bluuebunny/crossref_metadata_2025_split huggingface dataset:
The overmethylated genes in Helicobacter pylori-infected gastric mucosa are demethylated in gastric cancers
Authors: Hong Seung-Jin , Oh Jung-Hwan , Jeon Eun-Jung , Min Ki-Ouk , Kang Moo-Il , Choi Sang-Wook , Rhyu Mun-Gan 
Published: November 2010

Abstract

Background
The transitional-CpG sites between weakly methylated genes and densely methylated retroelements are overmethylated in the gastric mucosa infected with Helicobacter pylori (H. pylori) and they are undermethylated in the gastric cancers depending on the level of loss of heterozygosity (LOH) events. This study delineated the transitional-CpG methylation patterns of CpG-island-containing and -lacking genes in view of the retroelements.

Methods
The transitional-CpG sites of eight CpG-island-containing genes and six CpG-island-lacking genes were semi-quantitatively examined by performing radioisotope-labelling methylation-specific PCR under stringent conditions. The level of LOH in the gastric cancers was estimated using the 40 microsatellite markers on eight cancer-associated chromosomes. Each gene was scored as overmethylated or undermethylated based on an intermediate level of transitional-CpG methylation common in the H. pylori-negative gastric mucosa.

Results
The eight CpG-island genes examined were overmethylated depending on the proximity to the nearest retroelement in the H. pylori-positive gastric mucosa. The six CpG-island-lacking genes were similarly methylated in the H. pylori-positive and -negative gastric mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island genes distant from the retroelements remained overmethylated, whereas the overmethylation of short transitional-CpG segments close to the retroelements was not significant. Both the CpG-island-containing and -lacking genes tended to be decreasingly methylated in a LOH-level-dependent manner.

Conclusions
The overmethylated genes under the influence of retroelement methylation in the H. pylori-infected stomach are demethylated in the gastric cancers influenced by LOH.
The gene-reduction effect of chromosomal losses detected in gastric cancers
Authors: Hong Seung-Jin , Jeon Eun-Jung , Oh Jung-Hwan , Seo Eun-Joo , Choi Sang-Wook , Rhyu Mun-Gan 
Published: November 2010

AbstractBackgroundThe level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.MethodsThe pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).ResultsMost of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).ConclusionsThe cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.
Mechanical ventilation modulates Toll-like receptor-3-induced lung inflammation via a MyD88-dependent, TLR4-independent pathway: a controlled animal study
Authors: Chun Carrie D , Liles W Conrad , Frevert Charles W , Glenny Robb W , Altemeier William A 
Published: November 2010

Abstract

Background
Mechanical ventilation augments lung inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that ventilator-associated immune modulation requires MyD88-dependent signaling. Because MyD88 is a critical adapter protein utilized for pro-inflammatory signaling by all Toll-like receptors (TLRs), with the exception of TLR3, as well as by the IL-1 and IL-18 receptors, MyD88 dependence would implicate generation of an endogenous soluble ligand recognized by one or more of these receptors during mechanical ventilation and would provide an opportunity for a potential future therapeutic intervention.

Methods
We compared the effect of mechanical ventilation on lung inflammation and permeability between poly(I:C) exposed mice with or without expression of MyD88. Poly(I:C) is a synthetic ligand for TLR3, the only MyD88-independent TLR, allowing isolation of the effect of MyD88 deletion on ventilator-augmentation of lung inflammation. Lung inflammation was assessed by cytokine concentration in lung tissue homogenate and polymorphonuclear cell (PMN) number in bronchoalveolar lavage fluid (BALF). Lung permeability was assessed by total protein, IgM, and intravenously injected FITC-dextran concentrations in BALF.

Results
We found that MyD88 was required for mechanical ventilation augmentation of TLR3-induced lung inflammation and permeability. Because TLR4 is the most commonly reported receptor for endogenous ligands generated during tissue injury, we performed a second experiment comparing wildtype and TLR4-/- mice. We found that mechanical ventilation increased TLR3-mediated inflammation and permeability independent of TLR4.

Conclusion
These data support the hypothesis that mechanical ventilation with moderate tidal volumes generates an endogenous ligand(s) recognized by MyD88-dependent receptor(s) other than TLR4, and that this mechanism can contribute to the development of ventilator-associated lung inflammation and injury. Identification of these ligands and/or receptors could lead to new pharmacological treatments for ARDS.
Modulation of inhibitory activity of xylanase - α-amylase inhibitor protein (XAIP): binding studies and crystal structure determination of XAIP- II from Scadoxus multiflorus at 1.2 Å resolution
Authors: Kumar Sanjit , Singh Nagendra , Mishra Biswajit , Dube Divya , Sinha Mau , Singh S Baskar , Dey Sharmistha , Kaur Punit , Sharma Sujata , Singh Tej P 
Published: November 2010

Abstract

Background
Plants produce a wide range of proteinaceous inhibitors to protect themselves against hydrolytic enzymes. Recently a novel protein XAIP belonging to a new sub-family (GH18C) was reported to inhibit two structurally unrelated enzymes xylanase GH11 and α-amylase GH13. It was shown to inhibit xylanase GH11 with greater potency than that of α-amylase GH13. A new form of XAIP (XAIP-II) that inhibits α-amylase GH13 with a greater potency than that of XAIP and xylanase GH11 with a lower potency than that of XAIP, has been identified in the extracts of underground bulbs of Scadoxus multiflorus. This kind of occurrence of isoforms of inhibitor proteins is a rare observation and offers new opportunities for understanding the principles of protein engineering by nature.

Results
In order to determine the structural basis of the enhanced potency of XAIP-II against α-amylase GH13 and its reduced potency against xylanase GH11 as compared to that of XAIP, we have purified XAIP-II to homogeneity and obtained its complete amino acid sequence using cloning procedure. It has been crystallized with 0.1 M ammonium sulphate as the precipitating agent and the three-dimensional structure has been determined at 1.2 Å resolution. The binding studies of XAIP-II with xylanase GH11 and α-amylase GH13 have been carried out with surface plasmon resonance (SPR).

Conclusion
The structure determination revealed that XAIP-II adopts the well known TIM barrel fold. The xylanase GH11 binding site in XAIP-II is formed mainly with loop α3-β3 (residues, 102 - 118) which has acquired a stereochemically less favorable conformation for binding to xylanase GH11 because of the addition of an extra residue, Ala105 and due to replacements of two important residues, His106 and Asn109 by Thr107 and Ser110. On the other hand, the α-amylase binding site, which consists of α-helices α6 (residues, 193 - 206), α7 (residues, 230 - 243) and loop β6-α6 (residues, 180 - 192) adopts a stereochemically more favorable conformation due to replacements of residues, Ser190, Gly191 and Glu194 by Ala191, Ser192 and Ser195 respectively in α-helix α6, Glu231 and His236 by Thr232 and Ser237 respectively in α-helix α7. As a result, XAIP-II binds to xylanase GH11 less favorably while it interacts more strongly with α-amylase GH13 as compared to XAIP. These observations correlate well with the values of 4.2 × 10-6 M and 3.4 × 10-8 M for the dissociation constants of XAIP-II with xylanase GH11 and α-amylase GH13 respectively and those of 4.5 × 10-7 M and 3.6 × 10-6 M of XAIP with xylanase GH11 and α-amylase GH13 respectively.
PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients
Authors: Shen Tao , Zheng Jiajia , Xu Chunhui , Liu Jia , Zhang Weidong , Lu Fengmin , Zhuang Hui 
Published: November 2010

Abstract

Background
Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression.

Methods
PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied.

Results
Declined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p < 0.0001) and TEMRA (p = 0.0015) was positively correlated with HCV viral load while HLA-DR expression on non-naive CD8+ T cell subsets (p < 0.05) was negatively correlated with HCV viral load.

Conclusion
PD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.
Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10
Authors: Rodríguez-García Marta , Porichis Filippos , de Jong Olivier G , Levi Karen , Diefenbach Thomas J , Lifson Jeffrey D , Freeman Gordon J , Walker Bruce D , Kaufmann Daniel E , Kavanagh Daniel G 
Published: November 2010

ABSTRACTPD-1 plays an important role in T cell exhaustion during HIV infection. PD-1 has two ligands: PD-L1, expressed on hematopoietic and nonhematopoietic cells, and PD-L2, limited to DCs and macrophages. Little is known about PD-L1 expression and regulation in human macrophages. Previous reports have found few immediate effects of macrophage exposure to HIV, suggesting that macrophages lack PRRs for this virus. Using quantitative confocal microscopy and a multiplexed cytokine bead array, we measured induction of PD-L1, PD-L2, and innate response cytokines in human MDMs in response to chemically inactivated HIV virions. Consistent with previous reports, no cytokines were induced by HIV virion exposure. Whereas PD-L1 and PD-L2 had low baseline expression, TLR ligands (LPS and CL097) up-regulated PD-L1 but not PD-L2. Unlike what we found for cytokine expression, PD-L1 and PD-L2 were up-regulated in response to exposure with inactivated HIV virions or with replication-competent HIV. Expression of PD-L1 was differentially modulated by IL-10, which induced up-regulation of PD-L1 but not of PD-L2, and IL-10 blockade enhanced only PD-L2 expression. We discuss implications for innate recognition of HIV by macrophages and potential, different roles for PD-L1 and PD-L2 in immunity and pathogenesis.
Opportunity Spaces in Innovation: Empirical Analysis of Large Samples of Ideas
Authors: Kornish Laura J. , Ulrich Karl T. 
Published: November 2010

A common approach to innovation, parallel search, is to identify a large number of opportunities and then to select a subset for further development, with just a few coming to fruition. One potential weakness with parallel search is that it permits repetition. The same, or a similar, idea might be generated multiple times, because parallel exploration processes typically operate without information about the ideas that have already been identified. In this paper we analyze repetition in five data sets comprising 1,368 opportunities and use that analysis to address three questions: (1) When a large number of efforts to generate ideas are conducted in parallel, how likely are the resulting ideas to be redundant? (2) How large are the opportunity spaces? (3) Are the unique ideas more valuable than those similar to many others? The answer to the first question is that although there is clearly some redundancy in the ideas generated by aggregating parallel efforts, this redundancy is quite small in absolute terms in our data, even for a narrowly defined domain. For the second question, we propose a method to extrapolate how many unique ideas would result from an unbounded effort by an unlimited number of comparable idea generators. Applying that method, and for the settings we study, the estimated total number of unique ideas is about one thousand for the most narrowly defined domain and greater than two thousand for the more broadly defined domains. On the third question, we find a positive relationship between the number of similar ideas and idea value: the ideas that are least similar to others are not generally the most valuable ones.This paper was accepted by Lee Fleming, entrepreneurship and innovation.
Recruiting for Ideas: How Firms Exploit the Prior Inventions of New Hires
Authors: Singh Jasjit , Agrawal Ajay 
Published: November 2010

When firms recruit inventors, they acquire not only the use of their skills but also enhanced access to their stock of ideas. But do hiring firms actually increase their use of new recruits' prior inventions? Our estimates suggest they do, quite significantly in fact, by approximately 219% on average. However, this does not necessarily reflect widespread “learning by hiring.” In fact, we estimate that a recruit's exploitation of her own prior ideas accounts for almost half of the above effect, with much of the diffusion to others being limited to the recruit's immediate collaborative network. Furthermore, although one might expect the recruit's role to diminish rapidly as her tacit knowledge diffuses across her new firm, our estimates indicate that her importance is surprisingly persistent over time. We base these findings on an empirical strategy that exploits the variation over time in hiring firms' citations to the recruits' premove patents. Specifically, we employ a difference-in-differences approach to compare premove versus postmove citation rates for the recruits' prior patents and corresponding matched-pair control patents. Our methodology has three benefits compared to previous studies that also examine the link between labor mobility and knowledge flow: (1) it does not suffer from the upward bias inherent in the conventional cross-sectional comparison, (2) it generates results that are robust to a more stringently matched control sample, and (3) it enables a temporal examination of knowledge flow patterns.This paper was accepted by Kamalini Ramdas, entrepreneurship and innovation.
An Investigation of Earnings Management Through Marketing Actions
Authors: Chapman Craig J. , Steenburgh Thomas J. 
Published: November 2010

Prior research hypothesizes managers use “real actions,” including the reduction of discretionary expenditures, to manage earnings to meet or beat key benchmarks. This paper examines this hypothesis by testing how different types of marketing expenditures are used to boost earnings for a durable commodity consumer product that can be easily stockpiled by end consumers. Combining supermarket scanner data with firm-level financial data, we find evidence that differs from prior literature. Instead of reducing expenditures to boost earnings, soup manufacturers roughly double the frequency and change the mix of marketing promotions (price discounts, feature advertisements, and aisle displays) at the fiscal quarter-end when they have greater incentive to boost earnings. Our results confirm managers' stated willingness to sacrifice long-term value in order to smooth earnings and their stated preference to use real actions to boost earnings to meet different types of earnings benchmarks. We estimate that marketing actions can be used to boost quarterly net income by up to 5% depending on the depth and duration of promotion. However, there is a price to pay, with the cost in the following period being approximately 7.5% of quarterly net income. Finally, a unique aspect of the research setting allows tests of who is responsible for the earnings management. Although firms appear unable to increase the frequency of aisle display promotions in the short run, they can reallocate these promotions within their portfolio of brands. Results show firms shifting display promotions away from smaller revenue brands toward larger ones following periods of poor financial performance. This indicates the behavior is determined by parties above brand managers in the firm. These findings are consistent with firms engaging in real earnings management and suggest that effects on subsequent reporting periods and competitor behavior are greater than previously documented. This paper was accepted by Stefan Reichelstein, accounting.
Competing to Be Certain (But Wrong): Market Dynamics and Excessive Confidence in Judgment
Authors: Radzevick Joseph R. , Moore Don A. 
Published: November 2010

In this paper, we investigate how market competition contributes to the expression of overconfidence among those competing for influence. We find evidence that market competition exacerbates the tendency to express excessive confidence. This evidence comes from experiments in which advisors attempt to sell their advice. In the first, advisors must compete with other advice sellers. In the second, advisors and their customers are paired. Advisors are overconfident in both studies and it helps advisors sell their advice. However, competition between advisors in the market further exacerbates overconfidence. In a third study, we demonstrate that the market competition drives overconfidence even when advisors vary in quality. We also investigate the strategic expressions and interpretations of confidence by both sides in the exchange. This paper was accepted by Peter Wakker, decision analysis.
Commutability Limitations Influence Quality Control Results with Different Reagent Lots
Authors: Miller WGreg , Erek Aybala , Cunningham Tina D , Oladipo Olajumoke , Scott Mitchell G , Johnson Robert E 
Published: November 2010

BACKGROUNDGood laboratory practice includes verifying that each new lot of reagents is suitable for use before it is put into service. Noncommutability of quality control (QC) samples with clinical patient samples may preclude their use to verify consistency of results for patient samples between different reagent lots.METHODSPatient sample results and QC data were obtained from reagent lot change verification records for 18 QC materials, 661 reagent lot changes, 1483 reagent lot change–QC events, 82 analytes, and 7 instrument platforms. The significance of between-lot differences in the results for QC samples compared with those for patient samples was assessed by a modified 2-sample t test adjusted for heterogeneity of QC and patient sample measurement variances.RESULTSOverall, 40.9% of reagent lot change–QC events had a significant difference (P &lt; 0.05) between results for QC samples compared with results for patient samples between 2 reagent lots. For QC results with differences &lt;1.0 SD interval (83.1% of total), 37.7% were significantly different from the changes observed for patient samples. For QC results with differences ≥1.0 SD interval (16.9% of total), 57.0% were significantly different from those for patient samples.CONCLUSIONSOccurrence of noncommutable results for QC materials was frequent enough that the QC results could not be used to verify consistency of results for patient samples when changing lots of reagents.
Inverse Log-Linear Relationship between Thyroid-Stimulating Hormone and Free Thyroxine Measured by Direct Analog Immunoassay and Tandem Mass Spectrometry
Authors: van Deventer Hendrick E , Mendu Damodara R , Remaley Alan T , Soldin Steven J 
Published: November 2010

BACKGROUNDAccurate measurement of free thyroxine (FT4) is important for diagnosing and managing thyroid disorders. Most laboratories measure FT4 by direct analogue immunoassay methods. The validity of these methods have recently been questioned. The inverse log-linear relationship between FT4 and thyroid-stimulating hormone (TSH) is well described and provides a physiological rationale on which to base an evaluation of FT4 assays.METHODSThe study included 109 participants for whom FT4 measurement was requested by their clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH and albumin results. FT4 and TSH were measured by use of the Siemens Immulite immunoassay (IA). FT4 was also measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) (MS-FT4).RESULTSThe inverse log-linear correlation coefficient between TSH and FT4 was significantly better (P &lt; 0.0001) for MS-FT4 (0.84, 95% CI, 0.77–0.88) than for IA-FT4 (0.45, 95% CI, 0.29–0.59). IA-FT4 showed a significant correlation with albumin (Spearman correlation coefficient 0.45, 95% CI, 0.29–0.5, P &lt; 0.0001) and thyroxine-binding globulin (TBG) (Spearman correlation coefficient 0.23, 95% CI, 0.05–0.41, P = 0.02). In contrast, FT4 measurement by LC-MS/MS did not show a significant correlation with albumin or TBG.CONCLUSIONSThe inverse log-linear relationship between FT4 and TSH was significantly better for FT4 measured by LC-MS/MS than by IA. The MS-FT4 method therefore provides FT4 results that agree clinically with those obtained for TSH. Additionally, the significant correlation between IA-FT4 with albumin and TBG suggests that this FT4 method depends on binding protein concentrations and consequently does not accurately reflect FT4.