Structural Properties of MHC Class II Ligands, Implications for the Prediction of MHC Class II Epitopes

Major Histocompatibility class II (MHC-II) molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule, allowing binding of peptides extending out of the binding groove. Furthermore, only a few HLA-DR alleles have been characterized with a sufficient number of peptides (100–200 peptides per allele) to derive accurate description of their binding motif. Little work has been performed characterizing structural properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC class II ligands by integrating prediction of MHC- peptide binding with prediction of surface exposure and protein secondary structure. This combined prediction method was shown to significantly outperform the state-of-the-art MHC class II peptide binding prediction method when used to identify MHC class II ligands. We also tried to integrate N- and O-glycosylation in our prediction methods but this additional information was found not to improve prediction performance. In summary, these findings strongly suggest that local structural properties influence antigen processing and/or the accessibility of peptides to the MHC class II molecule

Phase Ib study of NGR–hTNF, a selective vascular targeting agent, administered at low doses in combination with doxorubicin to patients with advanced solid tumours

Contains fulltext : 81937timmer-bonte.pdf (publisher's version ) (Closed access)BACKGROUND: Asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF) is a vascular targeting agent exploiting a tumour-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13, overexpressed on tumour blood vessels. Significant preclinical synergy was shown between low doses of NGR-TNF and doxorubicin. METHODS: The primary aim of this phase I trial was to verify the safety of low-dose NGR-hTNF combined with doxorubicin in treating refractory/resistant solid tumours. Secondary objectives included pharmacokinetics (PKs), pharmacodynamics, and clinical activity. In all 15 patients received NGR-hTNF (0.2-0.4-0.8-1.6 microg m(-2)) and doxorubicin (60-75 mg m(-2)), both given intravenously every 3 weeks. RESULTS: No dose-limiting toxicity occurred and the combination was well tolerated. Around two cases of neutropenic fevers, lasting 2 days, and two cases of cardiac ejection-fraction drops, one asymptomatic and the other symptomatic, were registered. Only 11% of the adverse events were related to NGR-hTNF and were short-lasting and mild-to-moderate in severity. There was no apparent PK interaction and the shedding of soluble TNF-receptors did not increase to 0.8 microg m(-2). One partial response (7%), at dose level 0.8 microg m(-2), and 10 stable diseases (66%), lasting for a median duration of 5.6 months, were observed. CONCLUSIONS: NGR-hTNF plus doxorubicin was administered safely and showed promising activity in patients pre-treated with anthracyclines. The dose level of 0.8 microg m(-2) NGR-hTNF plus doxorubicin 75 mg m(-2) was selected for phase II development

Capture mechanism of la and Cu ions in mixed solutions by clay and organoclay

In this work, Ca-montmorillonite (STx), natural and modified (STx-L6) with a linear penta-ethylene-hexamine (L6), were tested as sorbents in a liquid/solid process for La and Cu capture in bionic model solutions. Twelve La/Cu ratios in solution were set and analyzed with the final target of investigating the capture mechanisms when both Cu and La are present. The liquid phase was characterized via inductively coupled plasmaoptical emission spectroscopy (ICP-OES), while the solids were studied by means of X-ray powder diffraction (XRPD). No direct competition between Cu and La ions for the capture sites was found but rather the modification of the acidâ'base condition of the solution and the related equilibria due to aquo- A nd hydroxycopper complexes formation. Cu complexes are responsible for pH modification and the related influence on the capture of La ions. Three distinct mechanisms were identified to be active in the capture process, i.e., ion exchange, surface adsorption, and coordination of the metal by the polyamine, when present. Only La is involved in the ionic exchange process, since no Cu was captured by pristine clays, while only Cu is coordinated to the polyamine, in view of its preferential interaction with amino groups. The different capture mechanisms are responsible for the higher efficiency of the organoclay, with respect to the pristine one. This study lays the groundwork for the development of an efficient method for rare earths (REs) and precious metal recovery from waste electrical and electronical equipment (WEEE) by a liquid/solid process

Evaluation of Graphene Nanoplatelets as a Microporous Layer Material for PEMFC: Performance and Durability Analysis

In this paper, the effect of different carbonaceous phases in microporous layers (MPLs) for polymer electrolyte membrane fuel cells (PEMFCs) is reported. A conventional ink with carbon black (CB) powder and an innovative one featuring graphene nanoplatelets (GNPs) have been produced and used to coat carbon cloth gas diffusion layers (GDLs). Morphological and electrical properties of these samples have been assessed and then compared to determine which characteristics contribute to a possible enhancement of the fuel cell performance. Static contact angle measurements have revealed a similar hydrophobic character for both samples. Through-plane water permeability and porosity of the samples have been correlated to the optimal working temperature: GNPs-based MPLs provide the best performance in dry condition (T = 80 °C, RH = 60%), while CB-based samples work better in more humid conditions. Instead, the electrical conductivity of the samples have not displayed a strong influence on the polarization curve of the cell. In addition, an ex situ mechanical accelerated stress test (AST) has been performed on both samples to assess their durability and understand which factors could lengthen their lifetime. GNPs-based samples resisted better under the harsh conditions imposed during the AST and a possible optimization of this ink composition is proposed for future development

Evaluation of Graphene Nanoplatelets as a Microporous Layer Material for PEMFC: Performance and Durability Analysis

In this paper, the effect of different carbonaceous phases in microporous layers (MPLs) for polymer electrolyte membrane fuel cells (PEMFCs) is reported. A conventional ink with carbon black (CB) powder and an innovative one featuring graphene nanoplatelets (GNPs) have been produced and used to coat carbon cloth gas diffusion layers (GDLs). Morphological and electrical properties of these samples have been assessed and then compared to determine which characteristics contribute to a possible enhancement of the fuel cell performance. Static contact angle measurements have revealed a similar hydrophobic character for both samples. Through-plane water permeability and porosity of the samples have been correlated to the optimal working temperature: GNPs-based MPLs provide the best performance in dry condition (T = 80 °C, RH = 60%), while CB-based samples work better in more humid conditions. Instead, the electrical conductivity of the samples have not displayed a strong influence on the polarization curve of the cell. In addition, an ex situ mechanical accelerated stress test (AST) has been performed on both samples to assess their durability and understand which factors could lengthen their lifetime. GNPs-based samples resisted better under the harsh conditions imposed during the AST and a possible optimization of this ink composition is proposed for future development

Optimization of perfluoropolyether-based gas diffusion media preparation for PEM fuel cells

A hydrophobic perfluoropolyether (PFPE)-based polymer, namely Fluorolink® P56, was studied instead of the commonly used polytetrafluoroethylene (PTFE), in order to enhance gas diffusion media (GDM) water management behavior, on the basis of a previous work in which such polymer had already proved to be superior. In particular, an attempt to optimize the GDM production procedure and to improve the microporous layer (MPL) adhesion to the substrate was carried out. Materials properties have been correlated with production routes by means of both physical characterization and electrochemical tests. The latter were performed in a single PEM fuel cell, at different relative humidity (namely 80 % on anode side and 60/100 % on cathode side) and temperature (60 °C and 80 °C) conditions. Additionally, electrochemical impedance spectroscopy measurements were performed in order to assess MPLs properties and to determine the influence of production procedure on cell electrochemical parameters. Durability of the best performing sample was also evaluated and compared to a previously developed benchmark. It was found that a final dipping step into PFPE-based dispersion, following MPL deposition, seems to improve adhesion of the MPL to the macro-porous substrate and to reduce diffusive limitations during fuel cell operation

Reduced Graphene Oxide Membranes as Potential Self-Assembling Filter for Wastewater Treatment

This work focuses on the investigation of the capability of reduced graphene oxide (rGO) filters to remove metals from various wastewater. The process to produce rGO membranes is reported and discussed, as well as their ability to capture ions in complex solutions, such as tap or industrial wastewater. Multi-ion solutions, containing Cu2+, Fe3+, Ni2+, and Mn2+ to simulate mine wastewater, or Ca2+ and Mg2+ to mimic drinkable water, were used as models. In mono-ionic solutions, the best capture efficiency values were proved for Ca2+, Fe3+, and Ni2+ ions, while a matrix effect was found for multi-ion solutions. However, interesting capture efficiencies were measured in the range of 30–90%, depending on the specific ion, for both single and multi-ion solutions. An attempt is proposed to correlate ions capture efficiency with ions characteristics, such as ionic radius or charge. Combining a satisfactory capture efficiency with low costs and ease of treatment unit operations, the approach here proposed is considered promising to replace other more complex and expensive filtration techniques

Characterization of novel graphene-based microporous layers for Polymer Electrolyte Membrane Fuel Cells operating under low humidity and high temperature

Water management is one of the major issues hindering the employment of Polymer Electrolyte Membrane Fuel Cells on a large scale. Microporous layers are fundamental for water removal from the cathode, oxygen mass transfer and electrolyte hydration. In this paper, we have employed multiple carbon phases in the MPL composition to identify possible strategies for cell performance improvement at critical conditions such as high temperature and low relative humidity. In particular, we have employed a series of graphene-based particles, in addition to conventional carbon black, because of their excellent electrical and thermal conductivities. Moreover, mixed compositions have been tested to assess possible synergic effects between the two phases. We have determined which properties are responsible for performance improvements at 80 °C and relative humidity of 60% and how MPLs morphological and microstructural features could be tuned in order to increase mass transfer while preserving the electrolyte membrane hydration. Promising results have been obtained and specific morphological properties of graphene nanoplatelets have been identified for a possible optimization of the MPL, however the samples produced are still at an early-stage development and further improvements are needed