Joshua Hamilton | Uooolll - Academia.edu (original) (raw)
Papers by Joshua Hamilton
Index of Texas Archaeology: Open Access Gray Literature from the Lone Star State, 2017
At the request of Carmel Devco, Inc., Pape-Dawson conducted an intensive archaeological survey of... more At the request of Carmel Devco, Inc., Pape-Dawson conducted an intensive archaeological survey of the eastern portion of the proposed Carmel Development Project in northeastern Travis County, Texas. The project involves the construction of a new municipal utility district (MUD 2) within the 341-acre (138.1hectare [ha]) project area. No impacts are planned adjacent to or within the floodplain of Wilbarger Creek and its tributaries, which composes approximately 70 acres (28.3 ha) of MUD 2. Thus, archaeological investigations were conducted within the remaining 271.4 acres (109.8 ha). The depths of impacts vary, but typically road construction impacts are 4 to 5 feet (ft) (1.22 to 1.52 meters [m]) deep, while underground utility installations may impact up to 12 ft (3.66 m) deep. A MUD is a political subdivision of the State of Texas authorized by the Texas Commission of Environmental Quality to provide water, sewage, drainage, and other services within the MUD boundaries. Based on MUD 2's status as a political subdivision of the state, compliance with the Antiquities Code of Texas is necessary. As no federal funding or permitting is anticipated for this project, compliance with Section 106 of the National Historic Preservation Act (NHPA) will not be necessary. The investigation was conducted in compliance with the Antiquities Code of Texas under Antiquities Permit No. 7519. The purpose of the investigations was to identify all historic or prehistoric cultural resources located within the project area and to evaluate the significance and eligibility of identified resources for designation as a State Antiquities Landmark (SAL). All work was done in accordance with the archaeological survey standards and guidelines as developed by the Council of Texas Archaeologists (CTA) and adopted by the Texas Historical Commission (THC).
Scientific Reports, 2021
In this work, the electromagnetic response of a mathematically interesting shape—a Möbius strip—i... more In this work, the electromagnetic response of a mathematically interesting shape—a Möbius strip—is presented, along with a ring resonator for comparison. Both resonators consist of a central lossy dielectric layer bounded by perfectly conducting layers. For the case of the Möbius strips, the computational results show that there are a family of half-integer wavelength modes within the dielectric layer. These additional modes result in increased absorption, and a corresponding reduction in the radar cross section. Interestingly, rotational scans show that these modes can be excited over a large angular range. This investigation gives an understanding of the electromagnetic response of these structures, paving the way for future experiments on Möbius strip resonators.
IET Microwaves, Antennas & Propagation, 2020
For guidance on citations see FAQs.
Physics of Fluids, 2018
Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and mic... more Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and microfluidic technology, including diagnostics and drug delivery. In this paper, we realize a macroscopic single particle ferromagnetic swimmer experimentally and investigate its swimming properties. The flagella-based swimmer is comprised of a hard ferromagnetic head attached to a flexible tail. We investigate the dynamic performance of the swimmer on the air-liquid interface as a function of the external magnetic field parameters (frequency and amplitude of an applied magnetic field). We show that the speed of the swimmer can be controlled by manipulating the strength and frequency of the external magnetic field (< 3.5 mT) and that the propagation direction has a dependence on parameters of the external magnetic field. The experimental results are compared to a theoretical model based on three beads, one of which having a fixed magnetic moment and the other two non-magnetic, connected via elastic filaments. The model shows sufficient complexity to satisfy the 'non-reciprocity' condition and gives good agreement with experiment. Via a simple conversion, we also demonstrate a fluid pump and investigate the induced flow. This investigation paves the way to the fabrication of such swimmers and fluid pump systems on a micro-scale, promising a variety of microfluidic applications.
Biochemistry, 2018
Microbiomes impact nearly every environment on Earth by modulating the molecular composition of t... more Microbiomes impact nearly every environment on Earth by modulating the molecular composition of the environment. Temporally changing environmental stimuli and spatial organization are major variables shaping the structure and function of microbiomes. The web of interactions among members of these communities and between the organisms and the environment dictates microbiome functions. Microbial interactions are major drivers of microbiomes and are modulated by spatiotemporal parameters. A mechanistic and quantitative understanding of ecological, molecular, and environmental forces shaping microbiomes could inform strategies to control microbiome dynamics and functions. Major challenges for harnessing the potential of microbiomes for diverse applications include the development of predictive modeling frameworks and tools for precise manipulation of microbiome behaviors.
Scientific reports, Jan 17, 2018
We propose a new class of magnetically actuated pumps and valves that could be incorporated into ... more We propose a new class of magnetically actuated pumps and valves that could be incorporated into microfluidic chips with no further external connections. The idea is to repurpose ferromagnetic low Reynolds number swimmers as devices capable of generating fluid flow, by restricting the swimmers' translational degrees of freedom. We experimentally investigate the flow structure generated by a pinned swimmer in different scenarios, such as unrestricted flow around it as well as flow generated in straight, cross-shaped, Y-shaped and circular channels. This demonstrates the feasibility of incorporating the device into a channel and its capability of acting as a pump, valve and flow splitter. Different regimes could be selected by tuning the frequency and amplitude of the external magnetic field driving the swimmer, or by changing the channel orientation with respect to the field. This versatility endows the device with varied functionality which, together with the robust remote contr...
Scientific reports, Mar 9, 2017
Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and mic... more Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and microfluidic technology, diagnostics and drug delivery etc. In this paper, we demonstrate the experimental verification of a new class of autonomous ferromagnetic swimming devices, actuated and controlled solely by an oscillating magnetic field. These devices are based on a pair of interacting ferromagnetic particles of different size and different anisotropic properties joined by an elastic link and actuated by an external time-dependent magnetic field. The net motion is generated through a combination of dipolar interparticle gradient forces, time-dependent torque and hydrodynamic coupling. We investigate the dynamic performance of a prototype (3.6 mm) of the ferromagnetic swimmer in fluids of different viscosity as a function of the external field parameters (frequency and amplitude) and demonstrate stable propulsion over a wide range of Reynolds numbers. We show that the direction of sw...
Microarrays Their Design and Use, Mar 30, 2009
Abstract : The decision path method developed in this report provides a step-by-step logical appr... more Abstract : The decision path method developed in this report provides a step-by-step logical approach to guidance for users of MIL-STD-810C. The method comprises systematic procedures for characterizing items of materiel and defining environments prior to designing tests. It is equally applicable as a general approach to all climatic environmental tests and as a specific approach to each climatic environmental test method in the Standard. Use of this approach should contribute to a better understanding of the MIL-STD's purpose, enhance its utility, and promote better correlation of test results. (Author)
Journal belge de rhumatologie et de médecine physique = Belgisch tijdschrift voor reumatologie en fysische geneeskunde
The Encyclopedia of Criminology and Criminal Justice, 2013
How and why do many serious adolescent offenders stop offending while others continue to commit c... more How and why do many serious adolescent offenders stop offending while others continue to commit crimes? This series of bulletins presents findings from the Pathways to Desistance study, a multidisciplinary investigation that attempts to answer this question.
Annals of the American Thoracic Society, 2014
In Brief An elderly woman with rheumatoid arthritis (RA) and chronic obstructive pulmonary diseas... more In Brief An elderly woman with rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) began experiencing new pulmonary complaints in the days leading up to a hospital admission. A chest radiograph revealed diffuse bilateral interstitial opacities that were not present on previously obtained radiographic images of her chest.
Toxicology and Applied Pharmacology, 1999
Cytochrome P-450IA1, the isozyme most closely associated with aryl hydrocarbon hydroxylase (AHH),... more Cytochrome P-450IA1, the isozyme most closely associated with aryl hydrocarbon hydroxylase (AHH), is regulated by two high-affinity binding proteins, the 4S polycyclic aromatic hydrocarbon (PAH)-binding protein which primarily binds PAHs and the 8S Ah (dioxin) receptor which binds 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and like congeners. The present study was conducted to determine whether the 4S protein existed in 14-day-old chick embryo liver when AHH activity is maximal to determine if they are linked as is the 8S Ah receptor and to confirm the existence of the dioxin receptor by investigating their ligand binding characteristics in the presence and absence of sodium molybdate, an agent that stabilizes steroid hormone receptors and partially stabilizes the dioxin receptor. Competitive ligand binding studies were performed with liver cytosol from livers of male 14-day-old chick embryos using [3H]-benzo[a]pyrene (B[a]P) or [3H]-TCDD in the presence and absence of a 200-fold excess of B[a]P, benzo[e]pyrene (B[e]P), 3-methylcholanthrene (3-MC), and tetrachlorodibenzofuran (TCDBF). Specific PAH-binding activity was assayed using sucrose gradient analysis. In the absence of molybdate, the 4S PAH-binding protein had high affinity for B[a]P, B[e]P, 3-MC, but very low affinity for TCDBF; the Ah receptor exhibited high affinity for TCDBF. In the presence of sodium molybdate, the Ah receptor was stabilized while the 4S PAH-binding protein was relatively unaffected. These results affirm the existence of two distinct PAH-binding proteins in 14-day-old chick embryo liver cytosol and suggest a linkage of the 4S protein to AHH.
Toxicology and Applied Pharmacology, 1987
The biochemical and histochemical measurement ofthe enzyme y-glutamyltransferase (GGT) was undert... more The biochemical and histochemical measurement ofthe enzyme y-glutamyltransferase (GGT) was undertaken in normal rat pancreas and in rat pancreas containing azaserine-induced preneoplastic nodules. A steady decrease in pancreatic GGT activity was observed in the normal animals as they aged from 5 to 34 weeks. The azaserine-induced nodules contained a lower average GGT activity than the control pancreas although a IO-fold variation was noted in the GGT activity of individual nodules. A significant increase in concentrations of both reduced glutathione and oxidized glutathione was noted in pancreatic nodules from azaserine-treated rats compared to concentrations found in both control pancreas from untreated rats and internodular pancreas from azaserine-treated rats. A pancreatic acinar cell carcinoma contained low GGT activity-similar to that found in large nodules and about 10% of the level found in control pancreas. Pancreatic GGT levels were higher in 5-and ?-week-old rats fed chow than in rats fed a purified diet. but this effect of chow was not observed at 34 weeks of age. Feeding a purified diet supplemented with a retinoid. N-2-hydroxyethylretinamide (2-HER), for a period of2 weeks did not influence the GGT activity level in either normal pancreas or in the azaserine-induced nodules. While decreased GGT activity does not serve as a marker for all atypical acinar cell nodules, deficient activity with concomitant increased glutathione levels appears to correlate generally with increased growth potential.
Toxicological Sciences, 2005
Trivalent inorganic arsenic (arsenite, arsenic trioxide, As(III)) is a primary contaminant of gro... more Trivalent inorganic arsenic (arsenite, arsenic trioxide, As(III)) is a primary contaminant of groundwater supplies worldwide. As(III), marketed as trisenox, is also an FDA-approved agent to treat cancer. It has been previously shown by our laboratory that As(III) administered at doses lower than a therapeutic anticancer dose results in an increase in tumor formation and blood vessel density of tumors. In this work it was found that chronic administration of As(III) approaching the EPA action level of 10 ppb, given in the drinking water of mice 5 weeks prior to B16-F10 melanoma implantation, increased the growth rate of primary tumors and the number of metastases to the lung. Further, levels of arsenic in the tumor and lung were found to be much greater than those in the blood and similar to pro-angiogenic As(III) doses. Levels of hypoxia inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) surrounding the blood vessels in the tumors of the As(III)-treated mice were also found to be increased. Exposure of isolated B16-F10 tumor cells to chronic (3 or 7 day) but not acute (4 h) low-dose As(III) was found to increase HIF-1a expression and secretion of VEGF. Finally, coadministration of an inhibitor of HIF (YC-1) or a VEGFR-2 kinase inhibitor (SU5416) was found to antagonize the proangiogenic effects of low-dose As(III). Together, these results suggest that chronic exposure to low-dose As(III) could stimulate growth of tumors through a HIF-dependent stimulation of angiogenesis.
Journal of Inorganic Biochemistry, 1989
Since chromium(VI) is unreactive toward DNA under physiological conditions in vitro, the ability ... more Since chromium(VI) is unreactive toward DNA under physiological conditions in vitro, the ability of carcinogenic chromium(VI) compounds to damage DNA depends on the presence of cellular redox components that reduce chromium(VI) to reactive species capable of interacting with DNA. We have examined the role of glutathione and hydrogen peroxide in chromium(VI)-induced DNA damage in vitro. Upon reaction with chromium(VI), glutathione produced chromium(V) and glutathione thiyl radical reactive intermediates, whereas hydrogen peroxide produced chromium(V) and hydroxyl radical. Reaction of DNA with chromium(VI) in the presence of glutathione resulted in binding of chromium and glutathione to DNA with little or no DNA strand breakage. Reaction of DNA with chromium(VI) in the presence of hydrogen peroxide produced the 8-hydroxydeoxyguanosine adduct and extensive DNA strand breakage in the absence of significant Cr-DNA adduct formation. These results suggest that the nature of chromium(VI)-induced DNA damage will be strongly dependent on reactive intermediates such as chromium(V), glutathione thiyl radical, and hydroxyl radical, produced by cellular components active in chromium(VI) metabolism. In order to assess the ability of chromium(VI)-induced DNA damage to affect the normal template function of DNA, we investigated the effects of chromium(VI) on steady-state mRNA levels of various genes in chick embryo liver in vivo, and compared the effects to the levels of DNA damage observed. Chromium(VI) induced DNA-protein and DNA interstrand cross-links in chick embryo liver in vivo and suppressed the induction of 5-aminolevulinic acid synthase and cytochrome P-450 mRNA expression by porphyrinogenic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Santa Clara L. Rev., 1997
Four-dimensional supersymmetric N = 1 vacua of type IIB supergravity are elegantly described by g... more Four-dimensional supersymmetric N = 1 vacua of type IIB supergravity are elegantly described by generalized complex geometry. However, this approach typically obscures the SL(2, R) covariance of the underlying theory. We show how to rewrite the pure spinor equations of Graña, Minasian, Petrini and Tomasiello (hep-th/0505212) in a manifestly SL(2, R) covariant fashion. Solutions to these equations fall into two classes: "charged" solutions, such as those containing D5-branes, and "chargeless" solutions, such as F-theory solutions in the Sen limit and AdS 4 solutions. We derive covariant supersymmetry conditions for the chargeless case, allowing general SU(3) × SU(3) structure. The formalism presented here greatly simplifies the study of the ten-dimensional geometry of general supersymmetric compactifications of F-theory.
Index of Texas Archaeology: Open Access Gray Literature from the Lone Star State, 2017
At the request of Carmel Devco, Inc., Pape-Dawson conducted an intensive archaeological survey of... more At the request of Carmel Devco, Inc., Pape-Dawson conducted an intensive archaeological survey of the eastern portion of the proposed Carmel Development Project in northeastern Travis County, Texas. The project involves the construction of a new municipal utility district (MUD 2) within the 341-acre (138.1hectare [ha]) project area. No impacts are planned adjacent to or within the floodplain of Wilbarger Creek and its tributaries, which composes approximately 70 acres (28.3 ha) of MUD 2. Thus, archaeological investigations were conducted within the remaining 271.4 acres (109.8 ha). The depths of impacts vary, but typically road construction impacts are 4 to 5 feet (ft) (1.22 to 1.52 meters [m]) deep, while underground utility installations may impact up to 12 ft (3.66 m) deep. A MUD is a political subdivision of the State of Texas authorized by the Texas Commission of Environmental Quality to provide water, sewage, drainage, and other services within the MUD boundaries. Based on MUD 2's status as a political subdivision of the state, compliance with the Antiquities Code of Texas is necessary. As no federal funding or permitting is anticipated for this project, compliance with Section 106 of the National Historic Preservation Act (NHPA) will not be necessary. The investigation was conducted in compliance with the Antiquities Code of Texas under Antiquities Permit No. 7519. The purpose of the investigations was to identify all historic or prehistoric cultural resources located within the project area and to evaluate the significance and eligibility of identified resources for designation as a State Antiquities Landmark (SAL). All work was done in accordance with the archaeological survey standards and guidelines as developed by the Council of Texas Archaeologists (CTA) and adopted by the Texas Historical Commission (THC).
Scientific Reports, 2021
In this work, the electromagnetic response of a mathematically interesting shape—a Möbius strip—i... more In this work, the electromagnetic response of a mathematically interesting shape—a Möbius strip—is presented, along with a ring resonator for comparison. Both resonators consist of a central lossy dielectric layer bounded by perfectly conducting layers. For the case of the Möbius strips, the computational results show that there are a family of half-integer wavelength modes within the dielectric layer. These additional modes result in increased absorption, and a corresponding reduction in the radar cross section. Interestingly, rotational scans show that these modes can be excited over a large angular range. This investigation gives an understanding of the electromagnetic response of these structures, paving the way for future experiments on Möbius strip resonators.
IET Microwaves, Antennas & Propagation, 2020
For guidance on citations see FAQs.
Physics of Fluids, 2018
Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and mic... more Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and microfluidic technology, including diagnostics and drug delivery. In this paper, we realize a macroscopic single particle ferromagnetic swimmer experimentally and investigate its swimming properties. The flagella-based swimmer is comprised of a hard ferromagnetic head attached to a flexible tail. We investigate the dynamic performance of the swimmer on the air-liquid interface as a function of the external magnetic field parameters (frequency and amplitude of an applied magnetic field). We show that the speed of the swimmer can be controlled by manipulating the strength and frequency of the external magnetic field (< 3.5 mT) and that the propagation direction has a dependence on parameters of the external magnetic field. The experimental results are compared to a theoretical model based on three beads, one of which having a fixed magnetic moment and the other two non-magnetic, connected via elastic filaments. The model shows sufficient complexity to satisfy the 'non-reciprocity' condition and gives good agreement with experiment. Via a simple conversion, we also demonstrate a fluid pump and investigate the induced flow. This investigation paves the way to the fabrication of such swimmers and fluid pump systems on a micro-scale, promising a variety of microfluidic applications.
Biochemistry, 2018
Microbiomes impact nearly every environment on Earth by modulating the molecular composition of t... more Microbiomes impact nearly every environment on Earth by modulating the molecular composition of the environment. Temporally changing environmental stimuli and spatial organization are major variables shaping the structure and function of microbiomes. The web of interactions among members of these communities and between the organisms and the environment dictates microbiome functions. Microbial interactions are major drivers of microbiomes and are modulated by spatiotemporal parameters. A mechanistic and quantitative understanding of ecological, molecular, and environmental forces shaping microbiomes could inform strategies to control microbiome dynamics and functions. Major challenges for harnessing the potential of microbiomes for diverse applications include the development of predictive modeling frameworks and tools for precise manipulation of microbiome behaviors.
Scientific reports, Jan 17, 2018
We propose a new class of magnetically actuated pumps and valves that could be incorporated into ... more We propose a new class of magnetically actuated pumps and valves that could be incorporated into microfluidic chips with no further external connections. The idea is to repurpose ferromagnetic low Reynolds number swimmers as devices capable of generating fluid flow, by restricting the swimmers' translational degrees of freedom. We experimentally investigate the flow structure generated by a pinned swimmer in different scenarios, such as unrestricted flow around it as well as flow generated in straight, cross-shaped, Y-shaped and circular channels. This demonstrates the feasibility of incorporating the device into a channel and its capability of acting as a pump, valve and flow splitter. Different regimes could be selected by tuning the frequency and amplitude of the external magnetic field driving the swimmer, or by changing the channel orientation with respect to the field. This versatility endows the device with varied functionality which, together with the robust remote contr...
Scientific reports, Mar 9, 2017
Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and mic... more Microscopic swimming devices hold promise for radically new applications in lab-on-a-chip and microfluidic technology, diagnostics and drug delivery etc. In this paper, we demonstrate the experimental verification of a new class of autonomous ferromagnetic swimming devices, actuated and controlled solely by an oscillating magnetic field. These devices are based on a pair of interacting ferromagnetic particles of different size and different anisotropic properties joined by an elastic link and actuated by an external time-dependent magnetic field. The net motion is generated through a combination of dipolar interparticle gradient forces, time-dependent torque and hydrodynamic coupling. We investigate the dynamic performance of a prototype (3.6 mm) of the ferromagnetic swimmer in fluids of different viscosity as a function of the external field parameters (frequency and amplitude) and demonstrate stable propulsion over a wide range of Reynolds numbers. We show that the direction of sw...
Microarrays Their Design and Use, Mar 30, 2009
Abstract : The decision path method developed in this report provides a step-by-step logical appr... more Abstract : The decision path method developed in this report provides a step-by-step logical approach to guidance for users of MIL-STD-810C. The method comprises systematic procedures for characterizing items of materiel and defining environments prior to designing tests. It is equally applicable as a general approach to all climatic environmental tests and as a specific approach to each climatic environmental test method in the Standard. Use of this approach should contribute to a better understanding of the MIL-STD's purpose, enhance its utility, and promote better correlation of test results. (Author)
Journal belge de rhumatologie et de médecine physique = Belgisch tijdschrift voor reumatologie en fysische geneeskunde
The Encyclopedia of Criminology and Criminal Justice, 2013
How and why do many serious adolescent offenders stop offending while others continue to commit c... more How and why do many serious adolescent offenders stop offending while others continue to commit crimes? This series of bulletins presents findings from the Pathways to Desistance study, a multidisciplinary investigation that attempts to answer this question.
Annals of the American Thoracic Society, 2014
In Brief An elderly woman with rheumatoid arthritis (RA) and chronic obstructive pulmonary diseas... more In Brief An elderly woman with rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) began experiencing new pulmonary complaints in the days leading up to a hospital admission. A chest radiograph revealed diffuse bilateral interstitial opacities that were not present on previously obtained radiographic images of her chest.
Toxicology and Applied Pharmacology, 1999
Cytochrome P-450IA1, the isozyme most closely associated with aryl hydrocarbon hydroxylase (AHH),... more Cytochrome P-450IA1, the isozyme most closely associated with aryl hydrocarbon hydroxylase (AHH), is regulated by two high-affinity binding proteins, the 4S polycyclic aromatic hydrocarbon (PAH)-binding protein which primarily binds PAHs and the 8S Ah (dioxin) receptor which binds 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and like congeners. The present study was conducted to determine whether the 4S protein existed in 14-day-old chick embryo liver when AHH activity is maximal to determine if they are linked as is the 8S Ah receptor and to confirm the existence of the dioxin receptor by investigating their ligand binding characteristics in the presence and absence of sodium molybdate, an agent that stabilizes steroid hormone receptors and partially stabilizes the dioxin receptor. Competitive ligand binding studies were performed with liver cytosol from livers of male 14-day-old chick embryos using [3H]-benzo[a]pyrene (B[a]P) or [3H]-TCDD in the presence and absence of a 200-fold excess of B[a]P, benzo[e]pyrene (B[e]P), 3-methylcholanthrene (3-MC), and tetrachlorodibenzofuran (TCDBF). Specific PAH-binding activity was assayed using sucrose gradient analysis. In the absence of molybdate, the 4S PAH-binding protein had high affinity for B[a]P, B[e]P, 3-MC, but very low affinity for TCDBF; the Ah receptor exhibited high affinity for TCDBF. In the presence of sodium molybdate, the Ah receptor was stabilized while the 4S PAH-binding protein was relatively unaffected. These results affirm the existence of two distinct PAH-binding proteins in 14-day-old chick embryo liver cytosol and suggest a linkage of the 4S protein to AHH.
Toxicology and Applied Pharmacology, 1987
The biochemical and histochemical measurement ofthe enzyme y-glutamyltransferase (GGT) was undert... more The biochemical and histochemical measurement ofthe enzyme y-glutamyltransferase (GGT) was undertaken in normal rat pancreas and in rat pancreas containing azaserine-induced preneoplastic nodules. A steady decrease in pancreatic GGT activity was observed in the normal animals as they aged from 5 to 34 weeks. The azaserine-induced nodules contained a lower average GGT activity than the control pancreas although a IO-fold variation was noted in the GGT activity of individual nodules. A significant increase in concentrations of both reduced glutathione and oxidized glutathione was noted in pancreatic nodules from azaserine-treated rats compared to concentrations found in both control pancreas from untreated rats and internodular pancreas from azaserine-treated rats. A pancreatic acinar cell carcinoma contained low GGT activity-similar to that found in large nodules and about 10% of the level found in control pancreas. Pancreatic GGT levels were higher in 5-and ?-week-old rats fed chow than in rats fed a purified diet. but this effect of chow was not observed at 34 weeks of age. Feeding a purified diet supplemented with a retinoid. N-2-hydroxyethylretinamide (2-HER), for a period of2 weeks did not influence the GGT activity level in either normal pancreas or in the azaserine-induced nodules. While decreased GGT activity does not serve as a marker for all atypical acinar cell nodules, deficient activity with concomitant increased glutathione levels appears to correlate generally with increased growth potential.
Toxicological Sciences, 2005
Trivalent inorganic arsenic (arsenite, arsenic trioxide, As(III)) is a primary contaminant of gro... more Trivalent inorganic arsenic (arsenite, arsenic trioxide, As(III)) is a primary contaminant of groundwater supplies worldwide. As(III), marketed as trisenox, is also an FDA-approved agent to treat cancer. It has been previously shown by our laboratory that As(III) administered at doses lower than a therapeutic anticancer dose results in an increase in tumor formation and blood vessel density of tumors. In this work it was found that chronic administration of As(III) approaching the EPA action level of 10 ppb, given in the drinking water of mice 5 weeks prior to B16-F10 melanoma implantation, increased the growth rate of primary tumors and the number of metastases to the lung. Further, levels of arsenic in the tumor and lung were found to be much greater than those in the blood and similar to pro-angiogenic As(III) doses. Levels of hypoxia inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) surrounding the blood vessels in the tumors of the As(III)-treated mice were also found to be increased. Exposure of isolated B16-F10 tumor cells to chronic (3 or 7 day) but not acute (4 h) low-dose As(III) was found to increase HIF-1a expression and secretion of VEGF. Finally, coadministration of an inhibitor of HIF (YC-1) or a VEGFR-2 kinase inhibitor (SU5416) was found to antagonize the proangiogenic effects of low-dose As(III). Together, these results suggest that chronic exposure to low-dose As(III) could stimulate growth of tumors through a HIF-dependent stimulation of angiogenesis.
Journal of Inorganic Biochemistry, 1989
Since chromium(VI) is unreactive toward DNA under physiological conditions in vitro, the ability ... more Since chromium(VI) is unreactive toward DNA under physiological conditions in vitro, the ability of carcinogenic chromium(VI) compounds to damage DNA depends on the presence of cellular redox components that reduce chromium(VI) to reactive species capable of interacting with DNA. We have examined the role of glutathione and hydrogen peroxide in chromium(VI)-induced DNA damage in vitro. Upon reaction with chromium(VI), glutathione produced chromium(V) and glutathione thiyl radical reactive intermediates, whereas hydrogen peroxide produced chromium(V) and hydroxyl radical. Reaction of DNA with chromium(VI) in the presence of glutathione resulted in binding of chromium and glutathione to DNA with little or no DNA strand breakage. Reaction of DNA with chromium(VI) in the presence of hydrogen peroxide produced the 8-hydroxydeoxyguanosine adduct and extensive DNA strand breakage in the absence of significant Cr-DNA adduct formation. These results suggest that the nature of chromium(VI)-induced DNA damage will be strongly dependent on reactive intermediates such as chromium(V), glutathione thiyl radical, and hydroxyl radical, produced by cellular components active in chromium(VI) metabolism. In order to assess the ability of chromium(VI)-induced DNA damage to affect the normal template function of DNA, we investigated the effects of chromium(VI) on steady-state mRNA levels of various genes in chick embryo liver in vivo, and compared the effects to the levels of DNA damage observed. Chromium(VI) induced DNA-protein and DNA interstrand cross-links in chick embryo liver in vivo and suppressed the induction of 5-aminolevulinic acid synthase and cytochrome P-450 mRNA expression by porphyrinogenic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Santa Clara L. Rev., 1997
Four-dimensional supersymmetric N = 1 vacua of type IIB supergravity are elegantly described by g... more Four-dimensional supersymmetric N = 1 vacua of type IIB supergravity are elegantly described by generalized complex geometry. However, this approach typically obscures the SL(2, R) covariance of the underlying theory. We show how to rewrite the pure spinor equations of Graña, Minasian, Petrini and Tomasiello (hep-th/0505212) in a manifestly SL(2, R) covariant fashion. Solutions to these equations fall into two classes: "charged" solutions, such as those containing D5-branes, and "chargeless" solutions, such as F-theory solutions in the Sen limit and AdS 4 solutions. We derive covariant supersymmetry conditions for the chargeless case, allowing general SU(3) × SU(3) structure. The formalism presented here greatly simplifies the study of the ten-dimensional geometry of general supersymmetric compactifications of F-theory.