bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular Klotho Deficiency Potentiates the Development of Human Artery Calcification and Mediates Resistance to Fibroblast Growth Factor 23
Authors: Lim Kenneth , Lu Tzong-Shi , Molostvov Guerman , Lee Christina , Lam F.T. , Zehnder Daniel , Hsiao Li-Li
Published: April 2012

Background—

Klotho is known to function as a cofactor for the phosphatonin, fibroblast growth factor (FGF)-23 at the kidney. FGF-23 levels rise in chronic kidney disease (CKD) despite progression of accelerated vascular calcification. There are currently conflicting data on whether FGF-23 may exhibit direct vasculoprotective effects in CKD.

Methods and Results—

In this study, we describe for the first time endogenous Klotho expression in human arteries and human aortic smooth muscle cells. We show that CKD is a state of vascular Klotho deficiency promoted by chronic circulating stress factors, including proinflammatory, uremic, and disordered metabolic conditions. Mechanistic studies demonstrated that Klotho knockdown potentiated the development of accelerated calcification through a Runx2 and myocardin-serum response factor–dependent pathway. Klotho knockdown studies further revealed that vascular cells are a Klotho-dependent target tissue for FGF-23. FGF-23 mediated cellular activation of p-ERK, p-AKT, and cellular proliferative effects, which were abrogated following Klotho knockdown. We next showed that vascular Klotho deficiency driven by procalcific stressors could be restored by vitamin D receptor activators, in vitro and further confirmed using human arterial organ cultures from CKD patients, in vivo. Furthermore, restoration of suppressed Klotho expression by vitamin D receptor activators conferred human aortic smooth muscle cells responsive to FGF-23 signaling and unmasked potential anticalcific effects.

Conclusions—

Chronic metabolic stress factors found in CKD promote vascular Klotho deficiency. Mechanistic studies revealed a bifunctional role for local vascular Klotho, first, as an endogenous inhibitor of vascular calcification and, second, as a cofactor required for vascular FGF-23 signaling. Furthermore, vitamin D receptor activators can restore Klotho expression and unmask FGF-23 anticalcific effects.
Relationship Between Neurologic Deficit Severity and Final Functional Outcome Shifts and Strengthens During First Hours After Onset
Authors: Saver Jeffrey L. , Altman Hernan
Published: April 2012

Background and Purpose—

Early neurological deficit severity is the most important determinant of final functional outcome in acute ischemic stroke. However, deficit severity frequently changes during the first hours and days postonset.

Methods—

Analysis of control group patients enrolled in the 2 National Institute of Neurological Disorders and Stroke tissue-type plasminogen activator trials. Neurological deficit severity was measured serially using the National Institutes of Health Stroke Scale (NIHSS) at 1 to 3 hours postonset, 3 to 5 hours, 24 hours, 7 to 10 days, and 90 days. Final global disability outcome was assessed at 90 days using the modified Rankin Scale.

Results—

Among the 312 patients, median neurological deficit severity on the NIHSS improved throughout the 90-day observation period, from 15 (interquartile range, 9.5–20) at 1 to 3 hours, to 12 (interquartile range, 6–19) at 24 hours, to 7 (interquartile range, 2–19) at 90 days. Between 1-to-3-hours to 24 hours, more patients spontaneously improved than worsened: 39.1% versus 17.6% (
P
<0.001). NIHSS scores associated with individual final modified Rankin Scale global disability ranks shifted to lower values over time; eg, patients with a final modified Rankin Scale of 2 had the following median NIHSS scores: 12 at 1 to 3 hours, 10 at 3 to 5 hours, 9 at 24 hours, and 3 at 90 days. Correlation coefficients between NIHSS and the final modified Rankin Scale increased over time, from 0.51 at 1 to 3 hours, to 0.72 at 24 hours, to 0.87 at 90 days.

Conclusions—

During the first 24 hours after onset, spontaneous improvement occurs in 2 of 5 acute ischemic stroke patients. The NIHSS scores associated with individual global disability ranks decrease over time. Neurological deficit severity increasingly predicts final disability outcome, accounting for one quarter of the variance at 1 to 3 hours, one half at 24 hours, and three quarters at 90 days.
Benefits of Matching Accommodative Demands to Vergence Demands in a Binocular Head-Mounted Display: A Study on Stereo Fusion Times
Authors: So Richard H. Y. , Wong W. S. , Yip Romeo , Lam Andrew K. C. , Ting Patrick
Published: April 2012

Current head-mounted displays (HMDs) provide only a fixed lens focus. Viewers have to decouple their accommodation and vergence responses when viewing stereoscopic images presented on an HMD. This study investigates the time taken to fuse a pair of stereoscopic images displayed on an HMD when the accommodative demand is matched to the vergence demand. Four testing conditions exhausting the factorial combinations of accommodative demands (2.5 D and 0.5 D) and vergence demands (2.5 MA and 0.5 MA) were investigated. The results indicate that viewers take a significantly shorter amount of time to fuse a pair of stereoscopic images (i.e., fusion time) when the accommodative demand and the stereoscopic depth cues match. Further analysis suggests that an unnatural demand for the eyes to verge toward stereoscopic images whose stereo depth is farther than the accommodative demand is associated with significantly longer fusion time. This study evaluates the potential benefits of using a dynamically adjustable lens focus in future designs of HMDs.
Beyond the Looking Glass: Fooling the Brain with the Augmented Mirror Box
Authors: Regenbrecht Holger T. , Franz Elizabeth A. , McGregor Graham , Dixon Brian G. , Hoermann Simon
Published: April 2012

Video mediated and augmented reality technologies can challenge our sense of what we perceive and believe to be real. Applied appropriately, the technology presents new opportunities for understanding and treating a range of human functional impairments as well as studying the underling psychological bases of these phenomena. This paper describes our augmented mirror box (AMB) technology which builds on the potential of optical mirror boxes by adding functions that can be applied in therapeutic and scientific settings. Here we test hypotheses about limb presence and perception, belief, and pain using laboratory studies to demonstrate proof of concept. The results of these studies provide evidence that the AMB can be used to manipulate beliefs and perceptions and alter the reported experience of pain. We conclude that the system has potential for use in experimental and in clinical settings.
Exercise, Diet, and Stress Management as Mediators Between Functional Disability and Health-Related Quality of Life in Multiple Sclerosis
Authors: Sung Connie , Chiu Chung-Yi , Lee Eun-Jeong , Bezyak Jill , Chan Fong , Muller Veronica
Published: April 2012

The main objective of this study was to examine the mediational and moderational effect of exercise, diet, and stress management on the relationship between functional disability and health-related quality of life. Quantitative descriptive research design using multiple regression and correlation techniques was used. Participants were 215 individuals with multiple sclerosis (MS). Outcome measure used was health-related quality of life as measured by the Medical Outcomes Study (MOS) Short-Form Health Survey (SF-12v2). Functional disability and health-promoting behaviors including exercise, diet, and stress management were found to be associated with health-related quality of life. Exercise and stress management (but not diet) were partial mediators between functional disability and health-related quality of life. Exercise was found to be a moderator between functional disability and health-related quality of life. Exercise had a stronger effect on health-related quality of life for individuals with lower functional disability than people with higher functional disability. Health-promoting behaviors are important for health-related quality of life, and health-related quality of life in turn is related to better employment outcomes. Health-promoting behaviors can also mediate the relationship between functional disability and health-related quality of life. Rehabilitation counselors should consider including health promotion interventions in vocational rehabilitation services for individuals with MS.
Predictive Ability of Pender’s Health Promotion Model for Physical Activity and Exercise in People With Spinal Cord Injuries
Authors: Keegan John P. , Chan Fong , Ditchman Nicole , Chiu Chung-Yi
Published: April 2012

The main objective of this study was to validate Pender’s Health Promotion Model (HPM) as a motivational model for exercise/physical activity self-management for people with spinal cord injuries (SCIs). Quantitative descriptive research design using hierarchical regression analysis (HRA) was used. A total of 126 individuals with SCI were recruited through the National Spinal Cord Injury Association, other SCI support groups, and professors in rehabilitation counseling across the United States. Outcome measures used were the International Physical Activity Questionnaire and the Physical Activity Stages of Change Instrument. The HRA results indicated that preinjury physical activity/exercise level, severity of SCI, and commitment to a plan for exercise and physical activity were predictive of postinjury exercise and physical activity level. In addition, friend/family support, perceived self-efficacy, and perceived benefits were the strongest predictors of commitment to a plan of action for exercise and physical activity. The research findings support the applicability of Pender’s HPM as a motivational model for exercise/physical activity for people with SCI. The information can be used to design health promotion behavioral interventions for people with SCI living in the community.
Altered interictal saccadic reaction time in migraine: a cross-sectional study
Authors: Chandna Arjun , Chandrasekharan Deepak P , Ramesh Aravind V , Carpenter RHS
Published: April 2012

Aims: The underlying mechanisms of migraine remain poorly understood, partly because we lack objective methods for quantitative analysis of neurological function. To address this issue, we measured interictal saccadic latency in migraineurs and controls.

Methods: In a cross-sectional study, we compared interictal saccadic latency distributions of 12,800 saccades in 32 migraineurs with 32 age- and sex-matched controls.

Results: The variability of migraineurs’ reaction time distributions was significantly smaller (σ = 1.01 vs. 1.13; p < 0.05) compared with controls. In addition, a smaller proportion of migraineurs generated ‘early’ saccades (31% vs. 56%: p < 0.05). Sensitivity/specificity analysis demonstrated the potential benefit of this technique to diagnostic discrimination.

Conclusions: The migraineur’s brain behaves significantly differently from that of a control during the interictal period. By analysing whole distributions, rather than just means, data can be related directly to current neurophysiological models: specifically, the observed decrease in variability suggests a functional deficit in the noradrenergic systems influencing the cerebral cortex. From a clinical perspective, this novel method of characterising neurological function in migraine is more rapid, practicable, inexpensive, objective and quantitative than previous methods such as evoked potentials and transcranial magnetic stimulation, and has the potential both to improve current diagnostic discrimination and to help guide future research into the underlying neural mechanisms.
Synthetic Resorbable Scaffolds for the Treatment of Isolated Patellofemoral Cartilage Defects in Young Patients
Authors: Joshi Nayana , Reverte-Vinaixa Mercè , Díaz-Ferreiro Eugenio Wenceslao , Domínguez-Oronoz Rosa
Published: April 2012

Background: Surgical management of patellar cartilage defects remains controversial. The ideal technique to regenerate hyaline cartilage is not yet defined. However, a synthetic resorbable osteochondral scaffold plug (TruFit CB) seems to offer a treatment option with good results at short-term follow-up, at least in the condylar setting.

Hypothesis: A synthetic implant provides a simple and efficacious means of treating the cartilage defects of the patellofemoral joint in young patients.

Study Design: Case series; Level of evidence, 4.

Methods: A study was designed to evaluate prospectively short- and medium-term results in patients with osteochondral patellar defects treated with synthetic reabsorbable scaffolds. Patient outcome scores (Short Form 36 [SF-36] and Knee injury and Osteoarthritis Outcome Score [KOOS]), demographics, prior surgeries, and data from a physical examination were collected at baseline (before implantation) and at 6, 12, and 24 months after surgery. Defect characteristics were collected during implantation. Diagnosis and monitoring were performed by magnetic resonance imaging.

Results: Ten patients with a mean age of 33.3 years (range, 16-49 years) were evaluated prospectively at 24 months’ follow-up. The number of plugs used for each patient ranged from 1 to 4. At 1-year follow-up, the results were satisfactory in 8 of 10 patients, and poor in 2, according to clinical assessment (KOOS, visual analog scale, and SF-36). At 18 months of follow-up, all patients except one complained of pain and knee swelling. Reoperation rate for implant failure at final follow-up was 70%. Magnetic resonance imaging at final follow-up showed a cylindrical cavity of fibrous tissue instead of subchondral bone restoration.

Conclusion: A synthetic implant can improve symptoms and joint function, especially for small lesions, only for a short period of time. However, 2 years of monitoring has shown its failure in restoring the subchondral bone despite the formation of predominant hyaline cartilage from synthetic resorbable scaffolds. Under current conditions and according to our experience, we do not recommend TruFit synthetic implants for osteochondral patellar defects in active patients.
Estimating the impact of the home appliances trade-in policy on WEEE management in China
Authors: Zhu Shuguang , He Wenzhi , Li Guangming , Zhuang Xuning , Huang Juwen , Liang Honggen , Han Yuebin
Published: April 2012

The ever-increasing amount of waste electric and electronic equipment (WEEE) has become a global problem. In view of the deleterious effects of WEEE on the environment and the valuable materials that can be reused in them, many countries have focused their attention on the management of WEEE and the recovery technologies of WEEE. The Chinese government has been active in creating a legislative and institutional framework to realize WEEE recycling. In June 2009, Chinese government launched home appliances and electronics trade-in implementation solution. This paper elaborates the home appliances trade-in policy and its significant impact on the WEEE management. The trade-in policy is not only conducive to expanding the consumption demand and promoting the balance of domestic and overseas demand, but also favorable to improving the energy efficiency and reducing environmental pollution. Under this policy, China has successfully established an effective WEEE recycling system, using the financial means and network design. Experiences gained from the trade-in policy have shown that management systems of WEEE need to be designed and implemented in a multi-stakeholder dialogue.
Cross-Cultural Evaluation of Item Wording Effects on an Attitudinal Scale
Authors: Yang Yanyun , Chen Yi-Hsin , Lo Wen-Juo , Turner Jeannine E.
Published: April 2012

Previous studies have shown that method effects associated with item wording produce artifactual factors and threaten scale validity. This study examines item wording effects on a scale of attitudes toward learning mathematics for Taiwanese and U.S. samples. Analyses from a series of CFA (confirmatory factor analysis) models support the presence of method effects for both samples. In addition, findings show that U.S. students tended to report higher means on not only the substantive factors but also the method factor, compared to Taiwanese students. The effect sizes on the mean differences are medium to large.
Confronting Urban Displacement
Authors: Hooper Michael , Ortolano Leonard
Published: April 2012

This article investigates whether urban social movement participation influences post-eviction resettlement success. Pre- and post-eviction interviews were conducted with sixty-four slum dwellers from Dar es Salaam, Tanzania, including members of the Tanzania Federation of the Urban Poor (TFUP). The majority of interviewees reported improved post-eviction housing but adverse employment impacts. TFUP membership was negatively associated with employment outcomes, particularly for property owners. Expecting TFUP to secure housing for them, members delayed finding accommodation. This led to resettlement farther from their former homes and negatively affected employment. Women were especially vulnerable following eviction, with their post-eviction pay falling because of the nature and location of their pre-eviction work.
DIY Activists
Authors: Hemphill David , Leskowitz Shari
Published: April 2012

This study explored innovative alternative processes of living, learning, and knowledge sharing of a loosely knit community of anarchist, anticapitalist “Do-It-Yourself” (DIY) activists. Generated through participant observation and interviews, findings reinforced adult education theories—that adults can diagnose their own learning needs and carry out appropriate learning activities. Participants also critiqued prevailing educational practices, suggesting alternatives such as autonomy, choice, critical thinking, cooperative learning, and deconstructing hierarchy. In particularly promising findings, the DIY activists described radical alternative channels for knowledge sharing: piracy, skillshares, Internet/open source media, the streets, and zines. Employing older and newer technologies, and legal and illegal methods, these modalities embodied in powerful ways the participants’ radical political commitments. The DIY activists also gave cause to reflect on the nature of cultural dialogism, community, and communities of practice as they struggled with the nature of their own identities, ideologies, and desires to broaden outreach beyond their immediate community.
Hydroxyapatite nanorods: Soft-template synthesis, characterization and preliminary in vitro tests
Authors: Nguyen Nga Kim , Leoni Matteo , Maniglio Devid , Migliaresi Claudio
Published: April 2012

Synthetic hydroxyapatite nanorods are excellent candidates for bone tissue engineering applications. In this study, hydroxyapatite nanorods resembling bone minerals were produced by using soft-template method with cetyltrimethylammonium bromide. Composite hydroxyapatite/poly(D, L)lactic acid films were prepared to evaluate the prepared hydroxyapatite nanorods in terms of cell affinity. Preliminary in vitro experiments showed that aspect ratio and film surface roughness play a vital role in controlling adhesion and proliferation of human osteoblast cell line MG 63. The hydroxyapatite nanorods with aspect ratios in the range of 5.94–7 were found to possess distinctive properties, with the corresponding hydroxyapatite/poly(D, L)lactic acid films promoting cellular confluence and a fast formation of collagen fibers as early as after 7 days of culture.
Biofunctionalisation of polymeric scaffolds for neural tissue engineering
Authors: Wang TY , Forsythe JS , Parish CL , Nisbet DR
Published: April 2012

Patients who experience injury to the central or peripheral nervous systems invariably suffer from a range of dysfunctions due to the limited ability for repair and reconstruction of damaged neural tissue. Whilst some treatment strategies can provide symptomatic improvement of motor and cognitive function, they fail to repair the injured circuits and rarely offer long-term disease modification. To this end, the biological molecules, used in combination with neural tissue engineering scaffolds, may provide feasible means to repair damaged neural pathways. This review will focus on three promising classes of neural tissue engineering scaffolds, namely hydrogels, electrospun nanofibres and self-assembling peptides. Additionally, the importance and methods for presenting biologically relevant molecules such as, neurotrophins, extracellular matrix proteins and protein-derived sequences that promote neuronal survival, proliferation and neurite outgrowth into the lesion will be discussed.
Enhanced visualization of biodegradable polymeric vascular scaffolds by incorporation of gold, silver and magnetite nanoparticles
Authors: Luderer Frank , Begerow Ivonne , Schmidt Wolfram , Martin Heiner , Grabow Niels , Bünger Carsten M , Schareck Wolfgang , Schmitz Klaus-Peter , Sternberg Katrin
Published: April 2012

Due to improved tissue regeneration and the enabling of post-operative minimally invasive interventions in the same vessel segment, biodegradable polymeric scaffolds represent a competitive approach to permanent metallic stents in vascular applications. Despite these advantages some challenges, such as the improvement of the scaffold mechanics and enhancement of scaffold visibility during the implantation procedure, are persisting. Therefore, the scope of our studies was to investigate the potential of gold, silver and magnetite nanoparticles incorporated in a polymeric blend of poly(L-lactide)/poly(4-hydroxybutyrate) for image enhancement in X-ray, magnetic resonance or near-infrared imaging. Their impact on mechanical properties of such modified scaffold materials was also evaluated.
Dielectric properties of carbon-nanotube/amino-functionalized poly(arylene ether ketone) composites
Authors: Zhang Yunhe , Liu Xiao , Zhu Ming , Rong Changru , Wang Guibin
Published: April 2012

Novel a-MWNTs/NH2PAEKK nanocomposite, with a high dielectric constant, low dielectric loss and high breakdown field, were prepared to use a solution blending technique. The uniform dispersion of a-MWNTs in the NH2PAEKK matrix was realized. The dielectric constant of percolating nanocomposites (the a-MWNTs volume fraction of 0.09) was as high as 60 at 103 Hz, it was about 20 times larger than the dielectric constant of NH2PAEKK, and the breakdown field was near 41.4 MV m−1. For [Formula: see text], the dielectric loss of a-MWNTs/NH2PAEKK nanocomposite was always less than 1. The nanocomposites had tensile strength of 69.2 MPa and tensile modulus of 3.0 GPa.
Polyimides containing cycloaliphatic segments for low dielectric material
Authors: Popovici Dumitru , Hulubei Camelia , Cozan Vasile , Lisa Gabriela , Bruma Maria
Published: April 2012

New polyimides have been synthesized by the reaction of 3,3′,4,4′-benzophenone tetracarboxylic dianhydride (BTDA) or/and 5-[2,5-(dioxotetrahydrofuryl)]-3-methyl-3-cyclohexene-1,2-dicarboxylic anhydride (DOCDA) with 4,4′-methylene dianiline (DDM). Polycondensation reactions were carried out in N, N-dimethylformamide solution and the resulting polyimides gave flexible free-standing films. The introduction of alicyclic moieties in the polyimide backbone improved the solubility of the resulting polymers and facilitated their processing while maintaining a high thermal stability. The dielectric constant values (measured at 106 Hz at room temperature), were found in the range of 3.14–2.83 and decreased with increasing of the alicyclic units content.
Sample size and power calculations for medical studies by simulation when closed form expressions are not available
Authors: Landau Sabine , Stahl Daniel
Published: April 2012

This paper shows how Monte Carlo simulation can be used for sample size, power or precision calculations when planning medical research studies. Standard study designs can lead to the use of analysis methods for which power formulae do not exist. This may be because complex modelling techniques with optimal statistical properties are used but power formulae have not yet been derived or because analysis models are employed that divert from the population model due to lack of availability of more appropriate analysis tools. Our presentation concentrates on the conceptual steps involved in carrying out power or precision calculations by simulation. We demonstrate these steps in three examples concerned with (i) drop out in longitudinal studies, (ii) measurement error in observational studies and (iii) causal effect estimation in randomised controlled trials with non-compliance. We conclude that the Monte Carlo simulation approach is an important general tool in the methodological arsenal for assessing power and precision.
Sequential Priming Measures of Implicit Social Cognition
Authors: Cameron C. Daryl , Brown-Iannuzzi Jazmin L. , Payne B. Keith
Published: April 2012

In a comprehensive meta-analysis of 167 studies, the authors found that sequential priming tasks were significantly associated with behavioral measures ( r = .28) and with explicit attitude measures ( r = .20). Priming tasks continued to predict behavior after controlling for the effects of explicit attitudes. These results generalized across a variety of study domains and methodological variations. Within-study moderator analyses revealed that priming tasks have good specificity, only predicting behavior and explicit measures under theoretically expected conditions. Together, these results indicate that sequential priming—one of the earliest methods of investigating implicit social cognition—continues to be a valid tool for the psychological scientist.
Perceived Consumer Navigational Control in Travel Websites
Authors: Manganari Emmanouela E. , Siomkos George J. , Vrechopoulos Adam P.
Published: April 2012

The purpose of this study is to provide a better understanding of the perceived online control effects on consumers’ behavior in the travel industry. The article uses a laboratory experiment to investigate how perceived consumer navigational control affects consumer behavior. An online travel store of a fictitious company was developed as the experimental stimulus. The findings imply that perceived navigational control affects consumers’ levels of pleasure and trust during the online navigation. In turn, pleasure and trust affect consumers’ attitude toward the online store and satisfaction. Surprisingly, consumers’ attitude is not directly affected by their perception of the level of navigational control over the travel website. Finally, gender moderates the relationship between the perceived navigational control and consumers’ attitude toward the travel website. Managerial implications regarding the development of travel websites and research opportunities are discussed.
A perspective on the future public health: an integrative and ecological framework
Authors: Hanlon Phil , Carlisle Sandra , Hannah Margaret , Lyon Andrew , Reilly David
Published: April 2012

Modernity has brought health and social benefits to many societies, not least through the insights of science and technology. Yet, modernity has also been associated with a number of cultural characteristics, such as materialism, individualism, consumerism and an addiction to continuing economic growth, that seem potentially harmful to health and well-being and inimical to social equity. There is an emerging body of evidence that suggests that, in the affluent world, some of our most intractable contemporary health problems are, in fact, the product of modernity. This suggests that the tools of modernity (its science and its technology) are ill suited to finding solutions. This poses a problem for public health, as this discipline is itself a product of modernity and thus appears ill equipped to deal with the conditions and challenges of a rapidly changing and unstable world, one where the very sustainability of human society is now in question. This paper argues that a new paradigm for the future public health is needed. It presents an integrative, ecological framework as a starting point from which public health might grasp the opportunities for change inherent in the ‘modern’ threats we face. It suggests a number of features that will need to underpin such a paradigm shift in thinking and practice. However, as this paper is written from the perspective of an affluent, developed society (albeit from a perspective that is explicitly critical of the goals, trends and values that seem to characterise such societies), other voices from other places need to be heard. We hope that others will want to engage with our arguments and suggestions, whether to challenge and refute these, or to further their development.
Identification, immunomodulatory activity, and immunogenicity of the major helper T-cell epitope on the K blood group antigen
Authors: Stephen Jillian , Cairns Lindsay S. , Pickford Wendy J. , Vickers Mark A. , Urbaniak Stanislaw J. , Barker Robert N.
Published: April 2012

The K blood group remains an important target in hemolytic disease of the newborn (HDN), with no immune prophylaxis available. The aim was to characterize the Th response to K as a key step in designing specific immunotherapy and understanding the immunogenicity of the Ag. PBMCs from K-negative women who had anti-K Abs after incompatible pregnancy, and PBMCs from unimmunized controls, were screened for proliferative responses to peptide panels spanning the K or k single amino acid polymorphism. A dominant K peptide with the polymorphism at the C terminus elicited proliferation in 90% of alloimmunized women, and it was confirmed that responding cells expressed helper CD3+CD4+ and “memory” CD45RO+ phenotypes, and were MHC class II restricted. A relatively high prevalence of background peptide responses independent of alloimmunization may contribute to K immunogenicity. First, cross-reactive environmental Ag(s) pre-prime Kell-reactive Th cells, and, second, the K substitution disrupts an N-glycosylation motif, allowing the exposed amino acid chain to stimulate a Th repertoire that is unconstrained by self-tolerance in K-negative individuals. The dominant K peptide was effective in inducing linked suppression in HLA-transgenic mice and can now be taken forward for immunotherapy to prevent HDN because of anti-K responses.
Transcriptome-wide identification and characterization of miRNAs from Pinus densata
Authors: Wan Li-Chuan , Zhang Haiyan , Lu Shanfa , Zhang Liang , Qiu Zongbo , Zhao Yuanyuan , Zeng Qing-Yin , Lin Jinxing
Published: April 2012

Background

MicroRNAs (miRNAs) play key roles in diverse developmental processes, nutrient homeostasis and responses to biotic and abiotic stresses. The biogenesis and regulatory functions of miRNAs have been intensively studied in model angiosperms, such as Arabidopsis thaliana, Oryza sativa and Populus trichocarpa. However, global identification of Pinus densata miRNAs has not been reported in previous research.

Results

Here, we report the identification of 34 conserved miRNAs belonging to 25 miRNA families from a P. densata mRNA transcriptome database using local BLAST and MIREAP programs. The primary and/or precursor sequences of 29 miRNAs were further confirmed by RT-PCR amplification and subsequent sequencing. The average value of the minimal folding free energy indexes of the 34 miRNA precursors was 0.92. Nineteen (58%) mature miRNAs began with a 5' terminal uridine residue. Analysis of miRNA precursors showed that 19 mature miRNAs were novel members of 14 conserved miRNA families, of which 17 miRNAs were further validated by subcloning and sequencing. Using real-time quantitative RT-PCR, we found that the expression levels of 7 miRNAs were more than 2-fold higher in needles than in stems. In addition, 72 P. densata mRNAs were predicted to be targets of 25 miRNA families. Four target genes, including a nodal modulator 1-like protein gene, two GRAS family transcription factor protein genes and one histone deacetylase gene, were experimentally verified to be the targets of 3 P. densata miRNAs, pde-miR162a, pde-miR171a and pde-miR482a, respectively.

Conclusions

This study led to the discovery of 34 conserved miRNAs comprising 25 miRNA families from Pinus densata. These results lay a solid foundation for further studying the regulative roles of miRNAs in the development, growth and responses to environmental stresses in P. densata.
Significance of EpCAM and TROP2 expression in non-small cell lung cancer
Authors: Pak Min Gyoung , Shin Dong Hoon , Lee Chang Hun , Lee Min Ki
Published: April 2012

Background

The tumor-associated calcium signal transducer (TACSTD) genes, originally designated epithelial cell adhesion molecule (EpCAM) and TROP2, represent true oncogenes. Little is known about EpCAM and TROP2 gene expression in non-small cell lung carcinoma (NSCLC). This study evaluated EpCAM and TROP2 protein expression and clinicopathologic significance in cases of NSCLC.

Methods

Tissue microarray blocks acquired from 164 cases of NSCLC, including 100 cases of adenocarcinoma (AdC) and 64 of squamous cell carcinoma (SCC), were examined by immunohistochemical staining for EpCAM, and TROP2. The results were correlated with clinicopathologic data.

Results

EpCAM and TROP2 were significantly overexpressed in SCC than in AdC (P < 0.01). In AdC, EpCAM overexpression was closely related to sex, histologic grade, pathologic T stage, pathologic N stage, and TNM stage, and TROP2 overexpression was only related to histologic grade (P < 0.05, respectively). In SCC, correlations were evident between EpCAM overexpression and TNM stage (P = 0.01), and between TROP2 overexpression and pathologic T stage (P = 0.02). EpCAM overexpression showed no significance with overall survival in AdC and SCC patients. However, TROP2 overexpression in AdC had a positive influence on overall survival (P = 0.02) and disease-free survival (P = 0.03). In particular, AdC patients with stage II or III showed better overall survival (P = 0.05) and disease-free survival (P = 0.04).

Conclusions

While EpCAM and TROP2 show weak and non-complete membranous staining in normal bronchial epithelium and pneumocyte, their complete membranous expression in carcinoma suggests their role in carcinogenesis. EpCAM and TROP2 were more frequently overexpressed in SCC. EpCAM overexpression had no prognostic value in this study, but TROP2 overexpression showed better survival in AdC patients and might be a better prognostic marker in advanced stage AdC.
Accumulation of starch in Zn-deficient rice
Authors: Suzuki Motofumi , Bashir Khurram , Inoue Haruhiko , Takahashi Michiko , Nakanishi Hiromi , Nishizawa Naoko K
Published: April 2012

Zinc (Zn) is an essential micronutrient for living organisms, and understanding the molecular mechanisms of Zn deficiency may help to develop strategies to mitigate this problem. Microarray analysis of Zn deficient rice revealed the up-regulation of several genes involved in Zn transport. Moreover many genes involved in starch synthesis/transport were up-regulated by Zn deficiency in rice roots and shoots. Furthermore, starch granules were detected mainly in the cortical cells of these tissues. The gene encoding inactive RNase was much more highly transcribed than those encoding active RNases. Although the level of RNA degradation in a crude extract of Zn-deficient shoots was higher than that of Zn-sufficient shoots, addition of Zn significantly reduced the level of degradation. These results indicate that RNA degradation could be regulated by the amount of Zn in the cell, and that the tolerance of rice plants to low levels of Zn is promoted by the accumulation of starch and inactive RNase.
FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation ofEtv5andBcl6bthrough MAP2K1 activation
Authors: Ishii Kei , Kanatsu-Shinohara Mito , Toyokuni Shinya , Shinohara Takashi
Published: April 2012

Fibroblast growth factor 2 (FGF2) and glial cell line-derived neurotrophic factor (GDNF) are required to recapitulate spermatogonial stem cell (SSC) self-renewal in vitro. Although studies have revealed the role of the GDNF signaling pathway in SSCs, little is known about how FGF2 is involved. In the present study, we assessed the role of the FGF2 signaling pathway using a mouse germline stem (GS) cell culture system that allows in vitro expansion of SSCs. Adding GDNF or FGF2 induced phosphorylation of MAPK1/3, and adding the MAP2K1 inhibitor PD0325091 reduced GS cell proliferation and MAPK1/3 phosphorylation. Moreover, GS cells transfected with an activated form of Map2k1 not only upregulated Etv5 and Bcl6b gene expression, but also proliferated in an FGF2-independent manner, suggesting that they act downstream of MAP2K1 signaling to drive SSC self-renewal. Although GS cells transfected with Map2k1, Etv5 or Bcl6b showed normal spermatogonial markers, transplanting GS cells expressing Bcl6b into infertile mouse testes resulted in the formation of a germ cell tumor, suggesting that excessive self-renewal signals causes tumorigenic conversion. These results show that FGF2 depends on MAP2K1 signaling to drive SSC self-renewal via upregulation of the Etv5 and Bcl6b genes.
Locally expressed IGF-1 propeptide improves function in induced dilated cardiomyopathy through blockade of myocardial fibrosis and SRF-dependent CTGF induction
Authors: Touvron Melissa , Escoubet Brigitte , Mericskay Mathias , Angelini Aude , Lamotte Luciane , Santini Maria Paola , Rosenthal Nadia , Daegelen Dominique , Tuil David , Decaux Jean-François
Published: April 2012

Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCM), which leads to cardiac dysfunction and heart failure (HF). Connective tissue growth factor (CTGF), a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF-1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized. We investigated the consequences of expressing a cardiac-specific transgene encoding locally acting IGF-1 propeptide (mIGF-1) on disease progression in a mouse model of DCM. This mouse model of cardiac-specific and inducible SRF gene disruption mimics some forms of human DCM. Cardiac-specific mIGF-1 expression substantially extended the lifespan of SRF mutant mice, markedly improved cardiac functions and delayed both DCM and HF. These protective effects were accompanied by an overall improvement in cardiomyocyte architecture and a massive reduction of myocardial fibrosis with a concomitant amelioration of inflammation. At least part of the beneficial effects of mIGF-1 transgene expression were due to counteracting the strong SRF-dependent increase in CTGF expression within cardiomyocytes, resulting in the blockade of fibroblast proliferation and related myocardial fibrosis. These findings demonstrate that SRF plays a key role in the modulation of cardiac fibrosis through repression of cardiomyocyte CTGF expression in a paracrine fashion. They also explain how impaired SRF function observed in human heart failure contributes to promote fibrosis and adverse cardiac remodeling. Locally acting mIGF-1 efficiently protects the myocardium from these adverse processes, and may thus represent a cardiac therapeutic avenue to counter DCM.
A high pressure liquid chromatography method for separation of prolactin forms
Authors: Bell Damon A , Hoad Kirsten , Leong Lillian , Bakar Juwaini Abu , Sheehan Paul , Vasikaran Samuel D
Published: April 2012

Background

Prolactin has multiple forms and macroprolactin, which is thought not to be bioavailable, can cause a raised serum prolactin concentration. Gel filtration chromatography (GFC) is currently the gold standard method for separating macroprolactin, but is labour-intensive. Polyethylene glycol (PEG) precipitation is suitable for routine use but may not always be accurate. We developed a high pressure liquid chromatography (HPLC) assay for macroprolactin measurement.

Methods

Chromatography was carried out using an Agilent Zorbax GF-250 (9.4 × 250 mm, 4 μm) size exclusion column and 50 mmol/L Tris buffer with 0.15 mmol/L NaCl at pH 7.2 as mobile phase, with a flow rate of 1 mL/min. Serum or plasma was diluted 1:1 with mobile phase and filtered and 100 μL injected. Fractions of 155 μL were collected for prolactin measurement and elution profile plotted. The area under the curve of each prolactin peak was calculated to quantify each prolactin form, and compared with GFC.

Results

Clear separation of monomeric-, big- and macroprolactin forms was achieved. Quantification was comparable to GFC and precision was acceptable. Total time from injection to collection of the final fraction was 16 min.

Conclusions

We have developed an HPLC method for quantification of macroprolactin, which is rapid and easy to perform and therefore can be used for routine measurement.
Development of an automatic laboratory computer flagging system to identify urine albumin samples potentially affected by antigen excess (‘hooking’)
Authors: Pullan N J , Hitch T
Published: April 2012

Background

Immunoassays for urinary albumin are often subject to the problem of antigen excess (the ‘hook’ effect) at high albumin concentrations. We developed an automated protocol to identify such samples based on urinary albumin to creatinine ratio (uACR) and urinary total protein (uTP) results.

Methods

An automated flagging system was designed and written into the laboratory computer system to alert technical staff to samples potentially affected by the ‘hook effect’. This flag was activated when there was a combination of an uTP of ≥2400 mg/L and an uACR of <30 mg/mmol.

Results

The potential rate of false-negative uACR results was approximately 0.17% in samples from primary care and diabetic clinic sources.

Conclusions

Samples with falsely low uACR results were identified, allowing the vast majority of results to be authorized without intervention. The protocol prevented the reporting of false-negative uACR results which might impact on the management of patients.
Tractable Open Loop Policies for Joint Overbooking and Capacity Control Over a Single Flight Leg with Multiple Fare Classes
Authors: Topaloglu Huseyin , Birbil S. Ilker , Frenk J. B. G. , Noyan Nilay
Published: April 2012

In this paper, we consider the joint overbooking and capacity control problem over a single flight leg with multiple fare classes. The objective is to maximize the net expected revenue, which is given by the difference between the expected revenue from the accepted requests and the expected penalty cost from the denied reservations. We study a class of open loop policies that accept the requests for each fare class with a fixed acceptance probability. In this case, the challenge becomes finding a set of acceptance probabilities that maximize the net expected revenue. We derive a simple expression that can be used to compute the optimal acceptance probabilities, despite the problem of finding the optimal acceptance probabilities being a high dimensional optimization problem. We show that the optimal acceptance probabilities randomize the acceptance decisions for at most one fare class, indicating that the randomized nature of our open loop policies is not a huge practical concern. We bound the performance loss of our open loop policies when compared with the optimal policy. Computational experiments demonstrate that open loop policies perform remarkably well, providing net expected revenues within two percent of the optimal on average.
Synthetic Population Generation Without a Sample
Authors: Barthelemy Johan , Toint Philippe L.
Published: April 2012

The advent of microsimulation in the transportation sector has created the need for extensive disaggregated data concerning the population whose behavior is modeled. Because of the cost of collecting this data and the existing privacy regulations, this need is often met by the creation of a synthetic population on the basis of aggregate data. Although several techniques for generating such a population are known, they suffer from a number of limitations. The first is the need for a sample of the population for which fully disaggregated data must be collected, although such samples may not exist or may not be financially feasible. The second limiting assumption is that the aggregate data used must be consistent, a situation that is most unusual because these data often come from different sources and are collected, possibly at different moments, using different protocols. The paper presents a new synthetic population generator in the class of the Synthetic Reconstruction methods, whose objective is to obviate these limitations. It proceeds in three main successive steps: generation of individuals, generation of household type's joint distributions, and generation of households by gathering individuals. The main idea in these generation steps is to use data at the most disaggregated level possible to define joint distributions, from which individuals and households are randomly drawn. The method also makes explicit use of both continuous and discrete optimization and uses the χ2 metric to estimate distances between estimated and generated distributions. The new generator is applied for constructing a synthetic population of approximately 10,000,000 individuals and 4,350,000 households localized in the 589 municipalities of Belgium. The statistical quality of the generated population is discussed using criteria extracted from the literature, and it is shown that the new population generator produces excellent results.
Queueing Models for Trajectory-Based Aircraft Operations
Authors: Nikoleris Tasos , Hansen Mark
Published: April 2012

This paper develops a queueing model for aircraft arrivals at a single server under trajectory-based flight operations, which are expected to prevail in the Next Generation Air Transportation System. Aircraft are assigned scheduled times of arrival at a server, which they meet with some normally distributed stochastic error. The Clark approximation method is employed to estimate expected queueing delays, and it is shown, through comparison with simulation, that the method yields very accurate estimates. Exact results are derived for a special case in which aircraft are metered into a capacity-constrained area with constant excess time separation between them. This allows analysis of the tradeoff between the “stochastic delay” that results from imperfect adherence to metered times of arrival and the additional “deterministic delay” from metering at a headway above the minimum required.
Opening Ground Handling Markets to Competition: Effects on Welfare
Authors: Barbot Cristina
Published: April 2012

This paper addresses the case of complementary services with vertical relations, using the example of airport handling activities. Our model investigates the effects on welfare and competitiveness of four handling market situations and confirms Cournot's result on competition in complementary goods, unless there are efficiency gaps. We find that horizontal competition in handling services leads to market foreclosure even if an airline performs self-handling. We add some remarks on regulatory issues, showing that regulation may be pointless or even anticompetitive. We show that Council Directive 96/67/EC, although intending to increase competition, may be anticompetitive and decrease consumer surplus. We develop an empirical study in which some of our theoretical results are confirmed.
Curbing the Dangers of High-Frequency Trading
Authors: Clements Matthew T.
Published: April 2012

High-frequency trading, as distinct from other forms of algorithmic trading, is of little or no social value. Implementation of resting rules would retain the benefits of algorithmic trading while eliminating the potential harm of high-frequency trading.