bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of Atorvastatin with Sulindac or Naproxen Profoundly Inhibits Colonic Adenocarcinomas by Suppressing the p65/β-Catenin/Cyclin D1 Signaling Pathway in Rats
Authors: Suh Nanjoo , Reddy Bandaru S. , DeCastro Andrew , Paul Shiby , Lee Hong Jin , Smolarek Amanda K. , So Jae Young , Simi Barbara , Wang Chung Xiou , Janakiram Naveena B. , Steele Vernon , Rao Chinthalapally V. 
Published: July 2011

Abstract
Evidence supports the protective role of nonsteroidal anti-inflammatory drugs (NSAID) and statins against colon cancer. Experiments were designed to evaluate the efficacies atorvastatin and NSAIDs administered individually and in combination against colon tumor formation. F344 rats were fed AIN-76A diet, and colon tumors were induced with azoxymethane. One week after the second azoxymethane treatment, groups of rats were fed diets containing atorvastatin (200 ppm), sulindac (100 ppm), naproxen (150 ppm), or their combinations with low-dose atorvastatin (100 ppm) for 45 weeks. Administration of atorvastatin at 200 ppm significantly suppressed both adenocarcinoma incidence (52% reduction, P = 0.005) and multiplicity (58% reduction, P = 0.008). Most importantly, colon tumor multiplicities were profoundly decreased (80%–85% reduction, P &lt; 0.0001) when given low-dose atorvastatin with either sulindac or naproxen. Also, a significant inhibition of colon tumor incidence was observed when given a low-dose atorvastatin with either sulindac (P = 0.001) or naproxen (P = 0.0005). Proliferation markers, proliferating cell nuclear antigen, cyclin D1, and β-catenin in tumors of rats exposed to sulindac, naproxen, atorvastatin, and/or combinations showed a significant suppression. Importantly, colon adenocarcinomas from atorvastatin and NSAIDs fed animals showed reduced key inflammatory markers, inducible nitric oxide synthase and COX-2, phospho-p65, as well as inflammatory cytokines, TNF-α, interleukin (IL)-1β, and IL-4. Overall, this is the first report on the combination treatment using low-dose atorvastatin with either low-dose sulindac or naproxen, which greatly suppress the colon adenocarcinoma incidence and multiplicity. Our results suggest that low-dose atorvastatin with sulindac or naproxen might potentially be useful combinations for colon cancer prevention in humans. Cancer Prev Res; 4(11); 1895–902. ©2011 AACR.
Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma
Authors: Wadhera Rishi K. , Kyle Robert A. , Larson Dirk R. , Dispenzieri Angela , Kumar Shaji , Lazarus Hillard M. , Rajkumar S. Vincent 
Published: July 2011

Abstract
During the course of multiple myeloma (MM), new monoclonal proteins of an isotype distinct from the original clone, referred to as secondary monoclonal gammopathy of undetermined significance (MGUS), have been described. We report on the frequency, characteristics, and outcome of secondary MGUS. Of the 1942 patients with MM, 128 (6.6%) developed a secondary MGUS, at a median of 12 months from the diagnosis of MM. The median duration of secondary MGUS was 5.9 months. Secondary MGUS was more common in patients after stem cell transplantation than in those who had not undergone such treatment (22.7% vs 1.6%, P &lt; .001). Overall survival was significantly superior in MM patients who developed secondary MGUS compared with the rest of the cohort (73 vs 38 months, respectively; P &lt; .001). The time of onset and the duration of secondary MGUS, as well as failure to resolve spontaneously, had an effect on overall survival and require further study.
Firm Strategies in the “Mid Tail” of Platform-Based Retailing
Authors: Jiang Baojun , Jerath Kinshuk , Srinivasan Kannan 
Published: July 2011

While millions of products are sold on its retail platform, Amazon.com itself stocks and sells only a very small fraction of them. Most of these products are sold by third-party sellers who pay Amazon a fee for each unit sold. Empirical evidence clearly suggests that Amazon tends to sell high-demand products and leave long-tail products for independent sellers to offer. We investigate how a platform owner such as Amazon, facing ex ante demand uncertainty, may strategically learn from these sellers' early sales which of the “mid-tail” products are worthwhile for its direct selling and which are best left for others to sell. The platform owner's “cherry-picking” of the successful products, however, gives an independent seller the incentive to mask any high demand by lowering his sales with a reduced service level (unobserved by the platform owner). We analyze this strategic interaction between a platform owner and an independent seller using a game-theoretic model with two types of sellers—one with high demand and one with low demand. We show that it may not always be optimal for the platform owner to identify the seller's demand. Interestingly, the platform owner may be worse off by retaining its option to sell the independent seller's product, whereas both types of sellers may benefit from the platform owner's threat of entry. The platform owner's entry option may reduce consumer surplus in the early period, although it increases consumer surplus in the later period. We also investigate how consumer reviews influence the market outcome.
Do Cultural Differences Between Contracting Parties Matter? Evidence from Syndicated Bank Loans
Authors: Giannetti Mariassunta , Yafeh Yishay 
Published: July 2011

We investigate whether cultural differences between professional decision makers affect financial contracts in a large data set of international syndicated bank loans. We find that more culturally distant lead banks offer borrowers smaller loans at a higher interest rate and are more likely to require third-party guarantees. These effects do not disappear following repeated interaction between borrower and lender and are economically sizable: A one-standard-deviation increase in cultural distance, approximately the distance between Canada and the United States or between Japan and South Korea, is associated with a 6.5 basis point higher loan spread; the loan spread increases by about 23 basis points if the bank-firm match involves culturally more distant parties, for example, from Japan and the United States. We also find that cultural differences not only affect the relation between borrower and lender, but also hamper risk sharing between participant banks and culturally distant lead banks. This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Imiquimod-Induced TLR7 Signaling Enhances Repair of DNA Damage Induced by Ultraviolet Light in Bone Marrow-Derived Cells
Authors: Fishelevich Rita , Zhao Yuming , Tuchinda Papapit , Liu Hannah , Nakazono Ayako , Tammaro Antonella , Meng Tzu-Ching , Lee Jim , Gaspari Anthony A. 
Published: July 2011

Abstract
Imiquimod is a TLR7/8 agonist that has anticancer therapeutic efficacy in the treatment of precancerous skin lesions and certain nonmelanoma skin cancers. To test our hypothesis that imiquimod enhances DNA repair as a mechanism for its anticancer activity, the nucleotide excision repair genes were studied in bone marrow-derived cells. Imiquimod enhanced the expression of xeroderma pigmentosum (XP) A and other DNA repair genes (quantitative real-time PCR analysis) and resulted in an increased nuclear localization of the DNA repair enzyme XPA. This was dependent on MyD88, as bone marrow-derived cells from MyD88−/− mice did not increase XPA gene expression and did not enhance the survival of MyD88−/−-derived bone marrow-derived cells after UV B exposure as was observed in bone marrow-derived cells from MyD88+/+ mice. Imiquimod also enhanced DNA repair of UV light (UVL)-irradiated gene expression constructs and accelerated the resolution of cyclobutane pyrimidine dimers after UVL exposures in P388 and XS52. Lastly, topical treatment of mouse skin with 5% imiquimod cream prior to UVL irradiation resulted in a decrease in the number of cyclobutane pyridimine dimer-positive APC that were found in local lymph nodes 24 h after UVL irradiation in both wild-type and IL-12 gene-targeted mice. In total, these data support the idea that TLR7 agonists such as imiquimod enhance DNA repair in bone marrow-derived cells. This property is likely to be an important mechanism for its anticancer effects because it protects cutaneous APC from the deleterious effects of UVL.
Stage prediction of embryonic stem cell differentiation from genome-wide expression data
Authors: Zagar Lan , Mulas Francesca , Garagna Silvia , Zuccotti Maurizio , Bellazzi Riccardo , Zupan Blaz 
Published: July 2011

Abstract
Motivation: The developmental stage of a cell can be determined by cellular morphology or various other observable indicators. Such classical markers could be complemented with modern surrogates, like whole-genome transcription profiles, that can encode the state of the entire organism and provide increased quantitative resolution. Recent findings suggest that such profiles provide sufficient information to reliably predict the cell's developmental stage.
Results: We use whole-genome transcription data and several data projection methods to infer differentiation stage prediction models for embryonic cells. Given a transcription profile of an uncharacterized cell, these models can then predict its developmental stage. In a series of experiments comprising 14 datasets from the Gene Expression Omnibus, we demonstrate that the approach is robust and has excellent prediction ability both within a specific cell line and across different cell lines.
Availability: Model inference and computational evaluation procedures in the form of Python scripts and accompanying datasets are available at http://www.biolab.si/supp/stagerank.
Contact: blaz.zupan@fri.uni-lj.si
Supplementary information: Supplementary data are available at Bioinformatics online.
Three Feruloyl Esterases in Cellulosilyticum ruminicola H1 Act Synergistically To Hydrolyze Esterified Polysaccharides
Authors: Li Jiabao , Cai Shichun , Luo Yuanming , Dong Xiuzhu 
Published: July 2011

ABSTRACTFeruloyl esterases (Faes) constitute a subclass of carboxyl esterases that specifically hydrolyze the ester linkages between ferulate and polysaccharides in plant cell walls. Until now, the described microbial Faes were mainly from fungi. In this study, we report thatCellulosilyticum ruminicolaH1, a previously described fibrolytic rumen bacterium, possesses three different active feruloyl esterases, FaeI, FaeII, and FaeIII. Phylogenetic analysis classified the described bacterial Faes into two types, FaeI and FaeII in type I and FaeIII in type II. Substrate specificity assays indicated that FaeI is more active against the ester bonds in natural hemicelluloses and FaeIII preferentially attacks the ferulate esters with a small moiety, such as methyl groups, while FaeII is active on both types of substrates. Among the three feruloyl esterase genes,faeIwas the only one induced significantly by xylose and xylan, while pectin appeared to moderately induce the three genes during the late log phase to stationary phase. Western blot analysis determined that FaeI and FaeIII were secreted and cytoplasmic proteins, respectively, whereas FaeII seemed to be cell associated. The addition of FaeI and FaeII but not FaeIII enhanced the activity of a xylanase on maize cob, suggesting a synergy of the former two with xylanase. Hence, we propose that the three feruloyl esterases work in concert to hydrolyze ferulate esters in natural hemicelluloses.
The Impact of Personal Experience on Behavior: Evidence from Video-Rental Fines
Authors: Haselhuhn Michael P. , Pope Devin G. , Schweitzer Maurice E. , Fishman Peter 
Published: July 2011

Personal experience matters. In a field setting with longitudinal data, we disentangle the effects of learning new information from the effects of personal experience. We demonstrate that experience with a fine, controlling for the effect of learning new information, significantly boosts future compliance. We also show that experience with a large fine boosts compliance more than experience with a small fine, but that the influence of experience with both large and small fines decays sharply over time. This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Natural Killer-22 Cells in the Synovial Fluid of Patients with Rheumatoid Arthritis Are an Innate Source of Interleukin 22 and Tumor Necrosis Factor-α
Authors: REN JIE , FENG ZHITAO , LV ZHUO , CHEN XIAOGUANG , LI JUAN 
Published: July 2011

Objective.To determine the role of natural killer (NK)-22 cells in the pathogenesis of rheumatoid arthritis (RA).Methods.Using flow cytometry, the proportions of NK-22 cells and intracellular contents of perforin, granzyme B, and interferon-γ (IFN-γ) were determined in the peripheral blood (PB) and synovial fluid (SF) of patients with RA and healthy individuals. The levels of interleukin 22 (IL-22) and tumor necrosis factor-α (TNF-α) in the NK-22 supernatant and gene expressions were measured using ELISA and QuantiGene Plex assay, respectively. The effect of NK-22 supernatant on the proliferation of fibroblast-like synoviocytes (FLS) and recombinant human IL-22 (rhIL-22) on the production of monocyte chemoattractant protein 1 (MCP-1) by RA FLS was detected using the yellow tetrazolium salt method and ELISA, respectively. The relationship between the proportions of NK-22 cells and disease activity was analyzed.Results.NKp44 and CCR6 were expressed in a larger population of SF NK cells than in the PB NK cells of patients with RA. NK-22 cells produce low content of perforin, granzyme B, and IFN-γ. NK-22 cellsin vitrocan secrete IL-22 and TNF-α and there was increased messenger RNA coding for IL-22 and TNF-α. NK-22 supernatant can induce the proliferation of RA FLS. Addition of IL-22 antibody plus TNF-α antibody inhibited the proliferation of FLS induced by the NK-22 supernatant. Both rhIL-22 1 ng/ml and rhIL-22 10 ng/ml induced the production of MCP-1 by RA FLS. The NK-22 proportions were positively correlated with disease activity.Conclusion.NK-22 cells are increased in patients with RA and might play a role in the pathogenesis of RA through the production of IL-22 and TNF-α. The proportion of NK-22 cells and disease activity were highly correlated.
Cd-Specific Mutants of Mercury-Sensing Regulatory Protein MerR, Generated by Directed Evolution
Authors: Hakkila Kaisa M. , Nikander Pia A. , Junttila Sini M. , Lamminmäki Urpo J. , Virta Marko P. 
Published: July 2011

ABSTRACT

The mercury-sensing regulatory protein, MerR (Tn
21
), which regulates mercury resistance operons in Gram-negative bacteria, was subjected to directed evolution in an effort to generate a MerR mutant that responds to Cd but not Hg. Oligonucleotide-directed mutagenesis was used to introduce random mutations into the key metal-binding regions of MerR. The effects of these mutations were assessed using a vector in which MerR controlled the expression of green fluorescent protein (GFP) and luciferase via the
mer
operator/promoter. An
Escherichia coli
cell library was screened by fluorescence-activated cell sorting, using a fluorescence-based dual screening strategy that selected for MerR mutants that showed GFP repression when cells were induced with Hg but GFP activation in the presence of Cd. Two Cd-responsive MerR mutants with decreased responses toward Hg were identified through the first mutagenesis/selection round. These mutants were used for a second mutagenesis/selection round, which yielded eight Cd-specific mutants that had no significant response to Hg, Zn, or the other tested metal(loid)s. Seven of the eight Cd-specific MerR mutants showed repressor activities equal to that of wild-type (wt) MerR. These Cd-specific mutants harbored multiple mutations (12 to 22) in MerR, indicating that the alteration of metal specificity with maintenance of repressor function was due to the combined effect of many mutations rather than just a few amino acid changes. The amino acid changes were studied by alignment against the sequences of MerR and other metal-responsive MerR family proteins. The analysis indicated that the generated Cd-specific MerR mutants appear to be unique among the MerR family members characterized to date.
Systematic Analysis of Diguanylate Cyclases That Promote Biofilm Formation by Pseudomonas fluorescens Pf0-1
Authors: Newell Peter D. , Yoshioka Shiro , Hvorecny Kelli L. , Monds Russell D. , O'Toole George A. 
Published: July 2011

ABSTRACT

Cyclic di-GMP (c-di-GMP) is a broadly conserved, intracellular second-messenger molecule that regulates biofilm formation by many bacteria. The synthesis of c-di-GMP is catalyzed by diguanylate cyclases (DGCs) containing the GGDEF domain, while its degradation is achieved through the phosphodiesterase activities of EAL and HD-GYP domains. c-di-GMP controls biofilm formation by
Pseudomonas fluorescens
Pf0-1 by promoting the cell surface localization of a large adhesive protein, LapA. LapA localization is regulated posttranslationally by a c-di-GMP effector system consisting of LapD and LapG, which senses cytoplasmic c-di-GMP and modifies the LapA protein in the outer membrane. Despite the apparent requirement for c-di-GMP for biofilm formation by
P. fluorescens
Pf0-1, no DGCs from this strain have been characterized to date. In this study, we undertook a systematic mutagenesis of 30 predicted DGCs and found that mutations in just 4 cause reductions in biofilm formation by
P. fluorescens
Pf0-1 under the conditions tested. These DGCs were characterized genetically and biochemically to corroborate the hypothesis that they function to produce c-di-GMP
in vivo
. The effects of DGC gene mutations on phenotypes associated with biofilm formation were analyzed. One DGC preferentially affects LapA localization, another DGC mainly controls swimming motility, while a third DGC affects both LapA and motility. Our data support the conclusion that different c-di-GMP-regulated outputs can be specifically controlled by distinct DGCs.
Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness
Authors: Mendonça Nancy T , Kenyon Jennifer , LaPrad Adam S , Syeda Sohera N , O'Connor George T , Lutchen Kenneth R 
Published: July 2011

Abstract

Background
Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (Rmin) is abnormally elevated in subjects with airway hyperresponsiveness.

Methods
The Rmin was measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. Rmin and spirometric indices were measured before and after bronchodilation (albuterol) and bronchoconstriction (methacholine). A preliminary study of 84 healthy subjects first established height dependence of baseline Rmin values.

Results
Asthmatics had a higher baseline Rmin % predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004). Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline Rmin was able to identify subjects with airway hyperresponsiveness (PC20 < 16 mg/mL) better than most spirometric indices (Area under curve = 0.85, 0.78, and 0.87 for Rmin % predicted, FEV1 % predicted, and FEF25-75 % predicted, respectively). Also, 80% of the subjects with baseline Rmin < 100% predicted did not have airway hyperresponsiveness while 100% of subjects with Rmin > 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic.

Conclusions
These findings suggest that baseline Rmin, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline Rmin to asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, Rmin could provide a clinically useful tool for assessing asthma and monitoring response to treatment.
A Survey of Arthrocentesis and Soft-Tissue Injection Procedures Performed in Primary Care Practice: Effect of Resident Training and Using Data to Shape Curriculum
Authors: BAKEWELL CATHERINE J. , GARDNER GREGORY C. 
Published: July 2011

Objective.The purpose of this study is (1) to survey graduates of our internal medicine program for use of musculoskeletal (MSK) procedures in primary care practice and assess the influence of participating in a first-year resident arthrocentesis and soft-tissue injection training course on their MSK procedure comfort/utilization; and (2) to use the results to modify our MSK procedure curriculum.Methods.A questionnaire designed to assess numbers of, comfort with, and effect of resident training on MSK procedures in the preceding year was sent to 2002–2006 graduates of the internal medicine training program in outpatient primary care (OPC). Graduates practicing hospital medicine (HM) also received the questionnaire and served as a comparison group.Results.There were 52 responses from this group of 84 graduates (64% response rate). OPC graduates (N = 32) were more comfortable doing procedures than those practicing HM exclusively (N = 20), and performed significantly more procedures in the preceding year (32.9 procedures per OPC/year vs 2.2 for HM). The most common procedures performed were knee joint, subacromial bursa, and trochanteric bursa, comprising > 75% of all procedures performed. A structured resident course in MSK procedures had a significant effect on the OPC physicians. Course participants (N = 17) performed almost twice the number of procedures/year as the nonparticipants (N = 15), were more comfortable with the procedures, and were significantly less likely to refer procedures to other clinicians. Written comments by respondents suggest additional MSK procedure training during and after residency is needed.Conclusion.Our results suggest a structured resident course in MSK procedures has a longterm influence. A progressively more focused approach to training is needed.
Optical detection and femtosecond spectroscopy of a single nanoparticle
Authors: Baida Hatim , Crut Aurélien , Maioli Paolo , Nguyen Thanh Binh , Nguyen Dai Hung , Fatti Natalia Del , Vallée Fabrice 
Published: July 2011

Abstract
An extension to semiconductor quantum dots of the spatial-modulation technique, demonstrated for the optical detection and linear spectroscopy of a single metal nanoparticle, is described. The association of this approach to a high sensitivity femtosecond pump–probe setup is discussed and applied to the investigation of the acoustic vibration of a single silver nanoparticle.
PGAT: a multistrain analysis resource for microbial genomes
Authors: Brittnacher M. J. , Fong C. , Hayden H. S. , Jacobs M. A. , Radey Matthew , Rohmer L. 
Published: July 2011

Abstract
Motivation: The Prokaryotic-genome Analysis Tool (PGAT) is a web-based database application for comparing gene content and sequence across multiple microbial genomes facilitating the discovery of genetic differences that may explain observed phenotypes. PGAT supports database queries to identify genes that are present or absent in user-selected genomes, comparison of sequence polymorphisms in sets of orthologous genes, multigenome display of regions surrounding a query gene, comparison of the distribution of genes in metabolic pathways and manual community annotation.
Availability and Implementation:The PGAT website may be accessed at http://nwrce.org/pgat.
Contact: mbrittna@uw.edu