The morphology and evolution of bipyramidal gold nanoparticles.

We examine the growth and evolution with time of bipyramidal gold nanoparticles grown by a seed-mediated process. The nanoparticles are characterized both by their physical dimensions determined by transmission electron microscopy and by the wavelength position of their localized surface plasmon resonance. Each growth's physical dimensions correspond to particular initial conditions, and we observe two distinct modes of temporal evolution during growth. The effects of varying silver nitrate concentration and growth time are also explored. We observe a linear relationship between the tip radius of curvature and the wavelength of the longitudinal localized surface plasmon resonance (LSPR) peak. Critical parameters for synthesizing bipyramidal nanoparticles with sharp tips and correct length to width ratio are determined.

Novel growth and properties of GaAs nanowires on Si substrates.

Straight, vertically aligned GaAs nanowires were grown on Si(111) substrates coated with thin GaAs buffer layers. We find that the V/III precursor ratio and growth temperature are crucial factors influencing the morphology and quality of buffer layers. A double layer structure, consisting of a thin initial layer grown at low V/III ratio and low temperature followed by a layer grown at high V/III ratio and high temperature, is crucial for achieving straight, vertically aligned GaAs nanowires on Si(111) substrates. An in situ annealing step at high temperature after buffer layer growth improves the surface and structural properties of the buffer layer, which further improves the morphology of the GaAs nanowire growth. Through such optimizations we show that vertically aligned GaAs nanowires can be fabricated on Si(111) substrates and achieve the same structural and optical properties as GaAs nanowires grown directly on GaAs(111)B substrates.

The effect of V/III ratio and catalyst particle size on the crystal structure and optical properties of InP nanowires.

InP nanowires were grown on 111B InP substrates by metal-organic chemical vapour deposition in the presence of colloidal gold particles as catalysts. Transmission electron microscopy and photoluminescence measurements were carried out to investigate the effects of V/III ratio and nanowire diameter on structural and optical properties. Results show that InP nanowires grow preferably in the wurtzite crystal structure than the zinc blende crystal structure with increasing V/III ratio or decreasing diameter. Additionally, time-resolved photoluminescence (TRPL) studies have revealed that wurtzite nanowires show longer recombination lifetimes of approximately 2500 ps with notably higher quantum efficiencies.

Environmentally superior technologies for swine waste management.

The high nitrogen content of animal waste provides opportunities for processing to marketable byproducts and challenges for proper management to avoid harmful impacts. Technologies are being developed to conserve and utilize nitrogen as well as other valuable constituents in animal waste. Advanced treatment technologies are also being developed for housing/waste management systems that address public concerns and protect soil, water and air quality. Smithfield Foods, Premium Standard Farms and Frontline Farmers have entered into an agreement with North Carolina to develop environmentally superior technologies that meet these goals. The 18 candidate technologies are identified and three with the longest operating period, and thus most data to date are discussed. Methods for distributing this information for implementation of cost-effective technologies through the Curriculum Project and the National Center for Manure and Animal Waste Management will be presented. This work supports priority goals to conserve and utilize valuable animal waste constituents while also protecting against negative impacts.

Quantitative evaluation of the biocompatible and osteogenic properties of a range of biphasic calcium phosphate (BCP) granules using primary cultures of human osteoblasts and monocytes.

A range of 50% porous gamma-sterilized biphasic calcium phosphate (BCP) granules, (20, 50, 80, and 100% tricalcium phosphate, TCP) were classified into two distinct size ranges, small 2-4 mm in diameter and large 4-6 mm in diameter, and their potential as bone graft extender materials was assessed in vitro using culture systems of primary-derived peripheral human blood monocytes and human osteoblasts isolated from bone. The effect of the in vitro culture conditions was evaluated prior to the introduction of the test substrates. The cellular response was assessed via quantification of viable cell adhesion to the materials, lactate dehydrogenase (LDH), the production and release of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). The higher content TCP materials, 80% and 100% TCP, had a detrimental effect on viable cell adhesion after day 1, which was not related to calcium release from the granules within the local environment. TCP granules (20% and 50%) initiated a controlled level of inflammatory response that sustained and promoted viable macrophage adhesion throughout the test period, The percentage of TCP within the BCP granules was a governing factor in determining the cellular response.

Quantitative assessment of the response of primary derived human osteoblasts and macrophages to a range of nanotopography surfaces in a single culture model in vitro.

The effect of nanotopography on a range of Ti oxide surfaces was determined. Flat Ti, 3%, 19%, 30% and 43% topography densities of 110 nm high hemispherical protrusions were cultured in contact with primary derived human macrophages and osteoblasts in single culture models. Prior to introduction of the test substrate the phenotype and optimum conditions for in vitro cell culture were established. The cellular response was investigated and quantified by assessments of cytoskeletal development and orientation, viable cell adhesion, cytokine production and release and RT-PCR analysis of osteogenic markers. The tested nanotopographies did not have a statistically significant effect on viable cell adhesion and subsequent cytoskeletal formation. Surface chemistry was the dominant factor as established via incorporation of a tissue culture polystyrene, TCPS, control. The topography surfaces induced a release of chemotactic macrophage activation agents at 1 day in conjunction with stress fibre formation and a subsequent fibronectin network formation. Osteoblasts migrated away from the topography surfaces to the exposed TCPS within the wells during the 7-day period.

Release and interconversion of P2 receptor agonists by human osteoblast-like cells.

Nucleotides, acting as agonists at P2 receptors, are important extracellular signaling molecules in many tissues. In bone they affect both bone-forming osteoblast and bone-resorbing osteoclast cell activity. The presence of nucleotides in the extracellular microenvironment is largely determined by their release from cells and metabolism by ecto-enzymes, both of which have scarcely been studied in bone. We have investigated adenosine 5'-triphosphate (ATP) release from SaOS-2 osteoblastic cells and the activities of cell surface ecto-enzymes on ATP metabolism. ATP, but not LDH, was detected in SaOS-2 cell conditioned medium, suggesting these cells were actively releasing ATP. Introduction of ADP resulted in increased ATP concentrations in the medium, which was found not to be receptor mediated. Nucleotide inhibition and substrate specificity studies revealed an ecto-nucleoside diphosphokinase (ecto-NDPK) was responsible for the ADP-->ATP conversion; PCR and immunocytochemistry confirmed its presence. Analysis of ATP metabolism over time demonstrated overall ATP degradation was increased by inhibiting ecto-NDPK activity; confirming that the combined action of multiple osteoblast-expressed ecto-enzymes affected extracellular nucleotide concentration. The data establish the coexistence of ATP-consuming, and for the first time, ATP-generating activities on the osteoblast cell surface, the discovery of which has significant implications for studies involving P2 receptor subtypes in bone.

IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis.

The International Programme on Chemical Safety (IPCS) is leading an activity to harmonize approaches to cancer risk assessment as a part of its larger project on the Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals. Through a series of workshops and the evaluation of case studies, a number of key components of risk assessments relating to harmonization were identified: transparency, terminology, weight of evidence, flexibility, and accessibility/communication. A major impediment to harmonization identified in the consideration of weight of evidence was the evaluation of mode of action. To address this need, a conceptual framework was developed, based on the general principles involved in considering the chemical induction of a specific tumor in animals. This is based partly on the Bradford Hill criteria for causality as modified by Faustman et al. (1997) for developmental toxicity. The framework is described in this paper followed by a worked example. It is recognized that the framework addresses only one stage in the overall characterization of hazard to humans of chemical carcinogens. Another important but separate step is the assessment of relevance to humans. This is a priority area for future work in this project.

Analysis of pFQ12, a 22.4-kb Frankia plasmid.

Frankia are gram-positive, filamentous bacteria capable of fixing atmospheric dinitrogen in symbiosis with a wide variety of woody plants and shrubs. Some isolates of Frankia harbor plasmids of 8.5 (pFQ11) and 22.4 kb (pFQ12) that have no known function but are transmitted through many generations in culture. We have sequenced the 22,437-bp pFQ12 plasmid that is present in isolates CpI1 and ArI3. This sequence, with 76% G+C, is almost totally unrelated to that of pFQ11 found in the same cells. However, four regions of identity, 40-90 bp each, are dispersed around the plasmids. The 22.4-kb plasmid has >50 open reading frames (ORFs) that encode putative proteins of more than 100 amino acids, with the largest being 2226 amino acids. Twenty of these ORFs are likely to encode proteins based on their codon bias as determined by two different algorithms. Transcripts from nine of these regions have been identified by reverse transcriptase-polymerase chain reaction (RT-PCR) or filter hybridization. The two Frankia plasmids each encode a protein similar to the korSA protein that regulates transmission of pSAM2 in Streptomyces. The origin of replication (ORI) region of pFQ12 was localized by intrastrand AT and GC equivalence switch. It includes a 40-bp, intergenic, A+T-rich region that has a strong identity in pFQ11.

1,3-Butadiene, isoprene and chloroprene: reviews by the IARC monographs programme, outstanding issues, and research priorities in epidemiology.

1,3-Butadiene, isoprene and chloroprene have all been evaluated more than once by the IARC Monographs Programme on the Evaluation of Carcinogenic Risks to Humans, most recently in February 1998 (Volume 71). Summaries are available on-line at http://monographs.iarc.fr. 1,3-Butadiene is currently classified in Group 2A (probably carcinogenic to humans), on the basis of limited evidence for increased occupational cancer risk in humans plus sufficient evidence of carcinogenicity at multiple organ sites in rats and especially in mice exposed by inhalation. Four epidemiologic studies are available on cancer risk among workers exposed to 1,3-butadiene, one large study among styrene-butadiene rubber (SBR) workers, and one large and two small studies among 1,3-butadiene production workers. The results of the study of SBR workers suggest an association between butadiene exposure and leukaemia risk, which is consistent with the results of the large study of production workers. This latter study also suggested an increased risk of lymphoreticulosarcoma (ICD-8, 200). The major factors hampering the assessment of the available results are (i) possible misclassification of lymphoid and haematopoietic neoplasms, (ii) limitations in the assessment of past exposure (with the exception of the study of SBR workers) and (iii) a potential confounding effect of agents other than butadiene. Future research priorities include (i) the incorporation of newly developed biomarkers of exposure, (ii) the possible application of intermediate biomarkers, (iii) the replication of the study among SBR workers, possibly in Europe, and (iv) reanalysis of existing data in light of revisions of the classifications of leukaemias and lymphomas in the International Classification of Diseases for Oncology, Third Edition (2000). Isoprene is classified in Group 2B (possibly carcinogenic to humans), on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats, especially male mice, exposed by inhalation. No epidemiologic studies are available on cancer risk from occupational exposure to isoprene. Such studies could be conducted within the framework of existing or future studies of SBR workers, assuming that isoprene exposure can be disentangled from butadiene and styrene exposure. Chloroprene is classified in Group 2B on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats exposed by inhalation. Studies of chloroprene exposed workers now include chemical workers from the United States, China and Armenia as well as shoe workers from Russia. The results of the studies from China, Armenia and Russia suggest an excess risk of liver cancer. The risk of other neoplasms was not consistently increased. Limitations of available studies include possible bias from cohort enumeration, follow-up, and choice of reference population. In most studies the exposure assessment was poor, the possible confounding effect of co-exposures was not addressed and the statistical power was low. The pathology of the cases of liver cancer should be reviewed. Future research priorities include a replication of available studies in well-defined populations and the development of biomarkers of exposure.

Analysis of pain behavior profiles and functional disability in outpatient physical therapy clinics.

STUDY DESIGN: Descriptive, ex post facto. OBJECTIVES: To determine the proportion of physical therapy outpatients with pain who exhibit various pain behavior profiles, and to determine whether there are differences in functional disability across the profiles. BACKGROUND: Physical therapists treat many patients who have chronic pain. Research suggests that early identification and multidisciplinary treatment are effective and economical for these patients. The Multidimensional Pain Inventory (MPI) and the Pain Disability Index (PDI) are potential screening tools that could be used in physical therapy clinics to determine which patients should be referred for multidisciplinary treatment. METHODS AND MEASURES: MPI and PDI data were gathered on 57 physical therapy outpatients (mean age 44.3 +/- 14.5 years, 22 men and 35 women) with pain of 3 or more months duration. ANOVA was used to analyze differences in mean PDI scores across the MPI profiles. RESULTS: Of all patients, 42.1% fit the Adaptive Coper profile, 29.8% fit the Interpersonally Distressed profile, and 28.1% fit the Dysfunctional profile. There were significant differences in PDI scores among profile groups. Post hoc analysis showed that the PDI scores of the Adaptive Coper and Interpersonally Distressed groups were different from the Dysfunctional group, but that there was no difference between the Adaptive Coper and Interpersonally Distressed groups. CONCLUSIONS: Many patients in outpatient physical therapy settings exhibit behavioral, affective, and cognitive characteristics associated with chronic pain. Thirty-three patients (57.9%) had MPI profiles (interpersonally distressed and dysfunctional) that suggest they might benefit from multidisciplinary treatment.

A review of the genetic and related effects of 1,3-butadiene in rodents and humans.

In this paper, the metabolism and genetic toxicity of 1,3-butadiene (BD) and its oxidative metabolites in humans and rodents is reviewed with attention to newer data that have been published since the latest evaluation of BD by the International Agency for Research on Cancer (IARC). The oxidative metabolism of BD in mice, rats and humans is compared with emphasis on the major pathways leading to the reactive intermediates 1,2-epoxy-3-butene (EB), 1,2:3, 4-diepoxybutane (DEB), and 3,4-epoxy-1,2-butanediol (EBdiol). Results from recent studies of DNA and hemoglobin adducts indicate that EBdiol may play a more significant role in the toxicity of BD than previously thought. All three metabolites are capable of reacting with macromolecules, such as DNA and hemoglobin, and have been shown to induce a variety of genotoxic effects in mice and rats as well as in human cells in vitro. DEB is clearly the most potent of these genotoxins followed by EB, which in turn is more potent than EBdiol. Studies of mutations in lacI and lacZ mice and of the Hprt mutational spectrum in rodents and humans show that mutations at G:C base pairs are critical events in the mutagenicity of BD. In-depth analyses of the mutational spectra induced by BD and/or its oxidative metabolites should help to clarify which metabolite(s) are associated with specific mutations in each animal species and which mutational events contribute to BD-induced carcinogenicity. While the quantitative relationship between exposure to BD, its genotoxicity, and the induction of cancer in occupationally exposed humans remains to be fully established, there is sufficient data currently available to demonstrate that 1,3-butadiene is a probable human carcinogen.

Species difference in thyroid, kidney and urinary bladder carcinogenesis.

It examines the scientific basis for possible species differences in mechanisms by which thyroid follicular-cell tumours in mice and rats, renal tubule-cell tumours in male rats and urinary bladder tumours in rats may be produced.

The use of short- and medium-term tests for carcinogens and data on genetic effects in carcinogenic hazard evaluation.

It evaluates the use of short- and medium-term assays with end-points of neoplasia or lesions that are precursors to neoplasia, and attempts to define the role of data from genetic toxicology in the prediction of carcinogenic hazard.

Lead as a carcinogen: experimental evidence and mechanisms of action.

Recent epidemiological and experimental work confirms that inorganic lead compounds are associated with increased risks of tumorigenesis. In animals, these risks can be induced at doses that are not associated with organ toxicity and in mice that do not produce alpha-2 urinary globulin in the kidney. Thus the mechanisms of lead carcinogenicity are unlikely to be fully explained as toxicity-related sequelae of high dose exposure or as a rat-specific response involving overexpression of a renal protein. Plausible mechanisms of lead carcinogenicity include direct DNA damage, clastogenicity, or inhibition of DNA synthesis or repair. Lead may also generate reactive oxygen species and cause oxidative damage to DNA. Recent data indicate that lead can substitute for zinc in several proteins that function as transcriptional regulators, including protamines. Lead further reduces the binding of these proteins to recognition elements in genomic DNA, which suggests an epigenetic involvement of lead in altered gene expression. These events may be of particular relevance in transplacental exposures and later cancer.

Genetic and immunohistochemical analyses of p53 independently predict regional metastasis of gastric cancers.

Either p53 gene mutation or immunohistochemical detection of p53 protein has not been consistently shown to have prognostic significance in human cancers, including gastric carcinomas. One hypothesis to explain this inconsistency is that some p53 mutations and p53 protein accumulation are not indicative of tumor progression. To test this hypothesis, we categorized p53 status in 105 gastric carcinomas according to types of mutations, numerical scores of immunohistochemical staining (IHC), or combinations thereof. The p53 status was then correlated with metastasis to liver or peritoneum. Gastric cancers with no p53 mutations were significantly less likely to metastasize than tumors with mutations. Intermediate IHC scores were inversely associated with metastasis. A substantial number of gastric cancers (31 of 105) showed positive p53 immunostaining without detectable mutations (p53-/IHC+), which suggested an accumulation of wild-type p53 protein, and also a significantly lower risk for metastasis. After adjusting for depth of invasion and lymph node involvement, the p53-/IHC+ combination predicted low metastatic risk better than either p53- or IHC+ with intermediate scores. These findings suggest that an accumulation of wild-type p53 protein occurs in gastric cancer cells and represents a stress-response mechanism that lowers metastatic potential.

Evaluation of the carcinogenic risks to humans associated with surgical implants and other foreign bodies - a report of an IARC Monographs Programme Meeting. International Agency for Research on Cancer.

A meeting was held within the International Agency for Research on Cancer (IARC) Programme on the Evaluation of Carcinogenic Risks to Humans of surgical implants and other foreign bodies. This meeting report summarises the types of materials considered, their wear and degradation, their cancer epidemiology in both humans and other animals, the published experimental carcinogenicity data and selected data on their toxic, including genotoxic, effects. Evaluations resulting in a classification of Group 2B (possibly carcinogenic to humans) were reached for: (1) polymeric implants prepared as thin smooth films [with the exception of poly(glycolic acid)]; (2) metallic implants prepared as thin smooth films; and (3) implanted foreign bodies consisting of metallic cobalt, metallic nickel and a particular alloy powder consisting of 66-67% nickel, 13-16% chromium and 7% iron. Group 3 classifications (not classifiable as to their carcinogenicity to humans) were made for: (1) organic polymeric materials as a group; (2) orthopaedic implants of complex composition and cardiac pacemakers; (3) silicone breast implants; (4) dental materials; and (5) ceramic implants.

Tumors of the nervous system in carcinogenic hazard identification.

In the absence of adequate data on humans, it is biologically plausible and prudent to regard agents and mixtures for which there is sufficient evidence of carcinogenicity in experimental animals, usually rats and mice, as if they presented a carcinogenic risk to humans. Prediction of cancer sites in humans from bioassay data in rodents is much less certain, however, regardless of organ or tissue. For tumors of the nervous system, there is practically no basis for judging the validity of such predictions, as only ionizing radiation is known to cause tumors of the central nervous system (CNS) in humans. Brain tumors are relatively uncommon findings in bioassays and are rare in untreated rodents, even in rats, which appear to be the most susceptible species. However, CNS tumors have been readily induced in rodents by systemic exposures to some chemicals, notably N-nitrosoalkylureas and other alkylating agents and certain alkyl hydrazine derivatives. CNS tumors in rodents have played a significant role in carcinogenic hazard evaluations of several other chemicals, including acrylonitrile, ethylene oxide, and acrylamide, and have been implicated as part of the tumor spectrum induced by vinyl chloride and certain inorganic lead compounds. In some of these evaluations, it is not certain that all tumors diagnosed as primary brain tumors were correctly identified. Diagnostic difficulties have been presented by undifferentiated small-cell tumors that may invade the brain, including carcinomas of the nasal cavity and undifferentiated schwannomas arising in cranial nerve ganglia, and by the difficulty of reliably distinguishing between focal reactive gliosis and early glial neoplasms. The most striking experimental finding regarding the induction by chemicals of tumors of the nervous system is the dramatically greater susceptibility of the fetal and neonatal nervous system to some carcinogens, as compared with the susceptibility of the nervous system in adults of the same species.

Activation of neu by missense point mutation in the transmembrane domain in schwannomas induced in C3H/HeNCr mice by transplacental exposure to N-nitrosoethylurea.

Transplacentally initiated schwannomas in mice and rats arise preferentially in the Gasserian ganglion of the trigeminal nerve and spinal root ganglia, while those of the Syrian golden hamster most commonly occur subcutaneously. Rat and hamster schwannomas almost invariably contain a mutationally activated neu oncogene. In rat schwannomas, the mutant allele predominates, while the relative abundance of mutant alleles is very low in hamster nerve tumors. We investigated whether neu is mutated in mouse schwannomas and whether the pattern and allelic ratio of the mutation resemble those for the hamster or the rat. Pregnant C3H/HeNCr mice received 0.4 micromol N-nitrosoethylurea/g body weight on day 19 of gestation. Ten trigeminal and one peripheral nerve schwannomas developed in 11 of the 201 offspring. Missense T --> A transversion mutations were detected in the neu transmembrane domain in eight of ten schwannomas analyzed, as determined by MnlI digestion of polymerase chain reaction products. The mutant allele was predominantly detected in two tumors and was abundant in six others. Transfection of eight out of ten mouse tumor DNAs into hamster cells yielded transformed foci; seven out of eight contained mutant mouse neu. Mouse schwannomas closely resembled those of rats both in the preferred anatomical site and in the mutant/wild-type neu allele ratios.