A NEW OIL SEEPAGE IN THE OMAN MOUNTAINS AND ITS GEOLOGICAL,GEOCHEMICAL AND PETROLEUM SYSTEMS CONTEXT

A minor natural oil seepage is described from an unlikely setting in the Oman Mountains. The host rocks are fractured pelagic limestones of the lower member of the Triassic – Lower Jurassic Matbat Formation of the Hamrat Duru Group in the lower part of the allochthonous Hawasina Complex. This paper summarises Oman's established oil families and documents previously recorded oil seepages as context for describing the new seepage, its geochemistry, and possible source rock. The seep oil is different to those known from Oman's oil fields and probably derived from a poor quality, Mesozoic clastic source rock containing a mix of terrigenous and marine organic matter. The most likely source appears to be the Toarcian turbiditic upper member of the Matbat Formation, equivalent to the clastic Mafraq Formation of the Arabian Platform. The occurrence of source rocks in the allochthonous sediments of the NeoTethyan Hawasina Basin has been suspected previously, though their commercial significance remains to be established.     

Lipidation of Antimicrobial Peptides as a Design Strategy for Future Alternatives to Antibiotics

Multi-drug-resistant bacteria are becoming more prevalent, and treating these bacteria is becoming a global concern. One alternative approach to combat bacterial resistance is to use antimicrobial (AMPs) or host-defense peptides (HDPs) because they possess broad-spectrum activity, function in a variety of ways, and lead to minimal resistance. However, the therapeutic efficacy of HDPs is limited by a number of factors, including systemic toxicity, rapid degradation, and low bioavailability. One approach to circumvent these issues is to use lipidation, i.e., the attachment of one or more fatty acid chains to the amine groups of the N-terminus or a lysine residue of an HDP. In this review, we examined lipidated analogs of 66 different HDPs reported in the literature to determine: (i) whether there is a link between acyl chain length and antibacterial activity; (ii) whether the charge and (iii) the hydrophobicity of the HDP play a role; and (iv) whether acyl chain length and toxicity are related. Overall, the analysis suggests that lipidated HDPs with improved activity over the nonlipidated counterpart had acyl chain lengths of 8–12 carbons. Moreover, active lipidated peptides attached to short HDPs tended to have longer acyl chain lengths. Neither the charge of the parent HDP nor the percent hydrophobicity of the peptide had an apparent significant impact on the antibacterial activity. Finally, the relationship between acyl chain length and toxicity was difficult to determine due to the fact that toxicity is quantified in different ways. The impact of these trends, as well as combined strategies such as the incorporation of d- and non-natural amino acids or alternative approaches, will be discussed in light of how lipidation may play a role in the future development of antimicrobial peptide-based alternatives to current therapeutics.     

Static pentane extraction as a potential alternative to Soxhlet extraction for polypropylene olive oil overall migration limit measurements

Static pentane extraction of olive oil from polypropylene was evaluated as a safer, higher throughput alternative to pentane Soxhlet extraction for the recovery of olive oil from polypropylene for overall migration limit determinations. Static, ambient temperature, pentane extraction achieved quantitative recovery of olive oil from polypropylene plaques prepared by using the OM‐5 overall migration limit protocol. In addition to validation data for static extractions, a modified esterification procedure is presented as a means to accommodate the larger sample sets that are enabled with static extraction.     

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cocaine is one of the most widely abused illicit drugs worldwide and has long been recognised as an agent of cardiac dysfunction in numerous cases of drug overdose. Cocaine has previously been shown to up-regulate cytoskeletal rearrangements and morphological changes in numerous tissues; however, previous literature observes such changes primarily in clinical case reports and addiction studies. An investigation into the fundamental cytoskeletal parameters of migration, adhesion and proliferation were studied to determine the cytoskeletal and cytotoxic basis of cocaine in cardiac cells. Treatment of cardiac myocytes with cocaine increased cell migration and adhesion (p < 0.05), with no effect on cell proliferation, except with higher doses eliciting (1–10 μg/mL) its diminution and increase in cell death. Cocaine downregulated phosphorylation of cofilin, decreased expression of adhesion modulators (integrin-β3) and increased expression of ezirin within three hours of 1 μg/mL treatments. These functional responses were associated with changes in cellular morphology, including alterations in membrane stability and a stellate-like phenotype with less compaction between cells. Higher dose treatments of cocaine (5–10 μg/mL) were associated with significant cardiomyocyte cell death (p < 0.05) and loss of cellular architecture. These results highlight the importance of cocaine in mediating cardiomyocyte function and cytotoxicity associated with the possible loss of intercellular contacts required to maintain normal cell viability, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.     

The corrosion of mild and stainless steel in alkaline anaerobic conditions representing the Belgian “supercontainer” concept and the Swiss L/ILW repository

Deep geological repositories for radioactive waste contain metallic materials, either used to construct disposal canisters or as low-/intermediate-level waste (L/ILW). The safety relevance of corrosion is linked to canister lifetime in the former case and gas generation in the latter. More specifically, the Belgian “supercontainer” concept envisages mild steel for the used fuel disposal canister, and in the case of the Swiss L/ILW repository, mild steels are the largest metallic waste component due to the decommissioning of civilian power-generating facilities. For these circumstances, the corrosion environment is dominated by the chemistry of cement, which is used as buffer or backfill material. The corrosion behaviour of mild steel in anoxic environments was studied through the analysis of the hydrogen end-product. Hydrogen analysis was conducted by periodically purging the cell head-space and analysing the gas using a solid-state hydrogen sensor. While this method is limited to providing only uniform corrosion rates averaged over periods of time, ranging from weeks to months, it provides excellent resolution and sensitivity. The test cell environments were matched against the anticipated Belgian high-level waste and Swiss L/ILW repository environments, and also against experiments that have been conducted by other researchers for comparative purposes. Samples were exposed to synthetic cement pore waters, representing fresh and degraded cement. In young cement waters, the formation of initial corrosion products resulted in steel wire corrosion rates of the order of µm/year, which, at 80°C rapidly declined to ∼10 nm/year. In contrast, SA516 grade 70 steel plate corroded much more slowly under similar conditions. In aged cement waters, initial corrosion rates were higher but declined faster towards a longer-term rate of ∼10 nm/year. 316L stainless steel, embedded in cementitious material, corroded at a rate of <1 nm/year at 50°C.     

Association between patient psychosocial characteristics and receipt of in‐center nocturnal hemodialysis among prevalent dialysis patients

Introduction: Compared to traditional in‐center hemodialysis (HD), in‐center nocturnal dialysis (INHD) is characterized by longer sessions and nighttime administration, which may lead to better outcomes for some patients. Given the importance of patient choice in the decision to initiate INHD, we explored associations between patients’ psychosocial characteristics and their receipt of INHD. Methods: Among hemodialysis patients at a medium‐sized dialysis organization, we identified INHD patients as those for whom ≥80% of dialysis sessions were INHD sessions—starting at 6:30 pm or later and lasting ≥5 hours—over the 3 months (≥20 sessions total) after their first INHD session. We extracted dialysis session data from electronic medical records and psychosocial data from social worker assessments. We tested associations of patients’ psychosocial characteristics—as well as demographic and clinical characteristics—with INHD receipt among all hemodialysis patients (INHD and HD) in bivariate analyses and multivariable logistic regression models. Findings: Among 759 patients with complete data, we identified 47 (6.2%) as INHD patients. On average, these patients were more likely than HD patients to be employed (full‐time 10.6% vs. 5.2%; part‐time 17.0% vs. 4.2%; P < 0.001), and they were significantly less likely to require ambulatory assistance (14.9% vs. 39.6%, P < 0.001). In multivariable regressions, we found that part‐time employment (versus being unemployed) was associated with a 7.1 percentage‐point higher likelihood of being an INHD patient (P = 0.01), and the negative association with ambulatory assistance needs approached statistical significance (P = 0.056). No other psychosocial factors included in this main regression analysis were statistically significantly associated with INHD patient status. Discussion: Researchers comparing the outcomes of patients undergoing INHD versus other treatment modalities will need to account for differences in employment status—and other factors like requiring ambulatory assistance and age which may predict the ability to work—between INHD users and comparison patients to avoid bias in estimates.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.