bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-related impairment of conducted dilation in human coronary arterioles
Authors: Feher Attila , Broskova Zuzana , Bagi Zsolt
Published: April 2014

Conducted vasodilation is essential to coordinate vascular resistance along distances to ensure adequate tissue perfusion. We hypothesized that conducted vasodilation of coronary resistance arteries declines with age. Coronary arterioles were dissected from right atrial appendage of patients ( n = 27) undergoing cardiac surgery. Arterioles (∼100 μm) were cannulated and pressurized (80 mmHg), and developed spontaneous myogenic tone. Conducted vasodilation was initiated by locally administering the endothelium-dependent agonist bradykinin (BK; 100 μM) ejected from a glass micropipette (∼3 μm tip opening, positioned in close proximity to the vessel wall). Diameter changes were measured at local and upstream sites (500 and 1,000 μm from the stimulus) with videomicroscopy. Local administration of BK elicited vasodilation, the magnitude of which increased with the duration of stimulus (69 ± 6, 81 ± 6, 90 ± 2%, after 1, 3, and 5 × 100 ms, respectively). BK-induced dilation remained substantial at upstream sites (500 μm: 53 ± 7%; 1,000 μm: 46 ± 9%). The gap junction uncoupler carbenoxolone or 18-α-glycyrrhetinic acid did not affect local responses, but diminished conducted vasodilation. Inhibitors of small/intermediate conductance calcium-activated potassium channels (SKCa/IKCa), apamin and TRAM34, reduced dilations both at local and remote sites. We found that conducted dilation, but not the local response, was significantly reduced in older (≥64 yr) patients. The nitric oxide (NO) synthesis inhibitor Nω-nitro-l-arginine methyl ester did not affect local responses, but markedly reduced conducted dilation in younger (<64 yr) individuals. Collectively, we show that human coronary arterioles exhibit SKCa/IKCa-mediated hyperpolarization spread through gap junctions, which contributes to conducted vasodilation initiated by focal application of BK. We demonstrate that conducted dilation declines with age, likely due to reduced NO availability, which plays a permissive role in propagating longitudinal vasomotor signaling.
Do Maternal Quality of Life and Breastfeeding Difficulties Influence the Continuation of Exclusive Breastfeeding?
Authors: Mortazavi Forough , Mousavi Seyed Abbas , Chaman Reza , Khosravi Ahmad
Published: April 2014

Objectives.This study was conducted to determine whether maternal quality of life (QOL) and breastfeeding difficulties influence the continuation of exclusive breastfeeding (EBF).Methods.In a survey, 358 consecutive pregnant women filled out a quality of life questionnaire in the third trimester of pregnancy and the breastfeeding experience scale at 4 weeks postpartum. We assessed breastfeeding practices every month up to 6 months postpartum.Results.Only 11.8% of women continued EBF at six months. Mothers who continued EBF at 2 and 4 months postpartum had better QOL in late pregnancy than mothers who discontinued it (P<0.05). There were no significant differences between the two groups in QOL scores at 6 months postpartum. Mothers who continued EBF at 2 months postpartum experienced less breastfeeding difficultties during one month postpartum than mothers who discontinued it (P<0.05).Conclusion.In attempts to promote EBF, mothers with poor QOL or breastfeeding difficulties in early postpartum should be identified and helped.
Bifurcation in a Discrete Competition System
Authors: Xu Li , Zou Lianjun , Chang Zhongxiang , Lou Shanshan , Peng Xiangwei , Zhang Guang
Published: April 2014

A new difference system is induced from a differential competition system by different discrete methods. We give theoretical analysis for local bifurcation of the fixed points and derive the conditions under which the local bifurcations such as flip occur at the fixed points. Furthermore, one- and two-dimensional diffusion systems are given when diffusion terms are added. We provide the Turing instability conditions by linearization method and inner product technique for the diffusion system with periodic boundary conditions. A series of numerical simulations are performed that not only verify the theoretical analysis, but also display some interesting dynamics.
A Case-Control Study of the Role of Human Papillomavirus in Oesophageal Squamous Cell Carcinoma in Australia
Authors: Liyanage Surabhi S. , Segelov Eva , Malik Aisha , Garland Suzanne M. , Tabrizi Sepehr N. , Cummins Eleanor , Seale Holly , Rahman Bayzidur , Moa Aye , Barbour Andrew P. , Crowe Philip J. , MacIntyre C. Raina
Published: April 2014

Objective. We investigate the prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) tissues compared to oesophageal tissue from healthy controls, in an Australian cohort.Methods. We conducted a hospital-based case-control study of 99 patients with OSCC and 100 healthy controls to examine the presence of HPV DNA. Paraffin tissues were tested using the PapType high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on the L1 consensus primer set PGMY09-PGMY11.Results. HPV DNA of the oncogenic genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95% CI: 30–5500). All control specimens were negative for HPV. Significantly higher rates of smoking, other aerodigestive cancers, and mortality were seen among cases than controls. A pooled analysis of this study and the only other Australian case-control study found that 9/321 cases and 0/155 controls were positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47–190.33).Conclusion. Our results suggest that in this multifactorial cancer HPV may be an additional risk factor; although a larger, better powered study is needed.
Increasing Bending Strength of Porcelain Stoneware via Pseudoboehmite Additions
Authors: Aguilar-García Omar , Lara-Hernández Rafael , Arellano-Lara Azucena , Gil-Vázquez José L. , Aguilar-García Jaime
Published: April 2014

Pseudoboehmite nanoparticles synthesized through the desulfation of Al2(SO4)3were used to investigate the reinforcement of commercial porcelain stoneware. Fractured specimens investigated by SEM suggest that the added pseudoboehmite precursor generated a nanometric primary mullite phase dispersed in the porcelain glassy phase that limited and stopped the intergranular crack propagation. The porcelain modulus of rupture increased twice the value of the modulus of rupture (108 MPa) as compared with that samples without pseudoboehmite additions. Pseudoboehmite also led to increased densification of porcelain stoneware bodies up to 1250°C as shown by thermodilatometry data.
Survivability-Aware Topology Evolution Model with Link and Node Deletion in Wireless Sensor Networks
Authors: Jin Yanliang , Zhou Xuqin , Bai Zhishu , Ma Wei , Xu Lina , Wu Zhuo , Ooi Su Ki , Liu Yue
Published: April 2014

The paper proposes the algorithm of survival topology evolution model. The model applies the survival analysis to the research on the topology of networks. On one hand, it takes the survivability of every node into account. Since the state of a node is affected by the node itself, the environment and so on, it's necessary to study the survivability of nodes. In addition, the survival analysis on the nodes can indicate whether the nodes work well in real time. On the other hand, it also takes the deletion of links and nodes determined by the survivability of the nodes into account. Then it reaches the conclusion by mean field method. The result shows that the degree distributions of WSNs are approximately power law as B-A model and that the survivability of the nodes is proportional to the degree distribution of the network consisting of the previous nodes. These are further confirmed by simulation example.
Quality of Sleep in an HIV Population on Antiretroviral Therapy at an Urban Tertiary Centre in Lagos, Nigeria
Authors: Oshinaike Olajumoke , Akinbami Akinsegun , Ojelabi Olaitan , Dada Akinola , Dosunmu Adedoyin , John Olabode Sarah
Published: April 2014

Aim. To determine the prevalence of sleep disturbance and its associated characteristics in HIV-positive outpatients on HAART using the PSQI.Methods. Using a cross-sectional design, 300 patients attending the outpatient HIV/AIDS clinic at the Lagos State University Teaching Hospital were recruited. Baseline data obtained included the participants’ demographic data, educational qualification, and marital status. Their treatment history, including duration since HIV diagnosis, the most recent CD4 cell count, and current antiretroviral therapies, was obtained from their case records. Each participant completed the PSQI questionnaire and those with scores ≥5 were diagnosed with poor sleep quality.Results. The participants were made up of 70.7% females and 29.3% males. Their ages ranged between 18 and 74 years with a mean of38.9±10.3years. According to the PSQI, 59.3% reported poor sleep quality. The mean score of those with poor quality sleep (9.2±3.3) was comparable to that of those with good quality sleep (1.26±1.4).P<0.001. Significant differences were observed in all the individual components of the PSQI (P<0.001). On multivariate analyses, the independent associations with sleep quality were the duration since HIV diagnosis (P=0.29), efavirenz based regimen (P<0.001), and lower CD4 cell count (P<0.001).Conclusions. Sleep disturbances are quite common in the HIV population even in the era of HAART. Early recognition via routine assessment and effective treatments could prevent the resultant complications and improve quality of life.
Color Distribution Differences in the Tongue in Sleep Disorder
Authors: Jung Chang Jin , Nam Ji Ho , Jeon Young Ju , Kim Keun Ho
Published: April 2014

Introduction.
According to traditional East Asian medicine (TEAM) theory, the tongue represents conditions of qi and blood. In the present study, the relationship between the tongue and the qi and blood in conditions with no apparent disease was investigated.
Methods. A total of 454 elderly people with no apparent disease were recruited. Two Korean oriental medicine doctors classified subjects into a normal group (n = 402) and a sleep disorder group (n = 52). Three to five weeks after the experiment, 153 subjects were rerecruited for a second experiment. Two‐dimensional color histograms, whose seven variables represent the color distribution in Commission Internationale de l′Éclairage 1976 (L*, a*, b*) color space, were produced from tongue images. Results. The color of the tongue body in the sleep disorder group appeared paler than that in the normal group, and the tongue coating in the normal group was less widely distributed compared with that in the sleep disorder group. The differences in tongue color between the normal at first experiment and sleep disorder at second experiment conditions were similar to the differences between the normal and the sleep disorder groups.
Conclusions. The tongue states in the sleep disorder group indicate a qi and blood deficiency according to TEAM theory.
Analysis of a Delayed Internet Worm Propagation Model with Impulsive Quarantine Strategy
Authors: Yao Yu , Feng Xiaodong , Yang Wei , Xiang Wenlong , Gao Fuxiang
Published: April 2014

Internet worms exploiting zero‐day vulnerabilities have drawn significant attention owing to their enormous threats to Internet in the real world. To begin with, a worm propagation model with time delay in vaccination is formulated. Through theoretical analysis, it is proved that the worm propagation system is stable when the time delay is less than the threshold τ0 and Hopf bifurcation appears when time delay is equal to or greater than τ0. Then, a worm propagation model with constant quarantine strategy is proposed. Through quantitative analysis, it is found that constant quarantine strategy has some inhibition effect but does not eliminate bifurcation. Considering all the above, we put forward impulsive quarantine strategy to eliminate worms. Theoretical results imply that the novel proposed strategy can eliminate bifurcation and control the stability of worm propagation. Finally, simulation results match numerical experiments well, which fully supports our analysis.
Axially Symmetric Vibrations of Composite Poroelastic Spherical Shell
Authors: Gurijala Rajitha , Perati Malla Reddy
Published: April 2014

This paper deals with axially symmetric vibrations of composite poroelastic spherical shell consisting of two spherical shells (inner one and outer one), each of which retains its own distinctive properties. The frequency equations for pervious and impervious surfaces are obtained within the framework of Biot’s theory of wave propagation in poroelastic solids. Nondimensional frequency against the ratio of outer and inner radii is computed for two types of sandstone spherical shells and the results are presented graphically. From the graphs, nondimensional frequency values are periodic in nature, but in the case of ring modes, frequency values increase with the increase of the ratio. The nondimensional phase velocity as a function of wave number is also computed for two types of sandstone spherical shells and for the spherical bone implanted with titanium. In the case of sandstone shells, the trend is periodic and distinct from the case of bone. In the case of bone, when the wave number lies between 2 and 3, the phase velocity values are periodic, and when the wave number lies between 0.1 and 1, the phase velocity values decrease.
Secure Data Aggregation in Wireless Multimedia Sensor Networks Based on Similarity Matching
Authors: Gao Rui , Wen Yingyou , Zhao Hong , Meng Yinghui
Published: April 2014

Given its importance, the problem of secure data aggregation in wireless multimedia sensor networks has attracted great attention in the literature. Wireless multimedia sensor networks present some challenges that are common to wireless sensor networks, such as the existence of limited resources, like sensors memory, energy consumption, and CPU performance. Many methods have been proposed to attempt to solve the problem. However, the existing data aggregations do not take into account the redundancy of the multimedia data. In order to improve the energy efficiency for multimedia data, we propose a similarity model and power model. The proposal scheme divides multimedia data into multiple different pieces, and transmits the effective pieces to the selected sensor nodes. Through theoretical justifications and empirical studies, we demonstrate that the proposed scheme achieves substantially superior performances over conventional methods in terms of energy efficiency and data transmission under the resource-constrained wireless multimedia sensor networks.
Model‐Based Water Wall Fault Detection and Diagnosis of FBC Boiler Using Strong Tracking Filter
Authors: Sun Li , Dong Junyi , Li Donghai , Zhang Yuqiong
Published: April 2014

Fluidized bed combustion (FBC) boilers have received increasing attention in recent decades. The erosion issue on the water wall is one of the most common and serious faults for FBC boilers. Unlike direct measurement of tube thickness used by ultrasonic methods, the wastage of water wall is reconsidered equally as the variation of the overall heat transfer coefficient in the furnace. In this paper, a model‐based approach is presented to estimate internal states and heat transfer coefficient dually from the noisy measurable outputs. The estimated parameter is compared with the normal value. Then the modified Bayesian algorithm is adopted for fault detection and diagnosis (FDD). The simulation results demonstrate that the approach is feasible and effective.
A Rare Collision Tumor Composed of Follicular Lymphoma and Adenocarcinoma in the Ampulla of Vater: A Case Report
Authors: Suzuki Shioto , Tanioka Fumihiko , Inaba Keisuke , Takatori Shingo , Ochiai Hideto , Suzuki Shohachi
Published: April 2014

The duodenum is infrequently affected by malignant lymphoma, and follicular lymphomas of the duodenum are rare histological subtypes. There are no reported cases of collision of follicular lymphoma and other tumors in the ampulla of Vater. A 57-year-old Japanese man presented with jaundice, and abdominal computed tomography revealed a tumor of the ampulla of Vater invading the pancreatic head with biliary dilatation and a thickened duodenal wall. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy. Histopathology of the resected specimen revealed lymphoid follicular formations with small-to-medium-sized centrocyte-like cells and some centroblast-like cells. The atypical lymphoid cells were immunohistochemically positive for CD10, CD20, and CD79a but negative for CD5 and cyclin D1. BCL2 protein was highly expressed in the follicle centers. The diagnosis was duodenal follicular lymphoma, Grade 1. The follicular lymphoma, 40 mm in diameter, involved duodenal submucosa and regional lymph nodes without distant metastasis. This duodenal follicular lymphoma was partially overlapped by adenocarcinoma of the ampulla of Vater, measuring25×20 mm, which involved the lower common bile duct, pancreas, and duodenum. We report the first case of a surgically treated collision tumor composed of a rare mass-forming follicular lymphoma and adenocarcinoma of the ampulla of Vater.
Effects of Treating Old Rats with an AqueousAgaricus blazeiExtract on Oxidative and Functional Parameters of the Brain Tissue and Brain Mitochondria
Authors: de Sá-Nakanishi Anacharis B. , Soares Andréia A. , de Oliveira Andrea Luiza , Fernando Comar Jurandir , Peralta Rosane M. , Bracht Adelar
Published: April 2014

Dysfunction of the mitochondrial respiratory chain and increased oxidative stress is a striking phenomenon in the brain of aged individuals. For this reason there has been a constant search for drugs and natural products able to prevent or at least to mitigate these problems. In the present study the effects of an aqueous extract ofAgaricus blazei, a medicinal mushroom, on the oxidative state and on the functionality of mitochondria from the brain of old rats (21 months) were conducted. The extract was administered intragastrically during 21 days at doses of 200 mg/kg. The administration of theA. blazeiextract was protective to the brain of old rats against oxidative stress by decreasing the lipid peroxidation levels and the reactive oxygen species content and by increasing the nonenzymic and enzymic antioxidant capacities. Administration of theA. blazeiextract also increased the activity of several mitochondrial respiratory enzymes and, depending on the substrate, the mitochondrial coupled respiration.
Dynamic Deduplication Decision in a Hadoop Distributed File System
Authors: Chang Ruay-Shiung , Liao Chih-Shan , Fan Kuo-Zheng , Wu Chia-Ming
Published: April 2014

Data are generated and updated tremendously fast by users through any devices in anytime and anywhere in big data. Coping with these multiform data in real time is a heavy challenge. Hadoop distributed file system (HDFS) is designed to deal with data for building a distributed data center. HDFS uses the data duplicates to increase data reliability. However, data duplicates need a lot of extra storage space and funding in infrastructure. Using the deduplication technique can improve utilization of the storage space effectively. In this paper, we propose a dynamic deduplication decision to improve the storage utilization of a data center which uses HDFS as its file system. Our proposed system can formulate a proper deduplication strategy to sufficiently utilize the storage space under the limited storage devices. Our deduplication strategy deletes useless duplicates to increase the storage space. The experimental results show that our method can efficiently improve the storage utilization of a data center using the HDFS system.
Conjugacy Systems Based on Nonabelian Factorization Problems and Their Applications in Cryptography
Authors: Gu Lize , Zheng Shihui
Published: April 2014

To resist known quantum algorithm attacks, several nonabelian algebraic structures mounted upon the stage of modern cryptography. Recently, Baba et al. proposed an important analogy from the integer factorization problem to the factorization problem over nonabelian groups. In this paper, we propose several conjugated problems related to the factorization problem over nonabelian groups and then present three constructions of cryptographic primitives based on these newly introduced conjugacy systems: encryption, signature, and signcryption. Sample implementations of our proposal as well as the related performance analysis are also presented.
Attitudes to Medication after Kidney Transplantation and Their Association with Medication Adherence and Graft Survival: A 2-Year Follow-Up Study
Authors: Tielen Mirjam , van Exel Job , Laging Mirjam , Beck Denise K. , Khemai Roshni , van Gelder Teun , Betjes Michiel G. H. , Weimar Willem , Massey Emma K.
Published: April 2014

Background. Nonadherence to medication is a common problem after kidney transplantation. The aim of this study was to explore attitudes towards medication, adherence, and the relationship with clinical outcomes.Method. Kidney recipients participated in a Q-methodological study 6 weeks after transplantation. As a measure of medication adherence, respondents completed the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©-interview). Moreover, the intrapatient variability in the pharmacokinetics of tacrolimus was calculated, which measures stability of drug intake. Data on graft survival was retrieved from patient records up to 2 years after transplantation.Results. 113 renal transplant recipients (19–75 years old) participated in the study. Results revealed three attitudes towards medication adherence—attitude 1: “confident and accurate,” attitude 2: “concerned and vigilant,” and attitude 3: “appearance oriented and assertive.” We found association of attitudes with intrapatient variability in pharmacokinetics of tacrolimus, but not with self-reported nonadherence or graft survival. However, self-reported nonadherence immediately after transplantation was associated with lower two-year graft survival.Conclusion. These preliminary findings suggest that nonadherence shortly after kidney transplantation may be a risk factor for lower graft survival in the years to follow. The attitudes to medication were not a risk factor.
On Lightlike Geometry of Para-Sasakian Manifolds
Authors: Acet Bilal Eftal , Yüksel Perktaş Selcen , Kılıç Erol
Published: April 2014

We study lightlike hypersurfaces of para-Sasakian manifolds tangent to the characteristic vector field. In particular, we define invariant lightlike hypersurfaces and screen semi-invariant lightlike hypersurfaces, respectively, and give examples. Integrability conditions for the distributions on a screen semi-invariant lightlike hypersurface of para-Sasakian manifolds are investigated. We obtain a para-Sasakian structure on the leaves of an integrable distribution of a screen semi-invariant lightlike hypersurface.
On a Class ofq-Bernoulli,q-Euler, andq-Genocchi Polynomials
Authors: Mahmudov N. I. , Momenzadeh M.
Published: April 2014

The main purpose of this paper is to introduce and investigate a class ofq-Bernoulli,q-Euler, andq-Genocchi polynomials. Theq-analogues of well-known formulas are derived. In addition, theq-analogue of the Srivastava-Pintér theorem is obtained. Some new identities, involvingq-polynomials, are proved.
Frequency and Intensive Care Related Risk Factors of Pneumothorax in Ventilated Neonates
Authors: Bhat Yellanthoor Ramesh , Ramdas Vidya
Published: April 2014

Objectives. Relationships of mechanical ventilation to pneumothorax in neonates and care procedures in particular are rarely studied. We aimed to evaluate the relationship of selected ventilator variables and risk events to pneumothorax.Methods. Pneumothorax was defined as accumulation of air in pleural cavity as confirmed by chest radiograph. Relationship of ventilator mode, selected settings, and risk procedures prior to detection of pneumothorax was studied using matched controls.Results. Of 540 neonates receiving mechanical ventilation, 10 (1.85%) were found to have pneumothorax. Respiratory distress syndrome, meconium aspiration syndrome, and pneumonia were the underlying lung pathology. Pneumothorax mostly (80%) occurred within 48 hours of life. Among ventilated neonates, significantly higher percentage with pneumothorax received mandatory ventilation than controls (70% versus 20%;P<0.01). Peak inspiratory pressure >20 cmH2Oand overventilation were not significantly associated with pneumothorax. More cases than controls underwent care procedures in the preceding 3 hours of pneumothorax event. Mean airway pressure change (P=0.052) and endotracheal suctioning (P=0.05) were not significantly associated with pneumothorax. Reintubation (P=0.003), and bagging (P=0.015) were significantly associated with pneumothorax.Conclusion. Pneumothorax among ventilated neonates occurred at low frequency. Mandatory ventilation and selected care procedures in the preceding 3 hours had significant association.
Compact Low Weight High Gain Broadband Antenna by Polarization-Rotation Technique for X-Band Radar
Authors: Dastkhosh Amir Reza , Dalili Oskouei Hamidreza , Khademevatan Gholamreza
Published: April 2014

Less efficiency and gain is achieved by existence of aperture blocking phenomena in cassegrain antenna caused by the presence of subreflector or antenna feed. Also, length of feed cables causes delay which is another undesirable problem in antennas, since errors and less precision of detecting targets are created. To overcome these problems, low weight and compact optimized polarization-rotation monopulse cassegrain antenna is designed in this paper. The goal of our proposed rotating antenna is achievement of sum and difference patterns for target tracking in monopulse radar. In our work, left part of hyperbolic subreflector instead of right one has been used for reducing size of the antenna. The antenna is fabricated by grid wires instead of solid sheet metal reflectors and with composite technology for decreasing its weight. Width and volume of the antenna reduce by about 50% in comparison to other reflector antennas. This antenna has been simulated and manufactured in X-band and simulation data are in good agreement with measured ones. The antenna has the average gain of 35 dB from 8.5 up to 9.5 GHz. Also the antenna feed bandwidth is more than 50% and the antenna has efficiency of about 50% from 8 up to 10 GHz.
An Advanced Review of the Relationships between Sahel Precipitation and Climate Indices: A Wavelet Approach
Authors: Okonkwo Churchill
Published: April 2014

The interannual and decadal to multidecadal variability of precipitation in western Sahel region was examined using wavelet transform and coherency analysis. The aim was to identify the major climate index that has a robust relationship with Sahel precipitation (drought). The results show that ENSO, North Atlantic Oscillation (NAO), Atlantic Multidecadal Oscillation (AMO), and Indian Ocean Dipole (IOD) all have some relationship with precipitation at different time scales which is in agreement with recent studies. There is an antiphase relationship between Sahel precipitation and ENSO at the 3-4-year band localized around 1982/83 El Niño episode. This indicates a cause and effect relationship between the droughts of 1983 and 1982/83 El Niño. In addition, wavelet transform coherence analysis also revealed a relatively antiphase relationship between AMO and precipitation signifying cause and effect. The wavelet analyses indicate that IOD control on rainfall variability in Sahel is limited to the east (15°E–35°E). Advancing this understanding of variability in rainfall and climate forcing could improve the accuracy of rainfall forecast.
Analysis of the Virulence of an Atypical EnteropathogenicEscherichia coliStrainIn VitroandIn Vivoand the Influence of Type Three Secretion System
Authors: Sampaio Suely C. F. , Moreira Fabiana C. , Liberatore Ana M. A. , Vieira Mônica A. M. , Knobl Terezinha , Romão Fabiano T. , Hernandes Rodrigo T. , Ferreira Claudete S. A. , Ferreira Antônio P. , Felipe-Silva Aloísio , Sinigaglia-Coimbra Rita , Koh Ivan H. J. , Gomes Tania A. T.
Published: April 2014

Atypical enteropathogenicEscherichia coli(aEPEC) inject various effectors into intestinal cells through a type three secretion system (T3SS), causing attaching and effacing (A/E) lesions. We investigated the role of T3SS in the ability of the aEPEC 1711-4 strain to interact with enterocytesin vitro(Caco-2 cells) andin vivo(rabbit ileal loops) and to translocate the rat intestinal mucosain vivo. A T3SS isogenic mutant strain was constructed, which showed marked reduction in the ability to associate and invade but not to persist inside Caco-2 cells. After rabbit infection, only aEPEC 1711-4 was detected inside enterocytes at 8 and 24 hours pointing to a T3SS-dependent invasive potentialin vivo. In contrast to aEPEC 1711-4, the T3SS-deficient strain no longer produced A/E lesions or induced macrophage infiltration. We also demonstrated that the ability of aEPEC 1711-4 to translocate through mesenteric lymph nodes to spleen and liver in a rat model depends on a functional T3SS, since a decreased number of T3SS mutant bacteria were recovered from extraintestinal sites. These findings indicate that the full virulence potential of aEPEC 1711-4 depends on a functional T3SS, which contributes to efficient adhesion/invasionin vitroandin vivoand to bacterial translocation to extraintestinal sites.
Retracted: Semantic Information Integration with Linked Data Mashups Approaches
Authors: Hoang Hanh Huu , Cung Tai Nguyen-Phuoc , Truong Duy Khanh , Hwang Dosam , Jung Jason J.
Published: April 2014

The introduction of semantic web and Linked Data helps facilitate sharing of data on the Internet more easily. Subsequently, the resource description framework (RDF) is the standard in publishing structured data resources on the Internet and is used in interconnecting with other data resources. To remedy the data integration issues of the traditional web mashups, the semantic web technology uses the Linked Data based on RDF data model as the unified data model for combining, aggregating, and transforming data from heterogeneous data resources to build Linked Data mashups. There have been tremendous amounts of efforts of semantic web community to enable Linked Data mashups but there is still lack of a systematic survey on concepts, technologies, applications, and challenges. Therefore, in this paper, we investigate in detail semantic mashups research and application approaches in the information integration. This paper also presents a Linked Data mashup application as an illustration of the proposed approaches.
The Wide and Complex Field of NAFLD Biomarker Research: Trends
Authors: Wichro Erika , Macheiner Tanja , Schmid Jasmin , Kavsek Barbara , Sargsyan Karine
Published: April 2014

Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression and prognosis of obesity related liver diseases. Methodology. We analyzed finally 62 articles accounting for 157 cohorts and 45,288 subjects. Results. Despite the various approaches, most cohorts were considerably small and rarely comparable. Also, we found that the same standard parameters were measured rather than novel biomarkers. Diagnostics approaches appeared incomparable. Conclusions. Further collaborative investigations on harmonizing ways of data acquisition and identifying such biomarkers for clinical use are necessary to yield sufficient significant results of potential biomarkers.
A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study
Authors: Pagliarini Sergio , Beatty Stephen , Lipkova Blandina , Perez-Salvador Garcia Eduardo , Reynders Stefaan , Gekkieva Margarita , Si Bouazza Abdelkader , Pilz Stefan
Published: April 2014

Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice.Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years.Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%–1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, –1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis.Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated.
Optogenetics: Novel Tools for Controlling Mammalian Cell Functions with Light
Authors: Kushibiki Toshihiro , Okawa Shinpei , Hirasawa Takeshi , Ishihara Miya
Published: April 2014

In optogenetics, targeted illumination is used to control the functions of cells expressing exogenous light-activated proteins. Adoption of the optogenetic methods has expanded rapidly in recent years. In this review, we describe the photosensitive channel proteins involved in these methods, describe techniques for their targeting to neurons and other cell types both within and outside the nervous system, and discuss their applications in the field of neuroscience and beyond. We focus especially on the channelrhodopsin protein ChR2, the photosensitive protein most commonly employed in optogenetics. ChR2 has been used by many groups to control neuronal activity, bothin vitroandin vivo, on short time scales and with exquisite anatomical precision. In addition, we describe more recently developed tools such as opsin/G protein-coupled receptor chimeric molecules and a light-activated transgene system. In addition, we discuss the potential significance of optogenetics in the development of clinical therapeutics. Although less than a decade old, optogenetics is already responsible for enormous progress in disparate fields, and its future is unquestionably bright.
Global Exponential Stability of Positive Almost Periodic Solutions for a Fishing Model with a Time-Varying Delay
Authors: Zhang Hong , Gong Shuhua , Shao Jianying
Published: April 2014

This paper is concerned with a nonautonomous fishing model with a time-varying delay. Under proper conditions, we employ a novel argument to establish a criterion on the global exponential stability of positive almost periodic solutions of the model with almost periodic coefficients and delays. Moreover, an example and its numerical simulation are given to illustrate the main results.
Vitamin D Binding Protein Impact on 25-Hydroxyvitamin D Levels under Different Physiologic and Pathologic Conditions
Authors: Yousefzadeh Pegah , Shapses Sue A. , Wang Xiangbing
Published: April 2014

There is a high prevalence of vitamin D deficiency worldwide, but how to define vitamin D deficiency is controversial. Currently, the plasma concentration of total 25-hydroxyvitamin D [25(OH)D] is considered an indicator of vitamin D status. The free hormone hypothesis states that protein-bound hormones are inactive while unbound hormones are free to exert biological activity. The majority of circulating 25(OH)D and 1,25(OH)2D is tightly bound to vitamin D binding protein (DBP), 10–15% is bound to albumin, and less than 1% of circulating vitamin D exists in an unbound form. While DBP is relatively stable in most healthy populations, a recent study showed that there are gene polymorphisms associated with race and ethnicity that could alter DBP levels and binding affinity. Furthermore, in some clinical situations, total vitamin D levels are altered and knowing whether DBP is also altered may have treatment implications. The aim of this review is to assess DBP concentration in different physiological and pathophysiological conditions. We suggest that DBP should be considered in the interpretation of 25(OH)D levels.
NCOA1 Directly Targets M-CSF1 Expression to Promote Breast Cancer Metastasis
Authors: Qin Li , Wu Ye-Lin , Toneff Michael J. , Li Dabing , Liao Lan , Gao Xiuhua , Bane Fiona T. , Tien Jean C.-Y. , Xu Yixiang , Feng Zhen , Yang Zhihui , Xu Yan , Theissen Sarah M. , Li Yi , Young Leonie , Xu Jianming
Published: April 2014

In breast cancer, overexpression of the nuclear coactivator NCOA1 (SRC-1) is associated with disease recurrence and resistance to endocrine therapy. To examine the impact of NCOA1 overexpression on morphogenesis and carcinogenesis in the mammary gland (MG), we generated MMTV-hNCOA1 transgenic [Tg(NCOA1)] mice. In the context of two distinct transgenic models of breast cancer, NCOA1 overexpression did not affect the morphology or tumor-forming capability of MG epithelial cells. However, NCOA1 overexpression increased the number of circulating breast cancer cells and the efficiency of lung metastasis. Mechanistic investigations showed that NCOA1 and c-Fos were recruited to a functional AP-1 site in the macrophage attractant CSF1 promoter, directly upregulating colony-simulating factor 1 (CSF1) expression to enhance macrophage recruitment and metastasis. Conversely, silencing NCOA1 reduced CSF1 expression and decreased macrophage recruitment and breast cancer cell metastasis. In a cohort of 453 human breast tumors, NCOA1 and CSF1 levels correlated positively with disease recurrence, higher tumor grade, and poor prognosis. Together, our results define an NCOA1/AP-1/CSF1 regulatory axis that promotes breast cancer metastasis, offering a novel therapeutic target for impeding this process. Cancer Res; 74(13); 3477–88. ©2014 AACR.
Immunotherapy for Brain Cancer: Recent Progress and Future Promise
Authors: Jackson Christopher M. , Lim Michael , Drake Charles G.
Published: April 2014

Immunotherapy is emerging as the newest pillar of cancer treatment, with the potential to assume a place alongside surgical debulking, radiotherapy, and chemotherapy. Early experiences with antitumor vaccines demonstrated the feasibility and potential efficacy of this approach, and newer agents, such as immune checkpoint blocking antibodies and modern vaccine platforms, have ushered in a new era. These efforts are headlined by work in melanoma, prostate cancer, and renal cell carcinoma; however, substantial progress has been achieved in a variety of other cancers, including high-grade gliomas. A recurrent theme of this work is that immunotherapy is not a one-size-fits-all solution. Rather, dynamic, tumor-specific interactions within the tumor microenvironment continually shape the immunologic balance between tumor elimination and escape. High-grade gliomas are a particularly fascinating example. These aggressive, universally fatal tumors are highly resistant to radiotherapy and chemotherapy and inevitably recur after surgical resection. Located in the immune-privileged central nervous system, high-grade gliomas also use an array of defenses that serve as direct impediments to immune attack. Despite these challenges, vaccines have shown activity against high-grade gliomas, and anecdotal, preclinical, and early clinical data bolster the notion that durable remission is possible with immunotherapy. Realizing this potential, however, will require an approach tailored to the unique aspects of glioma biology. Clin Cancer Res; 20(14); 3651–9. ©2014 AACR.
Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy
Authors: Manceau Gilles , Imbeaud Sandrine , Thiébaut Raphaële , Liébaert François , Fontaine Karine , Rousseau Francis , Génin Bérengère , Corre Delphine Le , Didelot Audrey , Vincent Marc , Bachet Jean-Baptiste , Chibaudel Benoist , Bouché Olivier , Landi Bruno , Bibeau Frédéric , Leroy Karen , Penault-Llorca Frédérique , Van Laethem Jean-Luc , Demetter Pieter , Tejpar Sabine , Rossi Simona , Mosakhani Neda , Österlund Pia , Ristamäki Raija , Sarhadi Virinder , Knuutila Sakari , Boige Valérie , André Thierry , Laurent-Puig Pierre
Published: April 2014

Purpose: To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).

Experimental Design: miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.

Results: After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1–15.3; P < 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1–5.4; P = 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r2 = 0.49; P = 0.0035) and risk status determined by hsa-miR-31-3p expression level (P = 0.02, Kruskal–Wallis rank test). Nomograms were built and validated to predict PFS-depending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p.

Conclusion: Hsa-miR-31-3p seems to be a new mCRC biomarker whose expression level allows for the identification of patients with wild-type KRAS mCRC who are more likely to respond to anti-EGFR therapy. Clin Cancer Res; 20(12); 3338–47. ©2014 AACR.
RNAi Screen Identifies a Synthetic Lethal Interaction between PIM1 Overexpression and PLK1 Inhibition
Authors: van der Meer Riet , Yong Song Ha , Park Seong-Hoon , Abdulkadir Sarki A. , Roh Meejeon
Published: April 2014

Purpose: To identify genes whose depletion is detrimental to Pim1-overexpressing prostate cancer cells and to validate this finding in vitro and in vivo.

Experimental Design: RNAi screening was used to identify genes whose depletion is detrimental to Pim1-overexpressing cells. Our finding was validated using shRNA or PLK1-specific inhibitor BI 2536. Xenograft studies were performed using both PLK1-knockdown cells and BI 2536 to investigate the effects of PLK1 inhibition on tumorigenesis in Pim1-overexpressing cells. Finally, PLK1 and PIM1 expression patterns in human prostate tumors were examined by immunohistochemistry using tissue microarrays.

Results: We identified the mitotic regulator polo-like kinase (PLK1) as a gene whose depletion is particularly detrimental to the viability of Pim1-overexpressing prostate cancer. Inhibition of PLK1 by shRNA or BI 2536 in Pim1-overexpressing prostate cancer xenograft models resulted in a dramatic inhibition of tumor progression. Notably, Pim1-overexpressing cells were more prone to mitotic arrest followed by apoptosis due to PLK1 inhibition than control cells. Furthermore, inhibition of PLK1 led to the reduction of MYC protein levels both in vitro and in vivo. Our data also suggest that PIM1 and PLK1 physically interact and PIM1 might phosphorylate PLK1. Finally, PLK1 and PIM1 are frequently co-expressed in human prostate tumors, and co-expression of PLK1 and PIM1 was significantly correlated to higher Gleason grades.

Conclusions: Our findings demonstrate that PIM1-overexpressing cancer cells are particularly sensitive to PLK1 inhibition, suggesting that PIM1 might be used as a marker for identifying patients who will benefit from PLK1 inhibitor treatment. Clin Cancer Res; 20(12); 3211–21. ©2014 AACR.
Canonical Androstenedione Reduction Is the Predominant Source of Signaling Androgens in Hormone-Refractory Prostate Cancer
Authors: Fankhauser Matthew , Tan Yuen , Macintyre Geoff , Haviv Izhak , Hong Matthew K.H. , Nguyen Anne , Pedersen John S. , Costello Anthony J. , Hovens Christopher M. , Corcoran Niall M.
Published: April 2014

Purpose: It has been recognized for almost a decade that concentrations of signaling androgens sufficient to activate the androgen receptor are present in castration-resistant prostate cancer tissue. The source of these androgens is highly controversial, with three competing models proposed. We, therefore, wished to determine the androgenic potential of human benign and malignant (hormone-naïve and treated) prostate tissue when incubated with various precursors and examine concomitant changes in enzyme expression.

Experimental Design: Freshly harvested prostate tissue [benign, hormone-naïve, and hormone-refractory prostate cancer (HRPC)] was incubated in excess concentrations of cholesterol, progesterone, DHEA, androstenedione, or testosterone for 96 hours, and steroid concentrations in the conditioned media measured by gas chromatography–mass spectroscopy. Changes in the expression of androgen synthetic and/or degradative enzymes were determined by expression microarray and qPCR. Significant changes were confirmed in an independent dataset.

Results: Of the precursor molecules tested, only incubation with androstenedione gave rise to significant concentrations of signaling androgens. Although this was observed in all tissue types, it occurred to a significantly greater degree in hormone-refractory compared with hormone-naïve cancer. Consistent with this, gene set enrichment analysis of the expression microarray data revealed significant upregulation of 17HSD17B activity, with overexpression of the canonical enzyme AKR1C3 confirmed by qPCR in the same samples and in a publicly available expression dataset. Importantly, we found no evidence to support a significant contribution from either the “backdoor” or “5-α dione” pathway.

Conclusions: Reduction of androstenedione to testosterone by the canonical HSD17B AKR1C3 is the predominant source of signaling androgens in HRPC. Clin Cancer Res; 20(21); 5547–57. ©2014 AACR.