Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID. (C) 2009 Elsevier Inc. All rights reserved.

Discontinuous local semiflows for Kurzweil equations leading to LaSalle`s invariance principle for differential systems with impulses at variable times

In this paper, we consider an initial value problem for a class of generalized ODEs, also known as Kurzweil equations, and we prove the existence of a local semidynamical system there. Under certain perturbation conditions, we also show that this class of generalized ODEs admits a discontinuous semiflow which we shall refer to as an impulsive semidynamical system. As a consequence, we obtain LaSalle`s invariance principle for such a class of generalized ODEs. Due to the importance of LaSalle`s invariance principle in studying stability of differential systems, we include an application to autonomous ordinary differential systems with impulse action at variable times. (C) 2011 Elsevier Inc. All rights reserved.

Loops, Chains, Sheets, and Networks from Variable Coordination of Cu(hfac)(2) with a Flexibly Hinged Aminoxyl Radical Ligand

One pair of reactants, Cu(hfac)(2) = M and the hinge-flexible radical ligand 5-(3-N-tert-butyl-N-aminoxylphenyl)pyrimidine (3PPN = L), yields a diverse set of five coordination complexes: a cyclic loop M(2)L(1) dimer; a 1:1 cocrystal between an M(2)L(2) loop and an ML(2) fragment; a ID chain of M(2)L(2) loops linked by M; two 2D M(3)L(2) networks of (M-L)(n) chains crosslinked by M with different repeat length pitches; a 3D M(3)L(2) network of M(2)L(2) loops cross-linking (M-L)(n)-type chains with connectivity different from those in the 2D networks. Most of the higher dimensional complexes exhibit reversible, temperature-dependent spin-state conversion of high-temperature paramagnetic states to lower magnetic moment states having antiferromagnetic exchange within Cu-ON bonds upon cooling, with accompanying bond contraction. The 3D complex also exhibited antiferromagnetic exchange between Cu(II) ions linked in chains through pyrimidine rings.

Global minimization using an Augmented Lagrangian method with variable lower-level constraints

A novel global optimization method based on an Augmented Lagrangian framework is introduced for continuous constrained nonlinear optimization problems. At each outer iteration k the method requires the epsilon(k)-global minimization of the Augmented Lagrangian with simple constraints, where epsilon(k) -> epsilon. Global convergence to an epsilon-global minimizer of the original problem is proved. The subproblems are solved using the alpha BB method. Numerical experiments are presented.

Deciphering the role of the electrostatic interactions in the alpha-tropomyosin head-to-tail complex

Skeletal alpha-tropomyosin (Tm) is a dimeric coiled-coil protein that forms linear assemblies under low ionic strength conditions in vitro through head-to-tail interactions. A previously published NMR structure of the Tin head-to-tail complex revealed that it is formed by the insertion of the N-terminal coiled-coil of one molecule into a cleft formed by the separation of the helices at the C-terminus of a second molecule. To evaluate the contribution of charged residues to complex stability, we employed single and double-mutant Tm fragments in which specific charged residues were changed to alanine in head-to-tail binding assays, and the effects of the mutations were analyzed by thermodynamic double-mutant cycles and protein-protein docking. The results show that residues K5, K7, and D280 are essential to the stability of the complex. Though D2, K6, D275, and H276 are exposed to the solvent and do not participate in intermolecular contacts in the NMR structure, they may contribute to head-to-tail complex stability by modulating the stability of the helices at the Tm termini.

3D roll-forming of hat-profile with variable depth and width

The use of roll-formed products in automotive, furniture, buildings etc. increases every year due to the low part-production cost and the complicated cross-sections that can be produced. The limitation with roll-forming until recent years is that one could only produce profiles with a constant cross-section in the longitudinal direction. About eight years ago ORTIC AB [1] developed a machine in which it was possible to produce profiles with a variable width (“3D roll-forming”) for the building industry. Experimental equipment was recently built for research and prototyping of profiles with variable cross-section in both width and depth for the automotive industry. The objective with the current study is to investigate the new tooling concept that makes it possible to roll-form hat-profiles, made of ultra high strength steel, with variable cross-section in depth and width. The result shows that it is possible to produce 3D roll-formed profiles with close tolerances.

A Note on Proxy Variables and Instrument Variable Regression

This is a note about proxy variables and instruments for identification of structural parameters in regression models. We have experienced that in the econometric textbooks these two issues are treated separately, although in practice these two concepts are very often combined. Usually, proxy variables are inserted in instrument variable regressions with the motivation they are exogenous. Implicitly meaning they are exogenous in a reduced form model and not in a structural model. Actually if these variables are exogenous they should be redundant in the structural model, e.g. IQ as a proxy for ability. Valid proxies reduce unexplained variation and increases the efficiency of the estimator of the structural parameter of interest. This is especially important in situations when the instrument is weak. With a simple example we demonstrate what is required of a proxy and an instrument when they are combined. It turns out that when a researcher has a valid instrument the requirements on the proxy variable is weaker than if no such instrument exists

Variação, contato e mudança linguística em Moçambique e Cabo Verde : A concordância variável de número em sintagmas nominais do português

This study investigates variable noun phrase number agreement (VNA) in two second language varieties of Portuguese, spoken in Maputo, Mozambique and in Mindelo, Cape Verde. Quantitative VARBRUL analysis is carried out based on recordings made in Maputo and Mindelo 2007 and 2008. Previous quantitative studies on VNA in varieties of Brazilian Portuguese (Guy, 1981; Lopes, 2001; Andrade, 2003) as well as on VNA in first and second language varieties of Portuguese from São Tomé (Baxter, 2004; Figueiredo, 2008, 2010) indicate contact between Portuguese and African languages as the main origin of this phenomenon. VNA in Brazilian Portuguese is, however, interpreted by Scherre (1988) and Naro & Scherre (1993, 2007) as the result of language internal drift. Varieties of Portuguese from Mozambique and Cape Verde are particularly interesting to contrast in order to investigate influences from African languages on VNA, as in Mozambique Bantu languages are first languages of the vast majority of Portuguese speakers, whereas in Cape Verde, practically all Portuguese speakers are first language speakers of Cape Verdean Creole, whose substrates are West African, and not Bantu, languages. Comparison is also made with previous studies from Brazil and São Tomé. The results of this study comment previously postulated explanations for VNA in Portuguese in various ways. The analysis of the variables onset age and age stratum indicates that VNA in the analyzed varieties is a phenomenon linked to the acquisition of Portuguese as a second language and/or language contact rather than the result of internal drift. The fact that all the compared varieties tend to mark plural on pre-head components contradicts Bantu transfer as an explanation for this pattern, and raises the need to also consider more general explanations based on language contact. The basic structural similarity between the compared varieties suggests the existence of a grammatical restructuring continuum.

School leaders as agents of change : a case study on how two head teachers are trying to implement the learning study method in their school

This paper seeks to describe and discuss the impact of inspections of schools in Sweden. It outlines the political context, based on New Public Management (NPM) theory, according to what role the Schools Inspectorate is supposed to play in order to govern and control. Attention is also devoted, referring an on-going case study, to how inspections influence head teachers and their leadership in their everyday work.   Reports from the Schools inspectorate are public. This forces both politicians and head teachers to take measures. In this case, the head teachers perceived that the inspection reports confirmed what they already knew, but it also gave them an alibi and a tool to push their teachers to take part in everyday school development work. During the first year after the inspection the head teachers mainly strived to adjust formal deficiencies in local steering documents. However, some of the deviations reported from the Schools inspectorate are regarding pedagogical problems that are complicated and difficult to handle. As interventions in many cases will show up much later the results are, for example as increased goal fulfilment, in this case, still an open question. Nevertheless, it seems obvious that the Schools Inspectorate must be seen as a result of the governing philosophy that denotes New Public Management NPM).

Do inspections of schools influence head teachers’ leadership?

This paper seeks to describe and discuss the impact of inspections of schools in Sweden. It outlines the political context, based on New Public Management (NPM) theory, according to what role the Schools Inspectorate is supposed to play in order to govern and control. Attention is also devoted, referring an on-going case study, to how inspections influence head teachers and their leadership in their everyday work.   Reports from the Schools inspectorate are public. This forces both politicians and head teachers to take measures. In this case, the head teachers perceived that the inspection reports confirmed what they already knew, but it also gave them an alibi and a tool to push their teachers to take part in everyday school development work. During the first year after the inspection the head teachers mainly strived to adjust formal deficiencies in local steering documents. However, some of the deviations reported from the Schools inspectorate are regarding pedagogical problems that are complicated and difficult to handle. As interventions in many cases will show up much later the results are, for example as increased goal fulfilment, in this case, still an open question. Nevertheless, it seems obvious that the Schools Inspectorate must be seen as a result of the governing philosophy that denotes New Public Management NPM).

'Off with his head!' : Inexplicable Faith in Bulgakov's Master and Margarita

Examining how, in the novel, Bulgakov shows the conflict between logic and faith through the actions of his characters : the characters who are logical are generally not portrayed as wise and are said to not appreciate, nor understand, faith.