bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Relapse in Patients With Medulloblastoma by Integrating Evidence From Clinical and Genomic Features
Authors: Tamayo Pablo , Cho Yoon-Jae , Tsherniak Aviad , Greulich Heidi , Ambrogio Lauren , Schouten-van Meeteren Netteke , Zhou Tianni , Buxton Allen , Kool Marcel , Meyerson Matthew , Pomeroy Scott L. , Mesirov Jill P.
Published: March 2011

Purpose

Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis.

Patients and Methods

A Bayesian cumulative log-odds model of outcome was developed from a training cohort of 96 children treated for medulloblastoma, starting with the evidence provided by clinical features of metastasis and histology (model A) and incrementally adding the evidence from gene-expression–derived features representing disease subtype–independent (model B) and disease subtype–dependent (model C) pathways, and finally high-level copy-number genomic abnormalities (model D). The models were validated on an independent test cohort (n = 78).

Results

On an independent multi-institutional test data set, models A to D attain an area under receiver operating characteristic (au-ROC) curve of 0.73 (95% CI, 0.60 to 0.84), 0.75 (95% CI, 0.64 to 0.86), 0.80 (95% CI, 0.70 to 0.90), and 0.78 (95% CI, 0.68 to 0.88), respectively, for predicting relapse versus no relapse.

Conclusion

The proposed models C and D outperform the current clinical classification schema (au-ROC, 0.68), our previously published eight-gene outcome signature (au-ROC, 0.71), and several new schemas recently proposed in the literature for medulloblastoma risk stratification.
From Versailles to Paris: The Creative Communities of the Physiocratic Movement
Authors: Charles Loïc , Théré Christine
Published: March 2011

This article investigates the scientific practices—and their transformations across time—of the physiocrats in relation to their social background. Our contention is that, in this regard, the physiocratic movement can be broken down in two successive creative communities: The writing workshop of Quesnay (ca.1756–ca.1764) and the physiocratic school (ca.1764–ca.1777). This transformation is related to the specific places and cultural spaces in which the two communities evolved; that is, respectively, Versailles and the court, and Paris in the heyday of the Enlightenment. We want to show that the geographical and social context in which the scientific activities of the physiocrats took place structured the relationships inside each of the two communities and influenced their mode of production and dissemination of economic thought.
The Bloomsbury Group as Creative Community
Authors: Goodwin Craufurd D.
Published: March 2011

The Bloomsbury group was a multidisciplinary association of friends who came together early in the twentieth century. It contained John Maynard Keynes and others who had an interest in economic questions, including the art critic Roger Fry, the novelists Virginia Woolf and E. M. Forster, and the man of letters Leonard Woolf. The group had little formal organization but cooperated in various ways and resembled in some respects a pioneering think tank. They rejoiced in intellectual and artistic radicalism. They had fans and critics in Britain and elsewhere. They collaborated through Fry's Omega Workshops, the Woolfs' Hogarth Press, Keynes's magazine the Nation, and the Contemporary Art Society. They rejected the teachings of Jeremy Bentham and looked for enlightenment to modern psychology and biography. In their search for “civilization” they discussed how to achieve peace and economic progress through a new world order, how to sustain the arts in an advanced market economy, how to improve the position of women and minorities, and how to protect the environment. They were influenced by many thinkers including the American institutionalists.
Reinterpreting the Keynesian Revolution: A Research School Analysis
Authors: Cord Robert A.
Published: March 2011

Various explanations have been put forward as to why the Keynesian revolution occurred. Some of these point to the temporal relevance of the General Theory while others highlight the importance of more anecdotal evidence, such as Keynes's relations with the Cambridge Circus. However, no systematic effort has been made to bring together these and other factors under one recognized framework of analysis. The present essay fills this gap by making use of an established tradition of work within the history of science literature devoted to identifying the intellectual, technical, institutional, psychological, and financial factors that help to explain why some research schools are successful and why others fail. The evidence suggests that this approach does indeed provide a coherent explanation as to why the revolution in macroeconomics during the 1930s and 1940s was Keynesian, this despite the fact that Keynes was far from being the only economist attempting to gain dominance for his ideas.
A Tale of Two Communities: Fighting Poverty in the Great Society (1964–68)
Authors: Forget Evelyn L.
Published: March 2011

The Office of Economic Opportunity was established, under the leadership of Sargent Shriver, to fight President Johnson's War on Poverty as part of the Great Society program. Between 1964 and 1968, two intellectual communities vied for supremacy within that office. In the early years, a group of intellectual radicals drew inspiration from social psychology and gave their support to the controversial community action programs that drew criticism from the Senate, Congress, local governments, and Democratic Party insiders. Over time, a second community, built upon the values and insights associated with the Office of Research, Plans, Programs, Evaluation, brought the evaluation perspective of RAND to government spending and gradually began to dominate. This essay examines the internal and external pressures of the period and uses the insights of Randall Collins, Michael Farrell, and J. B. Morrell and G. L. Geison to explain why one intellectual community flourished while the other declined.
Polycomblike 2 facilitates the recruitment of PRC2 Polycomb group complexes to the inactive X chromosome and to target loci in embryonic stem cells
Authors: Casanova Miguel , Preissner Tanja , Cerase Andrea , Poot Raymond , Yamada Daisuke , Li Xiangzhi , Appanah Ruth , Bezstarosti Karel , Demmers Jeroen , Koseki Haruhiko , Brockdorff Neil
Published: March 2011

Polycomb group (PcG) proteins play an important role in the control of developmental gene expression in higher organisms. In mammalian systems, PcG proteins participate in the control of pluripotency, cell fate, cell cycle regulation, X chromosome inactivation and parental imprinting. In this study we have analysed the function of the mouse PcG protein polycomblike 2 (Pcl2), one of three homologues of the Drosophila Polycomblike (Pcl) protein. We show that Pcl2 is expressed at high levels during early embryogenesis and in embryonic stem (ES) cells. At the biochemical level, Pcl2 interacts with core components of the histone H3K27 methyltransferase complex Polycomb repressive complex 2 (PRC2), to form a distinct substoichiometric biochemical complex, Pcl2-PRC2. Functional analysis using RNAi knockdown demonstrates that Pcl2-PRC2 facilitates both PRC2 recruitment to the inactive X chromosome in differentiating XX ES cells and PRC2 recruitment to target genes in undifferentiated ES cells. The role of Pcl2 in PRC2 targeting in ES cells is critically dependent on a conserved PHD finger domain, suggesting that Pcl2 might function through the recognition of a specific chromatin configuration.
Human models of acute lung injury
Authors: Proudfoot Alastair G. , McAuley Danny F. , Griffiths Mark J. D. , Hind Matthew
Published: March 2011

Acute lung injury (ALI) is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.
‘Model’ or ‘tool’? New definitions for translational research
Authors: Sive Hazel
Published: March 2011

The term ‘model’ often describes non-human biological systems that are used to obtain a better understanding of human disorders. According to the most stringent definition, an animal ‘model’ would display exactly the same phenotype as seen in the relevant human disorder; however, this precise correspondence is often not present. In this Editorial, I propose the alternative, broader term ‘tool’ to describe a biological system that does not obviously (or precisely) recapitulate a human disorder, but that nonetheless provides useful insight into the etiology or treatment of that disorder. Applying the term ‘tool’ to biological systems used in disease-related studies will help to identify those systems that can most effectively address mechanisms underlying human disease. Conversely, differentiating ‘models’ from ‘tools’ will help to define more clearly the limitations of biological systems used in preclinical analyses.
Extraction Ability and Selectivity for Lithium Ion of Macrocyclic Trinuclear (Alkylbenzene)ruthenium(II) Complexes Bridged by 2,3-Pyridinediolato Ligands
Authors: Katsuta Shoichi , Nomura Hajime , Egashira Takuya , Imoto Takahiro , Kudo Yoshihiro , Takeda Yasuyuki
Published: March 2011

A series of macrocyclic trinuclear complexes of (η6-alkylbenzene)ruthenium(II) bridged by 2,3-pyridinediolato ligands were synthesized and their liquid–liquid extraction properties for Li+ and Na+ were investigated at 25 °C. The alkylbenzenes used were p-cymene, 1,2,3-trimethylbenzene, 1,3,5-trimethylbenzene, 1,3,5-triethylbenzene, 1,2,4,5-tetramethylbenzene, and hexamethylbenzene. Most of the trinuclear complexes were stable for 48 h or more in a dichloromethane–water system. The extraction constants (Kex = [ML+A−]o/([M+][A−][L]o); M+: alkali metal ion, L: trinuclear complex, A−: counter anion (picrate), and o: organic phase (dichloromethane)) were determined from analysis of the extraction equilibria. Each trinuclear complex exhibited a larger Kex value for Li+ than for Na+; particularly large separation factor, SF = Kex(Li+)/Kex(Na+), was observed for the complexes of Ru(1,3,5-trimethylbenzene) (SF = 1.7 × 103) and Ru(1,2,4,5-tetramethylbenzene) (SF = 1.6 × 103). The extraction separation of Li+ from seawater could be achieved by using the trinuclear complex of Ru(1,3,5-trimethylbenzene) with the aid of washing the organic phase with water to remove co-extracted Na+.
Doctors who become chief executives in the NHS: from keen amateurs to skilled professionals
Authors: Ham Chris , Clark John , Spurgeon Peter , Dickinson Helen , Armit Kirsten
Published: March 2011

Summary

Objectives

To investigate the experiences of doctors who become chief executives of NHS organizations, with the aim of understanding their career paths and the facilitators and barriers encountered along the way.

Design

Twenty-two medical chief executives were identified and of these 20 were interviewed. In addition two former medical chief executives were interviewed. Information was collected about the age at which they became chief executives, the number of chief executive posts held, the training they received, and the opportunities, challenges and risks they experienced.

Setting

All NHS organizations in the United Kingdom in 2009.

Results

The age of medical chief executives on first appointment ranged from 36 to 64 years, the average being 48 years. The majority of those interviewed were either in their first chief executive post or had stepped down having held only one such post. The training and development accessed en route to becoming chief executives was highly variable. Interviewees were positive about the opportunity to bring about organizational and service improvement on a bigger scale than is possible in clinical work. At the same time, they emphasized the insecurities associated with being a chief executive. Doctors who become chief executives experience a change in their professional identity and the role of leaders occupying hybrid positions is not well recognized.

Conclusions

Doctors who become chief executives are self-styled ‘keen amateurs’ and there is a need to provide more structured support to enable them to become skilled professionals. The new faculty of medical leadership and management could have an important role in this process.
Low Frequency Noise from Wind Turbines Mechanisms of Generation and its Modelling
Authors: Madsen Helge Aagaard
Published: March 2011

The objective of the present paper is to present an overview of LFN characteristics of modern MW turbines based on numerical simulations. Typical sizes of modern turbines are from 1–3 MW nominal generator power and a rotor diameter ranging from 80–100 m but larger prototypes up to 5 MW and with a rotor diameter of 126 m have now been installed. The numerical investigations comprise the common upwind rotor concept but also the turbines with a downwind rotor are considered. The reason to include the downwind rotor concept is that this turbine design has some advantages which could lead to future competitive designs compared with the upwind threebladed rotor. The simulation package comprises an aeroelastic time simulation code HAWC2 and an acoustic low frequency noise (LFN) prediction model. Computed time traces of rotor thrust and rotor torque from the aeroelastic model are input to the acoustic model which computes the sound pressure level (SPL) at a specified distance from the turbine. The influences on LFN on a number of turbine design parameters are investigated and the position of the rotor relative to the tower (upwind or downwind rotor) is found to be the most important design parameter. For an upwind rotor the LFN levels are so low that it should not cause annoyance of neighbouring people. Important turbine design parameters with strong influence on LFN are the blade tip speed and the distance between rotor and tower.
Study of Water Vapour Adsorption on Sandwich-Type CuO/NaX Adsorbent–Catalysts
Authors: Jaskunas Andrius , Brazlauskas Marius , Kitrys Saulius
Published: March 2011

Experimental data show that the adsorbent–catalyst CuO/NaX is hydrophilic with a similar water vapour adsorption capacity and adsorption rate to zeolite NaX. Equilibrium parameters were best described by a Freundlich-like equation. BET studies and Kelvin equation calculations confirmed that, at an ambient relative humidity of 37% or higher, water vapour condensation will occur in the prevailing 2.0–2.3 nm pores of the adsorbent–catalyst CuO/NaX. The kinetic parameters for the adsorption of water vapour are presented.
Removal of Furfural from Aqueous Solutions by Adsorption Using Organobentonite: Isotherm and Kinetic Studies
Authors: Mebrek Ouassila Rachedi , Derriche Zoubir
Published: March 2011

Lubricant refineries are facing pollution problems associated with the occasional loss of furfural. This constitutes both an economic loss and an environmental hazard, especially for aquatic organisms. Some studies on the removal of furfural by adsorption onto hydrophobic polymeric resins (XAD-4 and XAD-7), activated carbon and the nanoporous material MCM-48 have been published, but none provides information on the adsorption of furfural onto clays.

In the present work, we have studied the efficiency of sodium bentonite modified with the cationic surfactant cethyltrimethylammonium bromide (CTAB) in the adsorption of furfural. The structures of both natural and modified bentonites have been examined using XRD and FT-IR analyses. Adsorption studies were performed in a batch system, with the effects of various experimental parameters such as the contact time, the organobentonite concentration, pH, the initial furfural concentration and the temperature being evaluated. Kinetic results showed that furfural could be removed by CTAB–bentonite after contact for 6 h, with the adsorption process being well described by the pseudo-second-order reaction model. Furfural sorption onto CTAB–bentonite was characterized by a linear isotherm, with the adsorption capacity towards furfural being reduced by increasing temperature. A comparison of furfural adsorption capacities revealed that the capacities decreased in the following order: CTAB–bentonite > XAD-4 > XAD-7.
Efficient Adsorption of Chromium(VI) Ions from Aqueous Solution onto a Low-Cost Adsorbent Developed from Limonia Acidissima (Wood Apple) Shell
Authors: Sartape Ashish S. , Raut Prakash D. , Kolekar Sanjay S.
Published: March 2011

The removal of chromium(VI) ions from aqueous solution was studied using Limonia acidissima (wood apple) shell activated carbon. The removal extent was found to be a maximum at a pH value of 2, with the lowcost adsorbent having an adsorption capacity of 13.74 mg/g. The material employed was characterized by scanning electron microscopy (SEM), Fouriertransform infrared spectroscopy (FT-IR) and elemental analysis. The linear Freundlich and Langmuir adsorption isotherm models were applied to describe the experimental equilibrium isotherms. The results showed that the Langmuir equation gave a better fit to the experimental data than the Freundlich equation. The pseudo-first-order and pseudo-second-order models were applied to the adsorption kinetics of Cr(VI) ions onto wood apple shell activated carbon. Thermodynamic parameters such as the standard enthalpy (ΔH0), the Gibbs' free energy (ΔG0) and the standard entropy (ΔS0) were evaluated and indicated that the sorption process was spontaneous and endothermic in nature. The results demonstrated that wood apple shell activated carbon may be effectively used for the inexpensive removal of Cr(VI) ions from aqueous solution.
Crystal structure of Rcl1, an essential component of the eukaryal pre-rRNA processosome implicated in 18s rRNA biogenesis
Authors: Tanaka Naoko , Smith Paul , Shuman Stewart
Published: March 2011

Rcl1 is an essential nucleolar protein required for U3 snoRNA-guided pre-rRNA processing at sites flanking the 18S rRNA sequence. A potential catalytic role for Rcl1 during pre-rRNA cleavage has been suggested based on its primary structure similarity to RNA 3′-terminal phosphate cyclase (Rtc) enzymes, which perform nucleotidyl transfer and phosphoryl transfer reactions at RNA ends. Here, we report the 2.6 Å crystal structure of a biologically active yeast Rcl1, which illuminates its modular 4-domain architecture and overall homology with RNA cyclases while revealing numerous local differences that account for why Rtcs possess metal-dependent adenylyltransferase activity and Rcls do not. A conserved oxyanion-binding site in Rcl1 was highlighted for possible catalytic or RNA-binding functions. However, the benign effects of mutations in and around the anion site on Rcl1 activity in vivo militate against such a role.
The splice is right: Guarantors of fidelity in pre-mRNA splicing: FIGURE 1.
Authors: Horowitz David S.
Published: March 2011

Two recent papers, one from the Staley laboratory (Koodathingal and colleagues) and the other from the Cheng laboratory (Tseng and colleagues), show that the RNA-dependent ATPase Prp16, which is required for the second step of splicing, acts to reject slowly splicing pre-mRNAs immediately before the first catalytic reaction in pre-mRNA splicing. The results answer long-investigated questions about the actions of Prp16 and provide a wealth of molecular details on the proofreading process in pre-mRNA splicing. The discussion here reviews and integrates the results of the two papers and describes the implications for proofreading in splicing.
Arthroscopic femoral osteochondroplasty for cam femoroacetabular impingement in patients over 60 years of age
Authors: Javed A. , O’Donnell J. M.
Published: March 2011

We reviewed the clinical outcome of arthroscopic femoral osteochondroplasty for cam femoroacetabular impingement performed between August 2005 and March 2009 in a series of 40 patients over 60 years of age. The group comprised 26 men and 14 women with a mean age of 65 years (60 to 82). The mean follow-up was 30 months (12 to 54).

The mean modified Harris hip score improved by 19.2 points (95% confidence interval 13.6 to 24.9; p < 0.001) while the mean non-arthritic hip score improved by 15.0 points (95% confidence interval 10.9 to 19.1, p < 0.001). Seven patients underwent total hip replacement after a mean interval of 12 months (6 to 24 months) at a mean age of 63 years (60 to 70). The overall level of satisfaction was high with most patients indicating that they would undergo similar surgery in the future to the contralateral hip, if indicated. No serious complications occurred.

Arthroscopic femoral osteochondroplasty performed in selected patients over 60 years of age, who have hip pain and mechanical symptoms resulting from cam femoroacetabular impingement, is beneficial with a minimal risk of complications at a mean follow-up of 30 months.
Fast-track surgery for bilateral total knee replacement
Authors: Husted H. , Troelsen A. , Otte K. S. , Kristensen B. B. , Holm G. , Kehlet H.
Published: March 2011

Bilateral simultaneous total knee replacement (TKR) has been considered by some to be associated with increased morbidity and mortality. Our study analysed the outcome of 150 consecutive, but selected, bilateral simultaneous TKRs and compared them with that of 271 unilateral TKRs in a standardised fast-track setting. The procedures were performed between 2003 and 2009.

Apart from staying longer in hospital (mean 4.7 days (2 to 16) versus 3.3 days (1 to 25)) and requiring more blood transfusions, the outcome at three months and two years was similar or better in the bilateral simultaneous TKR group in regard to morbidity, mortality, satisfaction, the range of movement, pain, the use of a walking aid and the ability to return to work and to perform activities of daily living. Bilateral simultaneous TKR can therefore be performed as a fast-track procedure with excellent results.
The relationship between the angle of version and rate of wear of retrieved metal-on-metal resurfacings
Authors: Hart A. J. , Ilo K. , Underwood R. , Cann P. , Henckel J. , Lewis A. , Cobb J. , Skinner J.
Published: March 2011

We measured the orientation of the acetabular and femoral components in 45 patients (33 men, 12 women) with a mean age of 53.4 years (30 to 74) who had undergone revision of metal-on-metal hip resurfacings. Three-dimensional CT was used to measure the inclination and version of the acetabular component, femoral version and the horizontal femoral offset, and the linear wear of the removed acetabular components was measured using a roundness machine.

We found that acetabular version and combined version of the acetabular and femoral components were weakly positively correlated with the rate of wear. The acetabular inclination angle was strongly positively correlated with the rate of wear. Femoral version was weakly negatively correlated with the rate of wear. Application of a threshold of > 5 μm/year for the rate of wear in order to separate the revisions into low or high wearing groups showed that more high wearing components were implanted outside Lewinnek’s safe zone, but that this was mainly due to the inclination of the acetabular component, which was the only parameter that significantly differed between the groups.

We were unable to show that excess version of the acetabular component alone or combined with femoral version was associated with an increase in the rate of wear based on our assessment of version using CT.
Survival of metal-on-metal hip resurfacing arthroplasty
Authors: van der Weegen W. , Hoekstra H. J. , Sijbesma T. , Bos E. , Schemitsch E. H. , Poolman R. W.
Published: March 2011

We systematically reviewed the peer-reviewed literature to relate the survival of hybrid metal-on-metal hip resurfacing arthroplasty devices to a National Institute of Clinical Excellence (NICE) benchmark for choosing a primary total hip replacement, which is a survival rate of 90% at a follow-up of ten years.

A total of 29 articles (10 621 resurfaced hips) met the inclusion criteria. The mean follow-up ranged from 0.6 to 10.5 years and the survival of the implant ranged from 84% to 100%. Of the 10 621 hips, 370 were revised (3.5%), with aseptic loosening as the most frequent mode of failure.

None of the hip resurfacing arthroplasty implants used to date met the full ten-year NICE benchmark of survival. A total of 13 studies showed satisfactory survival compared with the three-year NICE benchmark.
High concentrations of asymmetric dimethylarginine are associated with ST-segment resolution failure after reperfusion for acute myocardial infarction
Authors: Yilmaz Akar , Bekpinar Seldag , Unlucerci Yesim , Gurdol Figen , Umman Berrin
Published: March 2011

Background: Increased concentrations of asymmetric dimethylarginine (ADMA) have been detected in patients with cardiovascular risk factors. In addition, high baseline plasma concentrations of ADMA have been shown to be an independent predictor of adverse outcomes in various disorders. This study aimed to evaluate the impact of admission ADMA concentrations on microvascular flow after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI).

Methods: Blood samples from 39 patients with STEMI were collected at admission to measure the concentrations of ADMA and other cardiovascular risk factors including inflammatory markers and the lipid profile. Primary PCI was performed in patients with STEMI. The maximum ST-segment elevation in standard 12-leads electrocardiogram (ECG) before and 24 h after PCI was measured, and patients were stratified as complete or incomplete ST-segment resolution (STR).

Results: Twenty-five patients had complete (≥70%) and 14 incomplete (<70%) STR. In patients with incomplete STR, ADMA concentrations were significantly higher than that seen in others (0.447±0.215 μmol/L vs. 0.310±0.134, p=0.019), and was independently associated with STR.

Conclusions: Admission concentrations of ADMA appeared to be useful for early risk stratification in reperfusion therapy for acute myocardial infarction.
Collective opinion paper on findings of the 2010 convocation of experts on laboratory quality
Authors: Cooper Greg , DeJonge Niels , Ehrmeyer Sharon , Yundt-Pacheco John , Jansen Rob , Ricós Carmen , Plebani Mario
Published: March 2011

As a part of a series of yearly meeting, in May 2010 over 40 medical laboratory opinion leaders, pathologists, clinical biochemists and physicians from Europe, Israel and South Africa gathered together in Bardolino, Italy to discuss issues and current challenges for laboratory medicine, including a) the use of biological variation 10 years after the Stockholm Conference; b) achieving quality in point-of-care testing; c) assessing risk and controlling sources of error in the laboratory; d) determining the appropriate frequency of quality control; and f) putting laboratory medicine at the core of patient care. The intended goal of the convocation was to give laboratory professionals from different countries and backgrounds the opportunity to share ideas, concerns and experiences in previously mentioned areas of interest. This paper provide a synopsis of the reports from each working group.
Generalized sensitivities and optimal experimental design
Authors: Banks H. T. , Dediu Sava , Ernstberger Stacey L. , Kappel Franz
Published: March 2011

We consider the problem of estimating amodeling parameter θ using a weighted least squares criterion for given data y by introducing an abstract framework involving generalized measurement procedures characterized by probability measures. We take an optimal design perspective, the general premise (illustrated via examples) being that in any data collected, the information content with respect to estimating θ may vary considerably from one time measurement to another, and in this regard some measurements may be much more informative than others. We propose mathematical tools which can be used to collect data in an almost optimal way, by specifying the duration and distribution of time sampling in the measurements to be taken, consequently improving the accuracy (i.e., reducing the uncertainty in estimates) of the parameters to be estimated.

We recall the concepts of traditional and generalized sensitivity functions and use these to develop a strategy to determine the “optimal” final time T for an experiment; this is based on the time evolution of the sensitivity functions and of the condition number of the Fisher information matrix. We illustrate the role of the sensitivity functions as tools in optimal design of experiments, in particular in finding “best” sampling distributions. Numerical examples are presented throughout to motivate and illustrate the ideas.
Identification of unknown terms in convolution integro-differential equations in a Banach space
Authors: Lorenzi Alfredo , Mola Gianluca
Published: March 2011

We consider the following identification problems in a general Banach space X: find a function u : [0, T] → X and a vector z ∈ X such that the initial-value problems

and

are fulfilled, along with the nonlocal additional condition ∫
[0,T]
u(t)dμ(t) = φ ∈ X, for some probability Borel probability measure μ on the interval [0, T]. Here A : D(A) ⊂ X → X is a (possibly unbounded) closed linear operator, h, k and ƒ are scalar functions and g is a X-valued source term. We recall that the same problem with h = k = 0 has been previously studied by Anikonov and Lorenzi in [J. Inverse Ill-posed Probl. 7: 669–681, 2007], Prilepko, Piskarev and Shaw in [J. Inverse Ill-Posed Probl. 15: 831–851, 2007], and subsequently generalized by Lorenzi and Vrabie in [Discr. Continuous Dynam. Syst., 2011]. Under suitable assumptions on the structural data of the problem, we prove local-in-time existence and uniqueness for the function u, and an explicit representation formula for z depending on u. Also, a continuous dependence of Lipschitz type of the solution (u, z) on the data is provided. Finally, two applications to parabolic integro-differential boundary value problems are considered.
Wear Rate in a Series of Retrieved RP Knee Bearings
Authors: Currier John H. , Mayor Michael B. , Collier John P. , Currier Barbara H. , Van Citters Douglas W.
Published: March 2011

Rotating platform mobile bearing knees are an appealing approach to the problems of tibial loosening and rotational mal-alignment that are of concern with fixed bearing knees. A potential disadvantage of rotating platform (RP) bearings is ultra-high molecular weight polyethylene (UHMWPE) wear debris from the large additional backside articular surface that accommodates tibio-femoral rotation. The investigation of a series of 76 rotating platform knees (Sigma® RP, DePuy/J&J, Warsaw, IN) indicates that UHMWPE bearing wear, as measured by change in through-thickness dimension, increases monotonically with time in vivo. Total wear penetration rate is 0.023 mm/year and shows a decreasing trend, though this trend is not statistically significant. The current study results are consistent with the decreasing wear rate previously reported in a series of LCS® RP (DePuy/J&J, Warsaw, IN) knee. This decreasing wear rate stands in contrast to an increasing backside-only wear rate reported in fixed bearing knees. An important contribution of the current study is that it provides a conservative measurement of total wear penetration and penetration rate in one mobile bearing design over time out to>8 years.
Bruchpilot, A Synaptic Active Zone Protein for Anesthesia-Resistant Memory
Authors: Knapek Stephan , Sigrist Stephan , Tanimoto Hiromu
Published: March 2011

InDrosophila, aversive associative memory of an odor consists of heterogeneous components with different stabilities. Here we report that Bruchpilot (Brp), a ubiquitous presynaptic active zone protein, is required for olfactory memory. Brp was shown before to facilitate efficient vesicle release, particularly at low stimulation frequencies. Transgenic knockdown in the Kenyon cells of the mushroom body, the second-order olfactory interneurons, revealed that Brp is required for olfactory memory. We further demonstrate that Brp in the Kenyon cells preferentially functions for anesthesia-resistant memory. Another presynaptic protein, Synapsin, was shown previously to be required selectively for the labile anesthesia-sensitive memory, which is less affected inbrpknockdown. Thus, consolidated and labile components of aversive olfactory memory can be dissociated by the function of different presynaptic proteins.
Common or Redundant Neural Circuits for Duration Processing across Audition and Touch
Authors: Butler John S. , Molholm Sophie , Fiebelkorn Ian C. , Mercier Manuel R. , Schwartz Theodore H. , Foxe John J.
Published: March 2011

Certain features of objects or events can be represented by more than a single sensory system, such as roughness of a surface (sight, sound, and touch), the location of a speaker (audition and sight), and the rhythm or duration of an event (by all three major sensory systems). Thus, these properties can be said to be sensory-independent or amodal. A key question is whether common multisensory cortical regions process these amodal features, or does each sensory system contain its own specialized region(s) for processing common features? We tackled this issue by investigating simple duration-detection mechanisms across audition and touch; these systems were chosen because fine duration discriminations are possible in both. The mismatch negativity (MMN) component of the human event-related potential provides a sensitive metric of duration processing and has been elicited independently during both auditory and somatosensory investigations. Employing high-density electroencephalographic recordings in conjunction with intracranial subdural recordings, we asked whether fine duration discriminations, represented by the MMN, were generated in the same cortical regions regardless of the sensory modality being probed. Scalp recordings pointed to statistically distinct MMN topographies across senses, implying differential underlying cortical generator configurations. Intracranial recordings confirmed these noninvasive findings, showing generators of the auditory MMN along the superior temporal gyrus with no evidence of a somatosensory MMN in this region, whereas a robust somatosensory MMN was recorded from postcentral gyrus in the absence of an auditory MMN. The current data clearly argue against a common circuitry account for amodal duration processing.
Spatiotemporal Tuning of the Facilitation of Biological Motion Perception by Concurrent Motor Execution
Authors: Christensen Andrea , Ilg Winfried , Giese Martin A.
Published: March 2011

The execution of motor behavior influences concurrent visual action observation and especially the perception of biological motion. The neural mechanisms underlying this interaction between perception and motor execution are not exactly known. In addition, the available experimental evidence is partially inconsistent because previous studies have reported facilitation as well as impairments of action perception by concurrent execution. Exploiting a novel virtual reality paradigm, we investigated the spatiotemporal tuning of the influence of motor execution on the perception of biological motion within a signal-detection task. Human observers were presented with point-light stimuli that were controlled by their own movements. Participants had to detect a point-light arm in a scrambled mask, either while executing waving movements or without concurrent motor execution (baseline). The temporal and spatial coherence between the observed and executed movements was parametrically varied. We found a systematic tuning of the facilitatory versus inhibitory influences of motor execution on biological motion detection with respect to the temporal and the spatial congruency between observed and executed movements. Specifically, we found a gradual transition between facilitatory and inhibitory interactions for decreasing temporal synchrony and spatial congruency. This result provides evidence for a spatiotemporally highly selective coupling between dynamic motor representations and neural structures involved in the visual processing of biological motion. In addition, our study offers a unifying explanation that reconciles contradicting results about modulatory effects of motor execution on biological motion perception in previous studies.
Nepal and Bhutan in 2010
Authors: Hangen Susan
Published: March 2011

Nepal made little headway in its peace process in 2010. The Constituent Assembly missed the May deadline for completing the new Constitution, and a crisis in governance followed the prime minister's resignation in June. Repeated rounds of voting failed to elect a new leader. Meanwhile, democratization in Bhutan progressed slowly because local elections were delayed.
Thailand in 2010
Authors: Dalpino Catharin
Published: March 2011

In the first half of 2010, political tensions in Thailand rose steadily until they literally burst into flames as anti-government protesters set a commercial district on fire in response to the government's crackdown to reclaim the area. The country's other internal conflict, communal violence in the Muslim-majority provinces of the South, was all but ignored in the broader political emergency.
Malaysia in 2010
Authors: O'Shannassy Michael
Published: March 2011

Malaysia in 2010 was best characterized by the efforts of the governing coalition to balance the "old" politics of communalism and patronage with a "new" political landscape focused on greater sociopolitical and economic inclusivity. However, it still remains unclear if this coalition is capable of successfully negotiating such a course.
Cambodia in 2010
Authors: Heder Steve
Published: March 2011

Prime Minister Hun Sen's power became more concentrated. The economy expanded but was said to need diversification. Inequality intensified conflicts, but development generated legitimacy, while the political opposition and civil society were attacked. A U.N.-assisted court convicted five ex-Khmer Rouge leaders. Ties with China, the U.S., and Thailand improved.
South Korea in 2010
Authors: Cha Victor D. , Katz Katrin
Published: March 2011

For the Obama administration, unforeseen dynamics in East Asia over the past year have escalated the importance of the U.S.-ROK alliance to unprecedented levels for the United States. But the alliance remains vulnerable to external shocks, rendering the continuation of the current phase of unmitigated harmonious ties far from certain.
Afghanistan in 2010
Authors: Maley William
Published: March 2011

Afghanistan in 2010 witnessed a number of important events including cabinet changes, legislative elections, and several major international conferences focused on its problems. It continued to be confronted by long-term problems of insecurity, compounded by uncertainty about both the trajectory of U.S. policy and the legitimacy of its own rulers.
A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels
Authors: Medici Marco , van der Deure Wendy M , Verbiest Michael , Vermeulen Sita H , Hansen Pia S , Kiemeney Lambertus A , Hermus Ad R M M , Breteler Monique M , Hofman Albert , Hegedüs Laszlo , Kyvik Kirsten Ohm , Heijer Martin den , Uitterlinden André G , Visser Theo J , Peeters Robin P
Published: March 2011

Objective

Minor variation in serum thyroid hormone (TH) levels can have important effects on various clinical endpoints. Although 45–65% of the inter-individual variation in serum TH levels is due to genetic factors, the causative genes are not well established. We therefore studied the effects of genetic variation in 68 TH pathway genes on serum TSH and free thyroxine (FT4) levels.

Design and methods

Sixty-eight genes (1512 polymorphisms) were studied in relation to serum TSH and FT4levels in 1121 Caucasian subjects. Promising hits (P<0.01) were studied in three independent Caucasian populations (2656 subjects) for confirmation. A meta-analysis of all four studies was performed.

Results

For TSH, eightPDE8Bpolymorphisms (P=4×10−17) remained significant in the meta-analysis. For FT4, twoDIO1(P=8×10−12) and oneFOXE1(P=0.0003) polymorphisms remained significant in the meta-analysis. Suggestive associations were detected for oneFOXE1(P=0.0028) and threeTHRB(P=0.0045) polymorphisms with TSH, and oneSLC16A10polymorphism (P=0.0110) with FT4, but failed to reach the significant multiple-testing correctedPvalue (P<0.0022 andP<0.0033 respectively).

Conclusions

Using a large-scale association analysis, we replicated previously reported associations with genetic variation inPDE8B,THRB, andDIO1. We demonstrate effects of genetic variation inFOXE1on serum FT4levels, and borderline significant effects on serum TSH levels. A suggestive association of genetic variation inSLC16A10with serum FT4levels was found. These data provide insight into the molecular basis of inter-individual variation in TH serum levels.
Histone deacetylase inhibitors upregulate Rap1GAP and inhibit Rap activity in thyroid tumor cells
Authors: Dong Xiaoyun , Korch Christopher , Meinkoth Judy L
Published: March 2011

Increases in Rap activity have been associated with tumor progression. Although activating mutations in Rap have not been described, downregulation of Rap1GAP is frequent in human tumors including thyroid carcinomas. In this study, we explored whether endogenous Rap1GAP expression could be restored to thyroid tumor cells. The effects of deacetylase inhibitors and a demethylating agent, individually and in combination, were examined in four differentiated and six anaplastic thyroid carcinoma (ATC) cell lines. Treatment with the structurally distinct histone deacetylase (HDAC) inhibitors, sodium butyrate and trichostatin A, increased Rap1GAP expression in all the differentiated thyroid carcinoma cell lines and in four of the six ATC cell lines. The demethylating agent, 5-aza-deoxycytidine, restored Rap1GAP expression in one anaplastic cell line and enhanced the effects of HDAC inhibitors in a second anaplastic cell line. Western blotting indicated that Rap2 was highly expressed in human thyroid cancer cells. Importantly, treatment with HDAC inhibitors impaired Rap2 activity in both differentiated and anaplastic tumor cell lines. The mechanism through which Rap activity is repressed appears to entail effects on the expression of multiple Rap regulators, including RapGEFs and RapGAPs. These results suggest that HDAC inhibitors may provide a tractable approach to impair Rap activity in human tumor cells.
Rapid non-genomic effects of corticosteroids and their role in the central stress response
Authors: Groeneweg Femke L , Karst Henk , de Kloet E Ron , Joëls Marian
Published: March 2011

In response to a stressful encounter, the brain activates a comprehensive stress system that engages the organism in an adaptive response to the threatening situation. This stress system acts on multiple peripheral tissues and feeds back to the brain; one of its key players is the family of corticosteroid hormones. Corticosteroids affect brain functioning through both delayed, genomic and rapid, non-genomic mechanisms. The latter mode of action has long been known, but it is only in recent years that the physiological basis in the brain is beginning to be unravelled. We now know that corticosteroids exert rapid, non-genomic effects on the excitability and activation of neurons in (amongst others) the hypothalamus, hippocampus, amygdala and prefrontal cortex. In addition, corticosteroids affect cognition, adaptive behaviour and neuroendocrine output within minutes. Knowledge on the identity of the receptors and secondary pathways mediating the non-genomic effects of corticosteroids on a cellular level is accumulating. Interestingly, in many cases, an essential role for the ‘classical’ mineralocorticoid and glucocorticoid receptors in a novel membrane-associated mechanism is found. Here, we systematically review the recent literature on non-genomic actions of corticosteroids on neuronal activity and functioning in selected limbic brain targets. Further, we discuss the relevance of these permissive effects for cognition and neuroendocrine control, and the integration of this novel mode of action into the complex balanced pattern of stress effects in the brain.
Phylogenetic and Functional Characterization of the hAT Transposon Superfamily
Authors: Arensburger Peter , Hice Robert H , Zhou Liqin , Smith Ryan C , Tom Ariane C , Wright Jennifer A , Knapp Joshua , O'Brochta David A , Craig Nancy L , Atkinson Peter W
Published: March 2011

Transposons are found in virtually all organisms and play fundamental roles in genome evolution. They can also acquire new functions in the host organism and some have been developed as incisive genetic tools for transformation and mutagenesis. The hAT transposon superfamily contains members from the plant and animal kingdoms, some of which are active when introduced into new host organisms. We have identified two new active hAT transposons, AeBuster1, from the mosquito Aedes aegypti and TcBuster from the red flour beetle Tribolium castaneum. Activity of both transposons is illustrated by excision and transposition assays performed in Drosophila melanogaster and Ae. aegypti and by in vitro strand transfer assays. These two active insect transposons are more closely related to the Buster sequences identified in humans than they are to the previously identified active hAT transposons, Ac, Tam3, Tol2, hobo, and Hermes. We therefore reexamined the structural and functional relationships of hAT and hAT-like transposase sequences extracted from genome databases and found that the hAT superfamily is divided into at least two families. This division is supported by a difference in target-site selections generated by active transposons of each family. We name these families the Ac and Buster families after the first identified transposon or transposon-like sequence in each. We find that the recently discovered SPIN transposons of mammals are located within the family of Buster elements.