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Chimeric antigen receptor (CAR) T cell therapy mediates unprecedented benefit in certain leukemias and lymphomas, but has yet to achieve similar success in combating solid tumors. A substantial body of work indicates that the accumulation of adenosine in the solid tumor microenvironment (TME) plays a crucial role in abrogating immunotherapies. Adenosine deaminase 1 (ADA) catabolizes adenosine into inosine and is indispensable for a functional immune system. We have, for the first time, engineered CAR T cells to overexpress ADA. To potentially improve the pharmacokinetic profile of ADA, we have modified the overexpressed ADA in two ways, through the incorporation of a (1) albumin-binding domain or (2) collagen-binding domain. ADA and modified ADA were successfully expressed by CAR T cells and augmented CAR T cell exhaustion resistance. In a preclinical engineered ovarian carcinoma xenograft model, ADA and collagen-binding ADA overexpression significantly enhanced CAR T cell expansion, tumor tissue infiltration, tumor growth control, and overall survival, whereas albumin-binding ADA overexpression did not. Furthermore, in a syngeneic colon cancer solid tumor model, the overexpression of mouse ADA by cancer cells significantly reduced tumor burden and remodeled the TME to favor antitumor immunity. The overexpression of ADA for enhanced cell therapy is a safe, straightforward, reproducible genetic modification that can be utilized in current CAR T cell constructs to result in an armored CAR T product with superior therapeutic potential.

Despite the remarkable success of chimeric antigen receptor-modified T (CAR-T) cell therapy for blood malignancies, the clinical efficacy of this novel therapy in solid tumor treatment is largely limited by the immunosuppressive tumor microenvironment (TME). For instance, immune checkpoints (e.g., programmed cell death protein 1 [PD-1]/programmed death ligand 1 [PD-L1]) in TME play an important role in inhibiting T cell proliferation and functions. Transforming growth factor β (TGF)-β secreted by cancer cells in TME induces regulatory T cells (Tregs) and inhibits cytotoxic T cells. To overcome the inhibitory effect of immune checkpoints, we have previously engineered CAR-T cells to secrete anti-PD-1 to block the PD-1/PD-L1 pathway activity, a step demonstrating superior antitumor efficacy compared with conventional CAR-T cells. In this study, we engineered CAR-T cells that secrete bispecific trap protein co-targeting PD-1 and TGF-β, with the aim of further improving antitumor immunity. Compared with conventional CAR-T cells and anti-PD-1-secreting CAR-T cells, data from in vitro and in vivo experiments showed that CAR-T cells with trap protein secretion further attenuated inhibitory T cell signaling, enhanced T cell persistence and expansion, and improved effector function and resistance to exhaustion. In the xenograft mouse model, CAR-T cells with trap protein secretion exhibited significantly enhanced antitumor immunity and efficacy. With these observations, we demonstrate the potential of trap protein self-secreting CAR-T cells as a potent therapy for solid tumors., Graphical abstract, CAR-T cells, engineered to secrete bispecific trap protein co-targeting PD-1 and TGF-β, can attenuate inhibitory T cell signaling, enhance T cell persistence and expansion, and improve effector function and resistance to exhaustion. In vivo studies confirm that such engineered CAR-T cells display significantly enhanced antitumor immunity and efficacy.

The exciton band dispersion in π-stacks of conjugated organic chromophores is a critical factor in determining the photophysical response and transport properties. In such stacks, the exciton band ...

Matrix metalloproteinase-12 (MMP-12), also known as macrophage elastase, is a potent inflammatory mediator and therefore an important pharmacological target. Clinical trial failures of broad-spectrum compound MMP inhibitors suggested that specificity is the key for a successful therapy. To provide the required selectivity, monoclonal antibody (mAb)-based inhibitors are on the rise. However, poor production of active recombinant human MMP-12 catalytic domain (cdMMP-12) presented a technical hurdle for its inhibitory mAb development. We hypothesized that this problem could be solved by designing an expression-optimized cdMMP-12 mutant without structural disruptions at its reaction cleft and surrounding area, and thus isolated active-site inhibitory mAbs could maintain their binding and inhibition functions toward wild-type MMP-12. We combined three advances in the field—PROSS algorithm for cdMMP-12 mutant design, convex paratope antibody library construction, and functional selection for inhibitory mAbs. As a result, isolated Fab inhibitors showed nanomolar affinity and potency toward cdMMP-12 with high selectivity and high proteolytic stability. Particularly, Fab LH11 targeted the reaction cleft of wild-type cdMMP-12 with 75 nM binding K(D) and 23 nM inhibition IC(50). We expect that our methods can promote the development of mAbs inhibiting important proteases, many of which are recalcitrant to functional production.

We demonstrate the synthesis of the first anionic aluminum metal-organic framework (MOFs) constructed from tetrahedral AlO4 sites. Al-Td-MOF-1 was obtained in a simple two-step synthesis by condensation of 1,4-dihydroxybenzene and lithium aluminum hydride into an amorphous aluminate framework before applying a solvothermal treatment under basic conditions to obtain the crystalline Al-Td-MOF-1 with a chemical composition of Li[Al(C6 H4 O2 )2 ]. The overall Al-Td-MOF-1 structure consists of one-dimensional chains of alternating edge-sharing AlO4 and LiO4 tetrahedral sites describing unidirectional pore channels with a square window aperture of ≈5×5 A2 , best described topologically as a uninodal 6-coordinated snp rod net. Al-Td-MOF-1 features the highest Li+ loading reported to date for a MOF (2.50 wt %) and proved to be an effective single-ion solid electrolyte. An ionic conductivity of 5.7×10-5 S cm-1 was measured for Al-Td-MOF-1 and the beneficial contribution of crystallinity was evidenced by an 8-fold increase in conductivity between the disordered and crystalline material.

BackgroundChimeric antigen receptor (CAR) T cell therapy has transformed the treatment of hematological malignancies but has yet to achieve similar success in solid tumors due to a lack of persistence and function in the tumor microenvironment. We previously reported the augmentation CAR T cell therapy in an engineered solid tumor model through the secretion of anti-PD-1 scFv, as shown by enhanced CAR T cell antitumor efficacy, expansion, and vitality.1 We have since matured the platform to create a superior cellular product – CAR T cells secreting single-chain trimeric 4-1BB ligand crosslinked to anti-PD-1 scFv (αPD1-41BBL). 4-1BB signaling promotes cytotoxic T lymphocytes proliferation and survival but targeting 4-1BB with agonist antibodies in the clinic has been hindered by low antitumor activity and high toxicity. CAR T cells using 4-1BB endodomain for costimulatory signals have demonstrated milder anti-tumor response and longer persistence compared to CAR T cells costimulated by CD28 endodomain. We have, for the first time, engineered CAR T cells to secrete a fusion protein containing the soluble trimeric 4-1BB ligand.MethodsWe hypothesized that crosslinking the current anti-PD-1 scFv with 4-1BB ligand would provide additional benefits to CAR T cells and is potentially of translational value in the management of tumors resistant to PD-1 blockade due to lack of T cell function. Therefore, we engineered CAR T cells to secrete a novel immunomodulatory fusion protein consisting of anti-PD-1 scFv crosslinked to a single-chain format of trimeric 4-1BB ligand, in which three extracellular domain units of 41BBL are connected with polypeptide linkers. The CAR T cells were then characterized in vitro and subcutaneous tumor models.ResultsIn vitro and in vivo, CAR19.αPD1-41BBL T cells exhibited reduced inhibitory receptor upregulation, enhanced persistence and proliferation, and a less differentiated memory status compared to CAR T cells without additional 4-1BB:4-1BBL costimulation. Accordingly, CAR19.αPD1-41BBL T cell-treated mice displayed significantly improved tumor growth control and overall survival. Spurred on by our preclinical success targeting CD19 as a model antigen, we produced mesothelin-targeting CAR T cells and confirmed the enhanced solid tumor efficacy and persistence of αPD1-41BBL secreting CAR T cells.ConclusionsGiven the significantly better therapeutic efficacy of αPD1-41BBL expressing T cells over αPD1 expressing T cells, we believe that it is of high translational value to adopt secretion of αPD1-41BBL fusion protein to improve CAR T cell solid tumor efficacy, especially given the large number of patients that are PD1/PD-L1 therapy resistant.ReferencesLi S, Siriwon N, Zhang X, Yang S, Jin T, He F, et al. Enhanced cancer immunotherapy by chimeric antigen receptor–modified T cells engineered to secrete checkpoint inhibitors. Clin Cancer Res 2017;23(22):6982–92.

Summary Ionogels have recently attracted attention as pseudo-solid-state electrolytes based on their ability to confine an ionic liquid electrolyte within the mesoporous network of a sol-gel-derived inorganic matrix. Herein we report on the development of two important capabilities for ionogels. In one case, we incorporated spin-coated, 600-nm Li + -conducting ionogel films in electrochemical cells of LiFePO 4 /ionogel/Li. A key feature in this work is the ability to have the sol thoroughly penetrate the LiFePO 4 electrode prior to gelation. Devices operating at C/2 achieved capacities of 125 mAh/g for some 150 cycles with minimal capacity loss. In the second case, we developed a UV crosslinking synthesis method and demonstrated photo-patterning of the ionogel. The realization of a photo-patterned pseudo-solid-state electrolyte increases the versatility of ionogels and potentially enables new fabrication routes for electrochemical device architectures.

Metal phosphate compounds are considered promising candidates as positive electrode materials for Na-ion batteries because they offer higher cation-insertion potentials than analogous metal oxides. One such example is sodium iron fluorophosphate (Na2FePO4F), a compound that is typically synthesized by high-temperature solid-state routes. In this study, we prepare phase-pure Na2FePO4F using the polyol route, a low-temperature process that allows for the synthesis of nanoparticles (15–25 nm), a form that enhances Na-ion insertion kinetics and cycling stability. We then apply two methods to enhance the electronic conductivity of Na2FePO4F: (i) converting residual organic byproducts of the polyol synthesis to conductive carbon coatings; and (ii) preparing a nanocomposite with reduced graphene oxide. The resulting electrode materials are characterized in nonaqueous Na-ion electrolytes, assessing such metrics as specific capacity, rate capability, and cycling stability. A thorough electrochemical kinetics analysis is performed to deconvolve surface-vs.-bulk Na-ion insertion as a function of composite structure. Specific capacities between 60–110 mA h g−1 were achieved in galvanostatic charge–discharge tests when cycling in the range from 10C to C/10, respectively.

Background & Aim BACKGROUND: Processing and delivering cell and gene therapy products is of vital importance to patients and has presented numerous challenges. Rotea's counterflow centrifugation technology enables cell separation, washing, and concentration of many cell types and can be easily programmed to serve many additional workflows. The single use kit and instrument are able to capture and sustain billions of cells in a stable, fluidized bed with flexible inputs and output volumes as low as 5 mL. AIM We set out to evaluate Rotea's ability to isolate PBMCs from leukopaks, and wash and concentrate T cells, two common and vital processes in cell therapy workflows. We also investigated the input and output capabilities of the instrument. Methods, Results & Conclusion METHODS: Protocols were written using the Rotea Protocol Builder. Results from Rotea were compared to density gradient separation for PBMC isolations. T Cells for wash and concentrate protocols were expanded for 12 days in complete Optimizer media with Glutamax, L-Gluamine, HSA (Human Serum Albumin) and Il2. Before and after processing with Rotea, cells were counted and phenotyped using flow cytometry to determine the recovery and change in viability and marker expression. RESULTS Rotea performed consistent lymphocyte separation from leukapheresis products with greater than 80% recovery. Similar to manual isolation methods, cells isolated and cryopreserved using Rotea exhibit high viability and robust expansion in culture for over 14 days. Processed cells also maintain similar percentages of helper T Cells, cytotoxic T Cells and exhausted cells before and after processing. For T Cell wash and concentrate protocols, recovery was consistently above 90% and viability was virtually unchanged after processing. The distribution of CD4 and CD8 cells was also relatively unchanged. As many as 5 billion T cells were captured in a fluidized cell bed and outputs as low as 5 mL were performed without a decrease in cell recovery. CONCLUSION Rotea is a flexible, efficient system that can isolate cells and perform wash and concentrate protocols with high recovery of cells and maintenance of viability. Cells that undergo Rotea processing maintain their phenotype and readily expand in culture. Rotea has the ability to support multiple cell therapy workflows and the scalability to take a therapy from process development to manufacturing.

Magnesium (Mg) and its alloys have shown attractive biocompatibility and mechanical strength for medical applications, but low corrosion resistance of Mg in physiological environment limits its broad clinical translation. Hydroxyapatite (HA) nanoparticles (nHA) are promising coating materials for decreasing degradation rates and prolonging mechanical strength of Mg-based implants while enhancing bone healing due to their osteoconductivity and osteoinductivity. Conformal HA coatings with nano-to-submicron structures, namely nHA and mHA coatings, were deposited successfully on Mg plates and rods using a transonic particle acceleration (TPA) process under two different conditions, characterized, and investigated for their effects on Mg degradation in vitro. The nHA and mHA coatings enhanced corrosion resistance of Mg and retained 86–90% of ultimate compressive strength after in vitro immersion in rSBF for 6 weeks, much greater than non-coated Mg that only retained 66% of strength. Mg-based rods with or without coatings showed slower degradation than the respective Mg-based plates in rSBF after 6 weeks, likely because of the greater surface-to-volume ratio of Mg plates than Mg rods. This indicates that Mg-based plate and screw devices may undergo different degradation even when they have the same coatings and are implanted at the same or similar anatomical locations. Therefore, in addition to locations of implantation, the geometry, dimension, surface area, volume, and mass of Mg-based implants and devices should be carefully considered in their design and processing to ensure that they not only provide adequate structural and mechanical stability for bone fixation, but also support the functions of bone cells, as clinically required for craniomaxillofacial (CMF) and orthopedic implants. When the nHA and mHA coated Mg and non-coated Mg plates were cultured with bone marrow derived mesenchymal stem cells (BMSCs) using the in vitro direct culture method, greater cell adhesion densities were observed under indirect contact conditions than that under direct contact conditions for the nHA and mHA coated Mg. In comparison with non-coated Mg, the nHA and mHA coated Mg reduced BMSC adhesion densities directly on the surface, but increased the average BMSC adhesion densities under indirect contact. Further long-term studies in vitro and in vivo are necessary to elucidate the effects of nHA and mHA coatings on cell functions and tissue healing.

Influenza is a highly contagious respiratory disease that causes high global morbidity and mortality each year. The dynamics of an influenza infection on the host metabolism, and how metabolism is altered in response to neuraminidase inhibitor drug therapy, is still in its infancy but of great importance. We aim to investigate the suitability of ferret nasal wash samples for metabolomics-based analysis and characterization of influenza infections and oseltamivir treatment. Virological and metabolic analyses were performed on nasal wash samples collected from ferrets treated with oseltamivir or a placebo. Untargeted metabolomics was performed using a gas chromatography coupled with mass spectrometery (GC-MS) based protocol that comprised a retention time (RT) locked method and the use of a commercial metabolomics library. Ferret activity was reduced at 2–3 days post infection, which coincided with the highest influenza viral titre. The metabolomics data indicated a shift in metabolism during various stages of infection. The neuraminidase inhibitor oseltamivir created considerable downregulation of energy center metabolites (glucose, sucrose, glycine and glutamine), which generated high levels of branched amino acids. This further increased branched amino acid degradation and deregulation via glycerate-type intermediates and biosynthesis of fatty acids in oseltamivir-treated animals where abrogated weight loss was observed. Metabolomics was used to profile influenza infection and antiviral drug treatment in ferrets. This has the potential to provide indicators for the early diagnosis of influenza infection and assess the effectiveness of drug therapies.

Fusarium oxysporum has a high affinity for lignin and cellulose-based substrates and is known to grow in a wide range of environments. It is these properties and its ability to produce mycotoxins that have contributed to its pathogenicity in cereal crops that can affect human and animal health when ingested. Identify the mechanisms of mycotoxin production and map the functional output of F. oxysporum under varying growth conditions. Liquid and gas-based chromatography coupled with mass spectrometry was used to identify and map the untargeted metabolic pathway of F. oxysporum grown using nitrogen limited and organic/inorganic nitrogen supplemented media. Over 1300 metabolites were identified, relating to 42 metabolic pathways. Of these, 520 metabolites merged at pyruvate (glycolysis), succinate (Krebs cycle) and aspartate-glutamate metabolic pathways. CoA depletion at the growth stage triggered the initiation of fatty acid and branched amino acid degradation. This in turn activated propionyl CoA carnitine acetyltransferase enzymes, resulting in nitrogen preservation (urea, putrescine and organic acids end-products). CoA then transferred into the TCA cycle via previously unreported β-alanine and propionyl CoA metabolic pathways, the latter likely being a novel methylmalonyl-CoA mutase activity for F. oxysporum. The lower supplementation of inorganic nitrogen compounds (≤ 50 mM) and the elimination of nitrates/organic nitrogen sources resulted in TCA autophagy events that boosted mycotoxin-based metabolism and decreased overall F. oxysporum growth. Such knowledge of functional mycotoxin production can be used to supplement agricultural crops and reduce the risk of mycotoxin contamination in human and animal food supplies.

Playing pivotal roles in tumor growth and metastasis, matrix metalloproteinase‐14 (MMP‐14) is an important cancer target. Potent inhibitory Fab 3A2 with therapy‐desired high selectivity has been isolated from a synthetic antibody library carrying long CDR‐H3s. However, like many standard mechanism protease inhibitors, Fab 3A2 can be cleaved by high concentrations of MMP‐14 after extended incubation at acidic pH. Edman sequencing of generated 3A2 fragments indicated that cleavage occurred within its CDR‐H3 between residues N100h (P1) and L100i (P1’). To improve proteolytic stability of 3A2, three positions adjacent to its cleavage site (P1, P1’, and P3’) were subjected to site‐saturation mutagenesis (SSM). Mutations at P1’ (L100i) resulted in loss of inhibition function, while screening of 3A2 Fab mutants at P1 (N100h) or P3’ (A100k) positions identified four clones exhibiting improvements in both stability and inhibition potency. The majority of these mutants with improved stability were substitutions to either hydrophobic (Lue, Trp) or basic residues (Arg, Lys, His). Combinations of these beneficial mutations resulted in a double mutant N100hR/A100kR, which prolonged half‐life twofold with an inhibition potency K (I) of 6.6 nM. Enzyme kinetics and competitive ELISA suggested that N100hR/A100kR was a competitive inhibitor overlapping its binding epitope with that of nTIMP‐2. This study demonstrated that site‐directed mutagenesis at or near the cleavage position reduced proteolytic liability of standard mechanism protease inhibitors especially inhibitory antibodies.

Streams and rivers are active processors of terrestrial carbon and significant sources of carbon dioxide (CO2) and methane (CH4) to the atmosphere. Recent studies suggest that ebullition may represent a sizable yet overlooked component of the total CH4 flux from these systems; however, there are no published CH4 ebullition estimates for streams or rivers in subarctic or arctic biomes, regions that store vast quantities of vulnerable, old organic carbon in permafrost soils. We quantified CH4 ebullition from headwater streams in a small arctic watershed in Northeastern Siberia. Ebullitive emissions were 0.64 mmol m−2 d−1, which is lower than the global average but approximately 2 times greater than the pan-arctic diffusive CH4 flux estimate reported in a recent synthesis of global freshwater CH4 emissions. The high CO2:CH4 of sediment bubbles (0.52) suggests that methane emissions may currently be constrained by resource competition between methanogens and microbes using more efficient metabolic st...

The structural, electronic, and elastic properties of pristine and carbon-doped boron suboxide (B6O) are calculated using density functional theory. The results indicate that it is energetically preferable for a single carbon atom to substitute into an oxygen site rather than a boron site. The lattice parameters and cell volume increase to relieve the residual stress created by the carbon substitution. The interstitial position is not favorable for a single atom substitution. However, if two carbon atoms substitute for two neighboring oxygen atoms, then it becomes energetically favorable to dope an interstitial oxygen, boron, or carbon atom along the C–C chain. If the interstitial dopant is either boron or carbon, a local B4C-like structure with either a C–B–C or C–C–C chain is created within the boron suboxide unit cell. The resulting structure shows improvements in the bulk modulus at the expense of the shear and Young's moduli. The moduli further improve if an additional carbon is substituted within a polar or equatorial site of the neighboring B12 icosahedron. Based on these calculations, we conclude that carbon doping can either harden or soften B6O depending on the manner in which the substitutions are populated. Furthermore, as B6O samples are often oxygen deficient, C doping can occupy such sites and improve the elastic properties.

Antimicrobial residues found to be present in milk can have both health and economic impacts. For these reasons, the widespread routine testing of milk is required. Due to delays with sample handling and test scheduling, laboratory-based tests are not always suited for making decisions about raw material intake and product release, especially when samples require shipping to a central testing facility. Therefore, rapid on-site screening tests that can produce results within a matter of minutes are required to facilitate rapid intake and product release processes. Such tests must be simple for use by non-technical staff. There is increasing momentum towards the development and implementation of multiplexing tests that can detect a range of important antimicrobial residues simultaneously. A simple in situ multiplexed planar waveguide device that can simultaneously detect chloramphenicol, streptomycin and desfuroylceftiofur in raw dairy milk, without sample preparation, has been developed. Samples are simply mixed with antibody prior to an aliquot being passed through the detection cartridge for 5 min before reading on a field-deployable portable instrument. Multiplexed calibration curves were produced in both buffer and raw milk. Buffer curves, for chloramphenicol, streptomycin and desfuroylceftiofur, showed linear ranges (inhibitory concentration (IC)20-IC80) of 0.1-0.9, 3-129 and 12-26 ng/ml, whilst linear range in milk was 0.13-0.74, 11-376 and 2-12 ng/ml, respectively, thus meeting European legislated concentration requirements for both chloramphenicol and streptomycin, in milk, without the need for any sample preparation. Desfuroylceftiofur-contaminated samples require only simple sample dilution to bring positive samples within the range of quantification. Assay repeatability and reproducibility were lower than 12 coefficient of variation (%CV), whilst blank raw milk samples (n = 9) showed repeatability ranging between 4.2 and 8.1%CV when measured on all three calibration curves. Graphical Abstract MBio SnapEsi reader and cartridge.

The UCLA team has successfully passivated perovskite film by controlling the film growth with functional polymers as additive., The solution processing of polycrystalline perovskite films introduces trap states that can adversely affect their optoelectronic properties. Motivated by the use of small-molecule surfactants to improve the optoelectronic performance of perovskites, we demonstrate the use of polymers with coordinating groups to improve the performance of solution-processed semiconductor films. The use of these polymer modifiers results in a marked change in the electronic properties of the films, as measured by both carrier dynamics and overall device performance. The devices grown with the polymer poly(4-vinylpyridine) (PVP) show significantly enhanced power conversion efficiency from 16.9 ± 0.7% to 18.8 ± 0.8% (champion efficiency, 20.2%) from a reverse scan and stabilized champion efficiency from 17.5 to 19.1% [under a bias of 0.94 V and AM (air mass) 1.5-G, 1-sun illumination over 30 min] compared to controls without any passivation. Treating the perovskite film with PVP enables a VOC of up to 1.16 V, which is among the best reported for a CH3NH3PbI3 perovskite solar cell and one of the lowest voltage deficits reported for any perovskite to date. In addition, perovskite solar cells treated with PVP show a long shelf lifetime of up to 90 days (retaining 85% of the initial efficiency) and increased by a factor of more than 20 compared to those without any polymer (degrading to 85% after ~4 days). Our work opens up a new class of chemical additives for improving perovskite performance and should pave the way toward improving perovskite solar cells for high efficiency and stability.

This paper presents an experimental study on autogenous healing in a recently developed shrinkable polymer cementitious material system. Small-scale hollow prismatic mortar beams with unbonded shrinkable polymer tendons were loaded until a crack of predefined width had formed. The specimens were then subjected to a range of combined heating/curing regimes to activate the shrinkable polymer and to promote autogenous healing of the cementitious material prior to reloading to failure. Upon reloading, specimens loaded with the shrinkable polymer tendons remaining after heating and curing achieved between 120 and 195% of their initial peak loads, whereas specimens tested with the shrinkable polymer tendons removed after the heating and curing stages recovered on average 80% of their initial peak loads. The overall conclusion was that, provided a supply of water is present and sufficient heat is applied for polymer activation, the material system is effective at not only closing cracks and applying a prestress, but also at enhancing the self-healing of cracks in cementitious materials.

This paper presents the application of metabolomic techniques to determine the presence of microbial influenced corrosion (MIC). In a previous study, the extracellular metabolites expressed from pipe biofilm was identified by analysing the passing water. This investigation extends this work by successfully applying a chemometric statistical analysis to the extracellular metabolomic profile of a number of water samples to identify critical metabolomic biomarkers. The chemometric analysis was able to differentiate samples due to a reduction of carboxylic acids in samples exposed to bacteria believed to cause MIC.

INTRODUCTION: Substituted indoles and related structures have been shown to exhibit potent anticancer activity against breast cancer cell lines. Here, the effects of structurally similar substituted indoles against the human glial cancer cell lines, 1321N1 and U87MG, have been investigated by comparing the effects of these compounds to conventional anti cancer drugs. METHODS: Cell viability in the presence of the test compounds was measured using an MTS assay and corroborated by an ATP cell proliferation assay as well as a Trypan blue exclusion test. The significance of reactive oxygen species (ROS) in the process was determined using an Image-iT® LIVE ROS kit from Invitrogen. RESULTS: Both cell lines were treated with four commercial anticancer drugs and IC50 values were only reached at concentrations of 20 µM for cisplatin and 50 µM for gemcitabine over 48hrs on the 1321N1 cell line. However, the more malignant U87MG cell line was resistant to all the drugs, except for cisplatin where the IC50 value was reached at 300 µM after treatment for 48hrs. Similar studies were carried out with various substituted indoles and the cytotoxicity results on both cell lines showed that the IC50 value was reached within 90 minutes for the most potent compound at a concentration of 600 µM (1321N1) and 800 µM (U87MG). The idea that the mechanism of action of these compounds may work through the generation of ROS was investigated and this was confirmed over a similar time course using a suitable fluorogenic marker. Moreover, it was shown that the addition of an antioxidant (ascorbic acid) abolished the potency of the most active compound. CONCLUSION: Here, it has been demonstrated that certain substituted indoles are able to have a rapid, deleterious effect on the viability of two glioma cell lines and indicated that ROS generation may induce cell death.

An investigation of the transient thermomechanical behavior of poly(ethylene terephthalate) (PET) is presented with respect to a new composite material system in which shrinkable PET tendons are incorporated into a cementitious matrix to provide a crack-closure mechanism. A series of parametric studies of the effects of the geometry, temperature, and soak time on the mechanical properties of the polymer are presented. In particular, this article focuses on the shrinkage behavior and the development of stresses under restrained shrinkage conditions. A one-dimensional numerical model, which is essentially a modification of Zener's standard linear solid model, is presented with the aim of simulating aspects of behavior of particular relevance to tendons within the composite material system. The model comprises a temperature-dependent dashpot and spring in parallel with a spring and thermal expansion element. The temperature-dependent functions are calibrated with the obtained data, and a final validation example that shows good accuracy in comparison with experimental data not used for the calibration is presented. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Human consumption of omega-3 Polyunsaturated Fatty Acids (n-3 PUFA) has increased due to reported health benefits. Despite the benefits of n-3 PUFA eggs, the addition of omega-3 enriched feedstuffs like flaxseed and fish oil may reduce egg quality. A standard n-PUFA diet containing flaxseed and fish oil (Diet A), a standard n-PUFA diet supplemented with vitamin B6 (Diet B), a standard n-PUFA diet without fish oil (Diet C) and a conventional milo ration (Diet D) were fed to four separate groups of laying hens to evaluate the effect of these diets on egg quality. Three individual shipments of eggs collected from hens fed these diets were received from a commercial layer operation, where these hens were reared. The eggs were stored for three weeks in a refrigerator to simulate consumer storage conditions. The eggs were evaluated for quality by determining whole egg weight, yolk weight, albumen thickness and Vitelline Membrane Strength (VMS). Significant increases in egg weights were observed in Diet B samples in the first egg shipment and Diets B, C and D in the third egg shipment. Yolk weights were significantly increased with Diet B samples from the third collection. No differences were observed in albumen thickness in any of the three shipments of eggs. Numerical increases in VMS were observed in Diets B, C and D in each of the three shipments, but only the third shipment had significant differences with these treatments. These data suggests that the addition of flaxseed and fish oil may negatively affect egg quality. The addition of vitamin B6 or the removal of fish oil to a standard n-PUFA diet may be comparable to a conventional layer ration’s effect on egg quality.

Slow strain rate tests were performed to evaluate the effect of simulated groundwater chemistry variations on the stress corrosion cracking (SCC) susceptibility of mill-annealed Alloy 22 (...

Raman spectroscopy has been identified as a potentially useful tool to collect evidence of past or present life on extraterrestrial bodies. However, it is limited by its inherently low signal strength. In this investigation, laboratory tests were conducted using surface-enhanced Raman spectroscopy (SERS) in an “inverted” mode to detect the presence of organic compounds that may be similar to possible biomarkers present on Mars. SERS was used to overcome the inherently low signal intensity of Raman spectroscopy and was an effective method for detecting small concentrations of organic compounds on a number of surfaces. For small organic molecules, dissolution of the molecule to be analyzed in a suitable solvent and depositing it on a prepared SERS substrate for analysis is possible. However, for larger molecules, an “inverted” SERS (iSERS) technique was shown to be effective. In iSERS, nanoparticles of silver or gold were deposited on the mineral substrate/organic compound to be analyzed. Benzotriazole, benzoic acid, and phthalic acid were used as test organic analogs and the iSERS technique was able to detect femtomole levels of the analytes. The interference from various mineral substrates was also examined. Different methods of depositing silver particles were evaluated, including ion beam-assisted vapor deposition and deposition from aqueous colloidal suspensions.

Existing metallographic preparation techniques for uranium are limited to elucidating specific microstructural characteristics, and some of the techniques are regarded as being environmentally unacceptable. This paper describes a newly developed technique, which is not only more environmentally friendly, but reveals most microstructural features simultaneously. Example microstructures of the various preparation stages are given to highlight the new technique.

We present the advances in Silicon Germanium Heterojunction Bipolar Transistor (SiGe HBT) and BiCMOS technology capabilities to address the emerging millimetre-wave (mmWave) applications. SiGe HBTs with fMAX performance reaching 350 GHz that are integrated with advanced CMOS and high-frequency passives is envisioned to allow better integration capability for mmWave applications. This capability of SiGe HBT BiCMOS technology is discussed relative to an InP HBT technology. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

A subtraction library was prepared from cultures of Aspergillus niger that had or had not been exposed to dithiothreitol (DTT), in order to identify genes involved in the unfolded protein response (UPR) or in the response to reductive stress. A large fraction of the clones in the library (40%) encoded two putative methyltransferases (MTs) whose function has yet to be determined. Other stress-responsive genes included a homologue of the Mn2+ -containing superoxide dismutase gene (sodB) and a number of genes predicted to code for products that function in protein turnover and in intra- and extracellular transport of molecules. Transcriptional microarray analysis was carried out with a group of 15 genes, comprising 11 from the cDNA library, two genes linked to the putative MT genes but not represented in the library, and two UPR control genes (bipA and pdiA). Eleven of the 15 genes were inducible with DTT. This was either reflected by the presence of transcripts in cells subjected to DTT stress compared to absence under control conditions, or by an induction ratio of between 1.4 and 8.0 in cases where transcripts were already detectable under control conditions. The MT genes were among the four most highly induced. None of the genes, apart from bipA and pdiA, showed significant induction in response to other stresses that are known to induce the UPR in fungi. We conclude that DTT alone does not provide for specific induction of UPR genes and that other stress conditions must also be examined.

Copper/copper sulphate electrodes are commonly used as reference electrodes in the cathodic protection of underground pipelines and storage tanks. They require periodic replacement of the internal electrolyte, owing to the seasonal wet/dry cycles of the soil. Also, they experience various problems including: (i) agglomeration of CuSO4 crystals at the electrode tip resulting in possible loss of the electrochemical connection between the cell and the soil solution; and (ii) leakage of the CuSO4 electrolyte into the surrounding soil, possibly resulting in the deposition of copper on the steel surface and consequent galvanic corrosion of the protected structure. In the present study, a new reference electrode has been developed in an attempt to: (i) provide quick recovery from dry-out when the soil re-wets; (ii) avoid salt agglomeration; and (iii) prevent accelerated corrosion of the structure as a result of the leakage of electrolyte from the electrode. In the present study, progress towards these g...

The susceptibility of as-received, solutionized, and short-term thermally aged mill-annealed (MA) and gas tungsten arc-welded (GTAW) alloy 22 to Pb-assisted stress corrosion cracking (PbSCC) was evaluated in supersaturated, deaerated, acidic PbCl2 solutions at 95 °C. Anodic polarization tests in acidic PbCl2 solutions showed that 16,000 ppm of Pb produced a strong anodic peak and an order of magnitude greater passive current density for both MA and GTAW alloy 22 as compared to pure NaCl solutions. Current spikes were also observed in the anodic polarization plots for the PbCl2 solutions, suggesting periodic events of passivity breakdown and repassivation. Constant deformation SCC tests were conducted using double U-bend samples of as-received, solutionized, and thermally aged MA and double U-groove welded alloy 22 plates. The results indicate that as-received, solutionized, and thermally aged MA and GTAW alloy 22 were resistant to PbSCC in supersaturated PbCl2 solutions at 95 °C, pH 0.5, and applied potentials near the anodic peak ranging from −100 to 50 mVSCE. Enhanced dissolution of alloy 22 was also observed in the crevice region of the double U-bend samples tested in the 16,000 ppm PbCl2 solutions. This Pb concentration is seven orders of magnitude greater than that found in the anticipated repository environments, and chemical speciation modeling showed that Pb2+ is strongly immobilized in J-13 Yucca Mountain waters through the precipitation of PbCO3 solids. Therefore, although enhanced dissolution of the inner U-bend did occur in our tests, the overall results from this PbSCC investigation suggest that as-fabricated, solutionized, and aged MA and GTAW alloy 22 are resistant to SCC in extremely aggressive, acidic, and supersaturated PbCl2 solutions at 95 °C. Provided that these high Pb concentrations are not attainable in the anticipated repository environments, alloy 22 is unlikely to be susceptible to SCC, localized corrosion, and enhanced dissolution by the presence of Pb.

The susceptibility to various forms of corrosion that could be experienced by the alloys considered by the U.S. Department of Energy for the waste package and drip shield, the principal components of the engineered barrier system for the proposed repository at Yucca Mountain, is evaluated on the basis of experimental studies conducted at the Center for Nuclear Waste Regulatory Analyses. Environmental, metallurgical, and mechanical conditions for the occurrence of uniform corrosion, localized corrosion, and environmentally assisted cracking of Alloy 22 (58Ni-22Cr-13Mo-3W-4Fe), the preferred material for the outer container, and Titanium-Grade 7 (Ti-0.15 Pd), the alloy proposed for the drip shield, are reported.

A number of alloys, including stainless steels, aluminum, and nickel-based alloys, are used in seawater for various applications. The localized corrosion of these materials is affected, among other factors, by temperature, microbial activity, chlorination, and flow rate. A predictive model, based on the calculation of repassivation and corrosion potentials, is presented and compared to field experiences of these alloys in seawater systems. An empirical model is used for calculating the repassivation potential of these alloys as a function of seawater composition. A mechanistic model is used for calculating the corrosion potential as a function of oxygen and chlorine concentrations. The parameters for the corrosion potential are derived from tests in flowing natural seawater or synthetic seawater. The model calculations agree with the relative ranking of these alloys in seawater. Limitations of the current model and improvements are suggested.

A general model for predicting the localized corrosion repassivation potential of alloys in multicomponent electrolyte solutions is described. The model assumes that the status of localized corrosion is determined by competitive processes at the metal–salt film–solution interfaces leading to either metal salt or oxide formation. The model successfully predicts the observed effects of aggressive species, such as chloride and bromide, inhibiting species, such as nitrate, and non-aggressive species, such as acetate, for a number of Fe–Ni–Cr–Mo alloys. Furthermore, the model accurately predicts the effect of nitrate in a three-component system of chloride + nitrate + acetate, based only on parameters regressed for the constituent binary systems.

Summary 1. It has recently become apparent that tissue plasminogen activator (tPA) modulates inflammation in diseases such as rheumatoid arthritis (RA) and acute respiratory distress syndrome (ARDS). 2. We have shown previously that tPA has anti-inflammatory activity in in vivo models of oedema or inflammation. 3. The present study investigated the ability of exogenous recombinant tPA (rtPA) to reduce carrageenan-mediated oedema in mice lacking the tPA gene, testing the hypothesis that rtPA treatment may be beneficial in diseases such as RA and ARDS in which there is a paucity of endogenous tPA. 4. Knockout mice deficient in the tPA gene and matching wild-type mice received an intraplantar injection (25 µL) of carrageenan (1.5%, w/v) following either vehicle (sterile water for injection) or tPA (12 mg/kg). 5. Footpad oedema was measured, an oedema index was calculated and tissue myeloperoxidase (MPO) activity was determined. Mean oedema indices were higher in untreated tPA (–/–) mice than untreated wild-type mice. Pretreatment with rtPA in either tPA (–/–) or wild-type mice reduced the mean measured peak footpad oedema index by 63 and 48%, respectively. Tissue MPO activity was not different between treatment groups. 6. We conclude that exogenous rtPA has the ability to reduce acute oedema without altering neutrophil infiltration into the site of injury in both tPA (–/–) and wild-type mice and that endogenous tPA may participate in the inflammatory process, as evidenced by higher oedema indices in untreated tPA (–/–) mice. These data provide support for the potential clinical utility of exogenous rtPA in the treatment of inflammatory diseases, such as RA and ARDS, in which there is a paucity of tPA.

The heterogeneous nature of energy deposition by ionizing radiation can be used to advantage by pulsing an electron beam at low dose per pulse and high pulse rates. Track overlap is avoided for a short period of time, sufficient to allow an essentially heterogeneous polymerization to take place. High pulse rates appear to maintain this advantage by terminating the incipient homogeneous kinetics while re-initiating the heterogeneous kinetics. Polymerization by this method shortens the residence time necessary for full conversion but beyond 50% conversion, there may no longer be any advantage in a diffusion-limited system. Lower temperature also helps to reduce termination in the early phase of polymerization.

Silicon–germanium (SiGe) heterojunction bipolar transistor (HBT) BICMOS technology is a stable, ultra-high performance, semiconductor technology capable of supporting mixed-signal, very large-scale integration (VLSI) circuit designs for a variety of emerging communication applications. This technology is supported by a computer-aided design (CAD) system that supports a variety of high-performance circuit designs, mixed-signal circuit block reuse, and the ability to accurately predict circuit performance at the highest frequencies. This paper summarizes the progress this technology has made in recent years in moving from the research laboratory to a production environment. We also specifically address performance, operating voltage, reliability and integration considerations for using 100–200 GHz SiGe HBTs in high-speed (10–40 Gb/s) network ICs, an application space previously only addressed by InP technology. All indications are that SiGe will be very successful at addressing this new application space, and all facets of the networking IC market.

Cell-mediated immunity can be detected in vitro by various reactions, many of which are mediated by soluble factors. The leukocyte adherence inhibition (LAI) test has been recently developed as a rapid in vitro test which may be a correlate of delayed-type hypersensitivity. LAI is a reaction in which leukocytes from sensitized donors, stimulated with the corresponding antigen in vitro, exhibit a decreased adherence to solid surfaces. The following studies were aimed at elucidating the mechanism of LAI.Contact hypersensitivity in mice to picryl chloride (PCl) was chosen as a suitable immunological system for investigating the cell types reacting with the specific antigen in vitro. After direct (1-stage) LAI tests were used initially to determine the optimal antigen concentration, the LAI effect was subsequently demonstrated in indirect (2-stage) assays. Supernatants were obtained from sensitized spleen cells (taken 7 days after sensitization) after in vitro incubation with antigen for 60 min, and tested on a population of normal indicator cells. The supernatants contained a soluble lymphokine-like factor (leukocyte adherence inhibition factor—LAIF) responsible for the final reduction in cellular adherence. This 2-stage activity (as opposed to the 1-stage activity) was poorly reproducible. It also appeared that "late" spleen cells (taken from mice at times greater than 7 days after sensitization) were almost never active in LAI assays, whereas cells taken before this time showed variable LAIF production.Sensitized spleen cells were fractionated on glass-bead or nylon-wool columns to determine the role of adherent cells (macrophages) in LAI phenomena. Glass-bead columns depleted macrophages (and B lymphocytes also to a slight extent), but under the particular conditions used, the nylon wool did not appear to deplete B lymphocytes. It was found that LAI activity of cells in 2-stage assays was abrogated by glass-bead columns, and that addition of a macrophage source (normal peritoneal cells or corresponding macrophage-enriched cells) to the resulting non-adherent cells allowed LAIF to be produced. This implied that macrophages were required for LAIF production in this system. Either syngeneic or allogeneic macrophages were effective in restoring the LAI response of glass-bead non-adherent cells. The reconstitution of LAI activity was observed regularly even with cells showing no initial activity, and with cells taken at times greater than 7 days after sensitization. Such effects were interpreted as being due to the concomitant removal, by the glass-bead columns, of cells suppressive for LAIF production along with the macrophage population. This was confirmed by demonstrating that glass-bead adherent cells could suppress LAIF production by unfractionated cells, in an antigen-specific manner. Passage of sensitized spleen cells through nylon-wool columns did not remove this suppressor cell fraction.Affinity columns were used to separate T and B lymphocyte classes from spleen cell populations, after initial depletion of macrophages on nylon wool. It was found that both of these major lymphocyte classes could produce LAIF, but only in the presence of normal peritoneal cells (macrophages). Moreover, LAIF activity was not seen with mixtures of T and B cells, indicating a mutual suppressive effect. The B cell LAI activity was resistant to anti-Thy-1.2 serum treatment, and treatment of unfractionated spleen cells with the same antiserum allowed LAI effects to be seen with initially unreactive cells. This confirmed the B cell LAIF production, and indicated that T cells were suppressing this B cell activity in the unfractionated populations. The B suppressor cells, the T suppressor cells, and the B cell subpopulation active in LAIF production, were glass-bead adherent. The LAIF-producing T cells were non-adherent. Suppressive phenomena did not extend to non-specific suppression of lymphocyte blastogenesis, as stimulation of sensitized spleen cells by concanavalin A (Con A) proceeded just as effectively as with normal spleen cells.LAI activity in vitro was compared with in vivo adoptive transfer of delayed-type hypersensitivity. The in vitro data were found to correlate with the in vivo test, since "late" sensitized spleen cells could not effect adoptive transfer until they had been passaged through glass-bead columns. The glass-bead adherent fraction suppressed adoptive transfer by "early" cells (taken 4 days after sensitization) in an antigen-specific manner. This strengthened the viewpoint that LAI tests are correlates of delayed-type hypersensitivity.The second major approach toward the study of LAI mechanisms was to attempt to characterize the soluble factors involved. Con A was initially used to stimulate normal spleen cells in the hope of obtaining large amounts of LAIF. It was found that Con A elicited both LAIF and a presumptive adherence stimulation factor. Both of these factors could also be demonstrated from antigen-stimulated cells under the correct conditions. The concentration of serum in the initial cell-antigen mixture appeared to be the critical factor in determining whether LAI or adherence stimulation effects were seen, and a high concentration of serum in the indicator cell^ supernatant mixtures was also necessary to demonstrate both antigen-stimulated and mitogen-stimulated LAIF. Supernatants obtained after stimulation of spleen cells by both Con A and antigen were fractionated on Sephacryl S-200. The mitogen-induced LAIF and adherence stimulation factor had molecular weights of 26-52,000 and 51-96,000 daltons respectively, whereas the specific antigen-induced LAIF and adherence stimulation factor had molecular weights of 44-≥96,000 and >113,000 daltons. This indicated that adherence-modulating factors, especially those from different sources, were heterogeneous. Con A-stimulated LAIF appeared to be sensitive to high pH and neuraminidase, and the corresponding adherence stimulation factor was also pH sensitive. Antigen-stimulated LAIF activity was abrogated by the presence of N-acetylglucosamine in the indicator cell-supernatant mixtures, indicating a role for this monosaccharide as a component of the LAIF receptor. Supernatants from PCl-sensitized T and B cells were passaged through anti-mouse γ-globulin affinity columns, which appeared to remove B cell LAIF, but not T cell LAIF. This demonstrated that these T and B cell factors were dissimilar.The general conclusions were that, especially with spleen cells from contact sensitized mice, both the cellular generation and the detection of LAIF were complex, with suppressive cellular interactions and adherence stimulation modulating the phenomenon of LAI. The physical nature of the soluble factors involved with LAI effects also appeared to be complex. Results obtained from LAI assays were correlated with observations on in vivo cell-mediated immunity.

An atomistic model for the effect of carbon (C) doping on the structural reorganization of boron suboxide (B6O) was developed from first principles density functional theory. The results indicate that it is energetically preferable for a single C atom to substitute into an oxygen (O) site rather than a B site. The lattice parameters and cell volume increase to relieve the residual stress created by the C substitution. Interstitial substitutions are not favorable for single atom substitutions. However, when 2 C atoms replace 2 neighboring O atoms within the B6O unit cell, it becomes energetically favorable to dope an interstitial O, B, or C atom along the C-C chain. If the interstitial dopant is either B or C, a local boron carbide (B4C)-like structure with either a C-B-C or C-C-C chain is created within the B6O unit cell, which could serve as an intermediate phase in the transformation of B6O into B4C. By promoting the formation of a local B4C-like structure, it may be possible to improve the mechanical stability and elastic properties of B6O.

Niobium is commonly alloyed with uranium to prevent surface oxidation, and determining how the niobium concentration is distributed throughout a sample is useful in explaining observed material properties. The niobium concentration distribution was determined across the surface of depleted uranium samples using micro-X-ray fluorescence (MXRF). To date, MXRF has been employed primarily as a qualitative tool for determining relative differences in elemental concentrations across a sample surface. Here, a process was developed to convert qualitative MXRF niobium distribution images from depleted uranium samples into images displaying concentration values. Thus, MXRF was utilized to determine elemental concentrations across a surface in a manner similar to that of the established method of electron microprobe X-ray analysis (EMPA). However, MXRF can provide such information from relatively large sample areas many cm2 in size that are too large to examine by the higher spatial resolution technique of EMPA. Although the sample surfaces were polished to the same degree as the standards, little or no sample preparation should be necessary for sample systems where a high energy analyte XRF line can be used for imaging.

The deformation of polycrystalline uranium 6 wt pct niobium (U6Nb) was studied in situ during uniaxial tensile loading by time-of-flight neutron diffraction. Diffraction patterns were recorded at incremental stresses to a maximum of 450 MPa (∼4 pct macroscopic strain). Consistent with reorientation of the martensite variants by twinning, significant changes in the diffraction peak intensities, which were proportional to the plastic contribution of the macroscopic strain, were observed. Both the lattice parameters (a, b, c, and γ) and interplanar spacings (dhkl) were determined as a function of applied stress. Phenomenologically, the highly anisotropic stress response of the lattice parameters as well as the individual lattice spacings can be related to deformation twinning. Preliminary transmission electron microscopy (TEM) studies identified the (\(\bar 1\)30) and (\(\bar 1\)72) as active deformation twinning systems of U6Nb in tension.

Results of a laboratory study of internal corrosion in wet gas pipelines under conditions involving a stagnant or slowly flowing aqueous phase indicate that the corrosion rate is not affected by calcium and magnesium scale-forming tendency of the test solutions, provided that they are buffered. It is possible that the scales formed are sufficiently porous to permit electrolyte contact with steel. However, an increase in pH and decrease in oxygen resulted in significant corrosion rate reduction. Thermodynamic analyses indicate that the formation of metastable iron sulfide (FeS) precipitates is promoted by higher pH and higher dissolved iron concentration, and hindered by the presence of carbon dioxide (CO2). The presence of oxygen on corrosion may lead to the transformation of a metastable FeS phase, mackinawite (Fe1+xS), to another metastable phase, greigite (Fe3S4). Electrochemical polarization data indicate that the steel behaves in an active manner symptomatic of a nonprotective corrosion prod...

The in vitro degradation of biodegradable polymer/ceramic composites was assessed in two different environments under both static and pseudodynamic conditions. The blends, consisting of polycaprolactone, poly(lactic-co-glycolic acid), and hydroxyapatite, have potential use in bone tissue engineering applications, thus it is essential to establish a standardized method of characterizing the degradation of new biomaterials. In this study, the variation in polymer blend ratio was examined to observe a change in degradation rate. The porous blends were degraded in water and serum-containing media. A previous study examined in vitro degradation in serum-free buffer. Molecular weight loss, gravimetric weight loss, pH changes and morphological changes were evaluated. The changes in porosity were observed with scanning electron microscopy and quantitatively assessed using image analysis. There was a significant difference in molecular weight loss and gravimetric weight loss between the blends after 10 weeks in vitro. Blends containing the greatest amount of poly(lactic-co-glycolic acid) degraded most rapidly. © 2001 Kluwer Academic Publishers

In-situ alternating current (AC) and direct current (DC) electrochemical techniques were used to determine the corrosion rate and corrosion potential of high-purity iron under alternate wet and dry conditions. Comparisons between DC electrochemical measurements and weight loss were conducted to verify the validity of the corrosion rate measurements. Identification of the corrosion products was performed using Raman spectroscopy. Corrosion products contained layers of iron oxides and oxyhydroxides. At low Cl− concentrations, corrosion products consisted of lepidocrocite (γ-FeOOH) and magnetite (Fe3O4). At higher Cl− concentrations, the formation of akaganeite (β-FeOOH) was observed. Corrosion rates and corrosion potentials fluctuated throughout the wet cycles depending on electrolyte layer thickness, ionic strength, and wetting cycle. Accelerated corrosion rates of high-purity iron, up to three times those observed under continuously immersed conditions, were the result of Fe(III) reduction in the...

Alloy 825, a former candidate material for radioactive high-level waste containers, was investigated to assess its thermal stability and the time-temperature conditions for sensitization. Alloy specimens with a carbon content of 0.01 wt pct in the mill-annealed (MA) and solution-annealed (SA) conditions were studied after thermal exposure to temperatures ranging from 600 °C to 800 °C for periods of up to 1000 hours. Sensitization was evaluated by using corrosion tests that were correlated to grainboundary chemistry analyses. Sensitized microstructures were found to contain M23C6-type carbides and a chromium-depleted region in the vicinity of the grain boundaries. Thermal aging at 700 °C for 100 hours resulted in the highest sensitization. While heat treatment at 640 °C showed a progressive development of sensitization with time, healing was found to occur after aging at 800 °C for 100 hours. The degree of sensitization, quantified by an equivalent chromium-depleted-zone size, correlates well with the corrosion rate in the nitric acid test. Thermodynamic models were used to calculate the interfacial chromium concentration, chromium depletion profile, and the depleted-zone width. Comparisons between experimental measurements and model calculations indicate that reliable prediction depends on the selection of key model parameters.

Sodium dodecyl sulfate (SDS)-templated sol−gel films formed by the rapid dip-coating method possess highly ordered lamellar phase structure. Thin film morphology allows both the chemistry and the dynamics of the assembly process to be traced in real time because the steps involved in the formation of the mesostructured material are separated both spatially and temporally. The dynamic processes that occur during film formation can be conveniently monitored by the combination of interferometry and luminescence spectroscopy of the incorporated molecular probes. The luminescence of the probe molecule is measured with a spatial resolution of 100 μm. The selected probes respond to changes in the surrounding solvent composition and polarity, and report these changes by changes in their luminescence characteristics. In situ luminescence spectra taken at various stages during the film formation process monitor changes in the solvent composition, onset of micelle formation, and its transformation to the final mesop...

Pyranine (trisodium 8-hydroxy-1,3,6-pyrenetrisulfonate) and PRODAN (6-propionyl-2-(dimethylamino)naphthalene) are used as in situ fluorescence probes to monitor the molecular mobility and chemical evolution during sol−gel silica thin film deposition by the dip-coating process. Measurements are made on the evolving film as it emerges from the sol at thicknesses changing from

Samples of varying abrasiveness, including rice hulls, rice straw, wheat grain, orange leaves, and filter paper, were ground to pass a 0.5‐mm screen in two cyclone mills (Tecator Cyclotec model 1093 and Newport Scientific model 6200) with original and modified internal components. The ground samples were then digested in nitric acid and analyzed for 12 elements by Inductive Coupled Plasma (ICP) spectroscopy. Analysis of aluminum (Al), copper (Cu), iron (Fe), and zinc (Zn) showed that the amount of metal contamination from each mill was related to the abrasiveness of the plant material and the metal composition of the internal components of the mill. Least contamination was achieved using the Newport Scientific 6200 mill fitted with a stainless steel impeller and an abrasive steel strap with industrial diamonds set in pure nickel. For abrasive samples such as rice hulls a stainless steel impeller was about six times more durable than an aluminum impeller. The Newport mill ground samples in less ti...

Background Atorvastatin is a potent inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, but its effect on bile acid synthesis is unknown. The objectives of the study were to determine the effect of atorvastatin on bile acid synthesis in patients in whom this process had not been or had been previously up-regulated by pharmacological or surgical means. Materials and methods Four patients with heterozygous familial hypercholesterolaemia (FH) and partial ileal bypass (PIB) and 19 FH heterozygotes without PIB were treated with placebo, atorvastatin 10 mg and atorvastatin 40 mg daily, each regimen for 4 weeks. The non-PIB group was subsequently treated with bile acid (BA) sequestrant 8–16 g daily followed by co-administration of atorvastatin 10 mg, each for 4 weeks. Plasma 7α-hydroxy-4-cholesten-3-one (7α-HCO), a well-validated marker of BA synthesis was measured using high-performance liquid chromatography with UV detection. Results The plasma 7α-HCO concentration was tenfold higher with placebo in the PIB than in the non-PIB group (418.5 ng mL−1 vs. 39.6 ng mL−1P = 0.0001). Levels decreased in PIB patients treated with atorvastatin 10 mg and 40 mg daily (350.1 ng mL−1 and 174.0 ng mL−1, P = 0.007 respectively) but did not change significantly in the non-PIB group (44.7 ng mL−1 and 28.3 ng mL− respectively). Administration of BA sequestrant to non-PIB patients increased 7α-HCO to 197.4 ng mL−1; this decreased to 106.0 ng mL−1 during co-administration of atorvastatin 10 mg daily (P = 0.0001). Conclusion Atorvastatin decreases the rate of BA synthesis only if the latter is up-regulated by PIB or BA sequestrants, presumably by limiting the supply of newly synthesized free cholesterol.