bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional profiling of the murine cutaneous response during initial and subsequent infestations with Ixodes scapularis nymphs
Authors: Heinze Dar M , Wikel Stephen K , Thangamani Saravanan , Alarcon-Chaidez Francisco J 
Published: February 2012

AbstractBackgroundIxodes scapularisticks are hematophagous arthropods capable of transmitting many infectious agents to humans. The process of blood feeding is an extended and continuous interplay between tick and host responses. While this process has been studied extensivelyin vitro, no global understanding of the host response to ticks has emerged.MethodsTo address this issue, we used PCR-arrays to measure skin-specific expression of 233 discrete genes at 8 time points during primary and secondary infestations of mice with pathogen-freeI. scapularisnymphs. Selected results were then validated at the mRNA and protein levels by additional real-time PCR and bioplex assay.ResultsPrimary infestation was characterized by the late induction of an innate immune response. Lectin pattern recognition receptors, cytokines, and chemokines were upregulated consistent with increased neutrophil and macrophage migration. Gene ontology and pathway analyses of downregulated genes suggested inhibition of gene transcription and Th17 immunity. During the secondary infestation, additional genes were modulated suggesting a broader involvement of immune cells including CD8 and CD4 positive T lymphocytes. The cytokine response showed a mixed Th1/Th2 profile with a potential for T regulatory cell activity. Key gene ontology clusters observed during the secondary infestation were cell migration and activation. Matrix metalloproteinases were upregulated, apoptosis-related genes were differentially modulated, and immunoreceptor signaling molecules were upregulated. In contrast, transcripts related to mitogenic, WNT, Hedgehog, and stress pathways were downregulated.ConclusionsOur results support a model of tick feeding where lectin pattern recognition receptors orchestrate an innate inflammatory response during primary infestation that primes a mixed Th1/Th2 response upon secondary exposure. Tick feeding inhibits gene transcription and Th17 immunity. Salivary molecules may also inhibit upregulation of mitogenic, WNT, Hedgehog, and stress pathways and enhance the activity of T regulatory cells, production of IL-10, and suppressors of cytokine signaling molecules (SOCS). This study provides the first comprehensive transcriptional analysis of the murine host response at theI. scapularisbite site and suggests both a potential model of the host cutaneous response and candidate genes for further description and investigation.
The neuropeptide neuromedin U promotes autoantibody-mediated arthritis
Authors: Rao Sindhuja M , Auger Jennifer L , Gaillard Philippe , Weissleder Ralph , Wada Etsuko , Torres Richard , Kojima Masayasu , Benoist Christophe , Mathis Diane , Binstadt Bryce A 
Published: February 2012

Abstract
Introduction
Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary goal of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects.

Methods
Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU deficiency impacted the early mast-cell-dependent vascular leak response induced by these autoantibodies. Bone-marrow chimeric mice were generated to determine whether pro-inflammatory NMU is derived from hematopoietic cells or stromal cells. Mice lacking the known NMU receptors singly and in combination were used to determine susceptibility to serum-transferred arthritis and in vitro cellular responses to NMU.

Results
NMU-deficient mice developed less severe arthritis than control mice. Vascular leak was not affected by NMU deficiency. NMU expression by bone-marrow-derived cells mediated the pro-arthritogenic effect. Deficiency of all of the known NMU receptors, however, had no impact on arthritis severity and did not affect the ability of NMU to stimulate intracellular calcium flux.

Conclusions
NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. NMU derived from hematopoietic cells, not neurons, promotes the development of autoantibody-induced inflammatory arthritis. This effect is mediated by a receptor other than the currently known NMU receptors.
Small interfering RNA library screen identified polo-like kinase-1 (PLK1) as a potential therapeutic target for breast cancer that uniquely eliminates tumor-initiating cells
Authors: Hu Kaiji , Law Jennifer H , Fotovati Abbas , Dunn Sandra E 
Published: February 2012

Abstract
Introduction
Triple-negative breast cancer (TNBC) high rate of relapse is thought to be due to the presence of tumor-initiating cells (TICs), molecularly defined as being CD44high/CD24-/low. TICs are resilient to chemotherapy and radiation. However, no currently accepted molecular target exists against TNBC and, moreover, TICs. Therefore, we sought the identification of kinase targets that inhibit TNBC growth and eliminate TICs.

Methods
A genome-wide human kinase small interfering RNA (siRNA) library (691 kinases) was screened against the TNBC cell line SUM149 for growth inhibition. Selected siRNAs were then tested on four different breast cancer cell lines to confirm the spectrum of activity. Their effect on the CD44high subpopulation and sorted CD44high/CD24-/low cells of SUM149 also was studied. Further studies were focused on polo-like kinase 1 (PLK1), including its expression in breast cancer cell lines, effect on the CD44high/CD24-/low TIC subpopulation, growth inhibition, mammosphere formation, and apoptosis, as well as the activity of the PLK1 inhibitor, BI 2536.

Results
Of the 85 kinases identified in the screen, 28 of them were further silenced by siRNAs on MDA-MB-231 (TNBC), BT474-M1 (ER+/HER2+, a metastatic variant), and HR5 (ER+/HER2+, a trastuzumab-resistant model) cells and showed a broad spectrum of growth inhibition. Importantly, 12 of 28 kinases also reduced the CD44high subpopulation compared with control in SUM149. Further tests of these 12 kinases directly on a sorted CD44high/CD24-/low TIC subpopulation of SUM149 cells confirmed their effect. Blocking PLK1 had the greatest growth inhibition on breast cancer cells and TICs by about 80% to 90% after 72 hours. PLK1 was universally expressed in breast cancer cell lines, representing all of the breast cancer subtypes, and was positively correlated to CD44. The PLK1 inhibitor BI 2536 showed similar effects on growth, mammosphere formation, and apoptosis as did PLK1 siRNAs. Finally, whereas paclitaxel, doxorubicin, and 5-fluorouracil enriched the CD44high/CD24-/low population compared with control in SUM149, subsequent treatment with BI 2536 killed the emergent population, suggesting that it could potentially be used to prevent relapse.

Conclusion
Inhibiting PLK1 with siRNA or BI 2536 blocked growth of TNBCs including the CD44high/CD24-/low TIC subpopulation and mammosphere formation. Thus, PLK1 could be a potential therapeutic target for the treatment of TNBC as well as other subtypes of breast cancer.
Uptake and Economic Impact of First-Cycle Colony-Stimulating Factor Use During Adjuvant Treatment of Breast Cancer
Authors: Hershman Dawn L. , Wilde Elizabeth T. , Wright Jason D. , Buono Donna L. , Kalinsky Kevin , Malin Jennifer L. , Neugut Alfred I. 
Published: February 2012

Purpose In 2002, pegfilgrastim was approved by the US Food and Drug Administration and the benefits of dose-dense breast cancer chemotherapy, especially for hormone receptor (HR) –negative tumors, were reported. We examined first-cycle colony-stimulating factor use (FC-CSF) before and after 2002 and estimated US expenditures for dose-dense chemotherapy. Methods We identified patients in Surveillance, Epidemiology, and End Results–Medicare greater than 65 years old with stages I to III breast cancer who had greater than one chemotherapy claim within 6 months of diagnosis(1998 to 2005) and classified patients with an average cycle length less than 21 days as having received dose-dense chemotherapy. The associations of patient, tumor, and physician-related factors with the receipt of any colony-stimulating factor (CSF) and FC-CSF use were analyzed by using generalized estimating equations. CSF costs were estimated for patients who were undergoing dose-dense chemotherapy. Results Among the 10,773 patients identified, 5,266 patients (48.9%) had a CSF claim. CSF use was stable between 1998 and 2002 and increased from 36.8% to 73.7% between 2002 and 2005, FC-CSF use increased from 13.2% to 67.9%, and pegfilgrastim use increased from 4.1% to 83.6%. In a multivariable analysis, CSF use was associated with age and chemotherapy type and negatively associated with black/Hispanic race, rural residence, and shorter chemotherapy duration. FC-CSF use was associated with high socioeconomic status but not with age or race/ethnicity. The US annual CSF expenditure for women with HR-positive tumors treated with dose-dense chemotherapy is estimated to be $38.8 million. Conclusion A rapid increase in FC-CSF use occurred over a short period of time, which was likely a result of the reported benefits of dose-dense chemotherapy and the ease of pegfilgrastim administration. Because of the increasing evidence that elderly HR-positive patients do not benefit from dose-dense chemotherapy, limiting pegfilgrastim use would combat the increasing costs of cancer care.
Screening for Measles Vaccination in Young Japanese Non‐healthcare Workers Through Self‐reported History
Authors: Nishiura Chihiro , Hashimoto Hideki 
Published: February 2012

Screening for Measles Vaccination in Young Japanese Non‐healthcare Workers Through Self‐reported History: Chihiro NISHIURA, et al. Department of Safety and Health, Tokyo Gas Co., Ltd.—ObjectivesThe aim of this study was to examine the efficacy of a self‐administered questionnaire as a prescreening tool to determine the immune status against measles among non‐healthcare workers.MethodsThe study subjects were Japanese non‐healthcare workers aged 19–30 yr employed at a gas company that underwent an annual health checkup in 2009. Their histories of measles infection, vaccination and possible contact with measles patients were collected through a self‐administered questionnaire. The sensitivity and specificity of these self‐reports were analyzed against a serum anti‐measles IgG assay as a gold standard.ResultsOf the 509 respondents, 93.3% had immunity against measles. The sensitivity, specificity and positive predictive values for the self‐report questionnaire were 14.1, 97.1 and 98.5% for infection history; 39.2, 73.5 and 95.4% for vaccination history; and 13.1, 85.3 and 92.5% for possible contact history, respectively.ConclusionsSelf‐reported histories poorly predicted immune status against measles in young Japanese non‐healthcare workers. The results suggest that a universal serological screening is still the most effective method available to identify those who require measles vaccination.
Pediatric Training and Career Intentions, 2003–2009
Authors: Frintner Mary Pat , Cull William L. 
Published: February 2012

OBJECTIVES:
To examine trends in pediatric residents’ training and job search experiences from 2003 through 2009.

METHODS:
Annual national random samples of 500 graduating pediatric residents from 2003 through 2005 and 1000 from 2006 through 2009 were surveyed. Responses were compared across years to identify trends. We examined resident demographics, training, satisfaction, career intentions, and job search experiences. Overall response rate was 61%.

RESULTS:
Between 2003 and 2009, there was an increase in the proportion of female graduating pediatric residents (69%–75%), residents from international medical schools (15%–23%), and levels of educational debt among the subgroup of residents with debt ($139 945 in 2003 to $166 972 in 2009). Residents consistently reported (&gt;90% of residents) that they would choose pediatrics again if they had the choice. By 2009, the majority was very satisfied with the quality of their training in most areas, with ratings improving across years in caring for children with special health care needs, evidence-based medicine, and using information technology in practice. Although primary care remained the most common clinical practice goal, there was a modest decline in interest in primary care practice across survey years, whereas interest in subspecialty practice increased. Residents accepting both general pediatric practice and hospitalist positions reported less difficulty in their job search over time.

CONCLUSIONS:
Despite continually changing demographics of pediatric training programs, residents overall remain very satisfied with their decision to become pediatricians. Pediatricians continue to face difficult financial challenges associated with rising debt, but they also report increasing job search success.
Resilience in Children Undergoing Stem Cell Transplantation: Results of a Complementary Intervention Trial
Authors: Phipps Sean , Peasant Courtney , Barrera Maru , Alderfer Melissa A. , Huang Qinlei , Vannatta Kathryn 
Published: February 2012

BACKGROUND:
Children undergoing stem cell transplantation (SCT) are thought to be at risk for increased distress, adjustment difficulties, and impaired health-related quality of life (HRQL). We report results of a multisite trial designed to improve psychological adjustment and HRQL in children undergoing SCT.

METHODS:
A total of 171 patients and parents from 4 sites were randomized to receive a child-targeted intervention; a child and parent intervention; or standard care. The child intervention included massage and humor therapy; the parent intervention included massage and relaxation/imagery. Outcomes included symptoms of depression and posttraumatic stress, HRQL, and benefit finding. Assessments were conducted by patient and parent report at admission and SCT week+24.

RESULTS:
Across the sample, significant improvements were seen on all outcomes from admission to week+24. Surprisingly, patients who had SCT reported low levels of adjustment difficulties at admission, and improved to normative or better than average levels of adjustment and HRQL at week+24. Benefit finding was high at admission and increased at week+24; however, there were no statistically significant differences between intervention arms for any of the measures.

CONCLUSIONS:
Although the results do not support the benefits of these complementary interventions in pediatric SCT, this may be explained by the remarkably positive overall adjustment seen in this sample. Improvements in supportive care, and a tendency for patients to find benefit in the SCT experience, serve to promote positive outcomes in children undergoing this procedure, who appear particularly resilient to the challenge.
Secondhand Smoke Exposure in Cars Among Middle and High School Students—United States, 2000–2009
Authors: King Brian A. , Dube Shanta R. , Tynan Michael A. 
Published: February 2012

OBJECTIVES:
Exposure to secondhand smoke (SHS) from cigarettes poses a significant health risk to nonsmokers. Among youth, the home is the primary source of SHS. However, little is known about youth exposure to SHS in other nonpublic areas, particularly motor vehicles.

METHODS:
Data were obtained from the 2000, 2002, 2004, 2006, and 2009 waves of the National Youth Tobacco Survey, a nationally representative survey of US students in grades 6 to 12. Trends in SHS exposure in a car were assessed across survey years by school level, gender, and race/ethnicity by using binary logistic regression.

RESULTS:
From 2000 to 2009, the prevalence of SHS exposure in cars declined significantly among both nonsmokers (39.0%–22.8%; trend P &lt; .001) and smokers (82.3%–75.3%; trend P &lt; .001). Among nonsmokers, this decline occurred across all school level, gender, and race/ethnicity subgroups.

CONCLUSIONS:
SHS exposure in cars decreased significantly among US middle and high school students from 2000 to 2009. Nevertheless, in 2009, over one-fifth of nonsmoking students were exposed to SHS in cars. Jurisdictions should expand comprehensive smoke-free policies that prohibit smoking in worksites and public places to also prohibit smoking in motor vehicles occupied by youth.
Improving the Organic Semiconductor- Metal Contact Interface in Printed High Performance Organic TFTs
Authors: Puntambekar Kanan , Stecker Lisa , Ulmer Kurt , Afentakis Themistokles , Droes Steven 
Published: February 2012

ABSTRACTOptimization of the interface between the organic semiconductor (OSC) & the source-drain (S/D) electrode is critical in order to improve organic thin film transistor (OTFT) device performance. This process typically involves coating the metal S/D electrodes with an optimal self-assembled thiol layer; a process that requires pristine metal surfaces for successful treatment. Obtaining contamination free surfaces can be challenging in the case of printed metal electrodes. Here we demonstrate an effective strategy to address this issue by introducing a brief low power forming gas plasma treatment prior to the surface coating step. We show a two orders of magnitude decrease in the contact resistance as a result of this treatment.
Potential for Measurement of Corrosion-Inhibitor-Micelle Presence as an Indicator of Optimum Dose
Authors: Mackenzie C.. , Rowley-Williams C.. , Achour M.. , Blumer D.. , Joosten M.. , Rowe M.. 
Published: February 2012

SummaryThis paper discusses the principle and proof of concept of a novel corrosion-management tool based on maintaining optimum corrosion-inhibitor dose in an inhibited environment. Film-forming corrosion inhibitors typically contain active ionic surfactant molecules, which adsorb on surfaces and form a protective barrier against corrosion. Upon saturation of surfaces by the inhibitor, the molecules are found in the aqueous phase as micelles or in the oil phase as reverse micelles. The proposed technique is based on the hypothesis that the presence of these micelles in the water phase could be used to indicate the total surface coverage and, therefore, the optimum dose.The technique has been applied in the laboratory simulating an actual inhibited multiphase production system. Fluorescent markers, which are extremely sensitive to micelle presence, have been developed and used during the laboratory testing. Results were compared with those from standard laboratory techniques, including interfacial tension (IFT) and particle-size analyses (diffraction), in order to determine the efficacy for micelle detection. Corrosion bubble tests were also used to determine any link to inhibitor efficiency.IFT results showed complex events occurring with increasing inhibitor concentration. The IFT vs. inhibitor concentration curve was nonclassical, probably because of the multicomponent nature of inhibitor formulations, but suggested micelle formation at approximately 150 ppm. Fluorescence analysis suggested that micelles formed starting at a 150-ppm dose. Particle-size analysis was consistent with micelle presence beyond this concentration. Separate experiments comparing fluorescence with corrosion rates demonstrated an apparent nonlinear variance with inhibitor concentration, supporting the hypothesis.The analytical comparisons supported the underlying principles of this micelle-detection technology. Development of a portable device is under way and will provide an important new tool for proactive corrosion management in the oil field as well as a useful laboratory qualification method.
Quantifying the Impact of Permeability Heterogeneity on Secondary-Recovery Performance
Authors: Rashid B.. , Muggeridge A.H.. H. , Bal A.. , Williams G.. 
Published: February 2012

Summary
An improved heterogeneity/homogeneity index is introduced that uses the shear-strain rate of the single-phase-velocity field to characterize heterogeneity and rank geological realizations in terms of their impact on secondary-recovery performance. The index is compared with the Dykstra-Parsons coefficient (Dykstra and Parsons 1950) and the dynamic Lorenz coefficient (Shook and Mitchell 2009). The results show that the index's ranking ability is preserved for miscible and immiscible displacements at different viscosity/mobility ratios. Neither the Dykstra-Parsons coefficient (Dykstra and Parsons 1950) nor the dynamic Lorenz coefficient (Shook and Mitchell 2009) can consistently discriminate between different realizations in terms of breakthrough time and oil recovery at 1 pore volume injected (PVI) for tracer flow or adverse-viscosity-ratio miscible and immiscible floods.
Storage of CO2 as Hydrate in Depleted Gas Reservoirs
Authors: Zatsepina Olga Ye. , Pooladi-Darvish Mehran 
Published: February 2012

Summary
With the increasing concern about climate change, the public, industry, and government are showing increased interest toward reducing carbon dioxide (CO2) emissions. Geological storage of CO2 is perceived to be one of the most promising methods to provide significant reduction in CO2 emissions over the short and medium term. However, one major concern regarding geological storage of CO2 is the possibility of leakage. CO2 under the pressure and temperature conditions encountered in most geological settings remains more buoyant than water. Processes that could lead to permanent trapping of CO2 include geochemical reactions, with the formation of solid minerals. This trapping mechanism is attractive because it converts the CO2 into a solid compound. However, the time scale of such reactions is perceived to be centuries to millennia. In contrast, the kinetics of CO2 -hydrate formation—leading to trapping of CO2 in the solid form—is quite fast, providing the opportunity for long-term storage of CO2. In this paper, geological settings suitable for formation of CO2 hydrate are investigated. We study storage of CO2 in depleted gas pools of northern Alberta.
Thermodynamic calculations suggest that CO2 hydrate is stable at temperatures that occur in a number of formations in northern Alberta, in an area where significant CO2 emissions are associated with production of oil sands and bitumen. Simulation results presented in this paper suggest that, upon CO2 injection into such depleted gas reservoirs, pressure would initially rise until conditions are appropriate for hydrate formation, enabling storage of large volumes of CO2 in solid form. Numerical-simulation results suggest that, because of tight packing of CO2 molecules in the solid (hydrate), the CO2 storage capacity of these pools is many times greater than their initial-gas-in-place capacity. This provides a local option for storage of a portion of the CO2 emissions there.
In this paper, we study the storage capacity of such depleted gas pools and examine the effect of various reservoir properties and operating conditions thereon. In particular, we study the effect of the in-situ gas in formation of mixed-gas hydrates; the effect of rise in temperature as a result of the exothermic reaction of hydrate formation; the effect of initial reservoir pressure, temperature, and porosity; and conditions for avoiding the deleterious formation of hydrate around the wellbore.