Battelle Columbus Laboratories Research Articles

Study of the Relationship between Abnormalities in Nuclear DNA and Drug Sensitivity of Human Gynecological Cancer Transplanted into Nude Mice

The relationship between abnormalities in nuclear DNA and anticancer-drug sensitivity of human gynecological cancer transplanted into nude mice is reported. Nuclear DNA content was expressed in terms of the DNA index (DI) and heterogeneity index score (HIS) using flow cytometry (FCM). Southern blot analysis was used to examine changes in DNA and in observed abnormal-size DNA fragments. Drug sensitivity was carried out according to a procedure described by Battelle Columbus Laboratories. The results were as follows: (1) Tumors with a high degree of DNA content were more sensitive to anticancer drugs than tumors with less DNA damage. (2) Severe heterogeneity of nuclear DNA caused drug resistance.

LOW-ACTIVITY RADIOACTIVE MATERIALS MANAGEMENT AT THE U.S. DEPARTMENT OF ENERGY

The U.S. Department of Energy (U.S. DOE) is making significant progress with the cleanup of its legacy radioactively-contaminated facilities and sites left from research and development and production of nuclear materials and weapons. Sites like Rocky Flats, Battelle Columbus Laboratories, Fernald, Mound, Brookhaven National Laboratory, Hanford, and Oak Ridge are faced daily with decisions related to disposition of waste and radioactive material. One key to this success is the disposition of waste arising from cleanup. Most of the generated waste volume has very low levels of radioactive contamination. The waste includes contaminated soil, debris from demolition, or scrap metal and equipment. The cost of disposing of large volumes of waste can be prohibitive, so there is incentive to find innovative ways to disposition wastes. This paper describes the current status of policy development in this area, such as development of a draft programmatic environmental impact statement and monitoring of related rulemaking at the U.S. Nuclear Regulatory Commission. The paper also provides an overview of draft U.S. DOE guidance on control and release of property with residual radioactive material, and site-specific applications of DOE guidance.

Study of the carbonation–calcination reaction applied to the hydrogen production from syngas

In the last years the interest in hydrogen as an energy carrier is significantly increased both for vehicle fuelling and stationary energy production by fuel cells. The benefits of a hydrogen energy policy are the reduction of the greenhouse effect and the centralization of the emission sources. Moreover, an improvement to the environmental benefits can be achieved if hydrogen is produced from renewable sources, as biomass. The present study relates the development of an innovative system for hydrogen production and CO2 capture starting from syngas. The plant is based on the carbonation and calcination reactions for CO2 absorption and desorption, respectively. In the carbonation reactor also steam methane reforming and CO-shift take place to enhance the hydrogen production. By means of a thermodynamic analysis, the system has been optimized in terms of the amount of the hydrogen produced and its purity. Different syngas compositions have been tested. The results confirm the effectiveness of the system proposed, which provides 99% H2 purity and zero CO2 emission in the case of the syngas derived from Battelle Columbus Laboratories gasifier.

Effects of recombinant human endostatin on a human neuroblastoma xenograft.

New antitumor agents must be added to the current neuroblastoma treatment regimens to improve the clinical results. We investigated whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against human neuroblastoma in the human neuroblastoma xenograft model designated TNB9. When tumors on the back of nude mice grew to a weight of 90-95 mg, rhEndostatin 10 mg/kg/day was administered subcutaneously every day for 10 consecutive days. Mean relative tumor weight in mice administered rhEndostatin (n=5) was significantly less than that in controls (n=12) on days 2, 4, and 6 after the start of administration (p<0.01 on day 2, p<0.05 on days 4 and 6), and regression of tumor growth (TRW<1.0) was marked on day 2. The maximum inhibition rate (MIR) by rhEndostatin was 46.4%, indicating inefficacy, but it may not be appropriate to apply Battelle Columbus Laboratories criteria to this experimental model because rhEndostatin is a protein. After day 8, tumors in the experimental group increased in weight and were not statistically significantly different from those in controls. Recombinant human endostatin was used in tumors in the arterial system of the mouse in this experiment because eventually rhEndostatin, not recombinant mouse endostatin, may be used to treat advanced neuroblastoma in the clinical setting. The results show that there is little cross-reactivity of rhEndostatin with the human and mouse models and indicate that rhEndostatin could become an effective agent for the treatment of human neuroblastoma.

00/00889 The Vermont biomass gasifier project—medium heating value gas for electric power applications

The Vermont Biomass Gasifier Project is part of a major DOE initiative to demonstrate indirect gasification of renewable biomass for electricity production. The Vermont Project has been undertaken to demonstrate the integration of the Battelle Columbus Laboratories (Battelle) indirectly-heated gasifier with a high-efficiency gas turbine. The demonstration and validation of this gasification/gas turbine system is being performed at the existing 50 MW wood-fired McNeil Power Generating Station in Burlington, Vermont, thereby significantly reducing the time scale for deployment and the necessary capital investment for DOE and the Vermont project partnership. The development and commercialization of this technology is important for several reasons: (1) it does not require a hot-gas clean-up for gas turbine operation, thus removing this technical hurdle from the commercialization path; (2) it is the only US biomass gasification system that has successfully powered a gas turbine, supporting its near-term viability for commercial deployment; and (3) it produces a medium-heating-value gas without employing an oxygen plant, thus allowing the use of existing unmodified industrial gas turbines. Gasifier construction was completed in late 1997; commissioning and parametric testing was completed during the spring and summer of 1998. This paper discusses the results of this testing and presents plans formore » both the next phase of testing and prospects for near-term commercialization.« less

Effects of CPT‐11 (a unique DNA topoisomerase I inhibitor) on a highly malignant xeno‐transplanted neuroblastoma

Although many advances have been made in the management of neuroblastoma, the prognosis of patients with advanced neuroblastoma remains poor, and constant efforts are being made to search for newer effective drugs. CPT-11 is a newly developed derivative of camptothecin and shows a unique anti-tumor activity by inhibiting DNA topoisomerase I. In this study the effects of CPT-11 on a human neuroblastoma xenograft, TNB9, were investigated according to the standard Battelle Columbus Laboratories protocol. TNB9 is one of the most malignant strains of neuroblastoma, showing a homogeneously staining resion (HSR) on chromosome 20 and 80-fold amplification of the N-myc gene. This study disclosed that CPT-11 was highly effective against TNB9. Maximum inhibition rate (IR) was 72.5% at a standard dose and 52.8% even at half the dose. No nude mouse used in this study lost weight after an administration of CPT-11. Plasma pharmacokinetics of CPT-11 administered in this experimental model were compared to that in clinical patients. Our data suggested that CPT-11 might be a promising new drug in the treatment of high-risk neuroblastoma patients and encouraged us to employ CPT-11 in the protocol of the Study Group of Japan.

Effects of newly introduced chemotherapeutic agents on a cytogenetically highly malignant neuroblastoma, xenotransplanted in nude mice

A human neuroblastoma xenograft, designated TNB9, was used in this experiment. This xenograft is known to have a homogeneously staining region (HSR) on chromosome 20 and to exhibit 60- to 100-fold amplification of clones 8, G21 and N- myc, and showed a rapid tumor weight doubling time of 5.9 days; it represents one of the most malignant strains of human neuroblastoma. The effects of nine different chemotherapeutic agents on this xenograft were studied according to the standard Battelle Columbus Laboratories protocol, and the in vivo chemotherapeutic sensitivity assessment disclosed that Mitomycin C, Ifosfamide, and Carboplatin were highly effective against it, while VP-16, NK-171, 5-Fluorouracil, and THP-Adriamycin were ineffective. Cytogenetic and molecular-cytogenetic analyses suggest that the present data may accurately predict the clinical results with these chemotherapeutic agents in treating patients in advanced stages, as did those from our previous studies. Inclusion of Mitomycin C, Ifosamide, and/or Carboplatin into a new chemotherapeutic protocol may be recommended.

Application of the 2D finite element method to simulation of cold-forging processes

In recent years, computer aided engineering (CAE) techniques have been increasingly applied with great success in metal-forming research, as well as in the cold- and hot-forging industry. Initially, computer simulation of metal flow and detailed stress analysis of dies were conducted by forging companies that supply the aerospace industry ( J. Mater. Process. Technol., 27 (1991) 43–51). During the last several years, however, the two dimensional computer code Deform, developed by Battelle Columbus Laboratories and supported by Scientific Forming Technologies Co., has been fully commercialized. This code is now used extensively also by non-aerospace forgers for the investigation of die fill, defect analysis and prevention, as well as for prediction of part properties. At the Engineering Research Center for Net Shape Manufacturing (ERC/NSM), Deform is one of the available computer aided tools used in cold-forging research and for educational purposes. This paper, adapted for cold-forging applications from an earlier publication ( J. Mater. Process. Technol., 33 (1992) 31–55) summarizes industrially relevant research results obtained with Deform. It reports on an investigation of a suck-in type extrusion defect, forging of bevel gears, stress analysis of forging tooling, design of multi-stage cold-forging operations, design of a net-shape cold-forging operation for pipe fittings and development of a new test to evaluate lubrication in cold forging.

Application of the 2D finite element method to simulation of various forming processes

In recent years, computer-aided engineering (CAE) techniques have been applied increasingly with great success in metal forming research, as well as in the cold and hot forming industry. Initially, computer simulation of metal flow and detailed stress analysis of dies were conducted by forging companies that supply the aerospace industry. During the last several years, however, the two-dimensional computer code DEFORM, developed by Battelle Columbus Laboratories, has been fully commercialized. This code is now also used extensively by non-aerospace forgers for the investigation of die fill, defect analysis and prevention, as well as for the prediction of part properties. At the Engineering Research Center for Net Shape Manufacturing (ERC/NSM), deform is one of the available computer-aided tools used in metal forming research and for educational purposes. This paper summarizes some of the industrially relevant research results obtained with deform, including the prediction of flow-induced defects, precision forging of aluminium alloys, investigation of a suck-in type extrusion defect, forging of bevel gears, stress analysis of forging dies, and development of a new test to evaluate lubrication in cold forging.

Analyzing the cold-nosing process using elasto-plastic and rigid-plastic methods

This paper used the rigid-plastic and elasto-plastic finite-element method in conjuction with eight-node and nine-node quadrilateral elements to develop a computer program to simulate cold-nosing processes. In the course of the study, simulation was carried out not only on cold nosing a curve die, with the results compared with available experimental data from Battelle Columbus Laboratories to verify the accuracy of the FEM program, but also on cold nosing using a straight die, analysed by means of the rigid-plastic FEM program to enlarge application of the latter. The results of the cold-nosing simulation were obtained in terms of load-displacement curves, thickness distributions, elongations, strain distributions and die-pressure distributions. According to these findings, the final shape and possible defects of the product can be predicted, thus facilitating better understanding of this type of metal-forming process.

Chemical Industry R&amp;D Spending To Increase Modestly

Most major U.S. chemical and diversified companies plan to increase research and development spending in 1991, but at a slower pace than last year. C&EN's just-completed survey of 14 chemical companies shows that the 10 who did supply figures plan to increase R&D spending this year an average of only 3% over last year. According to the same survey, the 14 companies' most recent accounting estimates show that their R&D spending in 1990 increased an average of 8% over 1989. The 3% increase for 1991 found in this survey agrees closely with Battelle Columbus Laboratories' justreleased estimate of a 3.5% rise for all industry. Battelle bases its forecast on data drawn from National Science Foundation reports, federal budget documents, and other sources. The Columbus, Ohio-based technology organization projects total 1991 R&D spending by all U.S. industry will reach $155 billion, including that financed by government. Battelle notes, however, that the real increase in R&D spending ...

The biological characteristics and chemosensitivity of anaplastic thyroid carcinoma transplanted into nude mice

Three xenografts established from three patients with anaplastic thyroid carcinoma were investigated for their biological characteristics and chemosensitivity. The histological and immunohistochemical findings of these tumors were almost the same as those of the original tumors. Although the growth rate of each xenograft was constant, the tumor doubling time varied from 4.8 per 9.0 days, and the labeling indexes, determined using bromodeoxyuridine pulse labeling, varied from 11.4 to 25.1 per cent. The chemosensitivity tests were performed according to the Battelle Columbus Laboratories Protocol, with adriamycin, cyclophosphamide, cisplatin, mitomycin C and tegafur administered intraperitoneally to tumor-bearing nude mice in maximum tolerable doses. Tumors with slower growth rates tended to be sensitive to more drugs. Furthermore, cyclophosphamide showed antitumor effects against all the tumors tested. Although previous treatments of the original tumors may have affected the results, our results suggest that a more suitable chemotherapy for anaplastic thyroid carcinoma could be developed.

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ヌードマウス可移植性ヒト下顎骨由来骨肉腫累代株における制癌剤感受性試験

An anti-cancer drug sensitivity test was performed using a transplantable human osteosarcoma originated in the mandible (HOSIVIN-1). The drugs tested in this study were Adriamycin (ADM), Cis-platinum (CDDP), and Methotrexate (MTX)(high and low-dose). The effect of the drugs were judged according to the Battelle Columbus Laboratories Protocol (BCLP), and the following results were obtained.1) Growth inhibition was seen with all drugs.2) With respect to the duration of effect and the maximum rate of tumor inhibition, the most effective drug was losv-dose MTX followed by CDDP, high-dose MTX and ADM in that order.3) In the substantial weight change, only low-dose MTX group showed no weight loss. Refering to its low incidence of side effect as well, it was suggested that low-dose MIX was most useful in this experiment.

Resilient Railpads: Their Dynamic Behaviour in the Laboratory and on Track

Resilient railpads in a variety of materials and with different surface profiling have been tested in the laboratory and in track. A laboratory impact test based on that initially developed at the Battelle Columbus Laboratories provides a reliable ranking of the extent to which railpads attenuate dynamic strain in concrete sleepers in track. The test is also a good indication of the average attenuation provided by a pad in track. If dynamic loads in track are particularly severe the fractional attenuation provided by a pad is greater than that indicated by the laboratory impact test. Laboratory resonance apparatus, in which the pad is the principal resilient element in a simple dynamic system, has been made to find the railpad's effective dynamic stiffness. There is good correlation between the stiffness measured in track and that measured in this apparatus. A pad's dynamic stiffness is consistently at least as great as its tangent stiffness found from the static load/deflection curve. The load/deflection behaviour of a pad in track can be found from measurements in an assembly of rail and sleeper in the laboratory.

Genotoxic effects of fly ash in bacteria, mammalian cells and animals.

The increasing use of fossil fuels has raised concerns about possible deleterious health effects of the final combustion product, fly ash. Seven ash samples from coal sources obtained from Battelle Columbus Laboratories were evaluated in the Salmonella/mammalian microsome mutagenicity assay to determine their mutagenic potential. While dimethyl sulfoxide extracts of five samples showed no mutagenicity, sample 102 caused an increase in the number of revertants per plate over controls in TA100 and TA98 with activation by liver homogenate (2-fold and 2.4-fold, respectively), and without (2-fold and 6-fold). This ash was thus evaluated in whole animal studies. Animals treated by inhalation or oral gavage were assayed for the presence of mutagens in the urine, micronuclei in polychromatic erythrocytes, and chromosomal aberrations in metaphase bone marrow cells. Those animals treated by inhalation were also examined for local damage in the lung. The assay for mutagens in the urine was negative as shown by the Ames assay with TA100 and TA98 and there was no increase in micronuclei or in metaphase aberrations. Histological sections from the animals treated by inhalation did not show the presence of particles, macrophage infiltrations and generalized lung damage. We tested the same fly ash with an in vitro cell transformation assay with the cell line Balb/c 3T3 subclone A31-1-13. Although there was not an increase in Type III foci, there was a dose-dependent increase of Type II foci in the treated cells over the controls. In one assay, there was approximately a 14-fold increase in Type II foci in the highest dose (2 mg/ml) compared to the solvent control. One other ash sample induced cell transformation without being markedly cytotoxic, while a third sample was highly toxic but did not induce transformation.

Combustion of pulverized coal using waste carbon dioxide and oxygen

Combustion of pulverized coal in CO 2 O 2 as well as in air atmospheres is studied. Predictions using a one-dimensional computer code were compared with actual experimental data from tests conducted by Battelle Columbus Laboratories. The comparison of predicted and measured data for all test cases show that the observed trends of distributions of temperature and of species concentrations are generally predictable. The study confirms that the combustion of pulverized coal can be completed in a CO 2 O 2 atmosphere over a range of CO 2-to-O 2 mole ratios between 2.23 and 3.65.

Finite element method approach to forging process design

Forging processes in the past have primarily been developed based on empirical relationships or trial and error. The finite element approach to forging process development and design has been found to be practically feasible and economical. The rigid-viscoplastic finite element method (FEM) code “ALPID” developed by Battelle Columbus Laboratories, has been successfully utilized to simulate metal forming processes. In the following paper, the application of finite element simulation to study deformation mechanics in the forging of gear blanks and axle shafts is discussed. An underfill problem on the gear blank was overcome and tool life was improved on the axle shaft hot heading process.

Migration of explosives in soil: analysis of rdx, tnt, and tetryl from a 14c lysimeter study

Abstract This report describes the chemical analysis results of 121 water and 24 soil samples from a 14C lysimeter study of TNT, RDX, and tetryl performed at Battelle Columbus Laboratories. Lysimeters were constructed at Battelle by pressing steel pipes into various soils. The lysimeters were withdrawn to preserve the soil columns intact. 14C ring-labeled munition compounds were than mixed into the surface layer (first 3 inches) of the soils and the lysimeters were irrigated on a regular basis over a six month period. Periodic water samples (leachate) were taken for analysis at selected intervals. The study described here was undertaken (a) to assess the environmental fate of these compounds in various soil samples - since soils within the production areas of U.S. munition plants have become contaminated with raw materials, munition compounds, as well as waste materials, and (b) to determine the persistence and movement of these compounds and their possible decomposition and/or biotransformation products ...

Chemical Industry R&amp;D Spending To Rise Modestly in 1988

The U.S. chemical industry projects only a modest increase in its research and development spending in 1988, according to C&EN's annual survey of large chemical producers. The survey indicates that R&D spending for 11 companies will increase 6% this year, following a similar increase in 1987. (Du Pont, which is usually included in the C&EN survey, declined to estimate 1987 spending or to forecast 1988 expenditures.) The 6% increase in planned R&D expenditures determined by C&EN's survey is only marginally lower than the 6.9% increase in R&D spending for all industry forecast by Battelle Columbus Laboratories for 1988. But the chemical industry's 6% increase means that, adjusted for inflation, chemical R&D spending will be up only 1.5% in 1988. This constant-dollar increase is figured using Battelle's estimate for 1988 R&D inflation of about 4.5%. If Du Pont's 1988 R&D spending increase turns out to be modest, constant-dollar spending could show a marginal decrease. Du Pont ...