bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Hybrid Public-Private Bodies: The World Anti-Doping Agency (WADA)
Authors: Casini Lorenzo 
Published: April 2010

AbstractActing in concert, States, sporting institutions and members of the international community have created a body that is emblematic of the emergence of the new forms of hybrid public-private governance mechanisms in the global sphere: the World Anti-Doping Agency (WADA). This article examines the structure and activities of this institution, in order to highlight a number of problems concerning the increasing use of public-private partnerships (PPPs) at the global level: the spread of normative functions carried out by global institutions and the binding force of these norms; the harmonization of different regulations at the global level; and the adoption of administrative law type mechanisms within global regimes and the emergence of global administrative law.
Clonal expansion and TCR-independent differentiation shape the HIV-specific CD8+ effector-memory T-cell repertoire in vivo
Authors: Meyer-Olson Dirk , Simons Brenna C. , Conrad Joseph A. , Smith Rita M. , Barnett Louise , Lorey Shelly L. , Duncan Coley B. , Ramalingam Ramesh , Kalams Spyros A. 
Published: April 2010

AbstractFlexibility of the HIV-specific T-cell receptor repertoire is a hallmark of HIV-1 infection. Altered differentiation of HIV-specific CD45RO+/CCR7− (TemRO) CD8+ effector-memory T cells into CD45RA+/CCR7− (TemRA) CD8+ effector-memory T cells as well as increased expression of the senescence marker CD57 has been frequently observed HIV-1 infection, but the structural relationship between clonal expansion and T-cell differentiation has not been defined. In this study, we demonstrate that HIV-specific clonotypes have differing degrees of TemRA differentiation but always maintain a significant proportion of TemRO-phenotype cells. These data indicate that structural constraints of the TCR/peptide major histocompatibility complex interaction play a central role in the TemRA differentiation of HIV-specific CD8+ T cells in chronic HIV-1 infection. Clonotypes with a predominantly TemRA phenotype had a substantial fraction of cells without expression of CD57; and in contrast to the high clonotypic variability of TemRA differentiation, expression of CD57 was highly correlated among T-cell clonotypes within epitope-specific responses, indicating TCR-independent expression of CD57 in vivo. Our data highlight the importance of the structural composition of the TCR repertoire for the effector-memory differentiation of the immune response in chronic viral infections and suggest that TCR-dependent and -independent homeostasis shapes the pathogen-specific effector-memory repertoire in vivo.
In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia
Authors: Choi Jaebok , Ritchey Julie , Prior Julie L. , Holt Matthew , Shannon William D. , Deych Elena , Piwnica-Worms David R. , DiPersio John F. 
Published: April 2010

Abstract
Regulatory T cells (Tregs) suppress graft-versus-host disease (GVHD) while preserving a beneficial graft-versus-leukemia (GVL) effect. Thus, their use in allogeneic stem cell transplantation (SCT) provides a promising strategy to treat GVHD. However, 3 obstacles prevent their routine use in human clinical trials: (1) low circulating number of Tregs in peripheral blood, (2) loss of suppressor function after in vitro expansion, and (3) lack of Treg-specific surface markers necessary for efficient purification. FOXP3 is exclusively expressed in Tregs and forced expression in CD4+CD25− T cells can convert these non-Tregs into Tregs with functional suppressor function. Here, we show that the FDA-approved hypomethylating agents, decitabine (Dec) and azacitidine (AzaC), induce FOXP3 expression in CD4+CD25− T cells both in vitro and in vivo. Their suppressor function is dependent on direct contact, partially dependent on perforin 1 (Prf1), but independent of granzyme B (GzmB), and surprisingly, Foxp3. Independence of Foxp3 suggests that genes responsible for the suppressor function are also regulated by DNA methylation. We have identified 48 candidate genes for future studies. Finally, AzaC treatment of mice that received a transplant of major histocompatibility complex mismatched allogeneic bone marrow and T cells mitigates GVHD while preserving GVL by peripheral conversion of alloreactive effector T cells into FOXP3+ Tregs and epigenetic modulation of genes downstream of Foxp3 required for the suppressor function of Tregs.
S100A10 regulates plasminogen-dependent macrophage invasion
Authors: O'Connell Paul A. , Surette Alexi P. , Liwski Robert S. , Svenningsson Per , Waisman David M. 
Published: April 2010

AbstractThe plasminogen activation system plays an integral role in the migration of macrophages in response to an inflammatory stimulus, and the binding of plasminogen to its cell-surface receptor initiates this process. Although previous studies from our laboratory have shown the importance of the plasminogen receptor S100A10 in cancer cell plasmin production, the potential role of this protein in macrophage migration has not been investigated. Using thioglycollate to induce a peritoneal inflammatory response, we demonstrate, for the first time, that compared with wild-type (WT) mice, macrophage migration across the peritoneal membrane into the peritoneal cavity in S100A10-deficient (S100A10−/−) mice was decreased by up to 53% at 24, 48, and 72 hours. Furthermore, the number of S100A10-deficient macrophages that infiltrated Matrigel plugs was reduced by 8-fold compared with their WT counterpart in vivo. Compared with WT macrophages, macrophages from S100A10−/− mice demonstrated a 50% reduction in plasmin-dependent invasion across a Matrigel barrier and a 45% reduction in plasmin generation in vitro. This loss in plasmin-dependent invasion was in part the result of a decreased generation of plasmin and a decreased activation of pro-MMP-9 by S100A10-deficient macrophages. This study establishes a direct involvement of S100A10 in macrophage recruitment in response to inflammatory stimuli.
High-throughput marker discovery in melon using a self-designed oligo microarray
Authors: Ophir Ron , Eshed Ravit , Harel-Beja Rotem , Tzuri Galil , Portnoy Vitaly , Burger Yoseph , Uliel Shai , Katzir Nurit , Sherman Amir 
Published: April 2010

AbstractBackgroundGenetic maps constitute the basis of breeding programs for many agricultural organisms. The creation of these maps is dependent on marker discovery. Melon, among other crops, is still lagging in genomic resources, limiting the ability to discover new markers in a high-throughput fashion. One of the methods used to search for molecular markers is DNA hybridization to microarrays. Microarray hybridization of DNA from different accessions can reveal differences between them--single-feature polymorphisms (SFPs). These SFPs can be used as markers for breeding purposes, or they can be converted to conventional markers by sequencing. This method has been utilized in a few different plants to discover genetic variation, using Affymetrix arrays that exist for only a few organisms. We applied this approach with some modifications for marker discovery in melon.ResultsUsing a custom-designed oligonucleotide microarray based on a partial EST collection of melon, we discovered 6184 putative SFPs between the parents of our mapping population. Validation by sequencing of 245 SFPs from the two parents showed a sensitivity of around 79%. Most SFPs (81%) contained single-nucleotide polymorphisms. Testing the SFPs on another mapping population of melon confirmed that many of them are conserved.ConclusionThousands of new SFPs that can be used for genetic mapping and molecular-assisted breeding in melon were discovered using a custom-designed oligo microarray. A portion of these SFPs are conserved and can be used in different breeding populations. Although improvement of the discovery rate is still needed, this approach is applicable to many agricultural systems with limited genomic resources.
Transcriptomic analysis of the venom gland of the red-headed krait (Bungarus flaviceps) using expressed sequence tags
Authors: Siang Ang Swee , Doley Robin , Vonk Freek J , Kini R Manjunatha 
Published: April 2010

AbstractBackgroundThe Red-headed krait (Bungarus flaviceps, Squamata: Serpentes: Elapidae) is a medically important venomous snake that inhabits South-East Asia. Although the venoms of most species of the snake genusBungarushave been well characterized, a detailed compositional analysis ofB. flavicepsis currently lacking.ResultsHere, we have sequenced 845 expressed sequence tags (ESTs) from the venom gland of aB. flaviceps. Of the transcripts, 74.8% were putative toxins; 20.6% were cellular; and 4.6% were unknown. The main venom protein families identified were three-finger toxins (3FTxs), Kunitz-type serine protease inhibitors (including chain B of β-bungarotoxin), phospholipase A2(including chain A of β-bungarotoxin), natriuretic peptide (NP), CRISPs, and C-type lectin.ConclusionThe 3FTxs were found to be the major component of the venom (39%). We found eight groups of unique 3FTxs and most of them were different from the well-characterized 3FTxs. We found three groups of Kunitz-type serine protease inhibitors (SPIs); one group was comparable to the classical SPIs and the other two groups to chain B of β-bungarotoxins (with or without the extra cysteine) based on sequence identity. The latter group may be functional equivalents of dendrotoxins inBungarusvenoms. The natriuretic peptide (NP) found is the first NP for any Asian elapid, and distantly related to Australian elapid NPs. Our study identifies several unique toxins inB. flavicepsvenom, which may help in understanding the evolution of venom toxins and the pathophysiological symptoms induced after envenomation.
HIV/AIDS knowledge in detention in Hunan province, China
Authors: Zhang Weidong , Wang Xinya , Chen Xi , Lv Fan 
Published: April 2010

Abstract

Background
Injection drug use (IDU) is one of the major modes of HIV transmission in China. Drug use is illegal in China, all identified drug users are registered by Public Security Bureau, and most were sent to detention; most detainees engaged in high risk behaviours. In order to well understand the HIV/AIDS knowledge among detainees, a survey was conducted in different detention settings in Hunan province in 2008 to assess knowledge and attitudes about HIV among detainees and to provide useful information for HIV prevention and intervention strategies in detention centers.

Methods
A cross-sectional survey was conducted in 10 detentions in Hunan province, China, and demographic information along with knowledge and attitude of HIV/AIDS was collected through standardized interviews. Descriptive statistics were used to describe HIV knowledge, attitudes, and education services among detainees.

Results
There were 956 detainees interviewed from 10 detention centers. The male to female ratio was 2.24:1. The majority detainees received nine years of compulsory education, accounting for 51.5%. There were nine questions to assess HIV/AIDS knowledge of detainees, and 35.7% of those surveyed answered all nine questions correctly. There were 92.3% (882/956) who consented to be informed about the HIV antibody test results when tested, and 81% (774/956) elected that their family members were also informed. All detention centers had an organized HIV/AIDS education program.

Conclusion
This study gives us an overview about HIV/AIDS knowledge in detention in Hunan province, and all detention sites in the study provided HIV/AIDS intervention services among detainees that focused on HIV/AIDS knowledge, attitude, and health behaviors.
5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase
Authors: Ji Hong-Tai , Chien Li-Ting , Lin Yu-Hsin , Chien Hsiung-Fei , Chen Chin-Tin 
Published: April 2010

Abstract
Photodynamic therapy (PDT) has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) signaling cascades are activated following 5-aminolevulinic acid (ALA)-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy.
The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD)
Authors: Liu Qing , Bengmark Stig , Qu Shen 
Published: April 2010

AbstractNonalcoholic fatty liver disease is increasingly regarded as a hepatic manifestation of metabolic syndrome, and the severity of nonalcoholic fatty liver disease seems to increase in parallel with other features of metabolic syndrome. Excess lipid accumulation in the liver cells is not only a mediator of Metabolic Syndrome and indicator of a lipid overload but also accompanied by a range of histological alterations varying from 'simple' steatosis to nonalcoholic steatohepatitis, with time progressing to manifest cirrhosis. Hepatocellular carcinoma may also occur in nonalcoholic steatohepatitis -related cirrhosis with a mortality rate similar to or worse than for cirrhosis associated with hepatitis C. This review summarizes the knowledge about the causal relationship between hepatic fat accumulation, insulin resistance, liver damage and the etiological role of hepatic fat accumulation in pathogenesis of extra- and intra-hepatic manifestations. Special emphasis is given suggestions of new targets treatment and prevention of nonalcoholic fatty liver disease.
High Human T Cell Leukemia Virus Type-1(HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders
Authors: Sasaki Daisuke , Doi Yuko , Hasegawa Hiroo , Yanagihara Katsunori , Tsukasaki Kunihiro , Iwanaga Masako , Yamada Yasuaki , Watanabe Toshiki , Kamihira Shimeru 
Published: April 2010

Abstract

Background
To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods.

Results
The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL.

Conclusion
The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.
Comparative effectiveness research: Challenges for medical journals
Authors: Sox Harold C , Helfand Mark , Grimshaw Jeremy , Dickersin Kay ,   The PLoS Medicine Editors, Tovey David , Knottnerus J André , Tugwell Peter 
Published: April 2010

Abstract
Editors from a number of medical journals lay out principles for journals considering publication of Comparative Effectiveness Research (CER). In order to encourage dissemination of this editorial, this article is freely available in PLoS Medicine and will be also published in Medical Decision Making, Croatian Medical Journal, The Cochrane Library, Trials, The American Journal of Managed Care, and Journal of Clinical Epidemiology.
The radiosensitizing effect of Ku70/80 knockdown in MCF10A cells irradiated with X-rays and p(66)+Be(40) neutrons
Authors: Vandersickel Veerle , Mancini Monica , Slabbert Jacobus , Marras Emanuela , Thierens Hubert , Perletti Gianpaolo , Vral Anne 
Published: April 2010

Abstract

Background
A better understanding of the underlying mechanisms of DNA repair after low- and high-LET radiations represents a research priority aimed at improving the outcome of clinical radiotherapy. To date however, our knowledge regarding the importance of DNA DSB repair proteins and mechanisms in the response of human cells to high-LET radiation, is far from being complete.

Methods
We investigated the radiosensitizing effect after interfering with the DNA repair capacity in a human mammary epithelial cell line (MCF10A) by lentiviral-mediated RNA interference (RNAi) of the Ku70 protein, a key-element of the nonhomologous end-joining (NHEJ) pathway. Following irradiation of control and Ku-deficient cell lines with either 6 MV X-rays or p(66)+Be(40) neutrons, cellular radiosensitivity testing was performed using a crystal violet cell proliferation assay. Chromosomal radiosensitivity was evaluated using the micronucleus (MN) assay.

Results
RNAi of Ku70 caused downregulation of both the Ku70 and the Ku80 proteins. This downregulation sensitized cells to both X-rays and neutrons. Comparable dose modifying factors (DMFs) for X-rays and neutrons of 1.62 and 1.52 respectively were obtained with the cell proliferation assay, which points to the similar involvement of the Ku heterodimer in the cellular response to both types of radiation beams. After using the MN assay to evaluate chromosomal radiosensitivity, the obtained DMFs for X-ray doses of 2 and 4 Gy were 2.95 and 2.66 respectively. After neutron irradiation, the DMFs for doses of 1 and 2 Gy were 3.36 and 2.82 respectively. The fact that DMFs are in the same range for X-rays and neutrons confirms a similar importance of the NHEJ pathway and the Ku heterodimer for repairing DNA damage induced by both X-rays and p(66)+Be(40) neutrons.

Conclusions
Interfering with the NHEJ pathway enhanced the radiosensitivity of human MCF10A cells to low-LET X-rays and high-LET neutrons, pointing to the importance of the Ku heterodimer for repairing damage induced by both types of radiation. Further research using other high-LET radiation sources is however needed to unravel the involvement of DNA double strand break repair pathways and proteins in the cellular response of human cells to high-LET radiation.
Stationary or onboard energy storage systems for energy consumption reduction in a metro network
Authors: Barrero R , Tackoen X , van Mierlo J 
Published: April 2010

This article will compare the benefits and constraints of onboard and stationary energy storage systems (ESS) with the aim of reducing the overall energy consumption on a low DC voltage metro network. A dedicated simulation tool that models a metro line with conventional or hybrid trains and stationary supercapacitor (SC)-based ESSs has been developed for this purpose. The model can simulate the energy exchange among simultaneously running vehicles of a conventional metro line and evaluate the effect of a stationary ESS when installed along the line. Different traffic scenarios are considered for the study: high, moderate, and low traffic volume as this element has a strong influence on the energy exchange among the running vehicles and therefore on the energy available for storage in the ESS. This will eventually determine the energy consumption reduction. This simulation tool is used to study the most convenient ESS alternative for the case of a Brussels metro line. When compared with a conventional metro line, the total energy consumption reduction achieved with stationary ESS varies in function of the traffic conditions, ESS size, and ESS distribution along the line. With efficient metro trains, values of energy savings up to 18.7, 25.1, and 36.4 per cent can be obtained at high, moderate, and low traffic volumes, respectively. In contrast, using onboard ESS on every vehicle, the maximum energy savings achieved vary between 27.3 and 36.3 per cent at high and low traffic volumes, respectively. Results show that even though the energy savings achieved are higher with onboard ESS, the amount of SC cells needed is lower when using stationary ESS. However, benefits such as peak power shaving, voltage drop reductions, and reduced line losses are better attained by onboard ESS.
Ghrelin affects the hypothalamus–pituitary–thyroid axis in humans by increasing free thyroxine and decreasing TSH in plasma
Authors: Kluge Michael , Riedl Stefan , Uhr Manfred , Schmidt Doreen , Zhang Xiaochi , Yassouridis Alexander , Steiger Axel 
Published: April 2010

ObjectiveGhrelin promotes a positive energy balance, e.g. by increasing food intake. Stimulation of the activity of the hypothalamus–pituitary–thyroid (HPT) axis promotes a negative energy balance, e.g. by increasing energy expenditure. We therefore hypothesized that ghrelin suppresses the HPT axis in humans, counteracting its energy-saving effect.Design and methodsIn this single-blind, randomized, cross-over study, we determined secretion patterns of free triiodothyronine (fT3), free thyroxine (fT4), TSH, and thyroid-binding globulin (TBG) between 2000 and 0700 h in 20 healthy adults (10 males and 10 females, 25.3±2.7 years) receiving 50 μg ghrelin or placebo at 2200, 2300, 0000, and 0100 h.ResultsFT4plasma levels were significantly higher after ghrelin administration than after placebo administration from 0000 h until 0620 h except for the time points at 0100, 0520, and 0600 h. TSH plasma levels were significantly lower from 0200 until the end of the study at 0700 h except for the time points at 0540, 0600, and 0620 h. The relative increase of fT4(area under the curve (AUC) 0130–0700 h (ng/dl×min): placebo: 1.31±0.03; ghrelin: 1.39±0.03;P=0.001) was much weaker than the relative decrease of TSH (AUC 0130–0700 h (mIU/ml×min): placebo: 1.74±0.12; ghrelin: 1.32±0.12;P=0.007). FT3and TBG were not affected.ConclusionsThis is the first study to report that ghrelin affects the HPT axis in humans. The early fT4increase was possibly induced by direct ghrelin action on the thyroid where ghrelin receptors have been identified. The TSH decrease might have been caused by ghrelin-mediated inhibition at hypothalamic level by feedback inhibition through fT4, or both.