bluuebunny/crossref_metadata_2025_split huggingface dataset:
A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines
Authors: Wada Yamato , Nithichanon Arnone , Nobusawa Eri , Moise Leonard , Martin William D. , Yamamoto Norio , Terahara Kazutaka , Hagiwara Haruhisa , Odagiri Takato , Tashiro Masato , Lertmemongkolchai Ganjana , Takeyama Haruko , De Groot Anne S. , Ato Manabu , Takahashi Yoshimasa 
Published: April 2017

AbstractInfluenza vaccines of H7N9 subtype are consistently less immunogenic in humans than vaccines developed for other subtypes. Although prior immunoinformatic analysis identified T-cell epitopes in H7 hemagglutinin (HA) which potentially enhance regulatory T cell response due to conservation with the human genome, the links between the T-cell epitopes and low immunogenicity of H7 HA remains unknown due to the lack of animal models reproducing the response observed in humans. Here, we utilized a humanized mouse model to recapitulate the low immunogenicity of H7 HA. Our analysis demonstrated that modification of a single H7 epitope by changing 3 amino acids so that it is homologous with a known H3 immunogenic epitope sequence significantly improved the immunogenicity of the H7 HA in the humanized mouse model, leading to a greater than 4-fold increase in HA-binding IgG responses. Thus, we provide experimental evidence for the important contribution of this H7-specific T cell epitope in determining the immunogenicity of an influenza vaccine. Furthermore, this study delineates strategies that can be used for screening and selecting vaccine strains using immunoinformatics tools and a humanized mouse model.
Facile control of nanoporosity in Cellulose Acetate using Nickel(II) nitrate additive and water pressure treatment for highly efficient battery gel separators
Authors: Lee Woong Gi , Kim Do Hyeong , Jeon Woo Cheol , Kwak Sang Kyu , Kang Seok Ju , Kang Sang Wook 
Published: April 2017

AbstractWe succeed in fabricating nearly straight nanopores in cellulose acetate (CA) polymers for use as battery gel separators by utilizing an inorganic hexahydrate (Ni(NO3)2·6H2O) complex and isostatic water pressure treatment. The continuous nanopores are generated when the polymer film is exposed to isostatic water pressure after complexing the nickel(II) nitrate hexahydrate (Ni(NO3)2·6H2O) with the CA. These results can be attributed to the manner in which the polymer chains are weakened because of the plasticization effect of the Ni(NO3)2·6H2O that is incorporated into the CA. Furthermore, we performed extensive molecular dynamics simulation for confirming the interaction between electrolyte and CA separator. The well controlled CA membrane after water pressure treatment enables fabrication of highly reliable cell by utilizing 2032-type coin cell structure. The resulting cell performance exhibits not only the effect of the physical morphology of CA separator, but also the chemical interaction of electrolyte with CA polymer which facilitates the Li-ion in the cell.
Families of stable solitons and excitations in the PT-symmetric nonlinear Schrödinger equations with position-dependent effective masses
Authors: Chen Yong , Yan Zhenya , Mihalache Dumitru , Malomed Boris A. 
Published: April 2017

AbstractSince the parity-time-($$\pmb{\mathscr{P}}\pmb{\mathscr{T}}$$
P
T
-) symmetric quantum mechanics was put forward, fundamental properties of some linear and nonlinear models with $$\pmb{\mathscr{P}}\pmb{\mathscr{T}}$$
P
T
-symmetric potentials have been investigated. However, previous studies of $$\pmb{\mathscr{P}}\pmb{\mathscr{T}}$$
P
T
-symmetric waves were limited to constant diffraction coefficients in the ambient medium. Here we address effects of variable diffraction coefficient on the beam dynamics in nonlinear media with generalized $$\pmb{\mathscr{P}}\pmb{\mathscr{T}}$$
P
T
-symmetric Scarf-II potentials. The broken linear $$\pmb{\mathscr{P}}\pmb{\mathscr{T}}$$
P
T
symmetry phase may enjoy a restoration with the growing diffraction parameter. Continuous families of one- and two-dimensional solitons are found to be stable. Particularly, some stable solitons are analytically found. The existence range and propagation dynamics of the solitons are identified. Transformation of the solitons by means of adiabatically varying parameters, and collisions between solitons are studied too. We also explore the evolution of constant-intensity waves in a model combining the variable diffraction coefficient and complex potentials with globally balanced gain and loss, which are more general than $$\pmb{\mathscr{P}}\pmb{\mathscr{T}}$$
P
T
-symmetric ones, but feature similar properties. Our results may suggest new experiments for $$\pmb{\mathscr{P}}\pmb{\mathscr{T}}$$
P
T
-symmetric nonlinear waves in nonlinear nonuniform optical media.
Neural coding of prior expectations in hierarchical intention inference
Authors: Chambon Valerian , Domenech Philippe , Jacquet Pierre O. , Barbalat Guillaume , Bouton Sophie , Pacherie Elisabeth , Koechlin Etienne , Farrer Chlöé 
Published: April 2017

AbstractThe ability to infer other people’s intentions is crucial for successful human social interactions. Such inference relies on an adaptive interplay of sensory evidence and prior expectations. Crucially, this interplay would also depend on the type of intention inferred, i.e., on how abstract the intention is. However, what neural mechanisms adjust the interplay of prior and sensory evidence to the abstractness of the intention remains conjecture. We addressed this question in two separate fMRI experiments, which exploited action scenes depicting different types of intentions (Superordinate vs. Basic; Social vs. Non-social), and manipulated both prior and sensory evidence. We found that participants increasingly relied on priors as sensory evidence became scarcer. Activity in the medial prefrontal cortex (mPFC) reflected this interplay between the two sources of information. Moreover, the more abstract the intention to infer (Superordinate > Basic, Social > Non-Social), the greater the modulation of backward connectivity between the mPFC and the temporo-parietal junction (TPJ), resulting in an increased influence of priors over the intention inference. These results suggest a critical role for the fronto-parietal network in adjusting the relative weight of prior and sensory evidence during hierarchical intention inference.
Importance of the novel organic cation transporter 1 for tyrosine kinase inhibition by saracatinib in rheumatoid arthritis synovial fibroblasts
Authors: Harrach Saliha , Edemir Bayram , Schmidt-Lauber Christian , Pap Thomas , Bertrand Jessica , Ciarimboli Giuliano 
Published: April 2017

AbstractRecent therapeutic approaches of rheumatoid arthritis (RA) address the use of small molecules such as tyrosine kinase inhibitors (TKIs). However, the TKIs developed to date have important side effects and/or scarce efficacy in inflammatory diseases such as RA. Since intracellular effective TKIs must enter the cell to reach their intracellular targets, here we investigated the interaction of the TKI saracatinib, a dual inhibitor of c-Src and c-Abl signaling, with transporters for organic cations as well as the role of these transporters for the biological effect of saracatinib in human RA-synovial fibroblasts (hRASF). Saracatinib significantly reduced proliferation of hRASF. The cellular saracatinib uptake was mainly dependent on the human novel organic cation transporter 1 (hOCTN1), which showed the highest apparent affinity for saracatinib among all other transporters for organic cations analyzed here. In hRASF, saracatinib biologic function was dependent on hOCTN1. Further analysis showed that disease specific factors (pH, inflammatory cytokines such as TNFα) regulated saracatinib uptake in hRASF. The knowledge of which transporters mediate the specific uptake of TKIs in target cells and of how the expression and function of such transporters are regulated in RA is of highest priority to develop effective drugs for successful therapy with minimal side-effects.
Left Ventricular Stiffness in Adolescents and Young Adults with Repaired Tetralogy of Fallot
Authors: Yu Clement Kwong-man , Wong Wilfred Hing-sang , Li Vivian Wing-yi , Cheung Yiu-fai 
Published: April 2017

AbstractLeft ventricular (LV) remodeling after tetralogy of Fallot (TOF) repair may influence LV stiffness. We hypothesized that LV stiffness is altered after TOF repair and related to myocardial calibrated integrated backscatter (cIB) and LV diastolic myocardial deformation. Seventy-seven TOF patients and 80 controls were studied. LV stiffness was assessed by diastolic wall strain (DWS) as defined by (LVPWsystole-LVPWdiastole)/LVPWsystole, where LVPW is LV posterior wall thickness, and stiffness index as defined by (E/e/LV end-diastolic dimension), where E and e are respectively early diastolic transmitral inflow and mitral annular velocities. Septal and LVPW cIB and LV diastolic strain rates were determined. Patients had significantly lower DWS (p < 0.001), higher stiffness index (p < 0.001), and greater cIB (p < 0.001). LV DWS correlated negatively with LV stiffness index (r = −0.31, p < 0.001), septal cIB (r = −0.21, p = 0.01), E/e ratio (r = −0.30, p < 0.001) and RV end-diastolic area (r = −0.31, p < 0.001), and positively with LV early (r = 0.33, p < 0.001) and late (r = 0.20, p = 0.01) diastolic strain rates and RV fractional area change (FAC) (r = 0.24, p = 0.003). Multivariate analysis revealed E/e (β = −0.26, p = 0.008), RV end-diastolic area (β = −0.20, p = 0.02), and RV FAC (β = 0.18, p = 0.01) as significant correlates of DWS. Left ventricular stiffening occurs after TOF repair and is related to impaired LV diastolic myocardial deformation, myocardial cIB, and RV volume overload.
Revisiting the IGF-1R as a breast cancer target
Authors: Ekyalongo Roudy Chiminch , Yee Douglas 
Published: April 2017

AbstractThe type I insulin-like growth factor-1 receptor is a well-described target in breast cancer and multiple clinical trials examining insulin-like growth factor-1 receptor have been completed. Unfortunately, monoclonal antibodies and tyrosine kinase inhibitors targeting insulin-like growth factor-1 receptor failed in phase III breast clinical trials for several reasons. First, insulin-like growth factor-1 receptor antibody therapy resulted in hyperglycemia and metabolic syndrome most likely due to disruption of insulin-like growth factor-1 homeostasis and subsequent growth hormone elevation. Growth hormone elevation induces insulin resistance, hence a subsequent elevation of insulin and the potential for activation of insulin receptor. Second, the insulin-like growth factor-1 receptor and insulin receptor are highly homologous in amino acid sequence, structure, and function. These two receptors bind insulin, insulin-like growth factor-1 and insulin-like growth factor-2, to regulate glucose uptake and other cellular functions. Hybrid receptors composed of one chain of insulin-like growth factor-1 receptor and insulin receptor also participate in signaling. Third, since all the monoclonal antibodies were specific for insulin-like growth factor-1 receptor, any pathophysiologic role for insulin receptor was not inhibited. While the insulin-like growth factor-1 receptor tyrosine kinase inhibitors effectively inhibited both insulin-like growth factor-1 receptor and insulin receptor, these drugs are not being further developed likely due to their metabolic toxicities. Insulin-like growth factor-1/2 neutralizing antibodies are still being studied in early phase clinical trials. Perhaps a more comprehensive strategy of targeting the insulin-like growth factor-1 receptor network would be successful. For example, targeting receptor, ligand and downstream signaling molecules such as phosphatidylinositol 3′-kinase or particularly the insulin receptor substrate adapter proteins might result in a complete blockade of insulin-like growth factor-1 receptor/insulin receptor biological functions.
A feasible strategy to balance the crystallinity and specific surface area of metal oxide nanocrystals
Authors: Zhang Q. P. , Xu X. N. , Liu Y. T. , Xu M. , Deng S. H. , Chen Y. , Yuan H. , Yu F. , Huang Y. , Zhao K. , Xu S. , Xiong G. 
Published: April 2017

AbstractPractical, efficient synthesis of metal oxide nanocrystals with good crystallinity and high specific surface area by a modified polymer-network gel method is demonstrated, taking ZnO nanocrystals as an example. A novel stepwise heat treatment yields significant improvement in crystal quality. Such nanophase materials can effectively degrade common organic dyes under solar radiation and can perform very well in photo-assisted detection of NO2 gas. Other typical metal oxide nanocrystals with good crystallinity and high specific surface area were also synthesized successfully under similar conditions. This work provides a general strategy for the synthesis of metal oxide nanocrystals, balancing the crystallinity and specific surface area.
Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients
Authors: Jiao Lijing , Dong Changsheng , Liu Jiaxiang , Chen Zhiwei , Zhang Lei , Xu Jianfang , Shen Xiaoyong , Che Jiaming , Yang Yi , Huang Hai , Li Hegen , Sun Jianli , Jiang Yi , Mao Zhujun , Chen Peiqi , Gong Yabin , Jin Xiaolin , Xu Ling 
Published: April 2017

AbstractThe aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control,n = 158) and NP/NC with additional TCM (intervention,n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57%vs4.02%,P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9vs22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens.
Higher risk of colorectal cancer in patients with newly diagnosed diabetes mellitus before the age of colorectal cancer screening initiation
Authors: de Kort Sander , Masclee Ad A. M. , Sanduleanu Silvia , Weijenberg Matty P. , van Herk-Sukel Myrthe P. P. , Oldenhof Nico J. J. , van den Bergh Joop P. W. , Haak Harm R. , Janssen-Heijnen Maryska L. 
Published: April 2017

AbstractType 2 diabetes mellitus (T2DM) is associated with greater risk for colorectal cancer (CRC). The age of onset of T2DM is decreasing worldwide. An increased CRC risk in young T2DM patients could be relevant for the age at which to initiate CRC screening. We report on CRC risk in T2DM patients with attention to age of diagnosis. We used pharmacy data (from 1998 to 2010) from the PHARMO Database Network linked to the Eindhoven Cancer Registry. Multivariable time-dependent Cox regression analyses were conducted to calculate hazard ratios (HR) for developing CRC comparing T2DM with non-T2DM. During 2,599,925 years of follow-up, 394 CRC cases among 41,716 diabetes patients (mean age 64.0 yr, 48% men) and 1,939 CRC cases among 325,054 non-diabetic patients (mean age 51.2 yr, 46% men) were identified. Diabetes was associated with an increased CRC risk in both men and women (HR 1.3, 95% CI 1.2–1.5), particularly in the first 6 months after T2DM diagnosis and pronounced in the proximal colon. This risk was even higher in men younger than 55 years (HR 2.0, 95% CI 1.0–3.8). T2DM was associated with a time-varying and subsite-specific increased CRC risk, which was even higher in men aged <55 years.
Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper–Hollow Silica Nanoparticles
Authors: Palanikumar L. , Jeena M. T. , Kim Kibeom , Yong Oh Jun , Kim Chaekyu , Park Myoung-Hwan , Ryu Ja-Hyoung 
Published: April 2017

AbstractCombination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment.
Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals
Authors: Cheedarla Narayanaiah , Precilla K. Lucia , Babu Hemalatha , Vijayan K. K. Vidya , Ashokkumar Manickam , Chandrasekaran Padmapriyadarsini , Kailasam Nandagopal , Sundaramurthi Jagadish Chandrabose , Swaminathan Soumya , Buddolla Viswanath , Vaniambadi S. Kalyanaraman , Ramanathan V. D. , Hanna Luke Elizabeth 
Published: April 2017

AbstractBroadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.
Rational design of non-resistant targeted cancer therapies
Authors: Martínez-Jiménez Francisco , Overington John P. , Al-Lazikani Bissan , Marti-Renom Marc A. 
Published: April 2017

AbstractDrug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy. Moreover, for these treatment-threatening mutations, the model proposes alternative therapies overcoming the resistance. We exemplified the applicability of the model using EGFR-gefitinib treatment for Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Cancer (LSCC) and the ERK2-VTX11e treatment for melanoma and colorectal cancer. Our model correctly identified the phenotype known resistance mutations, including the classic EGFR-T790M and the ERK2-P58L/S/T mutations. Moreover, the model predicted new previously undescribed mutations as potentially responsible of drug resistance. Finally, we provided a map of the predicted sensitivity of alternative ERK2 and EGFR inhibitors, with a particular highlight of two molecules with a low predicted resistance impact.
Elevated circulating levels of the interferon-γ–induced chemokines are associated with disease activity and cutaneous manifestations in adult-onset Still’s disease
Authors: Han Jae Ho , Suh Chang-Hee , Jung Ju-Yang , Ahn Mi-Hyun , Han Mi Hwa , Kwon Ji Eun , Yim Hyunee , Kim Hyoun-Ah 
Published: April 2017

AbstractC-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 are produced in response to interferon-γ (IFN-γ) and trigger inflammation with the accumulation of activated lymphocytes. It appears that these chemokines could play a role in the pathogenesis of adult-onset Still’s disease (AOSD). Therefore, we investigated the associations between the levels of these chemokine and clinical manifestations in patients with active AOSD. Serum levels of IFN-γ, CXCL9, CXCL10 and CXCL11 were determined using enzyme-linked immunosorbent assays. IFN-γ levels were higher in AOSD patients than in rheumatoid arthritis (RA) patients (p = 0.001) or healthy controls (HCs) (p = 0.032). AOSD patients also exhibited higher levels of CXCL9, CXCL10, and CXCL11 compared with RA patients (p < 0.001) and HCs (p < 0.001). In follow-up AOSD patients after treatment with corticosteroid, the levels of CXCL9, CXCL10 and CXCL11 fell significantly, whereas IFN-γ levels were not significantly different. On immunohistochemistry, the percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples from AOSD patients than in those from normal control (p = 0.012), eczema (p = 0.019), and psoriasis (p = 0.009) groups. Levels of the IFN-γ–induced chemokines, CXCL9, CXCL10 and CXCL11, were elevated and correlated with several disease activity markers. These interferon-γ–induced chemokines may contribute to inflammatory responses and skin manifestations in AOSD.
Definition of fractal topography to essential understanding of scale-invariance
Authors: Jin Yi , Wu Ying , Li Hui , Zhao Mengyu , Pan Jienan 
Published: April 2017

AbstractFractal behavior is scale-invariant and widely characterized by fractal dimension. However, the cor-respondence between them is that fractal behavior uniquely determines a fractal dimension while a fractal dimension can be related to many possible fractal behaviors. Therefore, fractal behavior is independent of the fractal generator and its geometries, spatial pattern, and statistical properties in addition to scale. To mathematically describe fractal behavior, we propose a novel concept of fractal topography defined by two scale-invariant parameters, scaling lacunarity (P) and scaling coverage (F). The scaling lacunarity is defined as the scale ratio between two successive fractal generators, whereas the scaling coverage is defined as the number ratio between them. Consequently, a strictly scale-invariant definition for self-similar fractals can be derived as D = log F /log P. To reflect the direction-dependence of fractal behaviors, we introduce another parameter Hxy, a general Hurst exponent, which is analytically expressed by Hxy = log Px/log Py where Px and Py are the scaling lacunarities in the x and y directions, respectively. Thus, a unified definition of fractal dimension is proposed for arbitrary self-similar and self-affine fractals by averaging the fractal dimensions of all directions in a d-dimensional space, which "Equation missing". Our definitions provide a theoretical, mechanistic basis for understanding the essentials of the scale-invariant property that reduces the complexity of modeling fractals.