bluuebunny/crossref_metadata_2025 huggingface dataset:
MultiCache: Multilayered Cache Implementation for I/O Virtualization
Authors: No Jaechun , Park Sung-soon
Published: August 2016

As the virtual machine technology is becoming the essential component in the cloud environment, VDI is receiving explosive attentions from IT market due to its advantages of easier software management, greater data protection, and lower expenses. However, I/O overhead is the critical obstacle to achieve high system performance in VDI. Reducing I/O overhead in the virtualization environment is not an easy task, because it requires scrutinizing multiple software layers of guest-to-hypervisor and also hypervisor-to-host. In this paper, we propose multilayered cache implementation, called MultiCache, which combines the guest-level I/O optimization with the hypervisor-level I/O optimization. The main objective of the guest-level optimization is to mitigate the I/O latency between the back end, shared storage, and the guest VM by utilizing history logs of I/O activities in VM. On the other hand, the hypervisor-level I/O optimization was implemented to minimize the latency caused by the “passing I/O path to the host” and the “contenting physical I/O device among VMs” on the same host server. We executed the performance measurement of MultiCache using the postmark benchmark to verify its effectiveness.
MicroRNA Expression Signature in Degenerative Aortic Stenosis
Authors: Shi Jing , Liu Hui , Wang Hui , Kong Xiangqing
Published: August 2016

Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n=4) and patients with degenerative AS (n=4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease.
Determination of the Elastic Behavior of Silicon Nanowires within a Scanning Electron Microscope
Authors: Wollschläger Nicole , Tasdemir Zuhal , Häusler Ines , Leblebici Yusuf , Österle Werner , Alaca B. Erdem
Published: July 2016

Three-point bending tests were performed on double-anchored,110silicon nanowire samples in the vacuum chamber of a scanning electron microscope (SEM) via a micromanipulator equipped with a piezoresistive force sensor. Nanowires with widths of 35 nm and 74 nm and a height of 168 nm were fabricated. The nanowires were obtained monolithically along with their 10 μm tall supports through a top-down fabrication approach involving a series of etching processes. The exact dimension of wire cross sections was determined by transmission electron microscopy (TEM). Conducting the experiments in an SEM chamber further raised the opportunity of the direct observation of any deviation from ideal loading conditions such as twisting, which could then be taken into consideration in simulations. Measured force-displacement behavior was observed to exhibit close resemblance to simulation results obtained by finite element modeling, when the bulk value of 169 GPa was taken as the modulus of elasticity for110silicon. Hence, test results neither show any size effect nor show evidence of residual stresses for the considered nanoscale objects. The increased effect of the native oxide with reduced nanowire dimensions was captured as well. The results demonstrate the potential of the developed nanowire fabrication approach for the incorporation in functional micromechanical devices.
Optimization on Emergency Resources Transportation Network Based on Bayes Risk Function: A Case Study
Authors: Zhu Changfeng , Fang Gang , Wang Qingrong
Published: July 2016

In order to coordinate the complex relationship between supplies distribution and path selection, some influential factors must be taken into account such as the insufficient remaining capacity of the road and uncertainty of travel time during supplies distribution and transportation. After the structure of emergency logistics network is analyzed, the travel time Bayes risk function of path and the total loss Bayes risk function of the disaster area are proposed. With the emergency supplies total transportation unit loss as the goal, an emergency logistics network optimization model under crowded conditions is established by the Bayes decision theory and solved by the improved ant colony algorithm. Then, a case of the model is validated to prove that the emergency logistics network optimization model is effective in congested conditions.
Preparation of Lanthanum Oxide and Lanthanum Oxycarbonate Layers on Titanium by Electrodeposition with Organic Solution
Authors: Choi Jeonghee , Chung Yong Hee
Published: August 2016

Layers of lanthanum oxide and lanthanum oxycarbonate were prepared on titanium by electrodeposition with organic solution. Four voltages ranging from 200 to 1000 V were applied for the electrodeposition at three concentrations of lanthanum ions. The organic solution was isobutanol and titanium foils were used as anodes and cathodes. Currents were monitored during the electrodeposition. Deposition layers were calcined at 700 K for 30 min or at 900 K for 60 and 200 min. The morphology and composition of the deposition layers were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Calcined deposition layers were assayed to be lanthanum oxycarbonate and lanthanum oxide. The average crystallite size was in the vicinity of 8 nm. Sizes of lanthanum oxycarbonate agglomerates in layers with 30 min electrodeposition and calcination at 700 K were ranging from 25 to 75 nm. Yields of lanthanum oxycarbonate at three concentrations of lanthanum ions were shown to be better at 400 V.
Evaluation of Hydrocalumite-Like Compounds as Catalyst Precursors in the Photodegradation of 2,4-Dichlorophenoxyacetic Acid
Authors: Sánchez-Cantú Manuel , Barcelos-Santiago Clara , Gomez Claudia M. , Ramos-Ramírez Esthela , Ruiz Peralta Ma. de Lourdes , Tepale Nancy , González-Coronel Valeria J. , Mantilla A. , Tzompantzi Francisco
Published: July 2016

Three hydrocalumite-like compounds in a Ca/Al ratio of 2 containing nitrate and acetate anions in the interlaminar region were prepared by a simple, economic, and environmentally friendly method. The solids were characterized by X-ray powder diffraction (XRD), thermogravimetric (TG) analysis, nitrogen adsorption-desorption at −196°C, scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and UV-Vis Diffuse Reflectance Spectroscopy (DRS). The catalytic activity of the calcined solids at 700°C was tested in the photodegradation of 2,4-dichlorophenoxyacetic acid (2,4-D) where 57% degradation of 2,4-D (40 ppm) and a mineralization percentage of 60% were accomplished within 150 minutes. The photocatalytic properties were attributed to mayenite hydration, since the oxide ions in the cages are capable of reacting with water to form hydroxide anions capable of breaking down the 2,4-D molecules.
Volumetric Magnetic Resonance Imaging Study of Brain and Cerebellum in Children with Cerebral Palsy
Authors: Kułak Piotr , Maciorkowska Elżbieta , Gościk Elżbieta
Published: August 2016

Introduction. Quantitative magnetic resonance imaging (MRI) studies are rarely used in the diagnosis of patients with cerebral palsy. The aim of present study was to assess the relationships between the volumetric MRI and clinical findings in children with cerebral palsy compared to control subjects.Materials and Methods. Eighty-two children with cerebral palsy and 90 age- and sex-matched healthy controls were collected.Results. The dominant changes identified on MRI scans in children with cerebral palsy were periventricular leukomalacia (42%) and posthemorrhagic hydrocephalus (21%). The total brain and cerebellum volumes in children with cerebral palsy were significantly reduced in comparison to controls. Significant grey matter volume reduction was found in the total brain in children with cerebral palsy compared with the control subjects. Positive correlations between the age of the children of both groups and the grey matter volumes in the total brain were found. Negative relationship between width of third ventricle and speech development was found in the patients. Positive correlations were noted between the ventricles enlargement and motor dysfunction and mental retardation in children with cerebral palsy.Conclusions. By using the voxel-based morphometry, the total brain, cerebellum, and grey matter volumes were significantly reduced in children with cerebral palsy.
On the Hyers-Ulam Stability of the First-Order Difference Equation
Authors: Jung Soon-Mo , Nam Young Woo
Published: August 2016

We prove Hyers-Ulam stability of the first-order difference equation of the formxi+1=F(i,xi), whereFis a given function with some moderate features. Moreover, we introduce some conditions for the functionFunder which the difference equation is not stable in the sense of Hyers and Ulam.
Bessel Equation in the Semiunbounded Intervalx∈[x0,∞]: Solving in the Neighbourhood of an Irregular Singular Point
Authors: Zhang Qing-Hua , Ma Jian , Qu Yuanyuan
Published: July 2016

This study expresses the solution of the Bessel equation in the neighbourhood ofx=∞as the product of a known-form singular divisor and a specific nonsingular function, which satisfies the corresponding derived equation. Considering the failure of the traditional irregular solution constructed with the power series, we adopt the corrected Fourier series with only limited smooth degree to approximate the nonsingular function in the interval[x0,∞]. In order to guarantee the series’ uniform convergence and uniform approximation to the derived equation, we introduce constraint and compatibility conditions and hence completely determine all undetermined coefficients of the corrected Fourier series. Thus, what we found is not an asymptotic solution atx→∞(not to mention a so-called formal solution), but a solution in the interval[x0,∞]with certain regularities of distribution. During the solution procedure, there is no limitation on the coefficient property of the equation; that is, the coefficients of the equation can be any complex constant, so that the solution method presented here is universal.
An Electrical Wave Height Measurement at Spatial Multipoint Locations in Liquid Dampers for Structural Vibration Mitigation
Authors: Kim Junhee , Jang Seok-Jung , Min Kyung-Won
Published: August 2016

Liquid dampers such as tuned liquid column dampers and tuned liquid dampers have been adopted to ensure serviceability of a vibratory building subjected to wind. In order to maximize efficiency of the vibration suppression, tuning frequency of the liquid dampers is supposed to be set to the first natural frequency of the building. Therefore, experimental evaluation of the natural frequency of liquid dampers is a primal factory task prior to their installation at the building. In this study, a novel liquid height measurement system based on variable resistance in an electric field is developed for observation of vertical motion of the liquid dampers. The proposed system can simultaneously measure the liquid height of multipoint locations in the electric field. In the experimental phase, natural frequency of the liquid dampers is experimentally evaluated utilizing the developed system. The performance of the proposed system is verified by comparison with the capacitive type wavemeter.
Solution of Strain-Softening Surrounding Rock in Deep Tunnel Incorporating 3D Hoek-Brown Failure Criterion and Flow Rule
Authors: Zou Jin-feng , Zuo Song-qing , Xu Yuan
Published: July 2016

In order to investigate the influence of the intermediate principal stress on the stress and displacement of surrounding rock, a novel approach based on 3D Hoek-Brown (H-B) failure criterion was proposed. Taking the strain-softening characteristic of rock mass into account, the potential plastic zone is subdivided into a finite number of concentric annulus and a numerical procedure for calculating the stress and displacement of each annulus was presented. Strains were obtained based on the nonassociated and associated flow rule and 3D plastic potential function. Stresses were achieved by the stress equilibrium equation and generalized Hoek-Brown failure criterion. Using the proposed approach, we can get the solutions of the stress and displacement of the surrounding rock considering the intermediate principal stress. Moreover, the proposed approach was validated with the published results. Compared with the results based on generalized Hoek-Brown failure criterion, it is shown that the plastic radius calculated by 3D Hoek-Brown failure criterion is smaller than those solved by generalized H-B failure criterion, and the influences of dilatancy effect on the results based on the generalized H-B failure criterion are greater than those based on 3D H-B failure criterion. The displacements considering the nonassociated flow rule are smaller than those considering associated flow rules.
A Practical Control Strategy for the Maglev Self-Excited Resonance Suppression
Authors: Li Jinhui , Fang Dong , Zhang Ding , Cai Ying , Ni Qi , Li Jie
Published: August 2016

This paper addresses the control strategy for the suppression of maglev vehicle-bridge interaction resonance, which worsens the ride comfort of vehicle and degrades the safety of the bridge. Firstly, a minimum model containing a flexible bridge and ten levitation units is presented. Based on the minimum model, we pointed out that magnetic flux feedback instead of the traditional current feedback is capable of simplifying the block diagram of the interaction system. Furthermore, considering the uncertainty of the bridge’s modal frequency, the stability of the interaction system is explored according to an improved root-locus technique. Motivated by the positive effects of the mechanical damping of bridges and the feedback channels’ difference between the levitation subsystem and the bridge subsystem, the increment of electrical damping by the additional feedback of vertical velocity of bridge is proposed and several related implementation issues are addressed. Finally, the numerical and experimental results illustrating the stability improvement are provided.
Positive Observer Design for Positive Delayed Markovian Jump Systems
Authors: Wang Guoliang
Published: July 2016

The positive observer design problem is considered for a class of positive delayed Markovian jump systems (PDMJSs). Firstly, a necessary and sufficient condition is established to check the positivity of delayed Markovian jump systems (DMJSs). Then, necessary and sufficient conditions for PDMJSs being asymptotically mean stable are established to be independent of time delay. Based on the proposed results, sufficient conditions for the existence of the desired positive observer gains including mode-independent case are provided. Additionally, more general cases that transition rate matrix (TRM) is partially unknown or uncertain are considered, respectively. Finally, a numerical example is used to demonstrate the effectiveness of the proposed methods.
SEFRE: Semiexoskeleton Rehabilitation System
Authors: Chonnaparamutt Winai , Supsi Witsarut
Published: August 2016

SEFRE (Shoulder-Elbow-Forearm Robotics Economic) rehabilitation system is presented in this paper. SEFRE Rehab System is composed of a robotic manipulator and an exoskeleton, so-called Forearm Supportive Mechanism (FSM). The controller of the system is developed as the Master PC consisting of five modules, that is, Intelligent Control (IC), Patient Communication (PC), Training with Game (TG), Progress Monitoring (PM), and Patient Supervision (PS). These modules support a patient to exercise with SEFRE in six modes, that is, Passive, Passive Stretching, Passive Guiding, Initiating Active, Active Assisted, and Active Resisted. To validate the advantages of the system, the preclinical trial was carried out at a national rehabilitation center. Here, the implement of the system and the preclinical results are presented as the verifications of SEFRE.
Characterization and Expression of Senescence Marker in Prolonged Passages of Rat Bone Marrow‐Derived Mesenchymal Stem Cells
Authors: Ridzuan Noridzzaida , Al Abbar Akram , Yip Wai Kien , Maqbool Maryam , Ramasamy Rajesh
Published: August 2016

The present study is aimed at optimizing the in vitro culture protocol for generation of rat bone marrow‐ (BM‐) derived mesenchymal stem cells (MSCs) and characterizing the culture‐mediated cellular senescence. The initial phase of generation and characterization was conducted using the adherent cells from Sprague Dawley (SD) rat’s BM via morphological analysis, growth kinetics, colony forming unit capacity, immunophenotyping, and mesodermal lineage differentiation. Mesenchymal stem cells were successfully generated and characterized as delineated by the expressions of CD90.1, CD44H, CD29, and CD71 and lack of CD11b/c and CD45 markers. Upon induction, rBM‐MSCs differentiated into osteocytes and adipocytes and expressed osteocytes and adipocytes genes. However, a decline in cell growth was observed at passage 4 onwards and it was further deciphered through apoptosis, cell cycle, and senescence assays. Despite the enhanced cell viability at later passages (P4‐5), the expression of senescence marker, β‐galactosidase, was significantly increased at passage 5. Furthermore, the cell cycle analysis has confirmed the in vitro culture‐mediated cellular senescence where cells were arrested at the G0/G1 phase of cell cycle. Although the currently optimized protocols had successfully yielded rBM‐MSCs, the culture‐mediated cellular senescence limits the growth of rBM‐MSCs and its potential use in rat‐based MSC research.
Current Psychopathological Symptoms in Children and Adolescents Who Suffered Different Forms of Maltreatment
Authors: De Rose Paola , Salvaguardia Fortunata , Bergonzini Paola , Cirillo Flavia , Demaria Francesco , Casini Maria Pia , Menghini Deny , Vicari Stefano
Published: August 2016

The aim of the present study is to evaluate the current psychopathological problems of different forms associated with maltreatment on children’s and adolescents’ mental health. Ninety-five females and ninety males with a mean age of 8.8 years who have suffered in the last six months different forms of abuse (physical, sexual, and emotional) and neglect were included in the study. The current reaction to trauma as directly observed by clinical instruments was examined. Differences in gender, age at the time of medical examination, familial psychiatric disorders, neuropsychiatric status, and type of maltreatment were also taken into account. Results documented that 95.1% of abused children and adolescents developed a psychiatric disorder or a subclinical form of a Posttraumatic Stress Disorder (PTSD). Moreover, our data demonstrate a role for gender, age, and familial psychiatric comorbidity in the current psychopathological problems associated with maltreatment. Overall, our findings can help clinicians make a diagnosis and provide efficient treatment and prevention strategies for child maltreatment and abuse.
Sorbents Coupled to Solar Light TiO2-Based Photocatalysts for Olive Mill Wastewater Treatment
Authors: Speltini Andrea , Maraschi Federica , Sturini Michela , Caratto Valentina , Ferretti Maurizio , Profumo Antonella
Published: July 2016

The aim of this work was to couple physical-chemical approaches with photocatalysis to reduce by a simple, inexpensive way the organic load of olive mill wastewater (OMW), mandatorily prior to the final discharge. Before irradiation, different sorbents were tested to remove part of the organic fraction, monitored by measuring chemical oxygen demand (COD) and polyphenols (PP). Different low-cost, safe materials were tested, that is, Y zeolite (ZY), montmorillonite, and sepiolite. Considerable decrease of organic load was obtained, with the highest abatement (40%) provided by ZY (10 g L−1in 1 : 10 OMW). Use of the three sorbents, in particular ZY, was convenient compared to commercial activated carbons. UV light photocatalytic tests, performed using P25 TiO2on ZY-treated OMW, yielded quantitative remediation (ca. 90%). Also solar light provided significative results, PP being lowered by 74% and COD by 56%. Sol-gel anatase TiO2and N-doped anatase TiO2were also tested, obtaining good results, around-80% PP and-40% COD. Finally, an integrated approach was experimented by ZY-supported anatase TiO2(TiO2@ZY). Thisphotoreactive sorbentallowedone-pottreatment of OMW significative abatements of PP (-77%) and COD (-39%) with only 1 g L−1material, under solar light.
A Novel Online Detection System for Wheelset Size in Railway Transportation
Authors: Cheng Xiaoqing , Chen Yuejian , Xing Zongyi , Li Yifan , Qin Yong
Published: July 2016

The online detection of wheelset size has important implications for ensuring the safety of railway operation and decreasing the maintenance costs. Based on laser displacement sensors (LDS), a novel online detection system of the wheel size is proposed using only six two-dimensional LDS and two one-dimensional LDS. The calculation principles of tread profile and wheel diameter are given, as well as the calibration method. Errors induced by wheel-rail vibration, misalignment, sensor noise, S-shape running, and wheelset differential are also analyzed. After system implementation, field experiments were performed using both standard wheel and several real trains. It turns out that the detection uncertainty of flange width and height is 0.1 mm and wheel diameter 0.3 mm, which can meet the requirements of maintenance.
An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma
Authors: Teh Jessica L.F. , Purwin Timothy J. , Greenawalt Evan J. , Chervoneva Inna , Goldberg Allison , Davies Michael A. , Aplin Andrew E.
Published: August 2016

Aberrant cell-cycle progression is a hallmark feature of cancer cells. Cyclin-dependent kinases 4 and 6 (CDK4/6) drive progression through the G1 stage of the cell cycle, at least in part, by inactivating the tumor suppressor, retinoblastoma. CDK4/6 are targetable and the selective CDK4/6 inhibitor, palbociclib, was recently FDA approved for the treatment of estrogen receptor–positive, HER2-negative advanced breast cancer. In cutaneous melanoma, driver mutations in NRAS and BRAF promote CDK4/6 activation, suggesting that inhibitors such as palbociclib are likely to provide therapeutic benefit in combination with BRAF inhibitors and/or MEK inhibitors that are FDA-approved. However, the determinants of the response to CDK4/6 inhibitors alone and in combination with other targeted inhibitors are poorly defined. Furthermore, in vivo systems to quantitatively and temporally measure the efficacy of CDK4/6 inhibitors and determine the extent that CDK activity is reactivated during acquired resistance are lacking. Here, we describe the heterogeneous effects of CDK4/6 inhibitors, the expression of antiapoptotic proteins that associate with response to CDK4/6 and MEK inhibitors, and the development of a luciferase-based reporter system to determine the effects of CDK4/6 inhibitors alone and in combination with MEK inhibitors in melanoma xenografts. These findings are likely to inform on-going and future clinical trials utilizing CDK4/6 inhibitors in cutaneous melanoma. Cancer Res; 76(18); 5455–66. ©2016 AACR.
Inducing Differentiation of Premalignant Hepatic Cells as a Novel Therapeutic Strategy in Hepatocarcinoma
Authors: Wolf Benita , Krieg Kathrin , Falk Christine , Breuhahn Kai , Keppeler Hildegard , Biedermann Tilo , Schmid Evi , Warmann Steven , Fuchs Joerg , Vetter Silvia , Thiele Dennis , Nieser Maike , Avci-Adali Meltem , Skokowa Yulia , Schöls Ludger , Hauser Stefan , Ringelhan Marc , Yevsa Tetyana , Heikenwalder Mathias , Kossatz-Boehlert Uta
Published: August 2016

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related deaths and is reported to be resistant to chemotherapy caused by tumor-initiating cells. These tumor-initiating cells express stem cell markers. An accumulation of tumor-initiating cells can be found in 2% to 50% of all HCC and is correlated with a poor prognosis. Mechanisms that mediate chemoresistance include drug export, increased metabolism, and quiescence. Importantly, the mechanisms that regulate quiescence in tumor-initiating cells have not been analyzed in detail so far. In this research we have developed a single cell tracking method to follow up the fate of tumor-initiating cells during chemotherapy. Thereby, we were able to demonstrate that mCXCL1 exerts cellular state-specific effects regulating the resistance to chemotherapeutics. mCXCL1 is the mouse homolog of the human IL8, a chemokine that correlates with poor prognosis in HCC patients. We found that mCXCL1 blocks differentiation of premalignant cells and activates quiescence in tumor-initiating cells. This process depends on the activation of the mTORC1 kinase. Blocking of the mTORC1 kinase induces differentiation of tumor-initiating cells and allows their subsequent depletion using the chemotherapeutic drug doxorubicin. Our work deciphers the mCXCL1–mTORC1 pathway as crucial in liver cancer stem cell maintenance and highlights it as a novel target in combination with conventional chemotherapy. Cancer Res; 76(18); 5550–61. ©2016 AACR.
Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk
Authors: Patel Yesha M. , Park Sunghim L. , Han Younghun , Wilkens Lynne R. , Bickeböller Heike , Rosenberger Albert , Caporaso Neil , Landi Maria Teresa , Brüske Irene , Risch Angela , Wei Yongyue , Christiani David C. , Brennan Paul , Houlston Richard , McKay James , McLaughlin John , Hung Rayjean , Murphy Sharon , Stram Daniel O. , Amos Christopher , Le Marchand Loïc
Published: August 2016

Metabolism of nicotine by cytochrome P450 2A6 (CYP2A6) is a suspected determinant of smoking dose and, consequently, lung cancer risk. We conducted a genome-wide association study (GWAS) of CYP2A6 activity, as measured by the urinary ratio of trans-3′-hydroxycotinine and its glucuronide conjugate over cotinine (total 3HCOT/COT), among 2,239 smokers in the Multiethnic Cohort (MEC) study. We identified 248 CYP2A6 variants associated with CYP2A6 activity (P < 5 × 10−8). CYP2A6 activity was correlated (r = 0.32; P < 0.0001) with total nicotine equivalents (a measure of nicotine uptake). When we examined the effect of these variants on lung cancer risk in the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium GWAS dataset (13,479 cases and 43,218 controls), we found that the vast majority of these individual effects were directionally consistent and associated with an increased lung cancer risk. Two hundred and twenty-six of the 248 variants associated with CYP2A6 activity in the MEC were available in TRICL. Of them, 81% had directionally consistent risk estimates, and six were globally significantly associated with lung cancer. When conditioning on nine known functional variants and two deletions, the top two SNPs (rs56113850 in MEC and rs35755165 in TRICL) remained significantly associated with CYP2A6 activity in MEC and lung cancer in TRICL. The present data support the hypothesis that a greater CYP2A6 activity causes smokers to smoke more extensively and be exposed to higher levels of carcinogens, resulting in an increased risk for lung cancer. Although the variants identified in these studies may be used as risk prediction markers, the exact causal variants remain to be identified. Cancer Res; 76(19); 5768–76. ©2016 AACR.
TG2 and NF-κB Signaling Coordinates the Survival of Mantle Cell Lymphoma Cells via IL6-Mediated Autophagy
Authors: Zhang Han , Chen Zheng , Miranda Roberto N. , Medeiros L. Jeffrey , McCarty Nami
Published: August 2016

Expression of the transglutaminase TG2 has been linked to constitutive activation of NF-κB and chemotherapy resistance in mantle cell lymphoma (MCL) cells. TG2 forms complexes with NF-κB components, but mechanistic insights that could be used to leverage therapeutic responses has been lacking. In the current study, we address this issue with the discovery of an unexpected role for TG2 in triggering autophagy in drug-resistant MCL cells through induction of IL6. CRISPR-mediated silencing of TG2 delayed apoptosis while overexpressing TG2 enhanced tumor progression. Under stress, TG2 and IL6 mediate enhanced autophagy formation to promote MCL cell survival. Interestingly, the autophagy product ATG5 involved in autophagosome elongation positively regulated TG2/NF-κB/IL6 signaling, suggesting a positive feedback loop. Our results uncover an interconnected network of TG2/NF-κB and IL6/STAT3 signaling with autophagy regulation in MCL cells, the disruption of which may offer a promising therapeutic strategy. Cancer Res; 76(21); 6410–23. ©2016 AACR.
The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma
Authors: Sandhu Vandana , Wedge David C. , Bowitz Lothe Inger Marie , Labori Knut Jørgen , Dentro Stefan C. , Buanes Trond , Skrede Martina L. , Dalsgaard Astrid M. , Munthe Else , Myklebost Ola , Lingjærde Ole Christian , Børresen-Dale Anne-Lise , Ikdahl Tone , Van Loo Peter , Nord Silje , Kure Elin H.
Published: August 2016

Despite advances in diagnostics, less than 5% of patients with periampullary tumors experience an overall survival of five years or more. Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater, an enlargement of liver and pancreas ducts where they join and enter the small intestine. In this study, we analyzed copy number aberrations using Affymetrix SNP 6.0 arrays in 60 periampullary adenocarcinomas from Oslo University Hospital to identify genome-wide copy number aberrations, putative driver genes, deregulated pathways, and potential prognostic markers. Results were validated in a separate cohort derived from The Cancer Genome Atlas Consortium (n = 127). In contrast to many other solid tumors, periampullary adenocarcinomas exhibited more frequent genomic deletions than gains. Genes in the frequently codeleted region 17p13 and 18q21/22 were associated with cell cycle, apoptosis, and p53 and Wnt signaling. By integrating genomics and transcriptomics data from the same patients, we identified CCNE1 and ERBB2 as candidate driver genes. Morphologic subtypes of periampullary adenocarcinomas (i.e., pancreatobiliary or intestinal) harbor many common genomic aberrations. However, gain of 13q and 3q, and deletions of 5q were found specific to the intestinal subtype. Our study also implicated the use of the PAM50 classifier in identifying a subgroup of patients with a high proliferation rate, which had impaired survival. Furthermore, gain of 18p11 (18p11.21-23, 18p11.31-32) and 19q13 (19q13.2, 19q13.31-32) and subsequent overexpression of the genes in these loci were associated with impaired survival. Our work identifies potential prognostic markers for periampullary tumors, the genetic characterization of which has lagged. Cancer Res; 76(17); 5092–102. ©2016 AACR.
Monocyte Induction of E-Selectin–Mediated Endothelial Activation Releases VE-Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade
Authors: Häuselmann Irina , Roblek Marko , Protsyuk Darya , Huck Volker , Knopfova Lucia , Grässle Sandra , Bauer Alexander T. , Schneider Stefan W. , Borsig Lubor
Published: August 2016

Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell–activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin–deficient mice. Tumor cell–derived CCL2 promoted endothelial activation, resulting in enhanced endothelial E-selectin expression. The recruitment of inflammatory monocytes to metastasizing tumor cells was dependent on the local endothelial activation and the presence of E-selectin. Monocytes promoted transendothelial migration of tumor cells through the induction of E-selectin–dependent endothelial retractions and a subsequent modulation of tight junctions through dephosphorylation of VE-cadherin. Thus, endothelial E-selectin shapes the tumor microenvironment through the recruitment, adhesion, and activation of monocytes that facilitate tumor cell extravasation and thereby metastasis. These findings provide evidence that endothelial E-selectin is a novel factor contributing to endothelial retraction required for efficient lung metastasis. Cancer Res; 76(18); 5302–12. ©2016 AACR.
ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet–associated Colon Cancer
Authors: Mustafi Reba , Dougherty Urszula , Mustafi Devkumar , Ayaloglu-Butun Fatma , Fletcher Michelle , Adhikari Sarbani , Sadiq Farhana , Meckel Katherine , Haider Haider I. , Khalil Abdurahman , Pekow Joel , Konda Vani , Joseph Loren , Hart John , Fichera Alessandro , Li Yan Chun , Bissonnette Marc
Published: August 2016

Purpose: Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein–coupled receptors, including CXCR4. Here we investigated CXCR4–ADAM17 crosstalk and examined the role of ADAM17 in tumorigenesis.

Experimental Design: We used CXCR4 inhibitor, AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4–ADAM17 crosstalk in colon cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in mice fed Western diet versus standard diet. Separately, mice were treated with marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from primary human colon cancers and adjacent mucosa.

Results: CXCL12 treatment activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced this activation. In vivo, Western diet increased CXCL12 in stromal cells and TGFα in colonocytes. Marimastat or AMD3100 caused >50% reduction in EGFR signals (P < 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and inhibited intestinal tumor multiplicity (P < 0.05). In the AOM model, colonocyte ADAM17 deletion reduced EGFR signals and colonic tumor development (P < 0.05). Finally, ADAM17 was upregulated >2.5-fold in human malignant colonocytes.

Conclusions: ADAM17 is a Western diet–inducible enzyme activated by CXCL12–CXCR4 signaling, suggesting the pathway: Western diet→CXCL12→CXCR4→ADAM17→TGFα→EGFR. ADAM17 might serve as a druggable target in chemoprevention strategies. Clin Cancer Res; 23(2); 549–61. ©2016 AACR.
Glasgow Gloom or Leeds Glue? Dialect-Specific Vowel Duration Constrains Lexical Segmentation and Access
Authors: Smith Rachel , Rathcke Tamara
Published: August 2016

Timing cues are important in many aspects of speech processing, fromidentifying segments to locating word and phrase boundaries. They vary across accents, yet representation and processing of this variation are poorly understood. We investigated whether an accent difference in vowel duration affects lexical segmentation and access. In Glasgow English (GE), /i u e o/ are shorter than in Leeds English (LE), especially for /i u/ before voiced stops and nasals. In a word-spotting experiment, GE and LE participants heard nonsense sequences (e.g. pobegloomezh) containing embedded words (gloom, glue), with segmental qualities intermediate between GE and LE. Critical vowel durations were manipulated according to accent (GE-appropriate vowels shorter than LE-appropriate ones) and phonological context (vowels shortest before voiceless stops < voiced stops/nasals < voiced fricatives). GE participants generally spotted words like gloom more accurately with GE-appropriate than LE-appropriate vowels. LE participants were less accurate than GE participants to spot words like gloom with GE-appropriate vowels, but more likely to spot embeddings like glue. These results were broadly as predicted based on the accent differences, but depended less than expected on the accent-specific phonological constraints. We discuss theoretical implications regarding the representation of duration and the time course of lexical access.
Neonatal Acute Kidney Injury and the Risk of Intraventricular Hemorrhage in the Very Low Birth Weight Infant
Authors: Stoops Christine , Sims Brian , Griffin Russell , Askenazi D.J.
Published: August 2016

Despite improvements in survival of premature infants, many have comorbid conditions. The role of the kidney in multiorgan dysfunction is unclear, particularly in regard to intraventricular hemorrhage (IVH). We hypothesized that infants diagnosed with acute kidney injury (AKI) have an increased risk of IVH independent of gestational age (GA) and other variables associated with both comorbidities. This prospective cohort study consisted of 125 infants with a birth weight ≤1,200 g and/or GA ≤31 weeks. A definition of AKI was used from KDIGO, not including urine output as nonoliguria is common in this population. IVH was based on serial head ultrasounds. Neonates with AKI had a higher trend towards having IVH compared to those without [14/35 (40%) vs. 22/83 (26.5%), p = 0.1]. Infants with AKI were more likely to have stage 2 IVH or higher than those without AKI [12/36 (33.3%) vs. 6/82 (7.3%); p < 0.01]. AKI was associated with a 3.6-fold increased risk of a grade 2 or higher IVH [hazard ratio (HR) 3.55, 95% confidence interval (CI) 1.39-9.07] and over 4-fold increase in risk of a grade 3 or higher IVH (HR 4.34, 95% CI 1.43-13.21). While there was no association between AKI and IVH overall, those with AKI had a higher hazard ratio to develop a grade 2 or higher IVH even when controlling for birth weight, antenatal steroid use, and 5-min Apgar score. Future studies are indicated to expand sample size and to control for other clinical variables that could be associated with both AKI and IVH.
Preoperative Predictors in Chronic Suppurative Otitis Media for Ossicular Chain Discontinuity: A Cross-Sectional Study
Authors: Sheikh Rashid , Haidar Hassan , Abdulkarim Hassanin , Aslam Waqar , Larem Aisha , Alsaadi Ali , Alqahtani Abdulsalam
Published: August 2016

Objective: Ossicular discontinuity may result from chronic suppurative otitis media and is usually detected intraoperatively. Our objective is to determine whether a preoperative audiogram can preoperatively predict the presence or absence of ossicular discontinuity. Methods: A cross-sectional study was prospectively run on our patients, aged 12-75 years, ultimately operated on for chronic suppurative otitis media. Preoperative audiograms were analyzed to measure frequency-specific air-bone gap (ABG) cutoff values. Intraoperatively, ossicular chain integrity was carefully checked. Logistic regression analysis was done to obtain a predictive model. Results: A total of 270 patients (306 ears) were included. Frequency-specific ABG cutoff values can predict ossicular discontinuity, namely: high ABGs at 1,000 Hz (>27.5 dB) and 2,000 Hz (>17.5 dB) are the most reliable variables associated with ossicular discontinuity. Conclusion: Preoperative audiograms can predict the presence of ossicular discontinuity in chronic suppurative otitis media. Large ABGs at both 1,000 and 2,000 Hz can predict ossicular discontinuity with a great degree of certainty.
Leveraging Methylome-Environment Interaction to Detect Genetic Determinants of Disease
Authors: Slade Emily , Kraft Peter
Published: August 2016

Objective: The association between DNA methylation and a trait of interest may depend on an environmental exposure, and incorrectly accounting for this dependence can lead to a reduction in power of the standard tests used in epigenome-wide association studies. We present the M-ME test to jointly test for the main effect of DNA methylation and methylation-environment interaction. Methods: Through simulation, we compare the power and type 1 error of the M-ME test to a standard marginal test (M test) and a standard interaction test (ME test) under 1,800 different underlying models. These models allow for methylation-environment correlation and measurement error in the exposure. Results: In many true underlying models, either the M test or the ME test has very low power, but the M-ME test has optimal or nearly optimal power to detect a DNA methylation effect in all models considered, including those with methylation- environment dependence and measurement error in the exposure. Type 1 error inflation occurs in the tests when the exposure is measured with error and correlated with DNA methylation. Conclusion: The M-ME test is an attractive choice for studies aiming to detect any DNA methylation association when little is known about the epigenetic associations a priori.
Frontal Alopecia after Repeated Botulinum Toxin Type A Injections for Forehead Wrinkles: An Underestimated Entity?
Authors: Di Pietro Antonino , Piraccini Bianca Maria
Published: August 2016

Background: Injections of botulinum toxin type A in the forehead have never been reported to cause hair side effects. Objective: The aim of this paper is to report a new type of alopecia, which we have seen in women undergoing periodic injections of botulinum toxin type A for forehead wrinkles, and to differentiate it from other types of hair loss. Methods: We conducted an observational study on 5 females recruited from a private and an institutional practice who complained of progressive recession of the hairline after periodic injections of botulinum toxin type A in the forehead. Results: Alopecia of the frontal hairline was evident in all 5 patients, with absence of skin atrophy or scarring and progressive hair miniaturization at trichoscopy. Conclusion: Dermatologists should be aware of the possible occurrence of frontal alopecia after repeated injections of botulinum toxin type A for forehead wrinkles.
Shifting from Enrollment- to Performance-Based Funding in Higher Education: What Can We Learn from Washington's Experience?
Authors: Kaikkonen Darby
Published: August 2016

Performance-based funding (PBF) in higher education has grown in recent years as a means of institutional accountability and incentive for improving student success. Although most states have successfully implemented their respective systems, research on early funding models suggests a difficult fiscal environment can introduce tension between theory and practice of the concept. This policy brief uses the case of Washington State's redesign of the Student Achievement Initiative to describe new implications around this tension. The revision focused on using a base reallocation as the funding source in the context of diminished state resources and the importance of college buy-in. Regression analyses tested the alignment between the principles and metrics for awarding funds, which resulted in a funding model that awarded the maximum dollars related to performance versus college characteristics. Policy makers considering new or revised PBF systems can benefit from critical lessons learned from Washington State's comprehensive process and final product.
What Do University Endowment Managers Worry About? An Analysis of Alternative Asset Investments and Background Income
Authors: Rosen Harvey S. , Sappington Alexander J. W.
Published: August 2016

This paper examines whether university endowment managers think only in terms of the assets they manage or also take into account background income, that is, the other flows of income to the university. Specifically, we test whether the level and variability of a university's background income (e.g., from tuition and government grants) affect its endowment's allocations to so-called alternative assets, such as hedge funds, private equity, and venture capital. We find that both the probability of investing in alternative assets and the proportion of the portfolio invested in such assets increase with expected background income and decrease with its variability.
A preliminary checklist of the skippers (Rhopalocera: Hesperiidae) of Guangxi, China
Authors: XUE GUO-XI , SUN HAO , SUN ZHOU , WANG SHAO-NENG
Published: August 2016

A survey of the literature shows that a total of 64 genera comprising 155 species/subspecies of skippers have been recorded in Guangxi. Based on a field survey and the examination of specimens, 1 subspecies, Burara gomata gomata (Moore, 1866), is recorded as new to China, and 1 species, Celaenorrhinus vietnamicus Devyatkin, 1998, is reported in Guangxi for the first time. Therefore, to date, a total of 57 genera with 109 species/subspecies in 4 subfamilies of Hesperiidae have been positively identified as the fauna of Guangxi. Four genera and 42 species/subspecies are considered as requiring confirmation, and 3 genera and 6 species/subspecies are excluded. Some taxonomic notes are provided when necessary.
The Seasonal Cycle of the Radiation Budget and Cloud Radiative Effect in the Amazon Rain Forest of Brazil
Authors: Marquardt Collow Allison B. , Miller Mark A.
Published: August 2016

Changes in the climate system of the Amazon rain forest of Brazil can impact factors that influence the radiation budget such as clouds, atmospheric moisture, and the surface albedo. This study examines the relationships between clouds and radiation in this region using surface observations from the first year of the deployment of the Atmospheric Radiation Measurement (ARM) Program’s Mobile Facility 1 (AMF1) in Manacapuru, Brazil, and satellite measurements from the Clouds and the Earth’s Radiant Energy System (CERES). The seasonal cycles of the radiation budget and cloud radiative effects (CREs) are evaluated at the top of the atmosphere (TOA), at the surface, and within the atmospheric column using these observations and are placed into a regional context using the Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2). Water vapor and clouds are abundant throughout the year, even though slight decreases are observed in the dry season. The column water vapor load is large enough that the longwave radiative flux divergence is nearly constant throughout the year. Clouds produce a significant shortwave CRE at the surface and TOA, exceeding 200 W m−2 during the wet season. Discrepancies, especially in column shortwave radiative absorption, between the observations and MERRA-2 are demonstrated that warrant additional analysis of the microphysical and macrophysical cloud properties in MERRA-2. More trustworthy fields in the MERRA-2 product suggest that the expansive nearby river system impacts the regional radiation budget and thereby renders AMF1 observations potentially biased relative to regions farther removed from rivers within the Amazon rain forest.