A quinary WTaCrVHf nanocrystalline refractory high-entropy alloy withholding extreme irradiation environments.

In the quest of new materials that can withstand severe irradiation and mechanical extremes for advanced applications (e.g. fission & fusion reactors, space applications, etc.), design, prediction and control of advanced materials beyond current material designs become paramount. Here, through a combined experimental and simulation methodology, we design a nanocrystalline refractory high entropy alloy (RHEA) system. Compositions assessed under extreme environments and in situ electron-microscopy reveal both high thermal stability and radiation resistance. We observe grain refinement under heavy ion irradiation and resistance to dual-beam irradiation and helium implantation in the form of low defect generation and evolution, as well as no detectable grain growth. The experimental and modeling results-showing a good agreement-can be applied to design and rapidly assess other alloys subjected to extreme environmental conditions.

Towards performing high-resolution inelastic X-ray scattering measurements at hard X-ray free-electron lasers coupled with energetic laser drivers.

High-resolution inelastic X-ray scattering is an established technique in the synchrotron community, used to investigate collective low-frequency responses of materials. When fielded at hard X-ray free-electron lasers (XFELs) and combined with high-intensity laser drivers, it becomes a promising technique for investigating matter at high temperatures and high pressures. This technique gives access to important thermodynamic properties of matter at extreme conditions, such as temperature, material sound speed, and viscosity. The successful realization of this method requires the acquisition of many identical laser-pump/X-ray-probe shots, allowing the collection of a sufficient number of photons necessary to perform quantitative analyses. Here, a 2.5-fold improvement in the energy resolution of the instrument relative to previous works at the Matter in Extreme Conditions (MEC) endstation, Linac Coherent Light Source (LCLS), and the High Energy Density (HED) instrument, European XFEL, is presented. Some aspects of the experimental design that are essential for improving the number of photons detected in each X-ray shot, making such measurements feasible, are discussed. A careful choice of the energy resolution, the X-ray beam mode provided by the XFEL, and the position of the analysers used in such experiments can provide a more than ten-fold improvement in the photometrics. The discussion is supported by experimental data on 10 µm-thick iron and 50 nm-thick gold samples collected at the MEC endstation at the LCLS, and by complementary ray-tracing simulations coupled with thermal diffuse scattering calculations.

Outstanding radiation resistance of tungsten-based high-entropy alloys.

A body-centered cubic W-based refractory high entropy alloy with outstanding radiation resistance has been developed. The alloy was grown as thin films showing a bimodal grain size distribution in the nanocrystalline and ultrafine regimes and a unique 4-nm lamella-like structure revealed by atom probe tomography (APT). Transmission electron microscopy (TEM) and x-ray diffraction show certain black spots appearing after thermal annealing at elevated temperatures. TEM and APT analysis correlated the black spots with second-phase particles rich in Cr and V. No sign of irradiation-created dislocation loops, even after 8 dpa, was observed. Furthermore, nanomechanical testing shows a large hardness of 14 GPa in the as-deposited samples, with near negligible irradiation hardening. Theoretical modeling combining ab initio and Monte Carlo techniques predicts the formation of Cr- and V-rich second-phase particles and points at equal mobilities of point defects as the origin of the exceptional radiation tolerance.

Heterogeneous to homogeneous melting transition visualized with ultrafast electron diffraction.

The ultrafast laser excitation of matters leads to nonequilibrium states with complex solid-liquid phase-transition dynamics. We used electron diffraction at mega-electron volt energies to visualize the ultrafast melting of gold on the atomic scale length. For energy densities approaching the irreversible melting regime, we first observed heterogeneous melting on time scales of 100 to 1000 picoseconds, transitioning to homogeneous melting that occurs catastrophically within 10 to 20 picoseconds at higher energy densities. We showed evidence for the heterogeneous coexistence of solid and liquid. We determined the ion and electron temperature evolution and found superheated conditions. Our results constrain the electron-ion coupling rate, determine the Debye temperature, and reveal the melting sensitivity to nucleation seeds.

Cr incorporated phase transformation in Y2O3 under ion irradiation.

Under irradiation, chemical species can redistribute in ways not expected from equilibrium behavior. In oxide-dispersed ferritic alloys, the phenomenon of irradiation-induced Cr redistribution at the metal/oxide interfaces has drawn recent attention. Here, the thermal and irradiation stability of the FeCr/Y2O3 interface has been systematically studied. Trilayer thin films of 90 nm Fe - 20 at.% Cr (1st layer)/100 nm Y2O3 (2nd layer)/135 nm Fe - 20 at.% Cr (3rd layer) were deposited on MgO substrates at 500 °C. After irradiation, Cr diffuses towards and enriches the FeCr/Y2O3 interface. Further, correlated with Cr redistributed into the oxide, an amorphous layer is generated at the interface. In the Y2O3 layer, the original cubic phase is observed to transform to the monoclinic phase after irradiation. Meanwhile, nanosized voids, with relatively larger size at interfaces, are also observed in the oxide layer. First-principles calculations reveal that Cr substitution of Y interstitials in Y2O3 containing excess Y interstitials is favored and the irradiation-induced monoclinic phase enhances this process. Our findings provide new insights that may aid in the development of irradiation resistant oxide-dispersed ferritic alloys.

What determines the interfacial configuration of Nb/Al2O3 and Nb/MgO interface.

Nb films are deposited on single crystal Al2O3 (110) and MgO(111) substrates by e-beam evaporation technique. Structure of Nb films and orientation relationships (ORs) of Nb/Al2O3 and Nb/MgO interface are studied and compared by the combination of experiments and simulations. The experiments show that the Nb films obtain strong (110) texture, and the Nb film on Al2O3(110) substrate shows a higher crystalline quality than that on MgO(111) substrate. First principle calculations show that both the lattice mismatch and the strength of interface bonding play major roles in determining the crystalline perfection of Nb films and ORs between Nb films and single crystal ceramic substrates. The fundamental mechanisms for forming the interfacial configuration in terms of the lattice mismatch and the strength of interface bonding are discussed.

Evaluating the solid electrolyte interphase formed on silicon electrodes: a comparison of ex situ X-ray photoelectron spectroscopy and in situ neutron reflectometry.

This work details the in situ characterization of the interface between a silicon electrode and an electrolyte using a linear fluorinated solvent molecule, 0.1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in deuterated dimethyl perfluoroglutarate (d6-PF5M2) (1.87 × 10(-2) mS cm(-1)). The solid electrolyte interphase (SEI) composition and thickness determined via in situ neutron reflectometry (NR) and ex situ X-ray photoelectron spectroscopy (XPS) were compared. The data show that SEI expansion and contraction (breathing) during electrochemical cycling were observed via both techniques; however, ex situ XPS suggests that the SEI thickness increases during Si lithiation and decreases during delithiation, while in situ NR suggests the opposite. The most likely cause of this discrepancy is the selective removal of SEI components (top 20 nm of the SEI) during the electrode rinse process, which is required to remove the electrolyte residue prior to ex situ analysis, demonstrating the necessity of performing SEI characterization in situ.

Inhalation developmental toxicity and reproduction studies with cyclohexane.

The reproductive and developmental toxicity of cyclohexane was assessed in a two-generation reproduction study with Crl:CD BR rats and in developmental toxicity studies with Crl:CD BR rats and Hra:(NZW)SPF rabbits. The animals were exposed whole-body to atmospheric concentrations of 0, 500, 2000, or 7000 ppm cyclohexane. In the two-generation reproduction study, parental effects included statistically significantly lower mean body weight, overall mean body weight gain, and overall mean food efficiency for P1 and F1 females of the 7000 ppm level and statistically significantly lower mean body weight for F1 males of that level. Adult rats exposed to 2000 ppm cyclohexane and above exhibited a transient diminished or absent response to a sound stimulus while in the chambers during exposure. Mean pup weight was statistically significantly lower than control from lactation day 7 throughout the remainder of the 25-day lactation period for both F1 and F2 7000 ppm litters. Changes observed at 500 ppm were either considered not to be compound related or not adverse. Therefore, the systemic-toxicity no-observed-effect level (NOEL) was 500 ppm and the reproductive NOEL was 2000 ppm. The reproductive NOEL was based solely on the decreased pup weights in both the F1 and F2 generations observed at 7000 ppm. In the developmental toxicity studies, only the rats showed evidence of maternal toxicity. For rats in the 7000 ppm group, statistically significant reductions were observed in overall maternal body weight gain and overall maternal food consumption for the treatment period. Rats exposed to 2000 ppm cyclohexane and above again exhibited a transient diminished or absent response to a sound stimulus while in the chambers during exposure. Therefore, for rats, the maternal no-observed-effect level (NOEL) was 500 ppm. In the rabbit developmental toxicity study, no compound-related maternal effects were observed at concentration levels of 7000 ppm and below. Therefore, the maternal NOEL for rabbits was 7000 ppm. No compound-related evidence of developmental toxicity was observed at any test concentration in either species. Therefore, the developmental NOEL for both species was 7000 ppm, the highest concentration tested.

Subchronic toxicity of 4-vinylcyclohexene in rats and mice by inhalation exposure.

This study was conducted to evaluate the subchronic toxicity of 4-vinylcyclohexene (VCH). Male and female Sprague-Dawley rats and B6C3F1 mice were exposed by inhalation to VCH 6 hr/day, 5 days/week for 13 weeks. Rats were exposed to 0, 250, 1000, or 1500 ppm, and mice were exposed to 0, 50, 250, or 1000 ppm. In addition, another group of rats and mice was exposed to 1000 ppm butadiene so that a comparison could be made between the two compounds. Exposure to 1000 ppm VCH resulted in deaths of all male mice and 5/10 female mice on Test Days 11 or 12. Three additional female mice exposed to 1000 ppm VCH died prior to study completion. The most notable compound-related clinical sign was lethargy observed in the 1500 ppm VCH-exposed rats and 1000 ppm VCH-exposed mice. Male rats exposed to 1500 ppm VCH had significantly lower body weights compared to controls, and male and female rats in the 1500 ppm group had significantly lower body weight gains. None of the VCH-exposed animals or butadiene-exposed rats showed any compound-related hematological effects. However, mice exposed to 1000 ppm butadiene exhibited mild macrocytic anemia. Clinical chemistry evaluation and urinalysis showed no compound-related effects in rats exposed to either VCH or butadiene. Male and female rats exposed to 1000 or 1500 ppm VCH or 1000 ppm butadiene had increased absolute and/or relative liver weights, and male rats in these same exposure groups had increased relative kidney weights. Microscopically, increased accumulation of hyaline droplets was observed in the kidneys of male rats from all VCH exposure groups. Although compound-related, the droplets were not accompanied by cytotoxicity. In mice, the most notable adverse histopathological effect was ovarian atrophy in females exposed to 1000 ppm VCH or 1000 ppm butadiene. The atrophy was slightly more severe in the VCH-exposed females than in the butadiene-exposed females. There were no other compound-related pathological effects in male or female mice exposed to VCH. Additionally, butadiene-exposed male mice had decreased testicular weights, accompanied by slight testicular degeneration and atrophy. For VCH exposure, the no-observed-adverse-effect-level is 1000 ppm for rats based on lethargy and lowered body weights and 250 ppm for mice based on mortality and ovarian atrophy.

Quality assurance and quality control in toxicology: how might these concepts apply to epidemiology?

Quality assurance and its distinction from quality control are defined in operational terms. The historical development of standards for scientific research supporting commercialization of materials leading to the current Good Laboratory Practice (GLP) standards is briefly outlined. The application of GLPs to toxicology studies and experience in the use of these standards over a broad range of activities is also presented. This background information provides a common starting point for consideration of the development and application of similar standards for epidemiological studies.

Quality assurance for epidemiologic studies.

Quality assurance (QA) has been successfully applied to scientific disciplines such as toxicology. Experience gained in the application of QA and quality control (QC) through a formal program of compliance with Good Laboratory Practice (GLPs) regulations has been beneficial in toxicology and can be used to develop and implement a similar program in epidemiology. We focus here on the specific ways in which GLP-mandated quality assurance can be adapted and used in epidemiology and on the consequent benefits of this effort.

Issues in data sharing and access: an industry perspective.

Epidemiologic data sharing and access, and information sharing and access, are complex issues with no consensus within the industrial community. The purpose of this paper is to provide an introduction, as well as some personal perspectives, to the issues of data access and sharing. These perspectives include a discussion of types of data sharing, advantages and barriers to openness, and alternatives that lower the need for sharing of the raw data.

Tumor-promoting activity of ethyl phenylpropiolate.

The ability of the hyperplasiogenic irritant ethyl phenylpropiolate (EPP) to act as a tumor promoter in two-stage carcinogenesis and to stimulate cellular events commonly cited as markers of tumor promoter action was evaluated. Treatment of adult, inbred SENCAR (SSIN) mice, initiated with 7,12-dimethylbenz(a)anthracene, with 5 mg of EPP twice weekly resulted in 100% of the mice developing tumors (4.8 tumors/mouse) after 40 weeks of promotion. Treatment with 3 mg EPP (twice weekly) resulted in 52% of the mice developing tumors (0.9 tumor/mouse). This treatment regimen with EPP produces a sustained epidermal hyperplasia without being overtly toxic. In addition, a 5-mg dose of EPP induced ornithine decarboxylase activity to a level comparable to that induced by the tumor promoter phorbol 12-myristate 13-acetate (PMA): 2.3 nmol CO2/mg protein/h for EPP versus 4.5 nmol CO2/mg protein/h for PMA versus 0.04 nmol CO2/mg protein/h for acetone control. Likewise, the time course of ornithine decarboxylase induction by EPP was the same as that seen with PMA (maximum induction at approximately 6 h). Vascular permeability of the dorsal skin increased significantly in response to EPP (8 times that seen in acetone controls) and exhibited the same kinetics as that seen after exposure to PMA. Activity of protein kinase C (PKC), the cellular receptor for PMA, decreased by 75 to 95% 48 h after treatment with PMA. In contrast, EPP treatment resulted in less than a 20% decrease in PKC activity 48 h after treatment. This slight decrease in PKC activity is thought to be an indirect effect caused by the hyperproliferative and inflammatory reactions, because EPP was found to be inactive as an in vitro activator of PKC. These results indicate not only that EPP is a good tumor promoter that causes morphological and biochemical responses similar to those induced by PMA, but also that the action of EPP is apparently mediated via a mechanism that does not involve direct interaction with PKC.

Arachidonic acid metabolism varies with the state of differentiation in density gradient-separated mouse epidermal cells.

Epidermal cells were isolated from adult inbred SENCAR (SSIN) mice and separated by density-gradient centrifugation. The cells were pooled into three fractions shown by previous work to differ in their state of differentiation and proliferative potential. The three fractions were examined for their capacity to metabolize exogenous 14C-arachidonic acid (AA) into prostaglandins (PG) and hydroxyeicosatetraenoic acids (HETE). Cells found in the upper two fractions, which are less dense, have less proliferative potential in vitro, and are more differentiated than cells in the lower more dense fraction, are much more active in producing PG from exogenous AA than are the more dense cells. This was observed in intact cells as well as cells disrupted by freeze-thawing following density separation. The same relationship was found for HETE production in that cytoplasmic preparations from the two fractions containing the less dense cells were much more active in the production of HETE than cytoplasmic preparations from the more dense fraction. The two upper fractions differed little from each other in the production of PG or HETE. These results indicate the presence of higher levels of active cyclooxygenase and lipoxygenases in fractions containing the less dense, more differentiated cells than in the fraction containing the more dense, less differentiated cells which are highly enriched for basal keratinocytes.

Correlation of phorbol ester promotion in the resistant C57BL/6J mouse with sustained hyperplasia but not ornithine decarboxylase or protein kinase C.

The activation of protein kinase C, induction of ornithine decarboxylase (ODC), and hyperplasia have been suggested to be linked, sequential processes resulting from phorbol ester application to mouse skin. However, evidence is presented indicating that these events are not necessarily linked or dependent on one another and that significant differences exist in these responses between phorbol ester promotion sensitive (SSIN) and resistant (C57BL/6J) mice. The epidermis from SSIN mice treated with a single application of 12-O-tetradecanoylphorbol-13-acetate (TPA) displayed a large induction of ODC and a subsequent extensive hyperplasia. A second TPA treatment at 24 or 48 h after the first did not result in ODC induction (refractory state), and protein kinase C was shown to be down-regulated at these times. By 72 h, however, a responsive state had returned even through protein kinase C remained down-regulated. The epidermis of C57BL/6J responds to a single application of TPA with a level of ODC induction similar to that of the SSIN mice. Protein kinase C was down-regulated by approximately 75% after 24 h and was virtually completely down-regulated at 48 and 72 h (95-97%). In contrast to the above findings for the sensitive mice, however, little, if any, hyperplasia was produced. In addition, while a second TPA treatment at 24 h did not result in ODC induction (refractory state), hyperplasia did occur within 24 to 48 h. When the second TPA application was given 48 h after the first, at a time when protein kinase C was down-regulated, an overinduction of ODC occurred, as well as subsequent hyperplasia. Furthermore, a significant number of papillomas resulted when these increased treatment frequencies, i.e., once a day or every other day, were used to promote dimethylbenz(a)anthracene-initiated C57BL/6J mice. It is concluded that, while hyperplasia remains an apparent requirement for tumor promotion, the ODC induction following an initial TPA treatment is insufficient for or not causally related to this hyperplasia. In addition, subsequent ODC induction, at least in the C57BL/6J mouse, is probably not mediated by protein kinase C.

The antioxidant effects of copper sulphate on the actions of a phorbol ester and a xanthine-xanthine oxidase superoxide-anion generating system in murine epidermal cells.

Aqueous solutions of CuSO(4) were shown to inhibit cytochrome c reduction by xanthine-xanthine oxidase. Such copper solutions also significantly inhibited oxidant production, induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), measured as chemiluminescence, in murine epidermal cells in vitro. At the non-toxic level of 250 mum, CuSO(4) inhibited by 40% the induction of ornithine decarboxylase by TPA in murine epidermal cultures. The superoxide generating system xanthine-xanthine oxidase was shown to induce ornithine decarboxylase by two- to threefold; such induction was partially inhibited by CuSO(4). Superoxide dismutase slightly inhibited TPA-induced, but not basal DNA synthesis in cultured epidermal cells. For unknown reasons, DNA synthesis was enhanced by CuSO(4) alone and was further enhanced in the presence of TPA. It appears that oxidants generated in response to TPA partially mediate the induction of ornithine decarboxylase and to a lesser extent DNA synthesis.

Mediation of phorbol ester-induced oxidant generation in murine epidermal cells by protein kinase C.

Murine epidermal cells have previously been shown to produce an oxidant response to the mouse skin tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA); however, the cellular source of these oxidants has not been well characterized. The demonstration that phospholipase C also elicits this oxidant response suggests that protein kinase C is the common mediator. In order to pursue this hypothesis, studies using protein kinase C inhibitors were carried out; both the induced oxidant response and the induction of ornithine decarboxylase (ODC), a known protein kinase C mediated event, were studied. At 100 µm-palmitoylcarnitine inhibited TPA-induced ODC by 50% and phospholipase C-induced ODC by 95%. At the same dose level, the negative analogue acetylcarnitine had no inhibitory effect on ODC with either inducer. The protein kinase C inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride (H-7) and its negative analogue N-(2-guanidinoethyl)-5-isoquinolinesulphonamide hydrochloride (HA-1004) were also used. At 100 µm, H-7 completely inhibited both TPA and phospholipase C-induced ODC; at the same dose HA-1004 had no effect. When these agents were included in the chemiluminescence assay for oxidant generation, similar results were seen: at 100 µm-palmitoylcarnitine and H-7, but not acetylcarnitine or HA-1004, suppressed the response by nearly 100%. These results suggest that the oxidant response to TPA in epidermal cells is mediated at least in part by protein kinase C.

Data audit as a management tool.

Management faces the three basic challenges of achieving cost efficiency, successfully applying new technology, and minimizing risk. This paper examines the ways in which data audits can help managers come to terms with each of these challenges. It emphasizes the role of data audits in providing reliable information on which to base decisions and stresses the importance of auditing data in process rather than retrospectively. The paper examines frequently encountered sources of error and discusses the ways audits benefit management by assuring the integrity of experimental design, by preventing misassignment of observations, and by preventing the loss of data.