Correlated rigidity percolation and colloidal gels

Rigidity percolation (RP) occurs when mechanical stability emerges in disordered networks as constraints or components are added. Here we discuss RP with structural correlations, an effect ignored in classical theories albeit relevant to many liquid-to-amorphous-solid transitions, such as colloidal gelation, which are due to attractive interactions and aggregation. Using a lattice model, we show that structural correlations shift RP to lower volume fractions. Through molecular dynamics simulations, we show that increasing attraction in colloidal gelation increases structural correlation and thus lowers the RP transition, agreeing with experiments. Hence colloidal gelation can be understood as a RP transition, but occurs at volume fractions far below values predicted by the classical RP, due to attractive interactions which induce structural correlation

Interaction between bottlenose dolphin (Tursiops truncatus) and trammel nets in the Archipelago de La Maddalena, Italy

Peer reviewedPublisher PD

Analysis of urinary oligosaccharides in lysosomal storage disorders by capillary high-performance anion-exchange chromatography–mass spectrometry

Many lysosomal storage diseases are characterized by an increased urinary excretion of glycoconjugates and oligosaccharides that are characteristic for the underlying enzymatic defect. Here, we have used capillary high-performance anion-exchange chromatography (HPAEC) hyphenated to mass spectrometry to analyze free oligosaccharides from urine samples of patients suffering from the lysosomal storage disorders fucosidosis, α-mannosidosis, GM1-gangliosidosis, GM2-gangliosidosis, and sialidosis. Glycan fingerprints were registered, and the patterns of accumulated oligosaccharides were found to reflect the specific blockages of the catabolic pathway. Our analytical approach allowed structural analysis of the excreted oligosaccharides and revealed several previously unpublished oligosaccharides. In conclusion, using online coupling of HPAEC with mass spectrometric detection, our study provides characteristic urinary oligosaccharide fingerprints with diagnostic potential for lysosomal storage disorders

Inkjet Metrology: High-Accuracy Mass Measurements of Microdroplets Produced by a Drop-on-Demand Dispenser

We describe gravimetric methods for measuring the mass of droplets generated by a drop-on-demand (DOD) microdispenser. Droplets are deposited, either continuously at a known frequency or as a burst of known number, into a cylinder positioned on a submicrogram balance. Mass measurements are acquired precisely by computer, and results are corrected for evaporation. Capabilities are demonstrated using isobutyl alcohol droplets. For ejection rates greater than 100 Hz, the repeatability of droplet mass measurements was 0.2%, while the combined relative standard uncertainty (uc) was 0.9%. When bursts of droplets were dispensed, the limit of quantitation was 72 μg (1490 droplets) with uc = 1.0%. Individual droplet size in a burst was evaluated by high-speed videography. Diameters were consistent from the tenth droplet onward, and the mass of an individual droplet was best estimated by the average droplet mass with a combined uncertainty of about 1%. Diameters of the first several droplets were anomalous, but their contribution was accounted for when dispensing bursts. Above the limits of quantitation, the gravimetric methods provided statistically equivalent results and permit detailed study of operational factors that influence droplet mass during dispensing, including the development of reliable microassays and standard materials using DOD technologies

Tracking Antigen-Specific T-Cells during Clinical Tolerance Induction in Humans

Allergen immunotherapy presents an opportunity to define mechanisms of induction of clinical tolerance in humans. Significant progress has been made in our understanding of changes in T cell responses during immunotherapy, but existing work has largely been based on functional T cell assays. HLA-peptide-tetrameric complexes allow the tracking of antigen-specific T-cell populations based on the presence of specific T-cell receptors and when combined with functional assays allow a closer assessment of the potential roles of T-cell anergy and clonotype evolution. We sought to develop tools to facilitate tracking of antigen-specific T-cell populations during wasp-venom immunotherapy in people with wasp-venom allergy. We first defined dominant immunogenic regions within Ves v 5, a constituent of wasp venom that is known to represent a target antigen for T-cells. We next identified HLA-DRB1*1501 restricted epitopes and used HLA class II tetrameric complexes alongside cytokine responses to Ves v 5 to track T-cell responses during immunotherapy. In contrast to previous reports, we show that there was a significant initial induction of IL-4 producing antigen-specific T-cells within the first 3–5 weeks of immunotherapy which was followed by reduction of circulating effector antigen-specific T-cells despite escalation of wasp-venom dosage. However, there was sustained induction of IL-10-producing and FOXP3 positive antigen-specific T cells. We observed that these IL-10 producing cells could share a common precursor with IL-4-producing T cells specific for the same epitope. Clinical tolerance induction in humans is associated with dynamic changes in frequencies of antigen-specific T-cells, with a marked loss of IL-4-producing T-cells and the acquisition of IL-10-producing and FOXP3-positive antigen-specific CD4+ T-cells that can derive from a common shared precursor to pre-treatment effector T-cells. The development of new approaches to track antigen specific T-cell responses during immunotherapy can provide novel insights into mechanisms of tolerance induction in humans and identify new potential treatment targets

Blinded predictions of distribution coefficients in the SAMPL5 challenge

In the context of the SAMPL5 challenge water-cyclohexane distribution coefficients for 53 drug-like molecules were predicted. Four different models based on molecular dynamics free energy calculations were tested. All models initially assumed only one chemical state present in aqueous or organic phases. Model A is based on results from an alchemical annihilation scheme; model B adds a long range correction for the Lennard Jones potentials to model A; model C adds charging free energy corrections; model D applies the charging correction from model C to ionizable species only. Model A and B perform better in terms of mean-unsigned error ([Formula: see text] D units − 95 % confidence interval) and determination coefficient [Formula: see text] , while charging corrections lead to poorer results with model D ([Formula: see text] and [Formula: see text] ). Because overall errors were large, a retrospective analysis that allowed co-existence of ionisable and neutral species of a molecule in aqueous phase was investigated. This considerably reduced systematic errors ([Formula: see text] and [Formula: see text] ). Overall accurate [Formula: see text] predictions for drug-like molecules that may adopt multiple tautomers and charge states proved difficult, indicating a need for methodological advances to enable satisfactory treatment by explicit-solvent molecular simulations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10822-016-9969-1) contains supplementary material, which is available to authorized users

A review of methods to assess connectivity and dispersal between fish populations in the Mediterranean Sea

Fish populations are linked to each other via dispersal of individuals as eggs, larvae, juveniles or adults. The understanding of this process, known as connectivity, has a pivotal role for the management of overexploited fish stocks and the development of accurate conservation strategies. Knowledge on connectivity and fish movements is considered fundamental toward the correct design of marine protected area (MPA) networks for the achievement of the benefits of protection. Connectivity patterns are still largely unknown worldwide. A general lack of knowledge is particularly evident for the Mediterranean Sea where few studies dealing with this topic have been carried out and some methods, currently available for assessing connectivity, have not been used yet. In this review we present the methods used for studying connectivity patterns and fish movements at different life history stages and the main results achieved until now in the Mediterranean Sea. We encompass the pros and cons of each method, and conclude with future perspectives on the use of these methodologies in the Mediterranean context. © 2013 © 2013 Taylor & Francis