Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines

Synthetic vaccines, based on antigenic peptides that comprise MHC−I and MHC-II T-cell epitopes expressed by tumors, show great promise for the immunotherapy of cancer. For optimal immunogenicity, the synthetic peptides (SPs) should be adjuvanted with suitable immunostimulatory additives. Previously, we have shown that improved immunogenicity in vivo is obtained with vaccine modalities in which an SP is covalently connected to an adjuvanting moiety, typically a ligand to Toll-like receptor 2 (TLR2). SPs were covalently attached to UPam, which is a derivative of the classic TLR2 ligand Pam₃CysSK₄. A disadvantage of the triply palmitoylated UPam is its high lipophilicity, which precludes universal adoption of this adjuvant for covalent modification of various antigenic peptides as it renders the synthetic vaccine insoluble in several cases. Here, we report a novel conjugatable TLR2 ligand, mini-UPam, which contains only one palmitoyl chain, rather than three, and therefore has less impact on the solubility and other physicochemical properties of a synthetic peptide. In this study, we used SPs that contain the clinically relevant neoepitopes identified in a melanoma patient who completely recovered after T-cell therapy. Homogeneous mini-UPam-SP conjugates have been prepared in good yields by stepwise solid-phase synthesis that employed a mini-UPam building block pre-prepared in solution and the standard set of Fmoc-amino acids. The immunogenicity of the novel mini-UPam-SP conjugates was demonstrated by using the cancer patient's T-cells.     

Performance of genetic algorithms in search for water splitting perovskites

We examine the performance of genetic algorithms (GAs) in uncovering solar water light splitters over a space of almost 19,000 perovskite materials. The entire search space was previously calculated using density functional theory to determine solutions that fulfill constraints on stability, band gap, and band edge position. Here, we test over 2500 unique GA implementations in finding these solutions to determine whether GA can avoid the need for brute force search, and thereby enable larger chemical spaces to be screened within a given computational budget. We find that the best GAs tested offer almost a 6 times efficiency gain over random search, and are comparable to the performance of a search based on informed chemical rules. In addition, the GA is almost 10 times as efficient as random search in finding half the solutions within the search space. By employing chemical rules, the performance of the GA can be further improved to approximately 12–17 better than random search. We discuss the effect of population size, selection function, crossover function, mutation rate, fitness function, and elitism on the final result, finding that selection function and elitism are especially important to GA performance. In addition, we determine that parameters that perform well in finding solar water splitters can also be applied to discovering transparent photocorrosion shields. Our results indicate that coupling GAs to high-throughput density functional calculations presents a promising method to rapidly search large chemical spaces for technological materials.     

Hot-Water Extraction Optimization of Sugar Maple (Acer saccharum Marsh.) and Red Maple (Acer rubrum L.) Bark Applying Principal Component Analysis

In the forest industry, bark is an abundant residue, predominantly converted into calorific energy. As the antioxidant potential of phenolic compounds from sugar maple (Acer saccharum Marsh.) and red maple (Acer rubrum L.) bark has previously been established, the present study focused on the hot-water extraction optimization of these barks. Several process parameters (maple species, temperature, duration, ratio bark/water, particle size) were thus studied and large disparities were found between the two species. Extraction yield, phenolic content, and antioxidant capacity of red maple extracts were several times higher than those of sugar maple extracts. Principal component analysis, applied to the selected best extraction conditions, identified 3–4 clusters depending on the maple species. These groups were sorted from the highest extraction yield and energy consumption combined with the lowest phenolic content and antioxidant capacity, to moderate extraction yield and energy consumption with the highest phenolic content and antioxidant capacity.     

Electro-thermal measurements and finite element method simulations of a spark plasma sintering device

Current, voltage and temperature measurements were performed at different points of the system to identify the controlling parameters of the spark plasma sintering (SPS) process. The very low inductance effects despite the high intensity current circulating through the SPS column justifies the use of Joule heating to characterize the phenomenon. The measurements also enabled the improvement and validation of an earlier electro-thermal numerical model developed using the finite element method (FEM). It has been shown that the electrical resistivity and the thermal conductivity of each of the elements are crucial parameters for the simulations. These parameters strongly modify the current modeled, thereby affecting the temperature distribution throughout the SPS column.     

Improvement of measurement techniques for damping induced by micro-sliding

This paper deals with the damping caused by friction in joints. A new test bench is presented and justified by comparisons made with devices described in the literature. The purpose of this academic bench is to measure the damping induced by partial slip and friction in a planar joint. Moreover, allows uncoupling normal static and dynamic tangential forces. A new method for so-called stopped-sine excitation was developed. It allows more precise monitoring of the evolution of the vibration frequency and damping of non-linear modes. This method is associated with piezoelectric exciters for greater efficiency when stopping excitation. A large number of experimental results are presented and discussed. They are used to characterize the damping induced by micro-sliding in the bonds.     

Fermentation by Amylolytic Lactic Acid Bacteria and Consequences for Starch Digestibility of Plantain, Breadfruit, and Sweet Potato Flours

The potential of tropical starchy plants such as plantain (Musa paradisiaca), breadfruit (Artocarpus communis), and sweet potato (Ipomoea batatas) for the development of new fermented foods was investigated by exploiting the capacity of some lactic acid bacteria to hydrolyze starch. The amylolytic lactic acid bacteria (ALAB) Lactobacillus plantarum A6 and Lactobacillus fermentum Ogi E1 were able to change the consistency of thick sticky gelatinized slurries of these starchy fruits and tubers into semiliquid to liquid products. Consequently, a decrease in apparent viscosity and an increase in Bostwick flow were observed. These changes and the production of maltooligosaccharides confirmed starch hydrolysis. Sucrose in sweet potato was not fermented by strain A6 and poorly fermented by strain Ogi E1, suggesting possible inhibition of sucrose fermentation. In all 3 starchy plants, rapidly digestible starch (RDS) was higher than slowly digestible starch (SDS) and resistant starch (RS) represented between 17% and 30% dry matter (DM). The digestibility of plantain was not affected by fermentation, whereas the RDS content of breadfruit and sweet potato decreased and the RS content increased after fermentation. Practical Application: The characteristics resulting from different combinations of gluten free starchy plants (plantain, breadfruit, sweet potato) and amylolytic lactic acid bacteria (ALAB) offer opportunities to develop new functional fermented beverages, mainly for breadfruit and sweet potato, after further investigation of their formulation, sensory attributes, nutritional, and prebiotic characteristics.     

Nonparametric modeling of carbon prices

This paper constitutes the first exercise of nonparametric modeling applied to carbon markets. The framework of analysis is carefully detailed, and the empirical application unfolds in the case of BlueNext spot and ECX futures prices. The data is gathered in daily frequency from April 2005 to April 2010. First, we document the presence of strong nonlinearities in the conditional mean functions. Second, the conditional volatility functions reveal an asymmetric and heteroskedastic behavior which is dramatically different between carbon spot and futures logreturns. The results for spot prices are also robust to subsamples' decomposition. Third, we show in an out-of-sample forecasting exercise that nonparametric modeling allows reducing the prediction error by almost 15% compared to linear AR models. This latter result is confirmed by the Diebold–Mariano pairwise test statistic.     

Timed verification of the generic architecture of a memory circuit using parametric timed automata

Using a variant of Clariso-Cortadella’s parametric method for verifying asynchronous circuits, we analyse some crucial timing behaviors of the architecture of SPSMALL memory, a commercial product of STMicroelectronics. Using the model of parametric timed automata and model checker HYTECH, we formally derive a set of linear constraints that ensure the correctness of the response times of the memory. We are also able to infer the constraints characterizing the optimal setup timings of input signals. We have checked, for two different implementations of this architecture, that the values given by our model match remarkably with the values obtained by the designer through electrical simulation. Partially supported by project MEDEA+ Blueberries. A preliminary version appeared in the Proceedings of 4th International Conference on Formal Modelling and Analysis of Timed Systems (FORMATS’06), Sept. 2006.     

In situ Li nuclear magnetic resonance observation of the electrochemical intercalation of lithium in graphite; 1st cycle

We show a continuous, in situ nuclear magnetic resonance (NMR) experiment on a lithium/graphite electrochemical cell. The objective is to study a commercial graphite currently used as negative electrodes in secondary lithium batteries. A plastic cell is made, with metallic lithium as the counter electrode and 1 mol dm⁻³ LiPF₆/ethylene carbonate (EC) + diethylcarbonate (DEC) electrolyte. The reversible capacity is 346 mAh/g and the irreversible capacity 55 mAh/g, measured in the galvanostatic mode, at a rate of C/20 (20 h for the theoretical capacity of LiC₆) for the first cycle. We show the first discharge and the first charge of the cell inside the magnet and record simultaneously and regularly (in real time) static ⁷Li NMR spectra. As expected, we observe the quadrupolar lines characteristic of the lithium graphite intercalation compounds (GICs). During the discharge, the two types of in-plane densities of Li are successively found that correspond to the dilute LiC₉, then to the dense LiC₆ configuration; during the charge, we observe the successive decrease of these states. The galvanostatic curve helps to identify the stages NMR signature and the stages coexistence.     

Interactions between Polymeric Dispersants and Calcium Silicate Hydrates

To better understand the mechanism of interaction between hydrating silicate-based cements and polymeric dispersants of the type used as "superplasticizers" in modern construction concretes, two different types of polymeric dispersant were added (at concentrations of 1 and 10 g/L) during the synthesis of calcium silicate hydrate (C-S-H) via the "pozzolanic reaction" in dilute slurries of lime and reactive silica, at Ca/Si ratios in the range of 0.66–1.50. Although both polymers gave degrees of adsorption of >79% in all cases studied, no significant structural modifications of the resulting C-S-H products were observed via X-ray diffraction or ²⁹Si magic angle spinning–nuclear magnetic resonance. These results differ from recent work in which it was shown that similar types of polymer could intercalate into the interlayers of C-S-H that was made using an alternative process. It is suggested that the process by which the C-S-H is formed may have a strong influence on whether C-S-H can intercalate polymers. This observation is relevant to understanding the fate of such polymers in concrete.