bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Wireless Multidevice Users
Authors: Das Aveek K. , Pathak Parth H. , Chuah Chen-Nee , Mohapatra Prasant
Published: December 2016

The number of wireless-enabled devices owned by a user has had huge growth over the past few years. Over one third of adults in the United States currently own three wireless devices: a smartphone, laptop, and tablet. This article provides a study of the network usage behavior of today’s multidevice users. Using data collected from a large university campus, we provide a detailed multidevice user (MDU) measurement study of more than 30,000 users. The major objective of this work is to study how the presence of multiple wireless devices affects the network usage behavior of users. Specifically, we characterize the usage pattern of the different device types in terms of total and intermittent usage, how the usage of different devices overlap over time, and uncarried device usage statistics. We also study user preferences of accessing sensitive content and device-specific factors that govern the choice of WiFi encryption type. The study reveals several interesting findings about MDUs. We see how the use of tablets and laptops are interchangeable and how the overall multidevice usage is additive instead of being shared among the devices. We also observe how current DHCP configurations are oblivious to multiple devices, which results in inefficient utilization of available IP address space. All findings about multidevice usage patterns have the potential to be utilized by different entities, such as app developers, network providers, security researchers, and analytics and advertisement systems, to provide more intelligent and informed services to users who have at least two devices among a smartphone, tablet, and laptop.
Hilbert Exclusion
Authors: Connor Richard , Cardillo Franco Alberto , Vadicamo Lucia , Rabitti Fausto
Published: December 2016

Most research into similarity search in metric spaces relies on the triangle inequality property. This property allows the space to be arranged according to relative distances to avoid searching some subspaces. We show that many common metric spaces, notably including those using Euclidean and Jensen-Shannon distances, also have a stronger property, sometimes called the four-point property: In essence, these spaces allow an isometric embedding of any four points in three-dimensional Euclidean space, as well as any three points in two-dimensional Euclidean space. In fact, we show that any space that is isometrically embeddable in Hilbert space has the stronger property. This property gives stronger geometric guarantees, and one in particular, which we name the Hilbert Exclusion property, allows any indexing mechanism which uses hyperplane partitioning to perform better. One outcome of this observation is that a number of state-of-the-art indexing mechanisms over high-dimensional spaces can be easily refined to give a significant increase in performance; furthermore, the improvement given is greater in higher dimensions. This therefore leads to a significant improvement in the cost of metric search in these spaces.
S-nitrosylation and S-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca2+ sensitivity in rat fast-twitch muscle fibers
Authors: Dutka T. L. , Mollica J. P. , Lamboley C. R. , Weerakkody V. C. , Greening D. W. , Posterino G. S. , Murphy R. M. , Lamb G. D.
Published: December 2016

Nitric oxide is generated in skeletal muscle with activity and decreases Ca2+ sensitivity of the contractile apparatus, putatively by S-nitrosylation of an unidentified protein. We investigated the mechanistic basis of this effect and its relationship to the oxidation-induced increase in Ca2+ sensitivity in mammalian fast-twitch (FT) fibers mediated by S-glutathionylation of Cys134 on fast troponin I (TnIf). Force-[Ca2+] characteristics of the contractile apparatus in mechanically skinned fibers were assessed by direct activation with heavily Ca2+-buffered solutions. Treatment with S-nitrosylating agents, S-nitrosoglutathione (GSNO) or S-nitroso- N-acetyl-penicillamine (SNAP), decreased pCa50 ( = −log10 [Ca2+] at half-maximal activation) by ~−0.07 pCa units in rat and human FT fibers without affecting maximum force, but had no effect on rat and human slow-twitch fibers or toad or chicken FT fibers, which all lack Cys134. The Ca2+ sensitivity decrease was 1) fully reversed with dithiothreitol or reduced glutathione, 2) at least partially reversed with ascorbate, indicative of involvement of S-nitrosylation, and 3) irreversibly blocked by low concentration of the alkylating agent, N-ethylmaleimide (NEM). The biotin-switch assay showed that both GSNO and SNAP treatments caused S-nitrosylation of TnIf. S-glutathionylation pretreatment blocked the effects of S-nitrosylation on Ca2+ sensitivity, and vice-versa. S-nitrosylation pretreatment prevented NEM from irreversibly blocking S-glutathionylation of TnIf and its effects on Ca2+ sensitivity, and likewise S-glutathionylation pretreatment prevented NEM block of S-nitrosylation. Following substitution of TnIf into rat slow-twitch fibers, S-nitrosylation treatment caused decreased Ca2+ sensitivity. These findings demonstrate that S-nitrosylation and S-glutathionylation exert opposing effects on Ca2+ sensitivity in mammalian FT muscle fibers, mediated by competitive actions on Cys134 of TnIf.
BMI-1 extends proliferative potential of human bronchial epithelial cells while retaining their mucociliary differentiation capacity
Authors: Munye Mustafa M. , Shoemark Amelia , Hirst Robert A. , Delhove Juliette M. , Sharp Tyson V. , McKay Tristan R. , O’Callaghan Christopher , Baines Deborah L. , Howe Steven J. , Hart Stephen L.
Published: December 2016

Air-liquid interface (ALI) culture of primary airway epithelial cells enables mucociliary differentiation providing an in vitro model of the human airway, but their proliferative potential is limited. To extend proliferation, these cells were previously transduced with viral oncogenes or mouse Bmi-1 + hTERT, but the resultant cell lines did not undergo mucociliary differentiation. We hypothesized that use of human BMI-1 alone would increase the proliferative potential of bronchial epithelial cells while retaining their mucociliary differentiation potential. Cystic fibrosis (CF) and non-CF bronchial epithelial cells were transduced by lentivirus with BMI-1 and then their morphology, replication kinetics, and karyotype were assessed. When differentiated at ALI, mucin production, ciliary function, and transepithelial electrophysiology were measured. Finally, shRNA knockdown of DNAH5 in BMI-1 cells was used to model primary ciliary dyskinesia (PCD). BMI-1-transduced basal cells showed normal cell morphology, karyotype, and doubling times despite extensive passaging. The cell lines underwent mucociliary differentiation when cultured at ALI with abundant ciliation and production of the gel-forming mucins MUC5AC and MUC5B evident. Cilia displayed a normal beat frequency and 9+2 ultrastructure. Electrophysiological characteristics of BMI-1-transduced cells were similar to those of untransduced cells. shRNA knockdown of DNAH5 in BMI-1 cells produced immotile cilia and absence of DNAH5 in the ciliary axoneme as seen in cells from patients with PCD. BMI-1 delayed senescence in bronchial epithelial cells, increasing their proliferative potential but maintaining mucociliary differentiation at ALI. We have shown these cells are amenable to genetic manipulation and can be used to produce novel disease models for research and dissemination.
Mechanisms of blood pressure salt sensitivity: new insights from mathematical modeling
Authors: Clemmer John S. , Pruett W. Andrew , Coleman Thomas G. , Hall John E. , Hester Robert L.
Published: December 2016

Mathematical modeling is an important tool for understanding quantitative relationships among components of complex physiological systems and for testing competing hypotheses. We used HumMod, a large physiological model, to test hypotheses of blood pressure (BP) salt sensitivity. Systemic hemodynamics, renal, and neurohormonal responses to chronic changes in salt intake were examined during normal renal function, fixed low or high plasma angiotensin II (ANG II) levels, bilateral renal artery stenosis, increased renal sympathetic nerve activity (RSNA), and decreased nephron numbers. Simulations were run for 4 wk at salt intakes ranging from 30 to 1,000 mmol/day. Reducing functional kidney mass or fixing ANG II increased salt sensitivity. Salt sensitivity, associated with inability of ANG II to respond to changes in salt intake, occurred with smaller changes in renal blood flow but greater changes in glomerular filtration rate, renal sodium reabsorption, and total peripheral resistance (TPR). However, clamping TPR at normal or high levels had no major effect on salt sensitivity. There were no clear relationships between BP salt sensitivity and renal vascular resistance or extracellular fluid volume. Our robust mathematical model of cardiovascular, renal, endocrine, and sympathetic nervous system physiology supports the hypothesis that specific types of kidney dysfunction, associated with impaired regulation of ANG II or increased tubular sodium reabsorption, contribute to BP salt sensitivity. However, increased preglomerular resistance, increased RSNA, or inability to decrease TPR does not appear to influence salt sensitivity. This model provides a platform for testing competing concepts of long-term BP control during changes in salt intake.
From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes
Authors: Corcoran Callan C. , Grady Cameron R. , Pisitkun Trairak , Parulekar Jaya , Knepper Mark A.
Published: December 2016

The organization of the mammalian genome into gene subsets corresponding to specific functional classes has provided key tools for systems biology research. Here, we have created a web-accessible resource called the Mammalian Metabolic Enzyme Database ( https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/MetabolicEnzymeDatabase.html ) keyed to the biochemical reactions represented on iconic metabolic pathway wall charts created in the previous century. Overall, we have mapped 1,647 genes to these pathways, representing ~7 percent of the protein-coding genome. To illustrate the use of the database, we apply it to the area of kidney physiology. In so doing, we have created an additional database ( Database of Metabolic Enzymes in Kidney Tubule Segments: https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/ ), mapping mRNA abundance measurements (mined from RNA-Seq studies) for all metabolic enzymes to each of 14 renal tubule segments. We carry out bioinformatics analysis of the enzyme expression pattern among renal tubule segments and mine various data sources to identify vasopressin-regulated metabolic enzymes in the renal collecting duct.
Effects of different stresses on cardiac autonomic control and cardiovascular coupling
Authors: Xie Lin , Liu Binbin , Wang Xiaoni , Mei Mengqi , Li Mengjun , Yu Xiaolin , Zhang Jianbao
Published: December 2016

The objective of this study was to investigate the impacts of different stresses on time-varying autonomic reactivity and cardiovascular coupling. In total, 25 male subjects were recruited. RR intervals (RRI), systolic and diastolic blood pressure (SBP, DBP), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) values were collected during rest, mental arithmetic task (MAT), and cold pressor test (CPT). Baroreflex sensitivity (BRS) was derived using the transfer function method. Continuous wavelet transformation of RRI was used to describe the time-variant patterns of autonomic neural activities. Wavelet cross correlation and phase synchronization were used to estimate the amplitude and phase coupling between RRI and SBP. MAT was characterized by increased heart rate (HR), SBP, DBP, and CO with decreased BRS attributable to prolonged parasympathetic withdrawal. Moreover, cardiovascular coupling was disrupted in MAT. These results indicated that baroreflex was depressed, and the top-down system started to take action under mental stress. In CPT, SBP, DBP, and SVR increased significantly, whereas HR and BRS remained unchanged. The increase of sympathetic activity was transient, and cardiovascular coupling did not change in CPT. Intriguingly, the frequency of the maximum cross-correlation coefficient in the low-frequency band (0.04–0.15 Hz) was significantly decreased in CPT, which may be due to the change of resonance frequency of the baroreflex loop.

NEW & NOTEWORTHY The study is the first to compare the time-variant pattern of autonomic nervous activities and cardiovascular coupling between the mental arithmetic task (MAT) and the cold pressor test (CPT). Our results demonstrated that MAT and CPT elicited different time-varying patterns of autonomic neural activities and cardiovascular synchronization. Both the amplitude and phase consistency of blood pressure and heart rate decreased in MAT. CPT may affect the harmonic frequency of the baroreflex loop.
Effect of acute aerobic exercise and histamine receptor blockade on arterial stiffness in African Americans and Caucasians
Authors: Yan Huimin , Ranadive Sushant M. , Lane-Cordova Abbi D. , Kappus Rebecca M. , Behun Michael A. , Cook Marc D. , Woods Jeffrey A. , Wilund Kenneth R. , Baynard Tracy , Halliwill John R. , Fernhall Bo
Published: December 2016

African Americans (AA) exhibit exaggerated central blood pressure (BP) and arterial stiffness measured by pulse wave velocity (PWV) in response to an acute bout of maximal exercise compared with Caucasians (CA). However, whether potential racial differences exist in central BP, elastic, or muscular arterial distensibility after submaximal aerobic exercise remains unknown. Histamine receptor activation mediates sustained postexercise hyperemia in CA but the effect on arterial stiffness is unknown. This study sought to determine the effects of an acute bout of aerobic exercise on central BP and arterial stiffness and the role of histamine receptors, in AA and CA. Forty-nine (22 AA, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either histamine receptor antagonist or control placebo. Central blood BP and arterial stiffness measurements were obtained at baseline, and at 30, 60, and 90 min after 45 min of moderate treadmill exercise. AA exhibited greater central diastolic BP, elevated brachial PWV, and local carotid arterial stiffness after an acute bout of submaximal exercise compared with CA, which may contribute to their higher risk of cardiovascular disease. Unexpectedly, histamine receptor blockade did not affect central BP or PWV in AA or CA after exercise, but it may play a role in mediating local carotid arterial stiffness. Furthermore, histamine may mediate postexercise carotid arterial dilation in CA but not in AA. These observations provide evidence that young and healthy AA exhibit an exaggerated hemodynamic response to exercise and attenuated vasodilator response compared with CA.

NEW & NOTEWORTHY African Americans are at greater risk for developing cardiovascular disease than Caucasians. We are the first to show that young and healthy African Americans exhibit greater central blood pressure, elevated brachial stiffness, and local carotid arterial stiffness following an acute bout of submaximal exercise compared with Caucasians, which may contribute to their higher risk of cardiovascular disease. Furthermore, African Americans exhibit attenuated vasodilator response compared with Caucasians.
Stiffness Characteristics of High-Speed Railway Turnout and the Effect on the Dynamic Train-Turnout Interaction
Authors: Xu Jingmang , Wang Ping , Ma Xiaochuan , Gao Yuan , Chen Rong
Published: December 2016

Track stiffness in railway turnouts is variable due to differences in structural composition along the longitudinal direction, which will lead to severe dynamic interaction between train and turnout. In this paper, a transient analysis model is presented to investigate the stiffness characteristics of high-speed railway turnouts based on the finite element method and is applied to optimise the stiffness of railway turnouts. Furthermore, the effect of the stiffness variations on the dynamic train-turnout interaction is analysed. The calculation results show that the track stiffness characteristics are similar in the main and diverging line of railway turnout, except for the check rail sections. Due to the existence of shared baseplates and spacer blocks between different rails, the stiffness variations in the crossing panel are most severe in high-speed railway turnouts. The stiffness differences (calculated as the ratio of the maximum and minimum stiffness) of the longitudinal and lateral direction for Chinese number 18 ballasted turnout are 216% and 229%, respectively. The graded stiffness of the tie pads has been redesigned to optimise the stiffness of railway turnout based on the transient analysis model and the stiffness differences of the turnout are decreased. Altogether, the dynamic train-turnout interaction is enhanced remarkably by considering the turnout’s stiffness characteristics.
Study on Millimeter-Wave Vivaldi Rectenna and Arrays with High Conversion Efficiency
Authors: Tan Guan-Nan , Yang Xue-Xia , Mei Huan , Lu Zhong-Liang
Published: December 2016

A novel Vivaldi rectenna operated at 35 GHz with high millimeter wave to direct current (MMW-to-DC) conversion efficiency is presented and the arrays are investigated. The measured conversion efficiency is 51.6% at 35 GHz and the efficiency higher than 30% is from 33.2 GHz to 36.6 GHz when the input MMW power is 79.4 mW. The receiving Vivaldi antenna loaded with metamaterial units has a high gain of 10.4 dBi at 35 GHz. A SIW- (substrate integrated waveguide-) to-microstrip transition is designed not only to integrate the antenna with the rectifying circuit directly but also to provide the DC bypass for the rectifying circuit. When the power density is 8.7 mW/cm2, the received MMW power of the antenna is 5.6 mW, and the maximum conversion efficiency of the rectenna element is 31.5%. The output DC voltage of the element is nearly the same as that of the parallel array and is about half of the series array. The DC power obtained by the 1 × 2 rectenna arrays is about two times as much as that of the element. The conversion efficiencies of the arrays are very close to that of the element. Large scale arrays could be expended for collecting more DC power.
Gene Expression Analysis of Alfalfa Seedlings Response to Acid-Aluminum
Authors: Zhou Peng , Su Liantai , Lv Aimin , Wang Shengyin , Huang Bingru , An Yuan
Published: December 2016

Acid-Aluminum (Al) is toxic to plants and greatly affects crop production worldwide. To understand the responses of plants to acid soils and Aluminum toxicity, we examined global gene expression using microarray data in alfalfa seedlings with the treatment of acid-Aluminum. 3,926 genes that were identified significantly up- or downregulated in response to Al3+ ions with pH 4.5 treatment, 66.33% of which were found in roots. Their functional categories were mainly involved with phytohormone regulation, reactive oxygen species, and transporters. Both gene ontology (GO) enrichment and KEGG analysis indicated that phenylpropanoid biosynthesis, phenylalanine metabolism, and flavonoid biosynthesis played a critical role on defense to Aluminum stress in alfalfa. In addition, we found that transcription factors such as the MYB and WRKY family proteins may be also involved in the regulation of reactive oxygen species reactions and flavonoid biosynthesis. Thus, the finding of global gene expression profile provided insights into the mechanisms of plant defense to acid-Al stress in alfalfa. Understanding the key regulatory genes and pathways would be advantageous for improving crop production not only in alfalfa but also in other crops under acid-Aluminum stress.
Pain Analysis in Patients with Pancreatic Carcinoma: Irreversible Electroporation versus Cryoablation
Authors: Li Jiannan , Sheng Shihou , Zhang Kai , Liu Tongjun
Published: December 2016

The aim of this article is to evaluate and compare the postprocedure pain in patients with pancreatic carcinoma treated with irreversible electroporation (IRE) and cryoablation (CRYO). We compared 22 patients with 22 lesions in pancreas treated with IRE and 26 patients with 27 lesions treated with cryosurgery. All the patients in the two groups were under celiac plexus block (CPB) treatment to alleviate the postprocedure pain. A numerical rating scale (VAS) consisting of 11-point scales and the 24 h total hydromorphone use were recorded for the analysis of the pain level in the patients who underwent these two technologies separately. Other parameters, such as the complications and the ECOG performance status, were also noted. Statistical analysis was performed by Fisher’s exact test, the Chi-square test, and Student’st-test. All the pancreatic carcinoma patients in our study were reported to have postprocedure pain in the two groups. But there was no significant difference in the mean pain score (4.95 (IRE) versus 4.85 (CRYO);P=0.52) and 24 h total hydromorphone use (3.89 mg (IRE) versus 3.97 mg (CRYO);P=0.30). IRE is comparable to cryotherapy in the amount of pain that patients with pancreatic carcinoma experience.
Respiratory Symptoms due to Occupational Exposure to Formaldehyde and MDF Dust in a MDF Furniture Factory in Eastern Thailand
Authors: Thetkathuek Anamai , Yingratanasuk Tanongsak , Ekburanawat Wiwat
Published: December 2016

The study aimed to investigate factors associated with respiratory symptoms in workers in a medium-density fiberboard (MDF) furniture factory in Eastern Thailand. Data were collected from 439 employees exposed to formaldehyde and MDF dust using questionnaire and personal sampler (Institute of Occupational Medicine; IOM). The average concentration of formaldehyde from MDF dust was 2.62 ppm (SD 367), whereas the average concentration of MDF dust itself was 7.67 mg/m3(SD 3.63). Atopic allergic history was a factor associated with respiratory irritation symptoms and allergic symptoms among the workers exposed to formaldehyde and were associated with respiratory irritation symptoms and allergic symptoms among those exposed to MDF dust. Exposure to MDF dust at high level (>5 mg/m3) was associated with respiratory irritation symptoms and allergic symptoms. Excluding allergic workers from the study population produced the same kind of results in the analysis as in all workers. The symptoms were associated with the high concentrations of formaldehyde and MDF dust in this factory. If the concentration of MDF dust was >5 mg/m3, the risk of irritation and allergic symptoms in the respiratory system increased. The respiratory health of the employees with atopic allergic history exposed to formaldehyde and MDF dust should be monitored closely.
Impact of Land-Use Change on Atmospheric Environment Using Refined Land Surface Properties in the Pearl River Delta, China
Authors: Lai Anqi , Liu Yiming , Chen Xiaoyang , Chang Ming , Fan Qi , Chan Pakwai , Wang Xuemei , Dai Jianing
Published: December 2016

We replaced the outdated land-use of the Weather Research and Forecasting-Chemistry (WRF-Chem) model with a refined dataset, the Global Land Cover 2009 (GLC2009) dataset, to investigate the impact of land-use change on the regional atmospheric environment in the Pearl River Delta (PRD) region. Simulations of two months in 2014 (January and July) showed that land-use change increased the monthly averaged 2 m temperature by 0.24°C and 0.27°C in January and July, respectively. The relative humidity decreased by 2.02% and 2.23% in January and July, respectively. Due to the increase in ground roughness, the monthly averaged wind speed in January and July decreased by 0.19 m/s and 0.16 m/s. The planetary boundary layer height increased throughout the day and with larger relative increase during the nighttime. These subtle changes caused by land-use resulted in discernable changes in pollutant concentrations. Monthly averaged surface O3 concentration increased by 0.93 µg/m3 and 1.61 µg/m3 in January and July, while PM2.5 concentration decreased by 1.58 µg/m3 and 3.76 µg/m3, and the changes in pollutant concentrations were more noticeable during the nighttime. Overall, the impacts of land-use change on the atmospheric environment are obvious throughout the PRD region, especially in the urbanized areas.
Validation of an LC-MS/MS Method for Urinary Lactulose and Mannitol Quantification: Results in Patients with Irritable Bowel Syndrome
Authors: Gervasoni Jacopo , Schiattarella Arcangelo , Giorgio Valentina , Primiano Aniello , Russo Consuelo , Tesori Valentina , Scaldaferri Franco , Urbani Andrea , Zuppi Cecilia , Persichilli Silvia
Published: December 2016

Aim. Lactulose/mannitol ratio is used to assess intestinal barrier function. Aim of this work was to develop a robust and rapid method for the analysis of lactulose and mannitol in urine by liquid chromatography coupled to tandem mass spectrometry. Lactulose/mannitol ratio has been measured in pediatric patients suffering from irritable bowel syndrome.Methods. Calibration curves and raffinose, used as internal standard, were prepared in water : acetonitrile 20 : 80. FiftyμL of urine sample was added to 450 μL of internal standard solution. The chromatographic separation was performed using a Luna NH2column operating at a flow rate of 200 μL/min and eluted with a linear gradient from 20% to 80% water in acetonitrile. Total run time is 9 minutes. The mass spectrometry operates in electrospray negative mode. Method was fully validated according to European Medicine Agency guidelines.Results and Conclusions. Linearity ranged from 10 to 1000 mg/L for mannitol and 2.5 to 1000 mg/L for lactulose. Imprecision in intra- and interassay was lower than 15% for both analytes. Accuracy was higher than 85%. Lactulose/mannitol ratio in pediatric patients is significantly higher than that measured in controls. The presented method, rapid and sensitive, is suitable in a clinical laboratory.
Hierarchical Structure and Molecular Dynamics of Metal-Organic Framework as Characterized by Solid State NMR
Authors: Chen Wei , Wu Yi-nan , Li Fengting
Published: December 2016

Metal-organic framework (MOF) stands out as a promising material with great potential in application areas, such as gas separation and catalysis, due to its extraordinary properties. In order to fully characterize the structure of MOFs, especially those without single crystal, Solid State NMR (SSNMR) is an indispensable tool. As a complimentary analytical technique to X-ray diffraction, SSNMR could provide detailed atomic level structure information. Meanwhile, SSNMR can characterize molecular dynamics over a wide dynamics range. In this review, selected applications of SSNMR on various MOFs are summarized and discussed.
The Effectiveness of Aromatherapy in Reducing Pain: A Systematic Review and Meta-Analysis
Authors: Lakhan Shaheen E. , Sheafer Heather , Tepper Deborah
Published: December 2016

Background. Aromatherapy refers to the medicinal or therapeutic use of essential oils absorbed through the skin or olfactory system. Recent literature has examined the effectiveness of aromatherapy in treating pain. Methods. 12 studies examining the use of aromatherapy for pain management were identified through an electronic database search. A meta-analysis was performed to determine the effects of aromatherapy on pain. Results. There is a significant positive effect of aromatherapy (compared to placebo or treatments as usual controls) in reducing pain reported on a visual analog scale (SMD = −1.18, 95% CI: −1.33, −1.03; p<0.0001). Secondary analyses found that aromatherapy is more consistent for treating nociceptive (SMD = −1.57, 95% CI: −1.76, −1.39, p<0.0001) and acute pain (SMD = −1.58, 95% CI: −1.75, −1.40, p<0.0001) than inflammatory (SMD = −0.53, 95% CI: −0.77, −0.29, p<0.0001) and chronic pain (SMD = −0.22, 95% CI: −0.49, 0.05, p=0.001), respectively. Based on the available research, aromatherapy is most effective in treating postoperative pain (SMD = −1.79, 95% CI: −2.08, −1.51, p<0.0001) and obstetrical and gynecological pain (SMD = −1.14, 95% CI: −2.10, −0.19, p<0.0001). Conclusion. The findings of this study indicate that aromatherapy can successfully treat pain when combined with conventional treatments.
Urinary Schistosomiasis among Children in Murbai and Surbai Communities of Ardo-Kola Local Government Area, Taraba State, Nigeria
Authors: Houmsou R. S. , Agere H. , Wama B. E. , Bingbeng J. B. , Amuta E. U. , Kela S. L.
Published: December 2016

Background. This cross-sectional study was conducted to determine the prevalence, intensity of infection, and risk factors associated with urinary schistosomiasis among children in Murbai and Surbai communities of Ardo-Kola Local Government Area (LGA), Taraba State, Nigeria.Methods. Urine samples were analysed by the standard filtration technique using 10 ml syringe, Swinnex polypropylene filter holder (13 mm diameter), and polycarbonate membrane filters (12 μm porosity). Sociodemographic data and water contact activities were collated from children using structured questionnaires.Results. A point prevalence of 58.54% was reported out of the urine samples examined. Males were significantly more infected than their female counterparts (71.15% versus 43.66%,χ2= 89.12,p=0.000). The age-related prevalence showed 6–10 and 11–15 years significantly infected with 78.70% and 73.02%, respectively (χ2= 89.12,p=0.000). Light intensity of infection, 62.51%, was significantly higher than heavy intensity, 37.48%, among the infected children (χ2= 365.8,p=0.000). Water contact activities such as fishing (OR = 4.01, CI = 3.04–5.61,p=0.000), rice farming (OR = 4.01, CI = 2.96–5.36,p=0.000), and dry season farming (OR = 4.78, CI = 3.68–6.22,p=0.000) were the risk factors exposing children to infection in the area.Conclusion. There is an urgent need to undertake a large scale deworming control programme using praziquantel in the area.
Abstract A22: Targeting S100p Sensitizes Pancreatic Cancer Cells towards Gemcitabine
Authors: Tang Shing Chun , Chen Yangchao
Published: December 2016

Introduction: S100P (S100 Calcium Binding Protein P) is a member of S100 family proteins and plays important roles in cancers. S100p is up-regulated in Pancreatic Ductal Adenocarcinoma (PDAC). There is an up-regulation of S100p in pancreatic intraepithelial neoplasia (PanIN) tissue samples as well as a correlation of its expression with the grade of PanIN. S100p interacts with Receptor for Advanced Glycation End product (RAGE), whose downstream signaling pathways MAPK and NF-kB are responsible for the tumor progression and chemo resistance of PDAC. Thus, abrogation of the RAGE activation may be beneficial towards pancreatic cancer treatment. Therefore, we would like to investigate the growth and chemosensitivity of PDAC cells upon silencing S100p.

Methodology: The S100p in PDAC cell lines Capan2 and CFPAC1 was knocked down by lentiviral shRNA. Cell growth, wound healing, colonies formation ability and the tumorigenicity of the S100p knocked down cell lines were evaluated. Moreover, the chemosensitivity of PDAC cells with S100p knockdown towards gemcitabine was evaluated with cell viability assay.

Result: Knock-down of S100p inhibited PDAC cell growth and cell migration. RNAi targeting S100p in PDAC cells inhibited cell proliferation. Knock-down of S100p inhibited PDAC tumor growth in nude mice. Enhanced sensitization to gemcitabine on PDAC cells with S100p knock-down was also observed.

Conclusion: Our findings suggest that silencing S100p not only can inhibit the in vitro and in vivo growth of PDAC, but also can sensitize PDAC towards gemcitabine treatment. Our result provides a promising alternative by targeting S100p in combinatorial chemotherapy development for pancreatic cancer .

Financial support: The work described in this paper was supported by grants from the General Research Fund, Research Grants Council of Hong Kong (CUHK462109, CUHK462713 and 14102714), National Natural Science Foundation of China (81101888) and Direct Grant from CUHK to YC.

Citation Format: Shing Chun Tang, Yangchao Chen.{Authors}. Targeting S100p Sensitizes Pancreatic Cancer Cells towards Gemcitabine. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A22.
Abstract A42: The stem cell signal Musashi is required for pancreatic cancer progression and therapy resistance
Authors: Lytle Nikki K. , Fox Raymond G. , Jaquish Dawn V. , Pham Nhat-Long , Frederick Park D. , Lowy Andrew M. , Reya Tannishtha
Published: December 2016

Pancreatic cancer is the 4th leading cause of cancer-related deaths in the United States due to advanced stage at diagnosis and poor response to current therapies. There is an urgent need to identify factors that contribute to tumor progression and drug resistance in order to develop novel, more effective therapeutic strategies. Here we show that the RNA binding protein Musashi2 (Msi2) is critically important for pancreatic tumorigenesis: genetic deletion of Msi2 slowed progression of premalignant lesions to adenocarcinoma in the KPf/fC mouse model of pancreatic cancer and led to a profound increase in overall survival. To better understand how Msi2 contributes to tumor progression, we developed a Msi2 reporter mouse and crossed it into the KPf/fC model. We found that Msi2-reporter positive tumor cells are preferentially able to propagate adenocarcinoma growth, and are highly enriched among circulating tumor cells. Importantly, our studies reveal that tumor cells expressing Msi2 are exceptionally resistant to chemotherapy and radiation. Collectively, these studies identify Msi2 as a central regulator of pancreatic cancer and raise the possibility that targeting Msi could be a new approach for the treatment of pancreatic cancer.

Citation Format: Nikki K. Lytle, Raymond G. Fox, Dawn V. Jaquish, Nhat-Long Pham, Park D. Frederick, Andrew M. Lowy, Tannishtha Reya.{Authors}. The stem cell signal Musashi is required for pancreatic cancer progression and therapy resistance. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A42.
Abstract A45: Neat1 is a p53-inducible lincRNA important for pancreatic cancer suppression
Authors: Mello Stephano S. , Sinow Carolyn , Mazur Pawel K. , Vogel Hannes , Rinn John , Attardi Laura D.
Published: December 2016

p53’s role as a critical tumor suppressor is well illustrated by the fact that it is found mutated in more than half of all human cancers. In addition, the highly penetrant cancer predisposition observed in Li-Fraumeni patients with germline mutations in p53 and in p53 null mice further highlight the importance of p53 in tumor suppression. p53 is a transcription factor, able to sense stress signals such as DNA damage and hyperproliferative signals, promoting in turn the expression of a network of target genes to induce anti-proliferative responses such as cell cycle arrest or apoptosis. Although studies of genes in the p53 network have largely focused on protein-coding genes, in recent years the role of p53-regulated non-coding (nc) RNAs in p53 biology has been increasingly recognized. To identify new p53-regulated ncRNAs that could contribute to tumor suppression, we leveraged chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing (RNA-seq) data we generated previously in p53 wild-type and p53-/- mouse embryonic fibroblasts (MEFs). This analysis uncovered the lincRNA Neat1 as a p53 target gene. We showed that Neat1 is induced by different DNA damaging agents in a p53-dependent manner in different mouse and human cell types, including pancreatic ductal cells. Although we found that Neat1 is not involved in DNA damage-induced p53-dependent cell cycle arrest or apoptosis responses, we found that it does play a role in p53-dependent transformation suppression in both oncogene-expressing fibroblasts and pancreatic cancer cells. Furthermore, using oncogene-expressing fibroblasts, we showed that Neat1 loss promotes cancer in vivo in a subcutaneous xenograft model. Preliminary evidence suggests also that Neat1 loss promotes acinar to ductal metaplasia, bolstering its importance in pancreatic cancer suppression. These findings highlight the importance of Neat1 for p53 tumor suppressor function. Detailed analyses of Neat1’s mechanism of action will provide insights in its function as a tumor suppressor.

Citation Format: Stephano S. Mello, Carolyn Sinow, Pawel K. Mazur, Hannes Vogel, John Rinn, Laura D. Attardi.{Authors}. Neat1 is a p53-inducible lincRNA important for pancreatic cancer suppression. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A45.
Abstract A56: Targeting eIF4A dependent translation as therapeutics in pancreatic cancer
Authors: Singh Kamini , Stark Stefan G. , Viale Agnes , Mohan Prathibha , Jiang Man , Rätsch Gunnar , Wendel Hans-Guido
Published: December 2016

Pancreatic cancer is one of the most aggressive cancers with no targeted therapy available. RNA translation is activated in aggressive pancreatic cancer and at the same time is also refractory to mTor inhibition. We have used a translation inhibitor for eIF4A, RNA helicase that is downstream of mTOR signaling and can be functionally targeted in pancreatic cancer. We establish that Silvestrol and its analog CR-31B showed potent anti-tumor activity in pancreatic cancer cell lines in vitro and in vivo. Silvestrol/CR-31B reduced pancreatic cancer cells and organoids growth derived from mouse model of pancreatic cancer and human patient samples in vitro. Further we identify the genome wide translational targets of Silvestrol in pancreatic cancer cell line that lacks response to mTOR signaling through loss of EIF4EBP1. Silvestrol down regulate translation of many key oncogenes and others cellular factors involved in oncogenic signaling in pancreatic cancer. Silvestrol targets were also enriched for G-quadruplex structure in their 5’UTR. With this study we establish a new mechanism of targeting pancreatic cancer cells through translation inhibition and identify more proteins as therapeutic targets that are regulated independent of mTOR signaling.

Citation Format: Kamini Singh, Stefan G. Stark, Agnes Viale, Prathibha Mohan, Man Jiang, Gunnar Rätsch, Hans-Guido Wendel.{Authors}. Targeting eIF4A dependent translation as therapeutics in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A56.
Abstract A59: Crosstalk of different macrophage populations with pancreatic acinar or PanIN cells and contribution to development of pancreatic cancer
Authors: Liou Geou-Yarh , Doeppler Heike , Bastea Ligia , Storz Peter
Published: December 2016

Pancreatic cancer is characterized by an inflammatory environment. Here we delineate the crosstalk between different macrophage populations with pancreatic cells carrying oncogenic Kras mutations. First, we show that pancreatic acinar cells that undergo oncogenic transformation by mutant Kras upregulate chemoattractants that attract inflammatory macrophages. These inflammatory macrophages contribute to acinar cell dedifferentiation to a progenitor-like cell type (acinar-to-ductal metaplasia; ADM). Resulting cells can give rise to PanIN lesions. We then provide insight at which stage of PanIN formation a switch between inflammatory and alternatively-activated macrophages occurs; and define one mechanism by which this can be mediated. Eventually, we provide insight of how alternatively-activated macrophages facilitate the further progression of PanIN lesions to a more aggressive phenotype.

Citation Format: Geou-Yarh Liou, Heike Doeppler, Ligia Bastea, Peter Storz.{Authors}. Crosstalk of different macrophage populations with pancreatic acinar or PanIN cells and contribution to development of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A59.
Abstract A66: Runx3 drives metastatic programs in pancreas cancer
Authors: Whittle Martin C. , Feng Libing , Dotson Ashley , Pakiam Fiona , Hingorani Sunil R.
Published: December 2016

The extreme proclivity of pancreatic ductal adenocarcinoma (PDA) for metastatic spread is the principal cause of mortality for this disease, even for patients who successfully undergo surgical resection of the primary tumor. We have engaged in a concerted effort to define the fundamental molecular and cellular drivers of PDA through the use of cognate genetically engineered mouse models that recapitulate the spectrum of human PDA. Recently, we incorporated conditional deletion of Smad4 into the KPC mouse model and noted a significant attenuation of metastatic burden in the resultant KPDC mice. Gene expression analysis identified the Runt family transcription factor Runx3 as highly expressed in metastatic KPC tumors, but minimally expressed in PDA from KPDC mice. We showed that aberrant expression of Runx3 strongly enhanced the metastatic potential of PDA through an orchestrated program that stimulated cancer cell invasion and migration and also helped generate a niche for disseminated cells to establish themselves in foreign tissues (such as the liver or lung) and form metastases. Runx3 expression additionally inhibited proliferation by upregulating expression of the cell cycle inhibitor Cdkn1a (p21), initiating a metastatic switch that favored PDA dissemination over local outgrowth. We have also identified influences of Runx3 expression on key developmental and immune-regulatory signaling pathways that are known to be aberrantly regulated in PDA. Because Runx3 has been shown to interact with Smad4 and p53, the genomic context of PDA expressing Runx3 critically modulates its function through de novo or altered protein complex formation. Defining the dichotomous, contextual roles of Runx3 as both a tumor “suppressor” and “promoter” may provide insight into the proximal cause of lethality in patients, thereby informing clinical prioritization of local versus systemic therapies for individual patients with PDA.

Citation Format: Martin C. Whittle, Libing Feng, Ashley Dotson, Fiona Pakiam, Sunil R. Hingorani.{Authors}. Runx3 drives metastatic programs in pancreas cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A66.
Abstract A91: Stage-specific transcriptome analysis of human pancreatic cancer progression
Authors: Kim Jungsun , Donahue Greg , Yang Wenli , Zaret Kenneth S.
Published: December 2016

Our goals are to discover gene networks that control the progression of pancreatic intraepithelial neoplasias (PanINs) to invasive stage pancreatic ductal adenocarcinoma (PDAC) and to understand how the pluripotency regulatory network can temporarily suppress the transition. Certain cancer cells are amenable to reprogramming to pluripotency by somatic cell nuclear transfer (SCNT) or defined transcription factors (iPS). Prior work showed that SCNT-cancer cells develop into normal appearing blastocysts, but later the cancer genome in SCNT-chimeric mice was reactivated during embryogenesis, re-expressing the cancer phenotype of the lineage from which they originated. We previously showed that when an iPS-like line, designated 10-22, derived from human pancreatic ductal adenocarcinoma (PDAC), was injected into immunodeficient mice, they consistently recapitulated pre-invasive, PanIN to invasive stages of PDAC (Kim et al., 2013 Cell Reports). Specifically, the PDAC-iPS cells differentiated into a ductal, PanIN2/3 epithelium with a collagen basement membrane, followed by progression to an invasive stage phenotype with basement membrane breakdown. Furthermore, the ductal cell lesions were surrounded by stroma that co-differentiated from the pluripotent 10-22 cells, indicative of signaling interactions with the epithelium. With this system, we now ask: 1) What gene regulatory networks for pluripotency can transiently attenuate the cancer genome; 2) Upon loss of pluripotency and differentiation, what are the regulatory network transitions during human PDAC progression? 3) What are the reciprocal signals between the PDAC epithelial cells and their surrounding stromal cells during pancreatic cancer progression? To address these questions, we have genetically tagged the PDAC-iPS 10-22 line with a lentiviral vector expressing a ubiquitous promoter driving GFP and a ductal K19 promoter driving infrared protein (iRFP), so that cells can be retrieved by FACS. While GFP+iRFP- cells include stroma derived from the 10-22 cells, GFP+iRFP+ allows isolation of precursor and invasive stages of PDAC. The tagged lines were injected into immunodeficient mice, the lesions were monitored in vivo by iRFP flourescence, and RNA was isolated in triplicate at multiple time points and subjected to RNA-Seq analysis. The human PDAC 10-22 cell system is being used to discover effectors and networks whereby pluripotency can dominate over cancer and new features of human PDAC progression, which would be ultimately used for developing novel cancer therapies.

Citation Format: Jungsun Kim, Greg Donahue, Wenli Yang, Kenneth S. Zaret.{Authors}. Stage-specific transcriptome analysis of human pancreatic cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A91.