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A primer coating system adherent to iron substrates based on graphene nano-platelets (GNPs) dispersed in polyvinylbutyral (PVB) is presented. Using a scanning Kelvin probe (SKP), the composite coatings are shown to exhibit exceptional resistance to an important corrosion-driven failure process, namely cathodic delamination, when aqueous chloride electrolyte is introduced to a penetrating coating defect. Delamination rate kinetics are shown to correlate strongly with reductions in the rate of oxygen permeation through the coating with increasing GNP pigment volume fraction. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), the most common primary brain malignancy in adults, is an aggressive cancer with limited life expectancy. The standard of care backbone for newly diagnosed GBM is intensity-modulated radiation therapy (IMRT) with concomitant and adjuvant temozolomide. AZD1390, an oral, highly potent, and selective ataxia telangiectasia mutated kinase inhibitor, is designed to augment the efficacy of IMRT without exacerbating neurotoxicity. AZD1390 is optimized for blood brain barrier penetration, confirmed in a human healthy volunteer PET study (NCT03215381) and a Phase 0 study in patients (pts) with GBM (NCT05182905). This global, Phase 1, open-label study (NCT03423628) evaluates the safety and preliminary efficacy of escalating doses of AZD1390 and radiation therapy (RT) in pts with GBM and brain metastases. Eligible adult pts received escalating once-daily AZD1390 doses following a Bayesian continual reassessment method, with IMRT 35 Gy in 10 fractions over 2 weeks (Arm A, recurrent GBM) or IMRT 60 Gy in 30 fractions over 6 weeks (Arm C, newly diagnosed, O-6-methylguanine-DNA methyltransferase unmethylated GBM). Pts in both Arms received 2 additional weeks of adjuvant AZD1390 post-IMRT. Arm B included pts with brain metastases but was closed due to low recruitment and is not reported. Primary objective was safety; secondary objectives included clinical efficacy and pharmacokinetics (PK). As of Feb 6, 2024, 115 pts have received AZD1390 (75 in Arm A; 40 in Arm C) at doses of 10–900 mg/day. PK was linear with a slightly more than dose-proportional increase and a mean terminal elimination half-life around 9–11 hours. Most patients had ≥1 treatment-emergent adverse event (AE); the most common were fatigue (51.3%), nausea (39.1%) and headache (38.3%). Grade ≥3 AZD1390-related AEs occurred in 18/115 pts (15.7%). The maximum tolerated dose was identified as 400 mg in Arm A and 300 mg in Arm C. Dose limiting toxicities included, but were not limited to, creatinine kinase elevation in Arm A and radiation skin injury in Arm C. Treatment was well tolerated, with the majority of reported AEs being low-grade. AEs led to discontinuation of AZD1390 in 13.0% of pts. The safety profile was consistent across Arms despite the different RT schedules; the most notable difference was in radiation skin injury, a reversible event, with higher frequency and severity in Arm C. At doses demonstrating target engagement in the Phase 0 study, median overall survival was 12.7 months (95% CI = 10.7, 18.9, n = 21) for Arm A and is still maturing for Arm C. Concurrent AZD1390 and IMRT administration is tolerated with a manageable safety profile, at doses shown to achieve clear target engagement in the Phase 0 study. Preliminary efficacy is encouraging in Arm A. These data suggest the potential for AZD1390 to act as a radiosensitizer for the treatment of GBM. Clinical investigation is ongoing. [ABSTRACT FROM AUTHOR]

Abstract: The width of the vacancy related photoluminescence from diamond is used to qualitatively measure the strain in type IIa diamonds of a range of brown colours and to measure the effect on the strain of high pressure high temperature annealing of the brown diamonds. The results indicate that for untreated type IIa diamonds the strain in colourless diamonds is generally less than that observed in brown ones. Annealing to remove the brown colour brings about a measurable reduction in the strain as assessed via the luminescence line width; but a dependence on the depth of the original brown colour is retained with the value remaining in most cases above 1.70meV, a width below which 92% of the untreated colourless diamonds lie. [Copyright &y& Elsevier]

The effect of altering water chemistry on acute silver toxicity to three invertebrate species, two Daphnids, Daphnia magna and Daphnia pulex, as well as an amphipod Gammarus pulex was assessed. In addition, the physiological basis of Ag(I) toxicity to G. pulex was examined. Daphnia magna and D. pulex were more sensitive than G. pulex and 48 h LC50 values in synthetic ion poor water were 0.47, 0.65 and 2.1 μg Ag(I) l−1, respectively. Increasing water [Cl−] reduced Ag(I) toxicity in all species, and increasing water [Ca2+] from 50 to 1500 μM reduced Ag(I) toxicity in G. pulex. Whole body Na+ content, but not K+ or Ca2+ was significantly reduced in G. pulex exposed to 6 μg Ag(I) l−1 for 24 h, but there was no inhibition of whole body Na+/K+-ATPase activity. Both increasing water [Cl−] and [Ca2+] reduced this Ag(I)-induced Na+ loss. For D. magna, the presence of 10 mg l−1 humic acid or 0.5 μM 3-mercaptoproprionic acid (3-MPA) increased the 48 h LC50 values by 5.9 and 58.5-fold, respectively, and for D. pulex the presence of 1 μM thiosulfate increased the 48 h LC50 value by four-fold. The D. magna toxicity data generated from this study were used to derive a Daphnia biotic ligand model (BLM). Analysis of the measured LC50 values vs. the predicted LC50 values for toxicity data from the present and published results where water Cl−, Ca2+, Na+ or humic acid were varied showed that 91% of the measured toxicity data fell within a factor of two of the predicted LC50 values. However, the daphnid BLM could not accurately predict G. pulex toxicity. Additionally, the Daphnia BLM was under-protective in the presence of the organic thiols 3-MPA or thiosulphate and predicted an increase in the LC50 value of 114- and 74-fold, respectively. The Daphnia toxicity based BLM derived from the present data set is successful in predicting Daphnia toxicity in laboratory data sets in the absence of sulfur containing compounds, but shows its limitations when applied to waters containing organic thiols or thiosulphate. [Copyright &y& Elsevier]

Assesses the clinical parameters that may predict stent patency in patients presenting early after coronary stenting. Baseline demographics of stented patients; Clinical characteristics of patients at time of recurrent chest pain; Electrocardiographic data at time of recurrent chest pain.

Abstract: Attenuated total internal reflection FTIR mapping was used to examine the coarse microscopic two-phase structure seen with some blended and recycled polymers. The blends studied were virgin and recycled ABS, HIPS and polycarbonate, typical of waste electrical and electronic plastics. The method was compared to optical microscopy both before and after etching with chromic acid. It was found that while optical microscopy showed up phase separation on a scale of tens of microns, the FTIR mapping allowed compositional details to be investigated. The phase structure could be quantified by using the standard deviation of band ratios and this correlated well with mechanical performance. The effects of processing method were more significant than whether material was recycled or not. Longer, less intensive processing produced more phase separation than shorter more intensive processing. [Copyright &y& Elsevier]

We studied the ability of heat shock, DnaJ-like-1 (HSJ1) proteins (which contain DnaJ and ubiquitin-interacting motifs) to reduce polyglutamine-mediated inclusion formation. The experiments demonstrated that expression of heat shock protein 70 (hsp70), hsp40, HSJ1a, and HSJ1b significantly reduced protein inclusion formation in a model of spinal and bulbar muscular atrophy (SBMA). HSJ1a also mediated a significant decrease in the number of inclusions formed in a primary neuronal model of protein aggregation. Studies to elucidate the mechanisms underlying these reductions showed that hsp70 and hsp40 increased chaperone-mediated refolding. In contrast, expression of HSJ1 proteins did not promote chaperone activity but caused an increase in ubiquitylation. Furthermore, HSJ1a was associated with a ubiquitylated luciferase complex, and in the presence of HSJ1a but not an HSJ1a UIM mutant (HSJ1a-ΔUIM) there was a reduction in luciferase protein levels. Together these results show that HSJ1 proteins mediated an increase in target protein degradation via the ubiquitin-proteasome system (UPS). We also found that the expression of HSJ1a significantly decreased the number of neurons containing inclusions in an in vivo model of polyglutamine disease. These findings indicate that targeted modification of the UPS to facilitate degradation of misfolded proteins may represent a highly effective therapeutic avenue for the treatment of polyglutamine disease.Molecular Therapy (2007) 15 6, 1100–1105. doi:10.1038/sj.mt.6300163 [ABSTRACT FROM AUTHOR]