bluuebunny/crossref_metadata_2025 huggingface dataset:
Constraints on the birth of the universe and origin of cosmic dark flow
Authors: Mathews G. J. , Gangopadhyay M. R. , Garnavich P. , Rose B. , Ichiki K. , Kajino T. , Yamazaki Dai
Published: October 2015

We summarize three recent efforts to constrain the first few moments of cosmic creation before and during the epoch of inflation. We consider two means to explain a slight dip in the power spectrum of the cosmic microwave background for multipoles in the range of [Formula: see text] from both the Planck and WMAP data. We show that such a dip could be the result of resonant creation of a massive particle that couples to the inflaton field. For best-fit models, the epoch of resonant particle creation reenters the horizon at wave numbers of [Formula: see text]. The amplitude and location of these features correspond to the creation of a number of degenerate fermion species of mass [Formula: see text] during inflation where [Formula: see text] is the coupling constant between the inflaton field and the created fermion species. Alternatively, one can explain the existence of such a dip as due to a jump in the inflation generating potential. We show that such a jump can also resolve the excessively large dark flow predicted from the M-theory landscape. Finally, we summarize our efforts to quantify constraints on the cosmic dark flow from a new analysis of the Type Ia supernova distance-redshift relation.
NBC: An Efficient Hierarchical Clustering Algorithm for Large Datasets
Authors: Zhang Wei , Zhang Gongxuan , Wang Yongli , Zhu Zhaomeng , Li Tao
Published: October 2015

Nearest neighbor search is a key technique used in hierarchical clustering and its computing complexity decides the performance of the hierarchical clustering algorithm. The time complexity of standard agglomerative hierarchical clustering is O(n3), while the time complexity of more advanced hierarchical clustering algorithms (such as nearest neighbor chain, SLINK and CLINK) is O(n2). This paper presents a new nearest neighbor search method called nearest neighbor boundary (NNB), which first divides a large dataset into independent subset and then finds nearest neighbor of each point in subset. When NNB is used, the time complexity of hierarchical clustering can be reduced to O(n log 2n). Based on NNB, we propose a fast hierarchical clustering algorithm called nearest-neighbor boundary clustering (NBC), and the proposed algorithm can be adapted to the parallel and distributed computing framework. The experimental results demonstrate that our algorithm is practical for large datasets.
Semantic Economic Models for Bioenergy Projects
Authors: Sapkota Krishna , Raju Pathmeswaran , Byrne Will , Chapman Craig
Published: October 2015

One of the sustainable solutions to the depleting fossils fuels is bioenergy, which is a renewable energy generated from biomass, and biofuel is a hydrocarbon fuel that is produced from biomass. Recently, bioenergy and biofuel projects are encouraged and supported by many governments and organizations in various ways such as providing incentives, technical supports, information, and decision support tools. The economic model is one of the decision support tools, which helps to estimate the costs and earnings involved in a project. It is constructed with various elements such as concepts, relations, logics, constants, and equations. In current economic models, all the elements are hard-coded into some programming code, which makes the model less reusable and extendable. To address the issue, we present an ontology-based economic model in this paper. In particular, we have leveraged the Semantic Web technologies to represent the knowledge about the bioenergy and biofuel economics and inferred the equations and other values required for economic calculations. The case study has been carried out in two of the INTERREG Projects and found promising results.
Semantic Computing for Education
Authors: Jin Jennifer , Kim Mira , Rivett Pete
Published: October 2015

There are challenges educators face in delivering the vast amount of teaching material to students. Using ontologies could solve some of these issues. We survey different types of ontologies available that could aid educators teach students. We discuss how ontologies may help improve the education system for K-12, higher education, curriculum creating, e-learning, etc. We analyze the efficacy of the ontologies available as well as the challenges educators face and how to make improvements.
Skylight—A Window on Shingled Disk Operation
Authors: Aghayev Abutalib , Shafaei Mansour , Desnoyers Peter
Published: October 2015

We introduce Skylight, a novel methodology that combines software and hardware techniques to reverse engineer key properties of drive-managed Shingled Magnetic Recording (SMR) drives. The software part of Skylight measures the latency of controlled I/O operations to infer important properties of drive-managed SMR, including type, structure, and size of the persistent cache; type of cleaning algorithm; type of block mapping; and size of bands. The hardware part of Skylight tracks drive head movements during these tests, using a high-speed camera through an observation window drilled through the cover of the drive. These observations not only confirm inferences from measurements, but resolve ambiguities that arise from the use of latency measurements alone. We show the generality and efficacy of our techniques by running them on top of three emulated and two real SMR drives, discovering valuable performance-relevant details of the behavior of the real SMR drives.
Active workspaces
Authors: Badouel Eric , Hélouët Loïc , Kouamou Georges-Edouard , Morvan Christophe , Fondze Nsaibirni Robert
Published: October 2015

This paper presents a purely declarative approach to artifact-centric collaborative systems, a model which we introduce in two stages. First, we assume that the workspace of a user is given by a mindmap, shortened to a map, which is a tree used to visualize and organize tasks in which he or she is involved, with the information used for the resolution of these tasks. We introduce a model of
guarded attribute grammar
, or GAG, to help the automation of updating such a map. A GAG consists of an underlying grammar, that specifies the logical structure of the map, with semantic rules which are used both to govern the evolution of the tree structure (how an open node may be refined to a subtree) and to compute the value of some of its attributes (which derives from contextual information). The map enriched with this extra information is termed an
active workspace.
Second, we define collaborative systems by making the various user's active workspaces communicate with each other. The communication uses message passing without shared memory thus enabling convenient distribution on an asynchronous architecture. We present some formal properties of the model of guarded attribute grammars, then a language for their specification and we illustrate the approach on a case study for a disease surveillance system.
Highly Sensitive Hydrazine Chemical Sensor Based on CNT‐PdPt Nanocomposites
Authors: Kim Sung Phil , Lee Seul Gi , Choi Myong Yong , Choi Hyun Chul
Published: October 2015

Bimetallic PdPt nanoparticles were prepared using the chemical reduction method. The PdPt nanoparticles were successfully deposited on thiolated carbon nanotubes (CNTs) to form a CNT‐PdPt nanocomposite as an electron mediator for the fabrication of a hydrazine sensor. The PdPt nanoparticles had an average particle size of 2.3 nm and were well dispersed on the surfaces of the CNTs in the prepared CNT‐PdPt nanocomposite, as demonstrated using transmission electron microscopy (TEM), energy dispersive X‐ray spectroscopy (EDX), and X‐ray diffraction (XRD). Based on X‐ray photoelectron spectroscopy (XPS) results, the estimated proportions of Pd and Pt in the CNT‐PdPt nanocomposite were approximately 3.0% and 3.2%, respectively. A fabricated chemical sensor based on CNT‐PdPt was found to exhibit better amperometric activity with respect to the hydrazine oxidation reaction than CNT‐Pd, CNT‐Pt, and commercial Pd/C and Pt/C catalysts. This sensor exhibited a linear range of 0.55–1,200 μM and a detection limit of 0.28 μM (S/N = 3) with a fast response time (within 5 s). Furthermore, the sensor could be used repeatedly for the consecutive detection of hydrazine with good reusability and storage stability. These properties demonstrate that the CNT‐PdPt nanocomposite is a promising electron mediator for the fabrication of amperometric hydrazine sensors.
Molecular Features and Methylation Status in Early Onset (≤40 Years) Colorectal Cancer: A Population Based, Case-Control Study
Authors: Magnani Giulia , Furlan Daniela , Sahnane Nora , Reggiani Bonetti Luca , Domati Federica , Pedroni Monica
Published: October 2015

Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression,KRASandBRAFmutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair,APCandMUTYHgenes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%).KRASmutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02). Finally both of the two groups were highly methylated inESR1,GATA5, andWT1genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation ofESR1,GATA5, andWT1genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.
Effect of EDTA Conditioning and Carbodiimide Pretreatment on the Bonding Performance of All-in-One Self-Etch Adhesives
Authors: Singh Shipra , Nagpal Rajni , Tyagi Shashi Prabha , Manuja Naveen
Published: October 2015

Objective. This study evaluated the effect of ethylenediaminetetraacetic acid (EDTA) conditioning and carbodiimide (EDC) pretreatment on the shear bond strength of two all-in-one self-etch adhesives to dentin.Methods. Flat coronal dentin surfaces were prepared on one hundred and sixty extracted human molars. Teeth were randomly divided into eight groups according to two different self-etch adhesives used [G-Bond and OptiBond-All-In-One] and four different surface pretreatments: (a) adhesive applied following manufacturer’s instructions; (b) dentin conditioning with 24% EDTA gel prior to application of adhesive; (c) EDC pretreatment followed by application of adhesive; (d) application of EDC on EDTA conditioned dentin surface followed by application of adhesive. Composite restorations were placed in all the samples. Ten samples from each group were subjected to immediate and delayed (6-month storage in artificial saliva) shear bond strength evaluation. Data collected was subjected to statistical analysis using three-way ANOVA and post hoc Tukey’s test at a significance level ofp<0.05.  Results and Conclusion. EDTA preconditioning as well as EDC pretreatment alone had no significant effect on the immediate and delayed bond strengths of either of the adhesives. However, EDC pretreatment on EDTA conditioned dentin surface resulted in preservation of resin-dentin bond strength of both adhesives with no significant fall over six months.
Wireless Body Area Networks for Healthcare Applications: Protocol Stack Review
Authors: Filipe Luis , Fdez-Riverola Florentino , Costa Nuno , Pereira António
Published: October 2015

Wireless Body Area Networks (WBANs) supporting healthcare applications are in early development stage but offer valuable contributions at monitoring, diagnostic, or therapeutic levels. They cover real-time medical information gathering obtained from different sensors with secure data communication and low power consumption. As a consequence of the increasing interest in the application of this type of networks, several articles dealing with different aspects of such systems have been published recently. In this paper, we compile and compare technologies and protocols published in the most recent researches, seeking WBAN issues for medical monitoring purposes to select the most useful solutions for this area of networking. The most important features under consideration in our analysis include wireless communication protocols, frequency bands, data bandwidth, transmission distance, encryption, authentication methods, power consumption, and mobility. Our study demonstrates that some characteristics of surveyed protocols are very useful to medical appliances and patients in a WBAN domain.
Antiphospholipase A2 Receptor Autoantibodies: A Step Forward in the Management of Primary Membranous Nephropathy
Authors: Obrisca Bogdan , Ismail Gener , Jurubita Roxana , Baston Catalin , Andronesi Andreea , Mircescu Gabriel
Published: October 2015

Since the identification of PLA2R (M-type phospholipase A2 receptor) as the first human antigenic target in primary membranous nephropathy (MN), perpetual progress has been made in understanding the pathogenesis of this disease. Accumulating clinical data support a pathogenic role for the anti-PLA2R antibodies (PLA2R ABs), but confirmation in an animal model is still lacking. However, PLA2R ABs were related to disease activity and outcome, as well as to response therapy. Accordingly, PLA2R ABs assay seems to be promising tool not only to diagnose MN but also to predict the course of the disease and could open the way to personalize therapy. Nevertheless, validation of a universal assay with high precision and definition of cut-off levels, followed by larger studies with a prolonged follow-up period, are needed to confirm these prospects.
Aggregation Behavior of Some Asymmetric Porphyrins versus Basic Biological Tests Response
Authors: Socoteanu Radu , Anastasescu Mihai , Oliveira Anabela , Dobrescu Gianina , Boscencu Rica , Constantin Carolina
Published: October 2015

Fractal analysis of free bases porphyrins was computed on atomic force microscopy (AFM) micrographs using two different methods: the correlation function method and the variable length scale method. The correlation function method provides fractal dimension only for short scale range; results indicate that only few images have fractal properties for short ranges; for the rest of them, no fractal dimension was found using the correlation function method. The variable length scale method occur information for long range scaling. All samples have fractal properties at higher scaling range. For three samples the correlation function method leads to the same fractal dimension as the variable length scale method and scaling ranges for both methods overlap. Results show the necessity to use both methods to describe the fractal properties of AB3  meso-porphyrins that may be used to predict their relative cell localization. In order to emphasize the influence of fractal and textural properties the results regarding their self-similarity and texture/morphology were further compared with their behavior in biological assessment, that is, functionality of some Jurkat cell lines.
Assessing Origins of Quality Gaps in Discharge Summaries: A Survey of Resident Physician Attitudes
Authors: Otto Mallory , Sterling Madeline , Siegler Eugenia , Eiss Brian
Published: October 2015

Because little is known about attitudes of primary authors of discharge summaries in academic institutions, namely, trainees and physician assistants (PAs), we sought to explore values, possible areas for improvement, and interest in formal discharge summary education. A survey composed of Likert scale analyses, dichotomous relationships, and open-ended questions was designed using focus groups and validated via expert committee review. Of 135 total residents (PGY 1–3), 79 residents and 10 PAs in a large academic hospital in New York City completed it. Of surveyed trainees, 77.2% reported that quality discharge summaries are useful in primary care. Interns had less outpatient experience with discharge summaries compared to PGY 2 and PGY 3 (23.7% versus 63.4%, p<0.001) and were less comfortable authoring discharge summaries for patients who were not as familiar to them (47.4% versus 24.4%, p=0.04). The majority (54.8%) of interns as well as all PAs reported never receiving feedback on discharge summaries. Finally, 63.2% of interns and 90% of PAs responded that formal teaching would be helpful. Interns’ greater discomfort may speak to their poor understanding of core components of a useful discharge summary, which teaching sessions may improve. Alternatively, shifting the authorship responsibility from interns to seniors could be explored as a quality improvement initiative.
Toll-Like Receptor 4 Promotes NO Synthesis by Upregulating GCHI Expression under Oxidative Stress Conditions in Sheep Monocytes/Macrophages
Authors: Deng Shoulong , Yu Kun , Zhang Baolu , Yao Yuchang , Wang Zhixian , Zhang Jinlong , Zhang Xiaosheng , Liu Guoshi , Li Ning , Liu Yixun , Lian Zhengxing
Published: October 2015

Many groups of Gram-negative bacteria cause diseases that are harmful to sheep. Toll-like receptor 4 (TLR4), which is critical for detecting Gram-negative bacteria by the innate immune system, is activated by lipopolysaccharide (LPS) to initiate inflammatory responses and oxidative stress. Oxidation intermediates are essential activators of oxidative stress, as low levels of free radicals form a stressful oxidative environment that can clear invading pathogens. NO is an oxidation intermediate and its generation is regulated by nitric oxide synthase (iNOS). Guanosine triphosphate cyclohydrolase (GCHI) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, which is essential for the production of inducible iNOS. Previously, we made vectors to overexpress the sheepTLR4gene. Herein, first generation (G1) of transgenic sheep was stimulated with LPSin vivoandin vitro, and oxidative stress and GCHI expression were investigated. Oxidative injury caused by TLR4 overexpression was tightly regulated in tissues. However, the transgenic (Tg) group still secreted nitric oxide (NO) when an iNOS inhibitor was added. Furthermore, GCHI expression remained upregulated in both serum and monocytes/macrophages. Thus, overexpression of TLR4 in transgenic sheep might accelerate the clearance of invading microbes through NO generation following LPS stimulation. Additionally, TLR4 overexpression also enhances GCHI activation.
Chronic Stress Facilitates the Development of Deep Venous Thrombosis
Authors: Dong Tao , Cheng Yu-Wen , Yang Fei , Sun Pei-Wen , Zhu Chen-Jie , Zhu Li , Zhang Guo-Xing
Published: October 2015

The increasing pressure of modern social life intensifies the impact of stress on the development of cardiovascular diseases, which include deep venous thrombosis (DVT). Renal sympathetic denervation has been applied as one of the clinical approaches for the treatment of drug-resistant hypertension. In addition, the close relationship between oxidative stress and cardiovascular diseases has been well documented. The present study is designed to explore the mechanism by which the renal sympathetic nerve system and the oxidative stress affect the blood coagulation system in the development of DVT. Chronic foot shock model in rats was applied to mimic a state of physiological stress similar to humans. Our results showed that chronic foot shock procedure could promote DVT which may be through the activation of platelets aggregation. The aggravation of DVT and activation of platelets were alleviated by renal sympathetic denervation or antioxidant (Tempol) treatment. Concurrently, the denervation treatment could also reduce the levels of circulating oxidation factors in rats. These results demonstrate that both the renal sympathetic nerve system and the oxidative stress contribute to the development of DVT in response to chronic stress, which may provide novel strategy for treatment of clinic DVT patients.
Genetic Polymorphisms ofIL-17FandTRAF3IP2Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease
Authors: Urabe Shigetoshi , Isomoto Hajime , Ishida Tetsuya , Maeda Kazumi , Inamine Tatsuo , Kondo Shinji , Higuchi Norihide , Sato Kayoko , Uehara Ryohei , Yajima Hiroyuki , Machida Haruhisa , Chen Chun Chuan , Fukuda Yasuhiro , Takeshima Fuminao , Nakao Kazuhiko , Tsukamoto Kazuhiro
Published: October 2015

Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn’s disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment.Methods. A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers.Results. Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 inIL-17F, and a C/C or C/A genotype of rs1883136 inTRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease.Conclusion.IL17FandTRAF3IP2are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs.
Knowledge, Attitude, and Practice of Health Workers in a Tertiary Hospital in Ile-Ife, Nigeria, towards Ebola Viral Disease
Authors: Olowookere Samuel Anu , Abioye-Kuteyi Emmanuel Akintunde , Adepoju Olusegun Kayode , Esan Oluwaseun Taiwo , Adeolu Temitope Michael , Adeoye Tolulope Kola , Adepoju Adesola Adebayo , Aderogba Adedayo Titilayo
Published: October 2015

Background. Health workers are more prone to Ebola viral disease (EVD) than the general population. This study assessed the preparedness of health workers in the control and management of EVD.Methods. A descriptive cross-sectional study. Consenting 400 health workers completed a semistructured questionnaire that assessed participants’ general knowledge, emergency preparedness, and control and management of EVD. Data were analysed using descriptive and inferential statistics.Results. The mean age (SD) was 34.5 ± 8.62 years ranging from 20 to 59 years. Most participants were medical doctors (24.6%) and nurses (52.2%). The majority had practised <10 years (73.8%) and were aware of the EVD outbreak in the West African subregion (85.5%). Colleagues (40%) and radio (37.2%) were their major sources of information. Only 42% had good knowledge while 27% knew that there was no vaccine presently to prevent EVD. About one-quarter (24.2%) had low risk perception. The majority (89%) felt the hospital infection control policy was inadequate to protect against EVD. The only predictor of good knowledge was participants’ occupation.Conclusion. There is knowledge gap and poor infection control preparedness among respondents. Thus, knowledge and practices of health workers towards EVD need improvement.
Heparan Sulfate Proteoglycans May Promote or Inhibit Cancer Progression by Interacting with Integrins and Affecting Cell Migration
Authors: Soares Mariana A. , Teixeira Felipe C. O. B. , Fontes Miguel , Arêas Ana Lúcia , Leal Marcelo G. , Pavão Mauro S. G. , Stelling Mariana P.
Published: October 2015

The metastatic disease is one of the main consequences of tumor progression, being responsible for most cancer-related deaths worldwide. This review intends to present and discuss data on the relationship between integrins and heparan sulfate proteoglycans in health and cancer progression. Integrins are a family of cell surface transmembrane receptors, responsible for cell-matrix and cell-cell adhesion. Integrins’ main functions include cell adhesion, migration, and survival. Heparan sulfate proteoglycans (HSPGs) are cell surface molecules that play important roles as cell receptors, cofactors, and overall direct or indirect contributors to cell organization. Both molecules can act in conjunction to modulate cell behavior and affect malignancy. In this review, we will discuss the different contexts in which various integrins, such asα5,αV,β1, andβ3, interact with HSPGs species, such as syndecans and perlecans, affecting tissue homeostasis.
Rules regarding Marijuana and Its Use in Personal Residences: Findings from Marijuana Users and Nonusers Recruited through Social Media
Authors: Berg Carla J. , Buller David B. , Schauer Gillian L. , Windle Michael , Stratton Erin , Kegler Michelle C.
Published: October 2015

Recent changes in policy and social norms related to marijuana use have increased its use and concern about how/where marijuana should be used. We aimed to characterize rules regarding marijuana and its use in homes. We recruited 1,567 US adults aged 18–34 years through Facebook advertisements to complete an online survey assessing marijuana use, social factors, perceptions of marijuana, and rules regarding marijuana and its use in the home, targeting tobacco and marijuana users to ensure the relevance of this topic. Overall, 648 (41.6%) were current marijuana users; 46.0% of participants reported that “marijuana of any type is not allowed in their home or on their property.” Of those allowing marijuana on their property, 6.4% prohibiteduseof marijuana in their home. Of the remainder, 29.2% prohibitedsmokingmarijuana, and 11.0% prohibitedvaping, eating, or drinkingmarijuana. Correlates of more restrictive rules included younger age, being female, having <Bachelor’s degree, not having parents or people living with them who use marijuana, perceiving use to be less socially acceptable and more harmful, and being a nonuser (p’s<.05). Attitudes and subjective norms regarding marijuana are correlates of allowing marijuana in residential settings. Future work should examine areas of risk regarding household marijuana rules.
Assessment of Immunotoxicity of Dextran Coated Ferrite Nanoparticles in Albino Mice
Authors: Syama Santhakumar , Gayathri Viswanathan , Mohanan Parayanthala Valappil
Published: October 2015

In this study, dextran coated ferrite nanoparticles (DFNPs) of size <25 nm were synthesized, characterized, and evaluated for cytotoxicity, immunotoxicity, and oxidative stress byin vitroandin vivomethods. Cytotoxicity was performedin vitrousing splenocytes with different concentrations of DFNPs. Gene expression of selected cytokines (IL-1, IL-10, and TNFβ) secretion by splenocytes was evaluated. Also, 100 mg of DFNPs was injected intraperitoneally to 18 albino mice for immunological stimulations. Six animals each were sacrificed at the end of 7, 14, and 21 days. Spleen was subjected to immunotoxic response and liver was analyzed for antioxidant parameters (lipid peroxidation, reduced glutathione, glutathione peroxidase, superoxide dismutase, and glutathione reductase). The results indicated that DFNPs failed to induce any immunological reactions and no significant alternation in antioxidant defense mechanism. Also, mRNA expression of the cytokines revealed an increase in IL-10 expression and subsequent decreased expression of IL-1 and TNFβ. Eventually, DNA sequencing of liver actin gene revealed base alteration in nonconserved regions (10–20 bases) of all the treated groups when compared to control samples. Hence, it can be concluded that the DFNPs were nontoxic at the cellular level and nonimmunotoxic when exposed intraperitoneally to mice.
High-Resolution and Quantitative X-Ray Phase-Contrast Tomography for Mouse Brain Research
Authors: Xi Yan , Lin Xiaojie , Yuan Falei , Yang Guo-Yuan , Zhao Jun
Published: October 2015

Imaging techniques for visualizing cerebral vasculature and distinguishing functional areas are essential and critical to the study of various brain diseases. In this paper, with the X-ray phase-contrast imaging technique, we proposed an experiment scheme for theex vivomouse brain study, achieving both high spatial resolution and improved soft-tissue contrast. This scheme includes two steps: sample preparation and volume reconstruction. In the first step, we use heparinized saline to displace the blood inside cerebral vessels and then replace it with air making air-filled mouse brain. After sample preparation, X-ray phase-contrast tomography is performed to collect the data for volume reconstruction. Here, we adopt a phase-retrieval combined filtered backprojection method to reconstruct its three-dimensional structure and redesigned the reconstruction kernel. To evaluate its performance, we carried out experiments at Shanghai Synchrotron Radiation Facility. The results show that the air-tissue structured cerebral vasculatures are highly visible with propagation-based phase-contrast imaging and can be clearly resolved in reconstructed cross-images. Besides, functional areas, such as the corpus callosum, corpus striatum, and nuclei, are also clearly resolved. The proposed method is comparable with hematoxylin and eosin staining method but represents the studied mouse brain in three dimensions, offering a potential powerful tool for the research of brain disorders.
Value of Contrast-Enhanced Ultrasound in Guidance of Percutaneous Biopsy in Peripheral Pulmonary Lesions
Authors: Dong Yi , Mao Feng , Wang Wen-Ping , Ji Zhen-Biao , Fan Pei-Li
Published: October 2015

Objectives. To investigate the value of contrast-enhanced ultrasound (CEUS) in guidance of percutaneous biopsy in peripheral pulmonary lesions.Methods. This study focused on 53 patients (male: 38, female: 15, and mean age: 55.7 years ± 10.7) with 53 single peripheral pulmonary lesions. Before core needle (16-gauge) percutaneous biopsy, CEUS were performed in all lesions, with injection of 2.4 mL SonoVue (Bracco, Italy). The contrast-enhancement pattern, display rate of internal necrosis (nonenhanced) and active (obviously enhanced) areas, biopsy success rate, and pathological diagnosis rate were recorded.Results. All the peripheral pulmonary lesions were proved pathologically as benign lesions (n=7), primary malignancies (n=41), or metastasis (n=5). Forty (86.9%) malignant lesions and 4 (57.1%) benign lesions showed internal necrosis areas on CEUS. The detection rate and average size of internal necrosis areas had been significantly improved compared to conventional ultrasound (P<0.05). After CEUS, core needle percutaneous biopsies were performed successfully in the active areas of all lesions. The sampling success rate and pathological diagnosis rate were 100% and 98.1%.Conclusions. CEUS before biopsy provided useful diagnostic information about peripheral pulmonary lesions. By depicting internal necrotic and active areas, it is a promising technique for guaranteeing the accuracy, success, and safety of core needle biopsy.
Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence
Authors: Yang Yafan , Li Shuangshuang
Published: October 2015

Ultraviolet (UV) irradiation causes damage in skin by generating excessive reactive oxygen species (ROS) and induction of matrix metalloproteinases (MMPs), leading to skin photoageing. Dandelion extracts have long been used for traditional Chinese medicine and native American medicine to treat cancers, hepatitis, and digestive diseases; however, less is known on the effects of dandelion extracts in skin photoageing. Here we found that dandelion leaf and flower extracts significantly protect UVB irradiation-inhibited cell viability when added before UVB irradiation or promptly after irradiation. Dandelion leaf and flower extracts inhibited UVB irradiation-stimulated MMP activity and ROS generation. Dandelion root extracts showed less action on protecting HDFs from UVB irradiation-induced MMP activity, ROS generation, and cell death. Furthermore, dandelion leaf and flower but not root extracts stimulated glutathione generation and glutathione reductase mRNA expression in the presence or absence of UVB irradiation. We also found that dandelion leaf and flower extracts help absorb UVB irradiation. In addition, dandelion extracts significantly protected HDFs from H2O2-induced cellular senescence. In conclusion, dandelion extracts especially leaf and flower extracts are potent protective agents against UVB damage and H2O2-induced cellular senescence in HDFs by suppressing ROS generation and MMP activities and helping UVB absorption.
The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation
Authors: Cozza Giorgio , Venerando Andrea , Sarno Stefania , Pinna Lorenzo A.
Published: October 2015

Many polyphenolic compounds have been reported to inhibit protein kinases, with special reference to CK2, a pleiotropic serine/threonine kinase, implicated in neoplasia, neurodegenerative disease, and viral infections. In general however these compounds are not endowed with stringent selectivity. Among them quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) turned out to be particularly potent (Ki = 0.058 μM) and quite selective as judged by profiling it on a small panel of 70 protein kinases. Here, by profiling quinalizarin on a larger panel of 140 kinases we reach the conclusion that quinalizarin is one of the most selective inhibitors of CK2, superior to the first-in-class CK2 inhibitor, CX-4945, now in clinical trials for the treatment of cancer. Moreover here we show that quinalizarin is able to discriminate between the isolated CK2 catalytic subunit (CK2α) and CK2 holoenzyme (CK2α2β2), consistent within silicoandin vitroanalyses.
A Sentiment Delivering Estimate Scheme Based on Trust Chain in Mobile Social Network
Authors: Li Meizi , Xiang Yang , Zhang Bo , Huang Zhenhua
Published: October 2015

User sentiment analysis has become a flourishing frontier in data mining mobile social network platform since the mobile social network plays a significant role in users’ daily communication and sentiment interaction. This study studies the scheme of sentiment estimate by using the users’ trustworthy relationships for evaluating sentiment delivering. First, we address an overview of sentiment delivering estimate scheme and propose its related definitions, that is, trust chain among users, sentiment semantics, and sentiment ontology. Second, this study proposes the trust chain model and its evaluation method, which is composed of evaluation of atomic, serial, parallel, and combined trust chains. Then, we propose sentiment modeling method by presenting its modeling rules. Further, we propose the sentiment delivering estimate scheme from two aspects: explicit and implicit sentiment delivering estimate schemes, based on trust chain and sentiment modeling method. Finally, examinations and results are given to further explain effectiveness and feasibility of our scheme.
CyberPsychological Computation on Social Community of Ubiquitous Learning
Authors: Zhou Xuan , Dai Genghui , Huang Shuang , Sun Xuemin , Hu Feng , Hu Hongzhi , Ivanović Mirjana
Published: October 2015

Under the modern network environment, ubiquitous learning has been a popular way for people to study knowledge, exchange ideas, and share skills in the cyberspace. Existing research findings indicate that the learners’ initiative and community cohesion play vital roles in the social communities of ubiquitous learning, and therefore how to stimulate the learners’ interest and participation willingness so as to improve their enjoyable experiences in the learning process should be the primary consideration on this issue. This paper aims to explore an effective method to monitor the learners’ psychological reactions based on their behavioral features in cyberspace and therefore provide useful references for adjusting the strategies in the learning process. In doing so, this paper firstly analyzes the psychological assessment of the learners’ situations as well as their typical behavioral patterns and then discusses the relationship between the learners’ psychological reactions and their observable features in cyberspace. Finally, this paper puts forward a CyberPsychological computation method to estimate the learners’ psychological states online. Considering the diversity of learners’ habitual behaviors in the reactions to their psychological changes, a BP-GA neural network is proposed for the computation based on their personalized behavioral patterns.
Charge-Based Inhibitors of Amylin Fibrillization and Toxicity
Authors: Patil Sharadrao M. , Alexandrescu Andrei T.
Published: October 2015

To test the hypothesis that electrostatic repulsion is an important force opposing amyloid fibril assembly, we designed peptides that substitute strings of positively or negatively charged residues into the sequence of the amyloidogenic hormone amylin, which contributes to type 2 diabetes pathology. Arg-1 and Arg-2 substitute four positively charged arginines for segments that in structural models of amylin fibrils form the end of strandβ1 and the beginning of strandβ2, respectively. Mem-T substitutes negatively charged aspartates for the peptide segment with the largest avidity for membranes. All three charge-loaded peptides fibrillize poorly on their own and inhibit fibril elongation of WT-amylin at physiological ionic strength. The inhibition of WT-amylin fibril elongation rates is salt-dependent indicating that the analogs act through electrostatic interactions. Arg-1 protects against WT-amylin cytotoxicity towards a MIN6 mouse model of pancreaticβ-cells, and Arg-2 protects at higher concentrations, whereas Mem-T has no effect. The most effective variant, Arg-1, inhibits WT-amylin fibril elongation rates with an IC50of ~1 µM and cytotoxicity with an IC50of ~50 µM, comparable to other types of fibrillization inhibitors reported in the literature. Taken together, these results suggest that electrostatic interactions can be exploited to develop new types of inhibitors of amyloid fibrillization and toxicity.
Merlin/NF2 Suppresses Pancreatic Tumor Growth and Metastasis by Attenuating the FOXM1-Mediated Wnt/β-Catenin Signaling
Authors: Quan Ming , Cui Jiujie , Xia Tian , Jia Zhiliang , Xie Dacheng , Wei Daoyan , Huang Suyun , Huang Qian , Zheng Shaojiang , Xie Keping
Published: October 2015

Merlin, the protein encoded by the NF2 gene, is a member of the band 4.1 family of cytoskeleton-associated proteins and functions as a tumor suppressor for many types of cancer. However, the roles and mechanism of Merlin expression in pancreatic cancer have remained unclear. In this study, we sought to determine the impact of Merlin expression on pancreatic cancer development and progression using human tissue specimens, cell lines, and animal models. Decreased expression of Merlin was pronounced in human pancreatic tumors and cancer cell lines. Functional analysis revealed that restored expression of Merlin inhibited pancreatic tumor growth and metastasis in vitro and in vivo. Furthermore, Merlin suppressed the expression of Wnt/β-catenin signaling downstream genes and the nuclear expression of β-catenin protein, and overexpression of Forkhead box M1 (FOXM1) attenuated the suppressive effect of Merlin on Wnt/β-catenin signaling. Mechanistically, Merlin decreased the stability of FOXM1 protein, which plays critical roles in nuclear translocation of β-catenin. Collectively, these findings demonstrated that Merlin critically regulated pancreatic cancer pathogenesis by suppressing FOXM1/β-catenin signaling, suggesting that targeting novel Merlin/FOXM1/β-catenin signaling is an effective therapeutic strategy for pancreatic cancer. Cancer Res; 75(22); 4778–89. ©2015 AACR.
JX06 Selectively Inhibits Pyruvate Dehydrogenase Kinase PDK1 by a Covalent Cysteine Modification
Authors: Sun Wenyi , Xie Zuoquan , Liu Yifu , Zhao Dan , Wu Zhixiang , Zhang Dadong , Lv Hao , Tang Shuai , Jin Nan , Jiang Hualiang , Tan Minjia , Ding Jian , Luo Cheng , Li Jian , Huang Min , Geng Meiyu
Published: October 2015

Pyruvate dehydrogenase kinase PDK1 is a metabolic enzyme responsible for switching glucose metabolism from mitochondrial oxidation to aerobic glycolysis in cancer cells, a general hallmark of malignancy termed the Warburg effect. Herein we report the identification of JX06 as a selective covalent inhibitor of PDK1 in cells. JX06 forms a disulfide bond with the thiol group of a conserved cysteine residue (C240) based on recognition of a hydrophobic pocket adjacent to the ATP pocket of the PDK1 enzyme. Our investigations of JX06 mechanism suggested that covalent modification at C240 induced conformational changes at Arginine 286 through Van der Waals forces, thereby hindering access of ATP to its binding pocket and in turn impairing PDK1 enzymatic activity. Notably, cells with a higher dependency on glycolysis were more sensitive to PDK1 inhibition, reflecting a metabolic shift that promoted cellular oxidative stress and apoptosis. Our findings offer new mechanistic insights including how to therapeutically target PDK1 by covalently modifying the C240 residue. Cancer Res; 75(22); 4923–36. ©2015 AACR.
Abstract A20: A leukemic model of acquired resistance to BET inhibition reveals a role for CBP/EP300 bromodomains in the regulation of c-MYC expression
Authors: Conery Andrew R. , Centore Richard C. , Hatton Charlie , Neiss Adrianne , Huang Hon-Ren , Keller Patricia J. , Taylor Alexander M. , Cote Alexandre , Hewitt Michael C. , Nasveschuk Christopher G. , Leblanc Yves , Yao Shihua , Pardo Eneida , Zawadzke Laura , Poy Florence , Jayaram Hari , Joshi Shivangi , Sandy Peter , Romero Anthony , Crawford Terry , Pastor Richard , Lai Tommy , Chen Kevin , Wang Jian , Magnuson Steven , Albrecht Brian K. , Bellon Steve , Bryant Barbara M. , Sims Robert J.
Published: October 2015

Pharmacological modulation of c-MYC expression has recently become possible through small molecule engagement of the BET bromodomain proteins. As multiple BET inhibitors (BETi) progress through clinical trials, understanding possible mechanisms of acquired resistance becomes imperative to maximize therapeutic efficacy, assess possible drug combination strategies, and identify characteristics of next generation BET inhibitors. In the present study, we describe a cellular model of BETi resistance, which demonstrates a significantly blunted phenotypic and molecular response to BETi. The expression of c-MYC mRNA, highly susceptible to BETi in the parental cells, is restored in resistant cells through transcriptional bypass of BET-mediated co-activation. Through the use of a novel CBP/EP300 bromodomain inhibitor (CBP/EP300i), we show that c-MYC expression in BETi-resistant cells is dependent on CBP/EP300 bromodomain function, and that co-treatment with CBP/EP300i restores phenotypic sensitivity. CBP/EP300i was additionally found to transcriptionally silence MYC expression in numerous myeloma and leukemia derived cell lines in a manner comparable to BETi, identifying a novel modality to pharmacologically target the MYC oncogenic axis. While both BET and CBP/EP300 bromodomains regulate the expression of MYC, their transcriptional and phenotypic effects are otherwise distinct, suggesting that CBP/EP300 bromodomain inhibition may represent an alternative or complementary therapeutic option to BET bromodomain inhibition.

Citation Format: Andrew R. Conery, Richard C. Centore, Charlie Hatton, Adrianne Neiss, Hon-Ren Huang, Patricia J. Keller, Alexander M. Taylor, Alexandre Cote, Michael C. Hewitt, Christopher G. Nasveschuk, Yves Leblanc, Shihua Yao, Eneida Pardo, Laura Zawadzke, Florence Poy, Hari Jayaram, Shivangi Joshi, Peter Sandy, Anthony Romero, Terry Crawford, Richard Pastor, Tommy Lai, Kevin Chen, Jian Wang, Steven Magnuson, Brian K. Albrecht, Steve Bellon, Barbara M. Bryant, Robert J. Sims, III. A leukemic model of acquired resistance to BET inhibition reveals a role for CBP/EP300 bromodomains in the regulation of c-MYC expression. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A20.
Abstract A43: Sequence specificity incompletely defines the genome-wide occupancy of Myc
Authors: Guo Jiannan , Li Tiandao , Schipper Joshua , Nilson Kyle A. , Fordjour Francis K. , Cooper Jeffrey J. , Gordan Raluca , Price David H.
Published: October 2015

Background: The Myc-Max heterodimer is a transcription factor that regulates expression of a large number of genes. Genome occupancy of Myc-Max is thought to be driven by Enhancer box (E-box) DNA elements (CACGTG or variants) to which the heterodimer binds in vitro in the context of accessible chromatin.

Results: By analyzing ChIP-Seq datasets, we demonstrated that the positions occupied by Myc-Max across the human genome correlate with the RNA polymerase II (Pol II) transcription machinery better than with E-boxes. Metagene analyses showed that in promoter regions, Myc was uniformly positioned about 100 bp upstream of essentially all promoter proximal paused polymerases with Max about 15 bp upstream of Myc. We re-evaluated the DNA binding properties of full length Myc-Max proteins using electrophoretic mobility shift assays (EMSA) and universal protein-binding microarrays (PBM). EMSA results demonstrated Myc-Max heterodimers display significant sequence preference, but have high affinity for any DNA. Quantification of the relative affinities of Myc-Max for all possible 8-mers using PBM assays showed that sequences surrounding core 6-mers significantly affect binding. Compared to the in vitro sequence preferences, Myc-Max genomic occupancy measured by ChIP-Seq was largely, although not completely, independent of sequence specificity.

Conclusions: Our results indicate that the genomic occupancy of Myc cannot be explained solely by its intrinsic DNA specificity and suggest that the transcription machinery and associated promoter accessibility play a predominant role in Myc recruitment.

Citation Format: Jiannan Guo, Tiandao Li, Joshua Schipper, Kyle A. Nilson, Francis K. Fordjour, Jeffrey J. Cooper, Raluca Gordan, David H. Price. Sequence specificity incompletely defines the genome-wide occupancy of Myc. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A43.