bluuebunny/crossref_metadata_2025 huggingface dataset:
Paleoclimate Data–Model Comparison and the Role of Climate Forcings over the Past 1500 Years*
Authors: Phipps Steven J. , McGregor Helen V. , Gergis Joëlle , Gallant Ailie J. E. , Neukom Raphael , Stevenson Samantha , Ackerley Duncan , Brown Josephine R. , Fischer Matt J. , van Ommen Tas D.
Published: March 2013

The past 1500 years provide a valuable opportunity to study the response of the climate system to external forcings. However, the integration of paleoclimate proxies with climate modeling is critical to improving the understanding of climate dynamics. In this paper, a climate system model and proxy records are therefore used to study the role of natural and anthropogenic forcings in driving the global climate. The inverse and forward approaches to paleoclimate data–model comparison are applied, and sources of uncertainty are identified and discussed. In the first of two case studies, the climate model simulations are compared with multiproxy temperature reconstructions. Robust solar and volcanic signals are detected in Southern Hemisphere temperatures, with a possible volcanic signal detected in the Northern Hemisphere. The anthropogenic signal dominates during the industrial period. It is also found that seasonal and geographical biases may cause multiproxy reconstructions to overestimate the magnitude of the long-term preindustrial cooling trend. In the second case study, the model simulations are compared with a coral δ18O record from the central Pacific Ocean. It is found that greenhouse gases, solar irradiance, and volcanic eruptions all influence the mean state of the central Pacific, but there is no evidence that natural or anthropogenic forcings have any systematic impact on El Niño–Southern Oscillation. The proxy climate relationship is found to change over time, challenging the assumption of stationarity that underlies the interpretation of paleoclimate proxies. These case studies demonstrate the value of paleoclimate data–model comparison but also highlight the limitations of current techniques and demonstrate the need to develop alternative approaches.
Extratropical Summertime Response to Tropical Interannual Variability in an Idealized GCM
Authors: Hall Nicholas M. J. , Douville Hervé , Li Laurent
Published: March 2013

A primitive equation model is used to investigate the role of the tropics in generating seasonal-mean anomalies in the extratropics. A nudging technique is applied to guide selected tropical regions toward 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) and the National Centers for Environmental Prediction (NCEP)/Department of Energy Reanalysis (NCEP-2). The time-independent linear response to these tropical anomalies is calculated for extratropical basic states taken from reanalysis climatologies and also from the climatological states of Action de Recherche Petite Echelle Grande Echelle (ARPEGE) and Laboratoire de Météorologie Dynamique (LMDZ) general circulation model simulations.

For summer case studies, time-independent linear solutions show that some seasonal anomalies can be attributed to linear wave propagation from the tropics, especially for lower extratropical latitudes. If nudging is applied to the anomaly part of the tropical flow, the linear response shows little dependence on the basic state. Regional tropical nudging experiments display a global extratropical response. The persistent European summer anomaly in 2003 is partly attributable to a linear response to both Central American and West African monsoon circulations. The African region also triggers a wave train along the Asian subtropical jet.

The model is then used in “simple GCM” mode to obtain extratropical responses that include a contribution from transient eddies. Tropical nudging improves the simple GCM's stationary wave climatology, and transient eddy forcing can produce substantial seasonal anomalies at high latitudes with better correspondence to some observed cases, especially in the Western Hemisphere, with stronger communication between the Asian monsoon and North America.
Recent Summer Rainfall Increase and Surface Cooling over Northern Australia since the Late 1970s: A Response to Warming in the Tropical Western Pacific
Authors: Li Xiao-Feng , Yu Jingjing , Li Yun
Published: March 2013

Rainfall over northern Australia (NA) in austral summer is the largest water source of Australia. Previous studies have suggested a strong zonal-dipole trend pattern in austral summer rainfall since 1950, with rainfall increasing in northwest Australia (NWA) but decreasing in northeast Australia (NEA). The dynamics of rainfall increase in NWA was linked to sea surface temperature (SST) in the south Indian Ocean and the rainfall decrease in NEA was associated with SST in the northeast Indian Ocean.

This study reports that, in contrast to a zonal-dipole trend pattern, a dominant wetting pattern over NA has recently been observed in the post-1979 satellite era. The recent NA rainfall increase also manifests as the first leading mode of summer rainfall variability over the Australian continent. Further investigation reveals that SST in the tropical western Pacific (TWP) has replaced the SST in the south and northeast Indian Ocean as the controlling factor responsible for the recent NA rainfall increase. Direct thermal forcing by increasing TWP SST gives rise to an anomalous Gill-type cyclone centered around NA, leading to anomalously high rainfall. As such, the increasing SST in the TWP induces over 50% of the observed rainfall wetting trend over NA. The increased rainfall in turn induces land surface cooling in NA. This mechanism can be confirmed with results obtained from sensitivity experiments of a numerical spectral atmospheric general circulation model. Thus, increasing SST in the TWP has contributed much of the recent summer rainfall increase and consequently the surface cooling over NA.
Long-Term Nitrate Measurements in the Ocean Using the in situ Ultraviolet Spectrophotometer: Sensor Integration into the APEX Profiling Float
Authors: Johnson Kenneth S. , Coletti Luke J. , Jannasch Hans W. , Sakamoto Carole M. , Swift Dana D. , Riser Stephen C.
Published: March 2013

Reagent-free optical nitrate sensors [in situ ultraviolet spectrophotometer (ISUS)] can be used to detect nitrate throughout most of the ocean. Although the sensor is a relatively high-power device when operated continuously (7.5 W typical), the instrument can be operated in a low-power mode, where individual nitrate measurements require only a few seconds of instrument time and the system consumes only 45 J of energy per nitrate measurement. Operation in this mode has enabled the integration of ISUS sensors with Teledyne Webb Research's Autonomous Profiling Explorer (APEX) profiling floats with a capability to operate to 2000 m. The energy consumed with each nitrate measurement is low enough to allow 60 nitrate observations on each vertical profile to 1000 m. Vertical resolution varies from 5 m near the surface to 50 m near 1000 m, and every 100 m below that. Primary lithium batteries allow more than 300 vertical profiles from a depth of 1000 m to be made, which corresponds to an endurance near four years at a 5-day cycle time. This study details the experience in integrating ISUS sensors into Teledyne Webb Research's APEX profiling floats and the results that have been obtained throughout the ocean for periods up to three years.
Rising Variability in Thunderstorm-Related U.S. Losses as a Reflection of Changes in Large-Scale Thunderstorm Forcing*
Authors: Sander J. , Eichner J. F. , Faust E. , Steuer M.
Published: March 2013

Thunderstorm-related normalized economic and insured losses in the United States east of the Rockies from the period 1970–2009 (March–September) exhibit higher peaks and greater variability in the last two decades than in the preceding two decades. To remove the bias from increasingly detected losses over time due to newly built-up locations, only large events that incurred normalized losses of at least $250 million (U.S. dollars) economically ($150 million insured) were selected. These are multistate damage events that are unlikely to have been missed at any time within the analysis period, thus providing for homogeneity of the events covered. Those losses, if aggregated, account for the major proportion (~80%) of all thunderstorm-related losses in the period 1970–2009. This study demonstrates that the pattern of variability in the time series of these losses can be seen as a reflection (“fingerprint”) of the temporal variability in severe thunderstorm forcing. The meteorological information on forcing is inferred from NCEP–NCAR reanalysis data. No final attribution of the climatic variability identified in thunderstorm forcing and losses—either to natural climate variability or to anthropogenic climate change—can be conclusively arrived at in this study because of the chosen methodology. Nevertheless, the expected impacts of anthropogenic climate change on the forcing of convective storms appear consistent with these findings.
The Decreasing Population Bias in Tornado Reports across the Central Plains
Authors: Elsner James B. , Michaels Laura E. , Scheitlin Kelsey N. , Elsner Ian J.
Published: March 2013

Tornado–hazard assessment is hampered by a population bias in the available data. Here, the authors demonstrate a way to statistically quantify this bias using the ratio of city to country report densities. The expected report densities come from a model of the number of reports as a function of distance from the nearest city center. On average since 1950, reports near cities with populations of at least 1000 in a 5.5° latitude × 5.5° longitude region centered on Russell, Kansas, exceed those in the country by 70% [54%, 84%; 95% confidence interval (CI)]. The model is applied to 10-yr moving windows to show that the percentage is decreasing with time. Over the most recent period (2002–11), the tornado report density in the city is slightly fewer than 3 reports (100 km2)−1 (100 yr)−1, and this value is statistically indistinguishable from the report density in the country. On average, the population bias is less pronounced for Fujita (F) scale F0 tornadoes, but the bias disappears more quickly over time for the F1 and stronger tornadoes. The authors show evidence that this decline could be related in part to an increase in the number of storm chasers. The population-bias model can enhance the usefulness of the Storm Prediction Center's tornado database and help create more meaningful spatial climatologies.
Docklands Dreamings: Illusions of Sustainability in the Melbourne Docks Redevelopment
Authors: Shaw Kate
Published: March 2013

The redevelopment of Melbourne’s docklands—the largest urban development project in Australia—has been the subject of various official narratives in the course of its 20-year realisation so far. Many of these have invoked aspirations—‘visions’ or imaginaries—of sustainability, including, variously, economic, environmental, social and cultural sustainability. Through documentary sources used to establish these narratives, this paper tracks the changes in vision against changes in the local political-economic context and examines their effects on the ground. The paper argues that, while each vision was intended to some degree to rescue the development from the failure of the preceding one, only the most recent phase represents any deviation from neoliberal development-as-usual, and this is more to do with the intensifying criticism of the project’s failure to demonstrate any kind of sustainability than it is the implementation of an articulated aspiration.
A comparison of treadmill training and overground walking in ambulant children with cerebral palsy: randomized controlled clinical trial
Authors: Grecco Luanda André Collange , Zanon Nelci , Sampaio Luciana Maria Malosá , Oliveira Claudia Santos
Published: March 2013

Objective:

Compare the effects of treadmill training and training with overground walking (both without partial weight support) on motor skills in children with cerebral palsy.

Design:

Randomized controlled clinical trial.

Setting:

Physical therapy clinics.

Subjects:

Thirty-six children with cerebral palsy (levels I–III of the Gross Motor Functional Classification System) randomly divided into two intervention groups.

Interventions:

Experimental group (17 children) submitted to treadmill training without partial weight support. Overground walking group (18 children) submitted to gait training on a fixed surface (ground). Training was performed for seven consecutive weeks (two sessions per week), with four subsequent weeks of follow-up.

Results:

Both groups demonstrated improvements on the 6-minute walk test (experimental group from 227.4 SD 49.4 to 377.2 SD 93.0; overground walking group from 222.6 SD 42.6 to 268.0 SD 45.0), timed up-and-go test (experimental group from 14.3 SD 2.9 to 7.8 SD 2.2; overground walking group from 12.8 SD 2.2 to 10.5 SD 2.5), Pediatric Evaluation Disability Inventory (experimental group from 128.0 SD 19.9 to 139.0 SD 18.4; overground walking group from 120.8 SD 19.0 to 125.8 SD 12.2), Gross Motor Function Measure-88 (experimental group from 81.6 SD 8.7 to 93.0 SD 5.7; overground walking group from 77.3 SD 7.0 to 80.8 SD 7.2), Berg Balance Scale (experimental group from 34.9 SD 8.5 to 46.7 SD 7.6; overground walking group from 31.9 SD 7.0 to 35.7 SD 6.8) after treatment. The experimental group demonstrated greater improvements than the overground walking group both after treatment and during follow up ( p < 0.05).

Conclusion:

Treadmill training proved more effective than training with overground walking regarding functional mobility, functional performance, gross motor function and functional balance in children with cerebral palsy.
Latina Teen Suicide and Bullying
Authors: Romero Andrea J. , Wiggs Christine Bracamonte , Valencia Celina , Bauman Sheri
Published: March 2013

Latina adolescents experience depression and suicidal ideations in a disproportionate manner compared to their non-Latina counterparts. We investigate suicide and depressive symptoms among a state-wide sample ( N = 650) of adolescent Latina girls with a focus on bullying as a predictor. Bullying rates are higher than previous studies have found for victimization at school (23%), cybervictimization (26%), school bully (18%), and cyberbully (18%). Rates for depressive symptoms (49%), suicide ideation (23%), suicide plan (17%), and suicide attempt(s; 13%) are higher than national averages. After controlling for depressive symptoms, girls who have been bullied were 1.5 times more likely to attempt suicide compared to girls who have not been victims. However, being a bully increased likelihood of suicide ideation (1.5) and suicide plan (1.4) compared to not being a bully. There is a continued need to prevent depressive symptoms and suicide among Latina girls and to further investigate the effects of bullying.
Common DNA Markers Can Account for More Than Half of the Genetic Influence on Cognitive Abilities
Authors: Plomin Robert , Haworth Claire M. A. , Meaburn Emma L. , Price Thomas S. ,   Wellcome Trust Case Control Consortium 2, Davis Oliver S. P.
Published: March 2013

For nearly a century, twin and adoption studies have yielded substantial estimates of heritability for cognitive abilities, although it has proved difficult for genomewide-association studies to identify the genetic variants that account for this heritability (i.e., the missing-heritability problem). However, a new approach, genomewide complex-trait analysis (GCTA), forgoes the identification of individual variants to estimate the total heritability captured by common DNA markers on genotyping arrays. In the same sample of 3,154 pairs of 12-year-old twins, we directly compared twin-study heritability estimates for cognitive abilities (language, verbal, nonverbal, and general) with GCTA estimates captured by 1.7 million DNA markers. We found that DNA markers tagged by the array accounted for .66 of the estimated heritability, reaffirming that cognitive abilities are heritable. Larger sample sizes alone will be sufficient to identify many of the genetic variants that influence cognitive abilities.
Simulating the contribution of a biospecimen and clinical data repository in a phase II clinical trial: A value of information analysis
Authors: Craig Benjamin M , Han Gang , Munkin Murat K , Fenstermacher David
Published: March 2013

The potential contributions of a centralized data warehouse or repository in clinical research include the expedited accrual of subjects for phase II trials. Understanding the contribution of data warehouses that integrate clinical, biospecimen, and molecular data for the conduct of clinical trials is essential to inform private and public decisions on resource allocation and investment. We conducted a value of information analysis using data from recent trials at the Moffitt Cancer Center and simulated the potential reductions in trial size due to possible alternative scenarios of expedited accrual. In this study, we compared alternative data sets using a single model to assess value of information. Our findings suggest that the reductions in trial size range from 0% to 43%, depending on the amount of censoring in overall survival. The ability to expedite the accrual of patients for clinical trial studies using large data repositories that store data on inclusion/exclusion criteria and response to standard of care therapies demonstrated significant improvement in reducing the number of subjects needed to achieve similar end-results, as evaluated using value of information analysis with a limited number of parameters and a parsimonious model of overall survival.
Feeding
Authors: Chai Hui Zhong , Krishna Lalit Kumar Radha , Wong Victoria Hwei May
Published: March 2013

Introduction:

The decision-making process underlying caregivers’ choice to continue feeding at the end of life is not well understood.

Objectives:

To provide a better understanding of the complex interplay of factors that influence the decision by caregivers to continue feeding.

Methods:

Palliative care patients and their main caregiver recruited at National Cancer Centre Singapore between May and July 2011 were included. Data were collected using an interviewer-administered questionnaire.

Results:

One hundred respondents were included. Three major prevailing themes were identified: filial piety, source of hope, and expression of affection. Nonparametric statistical testing showed that patients and caregivers shared similar views about feeding at the end of life.

Discussion:

The major themes identified above undergird the caregiver’s decision to continue feeding at the end of life.
Hardships of End-of-Life Care With Court-Appointed Guardians
Authors: Hastings Kylie B.
Published: March 2013

In the United States, the court-appointed guardians do not have the ability to make decisions regarding end-of-life (EOL) care for their clients. Additionally, the process of initiating EOL care measures can be slow and cumbersome, despite an existing process of getting approval for such care. This process has the potential to prolong suffering and delay imperative decisions. This article reviews the hardships that patients, court-appointed guardians, and health care staff endure while moving through the oppressive process of obtaining EOL care orders through the court. This article also proposes ways of tuning up the laws, regulations, and communications to make it easier and faster to obtain orders regarding EOL care to preserve the dignity of our patients and loved ones. “A guardianship is a legal relationship created when a person or institution named in a will or assigned by the court to take care of minor children or incompetent adults.”6
The rapture of the ride: Hearing (dis)abled masculinities in motorcycling
Authors: Loeser Cassandra
Published: March 2013

This article explores motorcycling as an arena for the choreography and performance of body practices of pleasure for young men with hearing disabilities. The article advances the argument that the discursive multiplicity of identities experienced in motorcycling destabilises precepts that privilege paid work and institutionalised competitive team sports as absolute bastions of masculine existence. Drawing on data collected from an interview with one young man with a severe hearing disability, it will be shown that his experience of both finding a stable occupation, and participating in institutionalised team sports, is marked by ongoing difficulties. By contrast, participation in motorcycling is an occasion by which he (re)constructs and enhances his masculine identity. The embodied experience of motorcycling invokes possibilities for an interconnection with the masculine, and dialogic exchange with the identity of hearing disability. This demonstrates an uncertainty of settlements regarding what constitutes ‘masculinity’ and ‘disability’ in different sites and contexts.
The effects of firm reputation and status on interorganizational network structure
Authors: Chandler David , Haunschild Pamela R , Rhee Mooweon , Beckman Christine M
Published: March 2013

In this article, we explore the differential effects of a firm’s reputation and status on its interorganizational network. We hypothesize that due to its stable, unitary, and relational characteristics, status has a stronger influence on partner selection than reputation, which is less stable, multidimensional, and based more on perceptions of product quality and financial performance. Results from our analyses of the director networks of the 300 largest US firms from 1985 to 1993 confirm that across multiple measures of network characteristics, it is status that is the stronger predictor. In particular, high-status firms have networks that are higher in partner quality but are less diverse and contain fewer opportunities to bridge structural holes than the networks of high-reputation firms. These results contribute to our understanding of the different effects of reputation and status on firm behavior by emphasizing the importance of studying both together in order to understand the effects of either. They also contribute to work on interorganizational networks by demonstrating how structure emerges primarily as a function of focal firm status.
Using the DLOQ to Support Learning in Republic of Korea SMEs
Authors: Kim Young-Saing , Marsick Victoria J.
Published: March 2013

The Problem

Watkins and Marsick (1993) recommend that interventions be sculpted to meet unique organizational contexts and conditions. They provide examples, but do not show how interventions can be designed based on the dimensions of the learning organization questionnaire (DLOQ).

The Solution

The Government of the Republic of Korea (ROK) used the DLOQ to guide development of a policy-oriented Learning Organization Initiative (LOI) to increase employee skills and capabilities in small and medium size enterprises (SMEs). Research was prompted by awareness of gaps in resource use and of differences in how employees prefer to learn in SMEs in comparison to large companies. This article shows how the DLOQ guided work with multiple stakeholders to create a customizable set of interventions for SMEs.

The Stakeholders

Scholar practitioners and policy specialists may be interested in ways that policy was crafted to suit the unique learning preferences of SMEs when developing solutions that support within-firm, across-firm, and national human resource development.
IQ and Delinquency
Authors: Yun Ilhong , Lee Julak
Published: March 2013

The purpose of this study is to examine the degree to which police arrest is influenced by an offenders’ level of verbal intelligence. Concomitantly, we examine whether the level of concentrated disadvantage of the neighborhood where the offender resides moderates the effect of verbal intelligence on arrest. To accomplish this, we employed the National Longitudinal Study of Adolescent Health (Add Health) to examine the extent to which persistent delinquent youths’ self-reported arrests are significantly related to their verbal IQ scores. Furthermore, we also analyzed the interaction of verbal IQ scores and neighborhood disadvantage net of an array of theoretically relevant control variables.
A Longitudinal Analysis of the Relationship Between School Victimization and Student Mobility
Authors: Carson Dena C. , Esbensen Finn-Aage , Taylor Terrance J.
Published: March 2013

Schools have generally been viewed as “safe havens” from victimization experiences. Yet, there is no question that youth experience a variety of victimization while attending school. The current study expands research on victimization at school by focusing on mobile youth. School mobility is of concern to both educators and practitioners and is associated with a number of harmful as well as beneficial outcomes (e.g., dropout and school failure, deviant behaviors, or increased test scores and grades). This research uses longitudinal data from a sample of approximately 2,000 youth to examine (1) the effect of in-school victimization on school mobility and (2) the consequences of school mobility on subsequent victimization. Findings from multilevel regression and change score analyses indicate that, in middle school, youth who are victimized are more likely to change schools and experience less victimization at the new school.
Canadian News Coverage of Intimate Partner Homicide
Authors: Fairbairn Jordan , Dawson Myrna
Published: March 2013

News coverage of intimate partner homicide can reveal and reproduce societal assumptions and beliefs that may influence social and political responses to violence against women. This study analyzes all male-perpetrated intimate partner homicides reported in three daily newspapers in Toronto, Canada within two separate time periods (1975-1979 and 1998-2002) to explore if and how this coverage has changed over time. Results suggest that, in more recent years, news coverage is more likely to report a previous history of intimate partner violence and less likely to employ news that excuses or justifies the perpetrator’s actions. However, coverage continues to employ victim-blaming news frames and to portray intimate partner homicide as an individual event, in part, through the absence of the voices of violence against women organizations, researchers, and service providers as legitimate authorities in both time periods. Thus, news coverage fails to encourage social and political responses to violence against women in intimate relationships that emphasize the need for social structural changes focusing on gender equality.
What Performance Characteristics Determine Elite Versus Nonelite Athletes in the Same Sport?
Authors: Lorenz Daniel S. , Reiman Michael P. , Lehecka B.J. , Naylor Andrew
Published: March 2013

Context:

There are significant data comparing elite and nonelite athletes in anaerobic field and court sports as well as endurance sports. This review delineates specific performance characteristics in the elite athlete and may help guide rehabilitation.

Evidence Acquisition:

A Medline search from April 1982 to April 2012 was undertaken for articles written in English. Additional references were accrued from reference lists of research articles.

Results:

In the anaerobic athlete, maximal power production was consistently correlated to elite performance. Elite performance in the endurance athlete is more ambiguous, however, and appears to be related to the dependent variable investigated in each individual study.

Conclusion:

In anaerobic field and court sport athletes, maximal power output is most predictive of elite performance. In the endurance athlete, however, it is not as clear. Elite endurance athletes consistently test higher than nonelite athletes in running economy, anaerobic threshold, and VO2max.
Rehabilitation of Low Back Pain in Golfers
Authors: Finn Christopher
Published: March 2013

Context:

Low back injuries are the most common injury in golf. Best practice guidelines for rehabilitation and prevention of these injuries are helpful for health care professionals and all golfers.

Objective:

To establish a best practice clinical model for low back pain in golfers from diagnosis through treatment and rehabilitation to return to golf.

Evidence Acquisition:

The PubMed database and Google Scholar were searched from 1993 to 2012 with the following keywords: golf and low back injury, low back injury, golf and low back pain, golf injury prevention, golf modern swing, muscles in golf swing, low back rehabilitation, diaphragm, and core stability. All studies addressed in some manner the rehabilitation, prevention, or return to sport from low back injury, preferably in direct relation to golf, as well as muscle firing patterns used during the golf swing.

Results:

Best practice for rehabilitation and prevention of low back injury in golf appears to be through a multidisciplinary approach.

Conclusion:

Movement patterns, muscle imbalances, and type of swing utilized all have a direct effect on the forces applied to the spine during the golf swing and need to be assessed to prevent or rehabilitate injury. Understanding the golf swing and how the body works during the swing is necessary.
Progress toward inducing immunologic tolerance to factor VIII
Authors: Scott David W. , Pratt Kathleen P. , Miao Carol H.
Published: March 2013

A major problem in treating hemophilia A patients with therapeutic factor VIII (FVIII) is that 20% to 30% of these patients produce neutralizing anti-FVIII antibodies. These antibodies block (inhibit) the procoagulant function of FVIII and thus are termed “inhibitors.” The currently accepted clinical method to attempt to eliminate inhibitors is immune tolerance induction (ITI) via a protocol requiring intensive FVIII treatment until inhibitor titers drop. Although often successful, ITI is extremely costly and is less likely to succeed in patients with high-titer inhibitors. During the past decade, significant progress has been made in clarifying mechanisms of allo- and autoimmune responses to FVIII and in suppression of these responses. Animal model studies are suggesting novel, less costly methods to induce tolerance to FVIII. Complementary studies of anti-FVIII T-cell responses using blood samples from human donors are identifying immunodominant T-cell epitopes in FVIII and possible targets for tolerogenic efforts. Mechanistic experiments using human T-cell clones and lines are providing a clinically relevant counterpoint to the animal model studies. This review highlights recent progress toward the related goals of lowering the incidence of anti-FVIII immune responses and promoting durable, functional immune tolerance to FVIII in patients with an existing inhibitor.
Coupled coincidence point theorems in (intuitionistic) fuzzy normed spaces
Authors: Cho YJ , Martínez-Moreno J , Roldán A , Roldán C
Published: March 2013

In this paper, we prove some coupled coincidence point theorems in fuzzy normed spaces. Our results improve and restate the proof lines of the main results given in the papers (Eshaghi Gordji et al. in Math. Comput. Model. 54:1897-1906, 2011) and (Sintunavarat et al. in Fixed Point Theory Appl. 2011:81, 2011).

MSC:47H10, 54H25, 34B15.
A detailed molecular analysis of complete Bovine Leukemia Virus genomes isolated from B-cell lymphosarcomas
Authors: Moratorio Gonzalo , Fischer Sabrina , Bianchi Sergio , Tomé Lorena , Rama Gonzalo , Obal Gonzalo , Carrión Federico , Pritsch Otto , Cristina Juan
Published: March 2013

It is widely accepted that the majority of cancers result from multiple cellular events leading to malignancy after a prolonged period of clinical latency, and that the immune system plays a critical role in the control of cancer progression. Bovine leukemia virus (BLV) is an oncogenic member of the Retroviridae family. Complete genomic sequences of BLV strains isolated from peripheral blood mononuclear cells (PBMC) from cattle have been previously reported. However, a detailed characterization of the complete genome of BLV strains directly isolated from bovine tumors is much needed in order to contribute to the understanding of the mechanisms of leukemogenesis induced by BLV in cattle. In this study, we performed a molecular characterization of BLV complete genomes from bovine B-cell lymphosarcoma isolates. A nucleotide substitution was found in the glucocorticoid response element (GRE) site of the 5' long terminal repeat (5'LTR) of the BLV isolates. All amino acid substitutions in Tax previously found to be related to stimulate high transcriptional activity of 5'LTR were not found in these studies. Amino acid substitutions were found in the nucleocapsid, gp51 and G4 proteins. Premature stop-codons in R3 were observed. Few mutations or amino acid substitutions may be needed to allow BLV provirus to achieve silencing. Substitutions that favor suppression of viral expression in malignant B cells might be a strategy to circumvent effective immune attack.
Identification and characterization of two distinct PPP1R2 isoforms in human spermatozoa
Authors: Korrodi-Gregório Luis , Ferreira Mónica , Vintém Ana Paula , Wu Wenjuan , Muller Thorsten , Marcus Katrin , Vijayaraghavan Srinivasan , Brautigan David L , da Cruz e Silva Odete A B , Fardilha Margarida , da Cruz e Silva Edgar F
Published: March 2013

Background

Protein Ser/Thr Phosphatase PPP1CC2 is an alternatively spliced isoform of PPP1C that is highly enriched in testis and selectively expressed in sperm. Addition of the phosphatase inhibitor toxins okadaic acid or calyculin A to caput and caudal sperm triggers and stimulates motility, respectively. Thus, the endogenous mechanisms of phosphatase inhibition are fundamental for controlling sperm function and should be characterized. Preliminary results have shown a protein phosphatase inhibitor activity resembling PPP1R2 in bovine and primate spermatozoa.

Results

Here we show conclusively, for the first time, that PPP1R2 is present in sperm. In addition, we have also identified a novel protein, PPP1R2P3. The latter was previously thought to be an intron-less pseudogene. We show that the protein corresponding to the pseudogene is expressed. It has PPP1 inhibitory potency similar to PPP1R2. The potential phosphosites in PPP1R2 are substituted by non-phosphorylable residues, T73P and S87R, in PPP1R2P3. We also confirm that PPP1R2/PPP1R2P3 are phosphorylated at Ser121 and Ser122, and report a novel phosphorylation site, Ser127. Subfractionation of sperm structures show that PPP1CC2, PPP1R2/PPP1R2P3 are located in the head and tail structures.

Conclusions

The conclusive identification and localization of sperm PPP1R2 and PPP1R2P3 lays the basis for future studies on their roles in acrosome reaction, sperm motility and hyperactivation. An intriguing possibility is that a switch in PPP1CC2 inhibitory subunits could be the trigger for sperm motility in the epididymis and/or sperm hyperactivation in the female reproductive tract.
Differential miRNA expression profiles in proliferating or differentiated keratinocytes in response to gamma irradiation
Authors: Joly-Tonetti Nicolas , Viñuelas José , Gandrillon Olivier , Lamartine Jérôme
Published: March 2013

Background

MicroRNAs (miRNAs), a group of short non-coding RNAs that negatively regulate gene expression, have recently emerged as potential modulators of cellular response to ionizing radiations both in vitro and in vivo in various cell types and tissues. However, in epidermal cells, the involvement of the miRNA machinery in the cellular response to ionizing radiations remains to be clarified. Indeed, understanding the mechanisms of cutaneous radiosensitivity is an important issue since skin is the most exposed organ to ionizing radiations and among the most sensitive.

Results

We settled up an expression study of miRNAs in primary human skin keratinocytes using a microfluidic system of qPCR assay, which permits to assess the expression of almost 700 annotated miRNAs. The keratinocytes were cultured to a proliferative or a differentiated state mimicking basal or suprabasal layers of human epidermis. These cells were irradiated at 10 mGy or 6 Gy and RNA was extracted 3 hours after irradiation. We found that proliferative cells irradiated at 6 Gy display a global fall of miRNA expression whereas differentiated cells exposed to the same dose display a global increase of miRNAs expression. We identified twenty miRNAs weakly but significantly modulated after 6 Gy irradiation, whereas only 2 miRNAs were modulated after low-dose irradiation in proliferating cells. To go further into the biological meaning of this miRNA response, we over-expressed some of the responding miRNA in proliferating cells: we observed a significant decrease of cell viability 72 hours after irradiation. Functional annotation of their predicted targets revealed that G-protein related pathways might be regulated by these responding miRNAs.

Conclusions

Our results reveal that human primary keratinocytes exposed to ionizing irradiation expressed a miRNA pattern strongly related to the differentiation status of irradiated cells. We also demonstrate that some miRNAs play a role in the radiation response to ensure the short-term survival of irradiated keratinocytes.
The protein translocation systems in plants – composition and variability on the example of Solanum lycopersicum
Authors: Paul Puneet , Simm Stefan , Blaumeiser Andreas , Scharf Klaus-Dieter , Fragkostefanakis Sotirios , Mirus Oliver , Schleiff Enrico
Published: March 2013

Background

Protein translocation across membranes is a central process in all cells. In the past decades the molecular composition of the translocation systems in the membranes of the endoplasmic reticulum, peroxisomes, mitochondria and chloroplasts have been established based on the analysis of model organisms. Today, these results have to be transferred to other plant species. We bioinformatically determined the inventory of putative translocation factors in tomato (Solanum lycopersicum) by orthologue search and domain architecture analyses. In addition, we investigated the diversity of such systems by comparing our findings to the model organisms Saccharomyces cerevisiae, Arabidopsis thaliana and 12 other plant species.

Results

The literature search end up in a total of 130 translocation components in yeast and A. thaliana, which are either experimentally confirmed or homologous to experimentally confirmed factors. From our bioinformatic analysis (PGAP and OrthoMCL), we identified (co-)orthologues in plants, which in combination yielded 148 and 143 orthologues in A. thaliana and S. lycopersicum, respectively. Interestingly, we traced 82% overlap in findings from both approaches though we did not find any orthologues for 27% of the factors by either procedure. In turn, 29% of the factors displayed the presence of more than one (co-)orthologue in tomato. Moreover, our analysis revealed that the genomic composition of the translocation machineries in the bryophyte Physcomitrella patens resemble more to higher plants than to single celled green algae. The monocots (Z. mays and O. sativa) follow more or less a similar conservation pattern for encoding the translocon components. In contrast, a diverse pattern was observed in different eudicots.

Conclusions

The orthologue search shows in most cases a clear conservation of components of the translocation pathways/machineries. Only the Get-dependent integration of tail-anchored proteins seems to be distinct. Further, the complexity of the translocation pathway in terms of existing orthologues seems to vary among plant species. This might be the consequence of palaeoploidisation during evolution in plants; lineage specific whole genome duplications in Arabidopsis thaliana and triplications in Solanum lycopersicum.
Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial
Authors: Ahmed Ali Usama , Issa Yama , Bruno Marco J , van Goor Harry , van Santvoort Hjalmar , Busch Olivier RC , Dejong Cornelis HC , Nieuwenhuijs Vincent B , van Eijck Casper H , van Dullemen Hendrik M , Fockens Paul , Siersema Peter D , Gouma Dirk J , van Hooft Jeanin E , Keulemans Yolande , Poley Jan W , Timmer Robin , Besselink Marc G , Vleggaar Frank P , Wilder-Smith Oliver H , Gooszen Hein G , Dijkgraaf Marcel GW , Boermeester Marja A ,   for the Dutch Pancreatitis Study Group
Published: March 2013

Background

In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis.

Methods/design

The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (≥ 5 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (≥ 4 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least 15 points on the Izbicki pain score during follow-up. To detect this difference a total of 88 patients will be randomized (alpha 0.05, power 90%, drop-out 10%).

Discussion

The ESCAPE trial will investigate whether early surgery in chronic pancreatitis is beneficial in terms of pain relief, pancreatic function and quality of life, compared with current step-up practice.

Trial registration

ISRCTN: ISRCTN45877994
αB-crystallin stimulates VEGF secretion and tumor cell migration and correlates with enhanced distant metastasis in head and neck squamous cell carcinoma
Authors: van de Schootbrugge Chantal , Bussink Johan , Span Paul N , Sweep Fred CGJ , Grénman Reidar , Stegeman Hanneke , Pruijn Ger JM , Kaanders Johannes HAM , Boelens Wilbert C
Published: March 2013

Background

αB-crystallin is able to modulate vascular endothelial growth factor (VEGF) secretion. In many solid tumors VEGF is associated with angiogenesis, metastasis formation and poor prognosis. We set out to assess whether αB-crystallin expression is correlated with worse prognosis and whether this is related to VEGF secretion and cell motility in head and neck squamous cell carcinoma (HNSCC).

Methods

αB-crystallin expression was determined immunohistochemically in tumor biopsies of 38 HNSCC patients. Locoregional control (LRC) and metastasis-free survival (MFS) of the patients were analyzed in relation to αB-crystallin expression. Additionally, the effects of αB-crystallin knockdown on VEGF secretion and cell motility were studied in vitro.

Results

Patients with higher staining fractions of αB-crystallin exhibited a significantly shorter MFS (Log-Rank test, p < 0.005). Under normoxic conditions αB-crystallin knockdown with two different siRNAs in a HNSCC cell line reduced VEGF secretion 1.9-fold and 2.1-fold, respectively. Under hypoxic conditions, a similar reduction of VEGF secretion was observed, 1.9-fold and 2.2-fold, respectively. The effect on cell motility was assessed by a gap closure assay, which showed that αB-crystallin knockdown decreased the rate by which HNSCC cells were able to close a gap by 1.5- to 2.0-fold.

Conclusions

Our data suggest that αB-crystallin expression is associated with distant metastases formation in HNSCC patients. This association might relate to the chaperone function of αB-crystallin in mediating folding and secretion of VEGF and stimulating cell migration.
Design of a randomized controlled trial for multiple cancer risk behaviors among Spanish-speaking Mexican-origin smokers
Authors: Castro Yessenia , Basen-Engquist Karen , Fernandez Maria E , Strong Larkin L , Eakin Elizabeth G , Resnicow Ken , Li Yisheng , Wetter David W
Published: March 2013

Background

Smoking, poor diet, and physical inactivity account for as much as 60% of cancer risk. Latinos experience profound disparities in health behaviors, as well as the cancers associated with them. Currently, there is a dearth of controlled trials addressing these health behaviors among Latinos. Further, to the best of our knowledge, no studies address all three behaviors simultaneously, are culturally sensitive, and are guided by formative work with the target population. Latinos represent 14% of the U.S. population and are the fastest growing minority group in the country. Efforts to intervene on these important lifestyle factors among Latinos may accelerate the elimination of cancer-related health disparities.

Methods/design

The proposed study will evaluate the efficacy of an evidence-based and theoretically-driven Motivation And Problem Solving (MAPS) intervention, adapted and culturally-tailored for reducing cancer risk related to smoking, poor diet, and physical inactivity among high-risk Mexican-origin smokers who are overweight/obese (n = 400). Participants will be randomly assigned to one of two groups: Health Education (HE) or MAPS (HE + up to 18 MAPS counseling calls over 18 months). Primary outcomes are smoking status, servings of fruits and vegetables, and both self-reported and objectively measured physical activity. Outcome assessments will occur at baseline, 6 months, 12 months, and 18 months.

Discussion

The current study will contribute to a very limited evidence base on multiple risk factor intervention studies on Mexican-origin individuals and has the potential to inform both future research and practice related to reducing cancer risk disparities. An effective program targeting multiple cancer risk behaviors modeled after chronic care programs has the potential to make a large public health impact because of the dearth of evidence-based interventions for Latinos and the extended period of support that is provided in such a program.

Trial registration

National Institutes of Health Clinical Trials Registry #NCT01504919