Search results for " Vectors"
showing 10 items of 286 documents
Microbial technologies for the discovery of novel bioactive metabolites
2002
Soil microbes represent an important source of biologically active compounds. These molecules present original and unexpected structure and are selective inhibitors of their molecular targets. At Biosearch Italia, discovery of new bioactive molecules is mostly carried out through the exploitation of a proprietary strain collection of over 50000 strains, mostly unusual genera of actinomycetes and uncommon filamentous fungi. A critical element in a drug discovery based on microbial extracts is the isolation of unexploited groups of microorganisms that are at the same time good producers of secondary metabolites. Molecular genetics can assist in these efforts. We will review the development an…
Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus.
2010
SummaryNeural stem cells (NSCs) in the adult hippocampus divide infrequently, and the molecules that modulate their quiescence are largely unknown. Here, we show that bone morphogenetic protein (BMP) signaling is active in hippocampal NSCs, downstream of BMPR-IA. BMPs reversibly diminish proliferation of cultured NSCs while maintaining their undifferentiated state. In vivo, acute blockade of BMP signaling in the hippocampus by intracerebral infusion of Noggin first recruits quiescent NSCs into the cycle and increases neurogenesis; subsequently, it leads to decreased stem cell division and depletion of precursors and newborn neurons. Consistently, selective ablation of Bmpr1a in hippocampal …
Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man.
2002
Mutations and aberrant expression of the p53 tumor suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy. We studied the immunogeneicity of a recombinant replication-defective adenoviral vector encoding human full-length wt p53 (rAd/hup53) in human leukocyte antigen (HLA)-A2K(b)-transgenic (Tg) mice and man. The generation of p53 epitope-specific cytotoxic T lymphocytes (CTLs) in p53-proficient and p53-deficient A2K(b)-Tg mice was …
A Multiple Surrogate Assisted Decomposition Based Evolutionary Algorithm for Expensive Multi/Many-Objective Optimization
2019
Many-objective optimization problems (MaOPs) contain four or more conflicting objectives to be optimized. A number of efficient decomposition-based evolutionary algorithms have been developed in the recent years to solve them. However, computationally expensive MaOPs have been scarcely investigated. Typically, surrogate-assisted methods have been used in the literature to tackle computationally expensive problems, but such studies have largely focused on problems with 1–3 objectives. In this paper, we present an approach called hybrid surrogate-assisted many-objective evolutionary algorithm to solve computationally expensive MaOPs. The key features of the approach include: 1) the use of mul…
Combined effect of AAV-U7-induced dystrophin exon skipping and soluble activin Type IIB receptor in mdx mice.
2012
Adeno-associated virus (AAV)-U7-mediated skipping of dystrophin-exon-23 restores dystrophin expression and muscle function in the mdx mouse model of Duchenne muscular dystrophy. Soluble activin receptor IIB (sActRIIB-Fc) inhibits signaling of myostatin and homologous molecules and increases muscle mass and function of wild-type and mdx mice. We hypothesized that combined treatment with AAV-U7 and sActRIIB-Fc may synergistically improve mdx muscle function. Bioactivity of sActRIIB-Fc on skeletal muscle was first demonstrated in wild-type mice. In mdx mice we show that AAV-U7-mediated dystrophin restoration improved specific muscle force and resistance to eccentric contractions when applied a…
On Prefix Normal Words
2011
We present a new class of binary words: the prefix normal words. They are defined by the property that for any given length $k$, no factor of length $k$ has more $a$'s than the prefix of the same length. These words arise in the context of indexing for jumbled pattern matching (a.k.a. permutation matching or Parikh vector matching), where the aim is to decide whether a string has a factor with a given multiplicity of characters, i.e., with a given Parikh vector. Using prefix normal words, we give the first non-trivial characterization of binary words having the same set of Parikh vectors of factors. We prove that the language of prefix normal words is not context-free and is strictly contai…
IoT -based adversarial attack's effect on cloud data platform services in a smart building context
2020
IoT sensors and sensor networks are widely employed in businesses. The common problem is a remarkable number of IoT device transactions are unencrypted. Lack of correctly implemented and robust defense leaves the organization's IoT devices vulnerable to numerous cyber threats, such as adversarial and man-in-the-middle attacks or malware infections. A perpetrator can utilize adversarial examples when attacking machine learning (ML) models, such as convolutional neural networks (CNN) or deep neural networks (DNN) used, e.g., in DaaS cloud data platform service of smart buildings. DaaS cloud data platform's function in this study is to connect data from multiple IoT sensors, databases, private…
Well-defined polypeptide-based systems as non-viral vectors for cytosolic delivery
2017
A convenient cytosolic drug delivery constitutes a very powerful tool for the treatment and/or prevention of several relevant human diseases. Along with recent advances in therapeutic technologies based on biomacromolecules (e.g. oligonucleotides or proteins), we also require the development of technologies which improve the transport of therapeutic molecules to the cell of choice. This has led to the emergence of a variety of promising methods over the last 20 years. Despite significant progress, these methods still suffer from several shortcomings including low/variable delivery efficiency, high cytotoxicity, and perhaps most importantly, ineffective endosomal/lysosomal escape. In this co…
Maladie du huanglongbing
2019
Maladie du huanglongbing. Analyse du risque phytosanitaire pour l’Union européenne
Polymeric nanoparticles for siRNA delivery: Production and applications
2017
Gene therapy through the use of siRNA and a polymeric carrier are becoming an efficient therapeutic option to conventional pharmaceutical formulations for the treatment of deadly diseases, such as cancer, pulmonary, ocular and neurodegenerative diseases. However, several considerations regarding the stability, formulation, and efficacy have to be faced up until these systems could be considered to be a marketable pharmaceutical products for to extend siRNA application to clinical practice. This review is focused on the key challenges of siRNA therapeutics, with special attention on the faced obstacles and on the formulation-related difficulties, providing a list of requirements needed for o…