Polysaccharide antigen-glycolipid conjugate vaccines

The present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydratebased vaccines. The new vaccines consist of a multi- modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines

Physical activity programs in older persons with Alzheimer’s disease: a need for dedicated trials

Recent works highlight the influence of different aspects of lifestyle on cognitive decline and the risk of dementia. Some data suggest that exercise could improve cognitive performance, especially executive functions and reduce the risk of cognitive decline and dementia in the elder. There is controversial data regarding the role of physical exercise on cognitive performance in older patients with dementia, which may be due to diverse study designs. Innovative interventional trials need to adapt their aims toward physical and cognitive changes in patients suffering from Alzheimer's disease (AD) in association with physical activity (PA). Future goals should include specific Adapted Physical Activity (APA) intervention programs on maintaining cognitive, emotional, and physical function in older persons with dementia at risk of rapid decline. In this commentary, we will provide novel insights on the use of potential physical activity programs in Alzheimer's Disease Day Centers

A dominant mutation in β-AMYLASE1 disrupts nighttime control of starch degradation in Arabidopsis leaves

Arabidopsis (Arabidopsis thaliana) leaves possess a mechanism that couples the rate of nighttime starch degradation to the anticipated time of dawn, thus preventing premature exhaustion of starch and nighttime starvation. To shed light on the mechanism, we screened a mutagenized population of a starvation reporter line and isolated a mutant that starved prior to dawn. The mutant had accelerated starch degradation, and the rate was not adjusted to time of dawn. The muta- tion responsible led to a single amino acid change (S132N) in the starch degradation enzyme BETA-AMYLASE1 (BAM1; mutant allele named bam1-2D), resulting in a dominant, gain-of-function phenotype. Complete loss of BAM1 (in bam1-1) did not affect rates of starch degradation, while expression of BAM1(S132N) in bam1-1 recapitulated the accelerated starch degradation phenotype of bam1-2D. In vitro analysis of recombinant BAM1 and BAM1(S132N) proteins revealed no differ- ences in kinetic or stability properties, but in leaf extracts, BAM1(S132N) apparently had a higher affinity than BAM1 for an established binding partner required for normal rates of starch degradation, LIKE SEX FOUR1 (LSF1). Genetic approaches showed that BAM1(S132N) itself is likely responsible for accelerated starch degradation in bam1-2D and that this activity requires LSF1. Analysis of plants expressing BAM1 with alanine or aspartate rather than serine at position 132 indicated that the gain-of-function phenotype is not related to phosphorylation status at this position. Our results strengthen the view that control of starch degradation in wild-type plants involves dynamic physical interactions of degradative enzymes and related proteins with a central role for complexes containing LSF1

Modelling and Simulation of Asynchronous Real-Time Systems using Timed Rebeca

In this paper we propose an extension of the Rebeca language that can be used to model distributed and asynchronous systems with timing constraints. We provide the formal semantics of the language using Structural Operational Semantics, and show its expressiveness by means of examples. We developed a tool for automated translation from timed Rebeca to the Erlang language, which provides a first implementation of timed Rebeca. We can use the tool to set the parameters of timed Rebeca models, which represent the environment and component variables, and use McErlang to run multiple simulations for different settings. Timed Rebeca restricts the modeller to a pure asynchronous actor-based paradigm, where the structure of the model represents the service oriented architecture, while the computational model matches the network infrastructure. Simulation is shown to be an effective analysis support, specially where model checking faces almost immediate state explosion in an asynchronous setting.Comment: In Proceedings FOCLASA 2011, arXiv:1107.584

Dynamics of a tunneling magnetic impurity: Kondo effect induced incoherence

We study how the formation of the Kondo compensation cloud influences the dynamical properties of a magnetic impurity that tunnels between two positions in a metal. The Kondo effect dynamically generates a strong tunneling impurity-conduction electron coupling, changes the temperature dependence of the tunneling rate, and may ultimately result in the destruction of the coherent motion of the particle at zero temperature. We find an interesting two-channel Kondo fixed point as well for a vanishing overlap between the electronic states that screen the magnetic impurity. We propose a number of systems where the predicted features could be observed.Comment: 4 pages, 3 figures, ReVTe

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Mean-field model for magnetic orders in NpTGa5 with T=Co, Ni or Rh

Characteristics of magnetic transitions in NpTGa$_5$ with T=Co, Ni, Rh are explained in a unified way with use of a crystalline electric field (CEF) model of localized 5$f^4$ electrons. The model takes a CEF doublet and a singlet as local states, and includes dipolar and quadrupolar intersite interactions in the mean-field theory. Diverse ordering phenomena are derived depending on the magnitude of interaction parameters, which qualitatively reproduce the experimentally observed magnetic behaviors in NpTGa$_5$. The quadrupole degrees of freedom are essential to the diverse magnetic orders. It is argued that NpRhGa$_5$ is close to a multicritical point where quadrupoles and dipoles with different directions are competing to order.Comment: 17 pages, 10 figure