Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge

Research Funding Wellcome Trust, UK. Grant Numbers: 086827, 080088 NIH. Grant Number: DE022550Peer reviewedPublisher PD

Estimation of Aneurysm Wall Motion from 4D Computerized Tomographic Angiography Images

It is widely accepted that wall shear stressis associated to aneurysm formation, growthand rupture. Early identification of potential risk factors may contribute to decide the treatment and improve patient care. Previous studies have shown associations between high aneurysm wall shear stress values and both elevated risk of rupture and localization of regions of aneurysm progression. Based on the assumption that damaged regions of the endothelium have different mechanical properties, regions with differentiated wall displacement amplitudes are expected. A previous approach based on the analysis ofbidimensional dynamic tomographic angiography images at a limited number of points during the cardiac cycle showed only small displacements in some patients using that simplified and semi-automatic low resolution methodology. The purpose of this work is to overcome some of those limitations. High time and spatial resolution four dimensional computerized tomographic angiography images of cerebral aneurysms were acquired and analyzed in order to identify and characterize wall motion. Images were filtered andsegmented at nineteentime points during the cardiac cycle.An average image was computed to generate the vascular model. Anunstructured mesh of tetrahedral elements was generated using an advancing front technique. A finite element blood flow simulationwas carried out under personalized pulsatile flow conditions. A fuzzy c-means clustering algorithm was used to estimate regions that exhibit wall motion within the aneurysm sac. A good correlation between localization of regions of elevated wall shear stress and regionsexhibiting wall motion was found.Fil: Castro, Marcelo Adrian. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ahumada Olivares, María C.. Universidad Favaloro; ArgentinaFil: Putman, Christopher M. . Inova Fairfax Hospital. Department of Interventional Neuroradiology; Estados UnidosFil: Cebral, Juan R.. George Mason University. Department of Computational and Data Sciences; Estados Unido

Random finite sets in multi-target tracking - efficient sequential MCMC implementation

Over the last few decades multi-target tracking (MTT) has proved to be a challenging and attractive research topic. MTT applications span a wide variety of disciplines, including robotics, radar/sonar surveillance, computer vision and biomedical research. The primary focus of this dissertation is to develop an effective and efficient multi-target tracking algorithm dealing with an unknown and time-varying number of targets. The emerging and promising Random Finite Set (RFS) framework provides a rigorous foundation for optimal Bayes multi-target tracking. In contrast to traditional approaches, the collection of individual targets is treated as a set-valued state. The intent of this dissertation is two-fold; first to assert that the RFS framework not only is a natural, elegant and rigorous foundation, but also leads to practical, efficient and reliable algorithms for Bayesian multi-target tracking, and second to provide several novel RFS based tracking algorithms suitable for the specific Track-Before-Detect (TBD) surveillance application. One main contribution of this dissertation is a rigorous derivation and practical implementation of a novel algorithm well suited to deal with multi-target tracking problems for a given cardinality. The proposed Interacting Population-based MCMC-PF algorithm makes use of several Metropolis-Hastings samplers running in parallel, which interact through genetic variation. Another key contribution concerns the design and implementation of two novel algorithms to handle a varying number of targets. The first approach exploits Reversible Jumps. The second approach is built upon the concepts of labeled RFSs and multiple cardinality hypotheses. The performance of the proposed algorithms is also demonstrated in practical scenarios, and shown to significantly outperform conventional multi-target PF in terms of track accuracy and consistency. The final contribution seeks to exploit external information to increase the performance of the surveillance system. In multi-target scenarios, kinematic constraints from the interaction of targets with their environment or other targets can restrict target motion. Such motion constraint information is integrated by using a fixed-lag smoothing procedure, named Knowledge-Based Fixed-Lag Smoother (KB-Smoother). The proposed combination IP-MCMC-PF/KB-Smoother yields enhanced tracking

Protection of outbred mice against a vaginal challenge by a Chlamydia trachomatis serovar E recombinant major outer membrane protein vaccine is dependent on phosphate substitution in the adjuvant.

Chlamydia trachomatis is the most common bacterial sexually-transmitted pathogen for which there is no vaccine. We previously demonstrated that the degree of phosphate substitution in an aluminum hydroxide adjuvant in a TLR-4-based C. trachomatis serovar E (Ser E) recombinant major outer membrane protein (rMOMP) formulation had an impact on the induced antibody titers and IFN-γ levels. Here, we have extended these observations using outbreed CD-1 mice immunized with C. trachomatis Ser E rMOMP formulations to evaluate the impact on bacterial challenge. The results confirmed that the rMOMP vaccine containing the adjuvant with the highest phosphate substitution induced the highest neutralizing antibody titers while the formulation with the lowest phosphate substitution induced the highest IFN-γ production. The most robust protection was observed in mice vaccinated with the formulation containing the adjuvant with the lowest phosphate substitution, as shown by the number of mice with positive vaginal cultures, number of positive cultures and number of C. trachomatis inclusion forming units recovered. This is the first report showing that vaccination of an outbred strain of mice with rMOMP induces protection against a vaginal challenge with C. trachomatis

Biodegradable ion-exchange microspheres based on modified polylysines

Poly-L-lysine was synthesized via a triethylamine initiated ring-opening polymerization of Z-L-lysine-N'~-carboxyanhydride,\ud followed by deprotection of the E-amino group. Subsequently the polylysine was sulfamated using a pyridinium-sulfate complex to obtain polymers with varying degrees of sulfamation ranging from 0 to 100%. Cytotoxicity of these materials was tested using tetrazolium metabolism (MTI') assays with B16F10 and P388 cell lines. Cytotoxicity of sulfamated polylysines with a degree of sulfamation of 80% and higher was significantly reduced as compared with the native polylysines. In both cell lines, LDso of the sulfamated materials was higher than 5 mg/ml, which was the highest dose tested. LDso of the native polylysines was lower than 0.1 mg/ml in the case of B16F10 and lower than 0.01 mg/ml in the case of P388 cells. Sulfamated polylysines with a degree of sulfamation of 80% were used to prepare microspheres (SPLMS). The microspheres were stabilized using glutaraldehyde or oxidized dextran as a crosslinking agent. The swelling ratio (defined as V~wollen/Vdr~ed) of the SPLMS in aqueous media decreased with increasing ionic strength and crosslink density. The pH (ranging from 3 to 11) had no influence on the swelling ratio of SPLMS. The maximal swelling ratio was approximately 35 (SPLMS crosslinked with 0.5% glutaraldehyde in distilled water). SPLMS could be loaded with adriamycin up to a payload of 60%, which was not influenced by the crosslinking method. The adriamycin release was controlled by the ionic strength of the release medium: no drug was released in non-ionic medium such as distilled water, while 80% of the drug was released in phosphate buffered saline. This effect of the change in ionic strength could be applied to prepare a microsphere suspension in non-ionic medium such as 5% glucose solution, which does not contain free adriamycin. The drug would only be release after intra-arterial administration of this suspension, due to\ud the presence of the blood

Age differences in encoding-related alpha power reflect sentence comprehension difficulties

When sentence processing taxes verbal working memory, comprehension difficulties arise. This is specifically the case when processing resources decline with advancing adult age. Such decline likely affects the encoding of sentences into working memory, which constitutes the basis for successful comprehension. To assess age differences in encoding-related electrophysiological activity, we recorded the electroencephalogram from three age groups (24, 43, and 65 years). Using an auditory sentence comprehension task, age differences in encoding-related oscillatory power were examined with respect to the accuracy of the given response. That is, the difference in oscillatory power between correctly and incorrectly encoded sentences, yielding subsequent memory effects (SME), was compared across age groups. Across age groups, we observed an age-related SME inversion in the alpha band from a power decrease in younger adults to a power increase in older adults. We suggest that this SME inversion underlies age-related comprehension difficulties. With alpha being commonly linked to inhibitory processes, this shift may reflect a change in the cortical inhibition–disinhibition balance. A cortical disinhibition may imply enriched sentence encoding in younger adults. In contrast, resource limitations in older adults may necessitate an increase in cortical inhibition during sentence encoding to avoid an information overload. Overall, our findings tentatively suggest that age-related comprehension difficulties are associated with alterations to the electrophysiological dynamics subserving general higher cognitive functions