Autoimmunity in common variable immunodeficiency

immunodeficiency (CVID), the most common symptomatic primary immunodeficiency in adulthood. Different authors report high prevalences of autoimmune diseases in CVID, and several mechanisms have been proposed to explain this apparent paradox. Genetic predisposition, under current surveillance, innate and adaptive immunity deficiencies leading to persistent/recurrent infections, variable degrees of immune dysregulation, and possible failure in central and peripheral mechanisms of tolerance induction or maintenance may all contribute to increased autoimmunity. Conclusions Data on the clinical/immunological profile of affected patients and treatment are available mostly concerning autoimmune cytopenias, the most common autoimmune diseases in CVID. Treatment is based on conventional alternatives, in association with short experience with new agents, including rituximab and infliximab. Benefits of early immunoglobulin substitutive treatment and hypothetical premature predictors of autoimmunity are discussed as potential improvements to CVID patients` follow-up.

Slower rescue of ER homeostasis by the unfolded protein response pathway associated with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia and recurrent infections. Herein we addressed the role of unfolded protein response (UPR) in the pathogenesis of the disease. Augmented unspliced X-box binding protein 1 (XBP-1) mRNA concurrent with co-localization of IgM and BiP/GRP78 were found in one CVID patient. At confocal microscopy analysis this patient`s cells were enlarged and failed to present the typical surface distribution of IgM, which accumulated within an abnormally expanded endoplasmic reticulum. Sequencing did not reveal any mutation on XBP-1, neither on IRE-1 alpha that could potentially prevent the splicing to occur. Analysis of spliced XBP-1, IRE-1 alpha and BiP messages after LPS or Brefeldin A treatment showed that, unlike healthy controls that respond to these endoplasmic reticulum (ER) stressors by presenting waves of transcription of these three genes, this patient`s cells presented lower rates of transcription, not reaching the same level of response of healthy subjects even after 48 h of ER stress. Treatment with DMSO rescued IgM and IgG secretion as well as the expression of spliced XBP-1. Our findings associate diminished splicing of XBP-1 mRNA with accumulation of IgM within the ER and lower rates of chaperone transcription, therefore providing a mechanism to explain the observed hypogammaglobulinemia. (C) 2008 Elsevier Ltd. All rights reserved.

5-HT(1B) receptor in the suprachiasmatic nucleus of the common marmoset (Callithrix jacchus)

Serotonin (5-HT) is involved in the fine adjustments at several brain centers including the core of the mammal circadian timing system (CTS) and the hypothalamic suprachiasmatic nucleus (SCN). The SCN receives massive serotonergic projections from the midbrain raphe nuclei, whose inputs are described in rats as ramifying at its ventral portion overlapping the retinohypothalamic and geniculohypothalamic fibers. In the SCN, the 5-HT actions are reported as being primarily mediated by the 5-HT1 type receptor with noted emphasis for 5-HT(1B) subtype, supposedly modulating the retinal input in a presynaptic way. In this study in a New World primate species, the common marmoset (Callithrix jacchus), we showed the 5-HT(1B) receptor distribution at the dorsal SCN concurrent with a distinctive location of 5-HT-immunoreactive fibers. This finding addresses to a new discussion on the regulation and synchronization of the circadian rhythms in recent primates. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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.

Effect on the heavy-ion fusion and elastic scattering cross sections of common approximations assumed in coupled-channel calculations

We study the effects of several approximations commonly used in coupled-channel analyses of fusion and elastic scattering cross sections. Our calculations are performed considering couplings to inelastic states in the context of the frozen approximation, which is equivalent to the coupled-channel formalism when dealing with small excitation energies. Our findings indicate that, in some cases, the effect of the approximations on the theoretical cross sections can be larger than the precision of the experimental data.

Repetition-free longest common subsequence

We study the following problem. Given two sequences x and y over a finite alphabet, find a repetition-free longest common subsequence of x and y. We show several algorithmic results, a computational complexity result, and we describe a preliminary experimental study based on the proposed algorithms. We also show that this problem is APX-hard. (C) 2009 Elsevier B.V. All rights reserved.

An all-substrings common subsequence algorithm

Given two strings A and B of lengths n(a) and n(b), n(a) <= n(b), respectively, the all-substrings longest common subsequence (ALCS) problem obtains, for every substring B` of B, the length of the longest string that is a subsequence of both A and B. The ALCS problem has many applications, such as finding approximate tandem repeats in strings, solving the circular alignment of two strings and finding the alignment of one string with several others that have a common substring. We present an algorithm to prepare the basic data structure for ALCS queries that takes O(n(a)n(b)) time and O(n(a) + n(b)) space. After this preparation, it is possible to build that allows any LCS length to be retrieved in constant time. Some trade-offs between the space required and a matrix of size O(n(b)(2)) the querying time are discussed. To our knowledge, this is the first algorithm in the literature for the ALCS problem. (C) 2007 Elsevier B.V. All rights reserved.

Temperature and common-ion effect on magnesium oxide (MgO) hydration

MgO based refractory castables draw wide technological interest because they have the versatility and installation advantages of monolithic refractories with intrinsic MgO properties, such as high refractoriness and resistance to basic slag corrosion. Nevertheless, MgO easily reacts with water to produce Mg(OH)(2), which is followed by a large volumetric expansion, limiting its application in refractory castables. In order to develop solutions to minimize this effect, a better understanding of the main variables involved in this reaction is required. In this work, the influence of temperature, as well as the impact of the chemical equilibrium shifting (known as the common-ion effect), on MgO hydration was evaluated. Ionic conductivity measurements at different temperatures showed that the MgO hydration reaction is accelerated with increasing temperature. Additionally, different compounds were added to evaluate their influence on the reaction rate. Among them, CaCl(2) delayed the reaction, whereas KOH showed an opposite behavior. MgCl(2) and MgSO(4) presented similar results and two other distinct effects, reaction delay and acceleration, which depended on their concentration in the suspensions. The results were evaluated by considering the kinetics and the thermodynamics of the reaction, and the mechanical damages in the samples that was caused by the hydration reaction. (C) 2009 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Solar thermal components adapted to common building standards (SCAS)

Pilot versions of a solar heating/natural gas burner system, of a solar heating/pellet burner system and of a façade/roof integrated polymeric collector have been installed in the summer of 2006 in a number of demonstration houses in Denmark, Sweden and Norway.These three new products have been evaluated by means of measurements of the thermal performance and energy savings of the pilot systems in practice and by means of a commercial evaluation.The conclusion of the evaluations is that the products are attractive for the industry partners METRO THERM A/S, Solentek and SOLARNOR. It is expected that the companies will bring the products into the market in 2007.Further, the results of the project have been presented atinternational and national congresses and seminars for the solar heating branch. The congresses and seminars attracted a lot of interested participants.Furthermore, the project results have been published in international congress papers as well as in national journals in the energy field.Consequently, the Nordic solar heating industry will benefit from the project.

Energy Efficiency through Thermal Energy Storage : Possibilities for the Swedish Building Stock

The need for heating and cooling in buildings constitutes a considerable part of the total energy use in a country and reducing this need is of outmost importance in order to reach national and international goals for reducing energy use and emissions. One important way of reaching these goals is to increase the proportion of renewable energy used for heating and cooling of buildings. Perhaps the largest obstacle with this is the often occurring mismatch between the availability of renewable energy and the need for heating or cooling, hindering this energy to be used directly. This is one of the problems that can be solved by using thermal energy storage (TES) in order to save the heat or cold from when it is available to when it is needed. This thesis is focusing on the combination of TES techniques and buildings to achieve increased energy efficiency for heating and cooling. Various techniques used for TES as well as the combination of TES in buildings have been investigated and summarized through an extensive literature review. A survey of the Swedish building stock was also performed in order to define building types common in Sweden. Within the scope of this thesis, the survey resulted in the selection of three building types, two single family houses and one office building, out of which the two residential buildings were used in a simulation case study of passive TES with increased thermal mass (both sensible and latent). The second case study presented in the thesis is an evaluation of an existing seasonal borehole storage of solar heat for a residential community. In this case, real measurement data was used in the evaluation and in comparisons with earlier evaluations. The literature reviews showed that using TES opens up potential for reduced energy demand and reduced peak heating and cooling loads as well as possibilities for an increased share of renewable energy to cover the energy demand. By using passive storage through increased thermal mass of a building it is also possible to reduce variations in the indoor temperature and especially reduce excess temperatures during warm periods, which could result in avoiding active cooling in a building that would otherwise need it. The analysis of the combination of TES and building types confirmed that TES has a significant potential for increased energy efficiency in buildings but also highlighted the fact that there is still much research required before some of the technologies can become commercially available. In the simulation case study it was concluded that only a small reduction in heating demand is possible with increased thermal mass, but that the time with indoor temperatures above 24 °C can be reduced by up to 20%. The case study of the borehole storage system showed that although the storage system worked as planned, heat losses in the rest of the system as well as some problems with the system operation resulted in a lower solar fraction than projected. The work presented within this thesis has shown that TES is already used successfully for many building applications (e.g. domestic hot water stores and water tanks for storing solar heat) but that there still is much potential in further use of TES. There are, however, barriers such as a need for more research for some storage technologies as well as storage materials, especially phase change material storage and thermochemical storage.

Testing common nonlinear features in vector nonlinear autoregressive models

This paper studies a special class of vector smooth-transition autoregressive (VSTAR) models that contains common nonlinear features (CNFs), for which we proposed a triangular representation and developed a procedure of testing CNFs in a VSTAR model. We first test a unit root against a stable STAR process for each individual time series and then examine whether CNFs exist in the system by Lagrange Multiplier (LM) test if unit root is rejected in the first step. The LM test has standard Chi-squared asymptotic distribution. The critical values of our unit root tests and small-sample properties of the F form of our LM test are studied by Monte Carlo simulations. We illustrate how to test and model CNFs using the monthly growth of consumption and income data of United States (1985:1 to 2011:11).

Residual-based Inference for Common Nonlinear Features

This paper investigates common nonlinear features in multivariate nonlinear autore-gressive models via testing the estimated residuals. A Wald-type test is proposed and itis asymptotically Chi-squared distributed. Simulation studies are given to examine thefinite-sample properties of the proposed test.

Student and library services in cooperation

Abstract At Ångström Laboratory, one of the largest campuses at Uppsala University, the Library and the Student Services Office merged in November 2012. This merger is a pilot project to improve service for students and faculty. Ångström Laboratory has around 900 staff and almost 10,000 students, of whom most also spend time at other campuses. In this paper we describe the background and the implementation of the pilot project. One of the main reasons for moving together was the wish to gather together all kinds of student services, including the distribution of written examinations in one place. The central location and open environment of the Library made it a good choice. The heart of the Library and Student Services is an open office consisting of two service desks located in the library area. There are silent study areas; computers for searching and printing, an area for relaxing with newspapers and journals, meeting rooms and offices for the staff. The result is a lively place with a cosy atmosphere. As the Library and the Student Services still belong to different parts of the University we are now starting to find out how best to collaborate. To understand more we log all the questions we get and the services we deliver. We also have meetings together and use the same lunch room to get to know each other and our different functions. We will define which matters can be solved in common, and how we can back each other up when necessary.