Morphing of Triangular Meshes in Shape Space

We present a novel approach to morph between two isometric poses of the same non-rigid object given as triangular meshes. We model the morphs as linear interpolations in a suitable shape space $\mathcal{S}$. For triangulated 3D polygons, we prove that interpolating linearly in this shape space corresponds to the most isometric morph in $\mathbb{R}^3$. We then extend this shape space to arbitrary triangulations in 3D using a heuristic approach and show the practical use of the approach using experiments. Furthermore, we discuss a modified shape space that is useful for isometric skeleton morphing. All of the newly presented approaches solve the morphing problem without the need to solve a minimization problem.Comment: Improved experimental result

Gaming with eutrophication: Contribution to integrating water quantity and quality management at catchment level

The Metropolitan Region of Sao Paulo (MRSP) hosts 18 million inhabitants. A complex system of 23 interconnected reservoirs was built to ensure its water supply. Half of the potable water produced for MRSP's population (35 m3/s) is imported from a neighbour catchment, the other half is produced within the Alto Tietê catchment, where 99% of the population lives. Perimeters of land use restriction were defined to contain uncontrolled urbanization, as domestic effluents were causing increasing eutrophication of some of these reservoirs. In the 90's catchment committees and sub committees were created to promote discussion between stakeholders and develop catchment plans. The committees are very well structured "on paper". However, they are not very well organised and face a lack of experience. The objective of this work was to design tools that would strengthen their discussion capacities. The specific objective of the AguAloca process was to integrate the quality issue and its relation to catchment management as a whole in these discussions. The work was developed in the Alto Tietê Cabeceiras sub-catchment, one of the 5 sub catchments of the Alto-Tietê. It contains 5 interconnected dams, and presents competitive uses such as water supply, industry, effluent dilution and irrigated agriculture. A RPG was designed following a companion modelling approach (Etienne et al., 2003). It contains a friendly game-board, a set of individual and collective rules and a computerized biophysical model. The biophysical model is used to simulate water allocation and quality processes at catchment level. It articulates 3 modules. A simplified nutrient discharge model permits the estimation of land use nutrient exportation. An arc-node model simulates water flows and associated nutrient charges from one point of the hydrographical network to another. The Vollenweider model is used for simulating specific reservoir dynamics. The RPG allows players to make individual and collective decisions related to water allocation and the management of its quality. Impacts of these decisions are then simulated using the biophysical model. Specific indicators of the game are then updated and may influence player's behaviour (actions) in following rounds. To introduce discussions on the management of water quality at a catchment level, an issue that is rarely explicitly dealt with, four game sessions were implemented involving representatives of basin committees and water and sanitation engineers. During the game session, the participants took advantage of the water quality output of the biophysical model to test management alternatives such as rural sewage collection or effluent dilution. The biophysical model accelerated calculations of flows and eutrophication rates that were then returned to the game board with explicit indicators of quantity and quality. Players could easily test decisions impacting on qualitative water processes and visualize the simulation results directly on the game board that was representing a friendly, virtual and simplified catchment. The Agualoca game proved its ability to turn complex water processes understandable for a non totally initiated public. This experience contributed to a better understanding of multiple-use water management and also of joint management of water quality and quantity. (Résumé d'auteur

Testing of aluminium composite panels in a cone calorimeter : a new specimen preparation method

Fire testing data consistency and repeatability are essential for regulatory scrutiny, product development, and fire modelling of the lightweight cladding system. Lightweight composite claddings such as aluminium composite panels (ACPs) have been challenging to assess in terms of combustibility and flammability due to their sandwiched composite structures, which led to inconsistent data during bench-scale fire testing and fire risk assessment. This study aims to improve the test data consistency of reaction-to-fire properties such as time to ignition (tign), peak heat release rate (pHRR), time to peak heat release rate (tpHRR), total heat release (THR), which are the critical parameters for fire assessment and regulatory screening of the ACP claddings used in buildings. Therefore, a modified test approach is proposed in this study to facilitate the proper combustion process with the formation of a steady fuel gas/air mixture during the testing of cladding panel. The test data repeatability, standard deviation (SD) and relative standard deviation percentage (RSD%) of reaction-to-fire properties have been improved significantly with the modified test approach compared with the existing test approach

Acute phase inflammation is characterized by rapid changes in plasma/peritoneal fluid N-glycosylation in mice.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Murine zymosan-induced peritonitis is a widely used model for studying the molecular and cellular events responsible for the initiation, persistence and/or resolution of inflammation. Among these events, it is becoming increasingly evident that changes in glycosylation of proteins, especially in the plasma and at the site of inflammation, play an important role in the inflammatory response. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based glycosylation profiling, we investigated the qualitative and quantitative effect of zymosan-induced peritonitis on N-glycosylation in mouse plasma and peritoneal fluid. Our results show that both N-glycomes exhibit highly similar glycosylation patterns, consisting mainly of diantennary and triantennary complex type N-glycans with high levels (>95 %) of galactosylation and sialylation (mostly NeuGc) and a medium degree of core fucosylation (30 %). Moreover, MS/MS structural analysis, assisted by linkage-specific derivatization of sialic acids, revealed the presence of O-acetylated sialic acids as well as disialylated antennae ("branching sialylation") characterized by the presence of α2-6-linked NeuGc on the GlcNAc of the NeuGcα2-3-Galβ1-3-GlcNAc terminal motif. A significant decrease of (core) fucosylation together with an increase of both α2-3-linked NeuGc and "branching sialylation" were observed in N-glycomes of mice challenged with zymosan, but not in control mice injected with PBS. Importantly, substantial changes in glycosylation were already observed 12 h after induction of peritonitis, thereby demonstrating an unexpected velocity of the biological mechanisms involved.Dutch Arthritis Association (Reumafonds) LLP-24 Innovative Medicines Initiative Joint Undertaking (IMI JU)/ 115142-2 Netherlands Genomic Initiative/93511033 info:eu-repo/grantAgreement/EC/FP7/278535info:eu-repo/grantAgreement/EC/FP7/27853

Intact and subunit-specific analysis of bispecific antibodies by sheathless CE-MS

Bispecific antibodies (BsAb) are next-generation, antibody-based pharmaceuticals which come with a great functional versatility and often a vast structural heterogeneity. Although engineering of the primary sequence of BsAbs guides the proper pairing of the different chains, several side products can often be observed contributing to the macroheterogeneity of these products. Furthermore, changes in the amino acid sequence can result in different protein modifications which can affect the properties of the antibody and further increase the structural complexity. A multi-methods approach can be used for the characterization of their heterogeneity but new analytical strategies are needed for a more accurate and in-depth analysis.Here, we present a combination of intact antibody and subunit-specific mass measurements using sheathless capillary electrophoresis-mass spectrometry for assessing the macro- and microheterogeneity of BsAbs. Two homologous BsAbs with the same bispecificity but slightly different amino acid sequences were analyzed. Intact measurements were performed using a positively coated capillary and a background electrolyte (BGE) consisting of 3% acetic acid. For intact BsAbs, the separation permitted the characterization of free light chains, homo- and heterodimers as well as incomplete assemblies. For subunit-specific measurements, BsAbs were hinge region cleaved using two different enzymes (SpeB and IdeS) followed by disulfide-bond reduction. The six different subunits (Lc1, Lc2, Fd'1, Fd'2, (Fc/2)1 and (Fc/2)2) were separated using the same positively-coated capillary and a BGE consisting of 20% acetic acid and 10% methanol. Mass measurements of hinge region cleaved antibodies were performed at isotopic resolution (resolving power 140000 at m/z 1100) for a more confident analysis of low abundance proteoforms. For both BsAbs several proteoforms with e.g. pyroglutamic acid (Pyro-Glu) or glycation which could not be properly assigned at the intact level, were accurately determined in the subunits showing the complementarity of both approaches. (C) 2020 Elsevier B.V. All rights reserved.Proteomic

{3D} Morphable Face Models -- Past, Present and Future

In this paper, we provide a detailed survey of 3D Morphable Face Models over the 20 years since they were first proposed. The challenges in building and applying these models, namely capture, modeling, image formation, and image analysis, are still active research topics, and we review the state-of-the-art in each of these areas. We also look ahead, identifying unsolved challenges, proposing directions for future research and highlighting the broad range of current and future applications

IgA N- and O-glycosylation profiling reveals no association with the pregnancy-related improvement in rheumatoid arthritis

Background: The Fc glycosylation of immunoglobulin G (IgG) is well known to associate with rheumatoid arthritis (RA) disease activity. The same may be true for other classes of Igs. In the present study, we sought to determine whether the glycosylation of IgA was different between healthy subjects and patients with RA, as well as whether it was associated with RA disease activity, in particular with the pregnancy-associated improvement thereof or the flare after delivery. Methods: A recently developed high-throughput method for glycoprofiling of IgA1 was applied to affinity-captured IgA from sera of patients with RA (n = 252) and healthy control subjects (n = 32) collected before, during and after pregnancy. Results: IgA1 O-glycans bore more sialic acids in patients with RA than in control subjects. In addition, levels of bisecting N-acetylglucosamine of the N-glycans at asparagine 144 were higher in the patients with RA. The levels of several N-glycosylation traits were shown to change with pregnancy, similar to what has been shown before for IgG. However, the changes in IgA glycosylation were not associated with improvement or a flare of disease activity. Conclusions: The glycosylation of IgA differs between patients with RA and healthy control subjects. However, our data suggest only a minor, if any, association of IgA glycosylation with RA disease activity

Anion exchange chromatography - Mass spectrometry for monitoring multiple quality attributes of erythropoietin biopharmaceuticals

Assessment of critical quality attributes of the biopharmaceutical erythropoietin (EPO) prior to product release requires the use of several analytical methods. We developed an MS-compatible anion exchange (AEX) method for monitoring multiple quality attributes of EPO biopharmaceuticals. AEX was performed using a stationary phase with quaternary ammonium functional groups and a pH gradient for elution. Baseline separation of charge variants and high-quality MS data were achieved using 30 mM ammonium formate pH 5.5 and 30 mM formic acid pH 2.5 as mobile phases. In a single experiment, assessment of critical quality attributes, such as charge heterogeneity, sialic acid content and number of N-ace-tyllactosamine units, was possible while providing additional information on other modifications such as O-acetylation and deamidation. In addition, good repeatability and robustness for the relative areas of the individual glycoforms and average number of Neu5Ac per EPO molecule were observed. The results were comparable to common pharmacopeia and standard methods with the advantage of requiring fewer analytical methods and less sample treatment saving time and costs. (C) 2020 The Authors. Published by Elsevier B.V.Proteomic

A robust nanoscale RP HPLC-MS approach for sensitive Fc proteoform profiling of IgG allotypes

The conserved region (Fc) of IgG antibodies dictates the interactions with designated receptors thus defining the immunological effector functions of IgG. Amino acid sequence variations in the Fc, recognized as subclasses and allotypes, as well as post-translational modifications (PTMs) modulate these interactions. Yet, the high similarity of Fc sequences hinders allotype-specific PTM analysis by state-of-the-art bottom-up methods and current subunit approaches lack sensitivity and face co-elution of near-isobaric allotypes.To circumvent these shortcomings, we present a nanoscale reversed-phase (RP) HPLC-MS workflow of intact Fc subunits for comprehensive characterization of Fc proteoforms in an allotype- and subclass-specific manner. Polyclonal IgGs were purified from individuals followed by enzymatic digestion releasing single chain Fc subunits (Fc/2) that were directly subjected to analysis. Chromatographic conditions were optimized to separate Fc/2 subunits of near-isobaric allotypes and subclasses allowing allotype and proteoform identification and quantification across all four IgG subclasses. The workflow was complemented by a semi-automated data analysis pipeline based on the open-source software Skyline followed by post-processing in R. The approach revealed pronounced differences in Fc glycosylation between donors, besides inter-subclass and inter-allotype variability within donors. Notably, partial occupancy of the N-glycosylation site in the CH3 domain of IgG3 was observed that is generally neglected by established approaches. The described method was benchmarked across several hundred runs and showed good precision and robustness.This methodology represents a first mature Fc subunit profiling approach allowing truly subclass- and allotype-specific Fc proteoform characterization beyond established approaches. The comprehensive information obtained paired with the high sensitivity provided by the miniaturization of the approach guarantees applicability to a broad range of research questions including clinically relevant (auto)antibody characterization or pharmacokinetics assessment of therapeutic IgGs.Pathophysiology and treatment of rheumatic disease

Integrated N- and O-glycomics of acute myeloid leukemia (AML) cell lines

Acute myeloid leukemia (AML) is characterized by a dysregulated expansion of poorly differentiated myeloid cells. Although patients are usually treated effectively by chemotherapy, a high rate of relapsed or refractory disease poses a major hurdle in its treatment. Recently, several studies have proposed implications of protein glycosylation in the pathobiology of AML including chemoresistance. Accordingly, associations have been found between specific glycan epitopes and the outcome of the disease. To advance this poorly studied field, we performed an exploratory glycomics study characterizing 21 widely used AML cell lines. Exploiting the benefits of porous graphitized carbon chromatography coupled to tandem mass spectrometry (PGC nano-LC-MS2), we qualitatively and quantitatively profiled N- and O-linked glycans. AML cell lines exhibited distinct glycan fingerprints differing in relevant glycan traits correlating with their cellular phenotype as classified by the FAB system. By implementing transcriptomics data, specific glycosyltransferases and hematopoietic transcription factors were identified, which are candidate drivers of the glycan phenotype of these cells. In conclusion, we report the varying expression of glycan structures across a high number of AML cell lines, including those associated with poor prognosis, identified underlying glycosyltransferases and transcription factors, and provide insights into the regulation of the AML glycan repertoire.Proteomic