spectrum kernel for classification
Authors: Shen Liang , Xu Qingsong , Cao Dongsheng , Liang Yizeng , Dai Hongshuai 
Published: November 2017

AbstractManifold learning classification, as an advanced semisupervised learning algorithm in recent years, has gained great popularity in a variety of fields. Moreover, kernel methods are a group of algorithms for pattern analysis, the task of which is to find and study general types of relations in datasets. Thus, under the framework of kernel methods, manifold learning classifier has been introduced and explored to directly detect the intrinsic similarity by local and global information hidden in datasets. Two validation approaches were used to evaluate the performance of our models. Experiments indicate that the proposed model can be considered as an effective and alternative modeling algorithm, and it could be further applied to the areas of biochemical science, environmental analysis, clinical, etc.
Structure‐based statistical modeling and analysis of peptide affinity and cross‐reactivity to human senile osteoporosis OSF SH3 domain
Authors: Zhang Wei , Zhong Biao , Zhan Yulin , Luo Congfeng 
Published: November 2017

AbstractHuman osteoclast‐stimulating factor (OSF) induces osteoclast formation and bone resorption in senile osteoporosis by recruiting multiple signaling complexes with cognate interacting partners through its N‐terminal Src homology 3 (SH3) peptide‐recognition domain. The domain can recognize and bind to the polyproline regions of its partner proteins, rendering a broad ligand specificity and cross‐reactivity. Here, the structural basis and physicochemical property of peptide affinity and cross‐reactivity to OSF SH3 domain were investigated systematically by using an integration of statistical analysis and molecular modeling. A structure‐based quantitative structure‐activity relationship method called cross‐nonbonded interaction characterization and statistical regression was used to characterize the intermolecular interactions involved in computationally modeled domain‐peptide complex structures and then to correlate the interactions with affinity for a panel of collected SH3‐binding peptide samples. Both the structural stability and generalization ability of obtained quantitative structure‐activity relationship regression models were examined rigorously via internal cross‐validation and external test, confirming that the models can properly describe even single‐residue mutations at domain‐peptide complex interface and give a reasonable extrapolation for the mutation effect on peptide affinity. Subsequently, the best model was used to investigate the promiscuity and cross‐reactivity of OSF SH3 domain binding to its various peptide ligands. It is found that few key residues in peptide ligands are primarily responsible for the domain affinity and selectivity, while most other residues only play a minor role in domain‐peptide binding affinity and stability. The peptide residues can be classified into 3 groups in terms of their contribution to ligand selectivity: key, assistant, and marginal residues. Considering that the key residues are very few so that many domain interacting partners share a similar binding profile, additional factors such as in vivo environments and biological contexts would also contribute to the specificity and cross‐reactivity of OSF SH3 domain.
Long‐term outcomes among 2‐year survivors of autologous hematopoietic cell transplantation for Hodgkin and diffuse large b‐cell lymphoma
Authors: Myers Regina M. , Hill Brian T. , Shaw Bronwen E. , Kim Soyoung , Millard Heather R. , Battiwalla Minoo , Majhail Navneet S. , Buchbinder David , Lazarus Hillard M. , Savani Bipin N. , Flowers Mary E. D. , D'Souza Anita , Ehrhardt Matthew J. , Langston Amelia , Yared Jean A. , Hayashi Robert J. , Daly Andrew , Olsson Richard F. , Inamoto Yoshihiro , Malone Adriana K. , DeFilipp Zachariah , Margossian Steven P. , Warwick Anne B. , Jaglowski Samantha , Beitinjaneh Amer , Fung Henry , Kasow Kimberly A. , Marks David I. , Reynolds Jana , Stockerl‐Goldstein Keith , Wirk Baldeep , Wood William A. , Hamadani Mehdi , Satwani Prakash 
Published: November 2017

BACKGROUNDAutologous hematopoietic cell transplantation (auto‐HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B‐cell lymphoma (DLBCL); however, long‐term outcomes are not well described.METHODSThis study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression‐free for ≥2 years after auto‐HCT for cHL or DLBCL between 1990 and 2008. The median age at auto‐HCT was 40 years; the median follow‐up was 10.6 years.RESULTSThe 5‐year overall survival rate was 90% (95% confidence interval [CI], 87%‐92%) for patients with cHL and 89% (95% CI, 87%‐91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6‐fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4‐fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto‐HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population.CONCLUSIONSDespite generally favorable outcomes, 2‐year survivors of auto‐HCT for cHL or DLBCL have an excess late‐mortality risk in comparison with the general population and experience an assortment of late complications. Cancer 2018;124:816‐25. © 2017 American Cancer Society.
A framework for designing patient‐specific bioprosthetic heart valves using immersogeometric fluid–structure interaction analysis
Authors: Xu Fei , Morganti Simone , Zakerzadeh Rana , Kamensky David , Auricchio Ferdinando , Reali Alessandro , Hughes Thomas J. R. , Sacks Michael S. , Hsu Ming‐Chen 
Published: November 2017

AbstractNumerous studies have suggested that medical image derived computational mechanics models could be developed to reduce mortality and morbidity due to cardiovascular diseases by allowing for patient‐specific surgical planning and customized medical device design. In this work, we present a novel framework for designing prosthetic heart valves using a parametric design platform and immersogeometric fluid–structure interaction (FSI) analysis. We parameterize the leaflet geometry using several key design parameters. This allows for generating various perturbations of the leaflet design for the patient‐specific aortic root reconstructed from the medical image data. Each design is analyzed using our hybrid arbitrary Lagrangian–Eulerian/immersogeometric FSI methodology, which allows us to efficiently simulate the coupling of the deforming aortic root, the parametrically designed prosthetic valves, and the surrounding blood flow under physiological conditions. A parametric study is performed to investigate the influence of the geometry on heart valve performance, indicated by the effective orifice area and the coaptation area. Finally, the FSI simulation result of a design that balances effective orifice area and coaptation area reasonably well is compared with patient‐specific phase contrast magnetic resonance imaging data to demonstrate the qualitative similarity of the flow patterns in the ascending aorta.
Rhodium Decahedral Nanocrystals: Facile Synthesis, Mechanistic Insights, and Experimental Controls
Authors: Lee Sujin R. , Vara Madeline , Hood Zachary D. , Zhao Ming , Gilroy Kyle D. , Chi Miaofang , Xia Younan 
Published: November 2017

AbstractDecahedral nanocrystals have received great attention owing to their unique symmetry and strain‐energy distribution. In contrast to other noble metals, it has been difficult to synthesize decahedral Rh nanocrystals. We report a robust, one‐pot method based on polyol reduction for the facile synthesis of Rh decahedral nanocrystals in high purity, with sub‐20 nm sizes. The success of the synthesis relied on our ability to manipulate reduction kinetics by systematically tuning experimental parameters. We found that the yield of Rh decahedral nanocrystals could be maximized by optimizing: i) the concentration of Rh(acac)3 (metal precursor); ii) the molecular weight and amount of poly(vinyl pyrrolidone) (colloidal stabilizer/capping agent); and iii) the chain length of the polyol (solvent/reducing agent), with tetraethylene glycol being the best. We believe the mechanisms elucidated herein can be extended to other syntheses to produce metal nanocrystals with multiply twinned structures.
Single‐Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology
Authors: Atsmon Jacob , Heffetz Daphna , Deutsch Lisa , Deutsch Frederic , Sacks Hagit 
Published: November 2017

AbstractCannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti‐inflammatory, antidepressant, and antipsychotic effects. PTL101 is an oral gelatin matrix pellets technology–based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design. Administration of PTL101 containing 10 CBD, led to a 1.7‐fold higher Cmax and 1.3‐fold higher AUC compared with the oromucosal spray. Tmax following both modes of delivery was 3–3.5 hours postdosing. CBD exhibited about a 1‐hour lag in absorption when delivered via PTL101. A 10‐fold increase in the dose resulted in an ∼15‐fold increase in Cmax and AUC. Bioavailability of CBD in the 10‐mg PTL101 dose was 134% relative to the reference spray. PTL101 is a pharmaceutical‐grade, user‐friendly oral formulation that demonstrated safe and efficient delivery of CBD and therefore could be an attractive candidate for therapeutic indications.
Measuring pH of the Coxiella burnetii Parasitophorous Vacuole
Authors: Samanta Dhritiman , Gilk Stacey D. 
Published: November 2017

Abstract
Coxiella burnetii is the causative agent of human Q fever, a zoonotic disease that can cause a debilitating, flu‐like illness in acute cases, or a life‐threatening endocarditis in chronic patients. An obligate intracellular bacterial pathogen, Coxiella survives and multiplies in a large lysosome‐like vacuole known as the Coxiella parasitophorous vacuole (CPV). A unique characteristic of the CPV is the acidic environment (pH ∼5.0), which is required to activate Coxiella metabolism and the Coxiella type 4 secretion system (T4SS), a major virulence factor required for intracellular survival. Further, inhibiting or depleting vacuolar ATPase, a host cell protein that regulates lysosomal pH, inhibits intracellular Coxiella growth. Together, these data suggest that CPV pH is an important limiting factor for Coxiella growth and virulence. This unit describes a method to determine CPV pH using live cell microscopy of a pH–sensitive fluorophore conjugated to dextran. This technique is useful to measure changes in CPV pH during infection or in response to drug treatment. © 2017 by John Wiley & Sons, Inc.
Efficient Microwave Irradiation‐Assisted Hydrothermal Synthesis of Ammonium Vanadate Flake
Authors: Wang Jing‐peng , Zhang Yi‐min , Huang Jing , Liu Tao 
Published: November 2017

AbstractThe major factors and affection for hydrothermal synthesis of ammonium vanadate in microwave irradiation was investigated and optimized. The obtained material was a pure (NH4)2V6O16 phase with regular spindle and rhombic crystal shapes. Transmission electron microscope and selected‐area electron diffraction patterns confirmed that the microwave irradiation‐assisted hydrothermal treatments altered the growth pattern and expanded the [–1 0 0] interplanar spacing by approximately ∼8%–12% compared to the standard powder diffraction file data.
Metal Phosphides as Co‐Catalysts for Photocatalytic and Photoelectrocatalytic Water Splitting
Authors: Cao Shuang , Wang Chuan‐Jun , Fu Wen‐Fu , Chen Yong 
Published: November 2017

AbstractSolar‐to‐hydrogen conversion based on photocatalytic and photoelectrocatalytic water splitting is considered as a promising technology for sustainable hydrogen production. Developing earth‐abundant H2‐production materials with robust activity and stability has become the mainstream in this field. Due to the unique properties and characteristics, transition metal phosphides (TMPs) have been proven to be high performance co‐catalysts to replace some of the classic precious metal materials in photocatalytic water splitting. In this Minireview, we summarize the recent significant progress of TMPs as cocatalysts for water splitting reaction with high activity and stability. Firstly, the characteristic of TMPs is briefly introduced. Then, we mainly discuss the recent research efforts toward their application as photocatalytic co‐catalysts in photocatalytic H2‐production, O2‐evolution and photoelectrochemical water splitting. Finally, the catalytic mechanism, current existing challenges and future working directions for improving the performance of TMPs are proposed.
Ruthenium Ion‐Complexed Graphitic Carbon Nitride Nanosheets Supported on Reduced Graphene Oxide as High‐Performance Catalysts for Electrochemical Hydrogen Evolution
Authors: Peng Yi , Pan Wanzhang , Wang Nan , Lu Jia‐En , Chen Shaowei 
Published: November 2017

AbstractCarbon‐based materials are promising, low‐cost electrocatalysts toward hydrogen evolution reaction (HER), although the catalytic performance needs to be further improved before commercialization. In this study, ruthenium ions are incorporated into graphitic carbon nitride/reduced graphene oxide (rGO) hybrids to form Ru−C3N4/rGO composites through Ru−N coordination bonds. The incorporation of Ru ions, at a loading of 1.93 at. %, leads to electron redistribution within the materials and dramatically enhances the HER performance over those of C3N4, C3N4/rGO, and Ru−C3N4, with an overpotential of only −80 mV to reach a current density of 10 mA cm−2, a Tafel slope of 55 mV dec−1, and an exchange current density of 0.462 mA cm−2. This performance is comparable to that of Pt/C, and ascribed to the positive shift of the conduction band of the composite, where the charge carrier density increases by a factor of about 250 over that of C3N4, leading to a lower energy barrier for hydrogen evolution. The results suggest a new strategy in the design and engineering of functional nanocomposites for effective HER electrocatalysis by embedding select metal ions into carbon‐based molecular skeletons.
A 99.95% linearity readout circuit with 72 dB dynamic range for active pixel sensors
Authors: de Sá Leonardo Bruno , Dias Mauricio Henrique Costa , Dupret Antoine , de Mesquita Filho Antonio Carneiro 
Published: November 2017

SummaryOne of the main sources of nonlinearity and sensitivity degradation in conventional active pixel sensor (APS) architectures is the source follower buffer amplifier that isolates the photodiode node from the column bus. To extend the linear region of the output voltage, correct the sensitivity degradation, and improve the imager dynamic range, an output regulated voltage follower is proposed. All these enhancements are achieved without decreasing the pixel fill factor nor increasing the number of transistors and the addressing circuits complexity of a conventional 4T CMOS APS. The performance of the circuit is assessed using a 0.35‐μm CMOS technology. The obtained results show a 14‐dB dynamic range improvement for highly linear applications over the conventional APS readout circuit.
Normal white matter microstructure in women long‐term recovered from anorexia nervosa: A diffusion tensor imaging study
Authors: Bang Lasse , Rø Øyvind , Endestad Tor 
Published: November 2017

AbstractObjectivesStudies point to white matter (WM) microstructure alterations in both adolescent and adult patients with anorexia nervosa (AN). These include reduced fractional anisotropy in several WM fiber tracts, suggesting reduced WM integrity. The extent to which these alterations are reversible with recovery from AN is unclear. There is a paucity of research investigating the presence of WM microstructure alterations in recovered AN patients, and results are inconsistent. This study aimed to investigate the presence of WM microstructure alterations in women long‐term recovered from AN.MethodTwenty‐one adult women who were recovered from AN for at least 1 year were compared to 21 adult comparison women. Participants were recruited via user‐organizations for eating disorders, local advertisements, and online forums. Diffusion tensor imaging was used to compare WM microstructure between groups. Correlations between WM microstructure and clinical characteristics were also explored.ResultsThere were no statistically significant between‐group differences in WM microstructure. These null findings remained when employing liberal alpha level thresholds. Furthermore, there were no statistically significant correlations between WM microstructure and clinical characteristics.DiscussionOur findings showed normal WM microstructure in long‐term recovered patients, indicating the alterations observed during the acute phase are reversible. Given the paucity of research and inconsistent findings, future studies are warranted to determine the presence of WM microstructure alterations following recovery from AN.