bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards Improving Meta-Search through Exploiting an Integrated Search Model
Authors: Maree Mohammed , Alhashmi Saadat M. , Belkhatir Mohammed
Published: January 2012

Meta-search engines are created to reduce the burden on the user by dispatching queries to multiple search engines in parallel. Decisions on how to rank the returned results are made based on the query's keywords. Although keyword-based search model produces good results, better results can be obtained by integrating semantic and statistical based relatedness measures into this model. Such integration allows the meta-search engine to search by meanings rather than only by literal strings. In this article, we present Multi-Search+, the next generation of Multi-Search general-purpose meta-search engine. The extended version of the system employs additional knowledge represented by multiple domain-specific ontologies to enhance both the query processing and the returned results merging. In addition, new general-purpose search engines are plugged-in to its architecture. Experimental results demonstrate that our integrated search model obtained significant improvement in the quality of the produced search results.
USING ATTRIBUTE BEHAVIOR DIVERSITY TO BUILD ACCURATE DECISION TREE COMMITTEES FOR MICROARRAY DATA
Authors: HAN QIAN , DONG GUOZHU
Published: January 2012

DNA microarrays (gene chips), frequently used in biological and medical studies, measure the expressions of thousands of genes per sample. Using microarray data to build accurate classifiers for diseases is an important task. This paper introduces an algorithm, called Committee of Decision Trees by Attribute Behavior Diversity (CABD), to build highly accurate ensembles of decision trees for such data. Since a committee's accuracy is greatly influenced by the diversity among its member classifiers, CABD uses two new ideas to "optimize" that diversity, namely (1) the concept of attribute behavior–based similarity between attributes, and (2) the concept of attribute usage diversity among trees. The ideas are effective for microarray data, since such data have many features and behavior similarity between genes can be high. Experiments on microarray data for six cancers show that CABD outperforms previous ensemble methods significantly and outperforms SVM, and show that the diversified features used by CABD's decision tree committee can be used to improve performance of other classifiers such as SVM. CABD has potential for other high-dimensional data, and its ideas may apply to ensembles of other classifier types.
MUNICIPAL WASTE MANAGEMENT STRATEGIES, STRATEGIC ENVIRONMENTAL ASSESSMENT AND THE CONSIDERATION OF CLIMATE CHANGE IN ENGLAND
Authors: FISCHER THOMAS B. , POTTER KAREN , DONALDSON STUART , SCOTT TONY
Published: January 2012

Municipal waste management strategies (MWMSs) are local level policy instruments, prepared in an area wide manner all over England, aiming to achieve more sustainable waste management practices. Their focus is on different aspects of the waste management hierarchy, including waste reduction, reuse, recycling/composting and residual waste management. In this paper, a systematic review of MWMS strategic environmental assessments (SEAs), completed by February 2010 is provided. SEA report quality and the extent to which climate change mitigation is considered are evaluated. Whilst there are strengths of current practice, there is also scope for improvement, particularly regarding a more effective consideration of the waste management hierarchy. Furthermore, whilst climate change mitigation is routinely considered as an overall objective, none of the SEAs set related targets, for example regarding carbon emission reduction.
Selective optogenetic stimulation of cholinergic axons in neocortex
Authors: Kalmbach Abigail , Hedrick Tristan , Waters Jack
Published: January 2012

Acetylcholine profoundly affects neocortical function, being involved in arousal, attention, learning, memory, sensory and motor function, and plasticity. The majority of cholinergic afferents to neocortex are from neurons in nucleus basalis. Nucleus basalis also contains projecting neurons that release other transmitters, including GABA and possibly glutamate. Hence, electrical stimulation of nucleus basalis evokes the release of a mixture of neurotransmitters in neocortex, and this lack of selectivity has impeded research on cholinergic signaling in neocortex. We describe a method for the selective stimulation of cholinergic axons in neocortex. We used the Cre-lox system and a viral vector to express the light-activated protein channelrhodopsin-2 in cholinergic neurons in nucleus basalis and their axons in neocortex. Labeled neurons depolarized on illumination with blue light but were otherwise unchanged. In anesthetized mice, illumination of neocortex desynchronized the local field potential, indicating that light evoked release of ACh. This novel technique will enable many new studies of the cellular, network, and behavioral physiology of ACh in neocortex.
Gene prioritization for livestock diseases by data integration
Authors: Jiang Li , Sørensen Peter , Thomsen Bo , Edwards Stefan M. , Skarman Axel , Røntved Christine M. , Lund Mogens S. , Workman Christopher T.
Published: January 2012

Identifying causal genes that underlie complex traits such as susceptibility to disease is a primary aim of genetic and biomedical studies. Genetic mapping of quantitative trait loci (QTL) and gene expression profiling based on high-throughput technologies are common first approaches toward identifying associations between genes and traits; however, it is often difficult to assess whether the biological function of a putative candidate gene is consistent with a particular phenotype. Here, we have implemented a network-based disease gene prioritization approach for ranking genes associated with quantitative traits and diseases in livestock species. The approach uses ortholog mapping and integrates information on disease or trait phenotypes, gene-associated phenotypes, and protein-protein interactions. It was used for ranking all known genes present in the cattle genome for their potential roles in bovine mastitis. Gene-associated phenome profile and transcriptome profile in response to Escherichia coli infection in the mammary gland were integrated to make a global inference of bovine genes involved in mastitis. The top ranked genes were highly enriched for pathways and biological processes underlying inflammation and immune responses, which supports the validity of our approach for identifying genes that are relevant to animal health and disease. These gene-associated phenotypes were used for a local prioritization of candidate genes located in a QTL affecting the susceptibility to mastitis. Our study provides a general framework for prioritizing genes associated with various complex traits in different species. To our knowledge this is the first time that gene expression, ortholog mapping, protein interactions, and biomedical text data have been integrated systematically for ranking candidate genes in any livestock species.
Do Parental Expectations Play a Role in Children's Sleep and Mothers' Distress? An Exploration of the Goodness of Fit Concept in 54 Mother-Child Dyads
Authors: Werner Helene , Jenni Oskar G.
Published: January 2012

This study describes parental expectations for sleep-wake patterns in healthy kindergarten children and explores their relation to children’s sleep quality and parental distress. Data analysis of 54 mother-child dyads (age range of the children: 4–7 years) indicated that parental expectations for children’s sleep-wake patterns differ between scheduled and free days and depend on children’s chronotype. Mothers of children with late chronotype showed less adequate expectations for children’s sleep onset time than mothers of children with early chronotype (e.g., morning types). Furthermore, children of mothers with less adequate expectations for children’s sleep onset time on scheduled days had longer settling periods during which sleep rituals may take place (r=0.31,P≤0.05), spent more time in bed than they actually sleep (r=0.35,P≤0.01), and had more frequently difficulties falling asleep (r=0.33,P≤0.01). However, less adequate expectations for children’s sleep onset time were not associated with parental distress (P>0.05). We conclude that parental expectations about their children’s sleep play a key role in understanding normal and abnormal sleep during childhood.
Homozygous Familial Hypercholesterolemia: Case Series and Review of the Literature
Authors: Palacio Carlos H. , Harring Theresa R. , Nguyen N. Thao T. , Goss John A. , O'Mahony Christine A.
Published: January 2012

Introduction. Familial hypercholesterolemia (FH) is caused by nonfunctioning low-density lipoprotein (LDL) receptors, resulting in high serum cholesterol. Two types of FH are described: the heterozygous form is diagnosed in adults and responds well to medical therapy; the homozygous form is rare, diagnosed in children, and often requires multiple treatments to prevent complications. Cholesterol accumulation in tissues produces common clinical manifestations including cutaneous xanthomas, coronary artery disease, and aortic stenosis. Treatment options consist of lifestyle modifications, lipid-lowering medications, LDL aphaeresis, and orthotopic liver transplantation (OLT).Case Presentation. Two patients with FH presented at young ages due to characteristic cutaneous xanthomas. The patients underwent cardiac testing that revealed atherosclerotic changes. The patients received maximal medical therapy, but only experienced a small decrease in serum cholesterol and LDL levels. After several years of medical treatment without improvement of symptoms, the patients were listed for OLT. The transplantations were successful, and only one patient had a postoperative complication of acute rejection, treated successfully. Currently, both patients are doing well with regression of the cutaneous xanthomas and atherosclerotic changes.Conclusion. OLT is a safe and effective option for patients with homozygous FH refractory to maximal medical therapy and may represent the optimal treatment for these patients.
An Adaptive Memory Model for Long-Term Navigation of Autonomous Mobile Robots
Authors: Hentschel M. , Wagner B.
Published: January 2012

This paper introduces an environmental representation for autonomous mobile robots that continuously adapts over time. The presented approach is inspired by human memory information processing and stores the current as well as past knowledge of the environment. In this paper, the memory model is applied to time-variant information about obstacles and driveable routes in the workspace of the autonomous robot and used for solving the navigation cycle of the robot. This includes localization and path planning as well as vehicle control. The presented approach is evaluated in a real-world experiment within changing indoor environment. The results show that the environmental representation is stable, improves its quality over time, and adapts to changes.
Synthesis of [2′-(N-Ethylamino)-5′-Alkyl]phenyl-5,6,7,8-Tetrahydroacridine-9-Carboxy-2-Sulfone Derivatives by the Proton-Catalyzed Rearrangement of Corresponding Sulfonamides
Authors: Sharma Anamika , Jain Sonika , Sirohi Reenu , Kishore D.
Published: January 2012

Synthesis of a new series of heteroaryl sulfones 6(a–f) in which the heteroaryl part is represented by acridine derivatives has been developed and reported here. The key step of this transformation involves the proton-catalyzed rearrangement of the sulphonamide derivatives 5(a–f) to the corresponding sulfones 6(a–f).
People Detection Based on Spatial Mapping of Friendliness and Floor Boundary Points for a Mobile Navigation Robot
Authors: Tasaki Tsuyoshi , Ozaki Fumio , Matsuhira Nobuto , Ogata Tetsuya , Okuno Hiroshi G.
Published: January 2012

Navigation robots must single out partners requiring navigation and move in the cluttered environment where people walk around. Developing such robots requires two different people detections: detecting partners and detecting all moving people around the robots. For detecting partners, we design divided spaces based on the spatial relationships and sensing ranges. Mapping the friendliness of each divided space based on the stimulus from the multiple sensors to detect people calling robots positively, robots detect partners on the highest friendliness space. For detecting moving people, we regard objects’ floor boundary points in an omnidirectional image as obstacles. We classify obstacles as moving people by comparing movement of each point with robot movement using odometry data, dynamically changing thresholds to detect. Our robot detected 95.0% of partners while it stands by and interacts with people and detected 85.0% of moving people while robot moves, which was four times higher than previous methods did.
Gene Expression in Leaves of Susceptible Glycine max during Infection with Phakopsora pachyrhizi Using Next Generation Sequencing
Authors: Tremblay Arianne , Hosseini Parsa , Alkharouf Nadim W. , Li Shuxian , Matthews Benjamin F.
Published: January 2012

Soybean rust is caused by the obligate biotrophic fungus Phakopsora pachyrhizi, an exotic pathogen causing important yield losses in soybean production. We used an mRNA-Seq strategy to analyze the expression pattern of soybean genes and better understand molecular events occurring in soybean following the infection. cDNA libraries were constructed from RNA isolated from whole infected soybean leaves 10 days after inoculation with P. pachyrhizi and sequenced using an Illumina platform to identify soybean genes that are affected by pathogen growth. We obtained 15 million sequences corresponding to soybean genes. Forty-two percent of the genes were downregulated including genes encoding proteins involved in amino acid metabolism, carbohydrate metabolism, and transport facilitation; 31% were upregulated including genes encoding proteins involved in lipid metabolism, glycan biosynthesis, and signal transduction. Candidate host genes identified in this study will be manipulated to assay their potential to control soybean rust disease.
Glomus intraradices Attenuates the Negative Effect of Low Pi Supply on Photosynthesis and Growth of Papaya Maradol Plants
Authors: Yolanda Nava-Gutiérrez , Ferrera-Cerrato Ronald , Santamaría Jorge M.
Published: January 2012

Low inorganic phosphorus (Pi) supply limits the photosynthetic process and hence plants growth and development. Contradictory reports exist in the literature on whether mycorrhyzal association can attenuate the negative effects of low Pi supply on photosynthesis and growth. In the present paper, the effect that low Pi supply may have on photosynthesis and growth of papaya Maradol plants was evaluated in intact plants and in those inoculated with two different strains of the arbuscular mycorrhizal fungi Glomus intraradices. Plant growth was significantly reduced as the Pi supply decreased. However, inoculation with any strain of G. intraradices was able to attenuate such effect. Without Pi in the nutrient solution, the mycorrhizal plants had on average 6.1 times and 7.5 higher photosynthesis than non mycorrhizal plants. The chlorophyll fluorescence values were significantly higher in mycorrhizal than in non-mycorrhizal plants. These results could be associated to an increased ability of mycorhyzal plants to take up Pi from the substrate, as they had higher Pi content than non-mycorrhizal plants. A high correlation was found between internal Pi content and plant biomass. The lower correlation between Pi content and photosynthesis, suggests that some photosynthates could had been used to maintain the symbiosis.
HPTLC Fingerprint Profile and Isolation of Marker Compound of Ruellia tuberosa
Authors: Chothani Daya L. , Patel M. B. , Mishra S. H.
Published: January 2012

The present study was aimed to identification, isolation, and quantification of marker in R. tuberosa (Acanthaceae). HPTLC fingerprinting was carried out for various extract of root, stem, and leaf of R. tuberosa. From the HPTLC fingerprint the florescent band (under 366 nm) at : 0.56 (mobile phase chloroform : toluene : ethyl acetate (6 : 3 : 1, v/v)) was found in leaf, root, and stem of R. tuberosa. So, the florescent band (under 366 nm) at : 0.56 was isolated as marker compound RT-F2 from root of R. tuberosa. The marker compound RT-F2 was quantified by using HPTLC technique. The percentage (W/W) amount of RT-F2 was found to 40.0% and 44.6% in petroleum ether and ethyl acetate extract of R. tuberosa roots, respectively. Further study is suggested to characterization and biological nature of marker compound.
Is Field of Study or Location Associated with College Students' Snacking Patterns?
Authors: McArthur Laura H. , Holbert Donald , Forsythe William
Published: January 2012

Objective. To compare on- and off-campus snacking patterns among college students pursuing degrees in health-related fields (HRFs) and nonhealth-related fields (NHRFs).Materials and Methods. Snack frequency questionnaire, scales measuring barriers, self-efficacy, and stage of change for healthy snacking, and a snack knowledge test (SKT).Participants. 513 students, 46% HRFs, and 54% NHRFs. The students' BMI was  kg/m2(range 14.6 to 43.8), and 32.2% were overweight/obese.Results. Softdrinks (on-campus), lowfat milk (off-campus), and sports drinks were popular among HRFs and NHRFs. Cost and availability were barriers to healthy snacking, students felt least confident to choose healthy snacks when emotionally upset, and 75% (65%) of HRFs (NHRFs) self-classified in the action stage of change for healthy snacking. The HRFs scored higher on the SKT.Conclusions. Neither location nor field of study strongly influenced snacking patterns, which featured few high-fiber foods.
A Prediction Method of Tensile Young's Modulus of Concrete at Early Age
Authors: Yoshitake Isamu , Rajabipour Farshad , Mimura Yoichi , Scanlon Andrew
Published: January 2012

Knowledge of the tensile Young's modulus of concrete at early ages is important for estimating the risk of cracking due to restrained shrinkage and thermal contraction. However, most often, the tensile modulus is considered equal to the compressive modulus and is estimated empirically based on the measurements of compressive strength. To evaluate the validity of this approach, the tensile Young's moduli of 6 concrete and mortar mixtures are measured using a direct tension test. The results show that the tensile moduli are approximately 1.0–1.3-times larger than the compressive moduli within the material's first week of age. To enable a direct estimation of the tensile modulus of concrete, a simple three-phase composite model is developed based on random distributions of coarse aggregate, mortar, and air void phases. The model predictions show good agreement with experimental measurements of tensile modulus at early age.
Relationship between Cariogenic Bacteria and pH of Dental Plaque at Margin of Fixed Prostheses
Authors: Tanaka Junko , Mukai Norio , Tanaka Muto , Tanaka Masahiro
Published: January 2012

Objective. The purpose of this study was to investigate whether teeth that have undergone prosthetic restoration are under conditions that promote caries recurrence.Methods. The subjects were 20 dentate adults with both a healthy tooth and an affected tooth entirely covered with a complete cast crown in the molar regions of the same arch. The pH was measured in plaque adhering to the margin of the tooth covered with a complete cast crown and adhering to the cervicobuccal area of the natural tooth. In addition, the numbers of cariogenic bacteria (mutans streptococci and lactobacilli) were measured employing the saliva test. The relationships between the number of cariogenic bacteria and plaque pH of the natural tooth and between the number of cariogenic bacteria and plaque pH of the tooth covered with a complete cast crown were investigated.Results. The plaque pH of the tooth covered with a complete cast crown decreased as the numbers of SM and LB increased. The natural tooth were also influenced by the number of SM.Conclusion. Secondary caries are likely to develop from the marginal region of the crown in the oral cavity with a high caries risk unless a preventive program is prepared and the oral environment is improved following the program.
Intravitreal Dexamethasone in the Management of Delayed-Onset Bleb-Associated Endophthalmitis
Authors: Jacobs David J. , Pathengay Avinash , Flynn Harry W. , Leng Theodore , Miller Darlene , Shi Wei
Published: January 2012

Purpose.To report the visual acuity (VA) outcomes and culture results of delayed-onset bleb-associated endophthalmitis (BAE) with and without intravitreal dexamethasone (IVD).Methods.Retrospective nonrandomized comparative case series of BAE at Bascom Palmer Eye Institute between January 1, 1996 and December 31, 2009. Clinical data were compared using the 2-sided Student'st-test for patients who received IVD and patients who did not receive IVD.Results.70/83 (84%) received IVD, and 13/83 (16%) did not receive IVD. Mean baseline VA was 20/90 in the IVD group and 20/70 in the group that did not receive IVD (P=0.57). Mean presenting VA was 0.9/200 in the IVD group and 1.7/200 in the group that did not receive IVD (P=0.23). Repeat cultures were positive in 2/70 (3%) IVD cases and 1/13 (8%) cases that did not receive IVD (P=0.57). Mean VA at 1 month was 5/200 in the IVD group and 1.8/200 in the group that did not receive IVD, logMARΔ of 0.85 and 1.56, respectively (P=0.02). Mean VA at 3 months was 7/200 in the IVD group and 3/200 in the group that did not receive IVD, logMARΔ of 0.74 and 1.33, respectively (P=0.14).Conclusion.In the current study of BAE, IVD was associated with improved short-term VA outcomes without an increased rate of persistent infection.
Changes in Precipitation Seasonality in West Africa Predicted by RegCM3 and the Impact of Dynamic Vegetation Feedback
Authors: Wang Guiling , Alo Clement A.
Published: January 2012

Using a regional climate model asynchronously coupled to a dynamic vegetation model, this study examines future climate predictions for the West Africa region and how dynamic vegetation feedback may influence such predictions. Without accounting for the impact of vegetation dynamics, the model predicts a future decrease of annual rainfall over Sahel. Dynamic vegetation feedback reverses this trend, leading to a substantial increase of annual rainfall. Regardless of how vegetation is treated, the predicted future trend of precipitation in the Sahel region follows a specific seasonal pattern, with a decrease during the pre- and early-monsoon season (May-June and early July) due to the warming-induced enhancement of spring convective barrier and an increase after the monsoon is fully established (typically in July-August-September) due to enhanced moisture import from a warmer ocean. Dynamic vegetation feedback reduces the magnitude of the predicted rainfall reduction in the early season and increases the magnitude of the predicted rainfall increase later in the rainy season. The future decrease of early-season rainfall has significant agronomic implications.
Ulam Stability for Fractional Differential Equation in Complex Domain
Authors: Ibrahim Rabha W.
Published: January 2012

The present paper deles with a fractional differential equation , 1 < α ≤ 2, where z ∈ U : = {z:|z | < 1} in sense of Srivastava‐Owa fractional operators. The existence and uniqueness of holomorphic solutions are established. Ulam stability for the approximation and holomorphic solutions are suggested.
A Quality Management Approach to Implementing Point-of-Care Technologies for HIV Diagnosis and Monitoring in Sub-Saharan Africa
Authors: Shott Joseph P. , Galiwango Ronald M. , Reynolds Steven J.
Published: January 2012

Technology advances in rapid diagnosis and clinical monitoring of human immunodeficiency virus (HIV) infection have been made in recent years, greatly benefiting those at risk of HIV infection, those needing care and treatment, and those on antiretroviral (ART) therapy in sub-Saharan Africa. However, resource-limited, geographically remote, and harsh climate regions lack uniform access to these technologies. HIV rapid diagnostic tests (RDTs) and monitoring tools, such as those for CD4 counts, as well as tests for coinfections, are being developed and have great promise in these settings to aid in patient care. Here we explore the advances in point-of-care (POC) technology in the era where portable devices are bringing the laboratory to the patient. Quality management approaches will be imperative for the successful implementation of POC testing in endemic settings to improve patient care.
Differences in Chemical Sexual Signals May Promote Reproductive Isolation and Cryptic Speciation between Iberian Wall Lizard Populations
Authors: Gabirot Marianne , López Pilar , Martín José
Published: January 2012

Interpopulational variation in sexual signals may lead to premating reproductive isolation and speciation. Genetic and morphological studies suggest that the Iberian wall lizard,Podarcis hispanica, forms part of a “species complex” with several cryptic species. We explored the role of chemical sexual signals in interpopulational recognition between five distinct populations of Iberian wall lizards in Central Spain. Results showed that these populations differed in morphology and in composition and proportion of chemical compounds in femoral gland secretions of males. Tongue-flick experiments indicated that male and female lizards discriminated and were more interested in scents of lizards from their own area (i.e., Northern versus Southern populations), but did not discriminate between all populations. Moreover, only males from the populations that are geographically located more far away preferred scent of females from their own population. These data suggest that, at least between some populations, there may be reproductive isolation mediated by chemical signals and cryptic speciation.
Inflammation and Immune Response of Intra-Articular Serotype 2 Adeno-Associated Virus or Adenovirus Vectors in a Large Animal Model
Authors: Ishihara Akikazu , Bartlett Jeffrey S. , Bertone Alicia L.
Published: January 2012

Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative gene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad), serotype 2 adeno-associated virus vectors (rAAV2), or self-complementary (sc) AAV2 vectors carrying green fluorescent protein (GFP). Using 6 horses, bilateral metacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint inflammation and neutralizing antibody (NAb) titer in serum and joint fluid. In vitro, the greater transduction efficiency and sustained gene expression were achieved by scAAV2 compared to rAAV2 in equine chondrocytes and synovial cells. In vivo, AAV2 demonstrated less joint inflammation than Ad, but similar NAb titer. The scAAV2 vectors can induce superior gene transduction than rAAV2 in articular cells, and both rAAV2 and scAAV2 vectors were showed to be safer for intra-articular use than Ad vectors.
Food-Based Dietary Guidelines for the Arab Gulf Countries
Authors: Musaiger Abdulrahman O. , Takruri Hamed R. , Hassan Abdelmonem S. , Abu-Tarboush Hamza
Published: January 2012

The concept of food-based dietary guidelines (FBDG) has been promoted by several international organizations. However, there are no FBDG for the countries in the Arab region. As the Arab Gulf countries share similar a socioeconomic and nutrition situation, an attempt was made to develop FBDG for these countries. This paper summarizes the steps taken to develope such guidelines by the Arab Center for Nutrition. The FBDG were developed through 6 steps: (1) determination of the purpose and goals for establishing FBDG, (2) characteristics of FBDG, (3) determination of the food consumption patterns, (4) review the current nutrition situation, (5) determination of the lifestyle patterns that are associated with diet-related diseases and (6) formulating the FBDG. The FBDG consist of 14 simple and practical pieces of advice taking into consideration the sociocultural status and nutritional problems in the Arab Gulf countries. The FBDG can be a useful tool in educating the public in healthy eating and prevention of diet-related chronic diseases.
Evaluation of Differentiated Human Bronchial Epithelial Cell Culture Systems for Asthma Research
Authors: Stewart Ceri E. , Torr Elizabeth E. , Mohd Jamili Nur H. , Bosquillon Cynthia , Sayers Ian
Published: January 2012

The aim of the current study was to evaluate primary (human bronchial epithelial cells, HBEC) and non-primary (Calu-3, BEAS-2B, BEAS-2B R1) bronchial epithelial cell culture systems as air-liquid interface- (ALI-) differentiated models for asthma research. Ability to differentiate into goblet (MUC5AC+) and ciliated (β-Tubulin IV+) cells was evaluated by confocal imaging and qPCR. Expression of tight junction/adhesion proteins (ZO-1, E-Cadherin) and development of transepithelial electrical resistance (TEER) were assessed. Primary cells showed localised MUC5AC,β-Tubulin IV, ZO-1, and E-Cadherin and developed TEER with, however, a large degree of inter- and intradonor variation. Calu-3 cells developed a more reproducible TEER and a phenotype similar to primary cells although with diffuseβ-Tubulin IV staining. BEAS-2B cells did not differentiate or develop tight junctions. These data highlight the challenges in working with primary cell models and the need for careful characterisation and selection of systems to answer specific research questions.
Silicon-Based Technology for Ligand-Receptor Molecular Identification
Authors: Lamberti Annalisa , Sanges Carmen , Migliaccio Nunzia , De Stefano Luca , Rea Ilaria , Orabona Emanuele , Scala Giuseppe , Rendina Ivo , Arcari Paolo
Published: January 2012

One of the most important goals in the fields of biology and medicine is the possibility to dispose of efficient tools for the characterization of the extraordinary complexity of ligand-receptor interactions. To approach this theme, we explored the use of crystalline silicon (cSi) technology for the realization of a biotechnological device in which the ligand-receptor interactions are revealed by means of optical measurements. Here, we describe a chemical procedure for the functionalization of microwell etched on silicon wafers, and the subsequent anchoring of biological molecules like an antibody anti-A20 murine lymphoma cell line. The optical analysis of the interaction on the biochips between the bound biomolecule and their corresponding ligand indicated that the functionalized cSi is suitable for this application.
Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery
Authors: Baird Marianne F. , Graham Scott M. , Baker Julien S. , Bickerstaff Gordon F.
Published: January 2012

The appearance of creatine kinase (CK) in blood has been generally considered to be an indirect marker of muscle damage, particularly for diagnosis of medical conditions such as myocardial infarction, muscular dystrophy, and cerebral diseases. However, there is controversy in the literature concerning its validity in reflecting muscle damage as a consequence of level and intensity of physical exercise. Nonmodifiable factors, for example, ethnicity, age, and gender, can also affect enzyme tissue activity and subsequent CK serum levels. The extent of effect suggests that acceptable upper limits of normal CK levels may need to be reset to recognise the impact of these factors. There is a need for standardisation of protocols and stronger guidelines which would facilitate greater scientific integrity. The purpose of this paper is to examine current evidence and opinion relating to the release of CK from skeletal muscle in response to physical activity and examine if elevated concentrations are a health concern.
Optical Imaging with Her2-Targeted Affibody Molecules Can Monitor Hsp90 Treatment Response in a Breast Cancer Xenograft Mouse Model
Authors: van de Ven Stephanie M.W.Y. , Elias Sjoerd G. , Chan Carmel T. , Miao Zheng , Cheng Zhen , De Abhijit , Gambhir Sanjiv S.
Published: January 2012

Purpose: To determine whether optical imaging can be used for in vivo therapy response monitoring as an alternative to radionuclide techniques. For this, we evaluated the known Her2 response to 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG) treatment, an Hsp90 inhibitor.

Experimental Design: After in vitro 17-DMAG treatment response evaluation of MCF7 parental cells and 2 HER2-transfected clones (clone A medium, B high Her2 expression), we established human breast cancer xenografts in nude mice (only parental and clone B) for in vivo evaluation. Mice received 120 mg/kg of 17-DMAG in 4 doses at 12-hour intervals intraperitonially (n = 14) or PBS as carrier control (n = 9). Optical images were obtained both pretreatment (day 0) and posttreatment (day 3, 6, and 9), always 5 hours postinjection of 500 pmol of anti-Her2 Affibody-AlexaFluor680 via tail vein (with preinjection background subtraction). Days 3 and 9 in vivo optical imaging signal was further correlated with ex vivo Her2 levels by Western blot after sacrifice.

Results: Her2 expression decreased with 17-DMAG dose in vitro. In vivo optical imaging signal was reduced by 22.5% in clone B (P = 0.003) and by 9% in MCF7 parental tumors (P = 0.23) 3 days after 17-DMAG treatment; optical imaging signal recovered in both tumor types at days 6 to 9. In the carrier group, no signal reduction was observed. Pearson correlation of in vivo optical imaging signal with ex vivo Her2 levels ranged from 0.73 to 0.89.

Conclusions: Optical imaging with an affibody can be used to noninvasively monitor changes in Her2 expression in vivo as a response to treatment with an Hsp90 inhibitor, with results similar to response measurements in positron emission tomography imaging studies. Clin Cancer Res; 18(4); 1073–81. ©2012 AACR.
Acute Stress Differently Modulates Beta 1, Beta 2 and Beta 3 Adrenoceptors in T Cells, but Not in B Cells, from the Rat Spleen
Authors: Laukova Marcela , Vargovic Peter , Csaderova Lucia , Chovanova Lucia , Vlcek Miroslav , Imrich Richard , Krizanova Olga , Kvetnansky Richard
Published: January 2012

Objectives: Stress-induced rise in circulating catecholamines (CAs), followed by modulation of β-adrenergic receptors (adrenoceptors, ARs), is one of the pathways involved in the stress-mediated effects of immune functions. The spleen is an organ with a high number of lymphocytes and provides a unique microenvironment in which they reside. Thus, lymphocytes may respond differently to CAs in the spleen than in the circulation. No reports exist concerning the involvement of β-ARs in stress-mediated effects on T and B cells isolated from the spleen. Therefore, our aim was to investigate the effect of single stress exposure on gene expression and cellular localization of β-adrenoceptor subtypes in splenic T and B cells. We tried to correlate changes in adrenoceptors with the expression of apoptotic proteins. Methods: Immobilization (IMMO) was used as a stress model. T and B cells were isolated from rat spleen using magnetically labeled antibodies. The gene expression of individual adrenoceptors and apoptotic proteins was evaluated by real-time PCR. Immunofluorescence was used to evaluate localization and adrenoceptor expression. Results: We have found T cells to be more vulnerable to stress compared to B cells, because of increased β1-, β2- and β3-ARs after a single IMMO. Moreover, β2-ARs translocated from the nucleus to the plasma membrane in T cells after IMMO. The rise in β-ARs most probably led to the rise of Bax mRNA and Bax to Bcl-2 mRNA ratio. This might suggest the induction of an apoptotic process in T cells. Conclusion: Higher susceptibility of T cells to stress via modulation of β-ARs and apoptotic proteins might shift the immune responsiveness in the spleen.
DNMT3B (C46359T) Polymorphisms and Immunoexpression of DNMT3b and DNMT1 Proteins in Oral Lichen Planus
Authors: Fonseca-Silva Thiago , de Oliveira Marcos Vinícius Macedo , Fraga Carlos Alberto de Carvalho , Farias Lucyana Conceição , Gomes Érika Patrícia Pereira , Barros Lucas Oliveira , Roy Ashbeel , Santiago Gomez Ricardo , De Paula Alfredo Maurício Batista , Guimarães André Luiz Sena
Published: January 2012

Objective: To investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in oral lichen planus (OLP) compared to a control group. Methods: We aimed to investigate the DNMT3B (C46359T) polymorphism and immunoexpression of DNMT3b and DNMT1 in OLP (n = 32), comparing it with oral mucosa (control; n = 24). The DNMT3B (C46359T) polymorphism was analyzed using the RFLP-PCR and DNMT1, and DNMT3a proteins were identified using immunohistochemistry. We also compared the DNMT3B expression in OLP and oral inflammatory fibrous hyperplasia (OIFH), another oral inflammatory disease. Differences between the groups were determined by specific statistical analyses. Results: The CT genotype of DNMT3B was associated with OLP development (p = 0.012). Increased expression of DNMT3B and DNMT1 was observed in OLP compared to the control group (p = 0.014 and p = 0.001, respectively). A significant increase in DNMT3B protein levels was observed in the genotype CT in DNMT3B (C46359T) polymorphisms (p = 0.045). No DNMT3B expression differences between OLP and OIFH were observed. Conclusions: Our data show that the DNMT3B (C46359T) polymorphism is associated with OLP development. Furthermore, increased expression of the enzyme DNMT3B, an epigenetic-associated protein, is present in OLP.
Immunomodulation of the Inflammatory Response Induced by Androctonus australis hector Neurotoxins: Biomarker Interactions
Authors: Raouraoua-Boukari Ryma , Sami-Merah Sassia , Hammoudi-Triki Djelila , Martin-Eauclaire Marie-France , Laraba-Djebari Fatima
Published: January 2012

Objective:Androctonus australis hector (Aah) is the most dangerous scorpion in the Maghreb countries. Its venom contains three major neurotoxins (Aah I, Aah II and Aah III), which are responsible for almost all the lethal effects caused in mammals. These toxins act on the voltage-gated sodium channels of excitable cells. The targets and the lethal effects of these toxins have been extensively studied. However, their effects on the induced immune response after envenoming have not deeply elicited. We therefore investigated the effects induced by Aah venom and its toxic components, mainly its main toxin Aah II, on the activation of the inflammatory process. Methods: Wistar rats were injected by intraperitoneal route with a sublethal dose of Aah venom, FTox-G50, the purified Aah II toxin or with 400 µl of sterile physiological saline solution. Immunological biomarkers such as MPO, NO and ICAM-1 were analyzed in serum in lung tissue. Cytokine levels were also determined in serum at 3, 6 and 24 h after envenoming. Results: We report in this study that intraperitoneal injection of the venom or its toxins (the whole toxic fraction or Aah II toxin) caused an inflammatory reaction involving increased neutrophil release into blood and neutrophil accumulation in lung tissue. This cell infiltration was associated with the release of NO, histamine, cytokines (IL-1, IL-6, IL-12, IL-4 and IL-5) and ICAM. Conclusion: Aah II binding to its targets, in this case Na+ channels, may induce a cascade of events such as inflammatory mediator release and neutrophil migration that could contribute to the exacerbation of the systemic inflammatory response and the development of lung injury following scorpion envenoming.
Neuroinflammation: A Common Pathway in CNS Diseases as Mediated at the Blood-Brain Barrier
Authors: Erickson Michelle A. , Dohi Kenji , Banks William A.
Published: January 2012

The blood-brain barrier (BBB) is not simply a physical barrier but a regulatory interface between the central nervous system (CNS) and immune system. The BBB both affects and is affected by the immune system and connects at many levels with the CNS, including the following: (1) the BBB transports cytokines and secretes various substances with neuroinflammatory properties; (2) transporters are altered in disease states including traumatic injury, Alzheimer’s disease and inflammatory processes; (3) cytokines and other immune secretions from the cells comprising the BBB are both constitutive and inducible; (4) immune cells are transported across the BBB by the highly regulated process termed diapedesis, which involves communication and interactions between the brain endothelial cells and the immune cells; (5) the neuroimmune system has various effects on the BBB, including modulation of important transport systems and in extreme pathological conditions even disruption of the BBB, and (6) the brain-to-blood efflux transporter P-glycoprotein is altered in inflammatory conditions, thus affecting drug delivery to the brain. In summary, the BBB is an interactive interface that regulates and defines many of the ways that the CNS and the immune system communicate with one another.
Leptin, MUC2 and mTOR in Appendiceal Mucinous Neoplasms
Authors: Chang Mee Soo , Byeon Sun-ju , Yoon Sun Och , Kim Baek-hui , Lee Hye Seung , Kang Gyeong Hoon , Kim Woo Ho , Park Kyu Joo
Published: January 2012

Objective: Leptin contributes to mucin production in colonic epithelium and regulates carcinogenesis via various signalling pathways. We evaluated the proteins involved in mucin-producing carcinogenesis and putative targets for molecular therapy in appendiceal mucinous neoplasms. Methods: Immunohistochemistry and fluorescence in situ hybridization were performed in 22 cases of appendiceal mucinous adenoma, 20 mucinous neoplasms of uncertain malignant potential and 14 mucinous adenocarcinomas. Results: Leptin, MUC2, MUC5AC, mTOR and ERK were more frequently immunopositive in mucinous adenocarcinomas compared with mucinous adenomas or mucinous neoplasms of uncertain malignant potential (p < 0.05). STAT3 revealed immunopositivity in 82% of tumours, regardless of tumour category. MUC2 immunopositivity was associated with pseudomyxoma peritonei (p < 0.05). None of the tumours exhibited c-kitimmunoexpression, amplification of Her2 or EGFR, or translocation of ALK. The mTOR-immunopositive group of patients had a lower rate of disease-free survival compared with the mTOR-immunonegative group (p < 0.05). Conclusions: Leptin may collaborate with MUC2 and MUC5AC in mucin-producing carcinogenesis in an mTOR-, STAT3- and ERK-dependent manner. STAT3 may be activated early during tumorigenesis. MUC2 and mTOR (but not c-kit, Her2, EGFR and ALK) may represent targets for molecular therapy in pseudomyxoma peritonei and appendiceal mucinous adenocarcinoma, respectively.
Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data
Authors: Izzo Angelo A.
Published: January 2012

This article provides an overview of the clinical evidence of interactions between herbal and conventional medicines. Herbs involved in drug interactions – or that have been evaluated in pharmacokinetic trials – are discussed in this review. While many of the interactions reported are of limited clinical significance and many herbal products (e.g. black cohosh, saw palmetto, echinacea, hawthorn and valerian) seem to expose patients to minor risk under conventional pharmacotherapy, a few herbs, notably St. John’s wort, may provoke adverse events sufficiently serious to endanger the patients’ health. Healthcare professionals should remain vigilant for potential interactions between herbal medicines and prescribed drugs, especially when drugs with a narrow therapeutic index are used.
Effects of Adding Omalizumab, an Anti-Immunoglobulin E Antibody, on Airway Wall Thickening in Asthma
Authors: Hoshino Makoto , Ohtawa Junichi
Published: January 2012

Background: Omalizumab may inhibit allergic inflammation and could contribute to decreasing airway remodeling in patients with asthma. Objective: The aim of this study was to assess the effects of omalizumab on airway wall thickness using computed tomography (CT). Methods: Thirty patients with severe persistent asthma were randomized to conventional therapy with (n = 14) or without omalizumab (n = 16) for 16 weeks. The following airway dimensions were assessed by a validated CT technique: airway wall area corrected for body surface area (WA/BSA), percentage wall area (WA%), wall thickness (T)/√BSA, and luminal area (Ai)/BSA at the right apical segmental bronchus. The percentage of eosinophils in induced sputum, pulmonary function and the Asthma Quality of Life Questionnaire (AQLQ) were assessed as well. Results: Treatment with omalizumab significantly decreased WA/BSA (p < 0.01), WA% (p < 0.01), and T/√BSA (p < 0.01), and increased Ai/BSA (p < 0.05), whereas conventional therapy resulted in no change. In the omalizumab group (n = 14), a significant decrease in the percentage of sputum eosinophils (p < 0.01), improved forced expiratory volume in 1 s (FEV1), and an improved AQLQ score were recorded. The changes in FEV1% predicted and sputum eosinophils were significantly correlated with changes in WA% (r = 0.88, p < 0.001, and r = 072, p < 0.01, respectively). Conclusions: These findings suggest that omalizumab reduced airway wall thickness and airway inflammation. Larger patient studies with longer-term follow-up are needed to show whether omalizumab can truly maintain improved airway wall dimensions.
Correlation between 3D Ultrasound Appearance and Postnatal Findings in Bilateral Malformations of the Fetal Hands
Authors: Muscatello A. , Mastrocola N. , Di Nicola M. , Patacchiola F. , Carta G.
Published: January 2012

Malformations of the hand have an incidence of 1 in about 1,500 births. Ultrasound diagnosis and classification of the anomaly is not always easy because of the various positions taken by the hand. We describe the case of a 23-year-old patient with a fetus affected by a symmetrical and bilateral hand oligodactyly associated with deformities of the other fingers. 3D ultrasound evaluation allowed an exact prediction of the malformation and showed perfect correspondence with postnatal findings. The case illustrates the contribution of 3D ultrasound to the evaluation of fetal limb anomalies.