Search results for "VECTOR"
showing 10 items of 2660 documents
Sympatric Ixodes-tick species: pattern of distribution and pathogen transmission within wild rodent populations
2018
AbstractThe generalist tick Ixodes ricinus is the most important vector for tick-borne pathogens (TBP), including Borrelia burgdorferi sensu lato, in Europe. However, the involvement of other sympatric Ixodes ticks, such as the specialist vole tick I. trianguliceps, in the enzootic circulations of TBP remains unclear. We studied the distribution of I. ricinus and I. trianguliceps in Central Finland and estimated the TBP infection likelihood in the most common rodent host in relation with the abundance of the two tick species. Ixodes trianguliceps was encountered in all 16 study sites whereas I. ricinus was frequently observed only at a quarter of the study sites. The abundance of I. ricinus…
Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes'
2017
About 60% of emerging infectious diseases in humans are of zoonotic origin. Their increasing number requires the development of new methods for early detection and monitoring of infectious agents in wildlife. Here, we investigated whether blood meals from hematophagous flies could be used to identify the infectious agents circulating in wild vertebrates. To this aim, 1230 blood-engorged flies were caught in the forests of Gabon. Identified blood meals (30%) were from 20 vertebrate species including mammals, birds and reptiles. Among them, 9% were infected by different extant malaria parasites among which some belonged to known parasite species, others to new parasite species or to parasite …
Localized Interleukin-12 for Cancer Immunotherapy
2020
Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as a potential immunotherapy for cancer. Unfortunately, IL-12's remarkable antitumor efficacy in preclinical models has yet to be replicated in humans. Early clinical trials in the mid-1990's showed that systemic delivery of IL-12 incurred dose-limiting toxicities. Nevertheless, IL-12's pleiotropic activity, i.e., its ability to engage multiple effector mechanisms and reverse tumor-induced immunosuppression, continues to entice cancer researchers. The development of strategies which maximize IL-12 delivery to the tumor microenvironment while minimizing systemic exposure are of increasing interest…
A Library-Based Screening Strategy for the Identification of DARPins as Ligands for Receptor-Targeted AAV and Lentiviral Vectors
2021
Delivering genes selectively to the therapeutically relevant cell type is among the prime goals of vector development. Here, we present a high-throughput selection and screening process that identifies designed ankyrin repeat proteins (DARPins) optimally suited for receptor-targeted gene delivery using adeno-associated viral (AAV) and lentiviral (LV) vectors. In particular, the process includes expression, purification, and in situ biotinylation of the extracellular domains of target receptors as Fc fusion proteins in mammalian cells and the selection of high-affinity binders by ribosome display from DARPin libraries each covering more than 1012 variants. This way, DARPins specific for the …
Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies
2021
Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their cli…
Lipoproteins LDL versus HDL as nanocarriers to target either cancer cells or macrophages
2020
free open access article 31 p.; International audience; In this work, we have explored natural unmodified low- and high-density lipoproteins (LDL and HDL) as selective delivery vectors in colorectal cancer therapy. We show in vitro in cultured cells and in vivo (NanoSPECT/CT) in the CT-26 mice colorectal cancer model that LDLs are mainly taken up by cancer cells, while HDLs are preferentially taken up by macrophages. We loaded LDLs with cisplatin and HDLs with the heat shock protein-70 inhibitor AC1LINNC, turning them into a pair of “Trojan horses” delivering drugs selectively to their target cells as demonstrated in vitro in human colorectal cancer cells and macrophages, and in vivo. Coupl…
Hybrid State Feedback Position-Force Control of Hydraulic Cylinder
2019
A hybrid position-force control is proposed using a unified state feedback controller in combination with feedforward dead-zone compensation. Dead-zone compensator was constructed as inverse of the identified static map while the state feedback gains were obtained using a numerical optimization routine. An accurate state-space model affine in states and control, derived in a previous work, was used for closed-loop simulations and control tuning. A trigger event for automatic switching between position and force control was defined and integrated into overall control architecture alongside with a feedforward low-pass filter reducing high frequency components in the control signal. Experiment…
Defining classifier regions for WSD ensembles using word space features
2006
Based on recent evaluation of word sense disambiguation (WSD) systems [10], disambiguation methods have reached a standstill. In [10] we showed that it is possible to predict the best system for target word using word features and that using this 'optimal ensembling method' more accurate WSD ensembles can be built (3-5% over Senseval state of the art systems with the same amount of possible potential remaining). In the interest of developing if more accurate ensembles, w e here define the strong regions for three popular and effective classifiers used for WSD task (Naive Bayes – NB, Support Vector Machine – SVM, Decision Rules – D) using word features (word grain, amount of positive and neg…
Building an Optimal WSD Ensemble Using Per-Word Selection of Best System
2006
In Senseval workshops for evaluating WSD systems [1,4,9], no one system or system type (classifier algorithm, type of system ensemble, extracted feature set, lexical knowledge source etc.) has been discovered that resolves all ambiguous words into their senses in a superior way. This paper presents a novel method for selecting the best system for target word based on readily available word features (number of senses, average amount of training per sense, dominant sense ratio). Applied to Senseval-3 and Senseval-2 English lexical sample state-of-art systems, a net gain of approximately 2.5 – 5.0% (respectively) in average precision per word over the best base system is achieved. The method c…
Efficient Online Laplacian Eigenmap Computation for Dimensionality Reduction in Molecular Phylogeny via Optimisation on the Sphere
2019
Reconstructing the phylogeny of large groups of large divergent genomes remains a difficult problem to solve, whatever the methods considered. Methods based on distance matrices are blocked due to the calculation of these matrices that is impossible in practice, when Bayesian inference or maximum likelihood methods presuppose multiple alignment of the genomes, which is itself difficult to achieve if precision is required. In this paper, we propose to calculate new distances for randomly selected couples of species over iterations, and then to map the biological sequences in a space of small dimension based on the partial knowledge of this genome similarity matrix. This mapping is then used …