To investigate whether DNA damage arising in spermatogenic germ cells can be detected in resultan... more To investigate whether DNA damage arising in spermatogenic germ cells can be detected in resultant sperm, we have irradiated murine testis and collected spermatozoa from the vas deferens 45 days later. These cells were derived from spermatogonia present at the time of irradiation. Two forms of irradiation were used, external X-rays (4 Gy) and internal auger electrons from contamination of the male mouse with the isotope Indium-114m (1.85 MBq), which was localised in the testis. Both forms of irradiation produced a profound fall in vas deferens sperm count and testis weight, Indium-114m being more effective. Using the neutral Comet assay for double strand break detection, significant increases in sperm comet tail length and moment were observed. The levels of damage were similar for both treatments. Care had to be taken during the assay to distinguish between sperm and somatic cells as the proportion of the latter increased after irradiation. We conclude that the comet assay can detect DNA damage in spermatozoa after the in vivo exposure of male germ cells to a known testicular genotoxic agent. The assay may be useful for the assessment of sperm DNA damage (double stranded) associated with male infertility and post-fertilization developmental abnormalities in the offspring.
Examination of museum collections and published accounts were combined with visits to Adams Co., ... more Examination of museum collections and published accounts were combined with visits to Adams Co., Ohio, to determine the occurrence of reptiles and amphibians there. Nineteen salamander, 12 frog and toad, 4 lizard, 15 snake and at least 4 turtle species have been recorded in the county. This is more than has been recorded from any other county in Ohio and further substantiates the unusual nature of this part of Ohio.
Acton Lake is a 253-hectare impoundment located in a heavily used state park in southwestern Ohio... more Acton Lake is a 253-hectare impoundment located in a heavily used state park in southwestern Ohio. The length from inflow stream to spillway is 4.3 km, the total shoreline length is 13.9 km, the mean depth is 4.3 m and the maximum depth is 10.4 m. Sediment accumulation averaging 0.023 m annually provide a possible useful life of the lake for recreation of about 140 years. The lake stratifies chemically and thermally in the summer. Oxygen depletion occurs at the lower depths in the summer. Chironomids are the most numerous component of the macrobenthic fauna of the whole lake and chaoborids are quite abundant in deeper waters. The wet-weight benthic biomass is greatest in late winter before spring emergence. Funnel trapping has yielded a total of 1400 organisms per square meter for the emergence season from early spring to late fall. Annelids and pelecypods appear to have been increasing in numbers in recent years. INTRODUCTION Acton Lake is a 253-hectare impoundment about 64 kilometers northwest of Cincinnati in Hueston Woods State Park in northwestern Butler County and southwestern Preble County. Impoundment was begun in 1957, and limnological investigation has been continuous since 1959. During the period since impoundment, the lake and surrounding state park has had heavy recreational use. Mr. Maynard Dils, Hueston Woods Park Manager in 1970, supplied information on park use between 1964 and 1970 which is summarized in Table 1. The lake is drawn dow r n approximately 2 meters each winter to prevent ice damage to the docks. Acton Lake is located at the confluence of two branches of Four Mile Creek, with the impounded area extending 4.3 km northward from the spillway. Some of the original physical characteristics as compiled by Winner et al. (1962) are given in Table 2. The deepest portion of the lake, located near the dam, is 10.4 m deep. The watershed is composed of an area of 270 sq. km, which is largely The editor of The Ohio Journal of Science will be retiring from this position this winter. The Joint Administrative Board is therefore seeking a possible successor. The work is demanding but rewarding. If you are interested in applying for this position, please contact the Secretary-Treasurer of the Board, Dr.
Advances in Experimental Medicine and Biology, 1998
The comet assay is widely employed as a method to measure DNA damage in a wide variety of cell ty... more The comet assay is widely employed as a method to measure DNA damage in a wide variety of cell types following genotoxic insult. We have used this method in order to characterise DNA damage in spermatozoa following in vitro irradiation with 137Cs gamma rays. In contrast to somatic cells, the DNA of mammalian spermatozoa is bound by protamine molecules allowing a sixfold more highly compact structure and thus rendering conventional cell lysis protocols ineffective. Therefore, this new method uses an extensive lysis step to ensure effective removal of DNA-associated proteins allowing DNA damage to be scored reproducibly in both murine and human spermatozoa. Mouse spermatozoa collected from the vas deferens at post-mortem or human spermatozoa provided by donors were irradiated with doses of gamma-rays from 0-100 Gy using a 137Cs source and then processed for both alkaline and neutral comet assays. Under neutral electrophoresis conditions, which permits the measurement of double-stranded DNA breaks, a linear increase in the amount of DNA damage measured was observed with increasing radiation dose for both murine and human spermatozoa. Similarly, using alkaline electrophoresis conditions to examine DNA single-strand breaks and alkali-labile sites, a linear relationship was also observed for murine sperm but in contrast no such relationship was apparent for human spermatozoa subjected to the same radiation treatments. Interestingly, unirradiated sperm (both human and mouse) showed extensive DNA migration from the nucleus after alkaline assay. Since it is unlikely that the DNA of normal spermatozoa contains high numbers of single-strand breaks and damage was not detected for unirradiated sperm in the neutral assay, it is more likely that this DNA migration is due to the presence of high numbers of alkali labile sites within sperm DNA and that these may be related to the highly condensed structure of spermatozoal DNA. The large radiation doses used in these experiments to produce measurable amounts of DNA damage reflects the high radioresistance of spermatozoa compared to somatic cells and this may also be related to the differences in DNA packaging and conformation. In conclusion, this work shows that the comet assay represents a new method for examining DNA damage in spermatozoa and should be evaluated for use in reproductive toxicity testing.
Table S3 summarizes the complete blood count (CBC) and biochemistry assessment of alanine aminotr... more Table S3 summarizes the complete blood count (CBC) and biochemistry assessment of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes for ZR2002 alternate treatment (schedule #1).
Purpose:Glioblastoma (GBM) is a fatal primary malignant brain tumor. GBM stem cells (GSC) contrib... more Purpose:Glioblastoma (GBM) is a fatal primary malignant brain tumor. GBM stem cells (GSC) contribute to resistance to the DNA-damaging chemotherapy, temozolomide. The epidermal growth factor receptor (EGFR) displays genomic alterations enabling DNA repair mechanisms in half of GBMs. We aimed to investigate EGFR/DNA combi-targeting in GBM.Experimental Design:ZR2002 is a “combi-molecule” designed to inflict DNA damage through its chlorethyl moiety and induce irreversible EGFR tyrosine kinase inhibition. We assessed its in vitro efficacy in temozolomide-resistant patient-derived GSCs, mesenchymal temozolomide-sensitive and resistant in vivo–derived GSC sublines, and U87/EGFR isogenic cell lines stably expressing EGFR/wild-type or variant III (EGFRvIII). We evaluated its antitumor activity in mice harboring orthotopic EGFRvIII or mesenchymal TMZ-resistant GSC tumors.Results:ZR2002 induced submicromolar antiproliferative effects and inhibited neurosphere formation of all GSCs with margin...
Figure S4 shows body weights assessment for mice with orthotopic U87/EGFRvIII (A) or TMZ-resistan... more Figure S4 shows body weights assessment for mice with orthotopic U87/EGFRvIII (A) or TMZ-resistant GSC (1123IC7R) tumors (B) treated with vehicle control or ZR2002 using alternate (A) or continuous treatment (B).
Glioblastoma (GBM), the most common and advanced malignant primary brain tumor in adults remains ... more Glioblastoma (GBM), the most common and advanced malignant primary brain tumor in adults remains incurable. GBM tumor recurrence occurs within a short time reflecting the failure to eradicate chemo-radioresistant GBM stem cells (GSCs). GSCs alter the redox system including Thioredoxin (Trx) and glutathione (GSH) systems to counteract increased reactive oxygen species (ROS). We previously showed the role of O6-methylguanine-DNA methyltransferase (MGMT) in response to PRIMAMET, a drug that targets the TP53 tumor suppressor gene and decrease Thioredoxin reductase1 (TRxR1) levels and further identified a positive relationship between MGMT and TrxR1 in established GBM cell lines isogenic for MGMT. Auranofin (Au), an orally available ROS-inducing FDA-approved drug is a potent irreversible inhibitor of TrxR1. The effect of Au on GSCs and the potential relationship between TrXR1, MGMT and p53 specifically in GSCs remain unknown. We hypothesized that increased ROS levels in GSCs might affect...
Gear box casing is a critical segment in motor of an Automobile. Reason for Gearbox casing is to ... more Gear box casing is a critical segment in motor of an Automobile. Reason for Gearbox casing is to hold and guide the Gear transmission. Gearbox is a speed or Torque changing device between the motor and driving wheels. Gear box comprises of principle shaft and lay shaft with gears fit. This paper deals with modeling and analysis of the side engine cover of gear box casing for a mini truck with different composite materials. It is statically and dynamically analyzed by utilizing simulation software package ANSYS. After analysis its result will be studied and examined, and again it will be iterated again and again to achieve satisfactory result. Different composite materials are used in analysis to achieve the design which has better performance with no failure at greater loads. To check the design safety of gear box FEA will be done additionally. Finally mechanical properties will be characterized with best material.
IEEE journal of biomedical and health informatics, Jan 9, 2018
This paper presents a novel set of image texture features, generalizing standard grey-level co-oc... more This paper presents a novel set of image texture features, generalizing standard grey-level co-occurrence matrices (GLCM) to multi-modal image data through joint intensity matrices (JIMs). These are used to predict the survival of glioblastoma multiforme (GBM) patients from multi-modal MRI data. The scans of 73 GBM patients from the Cancer Imaging Archive are used in our study. Necrosis, active tumor and edema/invasion sub-regions of GBM phenotypes are segmented using the co-registration of contrast enhanced T1-weighted (CET1) images and its corresponding fluid-attenuated inversion recovery (FLAIR) images. Texture features are then computed from the JIM of these GBM sub-regions, and a random forest model employed to classify patients into short or long survival groups. Our survival analysis identified JIM features in necrotic (e.g., entropy and inverse-variance) and edema (e.g., entropy and contrast) sub-regions that are moderately correlated with survival time (i.e., Spearman rank ...
To investigate whether DNA damage arising in spermatogenic germ cells can be detected in resultan... more To investigate whether DNA damage arising in spermatogenic germ cells can be detected in resultant sperm, we have irradiated murine testis and collected spermatozoa from the vas deferens 45 days later. These cells were derived from spermatogonia present at the time of irradiation. Two forms of irradiation were used, external X-rays (4 Gy) and internal auger electrons from contamination of the male mouse with the isotope Indium-114m (1.85 MBq), which was localised in the testis. Both forms of irradiation produced a profound fall in vas deferens sperm count and testis weight, Indium-114m being more effective. Using the neutral Comet assay for double strand break detection, significant increases in sperm comet tail length and moment were observed. The levels of damage were similar for both treatments. Care had to be taken during the assay to distinguish between sperm and somatic cells as the proportion of the latter increased after irradiation. We conclude that the comet assay can detect DNA damage in spermatozoa after the in vivo exposure of male germ cells to a known testicular genotoxic agent. The assay may be useful for the assessment of sperm DNA damage (double stranded) associated with male infertility and post-fertilization developmental abnormalities in the offspring.
Examination of museum collections and published accounts were combined with visits to Adams Co., ... more Examination of museum collections and published accounts were combined with visits to Adams Co., Ohio, to determine the occurrence of reptiles and amphibians there. Nineteen salamander, 12 frog and toad, 4 lizard, 15 snake and at least 4 turtle species have been recorded in the county. This is more than has been recorded from any other county in Ohio and further substantiates the unusual nature of this part of Ohio.
Acton Lake is a 253-hectare impoundment located in a heavily used state park in southwestern Ohio... more Acton Lake is a 253-hectare impoundment located in a heavily used state park in southwestern Ohio. The length from inflow stream to spillway is 4.3 km, the total shoreline length is 13.9 km, the mean depth is 4.3 m and the maximum depth is 10.4 m. Sediment accumulation averaging 0.023 m annually provide a possible useful life of the lake for recreation of about 140 years. The lake stratifies chemically and thermally in the summer. Oxygen depletion occurs at the lower depths in the summer. Chironomids are the most numerous component of the macrobenthic fauna of the whole lake and chaoborids are quite abundant in deeper waters. The wet-weight benthic biomass is greatest in late winter before spring emergence. Funnel trapping has yielded a total of 1400 organisms per square meter for the emergence season from early spring to late fall. Annelids and pelecypods appear to have been increasing in numbers in recent years. INTRODUCTION Acton Lake is a 253-hectare impoundment about 64 kilometers northwest of Cincinnati in Hueston Woods State Park in northwestern Butler County and southwestern Preble County. Impoundment was begun in 1957, and limnological investigation has been continuous since 1959. During the period since impoundment, the lake and surrounding state park has had heavy recreational use. Mr. Maynard Dils, Hueston Woods Park Manager in 1970, supplied information on park use between 1964 and 1970 which is summarized in Table 1. The lake is drawn dow r n approximately 2 meters each winter to prevent ice damage to the docks. Acton Lake is located at the confluence of two branches of Four Mile Creek, with the impounded area extending 4.3 km northward from the spillway. Some of the original physical characteristics as compiled by Winner et al. (1962) are given in Table 2. The deepest portion of the lake, located near the dam, is 10.4 m deep. The watershed is composed of an area of 270 sq. km, which is largely The editor of The Ohio Journal of Science will be retiring from this position this winter. The Joint Administrative Board is therefore seeking a possible successor. The work is demanding but rewarding. If you are interested in applying for this position, please contact the Secretary-Treasurer of the Board, Dr.
Advances in Experimental Medicine and Biology, 1998
The comet assay is widely employed as a method to measure DNA damage in a wide variety of cell ty... more The comet assay is widely employed as a method to measure DNA damage in a wide variety of cell types following genotoxic insult. We have used this method in order to characterise DNA damage in spermatozoa following in vitro irradiation with 137Cs gamma rays. In contrast to somatic cells, the DNA of mammalian spermatozoa is bound by protamine molecules allowing a sixfold more highly compact structure and thus rendering conventional cell lysis protocols ineffective. Therefore, this new method uses an extensive lysis step to ensure effective removal of DNA-associated proteins allowing DNA damage to be scored reproducibly in both murine and human spermatozoa. Mouse spermatozoa collected from the vas deferens at post-mortem or human spermatozoa provided by donors were irradiated with doses of gamma-rays from 0-100 Gy using a 137Cs source and then processed for both alkaline and neutral comet assays. Under neutral electrophoresis conditions, which permits the measurement of double-stranded DNA breaks, a linear increase in the amount of DNA damage measured was observed with increasing radiation dose for both murine and human spermatozoa. Similarly, using alkaline electrophoresis conditions to examine DNA single-strand breaks and alkali-labile sites, a linear relationship was also observed for murine sperm but in contrast no such relationship was apparent for human spermatozoa subjected to the same radiation treatments. Interestingly, unirradiated sperm (both human and mouse) showed extensive DNA migration from the nucleus after alkaline assay. Since it is unlikely that the DNA of normal spermatozoa contains high numbers of single-strand breaks and damage was not detected for unirradiated sperm in the neutral assay, it is more likely that this DNA migration is due to the presence of high numbers of alkali labile sites within sperm DNA and that these may be related to the highly condensed structure of spermatozoal DNA. The large radiation doses used in these experiments to produce measurable amounts of DNA damage reflects the high radioresistance of spermatozoa compared to somatic cells and this may also be related to the differences in DNA packaging and conformation. In conclusion, this work shows that the comet assay represents a new method for examining DNA damage in spermatozoa and should be evaluated for use in reproductive toxicity testing.
Table S3 summarizes the complete blood count (CBC) and biochemistry assessment of alanine aminotr... more Table S3 summarizes the complete blood count (CBC) and biochemistry assessment of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes for ZR2002 alternate treatment (schedule #1).
Purpose:Glioblastoma (GBM) is a fatal primary malignant brain tumor. GBM stem cells (GSC) contrib... more Purpose:Glioblastoma (GBM) is a fatal primary malignant brain tumor. GBM stem cells (GSC) contribute to resistance to the DNA-damaging chemotherapy, temozolomide. The epidermal growth factor receptor (EGFR) displays genomic alterations enabling DNA repair mechanisms in half of GBMs. We aimed to investigate EGFR/DNA combi-targeting in GBM.Experimental Design:ZR2002 is a “combi-molecule” designed to inflict DNA damage through its chlorethyl moiety and induce irreversible EGFR tyrosine kinase inhibition. We assessed its in vitro efficacy in temozolomide-resistant patient-derived GSCs, mesenchymal temozolomide-sensitive and resistant in vivo–derived GSC sublines, and U87/EGFR isogenic cell lines stably expressing EGFR/wild-type or variant III (EGFRvIII). We evaluated its antitumor activity in mice harboring orthotopic EGFRvIII or mesenchymal TMZ-resistant GSC tumors.Results:ZR2002 induced submicromolar antiproliferative effects and inhibited neurosphere formation of all GSCs with margin...
Figure S4 shows body weights assessment for mice with orthotopic U87/EGFRvIII (A) or TMZ-resistan... more Figure S4 shows body weights assessment for mice with orthotopic U87/EGFRvIII (A) or TMZ-resistant GSC (1123IC7R) tumors (B) treated with vehicle control or ZR2002 using alternate (A) or continuous treatment (B).
Glioblastoma (GBM), the most common and advanced malignant primary brain tumor in adults remains ... more Glioblastoma (GBM), the most common and advanced malignant primary brain tumor in adults remains incurable. GBM tumor recurrence occurs within a short time reflecting the failure to eradicate chemo-radioresistant GBM stem cells (GSCs). GSCs alter the redox system including Thioredoxin (Trx) and glutathione (GSH) systems to counteract increased reactive oxygen species (ROS). We previously showed the role of O6-methylguanine-DNA methyltransferase (MGMT) in response to PRIMAMET, a drug that targets the TP53 tumor suppressor gene and decrease Thioredoxin reductase1 (TRxR1) levels and further identified a positive relationship between MGMT and TrxR1 in established GBM cell lines isogenic for MGMT. Auranofin (Au), an orally available ROS-inducing FDA-approved drug is a potent irreversible inhibitor of TrxR1. The effect of Au on GSCs and the potential relationship between TrXR1, MGMT and p53 specifically in GSCs remain unknown. We hypothesized that increased ROS levels in GSCs might affect...
Gear box casing is a critical segment in motor of an Automobile. Reason for Gearbox casing is to ... more Gear box casing is a critical segment in motor of an Automobile. Reason for Gearbox casing is to hold and guide the Gear transmission. Gearbox is a speed or Torque changing device between the motor and driving wheels. Gear box comprises of principle shaft and lay shaft with gears fit. This paper deals with modeling and analysis of the side engine cover of gear box casing for a mini truck with different composite materials. It is statically and dynamically analyzed by utilizing simulation software package ANSYS. After analysis its result will be studied and examined, and again it will be iterated again and again to achieve satisfactory result. Different composite materials are used in analysis to achieve the design which has better performance with no failure at greater loads. To check the design safety of gear box FEA will be done additionally. Finally mechanical properties will be characterized with best material.
IEEE journal of biomedical and health informatics, Jan 9, 2018
This paper presents a novel set of image texture features, generalizing standard grey-level co-oc... more This paper presents a novel set of image texture features, generalizing standard grey-level co-occurrence matrices (GLCM) to multi-modal image data through joint intensity matrices (JIMs). These are used to predict the survival of glioblastoma multiforme (GBM) patients from multi-modal MRI data. The scans of 73 GBM patients from the Cancer Imaging Archive are used in our study. Necrosis, active tumor and edema/invasion sub-regions of GBM phenotypes are segmented using the co-registration of contrast enhanced T1-weighted (CET1) images and its corresponding fluid-attenuated inversion recovery (FLAIR) images. Texture features are then computed from the JIM of these GBM sub-regions, and a random forest model employed to classify patients into short or long survival groups. Our survival analysis identified JIM features in necrotic (e.g., entropy and inverse-variance) and edema (e.g., entropy and contrast) sub-regions that are moderately correlated with survival time (i.e., Spearman rank ...
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Papers by Paul Daniel