bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirement for neuropeptide Y in the development of type 2 responses and allergen-induced airway hyperresponsiveness and inflammation
Authors: Oda Naohiro , Miyahara Nobuaki , Taniguchi Akihiko , Morichika Daisuke , Senoo Satoru , Fujii Utako , Itano Junko , Gion Yuka , Kiura Katsuyuki , Kanehiro Arihiko , Maeda Yoshinobu
Published: January 2019

Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y1 receptor. NPY modulates these cells via its Y1 receptor; however, involvement of NPY in the pathophysiology of bronchial asthma, particularly airway hyperresponsiveness (AHR), has not been defined. NPY-deficient and wild-type mice were intranasally sensitized and challenged to house dust mite (HDM) extract, and airway responses were monitored. After sensitization and challenge, NPY-deficient mice showed significantly lower AHR than wild-type mice, and numbers of eosinophils and levels of type 2 cytokines [interleukin (IL)-4, IL-5, and IL-13] in bronchoalveolar lavage fluid were significantly lower. Type 2 cytokine production from splenic mononuclear cells of HDM-sensitized mice was also significantly lower in NPY-deficient mice. Flow cytometry analysis showed that the number of CD4 T cells and CD11c+ antigen–presenting cells (APCs) was significantly lower in the lungs of NPY-deficient mice than in wild-type mice following sensitization and challenge. Significantly fewer CD11c+ APCs phagocytosed HDM in the mediastinal lymph nodes of NPY-deficient mice than in those of wild-type mice. Treatment with BIBO-3304, a NPY receptor antagonist, significantly suppressed development of HDM-induced AHR and inflammation in wild-type mice. These data identify an important contribution of NPY to allergen-induced AHR and inflammation through accumulation of dendritic cells in the airway and promotion of the type 2 immune response. Thus, manipulating NPY represents a novel therapeutic target to control allergic airway responses.
Exploring the underlying biology of intrinsic cardiorespiratory fitness through integrative analysis of genomic variants and muscle gene expression profiling
Authors: Ghosh Sujoy , Hota Monalisa , Chai Xiaoran , Kiranya Jencee , Ghosh Palash , He Zihong , Ruiz-Ramie Jonathan J. , Sarzynski Mark A. , Bouchard Claude
Published: January 2019

Intrinsic cardiorespiratory fitness (CRF) is defined as the level of CRF in the sedentary state. There are large individual differences in intrinsic CRF among sedentary adults. The physiology of variability in CRF has received much attention, but little is known about the genetic and molecular mechanisms that impact intrinsic CRF. These issues were explored in the present study by interrogating intrinsic CRF-associated DNA sequence variation and skeletal muscle gene expression data from the HERITAGE Family Study through an integrative bioinformatics guided approach. A combined analytic strategy involving genetic association, pathway enrichment, tissue-specific network structure, cis-regulatory genome effects, and expression quantitative trait loci was used to select and rank genes through a variation-adjusted weighted ranking scheme. Prioritized genes were further interrogated for corroborative evidence from knockout mouse phenotypes and relevant physiological traits from the HERITAGE cohort. The mean intrinsic V̇o2maxwas 33.1 ml O2·kg−1·min−1(SD = 8.8) for the sample of 493 sedentary adults. Suggestive evidence was found for gene loci related to cardiovascular physiology ( ATE1, CASQ2, NOTO, and SGCG), hematopoiesis ( PICALM, SSB, CA9, and CASQ2), skeletal muscle phenotypes ( SGCG, DMRT2, ADARB1, and CASQ2), and metabolism ( ATE1, PICALM, RAB11FIP5, GBA2, SGCG, PRADC1, ARL6IP5, and CASQ2). Supportive evidence for a role of several of these loci was uncovered via association between DNA variants and muscle gene expression levels with exercise cardiovascular and muscle physiological traits. This initial effort to define the underlying molecular substrates of intrinsic CRF warrants further studies based on appropriate cohorts and study designs, complemented by functional investigations.

NEW & NOTEWORTHY Intrinsic cardiorespiratory fitness (CRF) is measured in the sedentary state and is highly variable among sedentary adults. The physiology of variability in intrinsic cardiorespiratory fitness has received much attention, but little is known about the genetic and molecular mechanisms that impact intrinsic CRF. These issues were explored computationally in the present study, with further corroborative evidence obtained from analysis of phenotype data from knockout mouse models and human cardiovascular and skeletal muscle measurements.
Sustained Klotho delivery reduces serum phosphate in a model of diabetic nephropathy
Authors: Hum Julia M. , O’Bryan Linda M. , Tatiparthi Arun K. , Clinkenbeard Erica L. , Ni Pu , Cramer Martin S. , Bhaskaran Manoj , Johnson Robert L. , Wilson Jonathan M. , Smith Rosamund C. , White Kenneth E.
Published: January 2019

Diabetic nephropathy (DN) is a primary cause of end-stage renal disease and is becoming more prevalent because of the global rise in type 2 diabetes. A model of DN, the db/db uninephrectomized ( db/db-uni) mouse, is characterized by obesity, as well as compromised renal function. This model also manifests defects in mineral metabolism common in DN, including hyperphosphatemia, which leads to severe endocrine disease. The FGF23 coreceptor, α-Klotho, circulates as a soluble, cleaved form (cKL) and may directly influence phosphate handling. Our study sought to test the effects of cKL on mineral metabolism in db/db-uni mice. Mice were placed into either mild or moderate disease groups on the basis of the albumin-to-creatinine ratio (ACR). Body weights of db/db-uni mice were significantly greater across the study compared with lean controls regardless of disease severity. Adeno-associated cKL administration was associated with increased serum Klotho, intact, bioactive FGF23 (iFGF23), and COOH-terminal fragments of FGF23 ( P < 0.05). Blood urea nitrogen was improved after cKL administration, and cKL corrected hyperphosphatemia in the high- and low-ACR db/db-uni groups. Interestingly, 2 wk after cKL delivery, blood glucose levels were significantly reduced in db/db-uni mice with high ACR ( P < 0.05). Interestingly, several genes associated with stabilizing active iFGF23 were also increased in the osteoblastic UMR-106 cell line with cKL treatment. In summary, delivery of cKL to a model of DN normalized blood phosphate levels regardless of disease severity, supporting the concept that targeting cKL-affected pathways could provide future therapeutic avenues in DN.

NEW & NOTEWORTHY In this work, systemic and continuous delivery of the “soluble” or “cleaved” form of the FGF23 coreceptor α-Klotho (cKL) via adeno-associated virus to a rodent model of diabetic nephropathy (DN), the db/db uninephrectomized mouse, normalized blood phosphate levels regardless of disease severity. This work supports the concept that targeting cKL-affected pathways could provide future therapeutic avenues for the severe mineral metabolism defects associated with DN.
Exercise-induced hyperemia is associated with knee extensor fatigability in adults with type 2 diabetes
Authors: Senefeld Jonathon W. , Limberg Jacqueline K. , Lukaszewicz Kathleen M. , Hunter Sandra K.
Published: January 2019

The aim of this study was to compare fatigability, contractile function, and blood flow to the knee extensor muscles after dynamic exercise in patients with type 2 diabetes mellitus (T2DM) and controls. The hypotheses were that patients with T2DM would demonstrate greater fatigability than controls, and greater fatigability would be associated with a lower exercise-induced increase in blood flow and greater impairments in contractile function. Patients with T2DM ( n = 15; 8 men; 62.4 ± 9.0 yr; 30.4 ± 7.7 kg/m2; 7,144 ± 3,294 steps/day) and 15 healthy control subjects (8 men, 58.4 ± 6.9 yr; 28.4 ± 4.6 kg/m2; 7,893 ± 2,323 steps/day) were matched for age, sex, body mass index, and physical activity. Fatigability was quantified as the reduction in knee extensor power during a 6-min dynamic exercise. Before and after exercise, vascular ultrasonography and electrical stimulation were used to assess skeletal muscle blood flow and contractile properties, respectively. Patients with T2DM had greater fatigability (30.0 ± 20.1% vs. 14.6 ± 19.0%, P < 0.001) and lower exercise-induced hyperemia (177 ± 90% vs. 194 ± 79%, P = 0.04) than controls but similar reductions in the electrically evoked twitch amplitude (37.6 ± 24.8% vs. 31.6 ± 30.1%, P = 0.98). Greater fatigability of the knee extensor muscles was associated with postexercise reductions in twitch amplitude ( r = 0.64, P = 0.001) and lesser exercise-induced hyperemia ( r = −0.56, P = 0.009). Patients with T2DM had greater lower-limb fatigability during dynamic exercise, which was associated with reduced contractile function and lower skeletal muscle blood flow. Thus, treatments focused on enhancing perfusion and reversing impairments in contractile function in patients with T2DM may offset lower-limb fatigability and aid in increasing exercise capacity.

NEW & NOTEWORTHY Although prior studies compare patients with type 2 diabetes mellitus (T2DM) with lean controls, our study includes controls matched for age, body mass, and physical activity to more closely assess the effects of T2DM. Patients with T2DM demonstrated no impairment in macrovascular endothelial function, evidenced by similar flow-mediated dilation to controls. However, patients with T2DM had greater fatigability and reduced exercise-induced increase in blood flow (hyperemia) after a lower-limb dynamic fatiguing exercise compared with controls.
New Inequalities for Stronglyr-Convex Functions
Authors: Kadakal Huriye
Published: January 2019

In this study, firstly we introduce a new concept called “stronglyr-convex function.” After that we establish Hermite-Hadamard-like inequalities for this class of functions. Moreover, by using an integral identity together with some well known integral inequalities, we establish several new inequalities forn-times differentiable stronglyr-convex functions. In special cases, the results obtained coincide with the well-known results in the literature.
Seismic Behaviour of Straight‐Tenon Wood Frames with Column Foot Damage
Authors: Li Shengcai , Jiang Zhijun , Luo Hongzhen , Zhang Lei
Published: January 2019

Timber buildings might incur damages after a long service, because column foot damage affects the structural performance under the continued use. In this paper, six straight‐tenon joint wood frame specimens were prepared with varying degrees of two different damage conditions at a scale of 1 : 3.52. To obtain failure mode and hysteresis performance of the specimens, the low‐cycle reciprocating loading test was conducted. The stiffness degradation curves and equivalent viscous damping curves of the damaged wood frames were also analysed. The mechanical characteristics of the wood frames with column foot damage under the low‐cycle reciprocating load were then simulated using the finite element method, and the results were compared to the test results. It is determined that as the degree of column foot damage increases, the fullness and peak of the hysteresis curves for wood frames, the equivalent viscous damping coefficients, and the overall seismic behaviour of the wood frame all gradually decrease. The skeleton curves obtained by finite element analysis and tests showed good agreement, verifying the influence of column foot damage on the seismic behaviour of ancient wood frame structures.
Research on the Model and Algorithm for Multimodal Distribution of Emergency Supplies after Earthquake in the Perspective of Fairness
Authors: Xiong Xiaowen , Zhao Fan , Wang Yundou , Wang Yapeng
Published: January 2019

After the earthquake, it is important to ensure the emergency supplies are provided in time. However, not only the timeliness, but also the fairness from different perspectives should be considered. Therefore, we use a multilevel location‐routing problem (LPR) to study the fairness of distribution for emergency supplies after earthquake. By comprehensively considering the time window constraints, the partial road damage and dynamic recovery in emergency logistics network, the stochastic driving time of the vehicle, and the mixed load of a variety of emergency materials, we have developed a multiobjective model for the LRP in postearthquake multimodal and fair delivery of multivariety emergency supplies with a limited period. The goal of this model is to minimize the total time in delivering emergency supplies and to minimize the maximum waiting time for emergency supplies to reach demand points. A hybrid heuristic algorithm is designed to solve the model. The example shows that this algorithm has a high efficiency and can effectively realize the supply of emergency supplies after the earthquake within the specified period. This method might be particularly suitable for the emergency rescue scenarios where the victims of the earthquake are vulnerable to mood swings and the emergency supplies need to be fairly distributed.
Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis
Authors: Zhao Feiyan , Liu Wei , Yue Shaojie , Yang Lei , Hua Qingzhong , Zhou Yan , Cheng Haipeng , Luo Ziqiang , Tang Siyuan
Published: January 2019

Granulocyte colony-stimulating factor (G-CSF) can promote the repair of a variety of damaged tissues, but the underlying mechanisms have not yet been fully elucidated. Bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the repair of damaged tissue. The aim of this study was to explore whether pretreating BM-MSCs with G-CSF can promote their ability of homing to the lung after in vitro transplantation via upregulating the CXCR4 expression, potentially markedly increasing the antifibrotic effect of BM-MSCs. The BM-MSCs pretreated with G-CSF were transplanted into a mouse on day 14 after bleomycin injection. The antifibrotic effects of BM-MSCs in mice were tested on day 21 by using pathological examination and collagen content assay. Pretreatment of BM-MSCs with G-CSF significantly promoted their ability of homing to the lung and enhanced their antifibrotic effects. However, knocking down the CXCR4 expression in BM-MSCs significantly inhibited the ability of G-CSF to promote the migration and homing of BM-MSCs to the lung and the resulting antifibrotic effects. We also found that G-CSF significantly increased the CXCR4 expression and AKT phosphorylation in BM-MSCs, and the AKT pathway inhibitor LY294002 significantly diminished the ability of G-CSF to upregulate the CXCR4 expression in BM-MSCs. Pretreatment of BM-MSCs with G-CSF promotes the homing of BM-MSCs to the lung via upregulating the CXCR4 expression, leading to a marked increase in the antifibrotic effects of BM-MSCs. This study provides new avenues for the application of BM-MSCs in the repair of different tissues.
Fire Model Test on Temperature Field in the Rescue Station of an Extralong Railway Tunnel
Authors: Zeng Yanhua , Liu Kelin , Fang Yong , Zhang Xianfu , Bai Yun
Published: January 2019

A rescue station is necessary for an extralong railway tunnel, whose length is generally greater than 20 km. In the rescue station, passenger evacuation, fire fighting, and protection of passengers are organized. It is important to discover the temperature distribution in a rescue station where a train is on fire. This paper performs a similarity simulation model test at 1 : 10 geometric scale to investigate the temperature field in a rescue station. A gasoline pool fire was used as the fire source. The influences of the fire source position and ventilation condition on the temperature field were studied. The results show that (a) the temperature distribution along the tunnel is stable without ventilation, the temperature is lowest when the fire occurs 50 m from the entrance; (b) the fresh air stirred up by fans promotes burning and increases the temperature; (c) the chimney effect causes the temperature field to skew in an uphill direction; (d) the opening of both fans in the adit makes the high‐temperature zone to connect through; and (e) the temperature increase at the rescue station can be divided into four stages, and the response of different fire source positions to the opening of fans is not consistent. These findings provide a basis for personnel escape design and a foundation for further study of temperature distribution in a tunnel with a rescue station.
Effect of Low-Frequency Vibration on Muscle Response under Different Neurointact Conditions
Authors: Zhang Chaofei , Wang Wenjun , Anderson Dennis , Guan Sishu , Li Guofa , Xiang Hongyi , Zhao Hui , Cheng Bo
Published: January 2019

Stretch reflex is an important factor that influences the biomechanical response of the human body under whole-body vibration. However, there is a lack of quantitative evaluation at lower frequencies. Thus, the aim of this study was to investigate the effects of vibration on the stretch reflex and, in particular, to explore the quantitative relationship between dynamic muscle responses and low-frequency vibrations. The gastrocnemius muscle of 45 Sprague-Dawley rats was dissected. Sinusoidal vibrations of five discrete frequencies (2~16 Hz) with peak-to-peak amplitudes of 1 mm were applied to the gastrocnemius muscles with 2 mm or 3 mm prelengthening. Variables including dynamic muscle force, vibration acceleration, and displacement were recorded in two conditions, with and without the stretch reflex. Results showed that the dynamic muscle forces decreased by 20% on average for the 2 mm prelengthening group after the stretch reflex was blocked and by 24% for the 3 mm prelengthening group. Statistical analysis indicated that the amplitude of dynamic muscle force in the “with stretch reflex” condition was significantly larger than that in the “without stretch reflex” condition (p<0.001). The tension-length curve was found to be a nonlinear hysteresis loop that changed with frequency. The phase difference between the dynamic muscle force and the length change was affected significantly by vibration frequency (p<0.01), and the minimum frequency was 4–8 Hz. Experimental results of this study could benefit musculoskeletal model by providing a theoretical support to build a stretch reflex model for low-frequency vibration.
Nondestructive Evaluation of FRP‐Concrete Interface Bond due to Surface Defects
Authors: Yazdani Nur , Beneberu Eyosias , Riad Mina
Published: January 2019

Carbon fiber‐reinforced polymer (CFRP) laminates have been successfully used as externally bonded reinforcements for retrofitting, strengthening, and confinement of concrete structures. The adequacy of the CFRP‐concrete bonding largely depends on the bond quality and integrity. The bond quality may be compromised during the CFRP installation process due to various factors. In this study, the effect of four such construction‐related factors was assessed through nondestructive evaluation (NDE) methods, and quantification of the levels of CFRP debonding was achieved. The factors were surface cleanliness, surface wetness, upward vs. downward application, and surface voids. A common unidirectional CFRP was applied to small‐scale concrete samples with factorial combinations. Ground‐penetrating radar and thermography NDE methods were applied to detect possible disbonds at CFRP‐concrete interfaces. Thermography was found to clearly detect all four factors, while the GPR was only effective for detecting the surface voids only. The thermal images overpredicted the amount of debonded CFRP areas by about 25%, possibly due to scaling errors between the thermograph and the sample surface. The maximum debonded CFRP area in any sample was about two percent of the total CFRP area. This is a negligible amount of debonding, showing that the factors considered are unlikely to significantly affect the laminate performance or any CFRP contribution to the concrete member strength or confinement.
Yangyin Yiqi Mixture Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats through Inhibiting TGF-β1/Smad Pathway and Epithelial to Mesenchymal Transition
Authors: Meng Lihong , Zhang Xiaomei , Wang Hong , Dong Huan , Gu Xiaofeng , Yu Xiaolin , Liu Yushan
Published: January 2019

Objective. The aim of the current study was to investigate the protective effect of Yangyin Yiqi Mixture (YYYQ) on Bleomycin-induced pulmonary fibrosis in rats based on TGF-β1/Smad signal pathway and epithelial to mesenchymal transition (EMT). Methods. 120 Wistar rats were randomly divided into six groups: control group, BLM group, BLM + Pred group, BLM+YYYQ-L group, BLM+YYYQ-M group, and BLM+YYYQ-H group. Rats were given an intratracheal instillation of 3 mg/kg BLM to establish the pulmonary fibrosis model and followed by different dosages of YYYQ (11, 22, 44g/kg, via intragastric gavage) or prednisone soluble (4.2mg/kg, via intragastric gavage) or water. After 14 days and 28 days, tissue sections were stained with hematoxylin-eosin and Masson’s trichrome to observe histopathological changes. Protein levels of TGF-β1, CTGF, Interleukin 18, and hydroxyproline were detected by ELISA method, and mRNA expressions of TGF-β1, TβRI, TβRII, Smad3, Smad7, α-SMA, E-cadherin, laminin, and collagen I were detected by RT-PCR. Results. TGF-β1, CTGF, Interleukin 18, and hydroxyproline levels and mRNA expression of TGF-β1, TβRI, TβRII, Smad3, α-SMA, laminin, and collagen I were significantly increased (p <0.01), while Smad7 and E-cadherin levels were significantly decreased in BLM group (p <0.01). YYYQ-M and YYYQ-H group had downregulated the TGF-β1, CTGF, hydroxyproline contents, and mRNA expression of TGF-β1, TβRI, TβRII, Smad3, α-SMA, laminin, and collagen I and upregulated mRNA levels of Smad7 and E-cadherin significantly (p <0.01 or p <0.05). The result from the present study, which was also supported by histological evidence, suggested that YYYQ-M group and YYYQ-H group exhibited better treatment effect on Bleomycin-induced pulmonary fibrotic rats when compared to that of BLM + Pred group (p <0.01). Meanwhile, the effect of YYYQ, in three different dosages, on the level of interleukin 18 was not significant. Conclusion. These results showed that YYYQ has the potential of ameliorating the progression of pulmonary fibrosis, and the mechanism may be related to suppressing TGF-β1/Smad signal pathway and EMT in BLM-induced pulmonary fibrosis of rats.
Experimental Investigation of the Effect of Ice Blockage on Propeller Hydrodynamic Performance
Authors: Guo Chun-Yu , Xu Pei , Wang Chao , Xiong Wei-Peng
Published: January 2019

This experimental study investigates the influence of different sizes, quantities, and axial positions of model ice on propeller hydrodynamic performance. We used particle image velocimetry measurements to analyze the characteristics of the propeller wake flow field. The measurement results show that ice blockage leads to an increase in propeller thrust, torque, and efficiency. The smaller the advance coefficient of the propeller is, the smaller the influence of model ice on propeller blockage is. As the model ice becomes thicker and the thrust and efficiency of the propeller increase, the propeller torque is smaller for low advance coefficient and higher for high advance coefficient. The wider the model ice is, the larger the thrust and torque of the propeller are. Once the model ice width exceeds the propeller diameter, the change in its width has no effect on propeller efficiency. When the propeller is blocked with model ice, the fluid velocity in the wake flow reduces in the inflow direction, and the increase in fluid velocity in the horizontal transverse direction and variation of fluid velocity in the vertical direction are related to the model ice width.
Discrete Element Method‐ (DEM‐) Based Study on the Wear Mechanism and Wear Regularity in Scraper Conveyor Chutes
Authors: Xia Rui , Wang Xuewen , Li Bo , Wei Xing , Yang Zhaojian
Published: January 2019

The scraper conveyor is the key conveying equipment for fully mechanized coal mining. Wear failure of the chute is the main form of failure of the scraper conveyor. In this study, the discrete element method (DEM) was combined with the wear model. The wear mechanism and wear regularity of the chute were explored by tracking the changes in the position of coal particles during the wear process. After the validation of wear simulation, a wear test of coal for different intrinsic parameters was designed. In one wear cycle, the three‐body wear was about 32.84 times that of the two‐body wear. In the research range, the wear of the scraper conveyor chute increased with the increase of Poisson’s ratio, shear modulus, and density of the coal. The shear modulus showed remarkable effect on the wear of the chute, followed by Poisson’s ratio and density. There existed a linear relationship between the shear modulus and wear (R2 = 0.8232). This study is expected to be used to predict the wear of the scraper conveyor chute and provide a theoretical basis for the applicability of the chute in different mines.
The Numbers of Positive Solutions by the Lusternik-Schnirelmann Category for a Quasilinear Elliptic System Critical with Hardy Terms
Authors: Khiddi Mustapha
Published: January 2019

In this paper, we study the quasilinear elliptic system with Sobolev critical exponent involving both concave-convex and Hardy terms in bounded domains. By employing the technique introduced by Benci and Cerami (1991), we obtain at least cat(Ω)+1 distinct positive solutions.
The Role of Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Authors: Weng Dong , Chen Xian-Qiu , Qiu Hui , Zhang Yuan , Li Qiu-Hong , Zhao Meng-Meng , Wu Qin , Chen Tao , Hu Yang , Wang Liu-Sheng , Wei Ya-Ru , Du Yu-Kui , Chen Shan-Shan , Zhou Ying , Zhang Fen , Shen Li , Su Yi-Liang , Kolb Martin , Li Hui-Ping
Published: January 2019

Background. Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF. Objectives. Our purpose is to investigate the role of infection in AE-IPF. Methods. Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed. Results. Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN-γ, MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%).Conclusions. IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.
Hydroxyapatite Nanoparticle Coating on Polymer for Constructing Effective Biointeractive Interfaces
Authors: Galindo Tania Guadalupe Peñaflor , Chai Yadong , Tagaya Motohiro
Published: January 2019

Bone is an organic-inorganic composite with the ability to regenerate itself. Thus, several studies based on artificial organic-inorganic interface sciences have been tried to develop capable materials for effective regenerative bone tissues. Hydroxyapatite nanoparticles (HAp NPs) have extensively been researched in bone tissue engineering due to the compositional and shape similarity to the mineral bone and excellent biocompatibility. However, HAp alone has low mechanical strength, which limits its applications. Therefore, HAp NPs have been deposited on the biocompatible polymer matrix, obtaining composites with the enhanced mechanical, thermal, and rheological properties and with higher biocompatibility and bioactivity. For developing new biomedical applications, polymer-HAp interfacial interactions that provide biofusion should be investigated. This paper reviewed common coating techniques for obtaining HAp NPs/polymer fusion interfaces as well as in vitro studies of interfacial interactions with proteins and cells, demonstrating better biocompatibility. Studies based on interfacial interactions between biomolecules and HAp NPs were highlighted, and how these interactions can be affected by specific protein preadsorption was also summarized.
Paired-Agent Fluorescence Molecular Imaging of Sentinel Lymph Nodes Using Indocyanine Green as a Control Agent for Antibody-Based Targeted Agents
Authors: Li Chengyue , Xu Xiaochun , McMahon Nathan , Alhaj Ibrahim Omar , Sattar Husain A. , Tichauer Kenneth M.
Published: January 2019

Purpose. Paired-agent molecular imaging methods, which employ coadministration of an untargeted, “control” imaging agent with a targeted agent to correct for nonspecific uptake, have been demonstrated to detect 200 cancer cells in a mouse model of metastatic breast cancer. This study demonstrates that indocyanine green (ICG), which is approved for human use, is an ideal control agent for future paired-agent studies to facilitate eventual clinical translation. Methods. The kinetics of ICG were compared with a known ideal control imaging agent, IRDye-700DX-labeled antibody in both healthy and metastatic rat popliteal lymph nodes after coadministration, intradermally in the footpad. Results. The kinetics of ICG and antibody-based imaging agent in tumor-free rat lymph nodes demonstrated a strong correlation with each other (r = 0.98, p<0.001) with a measured binding potential of −0.102 ± 0.03 at 20 min postagent injection, while the kinetics of ICG and targeted imaging agent shows significant separation in the metastatic lymph nodes. Conclusion. This study indicated a potential for microscopic sensitivity to cancer spread in sentinel lymph nodes using ICG as a control agent for antibody-based molecular imaging assays.
Research on Hydrodynamics with Water Temperature Characteristics and Spring Algal Blooms in a Typical Tributary Bay of Three Gorges Reservoir
Authors: Lang Yun , Wang LingLing , Cai Xin , Hu Zijun
Published: January 2019

After the impoundment of the Three Gorges Reservoir (TGR) in China, water environment problems induced by water temperature stratification in the Xiangxi Bay (XXB, a typical tributary bay of TGR) received wide attention. In this study, a 3‐dimensional (3D) hydrodynamic and water temperature coupled model with the z‐coordinate in the vertical direction was established with Delft3D software to simulate the continuous hydrodynamic and water temperature process of XXB in 2009, and the static stability and mixing depth were also analyzed. The results show that the upstream inflow is prevented from entering TGR with nutrients enriching and mixing in the upper and middle reach of XXB from winter to early spring, which is the primary cause of spring algal blooms in XXB. Therefore, measures such as improving the upstream hydrodynamic conditions and forcing the nutrients to flow into TGR in winter should be more effective in alleviating spring algal blooms than the artificial tide operation of TGR proposed by previous studies.
Depression as a Neuroendocrine Disorder: Emerging Neuropsychopharmacological Approaches beyond Monoamines
Authors: Chávez-Castillo Mervin , Núñez Victoria , Nava Manuel , Ortega Ángel , Rojas Milagros , Bermúdez Valmore , Rojas-Quintero Joselyn
Published: January 2019

Depression is currently recognized as a crucial problem in everyday clinical practice, in light of ever-increasing rates of prevalence, as well as disability, morbidity, and mortality related to this disorder. Currently available antidepressant drugs are notoriously problematic, with suboptimal remission rates and troubling side-effect profiles. Their mechanisms of action focus on the monoamine hypothesis for depression, which centers on the disruption of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain. Nevertheless, views on the pathophysiology of depression have evolved notably, and the comprehension of depression as a complex neuroendocrine disorder with important systemic implications has sparked interest in a myriad of novel neuropsychopharmacological approaches. Innovative pharmacological targets beyond monoamines include glutamatergic and GABAergic neurotransmission, brain-derived neurotrophic factor, various endocrine axes, as well as several neurosteroids, neuropeptides, opioids, endocannabinoids and endovanilloids. This review summarizes current knowledge on these pharmacological targets and their potential utility in the clinical management of depression.
Using the Nonuniform Dynamic Mode Decomposition to Reduce the Storage Required for PDE Simulations
Authors: Hall Brenton T. , Chou Ching-Shan , Chen Jen-Ping
Published: January 2019

Partial Differential Equation simulations can produce large amounts of data. These datasets are very slow to transfer, for example, from an off-site supercomputer to a local research facility. There have been many model reduction techniques that have been proposed and utilized over the past three decades. Two of the most popular techniques are the Proper Orthogonal Decomposition and Dynamic Mode Decomposition. Nonuniform Dynamic Mode Decomposition (NU-DMD) is one of the newest techniques as it was introduced in 2015 by Guéniat et al. In this paper, the NU-DMD’s mathematics are explained in detail, and three versions of the NU-DMD’s algorithm are outlined. Furthermore, different numerical experiments were performed on the NU-DMD to ascertain its behavior with respect to errors, memory usage, and computational efficiency. It was shown that the NU-DMD could reduce an advection-diffusion simulation to 6.0075% of its original memory storage size. The NU-DMD was also applied to a computational fluid dynamics simulation of a NASA single-stage compressor rotor, which resulted in a reduced model of the simulation (using only three of the five simulation variables) that used only about 4.67% of the full simulation’s storage with an overall average percent error of 8.90%. It was concluded that the NU-DMD, if used appropriately, could be used to possibly reduce a model that uses 400 GB of memory to a model that uses as little as 18.67 GB with less than 9% error. Further conclusions were made about how to best implement the NU-DMD.
Existence and Nonexistence of Positive Solutions for Fractional Three-Point Boundary Value Problems with a Parameter
Authors: Li Yunhong , Jiang Weihua
Published: January 2019

In this work, we investigate the existence and nonexistence of positive solutions for p-Laplacian fractional differential equation with a parameter. On the basis of the properties of Green’s function and Guo-Krasnosel’skii fixed point theorem on cones, the existence and nonexistence of positive solutions are obtained for the boundary value problems. We also give some examples to illustrate the effectiveness of our main results.
Risk Assessment of Maize Drought in China Based on Physical Vulnerability
Authors: Chen Fang , Jia Huicong , Pan Donghua
Published: January 2019

Applying disaster system theory and with reference to the mechanisms that underlie agricultural drought risk, in this study, crop yield loss levels were determined on the basis of hazards and environmental and hazard-affected entities (crops). Thus, by applying agricultural drought risk assessment methodologies, the spatiotemporal distribution of maize drought risk was assessed at the national scale. The results of this analysis revealed that the overall maize drought risk decreases gradually along a northwest-to-southeast transect within maize planting areas, a function of the climatic change from arid to humid, and that the highest yield loss levels are located at values between 0.35 and 0.45. This translates to drought risks of once in every 10 and 20 years within 47.17% and 43.31% of the total maize-producing areas of China, respectively. Irrespective of the risk level, however, the highest maize yield loss rates are seen in northwestern China. The outcomes of this study provide the scientific basis for the future prevention and mitigation of agricultural droughts as well as the rationalization of related insurance.
Determination of Atenolol and Trimetazidine in Pharmaceutical Tablets and Human Urine Using a High Performance Liquid Chromatography-Photo Diode Array Detection Method
Authors: El-Alfy Walaa , Ismaiel Omnia A. , El-Mammli Magda Y. , Shalaby Abdalla
Published: January 2019

A simple RP-HPLC-PDA method for determination of atenolol (ATN) and trimetazidine (TMZ) in human urine and tablets has been developed. Analytes were separated on a Caltrex BI column (125× 4.0 mm, 5 μm) with 25mM potassium dihydrogen phosphate pH 3.3, methanol, and acetonitrile mobile phases. The PDA detector was operated at 210 nm for TMZ and 225 nm for ATN and the flow rate was 1.0 mL/ min. Linearity was obtained over a concentration range of (1.0-100 μg/mL) for both analytes in standard solutions and the method was successfully applied for determination of target analytes in their pharmaceutical tablets. Excellent linearity was also obtained over concentration ranges of (0.25-25 μg/mL) and (0.5-25 μg/mL) in human urine for TMZ and ATN, respectively. A simple liquid-liquid extraction was applied for urine sample clean-up and a gradient method was used for chromatographic separation. The lower limit of quantitation (LOQ) was 0.99 and 0.60 μg/mL for ATN and TMZ, respectively. The limit of detection (LOD) was 0.30 and 0.18 μg/mL for ATN and TMZ, respectively. Inter- and intraday precision and accuracy for ATN were within ±1.89% in pure form and within ±2.85% in urine samples. Inter- and intraday precision and accuracy for TMZ were within ± 3.99% in pure form and within ± 3.19% in urine samples.
A Novel Numerical Model for Fluid Flow in 3D Fractured Porous Media Based on an Equivalent Matrix-Fracture Network
Authors: Yao Chi , He Chen , Yang Jianhua , Jiang Qinghui , Huang Jinsong , Zhou Chuangbing
Published: January 2019

An original 3D numerical approach for fluid flow in fractured porous media is proposed. The whole research domain is discretized by the Delaunay tetrahedron based on the concept of node saturation. Tetrahedral blocks are impermeable, and fluid only flows through the interconnected interfaces between blocks. Fractures and the porous matrix are replaced by the triangular interface network, which is the so-called equivalent matrix-fracture network (EMFN). In this way, the three-dimensional seepage problem becomes a two-dimensional problem. The finite element method is used to solve the steady-state flow problem. The big finding is that the ratio of the macroconductivity of the whole interface network to the local conductivity of an interface is linearly related to the cubic root of the number of nodes used for mesh generation. A formula is presented to describe this relationship. With this formula, we can make sure that the EMFN produces the same macroscopic hydraulic conductivity as the intact rock. The approach is applied in a series of numerical tests to demonstrate its efficiency. Effects of the hydraulic aperture of fracture and connectivity of the fracture network on the effective hydraulic conductivity of fractured rock masses are systematically investigated.
CREBBP/EP300 Bromodomain Inhibition Affects the Proliferation of AR-Positive Breast Cancer Cell Lines
Authors: Garcia-Carpizo Veronica , Ruiz-Llorente Sergio , Sarmentero Jacinto , González-Corpas Ana , Barrero Maria J.
Published: January 2019

Inhibitors that prevent the binding of bromodomains to acetylated histones hold therapeutic potential. However, the effects of targeting most of the 60 different bromodomains found in the human proteome remain unexplored. Here, we investigate the molecular mechanisms responsible for the antiproliferative properties of CREBBP/EP300 bromodomain inhibition in ER-negative breast cancer cell lines. We show using genetic and chemical approaches that CREBBP/EP300 bromodomains are critical to support the proliferation of the triple-negative breast cancer cell line MDA-MB-453. Analysis of the transcriptional pathways affected by CREBBP/EP300 bromodomain inhibitors reveals that the expression of genes associated with super-enhancers is downregulated, which in turn are occupied by very high levels of androgen receptor (AR) in MDA-MB-453 cells. Treatment of MDA-MB-453 with CREBBP/EP300 bromodomain inhibitors downregulates the expression of an AR-dependent signature distinctive of breast cancer tumors that express AR and causes a decrease in H3K27ac levels at AR-binding sites. In accordance, in prostate cancer cell lines that express AR CREBBP/EP300 bromodomain inhibitors downregulate the expression of genes bound by AR and associated with super-enhancers. In summary, we report that triple-negative breast cancer cell lines that express AR are particularly sensitive to CREBBP/EP300 bromodomain inhibitors and consequently these inhibitors hold potential to treat this type of cancer.

Implications:

AR-dependent cancer cell lines are sensitive to CREBBP/EP300 bromodomain inhibitors
The Tumor Suppressor FBW7 and the Vitamin D Receptor Are Mutual Cofactors in Protein Turnover and Transcriptional Regulation
Authors: Salehi-Tabar Reyhaneh , Memari Babak , Wong Hilary , Dimitrov Vassil , Rochel Natacha , White John H.
Published: January 2019

The E3 ligase and tumor suppressor FBW7 targets drivers of cell-cycle progression such as the oncogenic transcription factor c-MYC, for proteasomal degradation. Vitamin D signaling regulates c-MYC expression and turnover in vitro and in vivo, which is highly significant as epidemiologic data link vitamin D deficiency to increased cancer incidence. We hypothesized that FBW7 and the vitamin D receptor (VDR) controlled each other's function as regulators of protein turnover and gene transcription, respectively. We found that hormonal 1,25-dihydroxyvitamin D3 (1,25D) rapidly enhanced the interaction of FBW7 with VDR and with c-MYC, whereas it blocked FBW7 binding to c-MYC antagonist MXD1. 1,25D stimulated the recruitment of FBW7, SCF complex subunits, and ubiquitin to DNA-bound c-MYC, consistent with 1,25D-regulated c-MYC degradation on DNA. 1,25D also accelerated the turnover of other FBW7 target proteins such as Cyclin E, c-JUN, MCL1, and AIB1, and, importantly, FBW7 depletion attenuated the 1,25D-induced cell-cycle arrest. Although the VDR contains a consensus FBW7 recognition motif in a VDR-specific insertion domain, its mutation did not affect FBW7–VDR interactions, and FBW7 ablation did not stabilize the VDR. Remarkably, however, FBW7 is essential for optimal VDR gene expression. In addition, the FBW7 and SCF complex subunits are recruited to 1,25D-induced genes and FBW7 depletion inhibited the 1,25D-dependent transactivation. Collectively, these data show that the VDR and FBW7 are mutual cofactors, and provide a mechanistic basis for the cancer-preventive actions of vitamin D.

Implications:

The key findings show that the VDR and the E3 ligase FBW7 regulate each other's functions in transcriptional regulation and control of protein turnover, respectively, and provide a molecular basis for cancer-preventive actions of vitamin D.

Visual Overview: http://mcr.aacrjournals.org/content/17/3/709/F1.large.jpg.
Overexpression of an Inulinase Gene in an Oleaginous Yeast, Aureobasidium melanogenum P10, for Efficient Lipid Production from Inulin
Authors: Li Yan-Feng , Jiang Hong , Hu Zhong , Liu Guang-Lei , Chi Zhen-Ming , Chi Zhe
Published: January 2019

In this study, in order to directly and efficiently convert inulin into a single-cell oil (SCO), an INU1 gene encoding inulinase from Kluyveromyces marxianus was integrated into the genomic DNA and actively expressed in an SCO producer Aureobasidium melanogenum P10. The transformant API41 obtained produced 28.5 U/mL of inulinase and its wild-type strain P10 yielded only 8.62 U/mL. Most (97.5%) of the inulinase produced by the transformant API41 was secreted into the culture. During a 10-L fermentation, 66.2% (w/w) lipid in the yeast cells of the transformant API41 and 14.38 g/L of cell dry weight were attained from inulin of 80.0 g/L within 120 h, high inulinase activity (23.7 U/mL) was also produced within 72 h, and the added inulin was actively hydrolyzed. This confirmed that the genetically engineered yeast of A. melanogenum P10 is suitable for direct production of lipids from inulin. The lipids produced could be used as feedstocks for biodiesel production.
Trichoscopy in the Differential Diagnosis of Pseudonits
Authors: Lacarrubba Francesco , Verzì Anna Elisa , Micali Giuseppe
Published: January 2019

Aim: The purpose of the study was to describe the trichoscopic features of pseudonits and to assess the usefulness of trichoscopy in their differential diagnosis. Methods: A retrospective study was performed on those patients seen for the suspicion of head or pubic lice and who underwent trichoscopy with polarized light at ×10 magnification for a more accurate diagnosis. Forty-two patients (28 males/14 females, mean age: 34.5 years, range: 7–59) were evaluated. Results: In 30 cases, trichoscopy confirmed the suspicion of head (24 cases) or pubic (6 cases) lice, whereas in 12 cases it allowed for a final diagnosis of seborrheic dermatitis (5 cases), hair casts (3 cases), trichobacteriosis (2 cases), white piedra (1 case), and trichorrhexis nodosa (1 case), by showing different types of pseudonits. Conclusion: Hair examination using trichoscopy in routine clinical practice may provide useful information for the correct diagnosis, ranging from common head and pubic lice infestations to rarer shaft abnormalities. Differentiating pseudonits from nits is essential to make the correct diagnosis in order to prevent unnecessary treatment, anxiety, and/or embarrassment.
Is BK Virus-Associated Cystitis a Generalized Epithelial Disease?
Authors: Schneidewind Laila , Neumann Thomas , Zimmermann Kathrin , Weigel Martin , Schmidt Christian Andreas , Krüger William
Published: January 2019

BK polyomavirus-associated haemorrhagic cystitis (BKHC) is a complication after allogeneic stem cell transplantation, which can occur in 5–60% of the cases. BK viruria alone can also occur in up to 100%. BKHC can lead to severe morbidity in stem cell-transplanted patients, but data about this disease is limited. Consequently, we conducted a prospective unicentric non-interventional trial on BKHC as well as BK viruria after first adult allogeneic stem cell transplantation with a follow-up time of 1 year after inpatient treatment. Between November 2013 and December 2015, we were able to include 40 adult patients with a mean age of 52.8 years. Twenty-seven (67.5%) of these patients were male and 13 (32.5%) were female. Acute myeloid leukaemia was the most frequent underlying disease (n = 15; 37.5%). Only 1 patient developed BKHC during inpatient treatment (n = 1; 2.5%), but BK viruria was frequent (n = 11; 27.5%) during inpatient treatment as well as in the follow-up time (n = 14; 35%). Interestingly, BK viruria was significantly associated with mucositis (p = 0.038) and number of transfused platelet concentrates (p = 0.001). This unexpected association will be discussed and needs further investigation.