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Purpose The use of Electronic Portal Imaging Devices (EPIDs) to acquire dosimetric information, especially for 3D-back-projection, has been increasingly extended. For a precise back-projection, the accurate knowledge of the movement characteristics of the EPID during gantry rotation is an essential requirement. Methods and material Measurements were conducted with different alignments of steel balls, which were mounted on the treatment table to avoid secondary effects such as the mechanical sag of gantry or jaws. The image movement of the EPID was determined by comparing the predicted projections of the phantoms with the EPID acquired image. Effects on dosimetric verifications were evaluated by γ -evaluation. Results The measurement results showed that the shift of the EPID image is larger in Y direction than in X direction. A maximum rotation of 0.3° and nodding of 2.4° of the detector was calculated. Changes in SDD were found up to 10 mm. The angles of nodding are overall higher at discrete gantry angles in comparison to images detected for continuous rotation. Using these results we were able to correct the EPID images used for verification measurements. γ -evaluation revealed a significantly improved agreement between planned and measured EPID signal values. Conclusion The measurement methods and algorithms introduced in this study are simple and comprehensive. Using these methods and algorithms we were able to quantify the major effects on geometrical and dosimetric characteristics. This allows the correction of EPID signal measurements for these effects related to the gantry angle, leading to an improved γ -evaluation for treatment plans. [ABSTRACT FROM AUTHOR]

The Hubbard model with large orbital degeneracy has recently gained relevance in the context of ultracold earth alkali-like atoms. We compute its static properties in the SU(2M) symmetric limit for up to M = 8 bands at half filling within dynamical mean-field theory, using the numerically exact multigrid Hirsch-Fye quantum Monte Carlo approach. Based on these unbiased data, we establish scaling laws which predict the phase boundaries of the paramagnetic Mott metal-insulator transition at arbitrary orbital degeneracy M with high accuracy. [ABSTRACT FROM AUTHOR]

The LDA+DMFT approach merges conventional band structure theory in the local density approximation (LDA) with a state-of-the-art many-body technique, the dynamical mean-field theory (DMFT). This new computational scheme has recently become a powerful tool for ab initio investigations of real materials with strong electronic correlations. In this paper an introduction to the basic ideas and the set-up of the LDA+DMFT approach is given. Results for the photoemission spectra of the transition metal oxide La[sub 1-x]Sr[sub x]TiO[sub 3], obtained by solving the DMFT equations by quantum Monte Carlo (QMC) simulations, are presented and are found to be in very good agreement with experiment. The numerically exact DMFT(QMC) solution is compared with results obtained by two approximative solutions, i.e. the iterative perturbation theory and the non-crossing approximation. [ABSTRACT FROM AUTHOR]

We present an algorithm for solving the self-consistency equations of the dynamical mean-field theory (DMFT) with high precision and efficiency at low temperatures. In each DMFT iteration, the impurity problem is mapped to an auxiliary Hamiltonian, for which the Green function is computed by combining determinantal quantum Monte Carlo (BSS-QMC) calculations with a multigrid extrapolation procedure. The method is numerically exact, i.e., yields results which are free of significant Trotter errors, but retains the BSS advantage, compared to direct QMC impurity solvers, of linear (instead of cubic) scaling with the inverse temperature. The new algorithm is applied to the half-filled Hubbard model close to the Mott transition; detailed comparisons with exact diagonalization, Hirsch-Fye QMC, and continuous-time QMC are provided. [ABSTRACT FROM AUTHOR]

We compute unbiased spectral functions of the two-dimensional Hubbard model by extrapolating Green functions, obtained from determinantal quantum Monte Carlo simulations, to the thermodynamic and continuous time limits. Our results clearly resolve the pseudogap at weak to intermediate coupling, originating from a momentum selective opening of the charge gap. A characteristic pseudogap temperature T*, determined consistently from the spectra and from the momentum dependence of the imaginary-time Green functions, is found to match the dynamical mean-field critical temperature, below which antiferromagnetic fluctuations become dominant. Our results identify a regime where pseudogap physics is within reach of experiments with cold fermions on optical lattices. [ABSTRACT FROM AUTHOR]

We compute the self-energy for the half-filled Hubbard model on a square lattice using lattice quantum Monte Carlo simulations and the dynamical vertex approximation. The self-energy is strongly momentum-dependent, but it can be parametrized via the noninteracting energy-momentum dispersion ɛk, except for pseudogap features right at the Fermi edge. That is, it can be written as Σ(ɛk,ω), with two energylike parameters (ɛ, ω) instead of three (kx, ky, and ω). The self-energy has two rather broad and weakly dispersing high-energy features and a sharp ω=ɛk feature at high temperatures, which turns to ω=-ɛk at low temperatures. Altogether this yields a Z- and reversed-Z-like structure, respectively, for the imaginary part of Σ(ɛk,ω). We attribute the change of the low-energy structure to antiferromagnetic spin fluctuations. [ABSTRACT FROM AUTHOR]

We have studied the impact of nonlocal electronic correlations at all length scales on the Mott-Hubbard metal-insulator transition in the unfrustrated two-dimensional Hubbard model. Combining dynamical vertex approximation, lattice quantum Monte Carlo, and variational cluster approximation, we demonstrate that scattering at long-range fluctuations, i.e., Slater-like paramagnons, opens a spectral gap at weak-to-intermediate coupling, irrespective of the preformation of localized or short-range magnetic moments. This is the reason why the two-dimensional Hubbard model has a paramagnetic phase which is insulating at low enough temperatures for any (finite) interaction and no Mott-Hubbard transition is observed. [ABSTRACT FROM AUTHOR]

Purpose: This study compares the quality of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans optimized for an Elekta Agility(TM) (Elekta, Stockholm, Sweden) multileaf collimator (MLC; leaf width 5 mm) and an Elekta MLCi2 (leaf width 10 mm) for complex target volumes (anal, AC; head and neck, H&N and prostate cancer, PC)., Patients and Methods: For plan comparisons, 15 patients who had been treated with IMRT or VMAT using the MLCi2 were selected. For each patient, a retrospective treatment plan using the MLCi2 for the technique not applied was created, as were treatment plans for both techniques using the Agility(TM) MLC. Dose-volume histograms (DHVs) for planning target volumes (PTVs) and organs at risk (OARs) were compared. Further parameters relating to dose conformity, dose homogeneity and mean dose (Dmean) to the PTV, compliance with the intended OAR dose criteria and overall dose to normal tissue were analyzed. Verification measurements were performed and optimization and treatment times were compared., Results: Compared to the MLCi2 plans, the Agility(TM) IMRT and VMAT plans show better or equivalent results in terms of PTV dose conformity and homogeneity. Compliance with the intended OAR dose criteria does not differ according to technique or MLC type. Slight differences are shown for dose distributions in OARs and normal tissue. Verification measurements show that all plans fulfill the acceptance criteria of a minimum of 95 % matched dose points for the 3 %/3 mm γ criterion. Optimization times for the VMAT plans increase compared to the IMRT plans, whereas treatment times decrease., Conclusion: With the MLCi2, treatment of complex target volumes with VMAT was only possible with compromises in terms of target coverage. Using the Agility(TM) MLC, even complex target volumes can be treated with VMAT without compromising target coverage or resulting in higher exposure of OARs or normal tissue.

We study the magnetic ordering transition for a system of harmonically trapped ultracold fermions with repulsive interactions in a cubic optical lattice, within a real-space extension of dynamical mean-field theory. Using a quantum Monte Carlo impurity solver, we establish that antiferromagnetic correlations are signaled, at strong coupling, by an enhanced double occupancy. This signature is directly accessible experimentally and should be observable well above the critical temperature for long-range order. Dimensional aspects appear less relevant than naively expected.

Background: Traditional farming represents a unique model situation to investigate the relationship of early-life farm-related exposure and allergy protection., Objectives: To investigate associations between maternal farm exposures and cytokine production in cord blood (CB) mononuclear cells in a prospective multinational birth cohort of 299 farm and 326 nonfarm children and their families., Methods: Supernatants from phorbol 12-myristate 13-acetate/ionomycin-stimulated CB mononuclear cells were assessed for the production of IFN-gamma, TNF-alpha, IL-5, IL-10, and IL-12., Results: Significantly higher levels of IFN-gamma and TNF-alpha in farm compared with nonfarm children were found, whereas IL-5, IL-10, and IL-12 levels did not differ between study groups. Maternal contact with different farm animal species and barns and consumption of farm-produced butter during pregnancy enhanced the production of proinflammatory CB cytokines, whereas maternal consumption of farm-produced yogurt resulted in significant lower levels of IFN-gamma and TNF-alpha in umbilical blood., Conclusion: Maternal exposure to farming activities and farm dairy products during pregnancy modulated cytokine production patterns of offspring at birth., (Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9(-/-) knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78-treated TLR2/3/4/7/9(-/-) homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78-exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.

Background: It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants., Objective: To investigate the relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences., Methods: As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-gamma, IL-10, and TNF-alpha., Results: Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-gamma production, but not with IL-5 and IL-10., Conclusion: Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-gamma production.

Background: Numerous epidemiologic studies have demonstrated an allergy-protective effect of farm life early in childhood. It has been hypothesized that environmental exposure to microbes may contribute to this effect. Because of their small size and thereby their potential for deposition in lower airways of small children, bacterial spores may be candidates for such allergy-protective effects., Objective: To investigate immune responses elicited by exposure to Bacillus spores in experimental settings., Methods: Animal shed and mattress dusts were analyzed for bacteria and fungi by aerobic and anaerobic growth. Bacillus licheniformis, the most prominent microorganism found in these samples, was investigated with respect to spore specific stimulation of pattern recognition receptors, monocyte-derived dendritic cells and T(H)-cell polarization in vitro as well as to the prevention of asthma development in a mouse model of allergic asthma., Results: In vitro, B. licheniformis spores activated a T(H)1 cytokine expression profile. In vivo application of these spores resulted in less spore-specific but long-lasting immune activation preventing eosinophilia and goblet cell hyperplasia; however, they provoked an influx of neutrophils in lung tissue of asthmatic mice., Conclusion: Bacterial spores may contribute to the allergy-protective properties of farming environments, but their persistence in the lung causes ongoing immune activation in mouse experiments.

Purpose of Review: There is recent evidence that immunological priming can start prenatally or in the very early life phase. This review summarizes recent progress in the field of early gut immunology with special attention to factors contributing to the intrauterine and early postnatal development of mucosal immune responses in the gut., Recent Findings: Development and maturation of the fetal gut immune system occurs under close control of the maternal environment. Examples include maternal antibodies, cytokines, sCD14 molecules and bacterial antigens. Mouse experiments reveal that activated T cells can be detected already at birth in the fetal gut, which are supposed to be activated by signals from the maternal microbial gut flora. Human milk sCD14 is involved in the immunological priming of the developing gut immune system to Gram-negative bacteria and modulates the microbial recognition system of the gut. The development of food allergies is associated with consumption of food components like polyunsaturated fatty acids acting prenatally or in the early postnatal life span as immunomodulators., Summary: The new findings highlight the importance of very early life factors for the development of the mucosal immune functions of the gut. Therefore, the gut might be a new target to establish preventive strategies with regard to different immunologic disorders.

Background: Children who grow up in a farming environment show lower levels of atopic sensitization, hay fever, and asthma than children of the same age not living in such an environment. A number of investigations provided good evidence that this is due to an early-life contact with cowsheds, farm animals, and/or consumption of products like raw milk. Also, it had been indicated that microorganisms might have an important effect on the development of allergies, and thus the question arose of which farm microbial organisms, their products, or both might induce or influence allergy-protective mechanisms., Objective: We sought to gain further insight into the potential allergy-protective properties of microbes isolated from the farming environment., Methods: Of a number of bacterial species identified in cowsheds of farms, 2 were selected, isolated, and characterized, namely Acinetobacter lwoffii F78 and Lactococcus lactis G121. The isolates were investigated with regard to their activation of pattern-recognition receptors, the maturation of human monocyte-derived dendritic cells, the upregulation of inflammatory cytokines, the T(H)1-polarizing Notch ligand expression, and their influence on the allergic phenotype., Results: It is shown that both bacterial isolates were able to reduce allergic reactions in mice, to activate mammalian cells in vitro, and to induce a T(H)1-polarizing program in dendritic cells., Conclusion: Our data strongly support the hygiene hypothesis, which states that an environment rich in microbiologic structures, such as a farming environment, might protect against the development of allergies., Clinical Implications: This work provides the first data on a potential application of cowshed bacteria in allergy protection.

The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants.

Epidemiological data suggest that dietary factors may have a role in recent increases of the prevalence of allergic diseases. One food-related component might be the reduced consumption of omega3-polyunsaturated fatty acids observed especially in the Western societies; yet, clinical trials supplementing omega3-fatty acids to adults with established allergies and bronchial asthma have generally been disappointing. However, it is known that the immature immune system is highly susceptible to immuno-modulatory environmental conditions particularly in the pre- and postnatal period. This review discusses the immuno-modulatory effects of omega3-fatty acids supplementation in the perinatal life phase on the immune system of the child. Evidence exists that perinatal omega3-fatty acid exposure affects T-cells and antigen presenting cells of the neonates likely due to altered eicosanoid metabolism. Although animal experiments strongly suggest a role of maternal omega3-fatty acid intake on allergic immune responses in the offspring, the beneficial effect of omega3-fatty acid supplementation has been studied in a small number of clinical trials. In these studies perinatal supplementation had some positive effects on distinct clinical phenotypes of the atopic syndrome. However, more studies are needed to fully explore the opportunity of perinatal immuno-modulation.

Worldwide, allergic diseases are increasing in prevalence and incidence. Early assessment of the immunoglobulin E (IgE) sensitisation status has a major impact on clinical outcome and selection of therapeutic options. Recently, a number of new IgE-detecting test systems have entered the market, including screening tests allowing identification of a wide spectrum of sensitising allergens. We evaluated the analytical and diagnostic performance of the newly developed Allergy Screen test panel for atopy (Mediwiss Analytic, Moers, Germany). The evaluation was performed for four major respiratory and four major nutritional allergens in 142 patients with clinical suspicion of respiratory and/or food allergies. For all allergens, the test showed acceptable concordance to the skin-prick test and the in vitro IgE CAP system (Pharmacia, Freiburg, Germany). The analytical performance was acceptable, with CVs between 2 and 8% in the positive range and good dilution linearity (R=0.9735). Imprecision in the low IgE concentration range dramatically improved by lowering the cut-off value to 0.2 IU/mL IgE. In conclusion, the Allergy Screen panel yields reliable results in the detection of allergic sensitisation to common allergens.

The Drosophila don juan (dj) gene encodes a basic protein that is expressed solely in the male germline and shows structural similarities to the linker histone H1. Don Juan is located in two different subcellular structures: in the nucleus during the phase of chromatin condensation and later in the mitochondrial derivatives starting with spermatid individualization. The don juan gene is transcribed in primary spermatocytes under the control of 23 bp upstream in combination with downstream sequences. During meiotic stages and in early spermatid stages don juan mRNA is translationally repressed for several days. Analysis of male sterile mutants which fail to undergo meiosis shows that release of dj mRNA from translational repression is independent of meiosis. In gel retardation assays 60 nucleotides at the end of the dj leader form four major complexes with proteins that were extracted from testes but not with protein extracts from ovaries. Transformation studies prove that in vivo 35 bp within that region of the dj mRNA is essential to confer translational repression. UV cross-linking studies show that a 62 kDa protein specifically binds to the same region within the 5' untranslated region. The dj translational repression element, TRE, is distinct from the translational control element, TCE, described earlier for all members of the Mst(3)CGP gene family. Moreover, expression studies in several male sterile mutants reveal that don juan mRNA is translated in earlier developmental stages during sperm morphogenesis than the Mst(3)CGP mRNAs. This proves that translational activation of dormant mRNAs in spermatogenesis occurs at different time-points which are characteristic for each gene, an essential feature for coordinated sperm morphogenesis.

The Drosophila don juan gene encodes a basic protein (Don Juan protein), which is solely expressed postmeiotically during spermiogenesis in elongated spermatids and in mature sperm. Transgenic expression of a GFP-tagged Don Juan protein (DJ-GFP) in the male germ line showed an association of the fusion protein with the sperm tail. Detailed examination of DJ-GFP localization revealed novel insights into its distinct temporal and spatial distribution along the sperm tail during the last phase of spermatid maturation. Co-localization of DJ-GFP with actin-labeled cysts demonstrated its emergence in elongated spermatids during individualization. Additionally, the endogenous Don Juan protein was detected with epitope-specific antibodies in finally elongated nuclei of spermatids. After completion of nuclear shaping Don Juan is no longer detectable in the sperm heads with the onset of individualization. Mislocalization of the DJ-GFP protein in flagella of a mutant with defective mitochondrial differentiation provides evidence of mitochondrial association of the fusion protein with flagellar mitochondrial arrays. Ectopically expressed DJ-GFP in premeiotic germ cells as well as salivary gland cells confirmed the capability of the fusion protein to associate with mitochondria. Therefore we suppose that Don Juan is a nuclear-encoded, germ-cell specifically expressed mitochondrial protein, which might be involved in the final steps of mitochondrial differentiation within the flagellum.

We identified and characterized the don juan gene (dj) of Drosophila melanogaster. The don juan gene codes for a sperm specific protein component with an unusual repetitive six amino acid motif (DPCKKK) in the carboxy-terminal part of the protein. The expression of Don Juan is limited to male germ cells where transcription of the dj gene is initiated during meiotic prophase. But Western blot experiments indicate that DJ protein occurs just postmeiotically. Examination of transgenic flies bearing a dj-promoter-lacZ reporter construct revealed lacZ mRNA distribution resembling the expression pattern of the endogenous dj mRNA in the adult testes, whereas beta-galactosidase expression is exclusively present in postmeiotic germ cells. Thus, these observations strongly suggest that dj transcripts are under translational repression until in spermiogenesis. To study the function and subcellular distribution of DJ in spermiogenesis we expressed a chimaeric dj-GFP fusion gene in the male germline exhibiting strong GFP fluorescence in the liver testes, where only elongated spermatids are decorated. With regard to the characteristic expression pattern of DJ protein and its conspicuous repeat units possible functional roles are discussed.