bluuebunny/crossref_metadata_2025 huggingface dataset:
ABCA1 inhibits PDGF‐induced proliferation and migration of rat airway smooth muscle cell through blocking TLR2/NF‐κB/NFATc1 signaling
Authors: Cheng Wei , Yan Kun , Chen Yanni , Zhang Wen , Ji Zongzheng , Dang Chengxue
Published: May 2018

Airway remodeling is a key feature of asthma, characterized by abnormal proliferation and migration of airway smooth muscle cells (ASMCs). ABCA1, a member of the ATP‐binding cassette family of active transporters, plays an essential role in the progression of lung diseases. However, the contributions of ABCA1 in ASMCs remain to be explored. The purpose of the present study was to investigate the functional role and potential molecular mechanism of ABCA1 in platelet derived growth factor (PDGF)‐induced primary rat ASMC proliferation and migration. We observed that PDGF‐ led to a significant decrease in the expression of ABCA1. Overexpression of ABCA1 strikingly suppressed PDGF‐induced ASMC proliferation accompanied by a decrease in the expression of PCAN stimulated by PDGF. Additionally, augmentation of ABCA1 dramatically restrained PDGF‐induced migration concomitant with attenuate the accumulation of MMP‐2 and MMP‐9 in response to PDGF. Furthermore, forced expression of ABCA1 enhanced contractile phenotype markers proteins including α‐SMA along with sm‐MHC, sm‐α‐actin, and calponin reduced by PDGF. Meanwhile, introduction of ABCA1 depressed ECM over‐deposition induced by PDGF as reflected by a decrease in the expression of ECM protein collagen I and fibronectin. More importantly, addition of ABCA1 effectively suppressed the activity of TLR2/NF‐κB signaling as well as diminished the expression of NFATc1 in rat ASMCs after PDGF stimulation. Interestingly, blockage of TLR2/NF‐κB signaling effectively inhibited PDGF‐induced proliferation and migration, these effects were similar to ABCA1. Taken together, these data implicated that ABCA1 suppressed PDGF‐induced proliferation, migration, and contraction in rat ASMCs at least partly through TLR2/NF‐κB/NFATc1 signaling, which might offer hope for the future treatment of airway remodeling in asthma.
Uroprotective mechanism of quercetin against cyclophosphamide‐induced urotoxicity: Effect on oxidative stress and inflammatory markers
Authors: Sherif Iman O.
Published: May 2018

The urotoxicity is a common complication associated with patients receiving cyclophosphamide (CYP). This study was designed to investigate the uroprotective mechanism of quercetin (Quer) flavonoid against CYP induced urotoxicity via determination of oxidative stress markers as well as inflammatory mediators in bladder tissue. Forty male Wistar rats were divided into four groups; Normal group: received saline for 10 days. Quer control group: received quercetin 50 mg/kg/day for 10 days. CYP group: received saline for 10 days and injected with a single dose of 150 mg/kg CYP intraperitoneal (i.p) at day 8. The Quer + CYP group: received Quer 50 mg/kg/day for 10 days plus CYP 150 mg/kg i.p. injection at day 8. The CYP injection produced a significant elevation in bladder contents of malondialdehyde (MDA), and nitric oxide (NO), and bladder protein levels and expressions of tumor necrosis factor‐alpha (TNF‐α), and interleukin‐6 (IL‐6) in addition to the upregulation of cyclooxygenase‐2 (COX‐2) bladder gene expression. Also, CYP injection showed a marked reduction in bladder levels of catalase, superoxide dismutase (SOD), and IL‐10 when compared with normal group. Moreover, histopathological examination of the bladder showed degenerative alterations, severe edema, and inflammation following CYP injection. Quer attenuated the biochemical markers and histopathological changes induced by CYP. The uroprotective effect of Quer was exerted by restoring the balance between oxidative/antioxidative status and pro‐/anti‐inflammatory cytokines via its antioxidant and anti‐inflammatory activities.
Protective and therapeutic effects of dexpanthenol on isoproterenol‐induced cardiac damage in rats
Authors: Kalkan Ferhat , Parlakpinar Hakan , Disli Olcay M. , Tanriverdi Lokman H. , Ozhan Onural , Polat Alaaddin , Cetin Aslı , Vardi Nigar , Otlu Yılmaz O. , Acet Ahmet
Published: May 2018

The purpose of the study was to explore the protective and therapeutic effects of dexpanthenol (DEX) on isoproterenol (ISO)‐induced cardiac damage. Forty rats were distributed into four groups: group I (Control); group II (ISO); ISO (150 mg/kg/day) was given to rats once a day for 2 consecutive days with an interval of 24 h; group III (DEX+ISO): DEX (250 mg/kg) was applied 30 min before the first ISO administration and continued in the next two days after second ISO administration; group IV (ISO+DEX): After the ISO treatment at 1st and 2nd days, DEX was given at 3rd and 4th days. Rats were monitored for mean arterial blood pressure (BP), heart rate, oxygen saturation (%SO2), and electrocardiography (ECG). Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), total oxidant status (TOS); total antioxidant capacity (TAC), oxidative stress index (OSI), and caspase‐3 were determined. BP and SO2 values indicated a significant decrease in the ISO group. Also, T wave negativity was observed in 6 of 10 rats, SOD, CAT, and GPX levels were significantly lower in ISO group than control group. ISO administration increased TOS and OSI levels, whereas DEX treatment significantly reduced these parameters. Also, ISO‐induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization whereas these histological damages were significantly decreased in ISO+DEX and DEX+ISO groups when compared to the ISO group. This study implies the cardioprotective effects of DEX on ISO‐induced cardiotoxicity.
Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies
Authors: Kar Sumit , Paglialunga Sabina , Islam Rafiqul
Published: May 2018

Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development.
Individual‐Specific QT Interval Correction for Drugs With Substantial Heart Rate Effect Using Holter ECGs Extracted Over a Wide Range of Heart Rates
Authors: Panicker Gopi Krishna , Kadam Pramod , Chakraborty Saikat , Kothari Snehal , Turner J. Rick , Karnad Dilip R.
Published: May 2018

Although fixed QT correction methods are typically used to adjust for the effect of heart rate on the QT interval in thorough QT/QTc studies, individual‐specific QT correction (QTcI = QT/RRI) is advisable for drugs that increase the heart rate by >5 to 10 beats/minute (bpm). QTcI is traditionally derived using resting drug‐free electrocardiograms (ECGs) collected at prespecified times. However, the resting heart rate range in healthy individuals is narrow, and extrapolation of inferences from these data to higher heart rates could be inappropriate. Accordingly, the QTcI derived from triplicate ECGs extracted at prespecified times (the traditional [T] method, yielding QTcIT) was compared with QTcIs obtained using ECGs with a wider heart rate range (alternative Holter [H] method, yielding QTcIH) from 24‐hour Holter recordings from 40 healthy individuals selected from a central ECG laboratory database. For QTcIH, 10‐second ECGs were extracted at stable heart rates in the ranges of 51‐60, 61‐70, 71‐80, and 81‐90 bpm (9 ECGs in each bin = 36 ECGs). An independent set of 40 ECGs with heart rates from 51 to 90 bpm was extracted from each individual to validate the accuracy of QTcI by the 2 methods. For the validation set, the QTcIH was a better QT correction method (slope of QTc vs heart rate closer to zero) than QTcIT. The mean difference between QTcIT and QTcIH increased from 3.1 milliseconds at 65 bpm to 10.0 milliseconds at 90 bpm (P < 0.01). The QTcIT exceeded QTcIH at heart rates > 60 bpm. Employment of the QTcIH may be more appropriate for studies involving drugs that increase heart rate.
Searching for a mitochondrial root to the decline in muscle function with ageing
Authors: Gonzalez‐Freire Marta , Adelnia Fatemeh , Moaddel Ruin , Ferrucci Luigi
Published: May 2018

Sarcopenia, the age‐related loss of muscle mass and strength, is linked to a range of adverse outcomes, such as impaired physical performance, cognitive function, and mortality. Preventing sarcopenia may reduce the burden of functional decline with aging and its impact on physiological and economic well‐being in older adults. Mitochondria in muscle cells lose their intrinsic efficiency and capacity to produce energy during aging, and it has been hypothesized that such a decline is the main driver of sarcopenia. Oxidative phosphorylation becomes impaired with aging, affecting muscle performance, and contributing to an age‐associated decline in mobility. However, it is unclear whether this deterioration is due to a reduced mitochondria population, decreased mitochondrial energetic efficiency, or a reduced capacity to dynamically transport oxygen and nutrients into the mitochondria, and addressing these questions is an active area of research. Further research in humans will require use of new “omics” technologies, progress in neuroimaging techniques that permit energy production assessment, and visualization of molecules critical for energetic metabolism, as well as proxy biomarkers of muscle perfusion.
Modeling effects of risk and social distance on vaccination choice
Authors: Jarmolowicz David P. , Reed Derek D. , Francisco Alex J. , Bruce Jared M. , Lemley Shea M. , Bruce Amanda S.
Published: May 2018

Despite vaccines' consistently demonstrated effectiveness, vaccination rates remain suboptimal due to vaccine refusal. Low vaccination rates are particularly problematic for individuals who cannot be vaccinated for medical reasons and thus must rely on herd immunity (i.e., protection of vulnerable individuals due to the high rate of vaccination of other—often socially distant—individuals). The current study uses a novel decision‐making task to examine how three variables impacted participants' highest acceptable probability of side effects to their children: 1) the severity of the side effects their children experience, 2) the social distance to the beneficiary of the vaccination, and 3) the probability that the vaccine will prevent disease for that designated beneficiary. Participants' willingness to risk potential side effects of vaccination systematically decreased as the 1) effectiveness of the vaccination decreased, 2) the beneficiary of the vaccination became more socially distant, and 3) the severity of side effects increased. These data were well‐described by behavioral economic models used to examine the discounting of other health behavior.
Study of hyperpigmentation in human skin disorder using different electron microscopy techniques
Authors: Noh Seulgi , Choi Hyosun , Kim Ji Soo , Kim Il‐Hwan , Mun Ji Young
Published: May 2018

There is a global trend of increase in the demand for three‐dimensional electron microscopy with high resolution. The ultrastructural change and related functional studies are necessary to investigate biological phenomena. In this study, currently available 3D reconstruction techniques of electron microscopes (serial block‐face scanning electron microscopy and focused ion beam—scanning electron microscopy) were used to investigate hyperpigmentary disorders in human skin. In the basal layer of the epidermis in the human skin, there are melanocytes that produce melanin and keratinocytes that act as a barrier against environmental damage. The 3D structure from serial images through scanning electron microscopy showed locations of melanosomes between melanocyte and keratinocyte in the hyperpigmentary disorder, in addition, the electron tomography showed pigment transfer through melanin instead melanosome. These results support the exocytosis‐endocytosis theory of pigment in human skin.
Alcohol enhances symptoms and propensity for infection in inflammatory bowel disease patients and a murine model of DSS-induced colitis
Authors: Cannon Abigail R , Kuprys Paulius V , Cobb Adrienne N , Ding Xianzhong , Kothari Anai N , Kuo Paul C , Eberhardt Joshua M , Hammer Adam M , Morris Niya L , Li Xiaoling , Choudhry Mashkoor A
Published: May 2018

Over 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammation, rectal bleeding, and dehydration. Interestingly, a widespread recommendation to IBD patients for avoidance of a flare period is “Don’t Drink Alcohol” as recent work correlated alcohol consumption with increased GI symptoms in patients with IBD. Alcohol alone not only induces a systemic pro-inflammatory response, but can also be directly harmful to gut barrier integrity. However, how alcohol could result in the exacerbation of UC in both patients and murine models of colitis has yet to be elucidated. Therefore, we conducted a retrospective analysis of patients admitted for IBD with a documented history of alcohol use in conjunction with a newly developed mouse model of binge alcohol consumption following dextran sulfate sodium (DSS)-induced colitis. We found that alcohol negatively impacts clinical outcomes of patients with IBD, specifically increased intestinal infections, antibiotic injections, abdomen CT scans, and large intestine biopsies. Furthermore, in our mouse model of binge alcohol consumption following an induced colitis flare, we found alcohol exacerbates weight loss, clinical scores, colonic shortening and inflammation, and propensity to infection. These findings highlight alcohol’s ability to potentiate symptoms and susceptibility to infection in UC and suggest alcohol as an underlying factor in perpetuating symptoms of IBD.

This study builds on previous findings that alcohol has adverse effects in IBD and establishes these effects in a mouse model of colitis.
Neuroinflammation and microglia in glaucoma: time for a paradigm shift
Authors: Wei Xin , Cho Kin‐Sang , Thee Eric F. , Jager Martine J. , Chen Dong Feng
Published: May 2018

Glaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i.e., normal tension glaucoma (NTG). Interestingly, patients who carry the gain‐of‐function mutation of the pro‐inflammatory gene TBK1 – tumor necrosis factor (TNF) receptor associated factor NF‐κB activator (TANK) binding kinase 1 – are at increased risk to develop NTG. This finding suggests a causal link between neuroinflammatory processes and glaucoma. Various studies have reported the presence of neuroinflammatory responses by microglia, astrocytes and other blood‐born immune cells in the optic nerve head (ONH) at early stages of experimental glaucoma. Inhibition of certain pro‐inflammatory pathways, particularly those associated with microglial activation, appears to be neuroprotective. In this review, we will focus on the inflammatory responses, in particular the proposed roles of microglia, in the pathogenesis of glaucoma.
Cement interface and bone stress in total hip arthroplasty: Relationship to head size
Authors: Alonso‐Rasgado Teresa , Del‐Valle‐Mojica Jose F. , Jimenez‐Cruz David , Bailey Colin G. , Board Tim N.
Published: May 2018

The use of larger prosthetic femoral heads in total hip arthroplasty (THA) has increased considerably in recent years in response to the need to improve joint stability and reduce risk of dislocation. However, data suggests larger femoral heads are associated with higher joint failure rates. For cemented implants, ensuring the continued integrity of the cement mantle is key to long term fixation. This paper describes an investigation into the effect of variation in femoral head size on stresses in the acetabular cement mantle and pelvic bone. Three commonly used femoral head sizes: 28, 32, and 36 mm diameter were investigated. The study was undertaken using a finite element model validated using surface strains obtained from Digital Image Correlation (DIC) during experimentation on a composite hemipelvis implanted with a cemented all‐polyethylene acetabular cup. Following validation, the models were used to investigate stresses in the pelvic bone and acetabular cement mantle resulting from two loading scenarios; an average weight subject (700 N) and an overweight subject (1,000 N) undertaking a single leg stand. We found that the highest peak stresses occurred in the anterosuperior and posterosuperior regions of the bone‐cement interface, in the line of action of the load, where debonding usually initiates. Stress on the cortical bone‐cement interface increased with femoral head diameter by up to 9% whilst stresses in the trabecular bone remained relatively invariant. Our findings may help to explain higher joint failure rates associated with larger femoral heads. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2966–2977, 2018.
Promoting the use of isotopic techniques to combat soil erosion: An overview of the key role played by the SWMCN Subprogramme of the Joint FAO/IAEA Division over the last 20 years
Authors: Mabit Lionel , Bernard Claude , Lee Zhi Yi Amelia , Fulajtar Emil , Dercon Gerd , Zaman Mohammad , Toloza Arsenio , Heng Lee
Published: May 2018

The International Atomic Energy Agency (IAEA), through the Joint Division with the Food and Agriculture Organization (FAO) of the United Nations, assists its Member States in applying nuclear techniques to alleviate challenges in food safety, food security and sustainable agricultural development. The Soil and Water Management & Crop Nutrition (SWMCN) Subprogramme, within the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, has made significant contributions to the development of isotopic techniques for the assessment of soil degradation and the development of efficient soil and land conservation approaches. These techniques include fallout radionuclides such as 137Cs, 210Pbex, 7Be, and 239+240Pu as well as 13C stable isotope and compound‐specific stable isotope analyses. These methodologies were developed and/or refined through the work of researchers from developed and developing countries who were selected to work within the frame of IAEA's Coordinated Research Projects (CRPs). Internal research activities implemented in the Joint FAO/IAEA's SWMCN Laboratory in Seibersdorf supported the work accomplished in the CRPs.

The methodologies thus developed have been subsequently disseminated to developing countries by IAEA's Technical Cooperation Programme to assist Member States to adopt climate‐smart agriculture and reduce soil degradation that poses a threat to food security and the environment. This review paper provides an overview of the activities conducted in the frame of CRPs for combating soil erosion over the last 20 years and highlights the major achievements. Examples of the success and the impact obtained in Morocco, Madagascar, and Vietnam in using these isotopic techniques are presented.
Vegetation dynamic trends and the main drivers detected using the ensemble empirical mode decomposition method in East Africa
Authors: Wei Fangli , Wang Shuai , Fu Bojie , Pan Naiqing , Feng Xiaoming , Zhao Wenwu , Wang Cong
Published: May 2018

Understanding vegetation changes and the underlying causes are critical to predict the future ecosystem dynamics. Water‐limited ecosystems in East Africa have been identified as particularly vulnerable to the impacts of increased environmental change, but relatively little is known about the vegetation dynamic trends and the main drivers. Taking the satellite‐derived normalized difference vegetation index (NDVI) as a proxy of vegetation growth, we detected the spatiotemporal evolution of NDVI trends and explored the main drivers based on the ensemble empirical mode decomposition method. Results showed that greening (restoration) and browning (degradation) coexisted in East Africa during 1982–2013. However, the early greening stalled or even reversed as the browning continuously intensified over time. Greening‐to‐browning prevailed in East Africa after 2000. Generally, more than half of the study area (54.77%, 13.77% with a significant decrease) experienced a browning trend during 1982–2013, with an average change rate of (−0.12 ± 1.10) × 10−3. We also found that the percentage of greening area in each land cover type overall decreased. Furthermore, the remarkable spatiotemporal correlations between NDVI and soil water suggested that water was a dominant factor governing the vegetation changes in East Africa. The effectiveness of different types of protected areas (PAs) on vegetation change varied, depending to some extent on management policy (legal laws and on‐site patrols). Therefore, a big challenge for sustainable management of protected areas is how to balance conservation and development objectives in East Africa.
Influence of Nanoclay Localization on Structure–Property Relationships of Polylactide‐Based Biodegradable Blend Nanocomposites
Authors: Salehiyan Reza , Ray Suprakas Sinha
Published: May 2018

This article highlights the recent research achievements regarding the development of nanoclay‐containing biodegradable composites of polylactide (PLA)‐based immiscible blends. The structure–property relationships of particular blends, namely, PLA/poly(ε‐caprolactone), PLA/poly(butylene succinate), and PLA/poly[(butylene succinate)‐adipate], are studied with respect to the nanoclay incorporations. For different nanoclay types and concentrations, the morphologies of these nanocomposites are probed and correlated to their viscoelastic, mechanical, and thermal properties, along with their crystallization behavior and kinetics and gas permeability. The nanoclay dispersion and distribution characteristics are found to be key parameters influencing the final properties. In particular, nanocomposites with a higher degree of nanoclay dispersion exhibit significant enhancement in their mechanical, thermal, and barrier properties, and some agglomerations are effective as regards favorable crystallization behavior. In terms of the clay localization, the positioning of nanoclays at the interface reduces the minor phase size remarkably, because of the droplet encapsulation that counteracts coalescence. However, for improved understanding of the influence of nanoclay localization on the structure–property relationships of these blends, further systematic study is required. That is, nanocomposites with different localizations but the same nanoclay loads should be compared. This can be achieved by tuning the processing protocols and the nanoclay inclusion orders in the blends.
Cheminformatics in Drug Discovery, an Industrial Perspective
Authors: Chen Hongming , Kogej Thierry , Engkvist Ola
Published: May 2018

Cheminformatics has established itself as a core discipline within large scale drug discovery operations. It would be impossible to handle the amount of data generated today in a small molecule drug discovery project without persons skilled in cheminformatics. In addition, due to increased emphasis on “Big Data”, machine learning and artificial intelligence, not only in the society in general, but also in drug discovery, it is expected that the cheminformatics field will be even more important in the future. Traditional areas like virtual screening, library design and high‐throughput screening analysis are highlighted in this review. Applying machine learning in drug discovery is an area that has become very important. Applications of machine learning in early drug discovery has been extended from predicting ADME properties and target activity to tasks like de novo molecular design and prediction of chemical reactions.
Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses
Authors: Yi Young‐Su
Published: May 2018

Inflammation is an innate immune response to noxious stimuli to protect the body from pathogens. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory cells increase expressions of inflammatory molecules, while in triggering, inflammasomes are activated, resulting in cell death and pro‐inflammatory cytokine secretion. Inflammasomes are protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g., nucleotide‐binding oligomerization domain‐like receptors (NLRs), absent in melanoma 2 (AIM2), and caspases‐4/5/11) and pro‐caspase‐1 with or without a bipartite adaptor molecule ASC. Inflammasome activation induces pyroptosis, inflammatory cell death, and stimulates caspase‐1‐mediated secretion of interleukin (IL)‐1b and IL‐18. Flavonoids are secondary metabolites found in various plants and are considered as critical ingredients promoting health and ameliorating various disease symptoms. Anti‐inflammatory activity of flavonoids and underlying mechanisms have been widely studied. This review introduces current knowledge on different types of inflammasomes and their activation during inflammatory responses and discusses recent studies regarding anti‐inflammatory roles of flavonoids as suppressors of inflammasomes in inflammatory conditions. Understanding the regulatory effects of flavonoids on inflammasome activation will increase our knowledge of flavonoid‐mediated anti‐inflammatory activity and provide new insights into the development of flavonoid preparations to prevent and treat human inflammatory diseases.
Accelerated pre‐senile systemic amyloidosis in PACAP knockout mice – a protective role of PACAP in age‐related degenerative processes
Authors: Reglodi Dora , Jungling Adel , Longuespée Rémi , Kriegsmann Joerg , Casadonte Rita , Kriegsmann Mark , Juhasz Tamas , Bardosi Sebastian , Tamas Andrea , Fulop Balazs Daniel , Kovacs Krisztina , Nagy Zsuzsanna , Sparks Jason , Miseta Attila , Mazzucchelli Gabriel , Hashimoto Hitoshi , Bardosi Attila
Published: May 2018

Dysregulation of neuropeptides may play an important role in aging‐induced impairments. Among them, pituitary adenylate cyclase‐activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue‐damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life and the well‐known general cytoprotective effects of PACAP lead to age‐related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP. Using young and aging CD1 PACAP knockout (KO) and wild type (WT) mice, we demonstrated pre‐senile amyloidosis in young PACAP KO animals and showed that senile amyloidosis appeared accelerated, more generalized, more severe, and affected more individuals. Histopathology showed age‐related systemic amyloidosis with mainly kidney, spleen, liver, skin, thyroid, intestinal, tracheal, and esophageal involvement. Mass spectrometry‐based proteomic analysis, reconfirmed with immunohistochemistry, revealed that apolipoprotein‐AIV was the main amyloid protein in the deposits together with several accompanying proteins. Although the local amyloidogenic protein expression was disturbed in KO animals, no difference was found in laboratory lipid parameters, suggesting a complex pathway leading to increased age‐related degeneration with amyloid deposits in the absence of PACAP. In spite of no marked inflammatory histological changes or blood test parameters, we detected a disturbed cytokine profile that possibly creates a pro‐inflammatory milieu favoring amyloid deposition. In summary, here we describe accelerated systemic senile amyloidosis in PACAP gene‐deficient mice, which might indicate an early aging phenomenon in this mouse strain. Thus, PACAP KO mice could serve as a model of accelerated aging with human relevance. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Poly(amino acid)/carbon nanotube nanocomposites with enhanced thermal, electrical, and mechanical properties
Authors: Fan Xiaoxia , Ren Haohao , Yan Yonggang
Published: May 2018

Poly(amino acid) (PAA)‐based nanocomposites were synthesized byin situmelting polycondensation with various carbon nanotube (CNT) loadings; the morphology, thermal, mechanical, electrical, and biocompatible properties of the resulting nanocomposites were investigated and characterized. The nanotubes were dispersed within the polymer matrix without the need for coupling agents or surfactants. The crystallization temperature showed a gradual rise with increasing CNT loading, confirming that the nanotubes act as nucleating agents for PAA crystallization. The nanotubes increased the thermal stability of the matrix, leading to an increase in the initial degradation temperature (Ti) and the maximum degradation temperature (Tm). The mechanical properties were gradually enhanced by increasing the CNT content except for the property of elongation at break, which showed its highest value at 1 wt% CNT content. The nanocomposites showed better electrical and biocompatible properties than CNT‐free PAA, suggesting that the incorporation of CNTs is effective for improving the PAA performance, and the nanocomposites are suitable as performance materials for the manufacture of medical apparatus. POLYM. COMPOS., 39:E1939–E1949, 2018. © 2018 Society of Plastics Engineers
Student engagement and mathematics achievement: Unraveling main and interactive effects
Authors: Fung Francis , Tan Cheng Yong , Chen Gaowei
Published: May 2018

The present study explored the relationships between student engagement and mathematics achievement for 295,416 15‐year‐old students from 11,767 secondary schools in 34 countries who participated in the Program for International Student Assessment (PISA) 2012. Affective engagement was measured by students’ mathematics interest (InterestMath) and perceived usefulness of schooling (PerceptionSch), behavioral engagement by behaviors facilitating mathematics learning (BehaviorMath) and participation in mathematics learning activities (ActivitiesMath), and cognitive engagement by openness (Openness) and perseverance (Perseverance) in problem‐solving. Results showed that students who were more engaged had higher levels of academic achievement, with cognitive engagement having the strongest association with achievement. Results also showed that students who were highly engaged in two domains had higher achievement levels than peers who were engaged in only one domain in six pairwise comparisons (InterestMath‐BehaviorMath, InterestMath‐Openness, InterestMath‐Perseverance, PerceptionSch‐BehaviorMath, PerceptionSch‐Openness, PerceptionSch‐Perseverance). These results highlighted the importance of a whole‐school based approach in enhancing student achievement.
Factors associated with self‐reported history of depression diagnosis among cancer survivors aged 18 years and over in the United States
Authors: Gerbi Gemechu B. , Ivory Stranjae , Archie‐Booker Elaine , Claridy Mechelle D. , Miles‐Richardson Stephanie
Published: May 2018

Objective

According to the American Cancer Society, 25% of cancer survivors in the United States develop depression. The objective of this study is to assess factors associated with self‐reported history of depression diagnosis among cancer survivors aged ≥18 years in the United States.

Methods

Data were analyzed from the 2014 Behavioral Risk Factor Surveillance System (N = 6079). The Behavioral Risk Factor Surveillance System collects data about US residents regarding their health‐related risk behaviors and events, chronic health conditions, and use of preventive services. Respondents were considered to have a history of depression diagnosis if they answered yes to the question “Has a doctor or other health care provider EVER told you that you have a depressive disorder, including depression, major depression, dysthymia, or minor depression?” Bivariate and multivariable logistic regression analyses were conducted to assess factors associated with depression in cancer survivors. Analyses were conducted using SAS 9.4.

Results

After adjusting for demographic and socioeconomic factors, females (AOR: 1.70; 95% CI, 1.50‐1.97); those with an annual household income of $24 999 or less (AOR: 2.48; 95% CI, 1.95‐3.16); $25 000 to $49 999 (AOR: 1.62; 95% CI, 1.31‐2.02), and $50 000 to $74 999 (AOR: 1.35; 95% CI, 1.10‐1.71); those who were not married (AOR = 1.37; 95% CI, 1.17‐1.60); and those who perceived their health as poor (AOR = 2.33; 95% CI, 2.01‐2.70), were significantly more likely to report a diagnosis of depression.

Conclusions

The results indicate that gender, income, marital status, and perceived health status were associated with self‐reported depression among cancer survivors aged ≥18 years in the United States.
Effect of High Magnetic Field on the Growth, Magnetic, and Electrical Properties of Nanocrystalline Ni Films with Different Thicknesses and Growth Rates
Authors: Du Jiaojiao , Li Guojian , Li Mengmeng , Wang Jianhao , Gao Yang , Wang Qiang
Published: May 2018

To realize the application of Ni films in magnetic recording media, giant magnetoresistive sensors and microelectromechanical systems, it is necessary to control and improve the magnetic and electrical properties of the films. In this paper, Ni nanocrystalline films with different thicknesses and growth rates are prepared with or without a high magnetic field (HMF). The effects of a HMF on the growth, magnetic and electrical properties of the Ni films are studied. The results show that HMF changes the growth structure of the Ni films from disordered stacked grains to columnar growth along the direction of the HMF. The columnar growth becomes more prominent at a high growth rate and large film thickness. The HMF increases the grain size but decreases the surface roughness of the Ni films. Due to changes in the growth structure, grain size and film quality, the saturation magnetization of the Ni films increase markedly (by 89%), and the resistivity and coercivity significantly decrease (by 89 and 58%, respectively) by the HMF. The remanence ratio of the Ni films is controlled by the HMF. This study shows that a HMF effectively controls the growth and improves the magnetic and electrical properties of Ni films.
Electrical, Optical, and Structural Characteristics of CH3NH3PbI3Perovskite Light‐Emitting Diodes
Authors: Oh Munsik , Jo Seung‐Il , Parida Bhaskar , Singh Arjun , Ko Keumjin , Kang Jae‐Wook , Kim Hyunsoo
Published: May 2018

Electrical, optical, and structural characteristics of perovskite light‐emitting diodes (PeLEDs) are investigated. The PeLED consisting of ITO/ZnO/MAPbI3(CH3NH3PbI3)/spiro‐OMeTAD/Ag structures shows a peak emission wavelength of 766 nm, turn‐on voltage of 1.7 V, reverse breakdown voltage of −5.4 V, current efficiency of 1.5 × 10−4 cdA−1, maximum luminance of 0.1 cdm−2, and an external quantum efficiency of 0.2% at bias voltage of 3 V (or a current density of 617 mA cm−2). The PeLED also shows a significant output drop at higher bias voltage. According to the analyses of forwardJ–Vcurves and structural studies, this could be associated with the anomalously large ideality factor of 12.8 and the high series resistance of 2.8 Ω cm2, that is, the leakage current through parasitic shunt path (possibly through pinholes in the perovskite) and accelerated Joule‐heating result in a significant output degradation.
A Review on Halide Perovskites as Color Conversion Layers in White Light Emitting Diode Applications
Authors: Guner Tugrul , Demir Mustafa M.
Published: May 2018

In the last decade, halide perovskites have attracted great interest due to many reasons, including their low cost, solution‐processability, superior PL properties, broad range of color tunability, color purity, and defect tolerance, among others. They are in increasing demand for a wide range of applications, such as solar cells, light emitting diodes (LEDs), white LEDs (WLED), and lasers. Yellow phosphors have been heavily employed in solid‐state lighting, since its illumination by blue yields white light with various optical features, such as high/low CRI, CCT, and luminous efficiency. However, phosphors as pigments are seldom found and are costly material. In this sense, halide perovskites may offer a promising alternative to phosphors for future solid‐state lighting. In this study, the synthesis and optical properties of halide perovskites, as well as their application in WLED as a conversion layer are investigated.
Clustering and variable selection in the presence of mixed variable types and missing data
Authors: Storlie C. B. , Myers S. M. , Katusic S. K. , Weaver A. L. , Voigt R. G. , Croarkin P. E. , Stoeckel R. E. , Port J. D.
Published: May 2018

We consider the problem of model‐based clustering in the presence of many correlated, mixed continuous, and discrete variables, some of which may have missing values. Discrete variables are treated with a latent continuous variable approach, and the Dirichlet process is used to construct a mixture model with an unknown number of components. Variable selection is also performed to identify the variables that are most influential for determining cluster membership. The work is motivated by the need to cluster patients thought to potentially have autism spectrum disorder on the basis of many cognitive and/or behavioral test scores. There are a modest number of patients (486) in the data set along with many (55) test score variables (many of which are discrete valued and/or missing). The goal of the work is to (1) cluster these patients into similar groups to help identify those with similar clinical presentation and (2) identify a sparse subset of tests that inform the clusters in order to eliminate unnecessary testing. The proposed approach compares very favorably with other methods via simulation of problems of this type. The results of the autism spectrum disorder analysis suggested 3 clusters to be most likely, while only 4 test scores had high (>0.5) posterior probability of being informative. This will result in much more efficient and informative testing. The need to cluster observations on the basis of many correlated, continuous/discrete variables with missing values is a common problem in the health sciences as well as in many other disciplines.
Flame‐Engraved Nickel–Iron Layered Double Hydroxide Nanosheets for Boosting Oxygen Evolution Reactivity
Authors: Zhou Daojin , Xiong Xuya , Cai Zhao , Han Nana , Jia Yin , Xie Qixian , Duan Xinxuan , Xie Tianhui , Zheng Xiaolin , Sun Xiaoming , Duan Xue
Published: May 2018

Introducing oxygen vacancies to metal oxide materials would improve their catalytic activity but usually needs reductive reagents (e.g., H2) and high temperatures (e.g., >600 °C), which is unsafe, complex, and time consuming. Herein, a fast (30 s) and facile (operated at ambient conditions) flame‐engraved method is used to introduce abundant oxygen vacancies and well‐defined hexagonal cavities with (110) edges to nickel–iron layered double hydroxides (NiFe‐LDH). Abundant oxygen vacancies, lower coordination numbers, and electron‐rich structures of Ni and Fe sites emerge in the flame‐engraved NiFe‐LDH array electrode, leading to its onset potential as low as 1.40 V (vs reversible hydrogen electrode) for oxygen evolution reaction. This highlights the importance and convenience of flame‐engraving method in preparing metal hydroxides with abundant oxygen vacancies, which can be used as efficient electrochemical catalysts.
High Water Oxidation Performance of W‐Doped BiVO4 Photoanodes Coupled to V2O5 Rods as a Photoabsorber and Hole Carrier
Authors: Oliveira Andreia T. , Rodriguez Mariandry , Andrade Tatiana S. , de Souza Helen E. A. , Ardisson José D. , Oliveira Henrique S. , Oliveira Luiz C. A. , Lorençon Eudes , Silva Adilson C. , Nascimento Lucas L. , Patrocínio Antonio O. T. , Pereira Márcio C.
Published: May 2018

Monoclinic BiVO4 is recognized as a promising photoanode for water oxidation, but its relatively wide bandgap energy (Eg ≈2.5 eV) and poor charge transport limit the light absorption (ηabs) and charge separation (ηsep) efficiencies, thus resulting in low photocurrents. To solve these drawbacks, here the ηabs × ηsep product has been decoupled by combining W‐doped BiVO4 and V2O5 rods (Eg ≈2.1 eV) for simultaneously increasing the light harvesting and the charge separation in photoanodes under back‐side illumination. In this strategy, V2O5 rods maximize the light absorption and hole transport throughout the W‐BiVO4 film, making more holes to achieve the V2O5/W‐BiVO4/H2O interface to trigger the water oxidation reaction with photocurrents as high as 6.6 mA cm−2 at 1.23 VRHE after 2 h reaction. Notably, under back‐side illumination, the W‐BiVO4/V2O5 photoanode exhibited ηabs × ηsep of 74.5 and 93.0% at 0.5 and 1.23 VRHE, respectively, the highest values reported up to date for BiVO4‐based photoelectrodes. This simple strategy brings us closer to develop efficient photoanodes for photoelectrochemical water splitting devices.
MMRUC3: A recommendation approach ofmove methodrefactoring using coupling, cohesion, and contextual similarity to enhance software design
Authors: Rahman Md. Masudur , Riyadh Rashed Rubby , Khaled Shah Mostafa , Satter Abdus , Rahman Md. Rayhanur
Published: May 2018

Placement of methods is one of the most important design activities for any object‐oriented application in terms of coupling and cohesion. Due to method misplacement, the application becomes tightly coupled and loosely cohesive, reflecting inefficient design. Therefore, a feature envy code smell emerges from the application, as many methods use more features of other classes than its current class. Hence, development and maintenance time, cost, and effort are increased. To refactor the code smell and enhance the design quality,move methodrefactoring plays a significant role through grouping similar behaviors of methods. This is because the manual refactoring process is infeasible due to the necessity of huge time and most of the existing techniques consider only coupling‐based and/or cohesion‐based information of nonstatic entities (methods and attributes) for the recommendation. However, this article proposes an approach that uses contextual information, based on information retrieval techniques, along with dependency (coupling and cohesion)‐based information of the application for the recommendation. In addition, the approach incorporates both static and nonstatic entities in the recommendation process. For validation, the approach is applied on seven well‐known open source projects. The results of the experimental evaluation indicate that the proposed approach provides better results with an average precision of 18.91%, a recall of 69.91%, and an F‐measure of 29.77% than the JDeodorant tool (a widely used eclipse plugin for refactorings). Moreover, this article establishes several relationships between the accuracy of the approach and project standards and sizes.
An investigation on the interaction of moment‐resisting frames and shear walls in RC dual systems using endurance time method
Authors: Estekanchi H.E. , Harati M. , Mashayekhi M.R.
Published: May 2018

Reinforced concrete (RC) dual systems are composed of RC moment‐resisting frames (MRFs) and RC shear walls, where MRFs are barely designed to handle gravity loads. Investigations have demonstrated that shear walls exert negative effects on the upper part of MRFs. In this paper, the interaction of shear walls and MRFs is inspected using endurance time (ET) method. ET is a dynamic time history‐based pushover procedure in which structures are exposed to a set of predefined intensifying ET acceleration functions. In this method, seismic performance of the considered structure is assessed based on earthquake return periods; during which, required predefined seismic performance objectives are fulfilled. In this study, several buildings with RC dual systems were designed based on the conventional codes. Next, their nonlinear duplicates were generated for the application of the ET analysis. It was revealed that shear wall elements impose considerable rotational demands—exceeding the criteria established by ASCE41‐13—on the beams and columns, especially those located on the upper parts of the buildings. This paper puts forth and reviews certain methods to cushion the negative effects brought about by RC shear walls, along with a detailed discussion on their merits and demerits.
Structural health monitoring for a 600 m high skyscraper
Authors: Li Qiusheng , He Yinghou , Zhou Kang , Han Xuliang , He Yuncheng , Shu Zhenru
Published: May 2018

Ping‐An Finance Center (PAFC), with a total height of 600 m, is the fourth tallest building in the world. An integrated structural health monitoring (SHM) system with total number of 553 sensors, which was designed based on the modular design methodology, is being installed in PAFC to monitor its structural performance and external excitations during both construction and service stages. This paper first gives a brief introduction of the architecture of the SHM system, followed by detailed descriptions on its 7 subsystems, including the components, functions, and interrelationship corresponding to each subsystem. The modular design of the SHM system ensures highly effective operation of the comprehensive monitoring system, and such an extensible system allows the subsystems to be deployed and augmented easily to meet the evolving monitoring needs. The second part of this paper introduces the research activities and selected results from the SHM system equipped in PAFC, including monitoring of vertical deformations of various structural components, verification of effectiveness of active tuned mass damper systems, and verification of numerous damage identification methods. Finally, representative monitoring results from the SHM system in PAFC during a typhoon are presented and discussed. This paper aims to provide useful information for the SHM, construction, and design of super‐tall buildings.