35 research outputs found
Engineered Antibody and Monobody Domains with T Cell Receptor-Like Selectivity for Tumor Associated Peptide-MHC Antigens
Monoclonal antibody (mAb)-based therapeutics have established themselves as meaningful components of the treatment paradigm for a variety of tumors. However, since the approval of rituximab in 1997 as the first mAb-based therapy for cancer, there has been a paucity of novel, validated cancer targets for therapeutic intervention by mAbs. In effect, numerous challenges lie in the discovery of suitable extracellular or transmembrane antigens that permit the differentiation of tumor from healthy tissue. The adaptive immune system, though, mediates recognition of foreign antigens derived from the intracellular proteome by T cell receptor (TCR) binding to peptide-loaded major histocompatibility complex (pMHC) molecules. Because cancer is associated with large-scale alterations in the genome, there are a vast number of novel epitopes presented to the adaptive immune system. Although natural TCRs have exquisite functionality in distinguishing these foreign epitopes, and several tumor-reactive TCRs have, in fact, been characterized, the molecules themselves are poorly developable as therapeutic candidates. Thus, in order to enable TCR-like binding of a broader class of protein agents, this study explores the transfer of TCR binding domains to other mAb-based scaffolds, including the fibronectin-derived Fn3 and the IgG-derived 4D5 scaffolds. By using a combination of rational design and directed evolution to guide binding domain transfer, evidence for TCR-like binding was demonstrated for several engineered molecules. In addition to conferring binding functionality, the grafted TCR domains had a deleterious effect on the biophysical properties of these inherently robust protein scaffolds. Thus, this work provides novel insight into the objective of developing mAb-based agents with TCR-like binding specificity for pMHC antigens, informing future efforts to target the abundance of intracellular tumor epitopes
Policy gradient learning methods for stochastic control with exit time and applications to share repurchase pricing
We develop policy gradients methods for stochastic control with exit time in
a model-free setting. We propose two types of algorithms for learning either
directly the optimal policy or by learning alternately the value function
(critic) and the optimal control (actor). The use of randomized policies is
crucial for overcoming notably the issue related to the exit time in the
gradient computation. We demonstrate the effectiveness of our approach by
implementing our numerical schemes in the application to the problem of share
repurchase pricing. Our results show that the proposed policy gradient methods
outperform PDE or other neural networks techniques in a model-based setting.
Furthermore, our algorithms are flexible enough to incorporate realistic market
conditions like e.g. price impact or transaction costs.Comment: 19 pages, 6 figure
Generative modeling for time series via Schr{\"o}dinger bridge
We propose a novel generative model for time series based on Schr{\"o}dinger
bridge (SB) approach. This consists in the entropic interpolation via optimal
transport between a reference probability measure on path space and a target
measure consistent with the joint data distribution of the time series. The
solution is characterized by a stochastic differential equation on finite
horizon with a path-dependent drift function, hence respecting the temporal
dynamics of the time series distribution. We can estimate the drift function
from data samples either by kernel regression methods or with LSTM neural
networks, and the simulation of the SB diffusion yields new synthetic data
samples of the time series. The performance of our generative model is
evaluated through a series of numerical experiments. First, we test with a toy
autoregressive model, a GARCH Model, and the example of fractional Brownian
motion, and measure the accuracy of our algorithm with marginal and temporal
dependencies metrics. Next, we use our SB generated synthetic samples for the
application to deep hedging on real-data sets. Finally, we illustrate the SB
approach for generating sequence of images
Application of PCR-DGGE to the study of dynamics and biodiversity of microbial contaminants during the processing of Hibiscus sabdariffa drinks and concentrates
Introduction. Bissap (Hibiscus sabdariffa L.) is a common plant in the tropics. In Senegal, the calyces are used to make a popular juice. In the food industry, small and medium-sized enterprises (SMEs) are responsible for the transformation of bissap calyces into drinks, concentrates, jam, etc. In spite of the very low pH of the juice (pH < 3), problems of contamination and fermentation are often observed in the final products post-pasteurization. They are mainly due to Pseudomonas spp., E. coli, Klebsiella spp. and Pichia opuntiae. To solve this issue, monitoring of the microbial ecology was performed during the full process of bissap products. Methods and results. Fresh calyces and dried mixed calyces of the two varieties of Hibiscus sabdariffa ('Koor' and 'Vimto'), as well as juice samples, were collected at every stage of the processing of a bissap drink and syrup in a Senegalese SME. The monitoring of microbial flora was performed by using molecular fingerprinting. The molecular technique PCR-DGGE was employed to evaluate the microbial dynamics using bacterial 16S rDNA, yeast 26S rDNA and 28S rDNA mold profiles at each critical stage of the process. Results and discussion. The genetic profiles generated contributed to identifying the critical points in the manufacturing processes. A multivariate analysis based on the presence or absence of spots in the denaturing gradient electrophoresis gels (DGGE) showed that the microbial flora (bacteria, yeasts, molds) of bissap evolved during the following phases: harvest (fresh flower), drying (dried calyces) and processing (before filtration, after pasteurization and before packaging). Conclusion. Our work contributed to determining the microorganisms responsible for the microbial contamination of the final products, and highlighted the origin of these contaminants. The most important critical point was identified as the pasteurization step. (Résumé d'auteur
Comparative genome analysis of the candidate functional starter culture strains Lactobacillus fermentum 222 and Lactobacillus plantarum 80 for controlled cocoa bean fermentation processes
Discrimination des procĂ©dĂ©s de transformation post-rĂ©colte du Cacao et du CafĂ© par analyse globale de lâĂ©cologie microbienne
Cocoa and coffee are the most traded agricultural commodities in the world. They undergo many post-harvest transformations in producing countries (tropical) before being exported. Post-harvest processes differ from one country to another and from one production site to another. The technological transformation of cocoa on commercial beans and of coffee to green coffee requires a primary process handling. These practices play a crucial role in global and organoleptic quality of the products that will be processed. Our work hypothesis isthat different post-harvest processing applied to coffee and cocoa have an influence on the structure of microbial communities. The main objective was to measure this effect by performing a global analysis of microbial ecology using a molecular biology tool (PCR-DGGE, PCR amplification coupled to denaturing gradient gel electrophoresis). This technique allows variations in microbial communities to be detected and the main microbial species to be identified by sequencing.Our approach permitted to discriminate treatments, and the geographical origin of Cameroonian and Indonesian coffees. Notably, we showed that geographical origin and coffee species have a minor impact on the structure of the microbial communities when compared to the type of process used (wet or dry).By applying the approach to cocoa, we could link the global analysis of microbial ecology (PCR-DGGE) to the analysis of volatile compounds (SPME-GC-MS) to discriminate the different post-harvest treatments. Micro-fermentation were carried out with strains isolated from cocoa (L. fermentum, A. pasteurianus, P. kudriavzevii and P. mashurica) in order to identify the origin of the volatile compounds detected in the fermented cocoa. This study contributed to to show that fermentation combined with a short storage duration before fermentation is the best method to obtain cocoa beans with more desirable aromatic compounds. The statistical analysis was used to combine the results of the two types of analyzes (microbial ecology and aromatic compounds) and get relations between the detected microbial species and volatile compounds. The identified aromatic profiles prompted us to consider the use of the tested microbial strains as starter culture for cocoa fermentation.Le cacao et le cafĂ© sont les produits agricoles les plus Ă©changĂ©s dans le monde. Ils subissent de nombreuses transformations post-rĂ©colte au niveau des pays producteurs (tropicaux) avant d'ĂȘtre exportĂ©s. Les procĂ©dĂ©s de traitements post-rĂ©colte diffĂšrent d'un pays Ă l'autre voire d'un agriculteur Ă l'autre. La transformation technologique du cacao en fĂšves marchandes et des grains de cafĂ© en cafĂ© vert nĂ©cessite un processus primaire de manutention. Ces pratiques participent et influencent, en gĂ©nĂ©ral, la qualitĂ© marchande et organoleptique des produits destinĂ©s Ă la transformation. Notre hypothĂšse de travail est que les diffĂ©rents procĂ©dĂ©s de transformation post-rĂ©colte appliquĂ©s sur le cafĂ© et le cacao ont une influence sur la structure des communautĂ©s microbiennes. L'objectif principal Ă©tait de pouvoir mesurer cet effet en rĂ©alisant l'analyse globale des communautĂ©s microbienne en utilisant un outil de biologie molĂ©culaire, la PCR-DGGE (Amplification par PCR couplĂ©e Ă l'Ă©lectrophorĂšse sur gel en gradient dĂ©naturant). Cette technique a Ă©tĂ© associĂ©e au sĂ©quençage afin d'identifier les espĂšces microbiennes majoritaires. Cette Ă©tude a montrĂ© que les communautĂ©s microbiennes associĂ©es aux grains de cafĂ© et aux fĂšves de cacao varient au cours des diffĂ©rentes Ă©tapes pour chaque type de traitement post-rĂ©colte appliquĂ©.Notre approche a permis de discriminer les voies de traitements, et l'origine gĂ©ographique du cafĂ© Camerounais et IndonĂ©sien. Notamment, nous avons montrĂ© que l'origine gĂ©ographique et l'espĂšce de cafĂ© utilisĂ©e ont un impact sur l'Ă©cologie microbienne du cafĂ© moins important par rapport Ă celui du procĂ©dĂ©. L'application au cacao nous a permis de relier l'analyse globale de l'Ă©cologie microbienne (DGGE) Ă l'analyse des composĂ©s volatils (SPME-GC-MS) afin de discriminer les diffĂ©rents traitements post-rĂ©colte. Des micro-fermentations ont Ă©tĂ© rĂ©alisĂ©es avec des souches microbiennes isolĂ©es du cacao (L. fermentum, A. pasteurianus, P. kudriavzevii et P. mashurica) dans le but dâidentifier l'origine des composĂ©s volatils dĂ©tectĂ©s sur le cacao fermentĂ©. Notre Ă©tude a contribuĂ© Ă montrer que la fermentation combinĂ©e Ă une courte durĂ©e de stockage avant fermentation est le procĂ©dĂ© qui permet d'obtenir des fĂšves contenant plus de composĂ©s aromatiques dĂ©sirables sur le cacao. Une analyse statistique a permis de combiner les rĂ©sultats des deux types d'analyses (Ă©cologie microbienne et composĂ©s aromatiques) et de crĂ©er des relations entre les espĂšces dĂ©tectĂ©es et les composĂ©s volatils prĂ©sents. Les profils aromatiques identifiĂ©s ont permis d'envisager l'utilisation des souches testĂ©es comme starters de culture pour la fermentation du cacao
Discrimination of post-harvest processing on microbial ecology of cacao and coffee
Le cacao et le cafĂ© sont les produits agricoles les plus Ă©changĂ©s dans le monde. Ils subissent de nombreuses transformations post-rĂ©colte au niveau des pays producteurs (tropicaux) avant d'ĂȘtre exportĂ©s. Les procĂ©dĂ©s de traitements post-rĂ©colte diffĂšrent d'un pays Ă l'autre voire d'un agriculteur Ă l'autre. La transformation technologique du cacao en fĂšves marchandes et des grains de cafĂ© en cafĂ© vert nĂ©cessite un processus primaire de manutention. Ces pratiques participent et influencent, en gĂ©nĂ©ral, la qualitĂ© marchande et organoleptique des produits destinĂ©s Ă la transformation. Notre hypothĂšse de travail est que les diffĂ©rents procĂ©dĂ©s de transformation post-rĂ©colte appliquĂ©s sur le cafĂ© et le cacao ont une influence sur la structure des communautĂ©s microbiennes. L'objectif principal Ă©tait de pouvoir mesurer cet effet en rĂ©alisant l'analyse globale des communautĂ©s microbienne en utilisant un outil de biologie molĂ©culaire, la PCR-DGGE (Amplification par PCR couplĂ©e Ă l'Ă©lectrophorĂšse sur gel en gradient dĂ©naturant). Cette technique a Ă©tĂ© associĂ©e au sĂ©quençage afin d'identifier les espĂšces microbiennes majoritaires. Cette Ă©tude a montrĂ© que les communautĂ©s microbiennes associĂ©es aux grains de cafĂ© et aux fĂšves de cacao varient au cours des diffĂ©rentes Ă©tapes pour chaque type de traitement post-rĂ©colte appliquĂ©.Notre approche a permis de discriminer les voies de traitements, et l'origine gĂ©ographique du cafĂ© Camerounais et IndonĂ©sien. Notamment, nous avons montrĂ© que l'origine gĂ©ographique et l'espĂšce de cafĂ© utilisĂ©e ont un impact sur l'Ă©cologie microbienne du cafĂ© moins important par rapport Ă celui du procĂ©dĂ©. L'application au cacao nous a permis de relier l'analyse globale de l'Ă©cologie microbienne (DGGE) Ă l'analyse des composĂ©s volatils (SPME-GC-MS) afin de discriminer les diffĂ©rents traitements post-rĂ©colte. Des micro-fermentations ont Ă©tĂ© rĂ©alisĂ©es avec des souches microbiennes isolĂ©es du cacao (L. fermentum, A. pasteurianus, P. kudriavzevii et P. mashurica) dans le but dâidentifier l'origine des composĂ©s volatils dĂ©tectĂ©s sur le cacao fermentĂ©. Notre Ă©tude a contribuĂ© Ă montrer que la fermentation combinĂ©e Ă une courte durĂ©e de stockage avant fermentation est le procĂ©dĂ© qui permet d'obtenir des fĂšves contenant plus de composĂ©s aromatiques dĂ©sirables sur le cacao. Une analyse statistique a permis de combiner les rĂ©sultats des deux types d'analyses (Ă©cologie microbienne et composĂ©s aromatiques) et de crĂ©er des relations entre les espĂšces dĂ©tectĂ©es et les composĂ©s volatils prĂ©sents. Les profils aromatiques identifiĂ©s ont permis d'envisager l'utilisation des souches testĂ©es comme starters de culture pour la fermentation du cacao.Cocoa and coffee are the most traded agricultural commodities in the world. They undergo many post-harvest transformations in producing countries (tropical) before being exported. Post-harvest processes differ from one country to another and from one production site to another. The technological transformation of cocoa on commercial beans and of coffee to green coffee requires a primary process handling. These practices play a crucial role in global and organoleptic quality of the products that will be processed. Our work hypothesis isthat different post-harvest processing applied to coffee and cocoa have an influence on the structure of microbial communities. The main objective was to measure this effect by performing a global analysis of microbial ecology using a molecular biology tool (PCR-DGGE, PCR amplification coupled to denaturing gradient gel electrophoresis). This technique allows variations in microbial communities to be detected and the main microbial species to be identified by sequencing.Our approach permitted to discriminate treatments, and the geographical origin of Cameroonian and Indonesian coffees. Notably, we showed that geographical origin and coffee species have a minor impact on the structure of the microbial communities when compared to the type of process used (wet or dry).By applying the approach to cocoa, we could link the global analysis of microbial ecology (PCR-DGGE) to the analysis of volatile compounds (SPME-GC-MS) to discriminate the different post-harvest treatments. Micro-fermentation were carried out with strains isolated from cocoa (L. fermentum, A. pasteurianus, P. kudriavzevii and P. mashurica) in order to identify the origin of the volatile compounds detected in the fermented cocoa. This study contributed to to show that fermentation combined with a short storage duration before fermentation is the best method to obtain cocoa beans with more desirable aromatic compounds. The statistical analysis was used to combine the results of the two types of analyzes (microbial ecology and aromatic compounds) and get relations between the detected microbial species and volatile compounds. The identified aromatic profiles prompted us to consider the use of the tested microbial strains as starter culture for cocoa fermentation
A novel fault location approach for radial power distribution systems
Power distribution systems (PDS) are increasingly complex and spread over long distances and in different locations. Given their radial configuration, the loads could be inserted at the same distances from the substation. This leads to multiple estimation of fault location (FL) and yields time consuming for iterative FL algorithms. In this article, we provide a novel practical approach to fault localization in order to defeat these limitations. The central idea of the proposed approach is to divide the multilateral distribution system into a possible number of mono-lateral sub systems (MLS) using a proposed communicating sensor. Next, we apply two different fault locator algorithms only to the defective MLS. The first variant of the approach is based on the impedance method, while the second variant is non-parametric used only when there is lack in the line data. To test the proposed technique in practice, we used the IEEE 13 Node test feeder, and a real Algerian PDS. The results obtained clearly show the contribution of the dedicated method for locating faults in the PDS
Preliminary PCR-TTGE analyses of bacterial communities associated with pollen from anemophilous trees: potential impacts on plants and human health
International audiencePollen from wind-pollinated plants is the predominant cause of pollinosis which corresponds mainly to allergic rhinitis and conjunctivitis. Bacterial communities associated to leaves and roots surface were analysed for many years with both culture-dependent and independent methods. However, microbiota of pollen grains was rarely investigated and never with a molecular fingerprint technique. The aim of this study was to perform a preliminary analysis of the pollen microbiota by applying PCR-TTGE method. Pollen samples were collected from various anemophilous trees genera (Cephalotaxus, Cupressus, Pinus, Platanus and Quercus) in Montpellier (France) in 2013. Thorough pollen preparation was essential to a successful recovery of DNA from pollen. Regarding the results, pollen microbiota was tree genus-dependent. In addition, intra-tree genus variations were also observed. The Gammaproteobacteria class was the most represented in pollen samples whatever the tree genus. Among this class, some bacteria were recognized as phytopathogens (Pseudomonas, Erwinia) but also opportunistic human pathogens (Pseudomonas, some enterobacteria). PCR-TTGE is a suitable tool to analyse the microbiota associated with pollen responsible for phytopathogenicity or affecting the human respiratory tract