Higher-order CpG-DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice

Mouse follicular B cells express TLR9 and respond vigorously to stimulation with single-stranded CpG-oligodeoxynucleotides (ODN). Surprisingly, follicular B cells do not respond to direct stimulation with other TLR9 ligands, such as bacterial DNA or class A(D) CpG-ODN capable of forming higher-order structures, unless other cell types are present. Here, we show that priming with interferons or with B cell-activating factor, or simultaneous co-engagement of the B cell receptor for antigen (BCR), can overcome this unresponsiveness. The effect of interferons occurs at the transcriptional level and is mediated through an autocrine/paracrine loop, which is dependent on IRF-1, IL-6 and IL-12 p40. We hypothesize that the lack of bystander activation of follicular B cells with more complex CpG ligands may be an important safety mechanism for avoiding autoimmunity. This will prevent resting B cells from responding to foreign or self-derived hypomethylated double-stranded CpG ligands unless these ligands are either delivered through the B cell receptor or under conditions where B cells are simultaneously co-engaged by activated plasmacytoid dendritic cells or TH1 cells. A corollary is that the heightened responsiveness of lupus B cells to TLR9-induced stimulation cannot be ascribed to unprimed follicular B cells, but is rather mediated by hypersensitive marginal zone B cells.

Fracture load and marginal fit of shrinkage-free ZrSiO4 all-ceramic crowns after chewing simulation

The aim of this in vitro study was to evaluate the fracture load and marginal accuracy of crowns made from a shrinkage-free ZrSiO4 ceramic cemented with glass-ionomer or composite cement after chewing simulation. Thirty-two human mandibular molars were randomly divided into two groups. All teeth were prepared for and restored with shrinkage-free ZrSiO4 ceramic crowns (Everest HPC (R), KaVo). The crowns of group A (N = 16) were luted to the teeth using KetacCem (R) and group B (N = 16) were adhesively cemented using Panavia (R) 21EX. Measurements of the marginal accuracy before and after cementation were made using replicas and an image analysis system. All specimens were exposed to 1.2 million cycles of thermo-mechanical fatigue in a chewing simulator. Surviving specimens were subsequently loaded until fracture in a static testing device. Fracture loads (N) were recorded. All specimens survived chewing simulation. The mean fracture loads (+/- s.d.) were Group A, 1622 N (+/- 433); group B, 1957 N (+/- 806). There was no significant difference between the two groups (P > 0.05). The marginal gap values before cementation were (mean +/- s.d.): Group A, 32.7 mu m (+/- 6.8); group B, 33.0 mu m (+/- 6.7).The mean marginal gap values after cementation were (+/- s.d.): Group A, 44.6 mu m (+/- 6.7); group B, 46.6 mu m (+/- 7.7). The marginal openings were significantly higher after cementation for both groups (P < 0.05). All test groups demonstrated fracture load and marginal accuracy values within the range of clinical acceptability.

Derivation of marginal effects of determinants of technical inefficiency

In efficiency studies using the stochastic frontier approach, the main focus is to explain inefficiency in terms of some exogenous variables and computation of marginal effects of each of these determinants. Although inefficiency is estimated by its mean conditional on the composed error term (the Jondrow et al., 1982 estimator), the marginal effects are computed from the unconditional mean of inefficiency (Wang, 2002). In this paper we derive the marginal effects based on the Jondrow et al. estimator and use the bootstrap method to compute confidence intervals of the marginal effects.

Reluctant donors? The Europeanization of international development policies in the New Member States

The European Union (EU) played an instrumental role in re-starting the international development policies in central and eastern European Member States, but questions remain about how far this policy area has been Europeanized since accession. Focusing on the Czech Republic, Hungary, Poland and Slovakia, this article investigates why the new donors have been reluctant to adopt the EU's development acquis more fully. The article traces the socialization processes offered by the EU's development policy rule-making and subsequent national rule implementation. The conclusions reveal three reasons why socialization has been weak: perceptions among the new Member States on the procedural legitimacy of the development acquis; low domestic resonance with the development acquis; and inconsistencies in the activities of norm entrepreneurs. The article contributes to our understanding of development policy in the EU – particularly how decision-making takes place within the Council and its working groups post-enlargement.

The East-Central European new donors:mapping capacity building and remaining challenges

In the past decade, the East-Central European countries were provided significant external capacity building assistance to help their emergence as donors of foreign aid. This paper aims to map these capacity development programmes and identify where they have helped and what challenges remain for the new donors. The main conclusion is that although capacity building has been instrumental in building organisational structures, working procedures and training staff, deeper underlying problems such as low levels of financing, lacking political will, the need for visibility and low staff numbers continue to hinder the new international development policies. Copyright © 2013 John Wiley & Sons, Ltd.

Aid allocation of the emerging Central and Eastern European donors

This paper examines the main characteristics of the (re-)emerging foreign aid policies of the Visegrád countries (the Czech Republic, Hungary, Poland, Slovakia), concentrating on the allocation of their aid resources. I adopt an econometric approach, similar to the ones used in the literature, for analysing the aid allocation of the OECD DAC donors. Using this approach, I examine the various factors that influence aid allocation of the Visegrád countries, using data for the years between 2001 and 2008. The most important conclusion is that the amount of aid a partner country gets from the four emerging donors is not influenced by the level of poverty or the previous performance of the recipients (measured by the level of economic growth or the quality of institutions). The main determining factor seems to be geographic proximity, as countries in the Western Balkans and the Post-Soviet region receive much more aid from the Visegrád countries than other recipients. Historical ties (pre-1989 development relations) and international obligations in the cases of Afghanistan and Iraq are also found to be significant explanatory factors. This allocation is in line with the foreign political and economic interests of these new donors. Although there are clear similarities between the four donors, this paper also identifies some individual country characteristics.

Characterization of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development

Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the full value of this emerging field can be realized. The characterization of input material for cell-based therapy bioprocesses from multiple donors is necessary to identify and understand the potential implications of input variation on process development. In this work, we have characterized bone marrow derived human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of the measurable input variation on the development of autologous and allogeneic cell-based therapy manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has been demonstrated that this variation results in a range in the process time between these donor hMSC lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of 29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent of donor variability throughout the expansion process. Measuring informative product attributes during process development will facilitate progress towards consistent manufacturing processes, a critical step in the translation cell-based therapies.

Some Marginal Densities of the Wishart Distribution

Евелина Илиева Велева - Разпределението на Уишарт се среща в практиката като разпределението на извадъчната ковариационна матрица за наблюдения над многомерно нормално разпределение. Изведени са някои маргинални плътности, получени чрез интегриране на плътността на Уишарт разпределението. Доказани са необходими и достатъчни условия за положителна определеност на една матрица, които дават нужните граници за интегрирането.

Minimum Description Length Principle in Discriminating Marginal Distributions

2010 Mathematics Subject Classification: 94A17, 62B10, 62F03.

Marginal Densities of the Wishart Distribution

2010 Mathematics Subject Classification: 62H10.