bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding type 2 diabetes causal single nucleotide polymorphism combinations and functional modules from genome-wide association data
Authors: Kang Chiyong , Yu Hyeji , Yi Gwan-Su
Published: April 2013

Background

Due to the low statistical power of individual markers from a genome-wide association study (GWAS), detecting causal single nucleotide polymorphisms (SNPs) for complex diseases is a challenge. SNP combinations are suggested to compensate for the low statistical power of individual markers, but SNP combinations from GWAS generate high computational complexity.

Methods

We aim to detect type 2 diabetes (T2D) causal SNP combinations from a GWAS dataset with optimal filtration and to discover the biological meaning of the detected SNP combinations. Optimal filtration can enhance the statistical power of SNP combinations by comparing the error rates of SNP combinations from various Bonferroni thresholds and p-value range-based thresholds combined with linkage disequilibrium (LD) pruning. T2D causal SNP combinations are selected using random forests with variable selection from an optimal SNP dataset. T2D causal SNP combinations and genome-wide SNPs are mapped into functional modules using expanded gene set enrichment analysis (GSEA) considering pathway, transcription factor (TF)-target, miRNA-target, gene ontology, and protein complex functional modules. The prediction error rates are measured for SNP sets from functional module-based filtration that selects SNPs within functional modules from genome-wide SNPs based expanded GSEA.

Results

A T2D causal SNP combination containing 101 SNPs from the Wellcome Trust Case Control Consortium (WTCCC) GWAS dataset are selected using optimal filtration criteria, with an error rate of 10.25%. Matching 101 SNPs with known T2D genes and functional modules reveals the relationships between T2D and SNP combinations. The prediction error rates of SNP sets from functional module-based filtration record no significance compared to the prediction error rates of randomly selected SNP sets and T2D causal SNP combinations from optimal filtration.

Conclusions

We propose a detection method for complex disease causal SNP combinations from an optimal SNP dataset by using random forests with variable selection. Mapping the biological meanings of detected SNP combinations can help uncover complex disease mechanisms.
Rule-based multi-scale simulation for drug effect pathway analysis
Authors: Hwang Woochang , Hwang Yongdeuk , Lee Sunjae , Lee Doheon
Published: April 2013

Background

Biological systems are robust and complex to maintain stable phenotypes under various conditions. In these systems, drugs reported the limited efficacy and unexpected side-effects. To remedy this situation, many pharmaceutical laboratories have begun to research combination drugs and some of them have shown successful clinical results. Complementary action of multiple compounds could increase efficacy as well as reduce side-effects through pharmacological interactions. However, experimental approach requires vast cost of preclinical experiments and tests as the number of possible combinations of compound dosages increases exponentially. Computer model-based experiments have been emerging as one of the most promising solutions to cope with such complexity. Though there have been many efforts to model specific molecular pathways using qualitative and quantitative formalisms, they suffer from unexpected results caused by distant interactions beyond their localized models.

Results

In this work, we propose a rule-based multi-scale modelling platform. We have tested this platform with Type 2 diabetes (T2D) model, which involves the malfunction of numerous organs such as pancreas, circulation system, liver, and adipocyte. We have extracted T2D-related 190 rules by manual curation from literature, pathway databases and converting from different types of existing models. We have simulated twenty-two T2D drugs. The results of our simulation show drug effect pathways of T2D drugs and whether combination drugs have efficacy or not and how combination drugs work on the multi-scale model.

Conclusions

We believe that our simulation would help to understand drug mechanism for the drug development and provide a new way to effectively apply existing drugs for new target. It also would give insight for identifying effective combination drugs.
Celecoxib reduces brain dopaminergic neuronaldysfunction, and improves sensorimotor behavioral performance in neonatal rats exposed to systemic lipopolysaccharide
Authors: Kaizaki Asuka , Tien Lu-Tai , Pang Yi , Cai Zhengwei , Tanaka Sachiko , Numazawa Satoshi , Bhatt Abhay J , Fan Lir-Wan
Published: April 2013

Background

Cyclooxygenase-2 (COX-2) is induced in inflammatory cells in response to cytokines and pro-inflammatory molecules, suggesting that COX-2 has a role in the inflammatory process. The objective of the current study was to examine whether celecoxib, a selective COX-2 inhibitor, could ameliorate lipopolysaccharide (LPS)-induced brain inflammation, dopaminergic neuronal dysfunction and sensorimotor behavioral impairments.

Methods

Intraperitoneal (i.p.) injection of LPS (2 mg/kg) was performed in rat pups on postnatal Day 5 (P5), and celecoxib (20 mg/kg) or vehicle was administered (i.p.) five minutes after LPS injection. Sensorimotor behavioral tests were carried out 24 h after LPS exposure, and brain injury was examined on P6.

Results

Our results showed that LPS exposure resulted in impairment in sensorimotor behavioral performance and injury to brain dopaminergic neurons, as indicated by loss of tyrosine hydroxylase (TH) immunoreactivity, as well as decreases in mitochondria activity in the rat brain. LPS exposure also led to increases in the expression of α-synuclein and dopamine transporter proteins and enhanced [3H]dopamine uptake. Treatment with celecoxib significantly reduced LPS-induced sensorimotor behavioral disturbances and dopaminergic neuronal dysfunction. Celecoxib administration significantly attenuated LPS-induced increases in the numbers of activated microglia and astrocytes and in the concentration of IL-1β in the neonatal rat brain. The protective effect of celecoxib was also associated with an attenuation of LPS-induced COX-2+ cells, which were double labeled with TH + (dopaminergic neuron) or glial fibrillary acidic protein (GFAP) + (astrocyte) cells.

Conclusion

Systemic LPS administration induced brain inflammatory responses in neonatal rats; these inflammatory responses included induction of COX-2 expression in TH neurons and astrocytes. Application of the COX-2 inhibitor celecoxib after LPS treatment attenuated the inflammatory response and improved LPS-induced impairment, both biochemically and behaviorally.
miR-411 is up-regulated in FSHD myoblasts and suppresses myogenic factors
Authors: Harafuji Naoe , Schneiderat Peter , Walter Maggie C , Chen Yi-Wen
Published: April 2013

Background

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disorder, which is linked to the contraction of the D4Z4 array at chromosome 4q35. Recent studies suggest that this shortening of the D4Z4 array leads to aberrant expression of double homeobox protein 4 (DUX4) and causes FSHD. In addition, misregulation of microRNAs (miRNAs) has been reported in muscular dystrophies including FSHD. In this study, we identified a miRNA that is differentially expressed in FSHD myoblasts and investigated its function.

Methods

To identify misregulated miRNAs and their potential targets in FSHD myoblasts, we performed expression profiling of both miRNA and mRNA using TaqMan Human MicroRNA Arrays and Affymetrix Human Genome U133A plus 2.0 microarrays, respectively. In addition, we over-expressed miR-411 in C2C12 cells to determine the effect of miR-411 on myogenic markers.

Results

Using miRNA and mRNA expression profiling, we identified 8 miRNAs and 1,502 transcripts that were differentially expressed in FSHD myoblasts during cell proliferation. One of the 8 differentially expressed miRNAs, miR-411, was validated by quantitative RT-PCR in both primary (2.1 fold, p<0.01) and immortalized (2.7 fold, p<0.01) myoblasts. In situ hybridization showed cytoplasmic localization of miR-411 in FSHD myoblasts. By analyzing both miRNA and mRNA data using Partek Genomics Suite, we identified 4 mRNAs potentially regulated by miR-411 including YY1 associated factor 2 (YAF2). The down-regulation of YAF2 in immortalized myoblasts was validated by immunoblotting (−3.7 fold, p<0.01). C2C12 cells were transfected with miR-411 to determine whether miR-411 affects YAF2 expression in myoblasts. The results showed that over-expression of miR-411 reduced YAF2 mRNA expression. In addition, expression of myogenic markers including Myod, myogenin, and myosin heavy chain 1 (Myh1) were suppressed by miR-411.

Conclusions

The study demonstrated that miR-411 was differentially expressed in FSHD myoblasts and may play a role in regulating myogenesis.
Inhibition of Streptococcus pneumoniae adherence to human epithelial cells in vitro by the probiotic Lactobacillus rhamnosus GG
Authors: Wong Sook-San , Quan Toh Zheng , Dunne Eileen M , Mulholland E Kim , Tang Mimi LK , Robins-Browne Roy M , Licciardi Paul V , Satzke Catherine
Published: April 2013

Background

Colonization of the nasopharynx by Streptococcus pneumoniae is considered a prerequisite for pneumococcal infections such as pneumonia and otitis media. Probiotic bacteria can influence disease outcomes through various mechanisms, including inhibition of pathogen colonization. Here, we examine the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on S. pneumoniae colonization of human epithelial cells using an in vitro model. We investigated the effects of LGG administered before, at the same time as, or after the addition of S. pneumoniae on the adherence of four pneumococcal isolates.

Results

LGG significantly inhibited the adherence of all the pneumococcal isolates tested. The magnitude of inhibition varied with LGG dose, time of administration, and the pneumococcal isolate used. Inhibition was most effective when a higher dose of LGG was administered prior to establishment of pneumococcal colonization. Mechanistic studies showed that LGG binds to epithelial cells but does not affect pneumococcal growth or viability. Administration of LGG did not lead to any significant changes in host cytokine responses.

Conclusions

These findings demonstrate that LGG can inhibit pneumococcal colonization of human epithelial cells in vitro and suggest that probiotics could be used clinically to prevent the establishment of pneumococcal carriage.
China’s biggest, most neglected health challenge: non-communicable diseases
Authors: Tang Shenglan , Ehiri John , Long Qian
Published: April 2013

Background

Over the past two decades, international health policies focusing on the fight against the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), tuberculosis (TB), malaria, and those diseases that address maternal and child health problems, among others, have skewed disease control priorities in China and other Asian countries. Although these are important health problems, an epidemic of chronic, non-communicable diseases (NCDs) in China has accounted for a much greater burden of disease due to the ongoing rapid socioeconomic and demographic transition.

Discussion

Although NCDs currently account for more than 80% of the overall disease burden in China, they remain very low on the nation’s disease control priorities, attracting marginal investment from central and local governments. This leaves the majority of patients with chronic conditions without effective treatment. International organizations and national governments have recognized the devastating social and economic consequences caused by NCDs in low- and middle-income countries, including China. Yet, few donor-funded projects that address NCDs have been implemented in these countries over the past decade. Due to a lack of strong support from international organizations and national governments for fighting against NCDs, affected persons in China, especially the poor and those who live in rural and less developed regions, continue to have limited access to the needed care. Costs associated with frequent health facility visits and regular treatment have become a major factor in medical impoverishment in China. This article argues that although China's ongoing health system reform would provide a unique opportunity to tackle current public health problems, it may not be sufficient to address the emerging threat of NCDs unless targeted steps are taken to assure that adequate financial and human resources are mapped for effective control and management of NCDs in the country.

The Chinese government needs to develop a domestically-driven and evidence-based disease control policy and funding priorities that respond appropriately to the country’s current epidemiological transition, and rapid sociodemographic and lifestyle changes.
Ethnic disparities in higher education
Authors: Zorlu Aslan
Published: April 2013

Using unique administrative individual data, this paper examines ethnic differences in degree performance in Dutch colleges and universities. The paper estimates parametric duration models and accounts for unobserved heterogeneity to assess the sources of ethnic disparities. The analysis shows that ethnic minorities from non-western countries have a significantly lower degree performance and higher risk of dropping-out. Especially, Turkish, Moroccan and Caribbean students are less likely to graduate, and graduates among them need much more time to complete their study. There is no evidence that this disadvantage stems from poor parental socioeconomic position and the choice of study subject.
Preparing for the CU-TEP Examination: Methods Used by Thai Students
Authors: Scrymgeour Jane M
Published: April 2013

This paper discusses how a group of students from Chulalongkorn University prepared for the CU-Tep examination. In order to gather the information, a questionnaire was given to 16 students from the Education Department of Chulalongkorn University. The findings indicated three things. First, was the general lack of preparation by approximately half of the candidates. Second, was that all of the students found the examination difficult, even those who said they did some preparation. Third, was the relatively poor scores received by Thai students as noted in the research cited. Some recommendations for the students: listen to and follow the advice of those who have previously taken the exam, do lots of preparation by taking practice tests and seek help from others.
Using Google Sites to Communicate with Parents: A Case Study
Authors: Liou Yeu-Han H
Published: April 2013

The paper summarizes a case study that took place in a Thai private alternative school - the Darunsikkhalai School for Innovative Learning (DSIL). More specifically, this paper focuses on the usefulness of a class website created by Google Sites in one of the mathematics classes in the school. Questionnaires are distributed to students, parents, and teachers in DSIL to discuss their attitudes, opinions, and experiences towards using class web pages as a medium of communication.
Application of Structural Equation Modeling in Assessing the Relationship Between Stuttering Students' Cognitive and Metacognitive Strategies and Their Reading Comprehension Performance
Authors: Ghaemi Hamed , Ghaemi Hamide
Published: April 2013

Language testing is not limited to assessing the performance of ordinary learners. It is also needed in other field such as assessing the ability of children with disabilities, those who have language disorders. Although a great deal of research has been carried out in the realm of stuttering, researchers still do not know why some children stutter, or why most children become fluent speakers while others become adult stutterers. Studies show that Stuttering students have many difficulties in Reading Comprehension (Roberts & Erdos, 1993). It is stated in the Reading Comprehension literature that cognitive and metacognitive strategies have a crucial role in reading comprehension performance. The present study aims at investigating the relationship between cognitive and metacognitive strategies of stuttering students through using Structural Equation Modeling (SEM). The findings of the study show that there is a meaningful relationship between Cognitive and Metacognitive strategies of stuttering students. However, there is no statistically significant relationship between the Cognitive strategies and Reading Comprehension of Stuttering Students.
An Evaluative Commentary of the Grade 1 EIKEN Test
Authors: Piggin Gabrielle
Published: April 2013

This paper aims to analyse the fit between the "use" and "usefulness" of the EIKEN Grade 1 test as a valid and reliable instrument to measure second language proficiency. The recent re-positioning of the EIKEN Grade 1 test as an internationally recognised higher stakes test of English proficiency, which allows successful test taker's access to higher education in international academic contexts, is discussed. The evaluation was based upon Bachman and Palmer's (1996) model of test usefulness in order to critically ascertain whether such test use is one that could be justified. This empirical investigation explicitly purports the need for further quantitative and qualitative analysis to justify EIKEN Grade 1's test usefulness.
Impact of interleukin-10, soluble CD25 and interferon-γ on the prognosis and early diagnosis of bacteremic systemic inflammatory response syndrome: a prospective observational study
Authors: Matera Giovanni , Puccio Rossana , Giancotti Aida , Quirino Angela , Pulicari Maria Concetta , Zicca Emilia , Caroleo Santo , Renzulli Attilio , Liberto Maria Carla , Focà Alfredo
Published: April 2013

Introduction

The pathophysiology of sepsis consists of two phases. A first phase characterized by a substantial increase of pro-inflammatory mediators including cytokines and systemic inflammatory markers, and a second phase (immunoparalysis, immunodysregulation) associated with the rise of anti-inflammatory mediators. In this study we prospectively analyzed 52 consecutive patients with diagnosis of systemic inflammatory response syndrome (SIRS) at hospital admission to evaluate prognostic and early diagnostic performance of interleukin-10 (IL-10), soluble CD25 (sCD25) and interferon-γ (IFN-γ) and to confirm the prognostic accuracy of the sequential organ failure assessment (SOFA) score.

Methods

Patients were divided in two groups (group 1, n = 28 patients with bacteremic SIRS and group 2, n = 24 patients with non-bacteremic SIRS) and then stratified into survivors (n = 39) and nonsurvivors (n = 13). Serum markers were evaluated on the day of hospital admission (D-1) and on the 7th day of hospital stay (D-7). Concentration of sCD25 was evaluated by a sandwich ELISA kit. Levels of IL-10 and IFN-γ were quantified by a cytokine biochip array by the evidence investigator analyzer. Differences between groups were established by the Mann-Whitney test. Accuracy, sensitivity and specificity of diagnostic markers were evaluated by the receiver-operating characteristic curve analysis. Multivariate analysis was carried out to evaluate whether studied biomarkers are independent predictors of poor outcome in prognosis, and of bacteremic SIRS in diagnosis.

Results

IL-10, sCD25 and SOFA scores of survivors and nonsurvivors were significantly different both at D-1 (P = 0.0014; P = 0.014 and P = 0.0311 respectively) and at D-7 (P = 0.0002, P = 0.014 and P = 0.0012 respectively). Between the above groups IFN-γ level was significantly different only at D-7 (P = 0.0013). Moreover IL-10 and sCD25 were significantly higher in bacteremic versus non-bacteremic SIRS patients at D-1 and at D-7 (P < 0.05). IFN-γ values showed a significant decrease (P < 0.05) in patients of group 1 only at D-7. The diagnostic accuracy of IL-10 and sCD25 was confirmed by the analysis of the AUROCC at D-1 and D-7 respectively. Multivariate analysis revealed that sCD25 and IL-10 are independent predictors of a poor outcome for our patients during the first day of hospital admission.

Conclusions

IL-10 and sCD25 gave a significant contribution to prognostic evaluation and early diagnosis of bacteremic SIRS. SOFA score appeared to be a reliable prognostic tool in this subset of patients.
Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing
Authors: Heitzer Ellen , Ulz Peter , Belic Jelena , Gutschi Stefan , Quehenberger Franz , Fischereder Katja , Benezeder Theresa , Auer Martina , Pischler Carina , Mannweiler Sebastian , Pichler Martin , Eisner Florian , Haeusler Martin , Riethdorf Sabine , Pantel Klaus , Samonigg Hellmut , Hoefler Gerald , Augustin Herbert , Geigl Jochen B , Speicher Michael R
Published: April 2013

Background

Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively.

Methods

We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC).

Results

The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone.

Conclusions

The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'.
Deep-tow 3C magnetic measurement: Solutions for calibration and interpretation
Authors: Bronner Adrien , Munschy Marc , Sauter Daniel , Carlut Julie , Searle Roger , Maineult Alexis
Published: April 2013

Two main problems are encountered in deep-tow 3C magnetic surveys. The first problem is related to instrumental error due to the manufacturing of the sensor, its integration in the towed fish structure, and the magnetization of the vehicle carrying the magnetometer; the second is related to the variation in altitude of the instruments during the dive. We evaluated a new type of calibration approach for deep-tow fluxgate magnetometers. We found that the magnetometer can be calibrated with no recourse to the vehicle attitude (pitch, roll, and heading, as it is usually achieved) but only using the three components recorded by the magnetometer and an approximation of the scalar intensity of the earth’s magnetic field. This method, called scalar calibration, allowed us to eliminate the intrinsic instrumental errors as well as the magnetization effect of the tow vehicle. Thus, despite the low maneuverability of the towed fish during the calibration experiment, we discovered a significant improvement in obtaining accurate magnetic anomaly profiles. Because only the total field anomaly and not the magnetic vector is suitable for this method, we investigated the possibility of calculating the three components via an equivalent-source approach. Therefore, assuming a 2D topographic equivalent layer, we found a stable and a meaningful magnetization of the oceanic crust. We discovered that although magnetic data are acquired along uneven tracks, this model, based on a single linear inversion, is sufficient to provide a first-order depth and magnetization intensity of the crust and also to carry out upward continuation of the total anomalous field as well as its associated vector.
Using isostatic gravity anomalies from spherical harmonic models and elastic plate compensation to interpret the lithosphere of the Bolivian Andes
Authors: Jekeli Christopher , Yang Hyo Jin , Ahlgren Kevin
Published: April 2013

We have determined for the Bolivian Andes that the new global gravity models derived from the Gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite mission may be used directly to study lithospheric structure. Toward this end, we have formulated Bouguer and isostatic gravity anomalies in spherical approximation, rather than in the usual planar approach, using spherical harmonic series consistent with the satellite-derived gravitational models. From the approximate equivalency of topographic masses and surface density layers using the Helmert condensation method we further derived and used isotropic transfer relations between the spherical spectra of topographic loads and elastic spherical shell deflections, where the Airy isostatic compensation is the special case of no flexural rigidity. A numerical comparison of these spherical harmonic models to conventional three-dimensional modeling based on topographic data and newly acquired surface gravity data in Bolivia confirmed their suitability for lithospheric interpretation. Specifically, the relatively high and uniform resolution of the satellite gravitational model (better than 83 km) produces detailed maps of the isostatic anomaly that clearly delineate the flexure of the Brazilian shield that is thrust under the Sub-Andes. Inferred values of the thickness of Airy-type roots and the flexural rigidity of the elastic lithosphere agree reasonably with published results based on seismic and surface gravity data. In addition, a local minimum in the flexural rigidity is evident at the sharp bend of the eastern margins of the Sub-Andes in Bolivia. This feature is consistent with earlier theories for counter rotations about a vertical axis at this minimum, associated with the confluence of the subducted Nazca plate and the Brazilian craton. The GOCE model thus generates high-resolution isostatic anomaly maps that offer additional structural detail not seen as clearly from previous seismic and gravity investigations in this region.
Cytosolic caspases mediate mislocalised SOD2 depletion in an in vitro model of chronic prion infection
Authors: Sinclair Layla , Lewis Victoria , Collins Steven J. , Haigh Cathryn L.
Published: April 2013

Oxidative stress as a contributor to neuronal death during prion infection is supported by the fact that various oxidative damage markers accumulate in the brain during the course of this disease. The normal cellular substrate of the causative agent, the prion protein, is also linked with protective functions against oxidative stress. Our previous work has found that, in chronic prion infection, an apoptotic subpopulation of cells exhibit oxidative stress and the accumulation of oxidised lipid and protein aggregates with caspase recruitment. Given the likely failure of antioxidant defence mechanisms within apoptotic prion-infected cells, we aimed to investigate the role of the crucial antioxidant pathway components, superoxide dismutases (SOD) 1 and 2, in an in vitro model of chronic prion infection. Increased total SOD activity, attributable to SOD1, was found in the overall population coincident with a decrease in SOD2 protein levels. When apoptotic cells were separated from the total population, the induction of SOD activity in the infected apoptotic cells was lost, with activity reduced back to levels seen in mock-infected control cells. In addition, mitochondrial superoxide production was increased and mitochondrial numbers decreased in the infected apoptotic subpopulation. Furthermore, a pan-caspase probe colocalised with SOD2 outside of mitochondria within cytosolic aggregates in infected cells and inhibition of caspase activity was able to restore cellular levels of SOD2 in the whole unseparated infected population to those of mock-infected control cells. Our results suggest that prion propagation exacerbates an apoptotic pathway whereby mitochondrial dysfunction follows mislocalisation of SOD2 to cytosolic caspases, permitting its degradation. Eventually, cellular capacity to maintain oxidative homeostasis is overwhelmed, thus resulting in cell death.
DNA-Conjugated Polymers for Reliable SNP Genotyping Based on Affinity Capillary Electrophoresis
Authors: Takarada Tohru , Maeda Mizuo
Published: April 2013

To quantitatively detect single-base mutations in genetic samples, free-solution affinity capillary electrophoresis was developed using a diblock copolymer probe composed of allele-specific oligodeoxyribonucleotide (ODN) and poly(ethylene glycol) (PEG). When the probe is designed to be complementary to a wild-type single-stranded DNA sample (WT), WT migrates more slowly than its single-base mutant (MT). This is because WT forms a reversible complex with the probe via hybridization during the electrophoresis, resulting in a large amount of hydrodynamic friction. In contrast, a negligibly weak interaction takes place between MT and the probe due to a single-base mismatch. Accordingly, the MT peak appears earlier than the WT peak on the electropherogram. The difference of the migration time between WT and MT depends on the thermodynamic stability of the complex and also on the amount of hydrodynamic friction that the complex encounters. Therefore, the peak resolution is rationally controlled by the base-number of the ODN segment and by the molecular weight of the PEG segment. Importantly, the peak area ratio provides the occurrence ratio of the single-base mutant within the given population. This facile and accurate method to estimate SNP allele frequency should find applications in various research fields.
Designing Random Allocation Mechanisms: Theory and Applications
Authors: Budish Eric , Che Yeon-Koo , Kojima Fuhito , Milgrom Paul
Published: April 2013

Randomization is commonplace in everyday resource allocation. We generalize the theory of randomized assignment to accommodate multi-unit allocations and various real-world constraints, such as group-specific quotas (“controlled choice”) in school choice and house allocation, and scheduling and curriculum constraints in course allocation. We develop new mechanisms that are ex ante efficient and fair in these environments, and that incorporate certain non-additive substitutable preferences. We also develop a “utility guarantee” technique that limits ex post unfairness in random allocations, supplementing the ex ante fairness promoted by randomization. This can be applied to multi-unit assignment problems and certain two-sided matching problems. (JEL C78, D82)
The Effect of Language on Economic Behavior: Evidence from Savings Rates, Health Behaviors, and Retirement Assets
Authors: Chen M. Keith
Published: April 2013

Languages differ widely in the ways they encode time. I test the hypothesis that the languages that grammatically associate the future and the present, foster future-oriented behavior. This prediction arises naturally when well-documented effects of language structure are merged with models of intertemporal choice. Empirically, I find that speakers of such languages: save more, retire with more wealth, smoke less, practice safer sex, and are less obese. This holds both across countries and within countries when comparing demographically similar native households. The evidence does not support the most obvious forms of common causation. I discuss implications for theories of intertemporal choice. (JEL D14, D83, E21, I12, J26, Z13)
Ad Revenue and Content Commercialization: Evidence from Blogs
Authors: Sun Monic , Zhu Feng
Published: April 2013

Many scholars argue that when incentivized by ad revenue, content providers are more likely to tailor their content to attract “eyeballs,” and as a result, popular content may be excessively supplied. We empirically test this prediction by taking advantage of the launch of an ad-revenue-sharing program initiated by a major Chinese portal site in September 2007. Participating bloggers allow the site to run ads on their blogs and receive 50% of the revenue generated by these ads. After analyzing 4.4 million blog posts, we find that, relative to nonparticipants, popular content increases by about 13 percentage points on participants' blogs after the program takes effect. About 50% of this increase can be attributed to topics shifting toward three domains: the stock market, salacious content, and celebrities. Meanwhile, relative to nonparticipants, participants' content quality increases after the program takes effect. We also find that the program effects are more pronounced for participants with moderately popular blogs, and seem to persist after participants enroll in the program.

This paper was accepted by Pradeep Chintagunta, marketing.
IFCAs: Stakeholder Perceptions of Roles, and Legal Impact
Authors: Lowther Jason , Rodwell Lynda D.
Published: April 2013

Inshore Fisheries and Conservation Authorities (IFCAs) established pursuant to the Marine and Coastal Access Act 2009 became operational in April 2011. IFCAs change the face of English fisheries' management: they retain local authority and industry representation, but a broader base of expertise in marine conservation and other marine stakeholder interests is provided for. Ultimately it is hoped that this will enable a true ecosystems approach to marine management to flourish in UK inshore waters. As a sector beset with considerable and competing interests, a broadening of the interest groups involved in regulatory decision making has been the preferred solution to promote such an approach and to move towards the ultimate goal of sustainable fisheries – using that term in its broadest sense. The aim is for IFCAs to overcome the more limited scope of the predecessor structures, the Sea Fisheries Committees, and to contribute to a contemporary, open and inclusive governance model. The researchers approached IFCA members and sought to establish how they envisaged their role in relation to a number of criteria as they embarked upon their management role. The article is intended to provide a snapshot of aspirations and initial perceptions of the IFCA as a more functional marine management model. A mix of views was discovered with an overall cautiously positive sense coming out of the respondents, who nonetheless were very aware of the challenges presented to improving inshore fisheries' sustainability in the context of regional, European Union driven policy imperatives and regulation.
Twenty Years of the Habitats Directive: A Case Study on Species Reintroduction, Protection and Management
Authors: Pillai A. , Heptinstall D.
Published: April 2013

Reintroduction of species is viewed as a conventional conservation tool across Europe. Yet, the reintroduction of a species into an area where it was formerly extinct in a country can involve considerable social and economic impacts. Effective national management strategies for European protected species must comply with the protection laid down in the Habitats or Birds Directives whilst, at the same time, addressing human socio-economic concerns. This case study on the Eurasian beaver (listed in Habitats Directive Annexes II and IV) examines the strict protection afforded to the beaver (Article 12) and the ways in which exceptions to that protection, or derogations (Article 16), may form part of national or regional species management strategies. Case studies from the Netherlands, Germany and Latvia illustrate conservation success but, at the same time, provide a cautionary tale about the management of a species with a well developed capacity for ecosystem engineering. What happens when a previously extinct or endangered species with the potential for impacts on human activities becomes abundant? While national law and policy makers must remain attentive to conservation concerns, ensuring the strict protection of the species, they must also be mindful of changes both in human political and socio-economic concerns and in the dynamic natural world. Twenty years on, is the protection afforded by the Habitats Directive sufficiently pragmatic and flexible to take account of changes in species conservation status and in the social, political and economic needs of Member States?
Reflections in the mirror of melancholia – on the narrative and male heritage in Napapiirin sankarit/Lapland Odyssey (Karukoski, 2010)
Authors: Soila Tytti
Published: April 2013

The article argues that Dome Karukoski’s Napapiirin sankarit/Lapland Odyssey (2010) inflects the journey narrative with irony and melancholy to reflect critically but comically on Finnish models of masculinity.
Matter and mutability: Presence and affect in other worlds
Authors: Grant Jane
Published: April 2013

The behaviour of matter and the affect of gravity, whether real or hypothetical, have often acted as a source for imaginative speculation. In science fiction many of these ideas have been discussed in relation to human consciousness. This article considers the literary work of Stanislaw
Lem and Italo Calvino, both of whom employ the metaphor of the mutability of matter to explore affect in other worlds. Extending the laws of physics by placing narratives in other, stranger worlds enables the writer to experiment with the interface or threshold between substance and thought.
Calvino moulds and structures the matter of the Universe to human form and thought, whereas in Solaris (Stanislaw Lem, 1970), Lem creates a cold and almost incomprehensible Universe outside of the limits of human intellect or consciousness.
Multiple-channel video installation as a precursor to transmedia-based art
Authors: Wu Ge , Gough Phillip , Wall Caitilin De Berigny (Onaclov)
Published: April 2013

The use of cross-media and transmedia-based art installation has generated new ways for the audience to appreciate, understand and experience art. Transmedia, the integration of multiple media forms to augment a single narrative, has not only been largely used in commercial films, but
has also been used by artists to communicate their message more effectively. In this article, we explore some remarkable multi-channel video installations and transmedia artworks to highlight how this technology has shaped new uses of technology as a new medium to express artistic concepts.
We discuss one artwork, an experimental collaboration between artists and scientists, entitled Reefs on the Edge, which communicates valuable information about climate change to a general audience.
Legal Aspects of Demand Side Management in Germany / Rechtliche Aspekte des Demand Side Management in Deutschland
Authors: Raabe Oliver , Ullmer Jan
Published: April 2013

Information and communication technologies (ICT) will play a key role in electricity distribution grids, especially with regard to grid monitoring and system services conducted through measures of demand side management (DSM). This paper outlines legal aspects to be taken into consideration when designing an ICT infrastructure to establish a market for demand side management and aims at pointing out the need for further legal research and for adaption of the existing legal and regulatory framework.
The effect of ageing on the axial capacity of piles in sand
Authors: Gavin Kenneth George , Igoe David John Paul , Kirwan Lisa
Published: April 2013

Open-ended steel pipe piles are used to support jacket structures in the offshore wind sector. These piles experience significant tensile axial loading in-service and the tensile shaft resistance thus governs their design. Although pile ageing (increased shaft resistance with time) has been noted by a number of workers and incorporation in design could lead to significant efficiencies, there is a dearth of high-quality field test data that measure its effects. This paper presents the results from an experimental investigation designed to examine the effect of ageing on the tension shaft resistance developed by open-ended piles in sand. As part of this investigation, four 340 mm diameter open-ended steel piles are driven 7 m into a dense sand deposit in Blessington, Ireland. Each pile is subjected to a series of static axial tension load tests at different time intervals after driving and the effects of ageing are assessed. The tension capacity of the piles is seen to increase by as much as 185% over a period of 7 months after driving.
Diltiazem-induced Transient Complete Atrioventricular Block in an Elderly Patient with Acute on Chronic Renal Failure
Authors: Brenes Jorge A , Cha Yong-Mei
Published: April 2013

Diltiazem is a calcium channel blocker commonly used in the treatment of various cardiovascular disorders such as hypertension, angina and supraventricular tachycardias. Metabolism occurs mainly in the liver, but a small percentage of unchanged drug and metabolites are excreted in the urine. Toxicity from this medication usually presents in the form of dysrrhytmias and heart block. Hence, we present a case of complete atrioventricular AV block in a patient receiving sustained- release diltiazem on a chronic basis. Risk factors such as advanced age and impaired renal function are dis-cussed.
The Skeletal Consequences of Growth Hormone Therapy in Dialyzed Children
Authors: Bacchetta Justine , Wesseling-Perry Katherine , Kuizon Beatriz , Pereira Renata C. , Gales Barbara , Wang He-jing , Elashoff Robert , Salusky Isidro B.
Published: April 2013

Background and objective

The effects of recombinant human growth hormone on renal osteodystrophy are unknown; thus, the effects of growth hormone (GH) on bone histomorphometry were assessed in pediatric patients with ESRD.

Design, setting, participants, & measurements

Thirty-three patients who underwent bone biopsy between July 1994 and May 1999 were randomly assigned to therapy with or without GH. Patients were stratified by bone formation rate; all patients with high bone turnover received intraperitoneal calcitriol. Serum biochemical values were obtained monthly, and bone biopsy was repeated after 8 months.

Results

Median patient age was 11.7 years (interquartile range [IQR], 7.6, 14.1 years); 45% of patients were male, and 52% were prepubertal. Median dialysis duration was 0.4 (IQR, 0.3, 0.8) year. Bone formation rate per bone surface increased from 15.0 (9.6, 21.8) to 154.6 (23.7, 174.3) μm2/μm3 per year (P=0.05) in patients with low bone turnover treated with GH, decreased from 103.3 (57.0, 173.4) to 60.3 (20.3, 13.7) μm2/μm3 per year in patients with high bone turnover receiving standard therapy (P=0.03), and was unchanged in the other two groups. Bone formation rates were higher with GH, irrespective of underlying bone histologic features (P=0.05). Parathyroid hormone did not differ between groups. GH therapy resulted in greater increases in height SD scores (estimated mean difference in change ± SD, 0.324±0.076; P<0.001), irrespective of underlying bone histologic features.

Conclusions

GH therapy improves height in pediatric dialysis patients, irrespective of underlying bone histologic features. Bone formation rates are higher in GH recipients, and GH therapy alters the relationship between circulating parathyroid hormone values and bone turnover.
Comparison of Health-Related Quality of Life, Work Status, and Health Care Utilization and Costs According to Hip and Knee Joint Disease Severity: A National Australian Study
Authors: Ackerman Ilana N. , Ademi Zanfina , Osborne Richard H. , Liew Danny
Published: April 2013

Background

No population-based studies have investigated how the impact of hip and knee joint disease may vary with increasing severity.

Objective

The purpose of this study was to evaluate health-related quality of life (HRQoL), work status, and health service utilization and costs according to severity of hip and knee joint disease.

Design

A national cross-sectional survey was conducted.

Methods

Five thousand individuals were randomly selected from the Australian electoral roll and invited to complete a questionnaire to screen for doctor-diagnosed hip arthritis, hip osteoarthritis (OA), knee arthritis, and knee OA. Severity was classified by means of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (range=0–100): <7=asymptomatic, 7–38=mild-moderate, and ≥39=severe. Health-related quality of life was evaluated by means of the Assessment of Quality of Life (AQoL) instrument (range=−0.04 to 1.00; scored worst-best). Self-reported data on work status and health service utilization were collected, with health care costs estimated with the use of government data.

Results

Data were available for 1,157 participants, with 237 (20%) reporting hip or knee joint disease. Of these, 16% (n=37) were classified as asymptomatic, 51% (n=120) as mild-moderate, and 27% (n=64) as severe. The severe group reported very low HRQoL (adjusted mean AQoL=0.43, 95% confidence interval [95% CI]=0.38–0.47) compared with the mild-moderate group (adjusted mean AQoL=0.72, 95% CI=0.69–0.75) and the asymptomatic group (adjusted mean AQoL=0.80, 95% CI=0.74–0.86). Compared with the asymptomatic group, the severe group was >3 times less likely to undertake paid work (adjusted odds ratio=0.28, 95% CI=0.09–0.88) and >4 times less likely to undertake unpaid work (adjusted odds ratio=0.24, 95% CI=0.10–0.62). Although physical therapy services were used infrequently, primary and specialist care utilization and costs were highest for the severe group.

Limitations

Other costs (including physical therapy consultations) were unavailable.

Conclusions

A clear pattern of worsening HRQoL, reduced work participation, and higher medical care utilization was seen with increasing severity of joint disease.