Synthesis,Characterization and Immunological Evaluation of Self‐Adjuvanting Group A Streptococcal Vaccine Candidates Bearing Various Lipidic Adjuvanting Moieties

Four group A streptococcal glycolipopeptide vaccine candidates with different lipidic adjuvanting moieties were prepared and characterized. The immunogenicity of the compounds was evaluated by macrophage and dendritic cell uptake studies and by in vivo quantification of systemic IgG antibody by ELISA. Three of the candidates showed significant induction of the IgG response.     

Stabilization of local structures by {pi}-CH and aromatic-backbone amide interactions involving prolyl and aromatic residues

Weakly polar interactions between the side-chain aromatic ringsand hydrogens of backbone amides (Ar–HN) and CHn of aliphaticgroups (     

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.     

Drop printing of pharmaceuticals: Effect of molecular weight on PEG coated‐naproxen/PEG 3350 solid dispersions

Solid dispersions have been used to enhance the bioavailability of poorly water‐soluble active pharmaceutical ingredients (APIs). However, the solid‐state phase, compositional uniformity, and scale‐up problems are issues that need to be addressed. To allow for highly controllable products, the drop printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two‐/three‐dimensional structures. DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG 3350) solid dispersions with PEG coatings of different molecular weights (MWs). A comparison of moisture‐accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy, second harmonic generation microscopy, and differential scanning calorimetry analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis was employed to measure the water content within each sample. The results suggest that the moisture‐accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API. © 2015 American Institute of Chemical Engineers AIChE J, 61: 4502–4508, 2015     

Adaptive Spatial Partitioning for Multidimensional Data Streams

We propose a space-efficient scheme for summarizing multidimensional data streams. Our sketch can be used to solve spatial versions of several classical data stream queries efficiently. For instance, we can track ε-hot spots, which are congruent boxes containing at least an ε fraction of the stream, and maintain hierarchical heavy hitters in d dimensions. Our sketch can also be viewed as a multidimensional generalization of the ε-approximate quantile summary. The space complexity of our scheme is O((1/ε) log R) if the points lie in the domain [0, R]^d, where d is assumed to be a constant. The scheme extends to the sliding window model with a log (ε n) factor increase in space, where n is the size of the sliding window. Our sketch can also be used to answer ε-approximate rectangular range queries over a stream of d-dimensional points.     

Simultaneous segmentation of prostatic zones using Active Appearance Models with multiple coupled levelsets

In this work we present an improvement to the popular Active Appearance Model (AAM) algorithm, that we call the Multiple-Levelset AAM (MLA). The MLA can simultaneously segment multiple objects, and makes use of multiple levelsets, rather than anatomical landmarks, to define the shapes. AAMs traditionally define the shape of each object using a set of anatomical landmarks. However, landmarks can be difficult to identify, and AAMs traditionally only allow for segmentation of a single object of interest. The MLA, which is a landmark independent AAM, allows for levelsets of multiple objects to be determined and allows for them to be coupled with image intensities. This gives the MLA the flexibility to simulataneously segmentation multiple objects of interest in a new image.In this work we apply the MLA to segment the prostate capsule, the prostate peripheral zone (PZ), and the prostate central gland (CG), from a set of 40 endorectal, T2-weighted MRI images. The MLA system we employ in this work leverages a hierarchical segmentation framework, so constructed as to exploit domain specific attributes, by utilizing a given prostate segmentation to help drive the segmentations of the CG and PZ, which are embedded within the prostate. Our coupled MLA scheme yielded mean Dice accuracy values of .81, .79 and .68 for the prostate, CG, and PZ, respectively using a leave-one-out cross validation scheme over 40 patient studies. When only considering the midgland of the prostate, the mean DSC values were .89, .84, and .76 for the prostate, CG, and PZ respectively.     

Determination of oxide in fluoride salts using an yttria-stabilized-zirconia oxygen pump

An improved method over a previous technique has been developed to determine the ppm oxide concentration of fluoride salts. The oxide is released as oxygen gas by the reaction of the test salt with potassium bromotetrafluoride at 450 °C. The molecular oxygen released is then passed through a zirconia oxygen pump which selectively removes the oxygen. The current response is recorded as a chronoamperogram, from which the ppm oxide content of the salt can be obtained. Oxygen recovery from an yttrium oxide standard was better than 99%. The precision of analysis of FLINAK was better than 13% for samples containing 110-170 ppm oxide. The LOD was 12 μg of oxygen, and the analytical range was 120 ppm to >20% for a 0.1-g sample.