Alexander B Kazansky - Academia.edu (original) (raw)

Papers by Alexander B Kazansky

Research paper thumbnail of Jumping Genes-mutators Can Rise Efficacy Of Evolutionary Search

Annual Conference on Genetic and Evolutionary Computation, 2002

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements-transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of coevolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach is usage of artificial transposons. We apply it to one of known benchmark problems-the John Muir ant's trail test. We found that our enhancement of GA technique by the artificial transposons obviously increase the efficacy of searching of the ant's navigation algorithm. We investigate in details the way of the transposons action as intelligent mutators of host-chromosomes.

Research paper thumbnail of What is Biosphere ? Modern approaches

Research paper thumbnail of Evolutionary Physiology and Biochemistry - Advances and Perspectives

Research paper thumbnail of Jumping Genes-mutators Can Rise Efficacy Of Evolutionary Search

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements - transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of co-evolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach...

Research paper thumbnail of Complexification of Gene Networks by Co-evolution of Genomes and Genomic Parasites

Proceedings of the 4th International Joint Conference on Computational Intelligence, 2012

The co-evolution of species with their genomic parasites (transposons) is thought to be one of th... more The co-evolution of species with their genomic parasites (transposons) is thought to be one of the primary ways of rewiring gene regulatory networks (GRNs). In this communication, we computationally explore some of the essential co-evolution aspects of hosts (GRNs) with their transposons. We implemented an evolutionary search of an appropriate GRN model design on the example of the Drosophila gap-gene network. Simple artificial transposons capable of spreading and transposition were implemented. With the model, we explored the hypothesis that targeting destruction of some of the regulatory connections in the GRN via the action of transposons can produce negative selection pressure. Functionally external genes can be recruited (co-opted) into the GRN under this selection pressure following transposon rewiring of the GRN. Over evolutionary time, transposition events are able to disrupt these new regulatory connections, leading to repeated cycles of recruitment, rewiring and optimization. This process can produce increasingly large GRNs with the same basic functions.

Research paper thumbnail of Development of the Biosphere in the Context of Some Fundamental Inventions of Biological Evolution

Evolutionary Physiology and Biochemistry - Advances and Perspectives, Feb 19, 2018

Traditionally, the evolution of flora and fauna on the Earth as well as the evolution of their ph... more Traditionally, the evolution of flora and fauna on the Earth as well as the evolution of their physical and chemical environment are considered separately. At the same time, when considering the global evolutionary changes, it becomes clear that the evolution of all these components occurs in close relationship and that they together constitute a unified evolutionary process. Thus, we should talk about their co-evolution and that the whole biosphere is a united functional system. In this chapter, we briefly discuss some of the major "inventions" of ancient life that are responsible for global biosphere transformations and which "worked" in the biosphere until now (photosynthesis, eukaryotic cell, multicellular organism, and the other findings). The evolution of the Precambrian life as well as the Phanerozoic stage of the biosphere evolution are considered in this context.

Research paper thumbnail of Agential Anticipation in the Central Nervous System

Cognitive Systems Monographs, 2015

Research paper thumbnail of Early Biosphere: Origin and Evolution

Research paper thumbnail of Planetary Bootstrap: A Prelude to Biosphere Phenomenology

AIP Conference Proceedings, 2004

This paper deals with systemic status as well as with some phenomenological and evolutionary aspe... more This paper deals with systemic status as well as with some phenomenological and evolutionary aspects of biosphere. Biosphere is represented as multilevel autopoietic system in which different organizational levels are nested into each other. The conceptual model of punctuated epigenesis, biosphere evolutionary process is suggested, in which endogenous planetary organizational crises play role of evolutionary mechanism, creating novelty. The hypothesis is proposed, that the biosphere reaction on the humankind destructive activity reminds the distributed immune response of biological organism, described by F.Varela in his “cognitive immunology”. The biosphere evolution is interpreted as the hermeneutical spiral of “Process Being” self-uncovering thus illustrating the historical process of transformation of biosphere as the type of Being in the periods of crises. Some arguments are adduced in favor of biosphere phenomenology development and application of the methods of second-order cybernetics to actual problems of planetary scale.

Research paper thumbnail of Jumping Genes-mutators Can Rise Efficacy Of Evolutionary Search

Proceedings of the Genetic and Evolutionary Computation Conference, Jul 9, 2002

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements -transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of coevolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach is usage of artificial transposons. We apply it to one of known benchmark problems -the John Muir ant's trail test. We found that our enhancement of GA technique by the artificial transposons obviously increase the efficacy of searching of the ant's navigation algorithm. We investigate in details the way of the transposons action as intelligent mutators of host-chromosomes.

Research paper thumbnail of Presentation at GECCO2002 NY: Jumping Mutators Increase Efficiency of Evolutionary Search

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements - transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity.

Research paper thumbnail of Early Biosphere: Origin and Evolution

Research paper thumbnail of Forced evolution in silico by artificial transposons and their genetic operators: The ant navigation problem

Information Sciences, 2015

Modern evolutionary computation utilizes heuristic optimizations based upon concepts borrowed fro... more Modern evolutionary computation utilizes heuristic optimizations based upon concepts borrowed from the Darwinian theory of natural selection. Their demonstrated efficacy has reawakened an interest in other aspects of contemporary biology as an inspiration for new algorithms. However, amongst the many excellent candidates for study, contemporary models of biological macroevolution attract special attention. We believe that a vital direction in this field must be algorithms that model the activity of "genomic parasites", such as transposons, in biological evolution. Many evolutionary biologists posit that it is the co-evolution of populations with their genomic parasites that permits the high efficiency of evolutionary searches found in the living world. This publication is our first step in the direction of developing a minimal assortment of algorithms that simulate the role of genomic parasites. Specifically, we started in the domain of genetic algorithms (GA) and selected the Artificial Ant Problem as a test case. This navigation problem is widely known as a classical benchmark test and possesses a large body of literature. We add new objects to the standard toolkit of GA - artificial transposons and a collection of operators that operate on them. We define these artificial transposons as a fragment of an ant's code with properties that cause it to stand apart from the rest. The minimal set of operators for transposons is a transposon mutation operator, and a transposon reproduction operator that causes a transposon to multiply within the population of hosts. An analysis of the population dynamics of transposons within the course of ant evolution showed that transposons are involved in the processes of propagation and selection of blocks of ant navigation programs. During this time, the speed of evolutionary search increases significantly. We concluded that artificial transposons, analogous to real transposons, are truly capable of acting as intelligent mutators that adapt in response to an evolutionary problem in the course of co-evolution with their hosts.

Research paper thumbnail of Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor

International Journal of Biological Sciences, 2013

STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progre... more STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progression. While the full form of STAT5B is thought to promote tumor progression, a naturally occurring truncated isoform acts as a tumor suppressor. We previously demonstrated that truncated STAT5 is generated by insertion of an alternatively spliced exon and results in the introduction of an early termination codon. Present approaches targeting STAT proteins based on inhibition of functional domains of STAT's, such as DNA-binding, cooperative binding (protein-protein interaction), dimerization and phosphorylation will halt the action of the entire gene, both the proto-oncogenic and tumor suppressor functions of Stat5B. In this report we develop a new approach aimed at inhibiting the expression of full-length STAT5B (a proto-oncogene) while simultaneously enhancing the expression of STAT5∆B (a tumor suppressor). We have demonstrated the feasibility of using steric-blocking splice-switching oligonucleotides (SSOs) with a complimentary sequence to the targeted exon-intron boundary to enhance alternative intron/exon retention (up to 10%). The functional effect of the intron/exon proportional tuning was validated by cell proliferation and clonogenic assays. The new scheme applies specific steric-blocking splice-switching oligonucleotides and opens an opportunity for anti-tumor treatment as well as for the alteration of functional abilities of other STAT proteins.

Research paper thumbnail of Reconstruction of the Dynamics of Drosophila Genes Expression from Sets of Images Sharing a Common Pattern

Research paper thumbnail of Bootstrapping of Life through Holonomy and Self-modification

Life on the Earth demonstrate not only adaptive, cognitive, particularly, anticipatory properties... more Life on the Earth demonstrate not only adaptive, cognitive, particularly, anticipatory properties, but also active, transformative function to its local and global environment. As V. Vernadsky stated, life is a powerful geological force. Charles Darwin realized that too. In his last work [1] he proved, that earthworms through their vital activity in geological time scale are able to form and

Research paper thumbnail of Biocompatible Gold Nanorod Conjugates for Preclinical Biomedical Research

Journal of Nanomedicine & Nanotechnology, 2012

Gold nanorods with a peak absorption wavelength of 760 nm were prepared using a seed-mediated met... more Gold nanorods with a peak absorption wavelength of 760 nm were prepared using a seed-mediated method. A novel protocol has been developed to replace hexadecyltrimethylammonium bromide on the surface of the nanorods with 16-mercaptohexadecanoic acid and metoxy-poly(ethylene glycol)-thiol, and the monoclonal antibody HER2. The physical chemistry properties of the conjugates were monitored through optical and zeta-potential measurements to confirm surface chemistry changes. The efficiency of the modifications was quantified through measurement of the average number of antibodies per gold nanorod. The conjugates were investigated for different cells lines: BT-474, MCF7, MCF10, MDCK, and fibroblast. The results show successful cell accumulation of the gold nanorod HER2 conjugates in cells with HER2 overexpression. Incubation of the complexes in heparinized mouse blood demonstrated the low aggregation of the metallic particles through stability of the spectral properties, as verified by UV/VIS spectrometry. Cytotoxicity analysis with LDH release and MTT assay confirms strong targeting and retention of functional activity of the antibody after their conjugation with gold nanorods. Silver staining confirms efficient specific binding to BT-474 cells even in cases where the nanorod complexes were incubated in heparinized mouse blood. This is confirmed through in vivo studies where, following intravenous injection of gold nanorod complexes, silver staining reveals noticeably higher rates of specific binding in mouse tumors than in healthy liver.The conjugates are reproducible, have strong molecular targeting capabilities, have long term stability in vivo and can be used in pre-clinical applications. The conjugates can also be used for molecular and optoacoustic imaging, quantitative sensing of biological substrates, and photothermal therapy.

Research paper thumbnail of Abstract P6-15-20: Development of PEA-15-Based Therapy in Breast Cancer in a Preclinical Study

Research paper thumbnail of Jumping genes-mutators can rise efficacy of evolutionary search

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements -transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of coevolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach is usage of artificial transposons. We apply it to one of known benchmark problems -the John Muir ant's trail test. We found that our enhancement of GA technique by the artificial transposons obviously increase the efficacy of searching of the ant's navigation algorithm. We investigate in details the way of the transposons action as intelligent mutators of host-chromosomes.

Research paper thumbnail of Nanostructured thermites based on iodine pentoxide for bio agent defeat systems

Bulletin of the American Physical Society, Oct 7, 2011

The risk for bioterrorist events involving the intentional airborne release of contagious agents ... more The risk for bioterrorist events involving the intentional airborne release of contagious agents has led to development of new approaches for bio agent defeat technologies both indoors and outdoors. Novel approaches to defeat harmful biological agents have generated a strong demand for new active materials. The preferred solutions are to neutralize the biological agents within the immediate target area by using aerosolized biocidal substances released in situ by high energetic reactions. By using nano-thermite ...

Research paper thumbnail of Jumping Genes-mutators Can Rise Efficacy Of Evolutionary Search

Annual Conference on Genetic and Evolutionary Computation, 2002

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements-transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of coevolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach is usage of artificial transposons. We apply it to one of known benchmark problems-the John Muir ant's trail test. We found that our enhancement of GA technique by the artificial transposons obviously increase the efficacy of searching of the ant's navigation algorithm. We investigate in details the way of the transposons action as intelligent mutators of host-chromosomes.

Research paper thumbnail of What is Biosphere ? Modern approaches

Research paper thumbnail of Evolutionary Physiology and Biochemistry - Advances and Perspectives

Research paper thumbnail of Jumping Genes-mutators Can Rise Efficacy Of Evolutionary Search

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements - transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of co-evolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach...

Research paper thumbnail of Complexification of Gene Networks by Co-evolution of Genomes and Genomic Parasites

Proceedings of the 4th International Joint Conference on Computational Intelligence, 2012

The co-evolution of species with their genomic parasites (transposons) is thought to be one of th... more The co-evolution of species with their genomic parasites (transposons) is thought to be one of the primary ways of rewiring gene regulatory networks (GRNs). In this communication, we computationally explore some of the essential co-evolution aspects of hosts (GRNs) with their transposons. We implemented an evolutionary search of an appropriate GRN model design on the example of the Drosophila gap-gene network. Simple artificial transposons capable of spreading and transposition were implemented. With the model, we explored the hypothesis that targeting destruction of some of the regulatory connections in the GRN via the action of transposons can produce negative selection pressure. Functionally external genes can be recruited (co-opted) into the GRN under this selection pressure following transposon rewiring of the GRN. Over evolutionary time, transposition events are able to disrupt these new regulatory connections, leading to repeated cycles of recruitment, rewiring and optimization. This process can produce increasingly large GRNs with the same basic functions.

Research paper thumbnail of Development of the Biosphere in the Context of Some Fundamental Inventions of Biological Evolution

Evolutionary Physiology and Biochemistry - Advances and Perspectives, Feb 19, 2018

Traditionally, the evolution of flora and fauna on the Earth as well as the evolution of their ph... more Traditionally, the evolution of flora and fauna on the Earth as well as the evolution of their physical and chemical environment are considered separately. At the same time, when considering the global evolutionary changes, it becomes clear that the evolution of all these components occurs in close relationship and that they together constitute a unified evolutionary process. Thus, we should talk about their co-evolution and that the whole biosphere is a united functional system. In this chapter, we briefly discuss some of the major "inventions" of ancient life that are responsible for global biosphere transformations and which "worked" in the biosphere until now (photosynthesis, eukaryotic cell, multicellular organism, and the other findings). The evolution of the Precambrian life as well as the Phanerozoic stage of the biosphere evolution are considered in this context.

Research paper thumbnail of Agential Anticipation in the Central Nervous System

Cognitive Systems Monographs, 2015

Research paper thumbnail of Early Biosphere: Origin and Evolution

Research paper thumbnail of Planetary Bootstrap: A Prelude to Biosphere Phenomenology

AIP Conference Proceedings, 2004

This paper deals with systemic status as well as with some phenomenological and evolutionary aspe... more This paper deals with systemic status as well as with some phenomenological and evolutionary aspects of biosphere. Biosphere is represented as multilevel autopoietic system in which different organizational levels are nested into each other. The conceptual model of punctuated epigenesis, biosphere evolutionary process is suggested, in which endogenous planetary organizational crises play role of evolutionary mechanism, creating novelty. The hypothesis is proposed, that the biosphere reaction on the humankind destructive activity reminds the distributed immune response of biological organism, described by F.Varela in his “cognitive immunology”. The biosphere evolution is interpreted as the hermeneutical spiral of “Process Being” self-uncovering thus illustrating the historical process of transformation of biosphere as the type of Being in the periods of crises. Some arguments are adduced in favor of biosphere phenomenology development and application of the methods of second-order cybernetics to actual problems of planetary scale.

Research paper thumbnail of Jumping Genes-mutators Can Rise Efficacy Of Evolutionary Search

Proceedings of the Genetic and Evolutionary Computation Conference, Jul 9, 2002

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements -transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of coevolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach is usage of artificial transposons. We apply it to one of known benchmark problems -the John Muir ant's trail test. We found that our enhancement of GA technique by the artificial transposons obviously increase the efficacy of searching of the ant's navigation algorithm. We investigate in details the way of the transposons action as intelligent mutators of host-chromosomes.

Research paper thumbnail of Presentation at GECCO2002 NY: Jumping Mutators Increase Efficiency of Evolutionary Search

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements - transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity.

Research paper thumbnail of Early Biosphere: Origin and Evolution

Research paper thumbnail of Forced evolution in silico by artificial transposons and their genetic operators: The ant navigation problem

Information Sciences, 2015

Modern evolutionary computation utilizes heuristic optimizations based upon concepts borrowed fro... more Modern evolutionary computation utilizes heuristic optimizations based upon concepts borrowed from the Darwinian theory of natural selection. Their demonstrated efficacy has reawakened an interest in other aspects of contemporary biology as an inspiration for new algorithms. However, amongst the many excellent candidates for study, contemporary models of biological macroevolution attract special attention. We believe that a vital direction in this field must be algorithms that model the activity of "genomic parasites", such as transposons, in biological evolution. Many evolutionary biologists posit that it is the co-evolution of populations with their genomic parasites that permits the high efficiency of evolutionary searches found in the living world. This publication is our first step in the direction of developing a minimal assortment of algorithms that simulate the role of genomic parasites. Specifically, we started in the domain of genetic algorithms (GA) and selected the Artificial Ant Problem as a test case. This navigation problem is widely known as a classical benchmark test and possesses a large body of literature. We add new objects to the standard toolkit of GA - artificial transposons and a collection of operators that operate on them. We define these artificial transposons as a fragment of an ant's code with properties that cause it to stand apart from the rest. The minimal set of operators for transposons is a transposon mutation operator, and a transposon reproduction operator that causes a transposon to multiply within the population of hosts. An analysis of the population dynamics of transposons within the course of ant evolution showed that transposons are involved in the processes of propagation and selection of blocks of ant navigation programs. During this time, the speed of evolutionary search increases significantly. We concluded that artificial transposons, analogous to real transposons, are truly capable of acting as intelligent mutators that adapt in response to an evolutionary problem in the course of co-evolution with their hosts.

Research paper thumbnail of Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor

International Journal of Biological Sciences, 2013

STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progre... more STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progression. While the full form of STAT5B is thought to promote tumor progression, a naturally occurring truncated isoform acts as a tumor suppressor. We previously demonstrated that truncated STAT5 is generated by insertion of an alternatively spliced exon and results in the introduction of an early termination codon. Present approaches targeting STAT proteins based on inhibition of functional domains of STAT's, such as DNA-binding, cooperative binding (protein-protein interaction), dimerization and phosphorylation will halt the action of the entire gene, both the proto-oncogenic and tumor suppressor functions of Stat5B. In this report we develop a new approach aimed at inhibiting the expression of full-length STAT5B (a proto-oncogene) while simultaneously enhancing the expression of STAT5∆B (a tumor suppressor). We have demonstrated the feasibility of using steric-blocking splice-switching oligonucleotides (SSOs) with a complimentary sequence to the targeted exon-intron boundary to enhance alternative intron/exon retention (up to 10%). The functional effect of the intron/exon proportional tuning was validated by cell proliferation and clonogenic assays. The new scheme applies specific steric-blocking splice-switching oligonucleotides and opens an opportunity for anti-tumor treatment as well as for the alteration of functional abilities of other STAT proteins.

Research paper thumbnail of Reconstruction of the Dynamics of Drosophila Genes Expression from Sets of Images Sharing a Common Pattern

Research paper thumbnail of Bootstrapping of Life through Holonomy and Self-modification

Life on the Earth demonstrate not only adaptive, cognitive, particularly, anticipatory properties... more Life on the Earth demonstrate not only adaptive, cognitive, particularly, anticipatory properties, but also active, transformative function to its local and global environment. As V. Vernadsky stated, life is a powerful geological force. Charles Darwin realized that too. In his last work [1] he proved, that earthworms through their vital activity in geological time scale are able to form and

Research paper thumbnail of Biocompatible Gold Nanorod Conjugates for Preclinical Biomedical Research

Journal of Nanomedicine & Nanotechnology, 2012

Gold nanorods with a peak absorption wavelength of 760 nm were prepared using a seed-mediated met... more Gold nanorods with a peak absorption wavelength of 760 nm were prepared using a seed-mediated method. A novel protocol has been developed to replace hexadecyltrimethylammonium bromide on the surface of the nanorods with 16-mercaptohexadecanoic acid and metoxy-poly(ethylene glycol)-thiol, and the monoclonal antibody HER2. The physical chemistry properties of the conjugates were monitored through optical and zeta-potential measurements to confirm surface chemistry changes. The efficiency of the modifications was quantified through measurement of the average number of antibodies per gold nanorod. The conjugates were investigated for different cells lines: BT-474, MCF7, MCF10, MDCK, and fibroblast. The results show successful cell accumulation of the gold nanorod HER2 conjugates in cells with HER2 overexpression. Incubation of the complexes in heparinized mouse blood demonstrated the low aggregation of the metallic particles through stability of the spectral properties, as verified by UV/VIS spectrometry. Cytotoxicity analysis with LDH release and MTT assay confirms strong targeting and retention of functional activity of the antibody after their conjugation with gold nanorods. Silver staining confirms efficient specific binding to BT-474 cells even in cases where the nanorod complexes were incubated in heparinized mouse blood. This is confirmed through in vivo studies where, following intravenous injection of gold nanorod complexes, silver staining reveals noticeably higher rates of specific binding in mouse tumors than in healthy liver.The conjugates are reproducible, have strong molecular targeting capabilities, have long term stability in vivo and can be used in pre-clinical applications. The conjugates can also be used for molecular and optoacoustic imaging, quantitative sensing of biological substrates, and photothermal therapy.

Research paper thumbnail of Abstract P6-15-20: Development of PEA-15-Based Therapy in Breast Cancer in a Preclinical Study

Research paper thumbnail of Jumping genes-mutators can rise efficacy of evolutionary search

Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology.... more Genetic Algorithms (GA) and Genetic Programming were inspired by ideas from evolutionary biology. However modern Evolutionary Computation (EC) only in outline reminds the strategies of biological evolution. The application of other algorithms and biological ideas may substantially improve the performance of this area of computer science. Namely, the selfish (or parasitic) mobile genetic elements -transposons are good candidates for this breakthrough. These genomic parasites live on a substratum of genomes of whole biological communities. Many biologists assume that processes in the world of transposons are the main source of evolution creativity. They thought to act as wise higher-level mutators for their hosts. In this communication we propose a strategy of construction of a new approach exploiting the most essential aspects of coevolution of the hosts-chromosomes and their genetic parasites. We named this strategy as the Two-level Evolving Worlds. The key feature of the approach is usage of artificial transposons. We apply it to one of known benchmark problems -the John Muir ant's trail test. We found that our enhancement of GA technique by the artificial transposons obviously increase the efficacy of searching of the ant's navigation algorithm. We investigate in details the way of the transposons action as intelligent mutators of host-chromosomes.

Research paper thumbnail of Nanostructured thermites based on iodine pentoxide for bio agent defeat systems

Bulletin of the American Physical Society, Oct 7, 2011

The risk for bioterrorist events involving the intentional airborne release of contagious agents ... more The risk for bioterrorist events involving the intentional airborne release of contagious agents has led to development of new approaches for bio agent defeat technologies both indoors and outdoors. Novel approaches to defeat harmful biological agents have generated a strong demand for new active materials. The preferred solutions are to neutralize the biological agents within the immediate target area by using aerosolized biocidal substances released in situ by high energetic reactions. By using nano-thermite ...