Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis

Myeloid-derived cells play important modulatory and effector roles in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells, composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can suppress T cell activities in EAE. Their role in MS remains poorly characterized. We found decreased numbers of circulating MDSCs, driven by lower frequencies of the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy subjects. To gain mechanistic insights, we interrogated the EAE model. MiR-223 knock out (miR-223 12/ 12) mice developed less severe EAE with increased MDSC numbers in the spleen and spinal cord compared to littermate controls. MiR-223 12/ 12 MO-MDSCs suppressed T cell proliferation and cytokine production in vitro and EAE in vivo more than wild-type MO-MDSCs. They also displayed an increased expression of critical mediators of MDSC suppressive function, Arginase-1(Arg1), and the signal transducer and activator of transcription 3 (Stat3), which herein, we demonstrate being an miR-223 target gene. Consistently, MDSCs from MS patients displayed decreased STAT3 and ARG1 expression compared with healthy controls, suggesting that circulating MDSCs in MS are not only reduced in numbers but also less suppressive. These results support a critical role for miR-223 in modulating MDSC biology in EAE and in MS and suggest potential novel therapeutic applications

Centralization of cleft care in the UK. Part 6:a tale of two studies

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service

A cross-sectional survey of 5-year-old children with non-syndromic unilateral cleft lip and palate:the Cleft Care UK study. Part 1: background and methodology

OBJECTIVES: We describe the methodology for a major study investigating the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after an initial survey, detailed in the Clinical Standards Advisory Group (CSAG) report in 1998, had informed government recommendations on centralization. SETTING AND SAMPLE POPULATION: This is a UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Children born between 1 April 2005 and 31 March 2007 were seen in cleft centre audit clinics. MATERIALS AND METHODS: Consent was obtained for the collection of routine clinical measures (speech recordings, hearing, photographs, models, oral health, psychosocial factors) and anthropometric measures (height, weight, head circumference). The methodology for each clinical measure followed those of the earlier survey as closely as possible. RESULTS: We identified 359 eligible children and recruited 268 (74.7%) to the study. Eleven separate records for each child were collected at the audit clinics. In total, 2666 (90.4%) were collected from a potential 2948 records. The response rates for the self-reported questionnaires, completed at home, were 52.6% for the Health and Lifestyle Questionnaire and 52.2% for the Satisfaction with Service Questionnaire. CONCLUSIONS: Response rates and measures were similar to those achieved in the previous survey. There are practical, administrative and methodological challenges in repeating cross-sectional surveys 15 years apart and producing comparable data

Trust and normative control in multi-agent systems: an empirical study

Despite relevant insights from socio-economics, little research in multi-agent systems has addressed the interconnections between trust and normative notions such as contracts and sanctions. Focusing our attention on scenarios of betrayal, in this paper we combine the use of trust and sanctions in a negotiation process. We describe a scenario of dyadic relationships between truster agents, which make use of trust and/or sanctions, and trustees characterized by their ability and integrity, which may influence their attitude toward betrayal. Both agent behavior models are inspired in socio-economics literature. Through simulation, we show the virtues and shortcomings of exploiting trust, sanctions and a combination of both

Investigation of the Exclusive 3He(e,e'pp)n Reaction

Cross sections for the 3He(e,e'pp)n reaction were measured over a wide range of energy and three- momentum transfer. At a momentum transfer q=375 MeV/c, data were taken at transferred energies omega ranging from 170 to 290 MeV. At omega=220 MeV, measurements were performed at three q values (305, 375, and 445 MeV/c). The results are presented as a function of the neutron momentum in the final-state, as a function of the energy and momentum transfer, and as a function of the relative momentum of the two-proton system. The data at neutron momenta below 100 MeV/c, obtained for two values of the momentum transfer at omega=220 MeV, are well described by the results of continuum-Faddeev calculations. These calculations indicate that the cross section in this domain is dominated by direct two-proton emission induced by a one-body hadronic current. Cross section distributions determined as a function of the relative momentum of the two protons are fairly well reproduced by continuum-Faddeev calculations based on various realistic nucleon-nucleon potential models. At higher neutron momentum and at higher energy transfer, deviations between data and calculations are observed that may be due to contributions of isobar currents.Comment: 14 pages, 1 table, 17 figure

Multi-wavelength interferometry of evolved stars using VLTI and VLBA

We report on our project of coordinated VLTI/VLBA observations of the atmospheres and circumstellar environments of evolved stars. We illustrate in general the potential of interferometric measurements to study stellar atmospheres and envelopes, and demonstrate in particular the advantages of a coordinated multi-wavelength approach including near/mid-infrared as well as radio interferometry. We have so far made use of VLTI observations of the near- and mid-infrared stellar sizes and of concurrent VLBA observations of the SiO maser emission. To date, this project includes studies of the Mira stars S Ori and RR Aql as well as of the supergiant AH Sco. These sources all show strong silicate emission features in their mid-infrared spectra. In addition, they each have relatively strong SiO maser emission. The results from our first epochs of S Ori measurements have recently been published and the main results are reviewed here. The S Ori maser ring is found to lie at a mean distance of about 2 stellar radii, a result that is virtually free of the usual uncertainty inherent in comparing observations of variable stars widely separated in time and stellar phase. We discuss the status of our more recent S Ori, RR Aql, and AH Sco observations, and present an outlook on the continuation of our project.Comment: 9 pages, to appear in the proceedings of the ESO workshop "The Power of Optical/IR Interferometry: Recent Scientific Results and 2nd Generation VLTI Instrumentation", ESO Astrophysics Symposi

On Classification of N=2 Supersymmetric Theories, (e-mail uncorrupted version)

We find a relation between the spectrum of solitons of massive $N=2$ quantum field theories in $d=2$ and the scaling dimensions of chiral fields at the conformal point. The condition that the scaling dimensions be real imposes restrictions on the soliton numbers and leads to a classification program for symmetric $N=2$ conformal theories and their massive deformations in terms of a suitable generalization of Dynkin diagrams (which coincides with the A--D--E Dynkin diagrams for minimal models). The Landau-Ginzburg theories are a proper subset of this classification. In the particular case of LG theories we relate the soliton numbers with intersection of vanishing cycles of the corresponding singularity; the relation between soliton numbers and the scaling dimensions in this particular case is a well known application of Picard-Lefschetz theory.Comment: 116 pages, HUTP-92/A064 and SISSA-203/92/E