bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expiratory model-based method to monitor ARDS disease state
Authors: van Drunen Erwin J , Chiew Yeong Shiong , Chase J Geoffrey , Shaw Geoffrey M , Lambermont Bernard , Janssen Nathalie , Damanhuri Nor Salwa , Desaive Thomas 
Published: June 2013

AbstractIntroductionModel-based methods can be used to characterise patient-specific condition and response to mechanical ventilation (MV) during treatment for acute respiratory distress syndrome (ARDS). Conventional metrics of respiratory mechanics are based on inspiration only, neglecting data from the expiration cycle. However, it is hypothesised that expiratory data can be used to determine an alternative metric, offering another means to track patient condition and guide positive end expiratory pressure (PEEP) selection.MethodsThree fully sedated, oleic acid induced ARDS piglets underwent three experimental phases. Phase 1 was a healthy state recruitment manoeuvre. Phase 2 was a progression from a healthy state to an oleic acid induced ARDS state. Phase 3 was an ARDS state recruitment manoeuvre. The expiratory time-constant model parameter was determined for every breathing cycle for each subject. Trends were compared to estimates of lung elastance determined by means of an end-inspiratory pause method and an integral-based method. All experimental procedures, protocols and the use of data in this study were reviewed and approved by the Ethics Committee of the University of Liege Medical Faculty.ResultsThe overall median absolute percentage fitting error for the expiratory time-constant model across all three phases was less than 10 %; for each subject, indicating the capability of the model to capture the mechanics of breathing during expiration. Provided the respiratory resistance was constant, the model was able to adequately identify trends and fundamental changes in respiratory mechanics.ConclusionOverall, this is a proof of concept study that shows the potential of continuous monitoring of respiratory mechanics in clinical practice. Respiratory system mechanics vary with disease state development and in response to MV settings. Therefore, titrating PEEP to minimal elastance theoretically results in optimal PEEP selection. Trends matched clinical expectation demonstrating robustness and potential for guiding MV therapy. However, further research is required to confirm the use of such real-time methods in actual ARDS patients, both sedated and spontaneously breathing.
Effects of hepatocyte nuclear factor-1A and -4A on pancreatic stone protein/regenerating protein and C-reactive protein gene expression: implications for maturity-onset diabetes of the young
Authors: Kyithar Ma P , Bonner Caroline , Bacon Siobhan , Kilbride Seán M , Schmid Jasmin , Graf Rolf , Prehn Jochen HM , Byrne Maria M 
Published: June 2013

Abstract

Background
There is a significant clinical overlap between patients with hepatocyte nuclear factor (HNF)-1A and HNF4A maturity-onset diabetes of the young (MODY), two forms of monogenic diabetes. HNF1A and HNF4A are transcription factors that control common and partly overlapping sets of target genes. We have previously shown that elevated serum pancreatic stone protein / regenerating protein A (PSP/reg1A) levels can be detected in subjects with HNF1A-MODY. In this study, we investigated whether PSP/reg is differentially regulated by HNF1A and HNF4A.

Methods
Quantitative real-time PCR (qPCR) and Western blotting were used to validate gene and protein expression in cellular models of HNF1A- and HNF4A-MODY. Serum PSP/reg1A levels and high-sensitivity C-reactive protein (hsCRP) were measured by ELISA in 31 HNF1A- and 9 HNF4A-MODY subjects. The two groups were matched for age, body mass index, diabetes duration, blood pressure, lipid profile and aspirin and statin use.

Results
Inducible repression of HNF1A and HNF4A function in INS-1 cells suggested that PSP/reg induction required HNF4A, but not HNF1A. In contrast, crp gene expression was significantly reduced by repression of HNF1A, but not HNF4A function. PSP/reg levels were significantly lower in HNF4A subjects when compared to HNF1A subjects [9.25 (7.85-12.85) ng/ml vs. 12.5 (10.61-17.87) ng/ml, U-test P = 0.025]. hsCRP levels were significantly lower in HNF1A-MODY [0.22 (0.17-0.35) mg/L] compared to HNF4A-MODY group [0.81 (0.38-1.41) mg/L, U-test P = 0.002], Parallel measurements of serum PSP/reg1A and hsCRP levels were able to discriminate HNF1A- and HNF4A-MODY subjects.

Conclusion
Our study demonstrates that two distinct target genes, PSP/reg and crp, are differentially regulated by HNF1A and HNF4A, and provides clinical proof-of-concept that serum PSP/reg1A and hsCRP levels may distinguish HNF1A-MODY from HNF4A-MODY subjects.
Location estimation using RSS measurements with unknown path loss exponents
Authors: Zeytinci Musa Bora , Sari Veli , Harmanci Frederic Kerem , Anarim Emin , Akar Mehmet 
Published: June 2013

Abstract
The location of a mobile station (MS) in a cellular network can be estimated using received signal strength (RSS) measurements that are available from control channels of nearby base stations. Most of the recent RSS-based location estimation methods that are available in the literature rely on the rather unrealistic assumption that signal propagation characteristics are known and independent of time variations and the environment. In this paper, we propose an RSS-based location estimation technique, so-called multiple path loss exponent algorithm (RSS-MPLE), which jointly estimates the propagation parameters and the MS position. The RSS-MPLE method incorporates antenna radiation pattern information into the signal model and determines the maximum likelihood estimate of unknown parameters by employing the Levenberg-Marquardt method. The accuracy of the proposed method is further examined by deriving the Cramer-Rao bound. The performance of the RSS-MPLE algorithm is evaluated for various scenarios via simulation results which confirm that the proposed scheme provides a practical position estimator that is not only accurate but also robust against the variations in the signal propagation characteristics.
Correlation of dynamic changes in γ-H2AX expression in peripheral blood lymphocytes from head and neck cancer patients with radiation-induced oral mucositis
Authors: Li Ping , Du Cheng-run , Xu Wen-cai , Shi Ze-liang , Zhang Qing , Li Zhao-bin , Fu Shen 
Published: June 2013

Abstract

Background
To evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy.

Methods
In vitro assays for evaluating DNA damage and repair kinetics were performed on blood samples withdrawn from 25 HNC patients undergoing radiotherapy or chemoradiotherapy before radiotherapy. As for the in vivo study, blood samples were also withdrawn before radiotherapy, and 1 hour after radiotherapy on the fourth and last days. Flow cytometry was used to assess the expression of γ-H2AX in PBLs. OM was assessed using the World Health Organization (WHO) scores twice a week and correlated with the expression of γ-H2AX.

Results
The in vitro assay results showed that patients with severe OM had higher γ-H2AX-specific relative fluorescence at various irradiation doses in the damage kinetics assay, with significantly higher γ-H2AX expression at 8 Gy (p = 0.039), and also at 24 hours after irradiation at a dose of 2 Gy in the repair kinetics assay, compared to the patients with mild OM (p = 0.008). The optimal cutoff value for relative fluorescence of γ-H2AX was 0.960, 24 hours post-irradiation. However, there were no significant differences in γ-H2AX expression at different times between the two groups, as assessed with the in vivo assay.

Conclusions
These results suggest that the damage and repair kinetics of γ-H2AX from PBLs in the in vitro study may have predictive value for identifying the grades of OM among HNC patients prior to radiotherapy.
Consensus and conflict cards for metabolic pathway databases
Authors: Stobbe Miranda D , Swertz Morris A , Thiele Ines , Rengaw Trebor , van Kampen Antoine HC , Moerland Perry D 
Published: June 2013

Abstract

Background
The metabolic network of H. sapiens and many other organisms is described in multiple pathway databases. The level of agreement between these descriptions, however, has proven to be low. We can use these different descriptions to our advantage by identifying conflicting information and combining their knowledge into a single, more accurate, and more complete description. This task is, however, far from trivial.

Results
We introduce the concept of Consensus and Conflict Cards (C2Cards) to provide concise overviews of what the databases do or do not agree on. Each card is centered at a single gene, EC number or reaction. These three complementary perspectives make it possible to distinguish disagreements on the underlying biology of a metabolic process from differences that can be explained by different decisions on how and in what detail to represent knowledge. As a proof-of-concept, we implemented C2CardsHuman, as a web application http://www.molgenis.org/c2cards, covering five human pathway databases.

Conclusions
C2Cards can contribute to ongoing reconciliation efforts by simplifying the identification of consensus and conflicts between pathway databases and lowering the threshold for experts to contribute. Several case studies illustrate the potential of the C2Cards in identifying disagreements on the underlying biology of a metabolic process. The overviews may also point out controversial biological knowledge that should be subject of further research. Finally, the examples provided emphasize the importance of manual curation and the need for a broad community involvement.
Sexual maturation in hens is not associated with increases in serum leptin and the expression of leptin receptor mRNA in hypothalamus
Authors: Ni Yingdong , Lv Jinfang , Wang Shaoqing , Zhao Ruqian 
Published: June 2013

Abstract

Background
In mammals, leptin is an attractive candidate for mediating the metabolic signal and the reproductive function via the specific receptor in hypothalamus. However, till now, the role of leptin on reproduction in birds is less well established. This experiment was conducted to elucidate the role of leptin on the onset of reproduction in bird, as a first step, to detect the changes of peripheral leptin and leptin receptor mRNA expression in hypothalamus between mature and immature hens at the same age. 120 ISA brown pullets at D60 were allocated randomly into two groups, long light (LL) group being raised under artificial light regimes with incrementally increased light phase (from 8 L:16D to 14 L:12D) and short light (SL) group raised on consistent light (8 L:16D) for 12 wk.

Results
The results showed that pullets in LL group reached sexual maturation 15 d earlier than those in SL group. Serum E2 showed a significant increase with age, but no difference was observed between two groups. Serum leptin concentration decreased significantly from D112 to D136 in LL, and was markedly higher in LL group than that in SL at D112, while there was no significant difference between two groups at D136. Leptin receptor and GnRH-I mRNA expression in hypothalamus were significantly increased with age, yet there was no significant difference between SL and LL chickens at the same age. The expression of FSH-β and LH-β mRNA in pituitary was increased with age but did not show significant difference between LL and SL group. GnRH-I mRNA expression was very rich in pineal gland, and decreased from D112 to D136 in LL but not in SL group, and there was no difference between two groups at the same age.

Conclusions
These results indicate that the earlier sexual maturation in hens induced by long-light regime is not accompanied with an increase in serum leptin or leptin receptor gene expression in hypothalamus, or genes expression in HPG axis.
FMNL1 promotes proliferation and migration of leukemia cells
Authors: Favaro Patricia , Traina Fabiola , Machado-Neto João Agostinho , Lazarini Mariana , Lopes Matheus Rodrigues , Pereira João Kleber Novais , Costa Fernando Ferreira , Infante Elvira , Ridley Anne J , Saad Sara Teresinha Olalla 
Published: June 2013

ABSTRACTThe human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation.
1,4-Dihydroxy-2-naphthoic acid fromPropionibacterium freudenreichiireduces inflammation in interleukin-10-deficient mice with colitis by suppressing macrophage-derived proinflammatory cytokines
Authors: Okada Yoshikiyo , Tsuzuki Yoshikazu , Narimatsu Kazuyuki , Sato Hirokazu , Ueda Toshihide , Hozumi Hideaki , Sato Shingo , Hokari Ryota , Kurihara Chie , Komoto Shunsuke , Watanabe Chikako , Tomita Kengo , Kawaguchi Atsushi , Nagao Shigeaki , Miura Soichiro 
Published: June 2013

ABSTRACTThe anti-inflammatory mechanism of prebiotics has recently been shown to have an impact on the host immune system. DHNA from Propionibacterium freudenreichii is known to promote the proliferation of Bifidobacterium and can ameliorate colitis, although its mode of action remains unknown. In this study, we investigated whether DHNA attenuates inflammation in piroxicam-treated IL-10−/− mice, particularly focusing on the changes of the host immune mechanism. DHNA was administered to IL-10−/− mice with colitis, and the expression of adhesion molecules and mRNA levels of proinflammatory cytokines were determined. DHNA pretreatment attenuated the piroxicam-induced histological changes. The increased F4/80-positive cell infiltration and VCAM-1 expression were decreased by DHNA administration. The increased mRNA levels of proinflammatory cytokines were also suppressed by DHNA. In in vitro experiments, increased mRNA levels of proinflammatory cytokines after endotoxin exposure were decreased significantly by DHNA pretreatment in RAW264.7, a macrophage cell line, and IL-10−/− mice BMMs, whereas the expression of VCAM-1 in bEnd.3 cells, a endothelial cell line, was not affected. Taken together, these findings suggest that administration of DHNA is useful for the treatment of colitis in piroxicam-treated IL-10−/− mice and that attenuation of colitis by DHNA may partly be a result of its direct action on intestinal macrophages to inhibit proinflammatory cytokine production.
The responses of neural stem cells to the level of GSK-3 depend on the tissue of origin
Authors: Holowacz Tamara , Alexson Tania O. , Coles Brenda L. , Doble Bradley W. , Kelly Kevin F. , Woodgett James R. , Van Der Kooy Derek 
Published: June 2013

Summary
Neural stem cells (NSCs) can be obtained from a variety of sources, but not all NSCs exhibit the same characteristics. We have examined how the level of glycogen synthase kinase-3 activity regulates NSCs obtained from different sources: the mouse embryonic striatum, embryonic hippocampus, and mouse ES cells. Growth of striatal NSCs is enhanced by mild inhibition of GSK-3 but not by strong inhibition that is accompanied by Wnt/TCF transcriptional activation. In contrast, the growth of hippocampal NSCs is enhanced by both mild inhibition of GSK-3 as well as stronger inhibition. Active Wnt/TCF signaling, which occurs normally in the embryonic hippocampus, is required for growth of neural stem and progenitor cells. In the embryonic striatal germinal zone, however, TCF signaling is normally absent and its activation inhibits growth of NSCs from this region. Using a genetic model for progressive loss of GSK-3, we find that primitive ES cell-derived NSCs resemble striatal NSCs. That is, partial loss of GSK-3 alleles leads to an increase in NSCs while complete ablation of GSK-3, and activation of TCF-signaling, leads to their decline. Furthermore, expression of dominant negative TCF-4 in the GSK-3-null background was effective in blocking expression of Wnt-response genes and was also able to rescue neuronal gene expression. These results reveal that GSK-3 regulates NSCs by divergent pathways depending on the tissue of origin. The responses of these neural precursor cells may be contingent on baseline Wnt/TCF signaling occurring in a particular tissue.
The Hippo pathway acts via p53 and microRNAs to control proliferation and proapoptotic gene expression during tissue growth
Authors: Zhang Wei , Cohen Stephen M. 
Published: June 2013

Summary
The Hippo pathway has a central role in coordinating tissue growth and apoptosis. Mutations that compromise Hippo pathway activity cause tissue overgrowth and have been causally linked to cancer. In Drosophila, the transcriptional coactivator Yorkie mediates Hippo pathway activity to control the expression of cyclin E and Myc to promote cell proliferation, as well as the expression of bantam miRNA and DIAP1 to inhibit cell death. Here we present evidence that the Hippo pathway acts via Yorkie and p53 to control the expression of the proapoptotic gene reaper. Yorkie further mediates reaper levels post-transcriptionally through regulation of members of the miR-2 microRNA family to prevent apoptosis. These findings provide evidence that the Hippo pathway acts via several distinct routes to limit proliferation-induced apoptosis.
Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
Authors: Bell Peter A. , Wagener Raimund , Zaucke Frank , Koch Manuel , Selley Julian , Warwood Stacey , Knight David , Boot-Handford Raymond P. , Thornton David J. , Briggs Michael D. 
Published: June 2013

Summary
Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration.
Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis.
Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis.
We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.
Challenges of SMR Licensing Practices
Authors: Söderholm K. 
Published: June 2013

This paper aims to increase the understanding of high level Nuclear Power Plant (NPP) licensing processes in Finland, France, the UK, Canada and the USA. These countries have been selected for this study because of their different licensing processes and recent actions in new NPP construction. After discussing their similarities and differences, suitable features for Small Modular Reactor licensing can be emphasized and suggested. Some of the studied licensing processes have elements that are already quite well suited for application to SMRs, but all of these different national processes can benefit from studying and implementing lessons learned from SMR specific licensing needs. The main SMR features to take into account in licensing are standardization of the design, modularity, mass production and serial construction. Modularity can be divided into two different categories: the first category is simply a single unit facility constructed of independently engineered modules (e.g., construction process for Westinghouse AP-1000 NPP) and the second is a facility structure composed of many reactor modules where modules are manufactured in factories and installed into the facility as needed (e.g., NuScale Power SMR design). Short construction schedules will not be fully benefitted from if the long licensing process prolongs the commissioning and approach to full-power operation. The focus area of this study is to better understand the possibility of SMR deployment in small nuclear countries, such as Finland, which currently has four operating NPPs. The licensing process needs to be simple and clear to make SMR deployment feasible from an economical point of view. This paper uses public information and interviews with experts to establish the overview of the different licensing processes and their main steps. A high-level comparison of the licensing steps has been carried out. Certain aspects of the aviation industry licensing process have also been studied and certain practices have been investigated as possibly suitable for use in nuclear licensing. All of the current licensing processes were found to be quite heavy and time-consuming and further streamlining could be possible without compromising safety or the need for public participation in the licensing process. Some examples of the modification possibilities for SMR applications are discussed. A profound discussion on SMR-specific licensing models, and on ways to simplify and harmonize them, will be needed in the near future in Europe too. This would be a natural continuation to the harmonization efforts underway for existing and new large reactors.