bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamma-Glutamylcyclotransferase: A Novel Target Molecule for Cancer Diagnosis and Treatment
Authors: Kageyama Susumu , Hanada Eiki , Ii Hiromi , Tomita Keiji , Yoshiki Tatsuhiro , Kawauchi Akihiro
Published: August 2015

Gamma-glutamylcyclotransferase (GGCT) is one of the major enzymes involved in glutathione metabolism. However, its gene locus was unknown for many years. Recently, the gene for GGCT was found to be identical to C7orf24, which is registered as a hypothetical protein. Orthologs have been found in bacteria, plants, and nematodes as well as higher organisms, and the GGCT gene is highly preserved among a wide range of species. GGCT (C7orf24) was also reported as an upregulated protein in various cancers. Although the function of GGCT in cancer cells has not been determined, the following important activities have been reported: (1) high expression in various cancer tissues and cancer cell lines, (2) low expression in normal tissues, (3) inhibition of cancer cell proliferation via anti-GGCT RNAi, (4) inhibition of cancer cell invasion and migration via anti-GGCT RNAi, (5) an epigenetic transcriptional regulation in cancer cells, and (6) an antitumor effect in cancer-bearing xenograft mice. Therefore, GGCT is promising as a diagnostic marker and a therapeutic target for various cancers. This review summarizes these interesting findings.
Dendritic Cell Activity Driven by RecombinantMycobacterium bovisBCG Producing Human IL-18, in Healthy BCG Vaccinated Adults
Authors: Szpakowski Piotr , Biet Franck , Locht Camille , Paszkiewicz Małgorzata , Rudnicka Wiesława , Druszczyńska Magdalena , Allain Fabrice , Fol Marek , Pestel Joël , Kowalewicz-Kulbat Magdalena
Published: August 2015

Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γbut also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γand IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.
The Pharmacokinetic Profile of a New Gastroresistant Capsule Preparation of Eicosapentaenoic Acid as the Free Fatty Acid
Authors: Scaioli Eleonora , Cardamone Carla , Liverani Elisa , Munarini Alessandra , Hull Mark A. , Belluzzi Andrea
Published: August 2015

Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for patients with inflammatory bowel diseases (IBD). In this study we analyzed the pharmacokinetic profile of eicosapentaenoic acid (EPA), as the free fatty acid (FFA), in an enteric-coated preparation, in 10 ulcerative colitis (UC) and 10 Crohn’s disease (CD) patients and 15 healthy volunteers (HV). Subjects received 2 g daily of EPA-FFA for 8 weeks. Plasma phospholipid and red blood cell (RBC) membrane fatty acid content were measured by gas chromatography-mass spectrometry. There was a rapid incorporation of EPA into plasma phospholipids by 2 weeks and a slower, but highly consistent, incorporation into RBC membranes (4% total fatty acid content; coefficient of variation 10–16%). There was a concomitant reduction in relative n-6 PUFA content. Elongation and desaturation of EPA into docosahexaenoic acid (DHA) via docosapentaenoic acid (DPA) were apparent and DHA content also increased in membranes. EPA-FFA is well tolerated and no difference in the pharmacokinetic profile of n-3 PUFA incorporation was detected between IBD patients and HV. Our data support the concept that EPA can be considered the “universal donor” with respect to key n-3 PUFAs and that this enteric-coated formulation allows long term treatment with a high level of compliance.
The Optimization of Transportation Costs in Logistics Enterprises with Time-Window Constraints
Authors: Yan Qingyou , Zhang Qian
Published: August 2015

This paper presents a model for solving a multiobjective vehicle routing problem with soft time-window constraints that specify the earliest and latest arrival times of customers. If a customer is serviced before the earliest specified arrival time, extra inventory costs are incurred. If the customer is serviced after the latest arrival time, penalty costs must be paid. Both the total transportation cost and the required fleet size are minimized in this model, which also accounts for the given capacity limitations of each vehicle. The total transportation cost consists of direct transportation costs, extra inventory costs, and penalty costs. This multiobjective optimization is solved by using a modified genetic algorithm approach. The output of the algorithm is a set of optimal solutions that represent the trade-off between total transportation cost and the fleet size required to service customers. The influential impact of these two factors is analyzed through the use of a case study.
One-Step Synthesis of High-Quality Water-Soluble CdSe Quantum Dots Capped byN-Acetyl-L-cysteineviaHydrothermal Method and Their Characterization
Authors: Wei Chunjin , Li Jinyu , Gao Fang , Guo Shuxia , Zhou Yongcui , Zhao Dan
Published: August 2015

Novel water-soluble CdSe quantum dots (QDs) have been prepared withN-acetyl-L-cysteine as new stabilizer through a one-step hydrothermal route. The influence of experimental conditions, including reaction time, molar ratio of reactants, and pH value, on the luminescent properties of the obtained CdSe QDs has been systematically investigated. The characterization of as-prepared QDs was carried out through different methods. In particular, we realized qualitative and semiquantitative studies on CdSe QDs through X-ray photoelectron spectroscopy and electron diffraction spectroscopy. The results show that the as-prepared CdSe QDs exhibit a high quantum yield (up to 26.7%), high stability, and monodispersity and might be widely used in biochemical detection and biochemical research.
Network Coding for Severe Packet Reordering in Multihop Wireless Networks
Authors: Lim Chansook
Published: August 2015

Network coding is known to be effective in overcoming packet losses and packet reordering in multihop wireless networks. Despite the benefits, network coding is hard to deploy without being compatible with TCP. To address this problem, a seminal paper proposed a network coding scheme that adopts an ACK-based sliding-widow network coding approach. In this paper we show that the previous scheme may not suffice to mitigate the effects of packets received out of order in multipath wireless networks where severe packet reordering persists. We propose a modified network coding layer where the receiver acknowledges every degree of freedom by using the sequence number of a newly seen packet instead of using that of the oldest unseen packet so that the network coding layer can be compatible with a TCP variant for severe packet reordering. To reduce the decoding matrix size and the coding buffer size, our scheme allows retransmission at the network coding layer. Simulation results show that our scheme outperforms the exiting scheme in multipath wireless networks particularly when severe packet reordering persists.
Study of Cytotoxic Effects of Benzonitrile Pesticides
Authors: Lovecka Petra , Thimova Marketa , Grznarova Petra , Lipov Jan , Knejzlik Zdenek , Stiborova Hana , Nindhia Tjokorda Gde Tirta , Demnerova Katerina , Ruml Tomas
Published: August 2015

The benzonitrile herbicides bromoxynil, chloroxynil, dichlobenil, and ioxynil have been used actively worldwide to control weeds in agriculture since 1970s. Even though dichlobenil is prohibited in EU since 2008, studies addressing the fate of benzonitrile herbicides in the environment show that some metabolites of these herbicides are very persistent. We tested the cytotoxic effects of benzonitrile herbicides and their microbial metabolites using two human cell lines, Hep G2 and HEK293T, representing liver and kidneys as potential target organs in humans. The cell viability and proliferation were determined by MTT test and RTCA DP Analyzer system, respectively. The latter allows real-time monitoring of the effect of added substances. As the cytotoxic compounds could compromise cell membrane integrity, the lactate dehydrogenase test was performed as well. We observed high toxic effects of bromoxynil, chloroxynil, and ioxynil on both tested cell lines. In contrast, we determined only low inhibition of cell growth in presence of dichlobenil and microbial metabolites originating from the tested herbicides.
Variations in Community Prevalence and Determinants of Recreational and Utilitarian Walking in Older Age
Authors: Procter-Gray Elizabeth , Leveille Suzanne G. , Hannan Marian T. , Cheng Jie , Kane Kevin , Li Wenjun
Published: August 2015

Background. Regular walking is critical to maintaining health in older age. We examined influences of individual and community factors on walking habits in older adults.Methods. We analyzed walking habits among participants of a prospective cohort study of 745 community-dwelling men and women, mainly aged 70 years or older. We estimated community variations in utilitarian and recreational walking, and examined whether the variations were attributable to community differences in individual and environmental factors.Results. Prevalence of recreational walking was relatively uniform while prevalence of utilitarian walking varied across the 16 communities in the study area. Both types of walking were associated with individual health and physical abilities. However, utilitarian walking was also strongly associated with several measures of neighborhood socioeconomic status and access to amenities while recreational walking was not.Conclusions. Utilitarian walking is strongly influenced by neighborhood environment, but intrinsic factors may be more important for recreational walking. Communities with the highest overall walking prevalence were those with the most utilitarian walkers. Public health promotion of regular walking should take this into account.
Different Plaque Composition and Progression in Patients with Stable and Unstable Coronary Syndromes Evaluated by Cardiac CT
Authors: Dalager Maiken Glud , Bøttcher Morten , Thygesen Jesper , Andersen Gratien , Bøtker Hans Erik
Published: August 2015

Objective.To compare the quantity, subtype, and progression of atherosclerosis by cardiac computed tomography (CT) and intravascular ultrasound (IVUS) in patients with stable (SAP) and unstable angina pectoris or non-ST-elevation myocardial infarction (UAP/n-STEMI).Methods.Forty patients with SAP and 20 with UAP/n-STEMI underwent cardiac CT and angiography with IVUS at baseline and after one year. Atherosclerotic segments were divided into calcified, mixed, or noncalcified subtypes, and significant stenoses were registered.Results.Thirty-two SAP and 15 UAP/n-STEMI patients completed the CT follow-up. At baseline, the number of atherosclerotic segments was higher in UAP/n-STEMI than in SAP (P=0.039). UAP/n-STEMI patients had more segments with noncalcified plaques (P=0.0005) whereas SAP patients had more segments with calcified plaques (P=0.013). The number of segments with significant stenosis did not differ between the groups, but noncalcified plaques more frequently caused significant stenoses in UAP/n-STEMI than in SAP patients (P=0.0002). After one year the number of segments with atherosclerosis increased in SAP patients (P=0.0001). The number of atherosclerotic segments remained unchanged in UAP/n-STEMI patients. However, composition was altered as the number of segments with noncalcified plaques decreased (P=0.018). IVUS data confirmed the CT findings.Conclusion.Quantity, subtype, and progression of atherosclerosis differ between SAP and UAP/n-STEMI patients.
ZnO Nanoparticles Treatment Induces Apoptosis by Increasing Intracellular ROS Levels in LTEP-a-2 Cells
Authors: Wang Caixia , Hu Xiaoke , Gao Yan , Ji Yinglu
Published: August 2015

Owing to the wide use of novel nanoparticles (NPs) such as zinc oxide (ZnO) in all aspects of life, toxicological research on ZnO NPs is receiving increasing attention in these days. In this study, the toxicity of ZnO NPs in a human pulmonary adenocarcinoma cell line LTEP-a-2 was testedin vitro. Log-phase cells were exposed to different levels of ZnO NPs for hours, followed by colorimetric cell viability assay using tetrazolium salt and cell survival rate assay using trypan blue dye. Cell morphological changes were observed by Giemsa staining and light microscopy. Apoptosis was detected by using fluorescence microscopy and caspase-3 activity assay. Both intracellular reactive oxygen species (ROS) and reduced glutathione (GSH) were examined by a microplate-reader method. Results showed that ZnO NPs (≥0.01 μg/mL) significantly inhibited proliferation (P<0.05) and induced substantial apoptosis in LTEP-a-2 cells after 4 h of exposure. The intracellular ROS level rose up to 30–40% corresponding to significant depletion (approximately 70–80%) in GSH content in LTEP-a-2 cells (P<0.05), suggesting that ZnO NPs induced apoptosis mainly through increased ROS production. This study elucidates the toxicological mechanism of ZnO NPs in human pulmonary adenocarcinoma cells and provides reference data for application of nanomaterials in the environment.
Timetable Design for Urban Rail Line with Capacity Constraints
Authors: Zhu Yu-Ting , Mao Bao-Hua , Liu Lu , Li Ming-Gao
Published: August 2015

To design an efficient and economical timetable for a heavily congested urban rail corridor, a scheduling model is proposed in this paper. The objective of the proposed model is to find the departure time of trains at the start terminal to minimize the system cost, which includes passenger waiting cost and operating cost. To evaluate the performance of the timetable, a simulation model is developed to simulate the detailed movements of passengers and trains with strict constraints of station and train capacities. It assumes that passengers who arrive early will have more chances to access a station and board a train. The accessing and boarding processes of passengers are all based on a first-come-first-serve basis. When a station is full, passengers unable to access must wait outside until the number of waiting passengers at platform falls below a given value. When a train is full, passengers unable to board must wait at the platform for the next train to arrive. Then, based on the simulation results, a two-stage genetic algorithm is introduced to find the best timetable. Finally, a numerical example is given to demonstrate the effectiveness of the proposed model and solution method.
Identifying and Assessing Interesting Subgroups in a Heterogeneous Population
Authors: Lee Woojoo , Alexeyenko Andrey , Pernemalm Maria , Guegan Justine , Dessen Philippe , Lazar Vladimir , Lehtiö Janne , Pawitan Yudi
Published: August 2015

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such ask-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability—the basis of cluster generation—is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.
Setting Reaction of Dental Resin-Modified Glass Ionomer Restoratives as a Function of Curing Depth and Postirradiation Time
Authors: Kim Young Kyung , Kim Kyo-Han , Kwon Tae-Yub
Published: August 2015

Specular reflectance Fourier transform infrared (SR-FTIR) spectroscopy was used to study the setting reaction of dental resin-modified glass ionomer (RMGI) restoratives as a function of curing depth and postirradiation time. Two light-cure and one tri-cure RMGI materials were selected and used according to the manufacturers’ instructions. Samples were prepared by filling the mixed materials into custom-made molds and then light-irradiating using a dental curing light. The degree of conversion and the extent of acid-base reaction of the materials at different depths (0, 1, 2, and 4 mm) and postirradiation times (10 min, 1 day, and 7 days) were determined using SR-FTIR spectroscopy in conjunction with the Kramers-Kronig (K-K) transformation. The setting reaction was also investigated using microhardness measurements. The results showed that the depth of cure increased over time by the continuous acid-base reaction rather than photopolymerization or chemical polymerization. Microhardness tests seemed less suitable for studying the setting reaction as a function of postirradiation time, probably due to softening from the humidity. Analysis using specular reflectance in conjunction with the K-K algorithm was an easy and effective method for monitoring the setting reaction of dental RMGI materials.
Sibling Death after Being Thrown from Window by Brother with Autism: Defenestration, an Emerging High-Risk Behavior
Authors: Sabuncuoglu Osman , Irmak Mustafa Yasin , Ucok Demir Nagehan , Murat Duygu , Tumba Can , Yilmaz Yuksel
Published: August 2015

Children diagnosed with autistic spectrum disorders (ASD) may have serious behavioral problems such as aggression, self-injury, and violence. However, the literature on ASD either overrules any correlation between aggression and ASD or maintains the fact that the efforts to link them have so far been inconclusive. Although severe forms of violence are extremely rare in children with autism, there are a few cases reported in the literature with significant harm to siblings. We hereby report an 8-year-old boy with ASD who caused the death of his sibling by throwing her out of the window. Shared similarities of all defenestration cases indicate a pattern of high-risk behavior threatening the survival of minors. We recommend precautions against this high-risk behavior in children with ASD.
Violacein: Properties and Production of a Versatile Bacterial Pigment
Authors: Choi Seong Yeol , Yoon Kyoung-hye , Lee Jin Il , Mitchell Robert J.
Published: August 2015

Violacein-producing bacteria, with their striking purple hues, have undoubtedly piqued the curiosity of scientists since their first discovery. The bisindole violacein is formed by the condensation of two tryptophan molecules through the action of five proteins. The genes required for its production,vioABCDE, and the regulatory mechanisms employed have been studied within a small number of violacein-producing strains. As a compound, violacein is known to have diverse biological activities, including being an anticancer agent and being an antibiotic againstStaphylococcus aureusand other Gram-positive pathogens. Identifying the biological roles of this pigmented molecule is of particular interest, and understanding violacein’s function and mechanism of action has relevance to those unmasking any of its commercial or therapeutic benefits. Unfortunately, the production of violacein and its related derivatives is not easy and so various groups are also seeking to improve the fermentative yields of violacein through genetic engineering and synthetic biology. This review discusses the recent trends in the research and production of violacein by both natural and genetically modified bacterial strains.
Accurately Identifying New QoS Violation Driven by High-Distributed Low-Rate Denial of Service Attacks Based on Multiple Observed Features
Authors: Kang Jian , Yang Mei , Zhang Junyao
Published: August 2015

We propose using multiple observed features of network traffic to identify new high-distributed low-rate quality of services (QoS) violation so that detection accuracy may be further improved. For the multiple observed features, we chooseF featurein TCP packet header as a microscopic feature and,P featureandD featureof network traffic as macroscopic features. Based on these features, we establishmultistream fused hidden Markov model(MF-HMM) to detect stealthy low-rate denial of service (LDoS) attacks hidden in legitimate network background traffic. In addition, the threshold value is dynamically adjusted by using Kaufman algorithm. Our experiments show that the additive effect of combining multiple features effectively reduces the false-positive rate. The average detection rate of MF-HMM results in a significant 23.39% and 44.64% improvement over typical power spectrum density (PSD) algorithm and nonparametric cumulative sum (CUSUM) algorithm.
Coevolution of Artificial Agents Using Evolutionary Computation in Bargaining Game
Authors: Lee Sangwook
Published: August 2015

Analysis of bargaining game using evolutionary computation is essential issue in the field of game theory. This paper investigates the interaction and coevolutionary process among heterogeneous artificial agents using evolutionary computation (EC) in the bargaining game. In particular, the game performance with regard to payoff through the interaction and coevolution of agents is studied. We present three kinds of EC based agents (EC-agent) participating in the bargaining game: genetic algorithm (GA), particle swarm optimization (PSO), and differential evolution (DE). The agents’ performance with regard to changing condition is compared. From the simulation results it is found that the PSO-agent is superior to the other agents.
Potential Utility of Novel Biomarkers in Active Surveillance of Low-Risk Prostate Cancer
Authors: Kim Jeong Hyun , Hong Sung Kyu
Published: August 2015

Active surveillance (AS) is now an accepted management strategy for men with low-risk localized prostate cancer (PCa). However, detecting disease progression in a patient selected for AS remains a challenge. It is crucial to know what will serve as the best parameter to correctly identify tumors that progress to a more aggressive phenotype so as not to miss the window of curability. Several biomarkers are now being actively investigated as novel tools to improve PCa risk assessments. To date, several serum, urinary, and tissue biomarkers have shown promising prognostic value. %[−2]proPSA and PHI showed improved predictive value for an unfavorable biopsy conversion at annual surveillance biopsy in the AS program. PCA3 and TMPRSS2:ERG had additional independent predictive value for the prediction of PCa detection and progression, although PCA3 was limited in predicting aggressive cancer. Other tissue biomarkers also showed promising ability to predict disease progression. Although several of these novel biomarkers have an improved predictive accuracy that is better than classical parameters, there is still a need for further well-designed, large, multicenter, prospective trials to avoid common bias and clinical validation.
Effect of Docosahexaenoic Acid on Apoptosis and Proliferation in the Placenta: Preliminary Report
Authors: Wietrak Ewa , Kamiński Krzysztof , Leszczyńska-Gorzelak Bożena , Oleszczuk Jan
Published: August 2015

Introduction.Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction (IUGR) and preeclampsia, with excessive apoptosis. One potential mechanism of action of docosahexaenoic acid (DHA) promoting a reduction in the risk of pathological pregnancy may be by influencing these processes in the placenta.Materials and Methods.We investigated 28 pregnant women supplemented with a fish oil product containing 300 mg DHA starting from pregnancy week 20 until delivery (DHA group). The control group consisted of 50 women who did not receive such supplementation (control group). We determined the expression of Ki-67 and p21 as markers of proliferation and caspase 3 activity as a marker of apoptosis and DHA levels in umbilical cord blood.Results.Caspase 3 activity was significantly lower in the DHA group in comparison to the control group. Umbilical cord blood DHA concentration was higher in the DHA group. The expression of the proteins p21 and Ki-67 did not differ significantly between the groups.Conclusions.We observed an association between DHA supplementation and inhibition of placental apoptosis. We did not find an association between DHA and proliferation process in the placenta.
Prognostic Significance of Serum Inflammatory Response Markers in Newly Diagnosed Non-Small Cell Lung Cancer before Chemoirradiation
Authors: Tolia Maria , Tsoukalas Nikolaos , Kyrgias George , Mosa Eftychia , Maras Apostolos , Kokakis Ioannis , Liakouli Zoi , Kouvaris John R. , Liaskonis Konstantinos , Charalampakis Nikolaos , Pistevou-Gombaki Kyriaki , Kelekis Nikolaos , Kouloulias Vassilis
Published: August 2015

Purpose. To identify whether the serum’s baseline C-reactive protein (CRP) and albumin (Alb) levels related to clinicopathological parameters and overall survival (OS) in non-small cell lung cancer (NSCLC).Methods. In total, 100 consecutive patients (mean age = 68.38 ± 10.85 years) that underwent chemoradiotherapy were studied. Measurements of CRP and Alb were performed before any treatment.Results. Serum CRP levels were significantly associated with histological grade(P<0.001), TNM stage(P<0.001), PS(P=0.009), and Alb(P<0.001). Additionally CRP and Alb levels were found significantly associated with overall survival in univariate analysis (log-rank test,P<0.001andP=0.002, resp.) and CRP remained significant after controlling for age, alcohol, performance status, and TNM stage, whereas albumin showed a borderline effect on the hazard rate(P=0.052).Conclusions. CRP and Alb are both promising biomarkers in identification of NSCLC patients with poor prognosis and form a possible target for intensifying their therapies.
Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments
Authors: de Mattos Bruno Rafael Ramos , Garcia Maellin Pereira Gracindo , Nogueira Julia Bier , Paiatto Lisiery Negrini , Albuquerque Cassia Galdino , Souza Caique Lopes , Fernandes Luís Gustavo Romani , Tamashiro Wirla Maria da Silva Cunha , Simioni Patricia Ucelli
Published: August 2015

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti‐TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.
Detecting Genetic Interactions for Quantitative Traits Usingm-Spacing Entropy Measure
Authors: Yee Jaeyong , Kwon Min-Seok , Jin Seohoon , Park Taesung , Park Mira
Published: August 2015

A number of statistical methods for detecting gene-gene interactions have been developed in genetic association studies with binary traits. However, many phenotype measures are intrinsically quantitative and categorizing continuous traits may not always be straightforward and meaningful. Association of gene-gene interactions with an observed distribution of such phenotypes needs to be investigated directly without categorization. Information gain based on entropy measure has previously been successful in identifying genetic associations with binary traits. We extend the usefulness of this information gain by proposing a nonparametric evaluation method of conditional entropy of a quantitative phenotype associated with a given genotype. Hence, the information gain can be obtained for any phenotype distribution. Because any functional form, such as Gaussian, is not assumed for the entire distribution of a trait or a given genotype, this method is expected to be robust enough to be applied to any phenotypic association data. Here, we show its use to successfully identify the main effect, as well as the genetic interactions, associated with a quantitative trait.
Superhydrophobic Polyimide via Ultraviolet Photooxidation: The Evolution of Surface Morphology and Hydrophobicity under Different Ultraviolet Intensities
Authors: Gu Hongyu , Song Lixin , Zhang Jinlin , Qi Zhenyi
Published: August 2015

Ultraviolet (UV) photooxidation has recently been developed to fabricate superhydrophobic polyimide (PI) films in combination with fluoroalkylsilane modification. However, it remains unclear whether the surface morphology and hydrophobicity are sensitive to technical parameters such as UV intensity and radiation environment. Herein, we focus on the effects of UV intensity on PI surface structure and wettability to gain comprehensive understanding and more effective control of this technology. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) results showed that UV intensity governed the evolutionary pattern of surface morphology: lower UV intensity (5 mW/cm2) facilitated in‐plane expansion of dendritic protrusions while stronger UV (10 and 15 mW/cm2) encouraged localized growth of protrusions in a piling‐up manner. Surface roughness and hydrophobicity maximized at the intensity of 10 mW/cm2, as a consequence of the slowed horizontal expansion and preferred vertical growth of the protrusions when UV intensity increased. Based on these results, the mechanism that surface micro/nanostructures developed in distinct ways when exposed to different UV intensities was proposed. Though superhydrophobicity (water contact angle larger than 150°) can be achieved at UV intensity not less than 10 mW/cm2, higher intensity decreased the effectiveness. Therefore, the UV photooxidation under 10 mW/cm2 for 72 h is recommended to fabricate superhydrophobic PI films.
Inflammatory Mediators of Leprosy Reactional Episodes and Dental Infections: A Systematic Review
Authors: Cortela D. C. B. , Souza Junior A. L. de , Virmond M. C. L. , Ignotti E.
Published: August 2015

Reactional episodes in leprosy are a result of complex interactions between the immune system, Mycobacterium leprae, and predisposing factors, including dental infections. To determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. A three‐stage literature search was performed (Stage I, “leprosy reactions” and “inflammatory mediators”; Stage II, “dental infections” and “inflammatory mediators”; and Stage III, “leprosy reactions,” “dental infections,” and “inflammatory mediators”). Of the 911 eligible publications, 10 were selected in Stage I, 68 in Stage II, and 1 in Stage III. Of the 27 studied inflammatory mediators, the main proinflammatory mediators were IL‐6, IFN‐γ, TNF‐α, IL‐1β, and IL‐17; the main anti‐inflammatory mediators were IL‐10 and IL‐4. Serum IL‐6 and TNF‐α concentrations were significant during periodontal and reactional lesion evolution; IFN‐γ and IL‐1β were associated with types 1 and 2 reactions and chronic periodontal disease. The proinflammatory mediators in dental infections and leprosy reactions, especially IL‐6 and TNF‐α, were similar across studies, regardless of the laboratory technique and sample type. IFN‐γ and IL‐1β were significant for leprosy reactions and periodontal diseases. This pattern was maintained in serum.
N-3 Polyunsaturated Fatty Acids and Inflammation in Obesity: Local Effect and Systemic Benefit
Authors: Wang Yue , Huang Feiruo
Published: August 2015

Overwhelming consensus emerges among countless evidences that obesity is characterized by a chronic low-grade inflammation in the adipose tissue (AT), which subsequently develops into a systemic inflammatory state contributing to obesity-associated diseases. N-3 Polyunsaturated fatty acids (n-3 PUFA), known as important modulators participating in inflammatory process, turn out to be an effective mitigating strategy dealing with local and systemic inflammation observed in obesity. Some of the effects of n-3 PUFA are brought about by regulation of gene expression through interacting with nuclear receptors and transcription factors; other effects are elicited by modulation of the amount and type of mediator derived from PUFAs. The metabolic effects of n-3 PUFA mainly result from their interactions with several organ systems, not limited to AT. Notably, the attenuation of inflammation in hard-hit AT, in turn, contributes to reducing circulating concentrations of proinflammatory cytokines and detrimental metabolic derivatives, which is beneficial for the function of other involved organs. The present review highlights a bridging mechanism between n-3 PUFA-mediated inflammation relief in AT and systemic benefits.
Ficolin B in Diabetic Kidney Disease in a Mouse Model of Type 1 Diabetes
Authors: Holt Charlotte Berg , Østergaard Jakob Appel , Axelgaard Esben , Nielsen Gitte Krogh , Endo Yuichi , Thiel Steffen , Hansen Troels Krarup
Published: August 2015

Background. The innate immune system may have adverse effects in diabetes and cardiovascular disease. The complement system seems to play a key role through erroneous complement activation via hyperglycaemia‐induced neoepitopes. Recently mannan‐binding lectin (MBL) was shown to worsen diabetic kidney changes. We hypothesize that mouse ficolin B exerts detrimental effects in the diabetic kidney as seen for MBL. Methods. We induced diabetes with streptozotocin in female wild‐type mice and ficolin B knockout mice and included two similar nondiabetic groups. Renal hypertrophy and excretion of urinary albumin and creatinine were quantified to assess diabetic kidney damage. Results. In the wild‐type groups, the kidney weighed 24% more in the diabetic mice compared to the controls. The diabetes‐induced increase in kidney weight was 29% in the ficolin B knockout mice, that is, equal to wild‐type animals (two‐way ANOVA, P = 0.60). In the wild‐type mice the albumin‐to‐creatinine ratio (ACR) was 32.5 mg/g higher in the diabetic mice compared to the controls. The difference was 62.5 mg/g in the ficolin B knockout mice, but this was not significantly different from the wild‐type animals (two‐way ANOVA, P = 0.21). Conclusions. In conclusion, the diabetes‐induced effects on kidney weight and ACR were not modified by the presence or absence of ficolin B.
On the Estimation of Heritability with Family-Based and Population-Based Samples
Authors: Kim Youngdoe , Lee Young , Lee Sungyoung , Kim Nam Hee , Lim Jeongmin , Kim Young Jin , Oh Ji Hee , Min Haesook , Lee Meehee , Seo Hyeon-Jeong , Lee So-Hyun , Sung Joohon , Cho Nam H. , Kim Bong-Jo , Han Bok-Ghee , Elston Robert C. , Won Sungho , Lee Juyoung
Published: August 2015

For a family-based sample, the phenotypic variance-covariance matrix can be parameterized to include the variance of a polygenic effect that has then been estimated using a variance component analysis. However, with the advent of large-scale genomic data, the genetic relationship matrix (GRM) can be estimated and can be utilized to parameterize the variance of a polygenic effect for population-based samples. Therefore narrow sense heritability, which is both population and trait specific, can be estimated with both population- and family-based samples. In this study we estimate heritability from both family-based and population-based samples, collected in Korea, and the heritability estimates from the pooled samples were, for height, 0.60; body mass index (BMI), 0.32; log-transformed triglycerides (log TG), 0.24; total cholesterol (TCHL), 0.30; high-density lipoprotein (HDL), 0.38; low-density lipoprotein (LDL), 0.29; systolic blood pressure (SBP), 0.23; and diastolic blood pressure (DBP), 0.24. Furthermore, we found differences in how heritability is estimated—in particular the amount of variance attributable to common environment in twins can be substantial—which indicates heritability estimates should be interpreted with caution.
A Comparative Study on Multifactor Dimensionality Reduction Methods for Detecting Gene-Gene Interactions with the Survival Phenotype
Authors: Lee Seungyeoun , Kim Yongkang , Kwon Min-Seok , Park Taesung
Published: August 2015

Genome-wide association studies (GWAS) have extensively analyzed single SNP effects on a wide variety of common and complex diseases and found many genetic variants associated with diseases. However, there is still a large portion of the genetic variants left unexplained. This missing heritability problem might be due to the analytical strategy that limits analyses to only single SNPs. One of possible approaches to the missing heritability problem is to consider identifying multi-SNP effects or gene-gene interactions. The multifactor dimensionality reduction method has been widely used to detect gene-gene interactions based on the constructive induction by classifying high-dimensional genotype combinations into one-dimensional variable with two attributes of high risk and low risk for the case-control study. Many modifications of MDR have been proposed and also extended to the survival phenotype. In this study, we propose several extensions of MDR for the survival phenotype and compare the proposed extensions with earlier MDR through comprehensive simulation studies.
Adsorption of Polymeric Additives Based on Vinyl Acetate Copolymers as Wax Dispersant and Its Relevance to Polymer Crystallization Mechanisms
Authors: Atta Ayman M. , El-Ghazawy Rasha A. , Morsy Fatma A. , Hebishy Ali M. S. , Elmorsy Abdullah
Published: August 2015

The present work has main target to study the effect of additives molecular weight and composition on the flow characteristics of wax crude oil at low temperature below pour point temperature. In this respect, maleic anhydride ester-co-vinyl acetate copolymers with varied monomers feed ratios and different alkyl ester lengths, namely, dodecyl, stearyl, and behenyl alkyl chains, were prepared. These polymeric materials were characterized by FTIR,1HNMR, and GPC. The performance of these additives as pour point depressants and flow improver for Egyptian waxy crude oil was evaluated through measurements of pour point and rheological parameters (viscosity and yield stress). It was observed that stearyl maleate-vinyl acetate copolymer with 1 : 2 feed ratio shows the best efficiency as pour point depressant even at low concentration while octadecyl maleate-vinyl acetate copolymers with 2 : 1 feed ratio are effective as flow improver.
Improved Production of Sublancin 168 Biosynthesized byBacillus subtilis168 Using Chemometric Methodology and Statistical Experimental Designs
Authors: Ji Shengyue , Li Weili , Xin Haiyun , Wang Shan , Cao Binyun
Published: August 2015

Sublancin 168, as a distinct S-linked antimicrobial glycopeptide produced byBacillus subtilis168, is effective in killing specific microorganisms. However, the reported yield of sublancin 168 is at a low level of no more than 60 mg from 1 L fermentation culture ofB. subtilis168 by using the method in the literature. Thus optimization of fermentation condition for efficiently producing sublancin 168 is required. Here, Box-Behnken design was used to determine the optimal combination of three fermentation parameters, namely, corn powder, soybean meal, and temperature that were identified previously by Plackett-Burman design and the steepest ascent experiment. Subsequently, based on the response surface methodology, the quadratic regression model for optimally producing sublancin 168 was developed, and the optimal combination of culture parameters for maximum sublancin 168 production of 129.72 mg/L was determined as corn powder 28.49 g/L, soybean meal 22.99 g/L, and incubation temperature 30.8°C. The results showed that sublancin 168 production obtained experimentally was coincident with predicted value of 125.88 mg/L, and the developed model was proved to be adequate, and the aim of efficiently producing sublancin 168 was achieved.
Factors Associated with Successful Treatment by Radiofrequency Treatment of the Soft Palate in Obstructive Sleep Apnea as the First-Line Treatment
Authors: Sonsuwan Nuntigar , Rujimethabhas Kongsak , Sawanyawisuth Kittisak
Published: August 2015

Background. Radiofrequency ablation (RFA) is recommended as the second-line treatment for obstructive sleep apnea (OSA). This study aims to study the factors associated with successful treatment by RFA in OSA patients as the first-line treatment.Methods. All patients diagnosed as mild to moderate OSA were enrolled prospectively and treated with RFA. Three points of soft palate were ablated: midline, left, and right paramedian sites. Baseline characteristics and clinical factors including snoring score (SS), Epworth Sleepiness Scale (ESS), and apnea-hypopnea index (AHI), with minimal oxygen saturation, were recorded at baseline and three months after treatment.Results. During the study period, there were 51 patients who met the study criteria and received RFA treatment. At three months, the SS, ESS, and AHI were significantly lower than baseline values, while the minimal oxygenation was significantly increased from the baseline values. There were 16 patients (31.37%) who had an AHI of < 5 times/h. Only baseline AHI was significantly associated with an AHI of < 5 times/h at three months after RFA treatment. The adjusted odds ratio was 0.804 (95% CI: 0.699, 0.924).Conclusion. Transoral RFA treatment may be effective in mild to moderate OSA as the first-line treatment. Baseline AHI is associated with preferable outcome by RFA treatment.
Similarities in Gene Expression Profiles duringIn VitroAging of Primary Human Embryonic Lung and Foreskin Fibroblasts
Authors: Marthandan Shiva , Priebe Steffen , Baumgart Mario , Groth Marco , Cellerino Alessandro , Guthke Reinhard , Hemmerich Peter , Diekmann Stephan
Published: August 2015

Replicative senescence is of fundamental importance for the process of cellular aging, since it is a property of most of our somatic cells. Here, we elucidated this process by comparing gene expression changes, measured by RNA-seq, in fibroblasts originating from two different tissues, embryonic lung (MRC-5) and foreskin (HFF), at five different time points during their transition into senescence. Although the expression patterns of both fibroblast cell lines can be clearly distinguished, the similar differential expression of an ensemble of genes was found to correlate well with their transition into senescence, with only a minority of genes being cell line specific. Clustering-based approaches further revealed common signatures between the cell lines. Investigation of the mRNA expression levels at various time points during the lifespan of either of the fibroblasts resulted in a number of monotonically up- and downregulated genes which clearly showed a novel strong link to aging and senescence related processes which might be functional. In terms of expression profiles of differentially expressed genes with age, common genes identified here have the potential to rule the transition into senescence of embryonic lung and foreskin fibroblasts irrespective of their different cellular origin.
Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis
Authors: Andrés Cerezo Lucie , Kuklová Markéta , Hulejová Hana , Vernerová Zdeňka , Kaspříková Nikola , Veigl David , Pavelka Karel , Vencovský Jiří , Šenolt Ladislav
Published: August 2015

Objective. Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA. Methods. PGRN levels were evaluated in patients with RA (n = 47) and OA (n = 42) and healthy controls (n = 41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C‐reactive protein (CRP), disease activity score (DAS28‐CRP), and health assessment questionnaire (HAQ) was studied. Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1 ± 100.2 and 221.5 ± 102.5 versus 128.1 ± 34.7 ng/mL; P < 0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5 ± 275.3 versus 241.4 ± 165.2 ng/mL; P = 0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r = 0.327, P = 0.049) and HAQ score (r = 0.323, P = 0.032), while synovial fluid PGRN correlated only with HAQ (r = 0.310, P = 0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies. Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.