Giga Scientists - Academia.edu (original) (raw)

Papers by Giga Scientists

Research paper thumbnail of Gene copy number studies in archived and fresh mouse tissue samples

Research paper thumbnail of Mitochondrial gene copy number variations in tissues from irradiated mice

Research paper thumbnail of Archive building and interrogation of archived samples: new techniques and old materials

Research paper thumbnail of Alterations in mitochondrial gene copy numbers following irradiation in radiosensitive mice

Research paper thumbnail of Reflections on Gene Editing Technology

Orthodox Christianity and Modern Science, 2021

Research paper thumbnail of Comparing radiation toxicities across species: An examination of radiation effects in Mus musculus and Peromyscus leucopus

International Journal of Radiation Biology, 2013

Life shortening and pathological complications in similarly irradiated cohorts of the laboratory ... more Life shortening and pathological complications in similarly irradiated cohorts of the laboratory mouse Mus musculus and the white-footed mouse Peromyscus leucopus were recorded in the course of the Janus studies conducted at Argonne National Laboratory from 1970-1992. This study examines how lifespan, tumor and non-tumor disease incidence, and tumor multiplicity are differentially affected by gamma-rays and neutron radiation exposure in two different animal species. Survival analyses examined differences in lifespan across species, while decision tree analyses examined statistically significant associations between lifespan, radiation exposure, and specific diseases. Logistic regression models were generated to examine the likelihood of disease incidence in these two species following gamma-ray or neutron radiation exposure. Life shortening in response to radiation was more significant in Peromyscus leucopus than in Mus musculus, irrespective of radiation quality. Many types of tumor and non-tumor diseases were found to be consistently species specific. Tumor multiplicity was observed in both species in response to radiation, although more pronounced in Mus musculus. The response to radiation was highly species specific, highlighting the difficulty in extrapolating conclusions from one species to another, irrespective of their phenotypic similarities and ecologic niches.

Research paper thumbnail of Past and Future Work on Radiobiology Mega-Studies: A Case Study at Argonne National Laboratory

Health Physics, 2011

Between 1952 and 1992 more than 200 large radiobiology studies were conducted in research institu... more Between 1952 and 1992 more than 200 large radiobiology studies were conducted in research institutes throughout Europe, North America and Japan to determine the effects of external irradiation and internal emitters on the life span and tissue toxicity development in animals. At Argonne National Laboratory, 22 external beam studies were conducted on nearly 700 beagle dogs and 50,000 mice between 1969 and 1992. These studies helped to characterize the effects of neutron and gamma irradiation on lifespan, tumorigenesis, and mutagenesis across a range of doses and dosing patterns. The records and tissues collected at Argonne during that time period have been carefully preserved and redisseminated. Using these archived data ongoing statistical work has been done and continues to characterize quality of radiation, dose, dose rate, tissue, and gender specific differences in the radiation responses of exposed animals. The ongoing application of newly developed molecular biology techniques to the archived tissues has revealed gene specific mutation rates following exposure to ionizing irradiation. The original and ongoing work with this tissue archive is presented here as a case study of a more general trend in the radiobiology mega studies. These experiments helped form the modern understanding of radiation responses in animals, and continue to inform development of new radiation models. Recent archival efforts have facilitated open access to the data and materials produced by these studies and so a unique opportunity exists to expand this continued research.

Research paper thumbnail of Peptide‐mediated cancer targeting of nanoconjugates

Wiley Interdisciplinary …, 2011

Targeted use of nanoparticles in vitro, in cells, and in vivo requires nanoparticle surface funct... more Targeted use of nanoparticles in vitro, in cells, and in vivo requires nanoparticle surface functionalization. Moieties that can be used for such a purpose include small molecules as well as polymers made of different biological and organic materials. Short amino acid polymers, peptides, can often rival target binding avidity of much larger molecules. At the same time, peptides are smaller than most nanoparticles and thus allow for multiple nanoparticle modifications and creation of pluripotent nanoparticles. Most nanoparticles provide multiple binding sites for different cargo and targeting peptides which can be used for the development of novel approaches for cancer targeting, diagnostics, and therapy. In this review, we will focus on peptides which have been used for the preparation of different nanoparticles designed for cancer research.

Research paper thumbnail of The Ubiquitin-Proteasome System and DNA Repair

intechopen.com

The Ubiquitin-Proteasome System and DNA Repair 257 2000). The catalytic subunits of the 20S prote... more The Ubiquitin-Proteasome System and DNA Repair 257 2000). The catalytic subunits of the 20S proteasome degrade proteins into a heterogeneous mixture of peptides rather than into single amino acids (Kisselev et al., 1999; Goldberg et al., 2002). Proteasomal inhibitors interfere with these activities to various degrees and with specificities for one or more of the main catalytic activities (Groll et al., 2009). The 19S proteasome is attached to one or both ends of the 20S proteasome, and the resulting complex is known as the 26S proteasome. Although no crystal structure for the 19S proteasome has yet been solved, it is currently believed that the 19S proteasome can be separated into two additional subcomplexes: the base and the lid. The base is composed of six AAA ATPase (ATPases Associated with diverse cellular Activities) subunits (Rpt1-6 in Saccharomyces cerevisiae) as well as three non-ATPase subunits (Rpn1, Rpn2, and Rpn13 in S. cerevisiae). The lid includes at least nine non-ATPase subunits (Rpn3, Rpn5-9, Rpn11, Rpn12, and Rpn15 in S. cerevisiae). Additionally, the yeast protein Rpn10 appears to stabilize the connection between the base and the lid (Finley, 2009; Xie, 2010). 2.2 Function of the UPS Protein substrates targeted for proteasomal degradation must first be tagged by ubiquitin, a highly conserved 76 amino acid protein. This process is carried out by the concerted activities of three categories of enzymes: a ubiquitin-activating enzyme (E1), a ubiquitinconjugating enzyme (E2), and a ubiquitin-protein ligase (E3) (

Research paper thumbnail of Endocytosis of titanium dioxide nanoparticles in prostate cancer PC-3M cells

… , Biology and Medicine, 2010

Nanotechnology has introduced many exciting new tools for the treatment of human diseases. One of... more Nanotechnology has introduced many exciting new tools for the treatment of human diseases. One of the obstacles in its application to that end is the lack of a fundamental understanding of the interaction that occurs between nanoparticles and living cells. This ...

Research paper thumbnail of Uptake and distribution of ultrasmall anatase TiO2 alizarin red S nanoconjugates in Arabidopsis thaliana

Nano letters, 2010

The application of nanotechnology to plant systems has lagged behind nanomedicine and nanopharmac... more The application of nanotechnology to plant systems has lagged behind nanomedicine and nanopharmacology despite its potential to generate new tools for the delivery of fertilizers, herbicides, and insecticides,(1) new ways to manipulate plant genomes,(2) and new methods to capture ...

Research paper thumbnail of Labeling TiO2 nanoparticles with dyes for optical fluorescence microscopy and determination of TiO2-DNA nanoconjugate stability

Small (Weinheim an …, 2009

Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant... more Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO 2 ) nanoparticles. These nanoparticles, when electronically linked to single stranded DNA ...

Research paper thumbnail of Nanoparticles for applications in cellular imaging

Nanoscale Research …, 2007

In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, an... more In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, and gold nanoparticles) and their impact on the ability to image biological components in fixed cells. The review also dis-cusses factors influencing nanoparticle imaging and ...

Research paper thumbnail of X‐ray fluorescence microprobe imaging in biology and medicine

Journal of cellular …, 2006

Characteristic X-ray fluorescence is a technique that can be used to establish elemental concentr... more Characteristic X-ray fluorescence is a technique that can be used to establish elemental concentrations for a large number of different chemical elements simultaneously in different locations in cell and tissue samples. Exposing the samples to an X-ray beam is the basis of X-ray ...

Research paper thumbnail of Gadolinium-conjugated TiO2-DNA oligonucleotide nanoconjugates show prolonged intracellular retention period and T1-weighted contrast enhancement in magnetic …

… , Biology and Medicine, 2008

Nanoconjugates composed of titanium dioxide (TiO 2 ) nanoparticles, DNA oligonucleotides, and a g... more Nanoconjugates composed of titanium dioxide (TiO 2 ) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these nanoconjugates showed them to ...

Research paper thumbnail of Ductal Carcinoma in Situ: X-ray Fluorescence Microscopy and Dynamic Contrast-enhanced MR Imaging Reveals Gadolinium Uptake within Neoplastic Mammary …

Radiology, 2009

Materials and Methods: C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with ins... more Materials and Methods: C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentration–time curves were fit to a ...

Research paper thumbnail of Evaluation of Gastrointestinal Toxicity Development in Mice Irradiated with Increasing Levels of Low-Dose Single Fraction Gamma Radiation

Research paper thumbnail of Past and future work on radiobiology mega-studies: a case study at Argonne National Laboratory

Between 1952 and 1992, more than 200 large radiobiology studies were conducted in research instit... more Between 1952 and 1992, more than 200 large radiobiology studies were conducted in research institutes throughout Europe, North America, and Japan to determine the effects of external irradiation and internal emitters on the lifespan and tissue toxicity development in animals. At Argonne National Laboratory, 22 external beam studies were conducted on nearly 700 beagle dogs and 50,000 mice between 1969 and 1992. These studies helped to characterize the effects of neutron and gamma irradiation on lifespan, tumorigenesis, and mutagenesis across a range of doses and dosing patterns. The records and tissues collected at Argonne during that time period have been carefully preserved and redisseminated. Using these archived data, ongoing statistical work has been done and continues to characterize quality of radiation, dose, dose rate, tissue, and gender-specific differences in the radiation responses of exposed animals. The ongoing application of newly-developed molecular biology techniques to the archived tissues has revealed gene-specific mutation rates following exposure to ionizing irradiation. The original and ongoing work with this tissue archive is presented here as a case study of a more general trend in the radiobiology megastudies. These experiments helped form the modern understanding of radiation responses in animals and continue to inform development of new radiation models. Recent archival efforts have facilitated open access to the data and materials produced by these studies, and so a unique opportunity exists to expand this continued research.

Research paper thumbnail of Fast-scanning high-flux microprobe for biological X-ray fluorescence microscopy and microXAS

Journal of Synchrotron Radiation, 2010

Research paper thumbnail of A proteomic approach to identification of plutonium-binding proteins in mammalian cells

Plutonium can enter the body through different routes and remains there for decades; however its ... more Plutonium can enter the body through different routes and remains there for decades; however its specific biochemical interactions are poorly defined. We, for the first time, have studied plutonium-binding proteins using a metalloproteomic approach with rat PC12 cells. A combination of immobilized metal ion chromatography, 2D gel electrophoresis, and mass spectrometry were employed to analyze potential plutonium-binding proteins. Our results show that several proteins from PC12 cells show affinity towards Pu 4+-NTA (plutonium bound to nitrilotriacetic acid). Proteins from seven different spots in the 2D gel were identified. In contrast to the previously known plutonium-binding proteins transferrin and ferritin, which bind ferric ions, most identified proteins in our experiment are known to bind calcium, magnesium, or divalent transition metal ions. The identified plutonium interacting proteins also have functional roles in downregulation of apoptosis and other pro-proliferative processes. MetaCore analysis based on this group of proteins produced a pathway with a statistically significant association with development of neoplastic diseases.

Research paper thumbnail of Gene copy number studies in archived and fresh mouse tissue samples

Research paper thumbnail of Mitochondrial gene copy number variations in tissues from irradiated mice

Research paper thumbnail of Archive building and interrogation of archived samples: new techniques and old materials

Research paper thumbnail of Alterations in mitochondrial gene copy numbers following irradiation in radiosensitive mice

Research paper thumbnail of Reflections on Gene Editing Technology

Orthodox Christianity and Modern Science, 2021

Research paper thumbnail of Comparing radiation toxicities across species: An examination of radiation effects in Mus musculus and Peromyscus leucopus

International Journal of Radiation Biology, 2013

Life shortening and pathological complications in similarly irradiated cohorts of the laboratory ... more Life shortening and pathological complications in similarly irradiated cohorts of the laboratory mouse Mus musculus and the white-footed mouse Peromyscus leucopus were recorded in the course of the Janus studies conducted at Argonne National Laboratory from 1970-1992. This study examines how lifespan, tumor and non-tumor disease incidence, and tumor multiplicity are differentially affected by gamma-rays and neutron radiation exposure in two different animal species. Survival analyses examined differences in lifespan across species, while decision tree analyses examined statistically significant associations between lifespan, radiation exposure, and specific diseases. Logistic regression models were generated to examine the likelihood of disease incidence in these two species following gamma-ray or neutron radiation exposure. Life shortening in response to radiation was more significant in Peromyscus leucopus than in Mus musculus, irrespective of radiation quality. Many types of tumor and non-tumor diseases were found to be consistently species specific. Tumor multiplicity was observed in both species in response to radiation, although more pronounced in Mus musculus. The response to radiation was highly species specific, highlighting the difficulty in extrapolating conclusions from one species to another, irrespective of their phenotypic similarities and ecologic niches.

Research paper thumbnail of Past and Future Work on Radiobiology Mega-Studies: A Case Study at Argonne National Laboratory

Health Physics, 2011

Between 1952 and 1992 more than 200 large radiobiology studies were conducted in research institu... more Between 1952 and 1992 more than 200 large radiobiology studies were conducted in research institutes throughout Europe, North America and Japan to determine the effects of external irradiation and internal emitters on the life span and tissue toxicity development in animals. At Argonne National Laboratory, 22 external beam studies were conducted on nearly 700 beagle dogs and 50,000 mice between 1969 and 1992. These studies helped to characterize the effects of neutron and gamma irradiation on lifespan, tumorigenesis, and mutagenesis across a range of doses and dosing patterns. The records and tissues collected at Argonne during that time period have been carefully preserved and redisseminated. Using these archived data ongoing statistical work has been done and continues to characterize quality of radiation, dose, dose rate, tissue, and gender specific differences in the radiation responses of exposed animals. The ongoing application of newly developed molecular biology techniques to the archived tissues has revealed gene specific mutation rates following exposure to ionizing irradiation. The original and ongoing work with this tissue archive is presented here as a case study of a more general trend in the radiobiology mega studies. These experiments helped form the modern understanding of radiation responses in animals, and continue to inform development of new radiation models. Recent archival efforts have facilitated open access to the data and materials produced by these studies and so a unique opportunity exists to expand this continued research.

Research paper thumbnail of Peptide‐mediated cancer targeting of nanoconjugates

Wiley Interdisciplinary …, 2011

Targeted use of nanoparticles in vitro, in cells, and in vivo requires nanoparticle surface funct... more Targeted use of nanoparticles in vitro, in cells, and in vivo requires nanoparticle surface functionalization. Moieties that can be used for such a purpose include small molecules as well as polymers made of different biological and organic materials. Short amino acid polymers, peptides, can often rival target binding avidity of much larger molecules. At the same time, peptides are smaller than most nanoparticles and thus allow for multiple nanoparticle modifications and creation of pluripotent nanoparticles. Most nanoparticles provide multiple binding sites for different cargo and targeting peptides which can be used for the development of novel approaches for cancer targeting, diagnostics, and therapy. In this review, we will focus on peptides which have been used for the preparation of different nanoparticles designed for cancer research.

Research paper thumbnail of The Ubiquitin-Proteasome System and DNA Repair

intechopen.com

The Ubiquitin-Proteasome System and DNA Repair 257 2000). The catalytic subunits of the 20S prote... more The Ubiquitin-Proteasome System and DNA Repair 257 2000). The catalytic subunits of the 20S proteasome degrade proteins into a heterogeneous mixture of peptides rather than into single amino acids (Kisselev et al., 1999; Goldberg et al., 2002). Proteasomal inhibitors interfere with these activities to various degrees and with specificities for one or more of the main catalytic activities (Groll et al., 2009). The 19S proteasome is attached to one or both ends of the 20S proteasome, and the resulting complex is known as the 26S proteasome. Although no crystal structure for the 19S proteasome has yet been solved, it is currently believed that the 19S proteasome can be separated into two additional subcomplexes: the base and the lid. The base is composed of six AAA ATPase (ATPases Associated with diverse cellular Activities) subunits (Rpt1-6 in Saccharomyces cerevisiae) as well as three non-ATPase subunits (Rpn1, Rpn2, and Rpn13 in S. cerevisiae). The lid includes at least nine non-ATPase subunits (Rpn3, Rpn5-9, Rpn11, Rpn12, and Rpn15 in S. cerevisiae). Additionally, the yeast protein Rpn10 appears to stabilize the connection between the base and the lid (Finley, 2009; Xie, 2010). 2.2 Function of the UPS Protein substrates targeted for proteasomal degradation must first be tagged by ubiquitin, a highly conserved 76 amino acid protein. This process is carried out by the concerted activities of three categories of enzymes: a ubiquitin-activating enzyme (E1), a ubiquitinconjugating enzyme (E2), and a ubiquitin-protein ligase (E3) (

Research paper thumbnail of Endocytosis of titanium dioxide nanoparticles in prostate cancer PC-3M cells

… , Biology and Medicine, 2010

Nanotechnology has introduced many exciting new tools for the treatment of human diseases. One of... more Nanotechnology has introduced many exciting new tools for the treatment of human diseases. One of the obstacles in its application to that end is the lack of a fundamental understanding of the interaction that occurs between nanoparticles and living cells. This ...

Research paper thumbnail of Uptake and distribution of ultrasmall anatase TiO2 alizarin red S nanoconjugates in Arabidopsis thaliana

Nano letters, 2010

The application of nanotechnology to plant systems has lagged behind nanomedicine and nanopharmac... more The application of nanotechnology to plant systems has lagged behind nanomedicine and nanopharmacology despite its potential to generate new tools for the delivery of fertilizers, herbicides, and insecticides,(1) new ways to manipulate plant genomes,(2) and new methods to capture ...

Research paper thumbnail of Labeling TiO2 nanoparticles with dyes for optical fluorescence microscopy and determination of TiO2-DNA nanoconjugate stability

Small (Weinheim an …, 2009

Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant... more Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO 2 ) nanoparticles. These nanoparticles, when electronically linked to single stranded DNA ...

Research paper thumbnail of Nanoparticles for applications in cellular imaging

Nanoscale Research …, 2007

In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, an... more In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, and gold nanoparticles) and their impact on the ability to image biological components in fixed cells. The review also dis-cusses factors influencing nanoparticle imaging and ...

Research paper thumbnail of X‐ray fluorescence microprobe imaging in biology and medicine

Journal of cellular …, 2006

Characteristic X-ray fluorescence is a technique that can be used to establish elemental concentr... more Characteristic X-ray fluorescence is a technique that can be used to establish elemental concentrations for a large number of different chemical elements simultaneously in different locations in cell and tissue samples. Exposing the samples to an X-ray beam is the basis of X-ray ...

Research paper thumbnail of Gadolinium-conjugated TiO2-DNA oligonucleotide nanoconjugates show prolonged intracellular retention period and T1-weighted contrast enhancement in magnetic …

… , Biology and Medicine, 2008

Nanoconjugates composed of titanium dioxide (TiO 2 ) nanoparticles, DNA oligonucleotides, and a g... more Nanoconjugates composed of titanium dioxide (TiO 2 ) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these nanoconjugates showed them to ...

Research paper thumbnail of Ductal Carcinoma in Situ: X-ray Fluorescence Microscopy and Dynamic Contrast-enhanced MR Imaging Reveals Gadolinium Uptake within Neoplastic Mammary …

Radiology, 2009

Materials and Methods: C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with ins... more Materials and Methods: C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentration–time curves were fit to a ...

Research paper thumbnail of Evaluation of Gastrointestinal Toxicity Development in Mice Irradiated with Increasing Levels of Low-Dose Single Fraction Gamma Radiation

Research paper thumbnail of Past and future work on radiobiology mega-studies: a case study at Argonne National Laboratory

Between 1952 and 1992, more than 200 large radiobiology studies were conducted in research instit... more Between 1952 and 1992, more than 200 large radiobiology studies were conducted in research institutes throughout Europe, North America, and Japan to determine the effects of external irradiation and internal emitters on the lifespan and tissue toxicity development in animals. At Argonne National Laboratory, 22 external beam studies were conducted on nearly 700 beagle dogs and 50,000 mice between 1969 and 1992. These studies helped to characterize the effects of neutron and gamma irradiation on lifespan, tumorigenesis, and mutagenesis across a range of doses and dosing patterns. The records and tissues collected at Argonne during that time period have been carefully preserved and redisseminated. Using these archived data, ongoing statistical work has been done and continues to characterize quality of radiation, dose, dose rate, tissue, and gender-specific differences in the radiation responses of exposed animals. The ongoing application of newly-developed molecular biology techniques to the archived tissues has revealed gene-specific mutation rates following exposure to ionizing irradiation. The original and ongoing work with this tissue archive is presented here as a case study of a more general trend in the radiobiology megastudies. These experiments helped form the modern understanding of radiation responses in animals and continue to inform development of new radiation models. Recent archival efforts have facilitated open access to the data and materials produced by these studies, and so a unique opportunity exists to expand this continued research.

Research paper thumbnail of Fast-scanning high-flux microprobe for biological X-ray fluorescence microscopy and microXAS

Journal of Synchrotron Radiation, 2010

Research paper thumbnail of A proteomic approach to identification of plutonium-binding proteins in mammalian cells

Plutonium can enter the body through different routes and remains there for decades; however its ... more Plutonium can enter the body through different routes and remains there for decades; however its specific biochemical interactions are poorly defined. We, for the first time, have studied plutonium-binding proteins using a metalloproteomic approach with rat PC12 cells. A combination of immobilized metal ion chromatography, 2D gel electrophoresis, and mass spectrometry were employed to analyze potential plutonium-binding proteins. Our results show that several proteins from PC12 cells show affinity towards Pu 4+-NTA (plutonium bound to nitrilotriacetic acid). Proteins from seven different spots in the 2D gel were identified. In contrast to the previously known plutonium-binding proteins transferrin and ferritin, which bind ferric ions, most identified proteins in our experiment are known to bind calcium, magnesium, or divalent transition metal ions. The identified plutonium interacting proteins also have functional roles in downregulation of apoptosis and other pro-proliferative processes. MetaCore analysis based on this group of proteins produced a pathway with a statistically significant association with development of neoplastic diseases.