bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases
Authors: Lewiecki E. Michael
Published: November 2013

Sclerostin is a small protein expressed by the SOST gene in osteocytes, bone cells that respond to mechanical stress applied to the skeleton and appear to play an important role in the regulation of bone remodeling. When sclerostin binds to its receptors on the cell surface of osteoblasts, a downstream cascade of intracellular signaling is initiated, with the ultimate effect of inhibiting osteoblastic bone formation. Recent studies have shown that the SOST gene is also expressed by articular chondrocytes and that modulation of its activity may have effects on articular cartilage and subchondral bone. The role of sclerostin in the pathogenesis of osteoarthritis in humans has not yet been defined, and the potential utility of treating osteoarthritis with interventions that alter sclerostin is not known. Rare genetic skeletal disorders in humans with low sclerostin levels, such as sclerosteosis and van Buchem disease, have been associated with a high bone mineral density (BMD) phenotype and low risk of fractures. This has led to the concept that antisclerostin interventions might be useful in the treatment of patients with osteoporosis and skeletal disorders associated with low bone mass. Compounds that inhibit sclerostin have been shown to stimulate bone formation and reduce bone resorption, with a robust increase in BMD. Investigational monoclonal antibodies to sclerostin, including romosozumab, blosozumab, and BPS804, have advanced to phase II clinical trials or beyond. If antisclerostin therapy is found to have beneficial effects on clinical endpoints, such as reduction of fracture risk or improvement in quality of life in patients with osteoarthritis, with a favorable balance of benefit and risk, then this class of compounds may become a prominent addition to the options for therapy of osteoporosis and other skeletal disorders.
Nonsuicidal Self-Injury, Pain, and Self-Criticism
Authors: Hooley Jill M. , St. Germain Sarah A.
Published: November 2013

People who engage in nonsuicidal self-injury (NSSI) endure physical pain for longer periods than do noninjuring individuals. Pain endurance is also predicted by the presence of highly self-critical beliefs. We tested the hypothesis that changing beliefs about the self would change pain endurance in NSSI individuals. NSSI ( n = 50) and control ( n = 84) participants were randomly assigned to hear positive music, to receive a brief cognitive intervention designed to improve feelings of personal self-worth, or to a neutral condition. Pain endurance was measured before and after the experimental manipulations. As predicted, there was a significant Group × Condition × Time interaction. After the cognitive intervention, NSSI participants showed a 69-s decrease in pain endurance compared with a 9-s decrease for control participants. For NSSI participants, improvement in self-worth was also significantly correlated with decreased willingness to endure pain. Cognitive approaches that focus on self-worth may provide a new treatment direction for NSSI.
The Impact of Market Scale on Standardization and Specialization
Authors: Cheung Waka , Ng Yew-Kwang
Published: November 2013

A Hotelling long-run equilibrium model based on the microeconomics of optimization is developed to analyze the impact of market scale on specialization and standardization. Among our conclusions is that the degree of vertical division of labour and the number of varieties produced in a production line increase, via a rise in the extent of market with population, average income and market transaction efficiency; however, the opposite effects also result from a rise in average income via the preference for individualized products. The net effect of average income varies in different cases. Using these conclusions we explain some phenomena in the garment and auto industries.
Effects of aging on precipitation and shape memory of Fe–Mn–Si–Cr–Ni based alloy with V and N addition
Authors: Guo Q. , Dong Z. , Liu Z. , Yu L. , Li K.
Published: November 2013

The effects of aging on the precipitation of the second phase and the shape memory effect (SME) of an Fe–Mn–Si–Cr–Ni based alloy containing V and N elements (0·9 wt-) have been investigated. The results showed that VN particles, precipitated during aging, could improve the shape recovery ratio to 56, compared with that of only 25 for the solution treated samples when the V and N bearing alloy was aged for 24 h. It was further confirmed by X-ray diffraction that the fitting relationship between shape recovery and martensite content is practically in agreement with linearity. Electron microscopic observation has shown that aging treatment gives rise to an increasing amount of VN precipitates, among which the small ones uniformly precipitated inside grains but would aggregate and grew quite remarkably to be large ones at the grain boundaries. These large particles do not appear to have much negative effects on the SME, whereas it is the fine nanosize VN particles inside grains that are the key factor to act as preferential nucleation sites for martensite, improving the SME.
Plasmodium falciparum picks (on) EPCR
Authors: Aird William C. , Mosnier Laurent O. , Fairhurst Rick M.
Published: November 2013

Of all the outcomes of Plasmodium falciparum infection, the coma of cerebral malaria (CM) is particularly deadly. Malariologists have long wondered how some patients develop this organ-specific syndrome. Data from two recent publications support a novel mechanism of CM pathogenesis in which infected erythrocytes (IEs) express specific virulence proteins that mediate IE binding to the endothelial protein C receptor (EPCR). Malaria-associated depletion of EPCR, with subsequent impairment of the protein C system promotes a proinflammatory, procoagulant state in brain microvessels.
High-throughput sequencing identification of novel and conserved miRNAs in the Brassica oleracea leaves
Authors: Lukasik Anna , Pietrykowska Halina , Paczek Leszek , Szweykowska-Kulinska Zofia , Zielenkiewicz Piotr
Published: November 2013

Background

Plant microRNAs are short (~21 nt) non-coding molecules that regulate gene expression by targeting the mRNA cleavage or protein translation inhibition. In this manner, they play many important roles in the cells of living organisms. One of the plant species in which the entire set of miRNAs has not been yet completely identified is Brassica oleracea var. capitata (cabbage). For this reason and for the economic and nutritional importance of this food crop, high-throughput small RNAs sequencing has been performed to discover the novel and conserved miRNAs in mature cabbage leaves.

Results

In this study, raw reads generated from three small RNA libraries were bioinformatically processed and further analyzed to select sequences homologous to known B. oleracea and other plant miRNAs. As a result of this analysis, 261 conserved miRNAs (belonging to 62 families) have been discovered. MIR169, MIR167 and MIR166 were the largest miRNA families, while the highest abundance molecules were miR167, miR166, miR168c and miR157a. Among the generated sequencing reads, miRNAs* were also found, such as the miR162c*, miR160a* and miR157a*. The unannotated tags were used in the prediction and evaluation of novel miRNAs, which resulted in the 26 potential miRNAs proposal. The expressions of 13 selected miRNAs were analyzed by northern blot hybridization. The target prediction and annotation for identified miRNAs were performed, according to which discovered molecules may target mRNAs encoding several potential proteins – e.g., transcription factors, polypeptides that regulate hormone stimuli and abiotic stress response, and molecules participating in transport and cell communication. Additionally, KEGG maps analysis suggested that the miRNAs in cabbage are involved in important processing pathways, including glycolysis, glycerolipid metabolism, flavonoid biosynthesis and oxidative phosphorylation.

Conclusions

Conclusively, for the first time, the large set of miRNAs was identified in mature cabbage leaves. Potential targets designation for these miRNAs may suggest their essential role in many plants primary biological processes. Presented study not only supplements the knowledge about B. oleracea miRNAs, but additionally it may be used in other research concerning the improvement of the cabbage cultivation.
A whole transcriptomal linkage analysis of gene co-regulation in insecticide resistant house flies, Musca domestica
Authors: Li Ming , Reid William R , Zhang Lee , Scott Jeffery G , Gao Xiwu , Kristensen Michael , Liu Nannan
Published: November 2013

Background

Studies suggest that not only is insecticide resistance conferred via multiple gene up-regulation, but it is mediated through the interaction of regulatory factors. However, no regulatory factors in insecticide resistance have yet been identified, and there has been no examination of the regulatory interaction of resistance genes. Our current study generated the first reference transcriptome from the adult house fly and conducted a whole transcriptome analysis for the multiple insecticide resistant strain ALHF (wild-type) and two insecticide susceptible strains: aabys (with morphological recessive markers) and CS (wild type) to gain valuable insights into the gene interaction and complex regulation in insecticide resistance of house flies,Musca domestica.

Results

Over 56 million reads were used to assemble the adult femaleM. domesticatranscriptome reference and 14488 contigs were generated from thede novotranscriptome assembly. A total of 6159 (43%) of the contigs contained coding regions, among which 1316 genes were identified as being co-up-regulated in ALHF in comparison to both aabys and CS. The majority of these up-regulated genes fell within the SCOP categories of metabolism, general, intra-cellular processes, and regulation, and covered three key detailed function categories: redox detailed function category in metabolism, signal transduction and kinases/phosphatases in regulation, and proteases in intra-cellular processes. The redox group contained detoxification gene superfamilies, including cytochrome P450s, glutathione S-transferases, and esterases. The signal transduction and kinases/phosphatases groups contained gene families of rhodopsin-like GPCRs, adenylate and guanylate cyclases, protein kinases and phosphatases. The proteases group contained genes with digestive,catalytic, and proteinase activities. Genetic linkage analysis with house fly lines comparing different autosomal combinations from ALHF revealed that the up-regulation of gene expression in the three key SCOP detailed function categories occurred mainly through the co-regulation of factors among multiple autosomes, especially between autosomes 2 and 5, suggesting that signaling transduction cascades controlled by GPCRs, protein kinase/phosphates and proteases may be involved in the regulation of resistance P450 gene regulation.

Conclusion

Taken together, our findings suggested that not only is insecticide resistance conferred via multi-resistance mechanisms or up-regulated genes, but it is mediated through thetransand/orcisco-regulations of resistance genes.
A look at the potential association between PICOT framing of a research question and the quality of reporting of analgesia RCTs
Authors: Borg Debono Victoria , Zhang Shiyuan , Ye Chenglin , Paul James , Arya Aman , Hurlburt Lindsay , Murthy Yamini , Thabane Lehana
Published: November 2013

Background

Methodologists have proposed the formation of a good research question to initiate the process of developing a research protocol that will guide the design, conduct and analysis of randomized controlled trials (RCTs), and help improve the quality of reporting such studies. Five constituents of a good research question based on the PICOT framing include: Population, Intervention, Comparator, Outcome, and Time-frame of outcome assessment. The aim of this study was to analyze if the presence a structured research question, in PICOT format, in RCTs used within a 2010 meta-analysis investigating the effectiveness of femoral nerve blocks after total knee arthroplasty, is independently associated with improved quality of reporting.

Methods

Twenty-three RCT reports were assessed for the quality of reporting and then examined for the presence of the five constituents of a structured research question based on PICOT framing. We created a PICOT score (predictor variable), with a possible score between 0 and 5; one point for every constituent that was included. Our outcome variable was a 14 point overall reporting quality score (OQRS) and a 3 point key methodological items score (KMIS) based on the proper reporting of allocation concealment, blinding and numbers analysed using the intention-to-treat principle. Both scores, OQRS and KMIS, are based on the Consolidated Standards for Reporting Trials (CONSORT) statement. A multivariable regression analysis was conducted to determine if PICOT score was independently associated with OQRS and KMIS.

Results

A completely structured PICOT score question was found in 2 of the 23 RCTs evaluated. Although not statistically significant, higher PICOT was associated with higher OQRS [IRR: 1.267; 95% confidence interval (CI): 0.984, 1.630; p = 0.066] but not KMIS (1.061 (0.515, 2.188); 0.872). These results are comparable to those from a similar study in terms of the direction and range of IRRs estimates. The results need to be interpreted cautiously due to the small sample size.

Conclusions

This study showed that PICOT framing of a research question in anesthesia-related RCTs is not often followed. Even though a statistically significant association with higher OQRS was not found, PICOT framing of a research question is still an important attribute within all RCTs.
Papillary thyroid carcinoma with massive metastasis in the uterine corpus: a case report
Authors: Wang Jian-hong , Yu Jing , Ning Chun-ping , Sun Yong-mei , Fang Shi-bao
Published: November 2013

Background

Distant metastases stemming from a papillary thyroid carcinoma (PTC) are quite rare. Here we report an exceptional case of PTC presenting with cervical lymphatic and uterine metastases. This is the first case report of a PTC with uterine involvement.

Case presentation

A 60-year-old Chinese woman came to our hospital complaining of discomfort in the throat that she had been experiencing for about half a month. PTC and cervical lymphatic metastasis were diagnosed after ultrasound examinations. A massive heterogeneous mass was found beside the uterus during the pre-operative checkup and a diagnosis of ovarian carcinoma was suspected after a thorough case discussion. However, it proved to be a metastasis from the PTC as determined by pathological and immunohistochemical examinations after the operation. The patient declined further treatments. She was followed for 22 months with no sign of recurrence detected.

Conclusions

In this report, an unusual case of PTC was presented. The patient had not only regional lymphatic metastasis, but also had a massive metastasis in the uterine corpus, which was initially misdiagnosed as ovarian carcinoma. This case is of interest because of its rarity and exceptionally good prognosis. The reason for the misdiagnosis was attributed to overlooking the possibility of a distant metastasis coming from a PTC. This case raises the issue that completing an iodine-131 scan before operating on patients with PTC may be warranted.
Polyphenol extract of Phyllanthus emblica (PEEP) induces inhibition of cell proliferation and triggers apoptosis in cervical cancer cells
Authors: Zhu Xinxian , Wang Jianjun , Ou Yang , Han Weiwei , Li Huaifang
Published: November 2013

Background

The aim of this study is to investigate the effects of polyphenol extract from Phyllanthus emblica (PEEP) on cervical cancer cells and to explore the underlying mechanism.

Methods

MTT assay was used to measure inhibition of proliferation of cervical cancer (HeLa) cells after treatment with PEEP at concentrations of 0, 50, 100, 150, and 200 mg/ml for 48 hours. HeLa cells were treated with PEEP (150 mg/ml) for 48 hours in the following analysis. Karyomorphism was assessed by immunofluorescence using DAPI staining, and cell apoptosis and cell cycle were assessed using flow cytometry. Three apoptotic marker proteins, namely, Fas, FasL, and cleaved caspase-8, were assessed by western blotting.

Results

PEEP inhibited the growth of HeLa cells, and the optimum concentration of PEEP was 150 mg/ml. In addition, the karyomorphism of HeLa cells after treatment with PEEP was abnormal. Furthermore, PEEP induced arrest of the HeLa cell cycle at G2/M phase, and triggered apoptosis. PEEP also induced significant Fas and FasL activation, and cleavage of caspase-8.

Conclusions

Our study indicates that PEEP is effective in inhibiting HeLa cell proliferation by inducing cell cycle arrest at G2/M phase and inducing apoptosis.
Offshore Wind Resource Assessment in Rhode Island Waters
Authors: Grilli Annette R. , Spaulding Malcolm L.
Published: November 2013

The validity and accuracy of the Weibull distribution to represent wind speed distributions and estimate the wind power resource is assessed for Southern New England coastal waters. Excellent agreement is found between Weibull-derived and measured mean power resource estimates, confirming the validity of the two-parameter Weibull distribution in the study area. The mean power resource and its spatial variability are assessed and mapped in terms of theoretical and technical power estimates. Finally, a sensitivity study is performed to assess the impact on power estimates at hub height of a hypothetical wind turbine, of uncertainties of three main controlling factors: (1) mean wind speed, (2) Weibull shape parameter, and (3) shear coefficient of the lower atmospheric boundary layer. Results are presented in terms of expected mean theoretical and technical power, and confidence interval, at a hypothetical 110 meters hub height, on a high resolution grid (10 arc-seconds) based on stochastic estimations.
Extreme Wind Speeds and Their Prediction for Wind Turbines
Authors: Rohatgi Janardan , Araújo Alex , Primo Ana Rosa
Published: November 2013

The precise knowledge of occurrence of extreme wind speed for wind turbine design is of utmost importance. This paper describes the extreme value theory, especially the Fisher-Tippett generalized extreme value distributions. On this basis, Gumbel's hypothesis that merely recording of annual extreme events for a duration of ten years or more can provide the probability of occurrence of an extreme event (maximum or minimum). Gumbel's cumulative distribution function (two parameter function) provides the exceedances of wind speed from a given value. The fitting of a regression to the data provides the unknown parameters. However, at the extreme end of the plot, the function is biased. This has been corrected by Gringorten method. The work also calculates the mean recurrence interval of, say, occurrence of a 50-year wind. The proposed methodology to estimate extreme wind speed is simple and straightforward. It is hoped that its use would be a valuable tool in designing wind turbines.
Biophysical characterization of G-quadruplex forming FMR1 mRNA and of its interactions with different fragile X mental retardation protein isoforms
Authors: Blice-Baum Anna C. , Mihailescu Mihaela-Rita
Published: November 2013

Fragile X syndrome, the most common form of inherited mental impairment in humans, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a CGG trinucleotide repeat expansion in the 5′-untranslated region (UTR) and subsequent translational silencing of the fragile x mental retardation-1 (FMR1) gene. FMRP, which is proposed to be involved in the translational regulation of specific neuronal messenger RNA (mRNA) targets, contains an arginine-glycine-glycine (RGG) box RNA binding domain that has been shown to bind with high affinity to G-quadruplex forming mRNA structures. FMRP undergoes alternative splicing, and the binding of FMRP to a proposed G-quadruplex structure in the coding region of its mRNA (named FBS) has been proposed to affect the mRNA splicing events at exon 15. In this study, we used biophysical methods to directly demonstrate the folding of FMR1 FBS into a secondary structure that contains two specific G-quadruplexes and analyze its interactions with several FMRP isoforms. Our results show that minor splice isoforms, ISO2 and ISO3, created by the usage of the second and third acceptor sites at exon 15, bind with higher affinity to FBS than FMRP ISO1, which is created by the usage of the first acceptor site. FMRP ISO2 and ISO3 cannot undergo phosphorylation, an FMRP post-translational modification shown to modulate the protein translation regulation. Thus, their expression has to be tightly regulated, and this might be accomplished by a feedback mechanism involving the FMRP interactions with the G-quadruplex structures formed within FMR1 mRNA.
Traditional medicine: a rare cause of lead poisoning in Western countries
Authors: Muller Halima , Regard Simon , Petriccioli Nicole , Kherad Omar
Published: November 2013

A 42-year-old man from Bhutan was admitted to the emergency department with a 5-day history of abdominal pain, nausea and vomiting. Enhanced abdominal CT scan was found negative, however laboratory tests showed hemolytic anemia and basophilic stippling which are often seen in lead and heavy metal poisoning. Additional tests revealed a high level of lead in blood and urine. The patient was administered a chelator treatment with rapid improvement of the symptoms. A detailed interview revealed that the patient had been taking daily Bhutanese traditional medicines to treat a Bell’s palsy from which he had been suffering for a few months. The analysis of these medicines confirmed the presence of a high level of lead.
Acetylcholinesterase Activity and Neurodevelopment in Boys and Girls
Authors: Suarez-Lopez Jose R. , Himes John H. , Jacobs David R. , Alexander Bruce H. , Gunnar Megan R.
Published: November 2013

BACKGROUND:

Organophosphate exposures can affect children’s neurodevelopment, possibly due to neurotoxicity induced by acetylcholinesterase (AChE) inhibition, and may affect boys more than girls. We tested the hypothesis that lower AChE activity is associated with lower neurobehavioral development among children living in Ecuadorian floricultural communities.

METHODS:

In 2008, we examined 307 children (age: 4–9 years; 52% male) and quantified AChE activity and neurodevelopment in 5 domains: attention/executive functioning, language, memory/learning, visuospatial processing, and sensorimotor (NEPSY-II test). Associations were adjusted for demographic and socioeconomic characteristics and height-for-age, flower worker cohabitation, and hemoglobin concentration.

RESULTS:

Mean ± standard deviation AChE activity was 3.14 ± 0.49 U/mL (similar for both genders). The range of scores among neurodevelopment subtests was 5.9 to 10.7 U (standard deviation: 2.6–4.9 U). Girls had a greater mean attention/executive functioning domain score than boys. In boys only, there were increased odds ratios of low (<9th percentile) neurodevelopment among those in the lowest tertile versus the highest tertile of AChE activity (odds ratios: total neurodevelopment: 5.14 [95% confidence interval (CI): 0.84 to 31.48]; attention/executive functioning domain: 4.55 [95% CI: 1.19 to 17.38], memory/learning domain: 6.03 [95% CI: 1.17 to 31.05]) after adjustment for socioeconomic and demographic factors, height-for-age, and hemoglobin. Within these domains, attention, inhibition and long-term memory subtests were most affected.

CONCLUSIONS:

Low AChE activity was associated with deficits in neurodevelopment, particularly in attention, inhibition, and memory in boys but not in girls. These critical cognitive skills affect learning and academic performance. Added precautions regarding secondary occupational pesticide exposure would be prudent.
Media Use and Sleep Among Boys With Autism Spectrum Disorder, ADHD, or Typical Development
Authors: Engelhardt Christopher R. , Mazurek Micah O. , Sohl Kristin
Published: November 2013

OBJECTIVE:

The current study examined the relationships between media use (television, computer, and video games) and sleep among boys with autism spectrum disorder (ASD) compared with those with attention-deficit/hyperactivity disorder (ADHD) or with typical development (TD).

METHODS:

Participants included parents of boys with ASD (n = 49), ADHD (n = 38), or TD (n = 41) (ages 8–17 years). Questionnaires assessed daily hours of media use, bedroom access to media, and average sleep hours per night.

RESULTS:

Bedroom media access was associated with less time spent sleeping per night, irrespective of diagnostic group. Bedroom access to a television or a computer was more strongly associated with reduced sleep among boys with ASD compared with boys with ADHD or TD. Multivariate models showed that, in addition to bedroom access, the amount of time spent playing video games was uniquely associated with less sleep among boys with ASD. In the ASD group only, the relationship between bedroom access to video games and reduced sleep was mediated by hours of video game play.

CONCLUSIONS:

The current results suggest that media-related variables may be an important consideration in understanding sleep disturbances in children with ASD. Further research is needed to better characterize the processes by which media use may affect sleep among individuals with ASD. Overall, the current findings suggest that screen-based media time and bedroom media access should be routinely assessed and may be important intervention targets when addressing sleep problems in children with ASD.
Žižek in Turkey: A philosopher’s introduction and integration to a target system
Authors: Eker-Roditakis Arzu
Published: November 2013

In Turkey, no Slovene writer has ever enjoyed the popularity that philosopher Slavoj Žižek has done so far. Almost all his books have been translated into Turkish, the lectures he gave in two different universities in 2007 and 2009 were crammed with students and academics alike, and his articles on politics have been published in various journals and the mainstream Turkish media. However, his translational journey in Turkish does not seem to be one without controversy. His books are translated (in one case, retranslated in a span of seven years) by various publishing houses which differ in their publishing policies and ideological stances. This study will focus on the Turkish translations of Žižek’s works and explore the challenges in the integration of his views to the Turkish cultural/social scene, as well as the inevitable connections between ideology, publishing and translation. It will argü that Žižek himself has emerged from this translation process as a translator of Lacan in Turkey, and that, especially in the systemic transfer and integration of models and theories in social sciences in Turkey, social scientists have had to take on the role of the translator, and translators the role of the social scientists in some cases.
Universities, Reflexivity and Critique: Uneasy Parallels in Practice
Authors: May Tim , Perry Beth
Published: November 2013

There are profound changes affecting universities. Under pressure from the forward march of neo-liberalism, there is a process of forgetting about the origins of the university and its distinctive place in society. Whilst responses by university management often amplify these consequences, there are similar tendencies within academic professional cultures. Both combine to enable forms of power to individualise issues around the pursuit of recognition for global excellence. Within universities, this creates an organisational space or ‘missing middle’ that needs to be the subject of reflexive consideration and action in order that the unique role of the university in society is not lost. This article examines these forces in order to contribute to a critical reflexive practice to resist current forces and develop resistant and imaginative cultures.
Spitzoid Melanoma in a Child with Li-Fraumeni Syndrome
Authors: Kollipara Ramya , Cooley Linda D. , Horii Kimberly A. , Hetherington Maxine L. , LeBoit Philip E. , Singh Vivekanand , Zwick David L.
Published: November 2013

Spitzoid melanoma of childhood is a rare malignancy. The histological features are at the upper end of a range encompassing Spitz nevus and atypical Spitz tumor, the unifying features including large oval, fusiform or polygonal melanocytes with abundant homogeneous-appearing cytoplasma and large vesicular nuclei. The presence of a “bottom-heavy” pattern, strikingly enlarged nuclei and nucleoli in both the upper and lower portions of the lesion, and deep mitotic figures are among the findings that distinguish most of the Spitzoid melanomas from Spitz nevi and atypical Spitz tumors. There are no syndromic associations reported for this malignancy. We report the occurrence of choroid plexus carcinoma, Spitzoid melanoma, and myelodysplasia in a child who was found to carry a germline mutation for TP53. While choroid plexus carcinoma and myelodysplasia have relatively frequently been described, melanomas have been very rarely described in Li-Fraumeni syndrome. The association of Spitzoid melanoma with Li-Fraumeni syndrome, especially in a pediatric patient, has not been reported before.
Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma
Authors: Richter Antje , Haag Tanja , Walesch Sara , Herrmann-Trost Peter , Marsch Wolfgang , Kutzner Heinz , Helmbold Peter , Dammann Reinhard
Published: November 2013

Merkel cell carcinoma (MCC) is one of the most aggressive cancers of the skin. RASSFs are a family of tumor suppressors that are frequently inactivated by promoter hypermethylation in various cancers. We studied CpG island promoter hypermethylation in MCC of RASSF2, RASSF5A, RASSF5C and RASSF10 by combined bisulfite restriction analysis (COBRA) in MCC samples and control tissue. We found RASSF2 to be methylated in three out of 43 (7%), RASSF5A in 17 out of 39 (44%, but also 43% in normal tissue), RASSF5C in two out of 26 (8%) and RASSF10 in 19 out of 84 (23%) of the cancer samples. No correlation between the methylation status of the analyzed RASSFs or between RASSF methylation and MCC characteristics (primary versus metastatic, Merkel cell polyoma virus infection, age, sex) was found. Our results show that RASSF2, RASSF5C and RASSF10 are aberrantly hypermethylated in MCC to a varying degree and this might contribute to Merkel cell carcinogenesis.
Exploring Graphics Processing Unit (GPU) Resource Sharing Efficiency for High Performance Computing
Authors: Li Teng , Narayana Vikram , El-Ghazawi Tarek
Published: November 2013

The increasing incorporation of Graphics Processing Units (GPUs) as accelerators has been one of the forefront High Performance Computing (HPC) trends and provides unprecedented performance; however, the prevalent adoption of the Single-Program Multiple-Data (SPMD) programming model brings with it challenges of resource underutilization. In other words, under SPMD, every CPU needs GPU capability available to it. However, since CPUs generally outnumber GPUs, the asymmetric resource distribution gives rise to overall computing resource underutilization. In this paper, we propose to efficiently share the GPU under SPMD and formally define a series of GPU sharing scenarios. We provide performance-modeling analysis for each sharing scenario with accurate experimentation validation. With the modeling basis, we further conduct experimental studies to explore potential GPU sharing efficiency improvements from multiple perspectives. Both further theoretical and experimental GPU sharing performance analysis and results are presented. Our results not only demonstrate the significant performance gain for SPMD programs with the proposed efficient GPU sharing, but also the further improved sharing efficiency with the optimization techniques based on our accurate modeling.
Toward an Efficient Prediction of Solar Flares: Which Parameters, and How?
Authors: Georgoulis Manolis
Published: November 2013

Solar flare prediction has become a forefront topic in contemporary solar physics, with numerous published methods relying on numerous predictive parameters, that can even be divided into parameter classes. Attempting further insight, we focus on two popular classes of flare-predictive parameters, namely multiscale (i.e., fractal and multifractal) and proxy (i.e., morphological) parameters, and we complement our analysis with a study of the predictive capability of fundamental physical parameters (i.e., magnetic free energy and relative magnetic helicity). Rather than applying the studied parameters to a comprehensive statistical sample of flaring and non-flaring active regions, that was the subject of our previous studies, the novelty of this work is their application to an exceptionally long and high-cadence time series of the intensely eruptive National Oceanic and Atmospheric Administration (NOAA) active region (AR) 11158, observed by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory. Aiming for a detailed study of the temporal evolution of each parameter, we seek distinctive patterns that could be associated with the four largest flares in the AR in the course of its five-day observing interval. We find that proxy parameters only tend to show preflare impulses that are practical enough to warrant subsequent investigation with sufficient statistics. Combining these findings with previous results, we conclude that: (i) carefully constructed, physically intuitive proxy parameters may be our best asset toward an efficient future flare-forecasting; and (ii) the time series of promising parameters may be as important as their instantaneous values. Value-based prediction is the only approach followed so far. Our results call for novel signal and/or image processing techniques to efficiently utilize combined amplitude and temporal-profile information to optimize the inferred solar-flare probabilities.
Biomass Fuel and Combustion Conditions Selection in a Fixed Bed Combustor
Authors: Arce María , Saavedra Ángeles , Míguez José , Granada Enrique , Cacabelos Antón
Published: November 2013

The biomass market has experienced an increase in development, leading to research and development efforts that are focused on determining optimal biofuel combustion conditions. Biomass combustion is a complex process that involves divergent parameters and thus requires the use of advanced analysis methods. This study proposes combining grey relational analysis (GRA) and error propagation theory (EPT) to select a biofuel and its optimal combustion conditions. This research will study three biofuels that are currently used in a region of South Europe (Spain), and the most important variables that affect combustion are the ignition front propagation speed and the highest temperature that is reached at the fixed bed combustor. The results demonstrate that a combination of both theories for the analysis of solid-state thermochemical phenomena enables a fast and simple way of choosing the best configuration for each fuel.
On the Integration of Leadership in Energy and Environmental Design (LEED)® ND Protocol with the Energy Planning and Management Tools in Italy: Strengths and Weaknesses
Authors: Dall'O' Giuliano , Galante Annalisa , Sanna Nicola , Miller Karin
Published: November 2013

Owners and municipalities face the choice to renovate or rebuild buildings in order to improve energy efficiency and sustainability. The process of upgrading the existing building stock can be supported by land management tools, i.e., municipal energy plans (MEP) or sustainable building codes (BC), that municipalities use to plan, check and monitor actions taken. Many local and regional authorities are involved in the Covenant of Mayors supported by the European Union (EU): the sustainable energy action plan (SEAP) is the key document in which the Covenant signatory outlines how it intends to reach CO2 reduction target by 2020. Sustainability at the urban scale is also supported by voluntary certification schemes such as Leadership in Energy and Environmental Design (LEED)® for neighbourhood development proposed by the United States Green Building Council (USGBC), Building Research Establishment Environmental Assessment Method (BREEAM) Communities proposed by UK Building Research Establishment (BRE) and Comprehensive Assessment System for Built Environment Efficiency (CASBEE) for Urban Development proposed by the Japan GreenBuild Council. The fact that there are so many tools to manage urban sustainability is positive, but what happens when multiple tools are applied to the same territory? Overlap, redundancy, and conflicts in management may be critical elements. The purpose of this article is to analyze these critical issues, highlighting the elements of integration and possible synergies for effective management of sustainability at the local level.
Design and Implementation of Real-Time Intelligent Control and Structure Based on Multi-Agent Systems in Microgrids
Authors: Kuo Ming-Tse , Lu Shiue-Der
Published: November 2013

By consulting various worldwide definitions of microgrids and distributed energy, this study presents a microgrid-structured multi-agent system and uses Matlab/Simulink to construct a circuit with microgrid features, which enables the changes in each electrical source and load in the microgrid to be monitored and controlled. This multi-agent system adheres to the Java Agent Development Framework (JADE) platform specifications of the Foundation for Intelligent Physical Agents (FIPA), facilitating communication, information transfers, and the receipt of real-time information regarding the microgrid and each component in the microgrid. Furthermore, the real-time state in the microgrid can be correspondingly controlled, achieving the most efficient real-time monitoring and control for electrical sources and load management in the microgrid.
Use of Optical Oxygen Sensors in Non-Destructively Determining the Levels of Oxygen Present in Combined Vacuum and Modified Atmosphere Packaged Pre-Cooked Convenience-Style Foods and the Use of Ethanol Emitters to Extend Product Shelf-Life
Authors: Hempel Andreas , Papkovsky Dmitri , Kerry Joseph
Published: November 2013

O2 sensors were used to non-destructively monitor O2 levels in commercially packed pre-cooked, convenience modified atmosphere packaging (MAP) foods. A substantial level of O2 (>15%) was present in packs resulting in a shorter than expected shelf-life, where the primary spoilage mechanism was found to be mould. Various combinations of vacuum (0–0.6 MPa) and gas flush (0.02–0.03 MPa) (30% CO2/70% N2) settings were assessed as treatments that result in the desired shelf-life (28 days). This was achieved using the combined treatment of vacuum 0.35 MPa and gas flush 0.02 MPa which resulted in a reduction of 6%–9% O2 in all three samples (battered sausages (BS), bacon slices (BA), and meat and potato pies (PP)). Reduced O2 levels reflect the microbial quality of products, which has been successfully reduced. Duplicate samples of all product packs were produced using ethanol emitters (EE) to see if shelf-life could be further extended. Results showed a further improvement in shelf-life to 35 days. Sensory analysis showed that ethanol flavour and aroma was not perceived by panellists in two of the three products assessed. This study demonstrates how smart packaging technologies, both intelligent and active, can be used to assist in the modification of conventional packaging systems in order to enhance product quality and safety and through the extension of product shelf-life.
HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival
Authors: Jiang Shi-Wen , Chen Haibin , Dowdy Sean , Fu Alex , Attewell John , Kalogera Eleftheria , Drapkin Ronny , Podratz Karl , Broaddus Russell , Li Jinping
Published: November 2013

We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC) tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.
Study of the Wavelength Dependence in Laser Ablation of Advanced Ceramics and Glass-Ceramic Materials in the Nanosecond Range
Authors: Sola Daniel , Peña Jose
Published: November 2013

In this work, geometrical dimensions and ablation yields as a function of the machining method and reference position were studied when advanced ceramics and glass-ceramic materials were machined with pulsed lasers in the nanosecond range. Two laser systems, emitting at 1064 and 532 nm, were used. It was shown that the features obtained depend on whether the substrate is processed by means of pulse bursts or by grooves. In particular, when the samples were processed by grooves, machined depth, removed volume and ablation yields reached their maximum, placing the sample out of focus. It was shown that these characteristics do not depend on the processing conditions, the wavelength or the optical configuration, and that this is intrinsic behavior of the processing method. Furthermore, the existence of a close relation between material hardness and ablation yields was demonstrated.
Synthesis of DNA/RNA and Their Analogs via Phosphoramidite and H-Phosphonate Chemistries
Authors: Roy Subhadeep , Caruthers Marvin
Published: November 2013

The chemical synthesis of DNA and RNA is universally carried out using nucleoside phosphoramidites or H-phosphonates as synthons. This review focuses on the phosphorus chemistry behind these synthons and how it has been developed to generate procedures whereby yields per condensation approach 100% with very few side products. Additionally the synthesis and properties of certain DNA and RNA analogs that are modified at phosphorus will also be discussed. These analogs include boranephosphonates, metallophosphonates, and alkylboranephosphines.
Tuning a 96-Well Microtiter Plate Fluorescence-Based Assay to Identify AGE Inhibitors in Crude Plant Extracts
Authors: Séro Luc , Sanguinet Lionel , Blanchard Patricia , Dang Bach , Morel Sylvie , Richomme Pascal , Séraphin Denis , Derbré Séverine
Published: November 2013

Advanced glycation end-products (AGEs) are involved in the pathogenesis of numerous diseases. Among them, cellular accumulation of AGEs contributes to vascular complications in diabetes. Besides using drugs to lower blood sugar, a balanced diet and the intake of herbal products potentially limiting AGE formation could be considered beneficial for patients’ health. The current paper presents a simple and cheap high-throughput screening (HTS) assay based on AGE fluorescence and suitable for plant extract screening. We have already implemented an HTS assay based on vesperlysines-like fluorescing AGEs quickly (24 h) formed from BSA and ribose under physiological conditions. However, interference was noted when fluorescent compounds and/or complex mixtures were tested. To overcome these problems and apply this HTS assay to plant extracts, we developed a technique for systematic quantification of both vesperlysines (λexc 370 nm; λem 440 nm) and pentosidine-like (λexc 335 nm; λem 385 nm) AGEs. In a batch of medicinal and food plant extracts, hits were selected as soon as fluorescence decreased under a fixed threshold for at least one wavelength. Hits revealed during this study appeared to contain well-known and powerful anti-AGE substances, thus demonstrating the suitability of this assay for screening crude extracts (0.1 mg/mL). Finally, quercetin was found to be a more powerful reference compound than aminoguanidine in such assay.
Lectin Staining Shows no Evidence of Involvement of Glycocalyx/Mucous Layer Carbohydrate Structures in Development of Celiac Disease
Authors: Toft-Hansen Henrik , Nielsen Christian , Biagini Matteo , Husby Steffen , Lillevang Søren
Published: November 2013

The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA) staining for Gal-β(1,3)-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates.