Modelling the corrosion behaviour of Al2CuMg coarse particles in copper-rich aluminium alloys

The corrosion behaviour of 2024 aluminium alloy in sulphate solutions was studied; attention was focused on the influence of coarse intermetallic Al2CuMg particles on the corrosion resistance of the alloy. Model alloys representative of the aluminium matrix and of Al2CuMg coarse intermetallics were synthesized by magnetron sputtering. Open-circuit potential measurements, current–potential curve plotting and galvanic coupling tests were performed in sulphate solutions with or without chlorides. Further explanations were deduced from the study of the passive films grown on model alloys in sulphate solutions. The results showed that model alloys are a powerful tool to study the corrosion behaviour of aluminium alloys

Electrochemical Behavior of Magnetron-Sputtered Al–Cu Alloy Films in Sulfate Solutions

Model alloys, generated by magnetron sputtering, have been employed to understand the role of copper on the corrosion behavior of aluminum alloys. Binary Al–Cu alloys, with copper contents between 0 and 100 atom %, were synthesized with well-controlled compositions, embracing single-phase alpha and theta alloys together with multiphase alloys. Electrochemical measurements confirmed the stability of the thin alloy films and revealed that the corrosion behavior of the alpha, theta, and eta2 phases differed strongly in the cathodic region. Further, in the anodic region, phases of high copper content suffered pitting in sulfate solutions, while the alpha phase remained passive

External validation of a mammography-derived AI-based risk model in a U.S. breast cancer screening cohort of White and Black women

Despite the demonstrated potential of artificial intelligence (AI) in breast cancer risk assessment for personalizing screening recommendations, further validation is required regarding AI model bias and generalizability. We performed external validation on a U.S. screening cohort of a mammography-derived AI breast cancer risk model originally developed for European screening cohorts. We retrospectively identified 176 breast cancers with exams 3 months to 2 years prior to cancer diagnosis and a random sample of 4963 controls from women with at least one-year negative follow-up. A risk score for each woman was calculated via the AI risk model. Age-adjusted areas under the ROC curves (AUCs) were estimated for the entire cohort and separately for White and Black women. The Gail 5-year risk model was also evaluated for comparison. The overall AUC was 0.68 (95% CIs 0.64-0.72) for all women, 0.67 (0.61-0.72) for White women, and 0.70 (0.65-0.76) for Black women. The AI risk model significantly outperformed the Gail risk model for all wome

Evaluation of PD 404,182 as an Anti-HIV and Anti-Herpes Simplex Virus Microbicide

PD 404,182 (PD) is a synthetic compound that was found to compromise HIV integrity via interaction with a nonenvelope protein viral structural component (A. M. Chamoun et al., Antimicrob. Agents Chemother. 56:672–681, 2012). The present study evaluates the potential of PD as an anti-HIV microbicide and establishes PD's virucidal activity toward another pathogen, herpes simplex virus (HSV). We show that the anti-HIV-1 50% inhibitory concentration (IC(50)) of PD, when diluted in seminal plasma, is ∼1 μM, similar to the IC(50) determined in cell culture growth medium, and that PD retains full anti-HIV-1 activity after incubation in cervical fluid at 37°C for at least 24 h. In addition, PD is nontoxic toward vaginal commensal Lactobacillus species (50% cytotoxic concentration [CC(50)], >300 μM), freshly activated human peripheral blood mononuclear cells (CC(50), ∼200 μM), and primary CD4(+) T cells, macrophages, and dendritic cells (CC(50), >300 μM). PD also exhibited high stability in pH-adjusted Dulbecco's phosphate-buffered saline with little to no activity loss after 8 weeks at pH 4 and 42°C, indicating suitability for formulation for transportation and storage in developing countries. Finally, for the first time, we show that PD inactivates herpes simplex virus 1 (HSV-1) and HSV-2 at submicromolar concentrations. Due to the prevalence of HSV infection, the ability of PD to inactivate HSV may provide an additional incentive for use as a microbicide. The ability of PD to inactivate both HIV-1 and HSV, combined with its low toxicity and high stability, warrants additional studies for the evaluation of PD's microbicidal candidacy in animals and humans

Psychometric Properties and Correlates of Precarious Manhood Beliefs in 62 Nations

Precarious manhood beliefs portray manhood, relative to womanhood, as a social status that is hard to earn, easy to lose, and proven via public action. Here, we present cross-cultural data on a brief measure of precarious manhood beliefs (the Precarious Manhood Beliefs scale [PMB]) that covaries meaningfully with other cross-culturally validated gender ideologies and with country-level indices of gender equality and human development. Using data from university samples in 62 countries across 13 world regions (N = 33,417), we demonstrate: (1) the psychometric isomorphism of the PMB (i.e., its comparability in meaning and statistical properties across the individual and country levels); (2) the PMB’s distinctness from, and associations with, ambivalent sexism and ambivalence toward men; and (3) associations of the PMB with nation-level gender equality and human development. Findings are discussed in terms of their statistical and theoretical implications for understanding widely-held beliefs about the precariousness of the male gender role

Modelling the corrosion behaviour of Al2CuMg coarse particles in copper-rich aluminium alloys

International audienceThe corrosion behaviour of 2024 aluminium alloy in sulphate solutions was studied; attention was focused on the influence of coarse intermetallic Al2CuMg particles on the corrosion resistance of the alloy. Model alloys representative of the aluminium matrix and of Al2CuMg coarse intermetallics were synthesized by magnetron sputtering. Open-circuit potential measurements, current–potential curve plotting and galvanic coupling tests were performed in sulphate solutions with or without chlorides. Further explanations were deduced from the study of the passive films grown on model alloys in sulphate solutions. The results showed that model alloys are a powerful tool to study the corrosion behaviour of aluminium alloys

Potent Strategy To Inhibit HIV-1 by Binding both gp120 and gp41 ▿ †

The development of an anti-HIV microbicide is critical in the fight against the spread of HIV. It is shown here that the covalent linking of compounds that bind gp120 with compounds that bind gp41 can inhibit HIV entry even more potently than individual inhibitors or noncovalent combinations. The most striking example involves griffithsin, a potent HIV inhibitor that binds to the surface of HIV gp120. While griffithsin inhibits HIV Env-mediated fusion in a CCR5-tropic cell-cell fusion assay with a 50% inhibitory concentration (IC50) of 1.31 ± 0.87 nM and the gp41-binding peptide C37 shows an IC50 of 18.2 ± 7.6 nM, the covalently linked combination of griffithsin with C37 (Griff37) has an IC50 of 0.15 ± 0.05 nM, exhibiting a potency 8.7-fold greater than that of griffithsin alone. Similarly, in CXCR4-tropic cell-cell fusion assays, Griff37 is 5.2-fold more potent than griffithsin alone. In viral assays, both griffithsin and Griff37 inhibit HIV replication at midpicomolar levels, but the linked compound Griff37 is severalfold more potent than griffithsin alone against both CCR5- and CXCR4-tropic virus strains. Another example of this strategy is the covalently linked combination of peptide C37 with a variant of the gp120-binding peptide CD4M33 (L. Martin et al., Nat. Biotechnol. 21:71-76, 2003). Also, nuclear magnetic resonance (NMR) spectra for several of these compounds are shown, including, to our knowledge, the first published NMR spectrum for griffithsin

Critical Design Features of Phenyl Carboxylate-Containing Polymer Microbicides

Recent studies of cellulose-based polymers substituted with carboxylic acids like cellulose acetate phthalate (CAP) have demonstrated the utility of using carboxylic acid groups instead of the more common sulfate or sulfonate moieties. However, the pK(a) of the free carboxylic acid group is very important and needs careful selection. In a polymer like CAP the pK(a) is approximately 5.28. This means that under the low pH conditions found in the vaginal lumen, CAP would be only minimally soluble and the carboxylic acid would not be fully dissociated. These issues can be overcome by substitution of the cellulose backbone with a moiety whose free carboxylic acid group(s) has a lower pK(a). Hydroxypropyl methylcellulose trimellitate (HPMCT) is structurally similar to CAP; however, its free carboxylic acids have pK(a)s of 3.84 and 5.2. HPMCT, therefore, remains soluble and molecularly dispersed at a much lower pH than CAP. In this study, we measured the difference in solubility and dissociation between CAP and HPMCT and the effect these parameters might have on antiviral efficacy. Further experiments revealed that the degree of acid substitution of the cellulose backbone can significantly impact the overall efficacy of the polymer, thereby demonstrating the need to optimize any prospective polymer microbicide with respect to pH considerations and the degree of acid substitution. In addition, we have found HPMCT to be a potent inhibitor of CXCR4, CCR5, and dual tropic strains of human immunodeficiency virus in peripheral blood mononuclear cells. Therefore, the data presented herein strongly support further evaluation of an optimized HPMCT variant as a candidate microbicide

Development of Hexadecyloxypropyl Tenofovir (CMX157) for Treatment of Infection Caused by Wild-Type and Nucleoside/Nucleotide-Resistant HIV ▿

CMX157 is a lipid (1-0-hexadecyloxypropyl) conjugate of the acyclic nucleotide analog tenofovir (TFV) with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. CMX157 was consistently >300-fold more active than tenofovir against multiple viruses in several different cell systems. CMX157 was active against all major subtypes of HIV-1 and HIV-2 in fresh human peripheral blood mononuclear cells (PBMCs) and against all HIV-1 strains evaluated in monocyte-derived macrophages, with 50% effective concentrations (EC50s) ranging between 0.20 and 7.2 nM. The lower CMX157 EC50s can be attributed to better cellular uptake of CMX157, resulting in higher intracellular levels of the active antiviral anabolite, TFV-diphosphate (TFV-PP), inside target cells. CMX157 produced >30-fold higher levels of TFV-PP in human PBMCs exposed to physiologically relevant concentrations of the compounds than did TFV. Unlike conventional prodrugs, including TFV disoproxil fumarate (Viread), CMX157 remains intact in plasma, facilitating uptake by target cells and decreasing relative systemic exposure to TFV. There was no detectable antagonism with CMX157 in combination with any marketed antiretroviral drug, and it possessed an excellent in vitro cytotoxicity profile. CMX157 is a promising clinical candidate to treat wild-type and antiretroviral drug-resistant HIV, including strains that fail to respond to all currently available nucleoside/nucleotide reverse transcriptase inhibitors