bluuebunny/crossref_metadata_2025 huggingface dataset:
On two critics of justificatory liberalism: A response to Wall and Lister
Authors: Gaus Gerald
Published: April 2010

In replying to Steven Wall’s and Andrew Lister’s thoughtful essays on my account of justificatory liberalism in this issue, I respond to many of their specific criticisms while taking the opportunity to explicate the foundations of justificatory liberalism. Justificatory liberalism takes seriously the moral requirement to justify all claims of authority over others, as well as all coercive interferences with their lives. If we do so, although we are by no means committed to libertarianism, we find that that many of our cherished values, moral intuitions, and political aspirations no longer ground the range of authority over others many of us would claim. In this sense, justificatory liberalism is a theory of limited authority and limited government — which is what a genuinely liberal theory must be.
Integrated Theoretical Model for Building Effective Teams
Authors: Gilley Jerry W. , Morris M. Lane , Waite Alina M. , Coates Tabitha , Veliquette Abigail
Published: April 2010

The purpose of this article is to construct an integrated theoretical model for building effective teams based on a literature review guided by several research questions on all aspects of teams, team building, team member selection, team development, and theoretical constructs that affect the development of effective teams. The principal outcome of this article is a relationship model that is grounded in the teams, teamwork, and team building literature and based on several theoretical frameworks. This rigorous model may be applied consistently among human resource development (HRD) practitioners and scholars to assist them in building effective teams.
Hydrogel Matrix to Support Stem Cell Survival After Brain Transplantation in Stroke
Authors: Zhong Jin , Chan Albert , Morad Leeron , Kornblum Harley I. , Guoping Fan  , Carmichael S. Thomas
Published: April 2010

Stroke is a leading cause of adult disability. Stem/progenitor cell transplantation improves recovery after stroke in rodent models. These studies have 2 main limitations to clinical translation. First, most of the cells in stem/progenitor transplants die after brain transplantation. Second, intraparenchymal approaches target transplants to normal brain adjacent to the stroke, which is the site of the most extensive natural recovery in humans. Transplantation may damage this tissue. The stroke cavity provides an ideal target for transplantation because it is a compartmentalized region of necrosis, can accept a high volume transplant without tissue damage, and lies directly adjacent to the most plastic brain area in stroke. However, direct transplantation into the stroke cavity has caused massive death in the transplant. To overcome these limitations, the authors tested stem/progenitor transplants within a specific biopolymer hydrogel matrix to create a favorable environment for transplantation into the infarct cavity after stroke, and they tested this in comparison to stem cell injection without hydrogel support. A biopolymer hydrogel composed of cross-linked hyaluronan and heparin sulfate significantly promoted the survival of 2 different neural progenitor cell lines in vitro in conditions of stress and in vivo into the infarct cavity. Quantitative analysis of the transplant and surrounding tissue indicates diminished inflammatory infiltration of the graft with the hydrogel transplant. This result indicates that altering the local environment in stem cell transplantation enhances survival and diminishes cell stress. Stem cell transplantation into the infarct cavity within a pro-survival hydrogel matrix may provide a translational therapy for stroke recovery.
Resistance Training for Women’s Health
Authors: Terre Lisa
Published: April 2010

This review discusses evidence-based perspectives on resistance training for women’s health. Future directions for inquiry and empirically driven public policy initiatives also are addressed.
Review: Chemical and structural modifications of pulmonary collectins and their functional consequences
Authors: Atochina-Vasserman Elena N. , Beers Michael F. , Gow Andrew J.
Published: April 2010

The lung is continuously exposed to inhaled pathogens (toxic pollutants, micro-organisms, environmental antigens, allergens) from the external environment. In the broncho-alveolar space, the critical balance between a measured protective response against harmful pathogens and an inappropriate inflammatory response to harmless particles is discerned by the innate pulmonary immune system. Among its many components, the surfactant proteins and specifically the pulmonary collectins (surfactant proteins A [SP-A] and D [SP-D]) appear to provide important contributions to the modulation of host defense and inflammation in the lung. Many studies have shown that multimerization of SP-A and SP-D are important for efficient local host defense including neutralization and opsonization of influenza A virus, binding Pneumocystis murina and inhibition of LPS-induced inflammatory cell responses. These observations strongly imply that oligomerization of collectins is a critical feature of its function. However, during the inflammatory state, despite normal pool sizes, chemical modification of collectins can result in alteration of their structure and function. Both pulmonary collectins can be altered through proteolytic inactivation, nitration, S-nitrosylation, oxidation and/or crosslinking as a consequence of the inflammatory milieu facilitated by cytokines, nitric oxide, proteases, and other chemical mediators released by inflammatory cells. Thus, this review will summarize recent developments in our understanding of the relationship between post-translational assembly of collectins and their modification by inflammation as an important molecular switch for the regulation of local innate host defense.
Brand Rights and Hotel Management Agreements
Authors: Dev Chekitan S. , Thomas John H. , Buschman John , Anderson Eric
Published: April 2010

In this article, the authors consider the managerial implications of a recent lawsuit, P. T. Karang Mas Sejahtera v. The Ritz-Carlton Hotel Company, LLC, in which a jury found for the plaintiff, the owner of the Ritz-Carlton Bali Resort and Spa, against the defendant, The Ritz-Carlton Hotel Company, LLC. Ritz-Carlton’s parent company, Marriott International, had previously formed a partnership with Bulgari S.p.A., the Italian luxury jewelry and accessories firm, to create Bulgari Hotels and Resorts, a new ultraexclusive line of luxury hotels. The first two Bulgari properties opened in Milan and Bali. Soon after the Bali project was announced, P. T. Karang Mas Sejahtera (KMS) sued Ritz-Carlton for breach of agreement. The authors show that this and other recent court decisions situate hotel management agreements squarely under agency law. Within the framework of agency law, an agent owes specific fiduciary duties to a principal that supersede contractual terms and a principal has a nearly absolute right to terminate such a agreement. In the Bali case, the violated duties included a duty not to compete with or assist the competitors of a property being managed under agreements within that property’s competitive market set. The authors argue that, as a consequence of these legal decisions, issues pertaining to brand rights and management agreements have been clarified. In this article, the authors outline these brand rights issues, review these precedent-setting legal cases, explain why Ritz-Carlton lost the suit to KMS, and draw several lessons pertaining to hotel management.
Voltage and Temperature Coefficients of Resistance of Polyethylene/ Nanocarbon-Based Thick Film Composites: Melt-Mixing Versus Melt-Infiltration Synthesis
Authors: Sandu Ion , Morjan Ion , Voicu Ion , Dumitrache Florian , Fleaca Claudiu Teodor , Gavrila-Florescu Lavinia
Published: April 2010

Carbon-composed resistors, thick film resistors, and chip resistors are commonly used in Electronics. They are prepared by mixing carbon-based materials with metal oxides or polymers and present not only some clear advantages such as low cost and easy processing, but also some unwanted characteristics such as voltage and temperature dependence of the electrical properties. Considering that the polymer-carbon mixing process induces high values for the voltage and temperature resistance coefficients (VCR, TCR) of the composites, we have developed a new method for preparing polymer/nanocarbon thick films (the melt-infiltration method) which minimizes these values. Direct current electrical measurements show VCR values of almost two orders of magnitude lower for polyethylene/nanocarbon thick film composites prepared by melt-infiltration than for composites prepared by melt-mixing (—0.04%/V and —2.5%/V, respectively).
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

Flexibility 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

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

The 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

Background

Genetic 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.

Results

Using 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.

Conclusion

Thousands 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

Background

The 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.

Results

Here, 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.

Conclusion

The 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

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

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

Nonalcoholic 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

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

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

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.
Phenotype ontologies for mouse and man: bridging the semantic gap
Authors: Schofield Paul N. , Gkoutos Georgios V. , Gruenberger Michael , Sundberg John P. , Hancock John M.
Published: April 2010

A major challenge of the post-genomic era is coding phenotype data from humans and model organisms such as the mouse, to permit the meaningful translation of phenotype descriptions between species. This ability is essential if we are to facilitate phenotype-driven gene function discovery and empower comparative pathobiology. Here, we review the current state of the art for phenotype and disease description in mice and humans, and discuss ways in which the semantic gap between coding systems might be bridged to facilitate the discovery and exploitation of new mouse models of human diseases.
A method for the in situ measurement of evolving elliptical cross-sections in initially cylindrical Taylor impact specimens
Authors: Wielewski E , Arthington M R , Siviour C R , Carter S , Hofmann F , Korsunsky A M , Petrinic N
Published: April 2010

This paper presents a novel approach to the classic Taylor impact experiment using an ultra-high-speed camera and mirror arrangement to measure the elliptical cross-section of a specimen in situ as a function of time. This optical measurement technique is used to quantify the key aspects of material behaviour, such as the area strain perpendicular to the impact direction and the lengths of the semimajor and semiminor axes of the elliptical sample cross-section, which were caused by anisotropic plastic deformation, as functions of time and the axial position. The application of this technique gives access to previously unattainable data on the anisotropic plastic deformation of Taylor impact specimens and therefore has the potential to provide a more rigorous method of validation for anisotropic constitutive material models. To demonstrate the feasibility of the new method, experiments were carried out on cylindrical Taylor impact specimens machined from strongly textured high-purity zirconium plate. The surface geometry of a recovered specimen was measured using a coordinate measurement machine and compared with the optically measured surface geometry reconstructed from post-impact images. Excellent agreement between the two methods was found.
Soft elastohydrodynamic analysis of rotary lip seals
Authors: Salant R F
Published: April 2010

The extensive literature on the elastohydrodynamic analysis of rotary lip seals is reviewed. Models that predict quantities such as film thickness and reverse pumping rate and that elucidate the physical processes governing the behaviour of rotary lip seals are described. Thermal effects, mixed lubrication, capillary effects, transients, viscoelasticity, statistical approaches, and so-called hydrodynamic seals are discussed.
Development of a common set of European high-level track maintenance cost categories
Authors: Bouch C J , Roberts C , Amoore J
Published: April 2010

The track maintenance and renewal cost categories used by infrastructure managers (IMs) have an important role to play in pricing transport infrastructure access, improving the efficiency of IM performance, and helping to focus efforts to reduce track costs. However, very little work has been done so far to identify a common set of European cost categories, capable of supporting progress in these areas. This paper describes an analysis of the IMs— existing cost categories, carried out to identify those accounting for the largest proportion of the annual maintenance budget and to develop a common European set of cost categories to support future pricing and efficiency work. The study found five maintenance activities, which account for over 80 per cent of the overall annual track maintenance expenditure, and on which further research should be focused to achieve cost reductions. These were, in the descending order of importance: switches and crossings, inspection, rail changing, tamping, and re-sleepering. It also identified the following categories as the basis for future recording of maintenance costs by IMs: track, inspection, geometry, grinding, welding, drainage, subgrade, periodic, and rail lubrication.
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.
Modular domains of the Dicistroviridae intergenic internal ribosome entry site
Authors: Jang Christopher J. , Jan Eric
Published: April 2010

The intergenic region internal ribosome entry site (IGR IRES) of the Dicistroviridae viral family can directly assemble 80S ribosomes and initiate translation at a non-AUG codon from the ribosomal A-site. These functions are directed by two independently folded domains of the IGR IRES. One domain, composed of overlapping pseudoknots II and III (PKII/III), mediates ribosome recruitment. The second domain, composed of PKI, mimics a tRNA anticodon–codon interaction to position the ribosome at the ribosomal A-site. Although adopting a common secondary structure, the dicistrovirus IGR IRESs can be grouped into two classes based on distinct features within each domain. In this study, we report on the modularity of the IGR IRESs and show that the ribosome-binding domain and the tRNA anticodon mimicry domain are functionally interchangeable between the Type I and the Type II IGR IRESs. Using structural probing, ribosome-binding assays, and ribosome positioning analysis by toeprinting assays, we show that the chimeric IRESs fold properly, assemble 80S ribosomes, and can mediate IRES translation in rabbit reticulocyte lysates. We also demonstrate that the chimeric IRESs can stimulate the ribosome-dependent GTPase activity of eEF2, which suggests that the ribosome is primed for a step downstream from IRES binding. Overall, the results demonstrate that the dicistrovirus IGR IRESs are composed of two modular domains that work in concert to manipulate the ribosome and direct translation initiation.
Use of two novel approaches to discriminate between closely related host microRNAs that are manipulated by Toxoplasma gondii during infection
Authors: Zeiner Gusti M. , Boothroyd John C.
Published: April 2010

MicroRNAs (miRNAs) are a class of small, endogenously encoded regulatory RNAs that function to post-transcriptionally regulate gene expression in a wide variety of eukaryotes. Within organisms, some mature miRNAs, such as paralogous miRNAs, have nearly identical nucleotide sequences, which makes them virtually indistinguishable from one another by conventional hybridization-based approaches. Here we describe two inexpensive, sensitive methods for rapidly discriminating between paralogous miRNAs or other closely related miRNAs and for quantifying their abundance. The first approach is a sequential ribonuclease-protection and primer-extension assay; the second approach is a primer-extension assay that employs short oligonucleotide probes to exacerbate the instability of mismatched probe:miRNA hybrids. Both approaches are rapid and can be easily performed in their entirety using common laboratory equipment. As a proof of concept, we have used these methods to determine the exact identities of the human miR-17 family members that are increased by infection with the intracellular parasite Toxoplasma gondii. These methods can be used to rapidly and inexpensively discriminate between any closely related miRNAs in any organism.
Rebuilding the RNOHT – The Political Way
Authors: Briggs Tim
Published: April 2010

My consultancy at the Royal National Orthopaedic Hospital Trust (RNOHT) commenced in 1992 with a reassurance that a new build was imminent. That was 18 years ago. Many things have changed in that time: multiple reorganisation of health authorities, new political leaders, new managers and reform after reform, changing the emphasis from patient-centred care to meeting government targets. While I welcome some of these, especially the reduction in waiting times, there has been a failure by successive administrations to recognise the importance of quality of care and the resulting outcome for patients and the value of specialist hospitals in delivering excellence and setting standards.
Working Together to Raise Standards
Authors: Lamb Norman
Published: April 2010

Over the next few years the NHS needs to face up to perhaps the most formidable challenge in its history. It must demonstrate that the NHS model can survive a looming age of austerity, in which rising costs associated with an ageing population are going to define whether the NHS thrives or comes under increasing challenge. Raising standards and improving efficency will be vital. It certainly won't be possible without the hard work and dedication of NHS staff.
Acorns to oak trees: the FGDP(UK)'s restorative dentistry programme
Authors: Brunton Paul
Published: April 2010

There has always been a need for and demand by primary dental care practitioners to develop their skills in general restorative dentistry. A certificate course in restorative dentistry was an idea that followed from a conversation I had many years ago with the late Malcolm Pendlebury, a previous Dean of the Faculty of General Dental Practice (UK). I was working at the University of Manchester at the time and initially it was thought that the certificate, now a diploma, would be run by the university though this did not prove possible. The FGDP(UK) was approached and it agreed to develop both the training programme and the qualification.
Languages and national identities in contact: the case of Latinos in Barcelona
Authors: Marshall Steve
Published: April 2010

Mass migration is having a dramatic effect on established minority groups in territories/regions/countries within larger pluri-nation states, especially where linguistic normalization policies are protecting national minority languages. Catalonia is one such case. With language recognized
as the symbol of many of Spain's historical and current identity crises (Mar-Molinero 1996), the recent mass migration of Spanish-speaking Latin American immigrants to Catalonia adds a new postcolonial twist to an already complex language-national identity dynamic. A spectrum of national identification
that has been historically dominated by essentialist and dual Catalan/Spanish national identities is now opening up to new national identities: entrenched essentialist Latin American identities, appropriated identities and multiple/hybrid identities associated with third space (Bhabha 1994).
This article presents data from a four-year ethnographic study of the languages and identities of Latinos in Barcelona. The data both confirm and problematize a range of theoretical perspectives on language, migration and national identity formation.
Cholesterol-Dependent Kinase Activity Regulates Transmitter Release from Cerebellar Synapses
Authors: Smith Alex J. , Sugita Shuzo , Charlton Milton P.
Published: April 2010

Changes in membrane cholesterol content can alter protein kinase activity, however, it is not known whether kinases regulating transmitter release are sensitive to membrane cholesterol content. Here we have used the cholesterol extracting agent methyl-β-cyclodextrin to measure the effects of acute cholesterol reduction on transmitter release from cultured cerebellar neurons. Cholesterol depletion increased the frequency of spontaneous transmitter release without altering the amplitude and time course of mEPSCs. Evoked transmitter release was decreased by cholesterol extraction and the paired pulse ratio was also decreased. Alterations in synaptic transmission were not associated with failure of action potential generation or changes in presynaptic Ca2+signaling. Both the increase in mEPSC frequency and the change in paired pulse ratio were blocked by the broad spectrum protein kinase inhibitor staurosporine. The increase in mEPSC frequency was also sensitive to selective inhibitors of PKC and PKA. Our results therefore demonstrate that the activity of presynaptic protein kinases that regulate spontaneous and evoked neurotransmitter release is sensitive to changes of membrane cholesterol content.
A Perisynaptic Ménage à Trois between Dlg,DLin-7, and Metro Controls Proper Organization of Drosophila Synaptic Junctions
Authors: Bachmann André , Kobler Oliver , Kittel Robert J. , Wichmann Carolin , Sierralta Jimena , Sigrist Stephan J. , Gundelfinger Eckart D. , Knust Elisabeth , Thomas Ulrich
Published: April 2010

Structural plasticity of synaptic junctions is a prerequisite to achieve and modulate connectivity within nervous systems, e.g., during learning and memory formation. It demands adequate backup systems that allow remodeling while retaining sufficient stability to prevent unwanted synaptic disintegration. The strength of submembranous scaffold complexes, which are fundamental to the architecture of synaptic junctions, likely constitutes a crucial determinant of synaptic stability. Postsynaptic density protein-95 (PSD-95)/ Discs-large (Dlg)-like membrane-associated guanylate kinases (DLG-MAGUKs) are principal scaffold proteins at both vertebrate and invertebrate synapses. AtDrosophilalarval glutamatergic neuromuscular junctions (NMJs) DlgA and DlgS97 exert pleiotropic functions, probably reflecting a few known and a number of yet-unknown binding partners. In this study we have identified Metro, a novel p55/MPP-likeDrosophilaMAGUK as a major binding partner of perisynaptic DlgS97 at larval NMJs. Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor proteinDLin-7. In a remarkably interdependent manner, Metro andDLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons. Using quantitative 3D-imaging we further demonstrate that the complex controls the size of postsynaptic glutamate receptor fields. Our findings accentuate the importance of perisynaptic scaffold complexes for synaptic stabilization and organization.
Canonical TGF-β Signaling Is Required for the Balance of Excitatory/Inhibitory Transmission within the Hippocampus and Prepulse Inhibition of Acoustic Startle
Authors: Sun Mu , Gewirtz Jonathan C. , Bofenkamp Lisa , Wickham Robert J. , Ge Hong , O'Connor Michael B.
Published: April 2010

Smad4 is a unique nuclear transducer for all TGF-β signaling pathways and regulates gene transcription during development and tissue homeostasis. To elucidate the postnatal role of TGF-β signaling in the mammalian brain, we generated forebrain-specific Smad4 knock-out mice. Surprisingly, the mutants showed no alteration in long-term potentiation and water maze, suggesting that Smad4 is not required for spatial learning and memory. However, these mutant mice did show enhancement of paired-pulse facilitation in excitatory synaptic transmission and stronger paired-pulse depression of GABAAcurrents in the hippocampus. The alteration of hippocampal electrophysiology correlated with mouse hyperactivity in homecage and open field tests. Mutant mice also showed overgrooming as well as deficits of prepulse inhibition, a widely used endophenotype of schizophrenia. With a specific real-time PCR array focused on TGF-β signaling pathway, we identified a novel regulation mechanism of the pathway in the hippocampal neurons, in which Smad4-mediated signaling suppresses the level of extracellular antagonism of TGF-β ligands through transcriptional regulation of follistatin, a selective inhibitor to activin/TGF-β signaling in the hippocampus. In summary, we suggest that the canonical TGF-β signaling pathway is critical for use-dependent modulation of GABAAsynaptic transmission and dendritic homeostasis; furthermore, a disruption in the balance of the excitatory and inhibitory hippocampal network can result in psychiatric-like behavior.
Differential Neuromodulation of Acquisition and Retrieval of Avoidance Learning by the Lateral Habenula and Ventral Tegmental Area
Authors: Shumake Jason , Ilango Anton , Scheich Henning , Wetzel Wolfram , Ohl Frank W.
Published: April 2010

Several studies suggest an opponent functional relationship between the lateral habenula (LHb) and the ventral tegmental area (VTA). Previous work has linked LHb activation to the inhibition of dopaminergic neurons during loss of reward, as well as to deficits in escape and avoidance learning. We hypothesized that a dopamine signal might underlie the negative reinforcement of avoidance responses and that LHb activation could block this signal and thereby cause avoidance deficits. To test this idea, we implanted stimulating electrodes in either the VTA or LHb of gerbils engaged in two-way active avoidance learning, a task that shows learning-associated dopamine changes and that is acquired faster following LHb lesions. We delivered brief electrical brain stimulation whenever the animal performed a correct response, i.e., when the successful avoidance of foot shock was hypothesized to trigger an intrinsic reward signal. During the acquisition phase, VTA stimulation improved avoidance performance, while LHb stimulation impaired it. VTA stimulation appeared to improve both acquisition and asymptotic performance of the avoidance response, as VTA-stimulated animals reached above-normal performance but reverted to normal responding when stimulation was discontinued. The effects of LHb stimulation during avoidance acquisition were long lasting and persisted even after stimulation was discontinued. However, when given after successful acquisition of avoidance behavior, LHb stimulation had no effect, indicating that LHb stimulation specifically impaired avoidance acquisition without affecting memory retrieval or motivation or ability to perform the avoidance response. These results demonstrate opponent roles of LHb and VTA during acquisition but not during retrieval of avoidance learning.