bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post‐translational modifications of orphan nuclear receptor TR2 – new insights into drug targets for stem cell therapy and the effect of retinoic acid
Authors: Wei Li‐Na 
Published: January 2009

AbstractTesticular receptor 2 (TR2) belongs to the nuclear receptor superfamily that constitutes one of the largest transcription factor families. Due to the lack of specific ligands for TR2 and because TR2 gene knockout mice exhibited no apparent pathological phenotypes in laboratories, it has been a challenge to pursue studies of this mysterious nuclear receptor. Recently, using gene knockdown approaches, we were able to detect its specific biological activity, primarily, in the maintenance of proliferation potential of embryonic stem cells. Further, with proteomic approaches, we have uncovered extensive PTMs of TR2. Specific PTMs of TR2 could differentially regulate its biological activity mediated by multiple signaling pathways including one elicited by the nongenomic action of retinoic acid. These PTMs are involved in TR2 activation, repression, DNA‐binding, protein stability, and subcellular distribution. The confirmed PTMs that have a functional consequence on the activity/property of TR2 include phosphorylation, ubiquitination, and SUMOylation. This review summarizes the effects of PTMs, as well as their signaling pathways, on TR2 receptor protein stability, recruitment of coregulators, and subcellular partition, and discusses the potential of developing therapeutics targeting at the regulatory components of stem/precursor cells.
Proteomics: New insights into rheumatic diseases
Authors: Camafeita Emilio , Lamas José Ramón , Calvo Enrique , López Juan Antonio , Fernández‐Gutiérrez Benjamín 
Published: January 2009

AbstractTremendous advances undergone in electrophoresis, chromatography, and MS have led proteomic research to unprecedented achievement over the last decade. Proteomics is presently employed for assessing protein expression levels, for monitoring cellular activities and for determination of biochemical pathways, revolutionizing the way we study disease by opening up the possibility to decipher the pathogenesis of clinical manifestations. Over 200 disorders including osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis are considered rheumatic diseases (RDs), which affect the musculoskeletal system (joints and other supporting structures of the body such as muscles, tendons, ligaments, and bones) and are a leading cause of disability among older adults. Despite that an autoimmune origin has been proposed for some RDs like RA, the pathogenesis of most of these diseases is still unclear. Therefore, proteomic research on RDs, notably OA and RA, can help clarify underlying disease mechanisms, develop biomarkers to improve early detection, measure response to treatment, and devise new therapies. Achievements in the field of proteomics research on RDs are summarized in this work.
Novel biomarkers of atherosclerosis and cardiovascular risk in autoimmune diseases: Genomics and proteomics approaches
Authors: López‐Pedrera Chary , Barbarroja Nuria , Villalba Jose Manuel 
Published: January 2009

AbstractAtherosclerosis (AT) and cardiovascular disease (CVD) are enhanced in autoimmune diseases such as antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). The reason for this accelerated process is still debatable and, although traditional risk factors are more prevalent in those patients than in general population, they do not fully explain that enhanced risk. Inflammatory components of the immune response, mainly interleukins, TNF‐α, and IFN‐γ, as well as some autoantibodies, including anti‐oxidized low density lipoproteins (anti‐oxLDL), anti‐beta‐2‐Glycoprotein 1 (anti‐ β2GPI), anti‐Heat shock proteins 60/65 (anti‐HSP60/65), and anti‐oxLDL/β2GPI have been shown to play a leading role in the pathogenesis of both, AT and CVD. However, the role of the autoantibodies in accelerated AT in autoimmune disease patients is still controversial. Recently, DNA microarray and proteomic‐based approaches have made substantial breakthrough into the study of various rheumatic diseases, thus allowing for the discovery of previously unknown proteins involved in CVD including some that may be suitable to be used as biomarkers. Herein, we review recent genomics and proteomic approaches that have been applied to the study of autoimmune diseases with atherosclerotic and CV risk. The pharmacogenomics and pharmacoproteomics studies given over to the analysis of ancient and new drugs used to relieve the physiopathology associated to these complex diseases are also discussed.
Sources of water vapour contributing to the Elbe flood in August 2002—A tagging study in a mesoscale model
Authors: Sodemann H. , Wernli H. , Schwierz C. 
Published: January 2009

AbstractIn this study we investigate the contribution of various moisture sources to the Elbe flood that occurred in Central Europe during August 2002. An 8‐day simulation with the mesoscale numerical weather prediction model CHRM, including newly implemented water vapour tracers, has been performed. According to the simulation, rather than drawing moisture from one single dominant source region, water vapour from widely separated moisture sources contributed to the extreme precipitation in the most affected area, notably at distinct, subsequent periods of time, and each in significant amounts. These moisture sources include the Atlantic and Mediterranean ocean areas inside the model domain, evapotranspiration from land areas, and long‐range advection from subtropical areas outside the model domain.The results highlight the importance of the concurrent upper‐level circulation and the mesoscale flow structures associated with the cyclone for producing extreme precipitation in parts of Germany, Austria, and the Czech Republic during that period. Furthermore, the numerical and technical problems of implementing water vapour tracers into a limited‐area model are discussed, including conservative tracer advection, initialization, boundary treatment, and the handling of precipitation parametrizations. An evaluation of the consistency of the method in terms of water vapour, cloud water, and precipitation is provided, with generally satisfying results. The model with its detailed water vapour tracer implementation can now be used for further case‐studies and climatological simulations, and serve as a reference for evaluating the performance of other moisture tracking methods, such as those based on backward trajectories. Copyright © 2009 Royal Meteorological Society
Cell proteomic footprint
Authors: Lokhov Petr , Balashova Elena , Dashtiev Maxim 
Published: January 2009

AbstractThe authentication of mammalian cell cultures and their subpopulations is of great demand in biotechnology and cell therapy. However, current techniques are either not efficient or can be very complex and expensive. Here we report a simple and straightforward approach for authentication of biological cells and their subpopulations with high speed, high throughput, low sample cost, and high sensitivity. We discovered that cell cultures treated with protease under soft, ‘non‐killing’ conditions release fragments of cell surface proteins, whose composition is a strong characteristic of the cells. Mass spectrometric analysis of the released fragments allows a direct comparison of the produced mass spectrum with the mass spectrum of known cells. As an example, we applied this technique to verify subpopulations of human fibroblasts with different origins and which exhibit different medical characteristics. Copyright © 2009 John Wiley & Sons, Ltd.
Composite measures for hospital quality using quality‐adjusted life years
Authors: Timbie Justin W. , Shahian David M. , Newhouse Joseph P. , Rosenthal Meredith B. , Normand Sharon‐Lise T. 
Published: January 2009

AbstractDeveloping clinically meaningful summary measures of health‐care quality is key to inferring quality of care. Current summary measures use a number of different approaches to weight their individual measures but rarely use weights based on clinical ‘importance’. Such an approach would help to focus quality improvement efforts on areas likely to have the largest impact on health outcomes. Using coronary artery bypass graft (CABG) surgery as a case study, we weight and combine 11 process, complication, and survival measures to summarize differences in quality‐adjusted life expectancy 1 year following surgery for a sample of hospitals. We use a fully Bayesian analysis to estimate 1‐year survival outcomes using a hierarchical exponential survival model. We then estimate the expected utility of the year following surgery for each patient using complication probabilities fitted from hierarchical models and utility values from the literature. We estimate quality‐adjusted life years (QALYs) for each hospital as the utility‐weighted average 1‐year survival probability and then estimate ‘incremental QALYs’ by taking the difference in QALYs for each hospital relative to a comparison group that reflects the average performance of all hospitals in the state. We illustrate our framework by estimating incremental QALYs for 14 hospitals performing CABG surgery in Massachusetts in 2003 and find that a composite measure based on QALYs can change the classification of quality outliers relative to conventional mortality measures. Copyright © 2009 John Wiley & Sons, Ltd.
C/EBPβ Mediates Synergistic Upregulation of Gene Expression by Interferon-γ and Tumor Necrosis Factor-α in Bone Marrow-Derived Mesenchymal Stem Cells
Authors: Xu Guangwu , Zhang Yingyu , Zhang Liying , Roberts Arthur I. , Shi Yufang 
Published: January 2009

AbstractMesenchymal stem cells (MSCs) are potent immunoregulators and have shown clinical utility in suppressing immunity. MSC function is modulated by cytokines, since inflammatory cytokines, such as interferon-γ (IFNγ) concomitant with tumor necrosis factor-α (TNFα), induce their immunoregulatory capability. Here, we show that IFNγ and TNFα act synergistically to induce high levels of expression of interleukin-6 (IL-6) and several other immune-related molecules in MSCs in vitro. We further found that, while either IFNγ or TNFα alone induced minor expression of C/EBPβ in MSCs, this transcription factor was dramatically upregulated when these cytokines were added together. A causal relationship between C/EBPβ upregulation and IL-6 expression was demonstrated by small interfering RNA knockdown of C/EBPβ. C/EBPβ knockdown also inhibited the synergistic expression of CXCL1, inducible nitric oxide synthase, and CCL5 in response to concomitant IFNγ and TNFα. We conclude that C/EBPβ is a key transcription factor in synergistic gene upregulation by IFNγ and TNFα. Importantly, C/EBPβ similarly mediated synergistic gene induction in response to IFNγ accompanied by IL-1β or lipopolysaccharide, suggesting that synergy between IFNγ and other stimuli share C/EBPβ as common mechanism. Furthermore, while STAT1 is critical in IFNγ signaling, we found that STAT1 knockdown in MSCs did not affect C/EBPβ expression or the synergistic induction of IL-6 and CXCL1 by IFNγ and TNFα. Thus, C/EBPβ is not regulated by STAT1. These results demonstrate the importance of cytokine interactions in MSC immunobiology, a better understanding of which will allow improved clinical application of these cells.Disclosure of potential conflicts of interest is found at the end of this article.
System aspects of 1100 kV AC transmission technologies in Japan
Authors: Zaima Eiichi 
Published: January 2009

AbstractThis paper describes the system aspects of 1100 kV AC transmission technologies with the UHV transmission project in Japan. For realization of technical and economical optimization throughout the design of the transmission line and the substation, solutions for network problems and insulation coordination specific to UHV AC transmission systems were studied in Japan. They include fast multiphase reclosing systems by HSGS (High Speed Grounding Switch) and overvoltage control by the application of surge arresters and circuit breakers with closing/opening resistors. These sophisticated technologies provide highly reliable and economical 1100 kV substations and transmission lines. Copyright © 2009 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
High‐voltage testing on UHV equipment: Overshoot and base curve for oscillating lightning impulse
Authors: Matsumoto Satoshi , Kawamura Tatsuo 
Published: January 2009

AbstractAs the higher impulse testing voltage, residual inductance of the test circuit or the stray capacitance of the test object increases with size. This means that the overshoot superposed on standard lightning impulse voltage would not be neglected because of its larger value during the lightning test. This paper describes the analysis of overshoot and oscillation based on the equivalent circuit containing a residual inductance. The waveform parameters such as relative overshoot magnitude, oscillation frequency are also derived to evaluate the influence of the residual inductance in the impulse testing circuit. The oscillating impulse waveform is related to the base curve of the standard lightning impulse. Furthermore, the base curve for oscillating impulse is proposed by the analysis. Copyright © 2009 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Plasmids with E2 epitope tags: tagging modules for N‐ and C‐terminal PCR‐based gene targeting in both budding and fission yeast, and inducible expression vectors for fission yeast
Authors: Tamm Tiina 
Published: January 2009

AbstractA single‐step PCR‐based epitope tagging enables fast and efficient gene targeting with various epitope tags. This report presents a series of plasmids for the E2 epitope tagging of proteins in Saccharomyces cerevisiae and Schizosaccharomyces pombe. E2Tags are 10‐amino acids (epitope E2a: SSTSSDFRDR)‐ and 12 amino acids (epitope E2b: GVSSTSSDFRDR)‐long peptides derived from the E2 protein of bovine papillomavirus type 1. The modules for C‐terminal tagging with E2a and E2b epitopes were constructed by the modification of the pYM‐series plasmid. The N‐terminal E2a and E2b tagging modules were based on pOM‐series plasmid. The pOM‐series plasmids were selected for this study because of their use of the Cre–loxP recombination system. The latter enables a marker cassette to be removed after integration into the loci of interest and, thereafter, the tagged protein is expressed under its endogenous promoter. Specifically for fission yeast, high copy pREP plasmids containing the E2a epitope tag as an N‐terminal or C‐terminal tag were constructed. The properties of E2a and E2b epitopes and the sensitivity of two anti‐E2 monoclonal antibodies (5E11 and 3F12) were tested using several S. cerevisiae and Sz. pombe E2‐tagged strains. Copyright © 2009 John Wiley & Sons, Ltd.
Familial Parathyroid Tumors: Diagnosis and Management
Authors: Stålberg Peter , Carling Tobias 
Published: January 2009

AbstractBackgroundThe management of hyperparathyroidism (HPT) in the familial setting is complex. Due to the rarity of familial HPT and its different presentation within and between the familial syndromes and individual kindreds, treatment recommendations based on high levels of evidence cannot be made. However, based on the molecular genetic studies and case series from institutions with significant experience, important management principles (grade C recommendations) have been developed.MethodsWe conducted a systematic review of the literature using evidence‐based criteria.ResultsIssue 1: initial operation in multiple endocrine neoplasia type 1 (MEN1), a grade C recommendation can be made for subtotal parathyroidectomy. Issue 2: initial surgery in MEN 2A, a grade C recommendation can be made for excision of enlarged glands only. Issue 3: surgery in familial isolated HPT and HPT‐jaw tumor (HPT‐JT) syndrome may be treated with parathyroidectomy that is subtotal or less, although the risk of parathyroid cancer in HPT‐JT requires attention (no grade of recommendation). Issue 4: parathyroid surgery in familial HPT syndromes in the setting of underlying mutations in the calcium receptor (CASR) gene involves subtotal parathyroidectomy (no grade of recommendation). Issue 5: the use of intraoperative PTH measurements in familial HPT may guide the extent of parathyroid resection (no grade of recommendation).ConclusionsThe goals of parathyroidectomy in familial HPT are to achieve and maintain normocalcemia for the longest time possible, avoid both iatrogenic hypocalcemia and operative complications, and facilitate future surgery for recurrent disease.
Stability, participation and transparency in renewable energy policy: Lessons from Denmark and the United States
Authors: Mendonça Miguel , Lacey Stephen , Hvelplund Frede 
Published: January 2009

Abstract
The expansion and long-term sustainability of the renewable energy industry will depend on many factors. Energy demand, energy access, energy security, the green collar jobs agenda and climate protection will all drive the industry forward. Public opposition and insufficient financial support can hold it back. To facilitate steady, sustainable growth of the renewable energy market, careful consideration of promotion policies will be necessary to ensure that the inherently distributed nature of renewable energy sources translates into diverse ownership, with broad support. Such support will drive the rapid deployment of these socially and economically beneficial and environmentally necessary technologies. This acceleration can be created through innovative democracy, which attempts to bring all actors into the decision-making process. When considered as a market driver for renewable energy, this equitable, participatory approach must be considered in conjunction with stable financial support schemes which allow diverse actors to engage the market. Lessons from Denmark and the United States show why this combination of conditions is central to the rapid deployment of renewable energy. Policymakers can assess the effectiveness of this approach by analysing which groups benefit most from the design of different policies. The authors suggest several criteria for performing this analysis.
Appearance and Reality
Authors: Wisdom John 
Published: January 2009

1. ‘How do we know the material world?’, ‘What is it to know the material world?’, ‘In what ways is knowledge of the material world like and in what ways is it unlike other sorts of knowledge?’We know how we know the material world and what it is to know the material world and in what ways such knowledge is like and unlike other sorts of knowledge. But a man who knows what poetry is like and how it is like and unlike prose may ask ‘What is poetry?’, and a mathematician who knows what it is like to do mathematics may ask ‘What is mathematics?’ It is in a rather like way that we ask ‘What is knowledge of the material world?’ The ways in which knowledge of the material world is like and unlike other sorts of knowledge are familiar to us but we wish for a still better grasp of these likenesses and unlikenesses.
Consciousness and Life
Authors: Matthews Gareth B. 
Published: January 2009

In L. Frank Baum's story, Ozma of Oz, which is a sequel to Baum's much more famous story, The Wonderful Wizard of Oz, Dorothy and her companion come upon a wound-down mechanical man bearing a label on which are printed the following words:Smith and Tinker'sPatent Double-Action, Extra-Responsive, Thought-CreatingPerfect-TalkingMECHANICAL MANFitted with our Special Clock-Work Attachment Thinks, Speaks, Acts, and Does Everything but Live(Ozma of Oz, Chicago, 1907, p. 43)As Dorothy and her companion are made to discover when they wind up this man (‘Tik-Tok’ is his name), he is indeed capable of doing all the things of which his label boasts—acting, speaking and even thinking. But as Tik-Tok himself insists, and no one in the story casts doubt on the matter, he is not alive.
Memory and Self: A Neuropathological Approach
Authors: Puccetti Roland 
Published: January 2009

[We understand by ‘person’] a thinking intelligent being, that has reason and reflection, and can consider itself, as itself, the same thinking thing, in different times and places… (John Locke).There has been a tendency among philosophers ever since Locke to conflate the problem of the self with the problem of personal identity, and since memory is clearly essential to a sense of one's identity through time, it is easy to suppose that having a concept of self requires memory too.
Understanding Proofs: Meno, 85d9–86c2, Continued
Authors: Anscombe G. E. M. 
Published: January 2009

Purely by questioning Socrates has elicited from an uninstructed slave the conclusion that the square on the diagonal of a square is twice the original square in area. Then comes a part of the dialogue which I translate:Socrates. This knowledge, then, that he has now, he either got some time, or always had?Meno. Yes.
Consequentialism, Moralities of Concern, and Selfishness
Authors: Honderich Ted 
Published: January 2009

Here are some kinds of reasons for taking an action to have been morally right.(1) It was done out of a good intention or a pure good will on the part of the agent, or was owed to a virtue of hers.(2) It issued from the agent's moral perception or intuition with respect to a situation, not from the application of a general principle or from calculation of the consequences of possible actions.(3) Although it would give rise to distress or worse, the action was one of integrity, autonomy, or self-concern, perhaps in accord with the agent's aversion to killing by her own hand, or true to her life-hope to achieve a success on her own.
Kierkegaard and Euthyphro
Authors: Wisdo David 
Published: January 2009

In Plato's dialogue the Euthyphro, Socrates poses a question that has come to be known as the ‘Euthyphro dilemma’. Since the first formulation of this problem is surely the best, I will quote from Socrates himself:… For consider: is the holy loved by the gods because it is holy? Or is it holy because it is loved by the gods?
Governing Danish Agencies by Contract: From Negotiated Freedom to the Shadow of Hierarchy
Authors: BINDERKRANTZ ANNE SKORKJÆR , CHRISTENSEN JØRGEN GRØNNEGAARD 
Published: January 2009

ABSTRACTIn the early 1990s the Danish Ministry of Finance initiated an experiment where a few ministerial departments negotiated performance agreements with their agencies. Since then internal contracting has spread and is now nearly universally used in central government. However, a close study demonstrates that in this process contract content has changed dramatically. The early contracts were quid-pro-quo agreements. Agencies committed themselves to improve efficiency but contracts at the same time admitted them increased managerial discretion. The mature contracts are quite different. Departmental ministries have exploited their considerable autonomy to set demands that are related to policy and service levels rather than internal management. Here ministries have adapted to the characteristics of their policy tasks and to the presumed concerns of the target groups dominating their political environment. Building on an analysis of all contracts in force in 1995, 2000, and 2005 the paper sees this change as a transformation of an ideal type NPM-instrument into a managerial tool adapted to a system where highly autonomous ministers act as unquestioned political executives.