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Search Results: 1 - 10 of 217 matches for " Gillis Otten "
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Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ
Yen Cu,Kate E. Broderick,Kaustuv Banerjee,Julie Hickman,Gillis Otten,Susan Barnett,Gleb Kichaev,Niranjan Y. Sardesai,Jeffrey B. Ulmer,Andrew Geall
Vaccines , 2013, DOI: 10.3390/vaccines1030367
Abstract: Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA.
Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy
John Gillis
Journal of Translational Medicine , 2006, DOI: 10.1186/1479-5876-4-27
Abstract: Principal Components Analyses with Promax rotational transformations were carried out with 90 cancer cell lines from 3 microarray datasets, which had been made available on the internet as supplementary information from prior publications.In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines.Since glutaminyl cyclase converts glutamine and glutamic acid into a pyroglutamic form, it may interfere with the tumor destructive process of vaccines using peptides having glutamine or glutamic acid at their N-terminals. Finding ways of inhibiting the activity of glutaminyl cyclase in the tumor microenvironment may help to increase the effectiveness of some melanoma vaccines.In recent decades considerable progress has been made in developing methods which use the immune system to treat cancer. One particularly noteworthy series of events was the discovery of the first genes encoding human tumor antigens recognized by cytolytic T lymphocytes (CTLs) [1-3]. Since then, dozens of other antigen genes have been identified [4], many of which contain several short sequences of DNA, coding for peptides called "epitopes." When epitopes are bound by members of the human leukocyte antigen (HLA) family, presented on the tumor cell surface, and recognized by CTLs; destruction of the tumor cell tends to occur. Scientists have become so adept at using such methods for reproducibly destroying tumor cells in the laboratory that many small scale clinical vaccine trials have been carried out [5]. Unfortunately, although there have been reports of some dramatic remissions, the overall degree of successful therapy has remained low [6].Explanations for the difficulty in translating findings from the laboratory to the clini
Robustness Analysis of Hottopixx, a Linear Programming Model for Factoring Nonnegative Matrices
Nicolas Gillis
Mathematics , 2012, DOI: 10.1137/120900629
Abstract: Although nonnegative matrix factorization (NMF) is NP-hard in general, it has been shown very recently that it is tractable under the assumption that the input nonnegative data matrix is close to being separable (separability requires that all columns of the input matrix belongs to the cone spanned by a small subset of these columns). Since then, several algorithms have been designed to handle this subclass of NMF problems. In particular, Bittorf, Recht, R\'e and Tropp (`Factoring nonnegative matrices with linear programs', NIPS 2012) proposed a linear programming model, referred to as Hottopixx. In this paper, we provide a new and more general robustness analysis of their method. In particular, we design a provably more robust variant using a post-processing strategy which allows us to deal with duplicates and near duplicates in the dataset.
Sparse and Unique Nonnegative Matrix Factorization Through Data Preprocessing
Nicolas Gillis
Mathematics , 2012,
Abstract: Nonnegative matrix factorization (NMF) has become a very popular technique in machine learning because it automatically extracts meaningful features through a sparse and part-based representation. However, NMF has the drawback of being highly ill-posed, that is, there typically exist many different but equivalent factorizations. In this paper, we introduce a completely new way to obtaining more well-posed NMF problems whose solutions are sparser. Our technique is based on the preprocessing of the nonnegative input data matrix, and relies on the theory of M-matrices and the geometric interpretation of NMF. This approach provably leads to optimal and sparse solutions under the separability assumption of Donoho and Stodden (NIPS, 2003), and, for rank-three matrices, makes the number of exact factorizations finite. We illustrate the effectiveness of our technique on several image datasets.
The Why and How of Nonnegative Matrix Factorization
Nicolas Gillis
Mathematics , 2014,
Abstract: Nonnegative matrix factorization (NMF) has become a widely used tool for the analysis of high-dimensional data as it automatically extracts sparse and meaningful features from a set of nonnegative data vectors. We first illustrate this property of NMF on three applications, in image processing, text mining and hyperspectral imaging --this is the why. Then we address the problem of solving NMF, which is NP-hard in general. We review some standard NMF algorithms, and also present a recent subclass of NMF problems, referred to as near-separable NMF, that can be solved efficiently (that is, in polynomial time), even in the presence of noise --this is the how. Finally, we briefly describe some problems in mathematics and computer science closely related to NMF via the nonnegative rank.
Successive Nonnegative Projection Algorithm for Robust Nonnegative Blind Source Separation
Nicolas Gillis
Mathematics , 2013, DOI: 10.1137/130946782
Abstract: In this paper, we propose a new fast and robust recursive algorithm for near-separable nonnegative matrix factorization, a particular nonnegative blind source separation problem. This algorithm, which we refer to as the successive nonnegative projection algorithm (SNPA), is closely related to the popular successive projection algorithm (SPA), but takes advantage of the nonnegativity constraint in the decomposition. We prove that SNPA is more robust than SPA and can be applied to a broader class of nonnegative matrices. This is illustrated on some synthetic data sets, and on a real-world hyperspectral image.
The Motor System: The Whole and its Parts
E. Otten
Neural Plasticity , 2001, DOI: 10.1155/np.2001.111
Abstract: Our knowledge of components of the human motor system has been growing steadily, but our understanding of its integration into a system is lagging behind. It is suggested that a combination of measurements of forces and movements of the motor system in a functionally meaningful environment in conjunction with computer simulations of the motor system may help us in understanding motor system properties. Neurotrauma can be seen as a natural deviation, with recovery as a slow path to yet another deviant state of the motor system. In that form they may be useful in explaining the close interaction between form and function of the human motor system.
Multi-Joint Dynamics and the Development of Movement Control
E. Otten
Neural Plasticity , 2005, DOI: 10.1155/np.2005.89
Abstract: The movement control of articulated limbs in humans has been explained in terms of equilibrium points and moving equilibrium points or virtual trajectories. One hypothesis is that the nervous system controls multi-segment limbs by simply planning in terms of these equilibrium points and trajectories. The present paper describes a planar computer simulation of an articulated three-segment limb, controlled by pairs of muscles. The shape of the virtual trajectory is analyzed when the limb is required to make fast movements with endpoint movements along a straight line with bell-shaped velocity profiles. Apparently, the faster the movement, the more the virtual trajectory deviates from the real trajectory and becomes up to eight times longer. The complexity of the shape of the virtual trajectories and its length in these fast movements makes it unlikely that the nervous system plans using these trajectories. it seems simpler to set up the required bursts of muscle activation, coupled in the nervous system to the direction of movement, the s peed, and the place in workspace. Finally, it is argued that the two types of explanation do not contradict each other: when a relation is established in the nervous system between muscle activation and movements, equilibrium points and virtual trajectories are necessarily part of that relation.
Review: Helga Kotthoff (Hrsg.) (2002). Kultur(en) im Gespr ch Review: Helga Kotthoff (Ed.) (2002). Kultur(en) im Gespr ch [Culture(s) in Conversation] Rese a: Helga Kotthoff (Ed.) (2002). Kultur(en) im Gespr ch [Cultura(s) en conversación]
Matthias Otten
Forum : Qualitative Social Research , 2003,
Abstract: Viele theoretische und empirische Untersuchungen zur interkulturellen Kommunikation entstehen in Deutschland h ufig an den disziplin ren Grenzfl chen zwischen Sprachwissenschaften, Soziologie, Ethnologie, P dagogik oder Psychologie. Hier l sst sich auch der interdisziplin re Band "Kultur(en) im Gespr ch" verorten, in dem anhand exemplarsicher Gespr chsanalysen in und zwischen Kulturen theoretische Konzepte und methodische Zug nge aus der Soziolinguistik und der linguistischen Anthropologie vorgestellt werden. Besondere Aufmerksamkeit wird der Methodenreflexion gewidmet, aus der sich wertvolle Anregungen für die qualitative interkulturelle Diskurs- und Gespr chsforschung gewinnen lassen. URN: urn:nbn:de:0114-fqs030345 Much of the theoretical and empirical research on intercultural communication in Germany emerges at the disciplinary edges of Linguistics, Sociology, Anthropology, Psychology or Educational Studies. The book "Kultur(en) im Gespr ch"—translated roughly as Culture(s) in Conversation—edited by Helga KOTTHOFF, covers a wide range of theoretical and methodical approaches to the analysis of intercultural conversation and discourse. Most of the contributions refer to concepts of Socio-Linguistics and Linguistic Anthropology. The focus on the reflection of applying qualitative research methods used in the scope of intercultural conversation and discourse analysis let this book become a source of inspiration for the own research practice. URN: urn:nbn:de:0114-fqs030345 Mucha de la investigación teórica y empírica sobre comunicación intercultural en Alemania emerge en los límites disciplinarios de los estudios de la Lingüística, la Sociología, la Antropología, la Psicología y los estudios educativos. El libro "Kultur(en) im Gespr ch" – traducido literalmente como Cultura(s) en Conversación – editado por Helga KOTTHOFF, cubre un amplio rango de enfoque teóricos y metodológicos para el análisis de la conversación y del discurso intercultural. La mayoría de las contribuciones se refieren a conceptos de la Sociolingüística y de la Antropología Lingüística. El foco en la reflexión de los métodos cualitativos de investigación usados en el horizonte de la conversación intercultural y el análisis del discurso, hace que este libro sea una fuente de inspiración para la propia práctica de la investigación. URN: urn:nbn:de:0114-fqs030345
Halme, Riikka 2004. A Tonal Grammar of Kwanyama
Otten, Dirk
Afrikanistik Online , 2006,
Abstract:
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