bluuebunny/crossref_metadata_2025 huggingface dataset:
A Circadian Surface of Entrainment: Varying T, τ, and Photoperiod in Neurospora crassa
Authors: Rémi Jan , Merrow Martha , Roenneberg Till
Published: September 2010

The two major prerequisites for a functional circadian system are the generation of an internal day (circadian cycle) and adjusting its length—and phase—to that of the external day (zeitgeber cycle). The generation of circadian cycles can be observed in constant conditions where organisms show a self-sustained, free-running rhythm. Their expression depends on the nature of the constant conditions (e.g., constant darkness, DD, or constant light, LL). The mechanism that synchronizes the circadian cycle length (τ) to that of the zeitgeber (T) can be explored by many experimental procedures (e.g., single light pulses), but it can only be fully understood under entertainment proper. When a clock is stably entrained, τLD is, on average, equal to T, but the phase relationship between the clock (ϕ) and the zeitgeber (Φ) (phase of entrainment, ψ = Φ— ϕ) depends on the relationship between τ in constant conditions (τDD or τ LL) and T. Phase of entrainment has traditionally been predicted by the clock’s phase response curve (PRC) for a given zeitgeber stimulus and τDD. But there is an additional quality of the natural environment—namely, photoperiod—which is not easily incorporated into this entrainment paradigm. The authors therefore investigated phase of entrainment for 162 combinations of T, τ, and photoperiod in Neurospora crassa, which lends itself to a high-throughput approach. They entrained different strains (with long, short, and wild-type free-running periods) to different cycle lengths of the zeitgeber (16-26 h) and photoperiods (16%-84% of each cycle). These combinations produce a circadian surface with highly systematic phases of entrainment. The results suggest that the traditional entrainment paradigms using the PRC and τDD have to be reevaluated.
JTK_CYCLE: An Efficient Nonparametric Algorithm for Detecting Rhythmic Components in Genome-Scale Data Sets
Authors: Hughes Michael E. , Hogenesch John B. , Kornacker Karl
Published: September 2010

Circadian rhythms are oscillations of physiology, behavior, and metabolism that have period lengths near 24 hours. In several model organisms and humans, circadian clock genes have been characterized and found to be transcription factors. Because of this, researchers have used microarrays to characterize global regulation of gene expression and algorithmic approaches to detect cycling. This article presents a new algorithm, JTK_CYCLE, designed to efficiently identify and characterize cycling variables in large data sets. Compared with COSOPT and the Fisher’s G test, two commonly used methods for detecting cycling transcripts, JTK_CYCLE distinguishes between rhythmic and nonrhythmic transcripts more reliably and efficiently. JTK_CYCLE’s increased resistance to outliers results in considerably greater sensitivity and specificity. Moreover, JTK_CYCLE accurately measures the period, phase, and amplitude of cycling transcripts, facilitating downstream analyses. Finally, JTK_CYCLE is several orders of magnitude faster than COSOPT, making it ideal for large-scale data sets. JTK_CYCLE was used to analyze legacy data sets including NIH3T3 cells, which have comparatively low amplitude oscillations. JTK_CYCLE’s improved power led to the identification of a novel cluster of RNA-interacting genes whose abundance is under clear circadian regulation. These data suggest that JTK_CYCLE is an ideal tool for identifying and characterizing oscillations in genome-scale data sets.
N-acetyl cysteine improves affinity of beta-tricalcium phosphate granules for cultured osteoblast-like cells
Authors: Yamada Masahiro , Minamikawa Hajime , Ueno Takeshi , Sakurai Kaoru , Ogawa Takahiro
Published: September 2010

Enhancement of bone substitute's biocompatibility may accelerate healing of surrounding bone. Although widely used as a biodegradable alloplastic bone substitute for alveolar bone augmentation, the osteocompatibility of beta-tricalcium phosphate (β-TCP) remains to be proven. The adverse cellular response to biomaterials is associated with oxidative stress. We hypothesized that commercially available β-TCP granules for clinical use, caused oxidative stress and was not optimal in osteocompatibility and that application of antioxidant amino acid derivative N-acetyl cysteine (NAC) would improve osteoblastic responses to the material. Only 20% of rat calvarial osteoblasts cultured on β-TCP granules remained viable at 24 h after seeding as opposed to 90% on polystyrene. Cell death on β-TCP granules was characterized by necrosis. However, the percentage of viable osteoblasts cultured on β-TCP granules showed a 100% increase with pre-treatment with NAC. NAC restored suppressed alkaline phosphatase activity on β-TCP granules at day 5. Intracellular ROS level on β-TCP granules was 16-fold greater than that on polystyrene, but decreased by half with pre-treatment with NAC. Cell death and intracellular ROS elevation were also induced in polystyrene culture under β-TCP granules even when the osteoblasts were not in direct contact with the β-TCP granules. NAC, however, prevented induction of cell death and elevation of intracellular ROS under β-TCP granules. These results indicate that commercially available β-TCP granules negatively affect cultured osteoblastic viability and function via oxidative stress and that NAC improves these negative responses to the material. This implies enhanced bone regeneration around biodegradable calcium phosphate-based bone substitute by NAC.
Mechanical Properties and In Vitro Bioactivity of Ca5(PO4)2SiO4 Bioceramic
Authors: Lu Wenhao , Duan Wei , Guo Yaping , Ning Congqin
Published: September 2010

Pure Ca5(PO4)2SiO4 bioceramic was first prepared by a sol–gel method using triethyl phosphate, tetraethoxysilane, and calcium nitrate tetrahydrate as original materials. Simulated body fluid (SBF) immersion tests revealed that Ca5(PO4)2SiO4 samples had a greater in vitro apatite-forming ability than hydroxyapatite (HA). After soaking Ca5(PO4)2SiO4 samples in the SBF for 1 day, bone-like apatite precipitated on the surfaces and the apatite layer became thicker with increasing the soaking time. However, few bone-like apatites precipitated on the HA samples even after soaking in the SBF for 7 days. The good in vitro bioactivity of Ca5(PO4)2SiO4 samples was attributed to the silanol (Si-OH) groups and greater solubility of Ca5(PO4)2SiO4. In addition, hot-pressed Ca5(PO4)2SiO4 ceramic exhibited lower bending strength and elastic modulus than hot-pressed HA, since the former had a lower relative density than the latter. The results have shown that Ca5(PO4)2SiO4 is a potential candidate material for bone repair.
Using Maternity Practices in Infant Nutrition and Care (mPINC) Survey Results as a Catalyst for Change
Authors: Edwards Roger A. , Philipp Barbara L.
Published: September 2010

Results from the US federally sponsored Maternity Practices in Infant Nutrition and Care (mPINC) Survey were leveraged to bring together facility leaders who influence hospital breastfeeding practices to improve adherence to the standard of care. Eighty Massachusetts hospital and birth center maternity care decision makers, representing 34 of the state’s 50 facilities (covering 74% of births), participated. Active engagement in problem solving generated a sense of enthusiasm and accomplishment. The collaborative spirit across traditionally competing hospitals demonstrated that these leaders clearly were committed to quality and to improving their facilities’ practices. An important aspect of the summit was to foster transformational leadership by supporting participants in their envisioning, energizing, and enabling roles within their organizations. Cooperation from a broad array of stakeholders is important to drive change.
Mediterranean Rift: Socio-Ecological Transformations in the Sicilian Bluefin Tuna Fishery
Authors: Longo Stefano B.
Published: September 2010

This article examines the social and ecological transformations in the Sicilian bluefin tuna fishery during the modern era. The analysis utilizes a sociological framework that draws on theory from environmental sociology, specifically metabolic rift theory. Escalating pressure on the fishery has contributed to a host of environmental and social problems, including pushing this important fishery to the brink of collapse. Using a combination of primary and secondary source data, this research employs sociological methods and analyzes recent changes in the socio-ecological metabolism of the fishery. The study explores the unsustainable nature of capitalist food production by examining the ‘rift’ in the society and nature metabolism that has emerged in the modern Sicilian bluefin tuna fishery. It advances the discussion on the ways in which the social relations of modern capitalist production have transformed the socio-ecological metabolism in agri-food production.
Gender Differences in the Correlates of Volunteering and Charitable Giving
Authors: Einolf Christopher J.
Published: September 2010

Psychological research has found that women score higher on most measures of the traits, motivations, and values that predict helping others, and women are more likely to help family and friends. However, sex differences in the institutional helping behaviors of volunteering and charitable giving are small. This article seeks to explain this apparent contradiction with the hypotheses that men have more resources and more social capital than women, which compensates for their lower level of motivation. The article tests these hypotheses using data from the 1995 Midlife in the United States (MIDUS) survey. The data show partial support for these hypotheses, as men score higher on measures of income, education, trust, and secular social networks. However, women have broader social networks through religious participation.
‘This war for men’s minds’: the birth of a human science in Cold War America
Authors: Martin-Nielsen Janet
Published: September 2010

The past decade has seen an explosion of work on the history of the human sciences during the Cold War. This work, however, does not engage with one of the leading human sciences of the period: linguistics. This article begins to rectify this knowledge gap by investigating the influence of linguistics and its concept of study, language, on American public, political and intellectual life during the postwar and early Cold War years. I show that language emerged in three frameworks in this period: language as tool, language as weapon, and language as knowledge. As America stepped onto the international stage, language and linguistics were at the forefront: the military poured millions of dollars into machine translation, American diplomats were required to master scores of foreign languages, and schoolchildren were exposed to language-learning on a scale never before seen in the United States. Together, I argue, language and linguistics formed a critical part of the rise of American leadership in the new world order — one that provided communities as dispersed as the military, the diplomatic corps, scientists and language teachers with a powerful way of tackling the problems they faced. To date, linguistics has not been integrated into the broader framework of Cold War human sciences. In this article, I aim to bring both language, as concept, and linguistics, as discipline, into this framework. In doing so, I pave the way for future work on the history of linguistics as a human science.
Interaction between subsurface ocean waters and calving of the Jakobshavn Isbræ during the late Holocene
Authors: Andresen Camilla S. , McCarthy David J. , Valdemar Dylmer Christian , Seidenkrantz Marit-Solveig , Kuijpers Antoon , Lloyd Jerry M.
Published: September 2010

A marine sediment core from Vaigat in Disko Bugt, West Greenland, has been analysed in terms of lithology, dinoflagellate cysts and foraminifera in order to evaluate the influence of oceanographic variability on West Greenland glacier stability. The data show that during the past 5200 years the Atlantic foraminiferal abundance in the subsurface waters of the West Greenland Current (WGC) episodically increased, indicating periods of increases in the inflow of subsurface warm Atlantic water at 2000—1500 cal. yr BP and 1300 cal. yr BP as well as periods of less pronounced increased bottom-water temperatures around 4700—4000 cal. yr BP, 3100—2800, 2600, 1000—800, 500—400, and at 200 cal. yr. The sedimentological and dinoflagellate cyst data indicate that these episodes with enhanced advection of Irminger Sea-derived waters are accompanied by increased iceberg rafting, which we link to increased iceberg calving in relation to destabilization of the Jakobshavn Isbrae. The long-term trend in the data documents the end of a late-Holocene Thermal Maximum between 5200 and 4300 cal. yr BP and a final onset of the Neoglaciation at 3500 cal. yr BP. Increased responses of the iceberg rafting after 3500 cal. yr BP, reflects a westward/seaward advance of the glacier margin in relation to onset of Neoglaciation and a development of the glacier into a floating tongue after 2000 cal. yr BP. A comparison of our record with a record from the eastern North Atlantic indicates that a NAO-like anomaly pattern between subsurface waters in West Greenland and atmospheric temperature in the Eastern North Atlantic may have been operating during most of the late Holocene. However, during the past 1000 years the NAO signal may have weakened as some other mode of climate variability overprints the anti-phase climate signal in this region.
Group sequential trials revisited: Simple implementation using SAS
Authors: Whitehead John
Published: September 2010

The methodology of group sequential trials is now well established and widely implemented. The benefits of the group sequential approach are generally acknowledged, and its use, when applied properly, is accepted by researchers and regulators. This article describes how a wide range of group sequential designs can easily be implemented using two accessible SAS functions. One of these, PROBBNRM is a standard function, while the other, SEQ, is part of the interactive matrix language of SAS, PROC IML. The account focuses on the essentials of the approach and reveals how straightforward it can be. The design of studies is described, including their evaluation in terms of the distribution of final sample size. The conduct of the interim analyses is discussed, with emphasis on the consequences of inevitable departures from the planned schedule of information accrual. The computations required for the final analysis, allowing for the sequential design, are closely related to those conducted at the design stage. Illustrative examples are given and listings of suitable of SAS code are provided.
Confidence interval construction for proportion ratio in paired studies based on hybrid method
Authors: Tang Man-Lai , Li Hui-Qiong , Tang Nian-Sheng
Published: September 2010

In this article, we consider confidence interval construction for proportion ratio in paired samples. Previous studies usually reported that score-based confidence intervals consistently outperformed other asymptotic confidence intervals for correlated proportion difference and ratio. However, score-based confidence intervals may not possess closed-form solutions and iterative procedures are therefore required. This article investigates the problem of confidence interval construction for ratio of two correlated proportions based on a hybrid method. Briefly, the hybrid method simply combines two separate confidence intervals for two individual proportions to produce a hybrid confidence interval for the ratio of the two individual proportions in paired studies. Most importantly, confidence intervals based on this hybrid method possess explicit solutions. Our simulation studies indicate that hybrid Wilson score confidence intervals based on Fieller's theorem performs well. The proposed confidence intervals will be illustrated with three real examples.
Assessing Vulnerable and Strategic Positions in a Criminal Network
Authors: Morselli Carlo
Published: September 2010

This study focuses on individual positioning within an illegal drug distribution network surrounding a reputed criminal organization (the Quebec Hells Angels). The aim is to distinguish between participants who were positioned vulnerably and/or strategically during a period when the network was targeted by an intensive law-enforcement investigation. Two centrality measures are used throughout the analysis. Degree centrality accounts for the number of direct contacts surrounding a participant. Betweenness centrality accounts for a participant’s brokerage leverage by measuring the scope of indirect relationships that s/he mediates. The final results reveal how differential positions in the network influence the judicial outcomes (arrests) within the case. Participants with high degree centrality were more likely to be arrested. Participants with high betweenness centrality were less likely to be arrested. Most importantly for law-enforcement concerns, those participants with high brokerage level were less likely to be members of the Hells Angels, thus suggesting that targeting strategies must take consider the patterns that represent an offender’s network at any given time, rather than simply focusing on an offender’s status and reputation within a criminal organization.
End-of-Life Caregiving Trajectories
Authors: Penrod Janice , Hupcey Judith E. , Baney Brenda L. , Loeb Susan J.
Published: September 2010

The purpose of this study is to illustrate variations in caregiving trajectories as described by informal family caregivers providing end-of-life care. Instrumental case study methodology is used to contrast the nature, course, and duration of the phases of caregiving across three distinct end-of-life trajectories: expected death trajectory , mixed death trajectory, and unexpected death trajectory. The sample includes informal family caregivers ( n = 46) providing unpaid end-of-life care to others suffering varied conditions (e.g., cancer, organ failure, amyotrophic lateral sclerosis). The unifying theme of end-of-life caregiving is “seeking normal” as family caregivers worked toward achieving a steady state, or sense of normal during their caregiving experiences. Distinct variations in the caregiving experience correspond to the death trajectory. Understanding caregiving trajectories that are manifest in typical cases encountered in clinical practice will guide nurses to better support informal caregivers as they traverse complex trajectories of end-of-life care.
Gauging the value of good data: Informational embodiment quantification
Authors: Thornton Chris
Published: September 2010

While there is increasing recognition of how relations of embodiment can be exploited for achievement of cognitive goals, we still lack any general method for formalizing the benefits that are then obtained, or for quantifying them. The present article describes a method that can be used to calculate the informational benefit obtained when embodiment becomes a vehicle for generation of ‘‘good data,’’ that is, data exhibiting behaviorally salient correlations.
The Life of Suggestions
Authors: Pearce Cathie
Published: September 2010

Using the notion of a suggestion, or rather charting the life of suggestions, this article considers the happenings of chance and embodiment as the “problems that got away.” The life of suggestions helps us to ask how connectivities are made, how desire functions, and how “immanence” rather than “transcendence” can open up the politics and ethics that are at play. The text explores movements in thought, what it means to bring the unthought into thought, and how what is “not yet” thought might regenerate positive and creative freedoms that we could tentatively call “hope” in soldering new scenarios for inquiry and pedagogy. Claire Colebrook asks, At what point do we begin or cease to imagine a future? This article explores and experiments with what it might mean to affirm life as suggestion and to let go of the allegiances and attachments that prevent us from seeing alternatives.1
Incidence of myelodysplastic syndromes in patients receiving concurrent myelosuppressive chemotherapy and pegfilgrastim
Authors: Covert Wendy M , Murillo Jose R , Cox James E
Published: September 2010

Background. The World Health Organization classifies myelodysplastic syndromes (MDS) as a group of hematologic malignancies where at least one myeloid lineage contains ≥10% cells with myelodysplasia. Therapy-related MDS (t-MDS) may result from treatment with myelosuppressive chemotherapy and/or radiation. Myeloid growth factors, such as pegfilgrastim, have also been investigated as a possible risk factor for development of t-MDS. National guidelines and myeloid growth factor prescribing information recommend administering myeloid growth factors after a minimum of 24 h following myelosuppressive chemotherapy. Some evidence suggests that administering myeloid growth factors and myelosuppressive chemotherapy concurrently may increase the risk of developing t-MDS.

Objective. To evaluate the incidence of t-MDS in patients who received pegfilgrastim and chemotherapy on the same day compared to patients receiving pegfilgrastim at least 1 day following completion of their chemotherapy.

Methods. A retrospective chart review was performed to identify all patients who received myelosuppressive chemotherapy and pegfilgrastim on the same day between January 2003 and December 2007. Any initial diagnosis of t-MDS was clinically confirmed.

Results. A total of 227 patients received myelosuppressive chemotherapy and pegfilgrastim on the same day. Median time to follow-up was 3.47 years (IQR 1.15). Two patients had a confirmed diagnosis of t-MDS. The incidence of t-MDS in patients receiving concurrent myelosuppressive chemotherapy and pegfilgrastim in our study population is 0.88%.

Conclusion. Administering pegfilgrastim at least 1 day after myelosuppressive chemotherapy may help reduce the risk of t-MDS, but more studies with longer follow-up are needed to confirm this finding.
Key components of intravenous chemotherapy labeling: A systematic review and practice guideline
Authors: Trudeau Maureen , Green Esther , Cosby Roxanne , Charbonneau Flay , Easty Tony , Ko Yooj , Marchand Patti , David U , Berger Nadia , Hertz Sherrie
Published: September 2010

Objective. To determine the necessary components and formatting of an intravenous chemotherapy label to maximize safe delivery and minimize errors.

Date sources. The MEDLINE and EMBASE databases (up to April 2009) were searched for relevant evidence. Reference lists from retained studies were then searched for additional trials. An environmental scan was also conducted to locate other published and unpublished sources of information.

Study selection. Relevant articles were selected and reviewed by one methodologist. Articles were selected for inclusion if they were published English language reports of Phases II or III randomized controlled trials, other comparative studies, single-arm studies, practice guidelines, or systematic reviews with or without meta-analyses, which related to the study question. MEDLINE and EMBASE searches yielded 685 potential studies of which 17 met the inclusion criteria. The environmental scan located one guideline. Three additional relevant studies were identified during the external review process. In total, 21 documents met the inclusion criteria.

Data extraction. Data were extracted by one methodologist. Quality of systematic reviews was assessed using the AMSTAR tool. All other studies were evaluated based on study characteristics applicable to the particular study design.

Data synthesis. The evidence collected and the consensus of expert opinion of Cancer Care Ontario’s Chemotherapy Labeling Panel form the basis of a series of recommendations for the generation of intravenous chemotherapy labels including formatting, required information, and order of information. These guidelines inform the efficient, effective, and safe administration of intravenous chemotherapy. Illustrative examples are provided.
Spectral Characteristics of UV Light Existing in Indoor Visual Environment
Authors: Hong Soo Lim  , Kim Gon
Published: September 2010

This paper deals with the spectral characteristics of ultraviolet (UV) ray in an architectural environment. Visual quality is one of the most important factors in the design of interior environment of building, conferring the necessary mood suitable to the built environment for the occupants’ required functions. Visual environment can also have an impact on the healthy status of the human beings affecting both the mental and physical wellbeing of the occupants. As a natural resource of lighting, daylight arrives on the surface of the earth as one of the electric waves composed of UV, visual and infrared rays. Visual ray plays a significant role in the formulation of the visual environment due to its superior sensitivity on human acuity. However, the UV rays being the more energetic ones would penetrate into built environments and they can be very harmful for the occupants. The spectral characteristics and intensities of UV rays can be affected by architectural features, such as the incident angles and locations of the measurement. This study investigated the impact of time on the measurement of the spectral characteristics of UV rays. Other factors such as the distance from the window and the incidence direction were also included in the study. The results were expressed in terms of distribution and intensity of the wavelength. The correlation among UV intensity, distance, time and direction was also established by the study.
Finite mixture models for clustering multilevel data with multiple cluster structures
Authors: Galimberti Giuliano , Soffritti Gabriele
Published: September 2010

Finite mixture models are useful tools for clustering two-way datasets within a sound statistical framework which can assess some important questions, such as how many clusters are there in the data. Models that can also be used for clustering multilevel data have been proposed, with the intent to produce clusterings of units at every level on the basis of all the available variables, considering the hierarchical structure of the dataset. This paper introduces a new class of mixture models for datasets with two levels that makes it possible to discover a clustering of level 2 units and different clusterings of level 1 units corresponding to different subsets of the variables (multiple cluster structures). This new class is obtained by adapting a mixture model proposed to identify multiple cluster structures in a data matrix to the multilevel situation. The usefulness of the new method is shown using simulated data and a real example.
Flexible hazard ratio curves for continuous predictors in multi-state models
Authors: Cadarso-Suárez Carmen , Meira-Machado Luís , Kneib Thomas , Gude Francisco
Published: September 2010

Multi-state models (MSMs) are very useful for describing complicated event history data. These models may be considered as a generalization of survival analysis where survival is the ultimate outcome of interest but where intermediate (transient) states are identified. One major goal in clinical applications of MSMs is to study the relationship between the different covariates and disease evolution. Usually, MSMs are assumed to be parametric, and the effects of continuous predictors on log-hazards are modelled linearly. In practice, however, the effect of a given continuous predictor can be unknown, and its form may be different in all transitions. In this paper,we propose a P-spline approach that allows for non-linear relationships between continuous predictors and survival in the multi-state framework. To better understand the effects at each transition, results are expressed in terms of hazard ratio curves, taking a specific covariate value as reference. Confidence bands for these curves are also derived. The proposed methodology was applied to a database on breast cancer, using a progressive three-state model. This application revealed hitherto unreported effects: whereas DNA index is only an important non-linear predictor of recurrence, the percentage of cells in phase S is a significant predictor of both recurrence and mortality.
Quantile regression analysis of the Italian school system
Authors: Furno Marilena
Published: September 2010

We analyze the score on a reading literacy test of 15-year-old Italian students. The data depict a fracture in the Italian school system. By means of quantile regressions (QR) and by repeatedly implementing a QR-based test for structural break, computed in different sub-samples and at various quantiles, we can not only pin down the determinants of the gap but also rank them. We find that the difference in curricula is the main factor in explaining the gap in the students’ scores, and the regional difference is linked to structural and behavioural variables, like poor library facilities and student absenteeism, both mirroring the economic lag of the southern Italian regions. In terms of policy actions, curbing absenteeism in the south could help reduce the regional gap. If instead the target is to enhance excellence, funds could be directed towards academic track and/or north-centre regions.
Sports Health Magnetic Resonance Imaging Challenge
Authors: Howell Gary A. , Stadnick Michael E. , Awh Mark H.
Published: September 2010

Injuries to the Lisfranc ligament complex are often suspected, particularly in the setting of midfoot pain without radiographic abnormality. Knowledge of the anatomy and magnetic resonance imaging findings of injuries to this region is helpful for the diagnosing and treating physicians.
Survey Identifies Barriers to AE-C Recertification
Authors: Grimes Kristen , Mercure Michelle
Published: September 2010

The goal of the certification of asthma educators is to improve the quality and consistency of standardized asthma education, based on the Guidelines for the Diagnosis and Management of Asthma (EPR-3). Certification also paves the way toward reimbursement for asthma education. The Wisconsin Asthma Coalition (WAC) was interested in the value of asthma educator certification and whether AE-C will seek recertification. The creation of the AE-C survey was led by the WAC education workgroup. The survey questions assessed intention to take the recertification exam, perceived value and utilization of AE-C at current place of employment, perceived benefits of AE-C, compensation received, and willingness to serve as a resource and mentor. The survey was posted on SurveyMonkey.com, and the link was e-mailed to 124 AE-Cs located in Wisconsin. The response rate was 56.6% (N = 60). Forty-two percent did not intend to retake the exam upon expiration. The 3 primary reasons for not retaking the exam included no longer working in the field, no benefit from being an AE-C, and exam cost. Fifty percent felt having an AE-C on staff was not valued by their current employer. AE-Cs alone are rarely required to provide asthma services (range, 1.8%-7.1%; n = 56). Most often, either the AE-C or another staff member performs asthma services (range, 41.1%-64.3%), with about a quarter of these preferring AE-C (range, 21.7%-27.8%). Seventy-five percent felt their employer should increase utilization of AE-C. The cost of the National Asthma Educator Certification Board exam, perception of little benefit of AE-C, and perceived value of AE-C by current employers serve as significant barriers for AE-Cs to seek recertification.
STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus–encoded protein LMP-1 in absence of EBNA-2: implications for the type II EBV latent gene expression in Hodgkin lymphoma
Authors: Kis Loránd L. , Gerasimčik Natalija , Salamon Daniel , Persson Emma K. , Nagy Noémi , Klein George , Severinson Eva , Klein Eva
Published: September 2010

In line with the B-lymphotropic nature of Epstein-Barr virus (EBV), the virus is present in several types of B-cell lymphomas. EBV expresses a different set of latent genes in the associated tumors, such as EBV nuclear antigen 1 (EBNA-1) and latent membrane proteins (LMPs; type II latency) in classical Hodgkin lymphomas (HLs). We previously reported that exposure of in vitro EBV-converted, HL-derived cell line KMH2-EBV to CD40-ligand and interleukin-4 (IL-4) induced the expression of LMP-1. Here, we show that exposure to IL-4 or IL-13 alone induced LMP-1 in the absence of EBNA-2. Induction of LMP-1 by IL-4 and IL-13 was mediated by the signal transducer signal transducer and activator of transcription 6 (STAT6) and a newly defined high-affinity STAT6-binding site in the LMP-1 promoter. IL-4 induced LMP-1 also in Burkitt lymphoma–derived lines and in tonsillar B cells infected with the EBNA-2–deficient EBV strain P3HR-1. Furthermore, coculture of EBV-carrying Burkitt lymphoma cells with activated CD4+ T cells resulted in the induction of LMP-1 in the absence of EBNA-2. Because Hodgkin/Reed-Sternberg cells are known to secrete IL-13, to have constitutively activated STAT6, and to be closely surrounded by CD4+ T cells, these mechanisms may be involved in the expression of LMP-1 in EBV-positive chronic HLs.
Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232)
Authors: Zonder Jeffrey A. , Crowley John , Hussein Mohamad A. , Bolejack Vanessa , Moore Dennis F. , Whittenberger Brock F. , Abidi Muneer H. , Durie Brian G. M. , Barlogie Bart
Published: September 2010

The Southwest Oncology Group conducted a randomized trial comparing lenalidomide (LEN) plus dexamethasone (DEX; n = 97) to placebo (PLC) plus DEX (n = 95) in newly diagnosed myeloma. Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 together with LEN 25 mg/day for 28 days or PLC. Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC. Crossover from PLC-DEX to LEN-DEX was encouraged on progression. One-year progression-free survival, overall response rate, and very good partial response rate were superior with LEN-DEX (78% vs 52%, P = .002; 78% vs 48%, P < .001; 63% vs 16%, P < .001), whereas 1-year overall survival was similar (94% vs 88%; P = .25). Toxicities were more pronounced with LEN-DEX (neutropenia grade 3 or 4: 21% vs 5%, P < .001; thromboembolic events despite aspirin prophylaxis: 23.5% [initial LEN-DEX or crossover] vs 5%; P < .001). This trial was registered at www.clinicaltrials.gov as #NCT00064038.
MetNetGE: interactive views of biological networks and ontologies
Authors: Jia Ming , Choi Suh-Yeon , Reiners Dirk , Wurtele Eve S , Dickerson Julie A
Published: September 2010

Background

Linking high-throughput experimental data with biological networks is a key step for understanding complex biological systems. Currently, visualization tools for large metabolic networks often result in a dense web of connections that is difficult to interpret biologically. The MetNetGE application organizes and visualizes biological networks in a meaningful way to improve performance and biological interpretability.

Results

MetNetGE is an interactive visualization tool based on the Google Earth platform. MetNetGE features novel visualization techniques for pathway and ontology information display. Instead of simply showing hundreds of pathways in a complex graph, MetNetGE gives an overview of the network using the hierarchical pathway ontology using a novel layout, called the Enhanced Radial Space-Filling (ERSF) approach that allows the network to be summarized compactly. The non-tree edges in the pathway or gene ontology, which represent pathways or genes that belong to multiple categories, are linked using orbital connections in a third dimension. Biologists can easily identify highly activated pathways or gene ontology categories by mapping of summary experiment statistics such as coefficient of variation and overrepresentation values onto the visualization. After identifying such pathways, biologists can focus on the corresponding region to explore detailed pathway structure and experimental data in an aligned 3D tiered layout. In this paper, the use of MetNetGE is illustrated with pathway diagrams and data from E. coli and Arabidopsis.

Conclusions

MetNetGE is a visualization tool that organizes biological networks according to a hierarchical ontology structure. The ERSF technique assigns attributes in 3D space, such as color, height, and transparency, to any ontological structure. For hierarchical data, the novel ERSF layout enables the user to identify pathways or categories that are differentially regulated in particular experiments. MetNetGE also displays complex biological pathway in an aligned 3D tiered layout for exploration.
BPDA - A Bayesian peptide detection algorithm for mass spectrometry
Authors: Sun Youting , Zhang Jianqiu , Braga-Neto Ulisses , Dougherty Edward R
Published: September 2010

Background

Mass spectrometry (MS) is an essential analytical tool in proteomics. Many existing algorithms for peptide detection are based on isotope template matching and usually work at different charge states separately, making them ineffective to detect overlapping peptides and low abundance peptides.

Results

We present BPDA, a Bayesian approach for peptide detection in data produced by MS instruments with high enough resolution to baseline-resolve isotopic peaks, such as MALDI-TOF and LC-MS. We model the spectra as a mixture of candidate peptide signals, and the model is parameterized by MS physical properties. BPDA is based on a rigorous statistical framework and avoids problems, such as voting and ad-hoc thresholding, generally encountered in algorithms based on template matching. It systematically evaluates all possible combinations of possible peptide candidates to interpret a given spectrum, and iteratively finds the best fitting peptide signal in order to minimize the mean squared error of the inferred spectrum to the observed spectrum. In contrast to previous detection methods, BPDA performs deisotoping and deconvolution of mass spectra simultaneously, which enables better identification of weak peptide signals and produces higher sensitivities and more robust results. Unlike template-matching algorithms, BPDA can handle complex data where features overlap. Our experimental results indicate that BPDA performs well on simulated data and real MS data sets, for various resolutions and signal to noise ratios, and compares very favorably with commonly used commercial and open-source software, such as flexAnalysis, OpenMS, and Decon2LS, according to sensitivity and detection accuracy.

Conclusion

Unlike previous detection methods, which only employ isotopic distributions and work at each single charge state alone, BPDA takes into account the charge state distribution as well, thus lending information to better identify weak peptide signals and produce more robust results. The proposed approach is based on a rigorous statistical framework, which avoids problems generally encountered in algorithms based on template matching. Our experiments indicate that BPDA performs well on both simulated data and real data, and compares very favorably with commonly used commercial and open-source software. The BPDA software can be downloaded from http://gsp.tamu.edu/Publications/supplementary/sun10a/bpda.
Identification and functional analysis of NOL7 nuclear and nucleolar localization signals
Authors: Zhou Guolin , Doçi Colleen L , Lingen Mark W
Published: September 2010

Background

NOL7 is a candidate tumor suppressor that localizes to a chromosomal region 6p23. This locus is frequently lost in a number of malignancies, and consistent loss of NOL7 through loss of heterozygosity and decreased mRNA and protein expression has been observed in tumors and cell lines. Reintroduction of NOL7 into cells resulted in significant suppression of in vivo tumor growth and modulation of the angiogenic phenotype. Further, NOL7 was observed to localize to the nucleus and nucleolus of cells. However, the mechanisms regulating its subcellular localization have not been elucidated.

Results

An in vitro import assay demonstrated that NOL7 requires cytosolic machinery for active nuclear transport. Using sequence homology and prediction algorithms, four putative nuclear localization signals (NLSs) were identified. NOL7 deletion constructs and cytoplasmic pyruvate kinase (PK) fusion proteins confirmed the functionality of three of these NLSs. Site-directed mutagenesis of PK fusions and full-length NOL7 defined the minimal functional regions within each NLS. Further characterization revealed that NLS2 and NLS3 were critical for both the rate and efficiency of nuclear targeting. In addition, four basic clusters within NLS2 and NLS3 were independently capable of nucleolar targeting. The nucleolar occupancy of NOL7 revealed a complex balance of rapid nucleoplasmic shuttling but low nucleolar mobility, suggesting NOL7 may play functional roles in both compartments. In support, targeting to the nucleolar compartment was dependent on the presence of RNA, as depletion of total RNA or rRNA resulted in a nucleoplasmic shift of NOL7.

Conclusions

These results identify the minimal sequences required for the active targeting of NOL7 to the nucleus and nucleolus. Further, this work characterizes the relative contribution of each sequence to NOL7 nuclear and nucleolar dynamics, the subnuclear constituents that participate in this targeting, and suggests a functional role for NOL7 in both compartments. Taken together, these results identify the requisite protein domains for NOL7 localization, the kinetics that drive this targeting, and suggest NOL7 may function in both the nucleus and nucleolus.
Identification and characterization of microRNAs in Clonorchis sinensis of human health significance
Authors: Xu Min-Jun , Liu Quan , Nisbet Alasdair J , Cai Xian-Quan , Yan Chao , Lin Rui-Qing , Yuan Zi-Guo , Song Hui-Qun , He Xian-Hui , Zhu Xing-Quan
Published: September 2010

Background

Clonorchis sinensis is a zoonotic parasite causing clonorchiasis-associated human disease such as biliary calculi, cholecystitis, liver cirrhosis, and it is currently classified as carcinogenic to humans for cholangiocarcinoma. MicroRNAs (miRNAs) are non-coding, regulating small RNA molecules which are essential for the complex life cycles of parasites and are involved in parasitic infections. To identify and characterize miRNAs expressed in adult C. sinensis residing chronically in the biliary tract, we developed an integrative approach combining deep sequencing and bioinformatic predictions with stem-loop real-time PCR analysis.

Results

Here we report the use of this approach to identify and clone 6 new and 62,512 conserved C. sinensis miRNAs which belonged to 284 families. There was strong bias on families, family members and sequence nucleotides in C. sinensis. Uracil was the dominant nucleotide, particularly at positions 1, 14 and 22, which were located approximately at the beginning, middle and end of conserved miRNAs. There was no significant "seed region" at the first and ninth positions which were commonly found in human, animals and plants. Categorization of conserved miRNAs indicated that miRNAs of C. sinensis were still innovated and concentrated along three branches of the phylogenetic tree leading to bilaterians, insects and coelomates. There were two miRNA strategies in C. sinensis for its parasitic life: keeping a large category of miRNA families of different animals and keeping stringent conserved seed regions with high active innovation in other places of miRNAs mainly in the middle and the end, which were perfect for the parasite to perform its complex life style and for host changes.

Conclusions

The present study represented the first large scale characterization of C. sinensis miRNAs, which have implications for understanding the complex biology of this zoonotic parasite, as well as miRNA studies of other related species such as Opisthorchis viverrini and Opisthorchis felineus of human and animal health significance.
An improved, high-quality draft genome sequence of the Germination-Arrest Factor-producing Pseudomonas fluorescens WH6
Authors: Kimbrel Jeffrey A , Givan Scott A , Halgren Anne B , Creason Allison L , Mills Dallice I , Banowetz Gary M , Armstrong Donald J , Chang Jeff H
Published: September 2010

Background

Pseudomonas fluorescens is a genetically and physiologically diverse species of bacteria present in many habitats and in association with plants. This species of bacteria produces a large array of secondary metabolites with potential as natural products. P. fluorescens isolate WH6 produces Germination-Arrest Factor (GAF), a predicted small peptide or amino acid analog with herbicidal activity that specifically inhibits germination of seeds of graminaceous species.

Results

We used a hybrid next-generation sequencing approach to develop a high-quality draft genome sequence for P. fluorescens WH6. We employed automated, manual, and experimental methods to further improve the draft genome sequence. From this assembly of 6.27 megabases, we predicted 5876 genes, of which 3115 were core to P. fluorescens and 1567 were unique to WH6. Comparative genomic studies of WH6 revealed high similarity in synteny and orthology of genes with P. fluorescens SBW25. A phylogenomic study also placed WH6 in the same lineage as SBW25. In a previous non-saturating mutagenesis screen we identified two genes necessary for GAF activity in WH6. Mapping of their flanking sequences revealed genes that encode a candidate anti-sigma factor and an aminotransferase. Finally, we discovered several candidate virulence and host-association mechanisms, one of which appears to be a complete type III secretion system.

Conclusions

The improved high-quality draft genome sequence of WH6 contributes towards resolving the P. fluorescens species, providing additional impetus for establishing two separate lineages in P. fluorescens. Despite the high levels of orthology and synteny to SBW25, WH6 still had a substantial number of unique genes and represents another source for the discovery of genes with implications in affecting plant growth and health. Two genes are demonstrably necessary for GAF and further characterization of their proteins is important for developing natural products as control measure against grassy weeds. Finally, WH6 is the first isolate of P. fluorescens reported to encode a complete T3SS. This gives us the opportunity to explore the role of what has traditionally been thought of as a virulence mechanism for non-pathogenic interactions with plants.