bluuebunny/crossref_metadata_2025 huggingface dataset:
Report of the 4th international workshop on principles of engineering service-oriented systems (PESOS 2012)
Authors: Lago Patricia , Lewis Grace A. , Metzger Andreas , Tosic Vladimir , Bianculli Domenico , Di Marco Antinisca , Polini Andrea , Plebani Pierluigi
Published: January 2013

The 4th International Workshop on Principles of Engineering Service-Oriented Systems (PESOS 2012) was held at the International Conference on Software Engineering, ICSE 2012, on June 4, 2012. The special theme of this 4th edition of PESOS was "The Internet of Services." PESOS 2012 brought together software engineering researchers from academia and industry, as well as practitioners working in the areas of service-oriented systems, to discuss research challenges, recent developments, novel application scenarios, as well as methods, techniques, experiences, and tools to support engineering, evolution and adaptation of large-scale, highly-dynamic serviceoriented systems. For the first time, PESOS featured a special session on "The Quest for Case Studies." This effort created an initial reference set of case studies, hosted on a publicly-available repository, for the research community in service-oriented systems. The multiple discussions throughout the day resulted in the identification service requirements for the Internet of Services.
Dynamic process model for identifying modified data using mobile agents in real time ETL processes
Authors: Mrunalini M. , Kumar T. V. Suresh , Kanth K. Rajani
Published: January 2013

Usability and accessibility issues are common causes why software fails to meet user requirements. However, requirements engineers still focus on functional requirements and might ignore to also elicit system usability and accessibility requirements. This is a high risk which can lead to project and software failure. Improving the usability and accessibility of a system in a later development stage is costly and time consuming. Targeting these concerns, the workshop envisioned that research must address the proper integration of system usability and accessibility requirements into the requirements engineering process and also must focus on how to manage and control the evaluation of these requirements in a systematic way.

UsARE 2012 provided a platform for discussing issues which are relevant for both fields, the Requirements Engineering (RE) and the Human Computer Interaction (HCI). The workshop aim was to bring\ together people from these two communities (RE and HCI) to explore this integration. Researchers and practitioners were invited to submit contributions including problem statements, technical solutions, experience reports, planned work and vision papers. Envisioned results may help aligning RE and HCI processes in order to overcome open issues in these fields.
Optimal component selection for component based software development using pliability metric
Authors: Pande Jeetendra , Garcia Christopher J. , Pant Durgesh
Published: January 2013

Component Based Software Development (CBSD) has gained widespread acceptance as it often results in higher quality software with a significant reduction in development time and costs. A key idea behind CBSD is the extensive reuse and composition of preexisting modules into new software. In this paper we introduce the pliability metric, which is well suited to a component-based orientation and extends previous metrics. Pliability is a flexible measure that assesses software quality across different quality attributes in terms of the quality of its components. In addition, we have developed an optimal component selection model based on integer programming, for maximizing pliability. Through computational experimentation we demonstrate that this model is capable of finding optimal solutions to problems with a very large number of components and requirements in a short time.
Massive Parallelization of Serial Inference Algorithms for a Complex Generalized Linear Model
Authors: Suchard Marc A. , Simpson Shawn E. , Zorych Ivan , Ryan Patrick , Madigan David
Published: January 2013

Following a series of high-profile drug safety disasters in recent years, many countries are redoubling their efforts to ensure the safety of licensed medical products. Large-scale observational databases such as claims databases or electronic health record systems are attracting particular attention in this regard, but present significant methodological and computational concerns. In this article we show how high-performance statistical computation, including graphics processing units, relatively inexpensive highly parallel computing devices, can enable complex methods in large databases. We focus on optimization and massive parallelization of cyclic coordinate descent approaches to fit a conditioned generalized linear model involving tens of millions of observations and thousands of predictors in a Bayesian context. We find orders-of-magnitude improvement in overall run-time. Coordinate descent approaches are ubiquitous in high-dimensional statistics and the algorithms we propose open up exciting new methodological possibilities with the potential to significantly improve drug safety.
A novel user-based collaborative filtering method by inferring tag ratings
Authors: Liu Jia , Wang Weiqing , Chen Zhenyu , Du Xingzhong , Qi Qi
Published: January 2013

User-based collaborative filtering is one of the most widely-used recommendation methods. It recommends items to a user based on her similar users' preferences. The essential part of user-based collaborative filtering is to infer users' similarities. A common method is to compute the similarity between two users according to their ratings to co-rated items. In many cases, two users rate only few common items, such that the similarity between them is inaccurate and it results in misleading recommendations. With the boost of social tagging systems, exploiting social tag information has been a popular way to improve recommender systems in recent years. In this paper, we propose a novel method to compute users' similarities using inferred tag ratings. A user's preference for a tag
t
can be inferred upon her ratings of items tagged with
t
. In a case that a user rates few such items, then the inferred rating to
t
may be inaccurate. Hence the relationships among tags are taken into consideration to compute her preference for
t
according to her all item ratings, such that the inferred preference of the user could be more accurate. Evaluations were done on the MovieLens data set. The results indicate that our method can outperform the traditional user-based collaborative filtering.
An Alternative Approach to Water Regulations for Public Health Protection at Bathing Beaches
Authors: Abdelzaher Amir M. , Solo-Gabriele Helena M. , Phillips Matthew C. , Elmir Samir M. , Fleming Lora E.
Published: January 2013

New approaches should be considered as the US Environmental Protection Agency (EPA) moves rapidly to develop new beach monitoring guidelines by the end of 2012, as these guidelines serve as the basis by which states and territories with coasts along the oceans and Great Lakes can then develop and implement monitoring programs for recreational waters. We describe and illustrate one possible approach to beach regulation termed as the “Comprehensive Toolbox within an Approval Process (CTBAP).” The CTBAP consists of three components. The first is a “toolbox” consisting of an inventory of guidelines on monitoring targets, a series of measurement techniques, and guidance to improve water quality through source identification and prevention methods. The second two components are principles of implementation. These include first, “flexibility” to encourage and develop an individualized beach management plan tailored to local conditions and second, “consistency” of this management plan to ensure a consistent national level of public health protection. The results of this approach are illustrated through a case study at a well-studied South Florida recreational marine beach. This case study explores different monitoring targets based on two different health endpoints (skin versus gastrointestinal illness) and recommends a beach regulation program for the study beach that focuses predominately on source prevention.
Morinda citrifolia(Noni) as an Anti-Inflammatory Treatment in Women with Primary Dysmenorrhoea: A Randomised Double-Blind Placebo-Controlled Trial
Authors: Fletcher H. M. , Dawkins J. , Rattray C. , Wharfe G. , Reid M. , Gordon-Strachan G.
Published: January 2013

Introduction. Noni (Morinda citrifolia) has been used for many years as an anti-inflammatory agent. We tested the efficacy of Noni in women with dysmenorrhea.Method. We did a prospective randomized double-blind placebo-controlled trial in 100 university students of 18 years and older over three menstrual cycles. Patients were invited to participate and randomly assigned to receive 400 mg Noni capsules or placebo. They were assessed for baseline demographic variables such as age, parity, and BMI. They were also assessed before and after treatment, for pain, menstrual blood loss, and laboratory variables: ESR, hemoglobin, and packed cell volume.Results. Of the 1027 women screened, 100 eligible women were randomized. Of the women completing the study, 42 women were randomized to Noni and 38 to placebo. There were no significant differences in any of the variables at randomization. There were also no significant differences in mean bleeding score or pain score at randomization. Both bleeding and pain scores gradually improved in both groups as the women were observed over three menstrual cycles; however, the improvement was not significantly different in the Noni group when compared to the controls.Conclusion. Noni did not show a reduction in menstrual pain or bleeding when compared to placebo.
Preventing Early Pregnancy and Pregnancy-Related Mortality and Morbidity in Adolescents in Developing Countries: The Place of Interventions in the Prepregnancy Period
Authors: Christiansen Charlotte Sigurdson , Gibbs Susannah , Chandra-Mouli Venkatraman
Published: January 2013

This paper applies a life-course perspective to the problem of early pregnancy and pregnancy-related mortality and morbidity in adolescents in developing countries. It describes the contribution that two categories of “pregnancy-focused” programmes make—firstly, the provision of effective care and support in the antenatal, childbirth, and postnatal periods (downstream programmes), and secondly, the provision of effective promotive, preventive, and curative care in the prepregnancy period (midstream programmes). It then makes the case for these pregnancy-focused programmes to be set within the context of a third type of programmes, upstream programmes, that is, the provision of promotive and preventive care that contributes to children and adolescents—both male and female—being well nourished, healthy, knowledgeable about their health, and motivated and empowered to protect their health. It provides examples of successful initiatives of all three types of programmes. Finally, it discusses some practical considerations in planning, implementing, and monitoring these three programmes in a coherent manner.
MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies
Authors: Sionov Ronit Vogt
Published: January 2013

The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.
Patterns of Use and Outcomes in Patients Treated with Etravirine in the HIV Research Network
Authors: Gebo Kelly , Voss Cindy , Mrus Joseph , HIV Research Network
Published: January 2013

This observational analysis examined the clinical outcomes of patients receiving etravirine-(ETR-) based therapy, particularly with protease inhibitors (PIs) other than darunavir (DRV) and with raltegravir (RAL). Data included treatment-experienced adults in the HIV Research Network who began ETR-containing antiretroviral regimens in 2008–2010. The primary objective was to assess 6-month outcomes (durability, i.e., still on an ETR-containing regimen; change in CD4+ cell count and HIV-1 RNA <400 copies/mL). The cohort included 587 patients receiving ETR; 42% of ETR use was in patients not on DRV/ritonavir (r). Patients receiving ETR plus DRV/r had longer durability versus those on ETR plus a PI other than DRV/r at months 6 (91.2% versus 85.5%) and 12 (77.4% versus 65.2%), respectively. Patients on regimens with a PI other than DRV/r were the least likely to be receiving ETR at month 6 (85.5%) versus patients on other ETR-based regimens. Patients on regimens without a PI and without RAL had lower virologic suppression (month 6, 54.2%; month 12, 63.2%) versus patients on other ETR-based regimens. In a clinical care, nontrial setting, ETR was used in regimens without DRV/r. In this population, the 6-month response rates were similar and durable across all regimens, except when ETR was used without RAL and without a PI.
Corrosion of WC-VC-Co Hardmetal in Neutral Chloride Containing Media
Authors: Machio C. N. , Konadu D. S. , Potgieter J. H. , Potgieter-Vermaak S. , Van der Merwe J.
Published: January 2013

The effect of varying VC content on the corrosion behavior of WC-10 wt% Co hardmetals in sodium chloride (NaCl) and synthetic mine water (SMW) solutions has been investigated using anodic polarization scans and surface analytical methods. It is shown that the polarization behavior is active-pseudopassive in NaCl and active in SMW regardless of the VC content, while the corrosion resistance is poorer and independent of VC content in NaCl but better at high VC contents in SMW. The corrosion behavior of samples is explained using the effect of VC on the chemical composition of the binder.
MRMPath and MRMutation, Facilitating Discovery of Mass Transitions for Proteotypic Peptides in Biological Pathways Using a Bioinformatics Approach
Authors: Crasto Chiquito , Narne Chandrahas , Kawai Mikako , Wilson Landon , Barnes Stephen
Published: January 2013

Quantitative proteomics applications in mass spectrometry depend on the knowledge of the mass-to-charge ratio (m/z) values of proteotypic peptides for the proteins under study and their product ions. MRMPath and MRMutation, web-based bioinformatics software that are platform independent, facilitate the recovery of this information by biologists. MRMPath utilizes publicly available information related to biological pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. All the proteins involved in pathways of interest are recovered and processed in silico to extract information relevant to quantitative mass spectrometry analysis. Peptides may also be subjected to automated BLAST analysis to determine whether they are proteotypic. MRMutation catalogs and makes available, following processing, known (mutant) variants of proteins from the current UniProtKB database. All these results, available via the web from well-maintained, public databases, are written to an Excel spreadsheet, which the user can download and save. MRMPath and MRMutation can be freely accessed. As a system that seeks to allow two or more resources to interoperate, MRMPath represents an advance in bioinformatics tool development. As a practical matter, the MRMPath automated approach represents significant time savings to researchers.
Solubility Enhancement of Raloxifene Using Inclusion Complexes and Cogrinding Method
Authors: Patil Payal H. , Belgamwar Veena S. , Patil Pratibha R. , Surana Sanjay J.
Published: January 2013

The objective of the present work was to enhance the solubility and dissolution of practically water-insoluble drug raloxifene HCl (RLX), for the same two approaches that were used. In the first approach, drug was kneaded with hydroxypropyl-β-cyclodextrin (HPβCD), and in the second one drug was cogrinded with modified guar gum (MGG). The drug-cyclodextrin complex and drug-MGG cogrind mixtures were characterized by differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy, and Fourier transform infrared spectroscopy. The solubility and dissolution study reveals that solubility and dissolution rate of RLX remarkably increased in both methods. It was concluded that the prepared inclusion complex showed a remarkable increase in solubility and dissolution of poorly water-soluble drug raloxifene. In the cogrinding mixture, a natural modified gum is used as a surfactant and enhances the solubility and dissolution of RLX without requiring addition of organic solvent or high temperature for its preparation; thus, process is less cumbersome and cost effective. But when both methods were compared; HPβCD complexation method showed significant enhancement of drug solubility.
Combined Lung Transfer of NO and CO in Patients Receiving Methotrexate or Bleomycin Therapy Compared to Normal Subjects
Authors: Viart-Ferber Chantal , Couraud Sébastien , Gormand Frédéric , Pacheco Yves
Published: January 2013

The first aim of the study is to determine whether combined lung diffusing capacities of nitric oxide (TLNO) and of carbon monoxide (TLCO) are accurate in the followup of patients receiving either methotrexate (MTX) or bleomycin (BLM). The second objective is to determine whether TLCO, TLNO, KCO, and TLCO/VI% (inspiratory volume expressed as percentage of predicted value) correlate better with the diffusing capacity of the membrane (Dm) and/or capillary lung volume (Vc). TLNO and TLCO were measured in three groups: 22 “normal” subjects (N group), 17 patients receiving MTX, and 12 patients treated with BLM. TLCO, TLNO, Dm, and Vc were much lower in the MTX and BLM groups compared to those of the N one. The ratio TLNO/TLCO was higher in the BLM group compared to that of the N group and compared to that of the MTX group. KCO correlated neither with Dc nor with Vc, whereas TLCO/VI% correlated significantly with both Dm and Vc. Combined measurement of TLCO and TLNO seems to be useful in the followup of patients receiving agents inducing lung toxicity and gives a good idea of the alveolar membrane and the capillary volume.
Specific Metabolic Fingerprint of a Dietary Exposure to a Very Low Dose of Endosulfan
Authors: Canlet Cécile , Tremblay-Franco Marie , Gautier Roselyne , Molina Jérôme , Métais Benjamin , Blas-Y Estrada Florence , Gamet-Payrastre Laurence
Published: January 2013

Like other persistent organochlorine pesticides, endosulfan residues have been detected in foods including fruit, vegetables, and fish. The aim of our study was to assess the impact of a dietary exposure to low doses of endosulfan from foetal development until adult age on metabolic homeostasis in mice and to identify biomarkers of exposure using an1H-NMR-based metabonomic approach in various tissues and biofluids. We report in both genders an increase in plasma glucose as well as changes in levels of factors involved in the regulation of liver oxidative stress, confirming the prooxidant activities of this compound. Some metabolic changes were distinct in males and females. For example in plasma, a decrease in lipid LDL and choline content was only observed in female. Lactate levels in males were significantly increased. In conclusion, our results show that metabolic changes in liver could be linked to the onset of pathologies like diabetes and insulin resistance. Moreover from our results it appears that the NMR-based metabonomic approach could be useful for the characterization in plasma of a dietary exposure to low dose of pesticide in human.
The Antiobesity Effect ofPolygonum aviculareL. Ethanol Extract in High-Fat Diet-Induced Obese Mice
Authors: Sung Yoon-Young , Yoon Taesook , Yang Won-Kyung , Kim Seung Ju , Kim Dong-Seon , Kim Ho Kyoung
Published: January 2013

The antiobesity effects of aP. aviculareethanol extract (PAE) in high-fat diet- (HFD-) induced obese mice were investigated. The mice were fed an HFD or an HFD supplemented with PAE (400 mg/kg/day) for 6.5 weeks. The increased body weights, adipose tissue weight, and adipocyte area as well as serum total triglyceride, leptin, and malondialdehyde concentrations were decreased in PAE-treated HFD-induced obese mice relative to the same measurements in untreated obese mice. Furthermore, PAE significantly suppressed the elevated mRNA expression levels of sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptorγ, fatty acid synthase, and adipocyte protein 2 in the white adipose tissue of obese mice. In addition, PAE treatment of 3T3-L1 cells inhibited adipocyte differentiation and fat accumulation in a dose-dependent manner. These results suggest that PAE exerts antiobesity effects in HFD-induced obese mice through the suppression of lipogenesis in adipose tissue and increased antioxidant activity.
A Characterization of the Diffuse Galactic Emissions in the Anticenter of the Galaxy
Authors: Fauvet L. , Macías-Pérez J. F. , Hildebrandt S. R. , Désert F.-X.
Published: January 2013

Using the Archeops and WMAP data, we perform a study of the anticenter Galactic diffuse emissions—thermal dust, synchrotron, free-free, and anomalous emissions—at degree scales. The high-frequency data are used to infer the thermal dust electromagnetic spectrum and spatial distribution allowing us to precisely subtract this component at lower frequencies. After subtraction of the thermal dust component, a mixture of standard synchrotron and free-free emissions does not account for the residuals at these low frequencies. Including the all-sky 408 MHz Haslam data we find evidence for anomalous emission with a spectral index of −2.5 in units. However, we are not able to provide coclusion regarding the nature of this anomalous emission in this region. For this purpose, data between 408 MHz and 20 GHz covering the same sky region are needed.
Ignition of Free Gas in the Peritoneal Cavity: An Explosive Complication
Authors: Mumith Aadil , Thuraisingham Justin , Gurunathan-Mani Sivaraman
Published: January 2013

We report an extremely rare event where the use of diathermy to enter the peritoneal cavity caused the free gas within it to ignite and consequently burn the surgeon during a standard right hemicolectomy procedure for a caecal perforation. This should be noted as a possible safety concern intraoperatively. We conclude that sharp dissection should always be used initially when entering the peritoneal cavity where free gas is present, cautery can subsequently be used once the free air has escaped.
Vesicocolonic Fistula: A Sequela of Missed Blunt Abdominal Injury
Authors: Ajape Abdulwahab Akanbi , Babata AbdulLateef , Kura Mustapha Mohammed , Nuhu Musa
Published: January 2013

A case of vesicocolonic fistula secondary to a missed abdominal injury is described. The patient, a 25-year-old male Hausa, Nigerian, was involved in a road traffic accident and sustained head injury with a fractured left femur and a missed blunt abdominal injury. He was referred to us about six months following the injury, on account of failure to micturate, recurrent passage of frequent watery stool, and recurrent fever and weight loss. A suspected diagnosis of intestinovesical fistula was confirmed on micturating cystography. He had a single stage repair of the vesico-colonic fistula. The repair of urethrocutaneous fistula was scheduled for a later date, which he later had. He was discharged but continued with orthopaedic consultation and management.
Prepregnancy Physical Activity in relation to Offspring Birth Weight: A Prospective Population-Based Study in Norway—The HUNT Study
Authors: Krogsgaard Silje , Gudmundsdottir Sigridur L. , Nilsen Tom I. L.
Published: January 2013

Background. The objective was to examine the association between prepregnancy physical exercise and offspring birth weight and to assess the combined association of pre-pregnancy body mass index (BMI) and physical exercise on birth weight.Methods. The study included 2,026 women aged 20–39 years participating in the Norwegian HUNT study and linked with the Medical Birth Registry. We calculated mean differences in birth weight and odds ratios (ORs) for a macrosomic infant (i.e., birth weight>4000 g) using linear and logistic regression analysis.Results. There was no clear association between leisure time physical exercise and mean birth weight. Women who reported no exercise had reduced risk of a macrosomic infant (OR, 0.6; 95% confidence interval (CI), 0.4–0.9) compared to women with a high exercise level. Overweight (BMI≥25.0 kg/m2) was associated with an OR of 1.9 (95% CI, 1.2–2.9) for a macrosomic infant among women who reported low exercise levels, whereas the OR was 1.2 (95% CI, 0.8–1.8) among women with higher exercise levels.Conclusion. There was some evidence that women who reported no exercise before pregnancy had lower risk for a macrosomic infant than women who exercised. Pre-pregnancy BMI was positively associated with birth weight and risk of macrosomia but only among the least active women.
Skin Ageing: Natural Weapons and Strategies
Authors: Binic Ivana , Lazarevic Viktor , Ljubenovic Milanka , Mojsa Jelena , Sokolovic Dusan
Published: January 2013

The fact that the skin is the most visible organ makes us aware of the ageing process every minute. The use of plant extracts and herbs has its origins in ancient times. Chronological and photo-ageing can be easily distinguished clinically, but they share important molecular features. We tried to gather the most interesting evidence based on facts about plants and plant extracts used in antiaging products. Our main idea was to emphasize action mechanisms of these plant/herbal products, that is, their “strategies” in fighting skin ageing. Some of the plant extracts have the ability to scavenge free radicals, to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin. There are some plants that can affect skin elasticity and tightness. Certainly, there is a place for herbal principles in antiaging cosmetics. On the other hand, there is a constant need for more evaluation and more clinical studies in vivo with emphasis on the ingredient concentration of the plant/herbal products, its formulation, safety, and duration of the antiaging effect.
Silver Nanoparticle-Doped Titanium Oxide Thin Films for Intermediate Layers in Organic Tandem Solar Cell
Authors: Nie Wanyi , Coffin Robert C. , Carroll David L.
Published: January 2013

In this work we investigate the Ag nanoparticle doping of TiOx used as an intermediate layer between subcells of a tandem organic photovoltaic. We use a model polymer cell structure of P3HT:TiOx:PEDOT:P3HT to observe charge-trapping effects as a function of nanoparticle content in the TiOx, as determined by the shape of the dark and illuminated current voltage curves of the devices. There is a direct correlation between the amount of Ag nanoparticles in the TiOx, and interfacial charge buildup, and charge trapping being completely mitigated at around 0.2% mol. This suggests that such doping schemes might provide a simple approach to the creation and use of TiOx layers for tandem cells.
Bariatric Surgery as Potential Treatment for Nonalcoholic Fatty Liver Disease: A Future Treatment by Choice or by Chance?
Authors: Hafeez Shuja , Ahmed Mohamed H.
Published: January 2013

Morbid obesity is strongly associated with nonalcoholic fatty liver disease (NAFLD) which is one of the most common causes of chronic liver disease worldwide. The current best treatment of NAFLD and NASH is weight reduction through life style modifications, antiobesity medication, and bariatric surgery. Importantly, bariatric surgery is the best alternative option for weight reduction if lifestyle modifications and pharmacological therapy have not yielded long-term success. Bariatric surgery is an effective treatment option for individuals who are grossly obese and associated with marked decrease in obesity-related morbidity and mortality. The most common performed bariatric surgery is Roux-en-Y gastric bypass (RYGB). The current evidence suggests that bariatric surgery in these patients will decrease the grade of steatosis, hepatic inflammation, and fibrosis. NAFLDper seis not an indication for bariatric surgery. Further research is urgently needed to determine (i) the benefit of bariatric surgery in NAFLD patients at high risk of developing liver cirrhosis (ii) the role of bariatric surgery in modulation of complications of NAFLD like diabetes and cardiovascular disease. The outcomes of the future research will determine whether bariatric surgery will be one of the recommended choice for treatment of the most progressive type of NAFLD.
Altered Knee Joint Mechanics in Simple Compression Associated with Early Cartilage Degeneration
Authors: Dabiri Y. , Li L. P.
Published: January 2013

The progression of osteoarthritis can be accompanied by depth-dependent changes in the properties of articular cartilage. The objective of the present study was to determine the subsequent alteration in the fluid pressurization in the human knee using a three-dimensional computer model. Only a small compression in the femur-tibia direction was applied to avoid numerical difficulties. The material model for articular cartilages and menisci included fluid, fibrillar and nonfibrillar matrices as distinct constituents. The knee model consisted of distal femur, femoral cartilage, menisci, tibial cartilage, and proximal tibia. Cartilage degeneration was modeled in the high load-bearing region of the medial condyle of the femur with reduced fibrillar and nonfibrillar elastic properties and increased hydraulic permeability. Three case studies were implemented to simulate (1) the onset of cartilage degeneration from the superficial zone, (2) the progression of cartilage degeneration to the middle zone, and (3) the progression of cartilage degeneration to the deep zone. As compared with a normal knee of the same compression, reduced fluid pressurization was observed in the degenerated knee. Furthermore, faster reduction in fluid pressure was observed with the onset of cartilage degeneration in the superficial zone and progression to the middle zone, as compared to progression to the deep zone. On the other hand, cartilage degeneration in any zone would reduce the fluid pressure in all three zones. The shear strains at the cartilage-bone interface were increased when cartilage degeneration was eventually advanced to the deep zone. The present study revealed, at the joint level, altered fluid pressurization and strains with the depth-wise cartilage degeneration. The results also indicated redistribution of stresses within the tissue and relocation of the loading between the tissue matrix and fluid pressure. These results may only be qualitatively interesting due to the small compression considered.
Involving the Family in the Care and Treatment of Women with Postpartum Psychosis: Swedish Psychiatrists’ Experiences
Authors: Engqvist I. , Nilsson K.
Published: January 2013

The aim of the study was to describe Swedish psychiatrists’ experiences of involving the family in the treatment of women with postpartum psychosis. A qualitative design was used, and semistructured qualitative research interviews were conducted with nine psychiatrists from the south of Sweden. Data were analysed using qualitative content analysis. Four categories were found:the family as a resource,the family as coworkers,preparing the family for the future, andthe family as a burden. The result showed that the psychiatrists considered the family to be a resource to which they devoted a great deal of care and effort. It was particularly important to involve the partner, informing about the course of the illness and the steps that need to be taken in the event of a relapse and reducing any guilt feelings. The psychiatrists instilled confidence and hope for a future of health and further child bearing. The family members’ limited understanding of the treatment may impede the involvement of the family. Conclusion of the study was that the goal for family involvement was to facilitate the women’s care and treatment. Further studies are needed to provide suggestions on how to develop family involvement in the care of women suffering from postpartum psychosis.
Marked Effects of Tachykinin in Myositis Both in the Experimental Side and Contralaterally: Studies on NK-1 Receptor Expressions in an Animal Model
Authors: Song Yafeng , Stål Per S. , Yu Jiguo , Forsgren Sture
Published: January 2013

Muscle injury and inflammation (myositis) in a rabbit model of an unilateral muscle overuse were examined. It is unknown if the tachykinin system has a functional role in this situation. In this study, therefore, the neurokinin-1 receptor (NK-1R) expression patterns were evaluated. White blood cells, nerve fascicles, fine nerve fibers, and blood vessel walls in myositis areas showed NK-1R immunoreaction. NK-1R mRNA reactions were observable for white blood cells and blood vessel walls of these areas. NK-1R immunoreaction and NK-1R mRNA reactions were also seen for muscle fibers showing degenerative and regenerative features. There were almost no NK-1R immunoreactions in normal muscle tissue. Interestingly, marked NK-1R expressions were seen for myositis areas of both the experimental side and the contralateral nonexperimental side. EIA analyses showed that the concentration of substance P in the muscle tissue was clearly increased bilaterally at the experimental end stage, as compared to the situation for normal muscle tissue. These observations show that the tachykinin system is very much involved in the processes that occur in muscle injury/myositis. The effects can be related to proinflammatory effects and/or tissue repair. The fact that there are also marked NK-1R expressions contralaterally indicate that the tachykinin system has crossover effects.
Computer-Aided Diagnosis Systems for Lung Cancer: Challenges and Methodologies
Authors: El-Baz Ayman , Beache Garth M. , Gimel'farb Georgy , Suzuki Kenji , Okada Kazunori , Elnakib Ahmed , Soliman Ahmed , Abdollahi Behnoush
Published: January 2013

This paper overviews one of the most important, interesting, and challenging problems in oncology, the problem of lung cancer diagnosis. Developing an effectivecomputer-aided diagnosis(CAD) system for lung cancer is of great clinical importance and can increase the patient’s chance of survival. For this reason, CAD systems for lung cancer have been investigated in a huge number of research studies. A typical CAD system for lung cancer diagnosis is composed of four main processing steps: segmentation of the lung fields, detection of nodules inside the lung fields, segmentation of the detected nodules, and diagnosis of the nodules as benign or malignant. This paper overviews the current state-of-the-art techniques that have been developed to implement each of these CAD processing steps. For each technique, various aspects of technical issues, implemented methodologies, training and testing databases, and validation methods, as well as achieved performances, are described. In addition, the paper addresses several challenges that researchers face in each implementation step and outlines the strengths and drawbacks of the existing approaches for lung cancer CAD systems.
ST6Gal-I Protein Expression Is Upregulated in Human Epithelial Tumors and Correlates with Stem Cell Markers in Normal Tissues and Colon Cancer Cell Lines
Authors: Swindall Amanda F. , Londoño-Joshi Angelina I. , Schultz Matthew J. , Fineberg Naomi , Buchsbaum Donald J. , Bellis Susan L.
Published: January 2013

The ST6Gal-I sialyltransferase adds an α2-6–linked sialic acid to the N-glycans of certain receptors. ST6Gal-I mRNA has been reported to be upregulated in human cancer, but a prior lack of antibodies has limited immunochemical analysis of the ST6Gal-I protein. Here, we show upregulated ST6Gal-I protein in several epithelial cancers, including many colon carcinomas. In normal colon, ST6Gal-I localized selectively to the base of crypts, where stem/progenitor cells are found, and the tissue staining patterns were similar to the established stem cell marker ALDH1. Similarly, ST6Gal-I expression was restricted to basal epidermal layers in skin, another stem/progenitor cell compartment. ST6Gal-I was highly expressed in induced pluripotent stem (iPS) cells, with no detectable expression in the fibroblasts from which iPS cells were derived. On the basis of these observations, we investigated further an association of ST6Gal-I with cancer stem cells (CSC). Selection of irinotecan resistance in colon carcinoma cells led to a greater proportion of CSCs compared with parental cells, as measured by the CSC markers CD133 and ALDH1 activity (Aldefluor). These chemoresistant cells exhibited a corresponding upregulation of ST6Gal-I expression. Conversely, short hairpin RNA (shRNA)-mediated attenuation of ST6Gal-I in colon carcinoma cells with elevated endogenous expression decreased the number of CD133/ALDH1-positive cells present in the cell population. Collectively, our results suggest that ST6Gal-I promotes tumorigenesis and may serve as a regulator of the stem cell phenotype in both normal and cancer cell populations. Cancer Res; 73(7); 2368–78. ©2012 AACR.
Inhibition of Protein Kinase CK2 Reduces Cyp24a1 Expression and Enhances 1,25-Dihydroxyvitamin D3 Antitumor Activity in Human Prostate Cancer Cells
Authors: Luo Wei , Yu Wei-Dong , Ma Yingyu , Chernov Mikhail , Trump Donald L. , Johnson Candace S.
Published: January 2013

Vitamin D has broad range of physiological functions and antitumor effects. 24-Hydroxylase, encoded by the CYP24A1 gene, is the key enzyme for degrading many forms of vitamin D including the most active form, 1,25D3. Inhibition of CYP24A1 enhances 1,25D3 antitumor activity. To isolate regulators of CYP24A1 expression in prostate cancer cells, we established a stable prostate cancer cell line PC3 with CYP24A1 promoter driving luciferase expression to screen a small molecular library for compounds that inhibit CYP24A1 promoter activity. From this screening, we identified, 4,5,6,7-tetrabromobenzimidazole (TBBz), a protein kinase CK2 selective inhibitor as a disruptor of CYP24A1 promoter activity. We show that TBBz inhibits CYP24A1 promoter activity induced by 1,25D3 in prostate cancer cells. In addition, TBBz downregulates endogenous CYP24A1 mRNA level in TBBz-treated PC3 cells. Furthermore, siRNA-mediated CK2 knockdown reduces 1,25D3-induced CYP24A1 mRNA expression in PC3 cells. These results suggest that CK2 contributes to 1,25D3-mediated target gene expression. Finally, inhibition of CK2 by TBBz or CK2 siRNA significantly enhances 1,25D3-mediated antiproliferative effect in vitro and in vivo in a xenograft model. In summary, our findings reveal that protein kinase CK2 is involved in the regulation of CYP24A1 expression by 1,25D3 and CK2 inhibitor enhances 1,25D3-mediated antitumor effect. Cancer Res; 73(7); 2289–97. ©2013 AACR.
A 12-Gene Set Predicts Survival Benefits from Adjuvant Chemotherapy in Non–Small Cell Lung Cancer Patients
Authors: Tang Hao , Xiao Guanghua , Behrens Carmen , Schiller Joan , Allen Jeffrey , Chow Chi-Wan , Suraokar Milind , Corvalan Alejandro , Mao Jianhua , White Michael A. , Wistuba Ignacio I. , Minna John D. , Xie Yang
Published: January 2013

Purpose: Prospectively identifying who will benefit from adjuvant chemotherapy (ACT) would improve clinical decisions for non–small cell lung cancer (NSCLC) patients. In this study, we aim to develop and validate a functional gene set that predicts the clinical benefits of ACT in NSCLC.

Experimental Design: An 18-hub-gene prognosis signature was developed through a systems biology approach, and its prognostic value was evaluated in six independent cohorts. The 18-hub-gene set was then integrated with genome-wide functional (RNAi) data and genetic aberration data to derive a 12-gene predictive signature for ACT benefits in NSCLC.

Results: Using a cohort of 442 stage I to III NSCLC patients who underwent surgical resection, we identified an 18-hub-gene set that robustly predicted the prognosis of patients with adenocarcinoma in all validation datasets across four microarray platforms. The hub genes, identified through a purely data-driven approach, have significant biological implications in tumor pathogenesis, including NKX2-1, Aurora Kinase A, PRC1, CDKN3, MBIP, and RRM2. The 12-gene predictive signature was successfully validated in two independent datasets (n = 90 and 176). The predicted benefit group showed significant improvement in survival after ACT (UT Lung SPORE data: HR = 0.34, P = 0.017; JBR.10 clinical trial data: HR = 0.36, P = 0.038), whereas the predicted nonbenefit group showed no survival benefit for 2 datasets (HR = 0.80, P = 0.70; HR = 0.91, P = 0.82).

Conclusions: This is the first study to integrate genetic aberration, genome-wide RNAi data, and mRNA expression data to identify a functional gene set that predicts which resectable patients with non–small cell lung cancer will have a survival benefit with ACT. Clin Cancer Res; 19(6); 1577–86. ©2013 AACR.
HER2-Targeted Hybrid Peptide That Blocks HER2 Tyrosine Kinase Disintegrates Cancer Cell Membrane and Inhibits Tumor GrowthIn Vivo
Authors: Kawamoto Megumi , Horibe Tomohisa , Kohno Masayuki , Kawakami Koji
Published: January 2013

HER2 is a transmembrane oncoprotein encoded by the HER2/neu gene and is overexpressed in approximately 20% to 30% of breast cancers. We have recently designed a novel class of drug, the hybrid peptide, which is chemically synthesized and is composed of a target-binding peptide and a lytic peptide containing cationic-rich amino acid components that disintegrate the cell membrane, leading to cancer cell death via membrane lysis. In this study, we designed a HER2-binding peptide linked to this novel lytic peptide, which we termed the HER2-lytic hybrid peptide and assessed the cytotoxic activity of this hybrid peptide in vitro and in vivo. The HER2-lytic hybrid peptide showed high cytotoxic activity against all ovarian and breast cancer cell lines, even trastuzumab- and/or lapatinib-resistant cells, but not against normal cells. Competition assays using anti-HER2 antibody and knockdown of this receptor by siRNA confirmed the specificity of the HER2-lytic hybrid peptide. In addition, it was shown that the HER2-lytic hybrid peptide can disintegrate the cancer cell membrane of HER2-overexpressing SK-BR-3 cancer cells in only 5 minutes, but not normal cells, and block HER2 signaling. Intravenous administration of the HER2-lytic peptide in the athymic mouse implanted with BT-474 and MDA-MB-453 cells significantly inhibited tumor progression. The HER2-lytic hybrid peptide was effective even in breast cancer cell lines that are resistant to trastuzumab and/or lapatinib in vitro and in vivo. Therefore, this hybrid peptide may provide a potent treatment option for patients with cancer. Mol Cancer Ther; 12(4); 384–93. ©2013 AACR.
Vascular Endothelial Growth Factor-Angiopoietin Chimera With Improved Properties for Therapeutic Angiogenesis
Authors: Anisimov Andrey , Tvorogov Denis , Alitalo Annamari , Leppänen Veli-Matti , An Yuri , Han Eun Chun , Orsenigo Fabrizio , Gaál Emília Ilona , Holopainen Tanja , Koh Young Jun , Tammela Tuomas , Korpisalo Petra , Keskitalo Salla , Jeltsch Michael , Ylä-Herttuala Seppo , Dejana Elisabetta , Koh Gou Young , Choi Chulhee , Saharinen Pipsa , Alitalo Kari
Published: January 2013

Background—

There is an unmet need for proangiogenic therapeutic molecules for the treatment of tissue ischemia in cardiovascular diseases. However, major inducers of angiogenesis such as vascular endothelial growth factor (VEGF/VEGF-A) have side effects that limit their therapeutic utility in vivo, especially at high concentrations. Angiopoietin-1 has been considered to be a blood vessel stabilization factor that can inhibit the intrinsic property of VEGF to promote vessel leakiness. In this study, we have designed and tested the angiogenic properties of chimeric molecules consisting of receptor-binding parts of VEGF and angiopoietin-1. We aimed at combining the activities of both factors into 1 molecule for easy delivery and expression in target tissues.

Methods and Results—

The VEGF–angiopoietin-1 (VA1) chimeric protein bound to both VEGF receptor-2 and Tie2 and induced the activation of both receptors. Detailed analysis of VA1 versus VEGF revealed differences in the kinetics of VEGF receptor-2 activation and endocytosis, downstream kinase activation, and VE-cadherin internalization. The delivery of a VA1 transgene into mouse skeletal muscle led to increased blood flow and enhanced angiogenesis. VA1 was also very efficient in rescuing ischemic limb perfusion. However, VA1 induced less plasma protein leakage and myeloid inflammatory cell recruitment than VEGF. Furthermore, angioma-like structures associated with VEGF expression were not observed with VA1.

Conclusions—

The VEGF–angiopoietin-1 chimera is a potent angiogenic factor that triggers a novel mode of VEGF receptor-2 activation, promoting less vessel leakiness, less tissue inflammation, and better perfusion in ischemic muscle than VEGF. These properties of VA1 make it an attractive therapeutic tool.
Apostolicity: Unresolved Issues in Anglican–Methodist Dialogue
Authors: Haar Miriam
Published: January 2013

This article attends to unresolved issues in Anglican–Methodist dialogue concerning apostolicity and its connection with the role of the historic episcopate and asks whether there has been progress since Baptism, Eucharist and Ministry [BEM] (1982) in more clearly explaining the relationship between the apostolicity of the whole church and of the historic episcopate. Having explored the theological relationship between apostolicity and the ‘historic episcopate’ – with particular reference to Anglican–Methodist dialogue at an international level, and dialogues in England, Ireland, and the USA – it is clear that despite important progress in other areas of Anglican–Methodist relationships, no agreement has been secured concerning the theological relationship between the apostolicity of the whole church and the historic episcopate.
What is Distinctive about Methodist Ecclesiology? A Response to Papers by Miriam Haar, Justus Hunter and Robert Martin
Authors: Wilson Kenneth
Published: January 2013

Does Methodism want a distinctive ecclesiology? British Methodism assumes its ecclesiology from the Church of England which explains its lack of ecclesiological thinking, its genuine desire for reunification, and indeed its focus on ecclesia in actu. But there can be no ecclesia in actu apart from ecclesia per se. Being and doing are one in God. The Church, grounded in the dynamic being of God in Trinity, celebrates in the action of the Eucharist the wholeness of God’s presence with his world. Proleptically the Church includes the whole of creation and all people. Hence, when as the Body of Christ we pray the Our Father with our Lord, we pray on behalf of all, not just for ourselves. But what then do we mean by apostolicity? Perhaps in Methodism we would be well occupied exploring more keenly with the Roman Catholic Church what we each mean by being a society within the church. Outler may have been right when he opined that Methodism needed a Catholic Church within which to be church.