Environmental behaviour of iron and steel slags in coastal settings.

Iron and steel slags have a long history of both disposal and beneficial use in the coastal zone. Despite the large volumes of slag deposited, comprehensive assessments of potential risks associated with metal(loid) leaching from iron and steel by-products are rare for coastal systems. This study provides a national-scale overview of the 14 known slag deposits in the coastal environment of Great Britain (those within 100 m of the mean high-water mark), comprising geochemical characterisation and leaching test data (using both low and high ionic strength waters) to assess potential leaching risks. The seaward facing length of slag deposits totalled at least 76 km, and are predominantly composed of blast furnace (iron-making) slags from the early to mid-20th Century. Some of these form tidal barriers and formal coastal defence structures, but larger deposits are associated with historical coastal disposal in many former areas of iron and steel production, notably the Cumbrian coast of England. Slag deposits are dominated by melilite phases (e.g. gehlenite), with evidence of secondary mineral formation (e.g. gypsum, calcite) indicative of weathering. Leaching tests typically show lower element (e.g. Ba, V, Cr, Fe) release under seawater leaching scenarios compared to deionised water, largely ascribable to the pH buffering provided by the former. Only Mn and Mo showed elevated leaching concentrations in seawater treatments, though at modest levels (<3 mg/L and 0.01 mg/L, respectively). No significant leaching of potentially ecotoxic elements such as Cr and V (mean leachate concentrations <0.006 mg/L for both) were apparent in seawater, which micro-X-Ray Absorption Near Edge Structure (µXANES) analysis show are both present in slags in low valence (and low toxicity) forms. Although there may be physical hazards posed by extensive erosion of deposits in high-energy coastlines, the data suggest seawater leaching of coastal iron and steel slags in the UK is likely to pose minimal environmental risk.

Characterisation of rare earth elements and toxic heavy metals in coal and coal fly ash.

Due to increasing demand for rare earth elements (REE), growing concerns over their sustainability, and domination of their supply by China, coal fly ash has recently emerged as a viable target for REE recovery. With billions of tonnes in repositories and still more being generated across the globe, it is necessary to develop environmentally friendly and economical extraction technologies for the recovery of the REEs from coal fly ash, and to consider the environmental implications of such a recovery process. This study reports characterisation of Nigerian simulant coal fly ash, and investigates the distribution and leaching of the REEs and U, Th, As, Cr, Cd and Pb from these materials using ethanoic acid. Significant amounts (14% to 31%) of the REEs were recovered in the acid-soluble fraction of a sequential extraction procedure using ethanoic acid. While the greatest amounts of U (53% to 62%) and Th (89% to 96%) were recovered in the stable residual fraction, significant amounts (3% to 13%) of U were recovered in the acid-soluble fraction. As was the most enriched element in the mobile acid-soluble fraction (46% to 60%), followed by Cd (15% to 34%). These results demonstrate that REEs contained within coal fly ash - especially those sourced from coal-fired power plants burning coal at temperatures between 700 °C and 1100 °C - can be recovered through an environmentally friendly procedure using the cost-effective heap leaching method, with ethanoic acid or the more cheaply-available vinegar as lixiviant. These results are also valuable for cost evaluation of rare earths recovery from coal fly ash generated by fluidised bed combustion coal fired power plants, and the development of methodologies for coal fly ash management.

Mid-infrared spectral classification of endometrial cancer compared to benign controls in serum or plasma samples.

This study demonstrates a discrimination of endometrial cancer versus (non-cancerous) benign controls based on mid-infrared (MIR) spectroscopy of dried plasma or serum liquid samples. A detailed evaluation was performed using four discriminant methods (LDA, QDA, kNN or SVM) to execute the classification task. The discriminant methods used in the study comprised methods that are widely used in the statistics (LDA and QDA) and machine learning literature (kNN and SVM). Of particular interest, is the impact of discrimination when presented with spectral data from a section of the bio-fingerprint region (1430 cm-1 to 900 cm-1) in contrast to the more extended bio-fingerprint region used here (1800 cm-1 to 900 cm-1). Quality metrics used were the misclassification rate, sensitivity, specificity, and Matthew's correlation coefficient (MCC). For plasma (with spectral data ranging from 1430 cm-1 to 900 cm-1), the best performing classifier was kNN, which achieved a sensitivity, specificity and MCC of 0.865 ± 0.043, 0.865 ± 0.023 and 0.762 ± 0.034, respectively. For serum (in the same wavenumber range), the best performing classifier was LDA, achieving a sensitivity, specificity and MCC of 0.899 ± 0.023, 0.763 ± 0.048 and 0.664 ± 0.067, respectively. For plasma (with spectral data ranging from 1800 cm-1 to 900 cm-1), the best performing classifier was SVM, with a sensitivity, specificity and MCC of 0.993 ± 0.010, 0.815 ± 0.000 and 0.815 ± 0.010, respectively. For serum (in the same wavenumber range), QDA performed best achieving a sensitivity, specificity and MCC of 0.852 ± 0.023, 0.700 ± 0.162 and 0.557 ± 0.012, respectively. Our findings demonstrate that even when a section of the bio-fingerprint region has been removed, good classification of endometrial cancer versus non-cancerous controls is still maintained. These findings suggest the potential of a MIR screening tool for endometrial cancer screening.

Experimental photoluminescence and lifetimes at wavelengths including beyond 7 microns in Sm3+-doped selenide-chalcogenide glass fibers.

1000 ppmw Sm3+-doped Ge19.4Sb9.7Se67.9Ga3 atomic % chalcogenide bulk glass and unstructured fiber are prepared. Near- and mid-infrared absorption spectra of the bulk glass reveal Sm3+ electronic absorption bands, and extrinsic vibrational absorption bands, due to host impurities. Fiber photoluminescence, centred at 3.75 µm and 7.25 µm, is measured when pumping at either 1300 or 1470 nm. Pumping at 1470 nm enables the photoluminescent lifetime at 7.3 µm to be measured for the first time which was ∼100 µs. This is the longest to date, experimentally observed lifetime in the 6.5-9 µm wavelength-range of a lanthanide-doped chalcogenide glass fiber.

Microplastic ingestion by pelagic and demersal fish species from the Eastern Central Atlantic Ocean, off the Coast of Ghana.

We present data on the occurrence of microplastics in fish from the Guinea current region off Ghana's Coast. Frequency of occurrence of microplastics in the fish species followed the order: Sardinella maderensis (41%) > Dentex angolensis > (33%) > Sardinella aurita (26%). Mean numbers of microplastics ingested were 40.0 ± 3.8, 32.0 ± 2.7 and 25.7 ± 1.6 for S. maderensis, D. angolensis and S. aurita respectively. Industrially produced pellets were the most dominant (31%) microplastic type followed by microbeads (29%), burnt film plastics (22%) and unidentified fragments (9%). Microfibers (2%), threads (2%) and foams (<0.1%) were the least occurring microplastics in the fish species. Condition factors estimated for D. angolensis and S. aurita were >1 and below 1 for S. maderensis. The findings of the study show the common occurrence of microplastics in fish stocks and pave the way for future studies on microplastics in this Region.

Trial-level prediction of long-term outcome based on pathologic complete response (pCR) after neoadjuvant chemotherapy for early-stage breast cancer (EBC).

BACKGROUND: The US Food and Drug Administration and European Medicines Agency have published guidance for industry on the use of pathologic complete response (pCR) as a surrogate endpoint to accelerate the regulatory approval of neoadjuvant agents in high-risk early-stage breast cancer (EBC). Three meta-analyses, the CTNeoBC consortium (Cortazar 2014), Berruti (2014), and Korn (2016), evaluated the association between the pCR odds ratio and the event hazards ratio but did not identify strong trial-level associations. Thus, uncertainties remain with respect to whether the magnitude of effect-size increase in pCR reasonably predicts long-term clinical benefit. FINDINGS: Trial-level data from CTNeoBC were used as the training data set to derive an empirical nonlinear model for predicting long-term outcomes based on pCR results. A Cox regression model was used to evaluate the relationship among treatments, event hazards, and pCR as joint covariates. The trial-level association between treatment and event hazard was derived and then linked with pCR rates. Magnitude of the patient-level association was also included in the analysis. Additional published trials were used to validate the predictive model. Numerical differences between the perfect surrogate prediction and observed effect followed normal distribution based on the Kolmogorov-Smirnov test. For event-free survival (EFS), the Student t-test P value of 0.02 suggested a statistically significant nonzero difference, with a mean value of -0.163 (SE 0.058). For overall survival (OS), the Student t-test P value of 0.0027 suggested a statistically significant nonzero difference, with a mean value of -0.153 (SE 0.038). Three studies, including GeparSixto, BOOG, and Neo-tAnGo, were used for validation. The F test suggested the model fit the test data well. IMPLICATIONS: The observed hazard ratios fit well with the predicted hazard ratios for both EFS and OS and suggest plausible trial-level associations with the new predictor. MAJOR FINDINGS: Our model predicted the correlation between pCR and EFS as well as OS. This model could be used as a supporting tool to help interpret positive pCR results in neoadjuvant clinical studies in patients with high-risk EBC.

The removal of uranium onto carbon-supported nanoscale zero-valent iron particles.

In the current work carbon-supported nanoscale zero-valent iron particles (CS nZVI), synthesised by the vacuum heat treatment of ferric citrate trihydrate absorbed onto carbon black, have been tested for the removal of uranium (U) from natural and synthetic waters. Two types of CS nZVI were tested, one vacuum annealed at 600 °C for 4 h and the other vacuum annealed at 700 °C for 4 h, with their U removal behaviour compared to nZVI synthesised via the reduction of ferrous iron using sodium borohydride. The batch systems were analysed over a 28-day reaction period during which the liquid and nanoparticulate solids were periodically analysed to determine chemical evolution of the solutions and particulates. Results demonstrate a well-defined difference between the two types of CS nZVI, with greater U removal exhibited by the nanomaterial synthesised at 700 °C. The mechanism has been attributed to the CS nZVI synthesised at 700 °C exhibiting (i) a greater proportion of surface oxide Fe2+ to Fe3+ (0.34 compared to 0.28); (ii) a greater conversion of ferric citrate trihydrate [2Fe(C6H5O7)·H2O] to Fe0; and (iii) a larger surface area (108.67 compared to 88.61 m2 g-1). Lower maximum U uptake was recorded for both types of CS nZVI in comparison with the borohydride-reduced nZVI. A lower decrease in solution Eh and DO was also recorded, indicating that less chemical reduction of U was achieved by the CS nZVI. Despite this, lower U desorption in the latter stages of the experiment (>7 days) was recorded for the CS nZVI synthesised at 700 °C, indicating that carbon black in the CS nZVI is likely to have contributed towards U sorption and retention. Overall, it can be stated that the borohydride-reduced nZVI were significantly more effective than CS nZVI for U removal over relatively short timescales (e.g. <48 h), however, they were more susceptible to U desorption over extended time periods.

Nanoscale Metallic Iron for Environmental Remediation: Prospects and Limitations.

The amendment of the subsurface with nanoscale metallic iron particles (nano-Fe(0)) has been discussed in the literature as an efficient in situ technology for groundwater remediation. However, the introduction of this technology was controversial and its efficiency has never been univocally established. This unsatisfying situation has motivated this communication whose objective was a comprehensive discussion of the intrinsic reactivity of nano-Fe(0) based on the contemporary knowledge on the mechanism of contaminant removal by Fe(0) and a mathematical model. It is showed that due to limitations of the mass transfer of nano-Fe(0) to contaminants, available concepts cannot explain the success of nano-Fe(0) injection for in situ groundwater remediation. It is recommended to test the possibility of introducing nano-Fe(0) to initiate the formation of roll-fronts which propagation would induce the reductive transformation of both dissolved and adsorbed contaminants. Within a roll-front, Fe(II) from nano-Fe(0) is the reducing agent for contaminants. Fe(II) is recycled by biotic or abiotic Fe(III) reduction. While the roll-front concept could explain the success of already implemented reaction zones, more research is needed for a science-based recommendation of nano-Fe(0) for subsurface treatment by roll-fronts.

Using Xenopus oocyte extracts to study signal transduction.

Xenopus oocytes are naturally arrested at G2/M in prophase I of meiosis. Stimulation with progesterone initiates a nontranscriptional signaling pathway that culminates in the activation of Cdc2/cyclin B and reentry into meiosis. This pathway presents a paradigm for nongenomic signaling by steroid hormones and for the G2/M cell cycle transition. It has been extensively studied using intact oocytes, which are amenable to microinjection and biochemical analyses described elsewhere in this book. However, there are several experimental advantages in using in vitro systems consisting of cytosolic fractions of prophase-arrested oocytes. Because of their homogeneous nature, extracts avoid the difficulties of signaling asynchrony between individual oocytes. They are also amenable to biochemical manipulations such as protein immunodepletions, and proteins and pharmacological agents can be added easily. Despite these features, oocyte extracts have yet to achieve the widespread utility of Xenopus egg extracts, which can proceed through rounds of deoxyribonucleic acid (DNA) replication and mitosis in vitro. Here, we review the historical development of oocyte extracts and discuss the factors most crucial to success in reproducing the signaling pathway and the G2/M transition in vitro.

Altered transmission of maternal angiotensin II receptor haplotypes in fetal growth restriction.

Fetal growth restriction (FGR) predisposes to significant short- and long-term health problems. Epidemiological studies have suggested a role for inherited factors in its pathogenesis. The angiotensin II receptor genes, AGTR1 and AGTR2, are candidate genes because they mediate processes that are important for placentation. This study investigated AGTR1 and AGTR2 haplotypes and genotypes in FGR. A total of 107 families (father, mother, and baby) with FGR, and 101 families with normal pregnancies were genotyped at five sites in AGTR1 and six sites across AGTR2. All of the participants were white western Europeans. FGR was identified antenatally by ultrasound scans and confirmed postnatally by correcting the birth weight centile for gestation, infant sex, maternal height, weight, and parity. Fetal genes were investigated using transmission disequilibrium testing (TDT), and a case-control comparison of maternal haplotypes was conducted. FGR was associated with maternal (but not paternal) transmission of the AGTR1 haplotype (GenBank AF245699.1) g.4955T, g.5052T, g.5245C, g.5612A, and haplotype g.4955T, g.5052T, g.5245T, g.5612A. Haplotype g.4955A, g.5052G, g.5245T, g.5612G was undertransmitted (P = 0.002). TDT of the AGTR1 genotype showed undertransmission of maternal AGTR1 genotypes g.4955T>A (odds ratio (OR), 0.34 (95% confidence interval (CI), 0.14-0.86); P = 0.02), g.5052T>G (OR, 0.18 (0.06-0.48); P<0.001), and g.5612A>G (OR, 0.21 (0.08-0.55); P < 0.001) in FGR. There were no differences in maternal haplotype frequencies between normal pregnancy and FGR for AGTR1 or AGTR2 (P > 0.10). This is the first study to show distortion of transmission of maternal AGTR1 haplotypes in FGR, which suggests that this gene plays a role in FGR. In particular, maternal-fetal gene sharing may be an important factor.

Activation of AP-1-dependent transcription by a truncated translation initiation factor.

Int6/eIF3e is a highly conserved subunit of eukaryotic translation initiation factor 3 (eIF3) that has also been reported to interact with subunits of the proteasome and the COP9 signalosome. Overexpression of full-length Int6 or a 13-kDa C-terminal fragment, Int6CT, in the fission yeast Schizosaccharomyces pombe causes multidrug resistance that requires the otherwise inessential AP-1 transcription factor Pap1. Here we show for the first time that Int6CT acts to increase the transcriptional activity of Pap1. Microarray hybridization data indicate that Int6CT overexpression resulted in the up-regulation of 67 genes; this expression profile closely matched that of cells overexpressing Pap1. Analysis of the upstream regulatory sequences of these genes showed that the majority contained AP-1 consensus binding sites. Partial defects in ubiquitin-dependent proteolysis have been suggested to confer Pap1-dependent multidrug resistance, but no such defect was seen on Int6CT overexpression. Indeed, none of the previously identified interactions of endogenous Int6 was required for the activation of Pap1 transcription described here. Moreover, Int6CT-induced activation of Pap1-responsive gene expression was independent of the ability of Pap1 to undergo a redox-regulated conformational change which mediates its relocalization to the nucleus and expression of oxidative stress response genes. Int6CT therefore activates Pap1-dependent transcription by a novel mechanism.

Requirements for the destruction of human Aurora-A.

The mitotic kinase Aurora A (Aur-A) is overexpressed in a high proportion of human tumors, often in the absence of gene amplification. In somatic cells, Aur-A protein levels fall following mitosis or upon overexpression of Cdh1, an activator of the ubiquitin ligase APC/C. Thus, mutations that reduce or block the rate of Aur-A destruction might also be expected to contribute to its oncogenic potential. Previous work had defined two short sequences of Xenopus Aur-A that are required for its Cdh1-inducible destruction in extracts of Xenopus eggs, an N-terminal A box and a C-terminal D box, and a serine residue within the A box whose phosphorylation might inhibit destruction. Here, we show that these same sequences are required for the destruction of human Aur-A during mitotic exit and G1 in the somatic cell cycle. Expression of a dominant negative Cdh1 protein leads to accumulation of Aur-A, further indicating that the Cdh1-activated form of the APC/C is responsible for destruction of Aur-A during the somatic cell cycle in vivo. During the course of this work, we found some previously unsuspected problems in commonly used in vitro destruction assays, which can result in misleading results. Potentially confounding factors include: (i) the presence of D-box- and A-box-dependent destruction-promoting activities in the reticulocyte in vitro translation mix that is used to produce radiolabeled substrates for destruction assays; and (ii) the ability of green-fluorescent-protein tags to reduce the destruction rate of Aur-A substantially. These findings have direct relevance for studies of Aur-A destruction itself, and for broader approaches that use in vitro translation products in screens for additional APC/C targets.

Aurora A, meiosis and mitosis.

The Aurora family kinases are pivotal to the successful execution of cell division. Together they ensure the formation of a bipolar mitotic spindle, accurate segregation of chromosomes and the completion of cytokinesis. They are also attractive drug targets, being frequently deregulated in cancer and able to transform cells in vitro. In this review, we summarize current knowledge about the three family members, Aur-A, Aur-B and Aur-C. We then focus on Aur-A, its roles in mitotic progression, and its emerging roles in checkpoint control pathways. Aur-A activity can be controlled at several levels, including phosphorylation, ubiquitin-dependent proteolysis and interaction with both positive regulators, such as TPX2, and negative ones, like the tumor suppressor protein p53. In addition, work in Xenopus oocytes and early embryos has revealed a second role for Aur-A, directing the polyadenylation-dependent translation of specific mRNAs important for cell cycle progression. This function extends to post-mitotic neurons, and perhaps even to cycling somatic cells.

Sum1, a component of the fission yeast eIF3 translation initiation complex, is rapidly relocalized during environmental stress and interacts with components of the 26S proteasome.

Eukaryotic translation initiation factor 3 (eIF3) is a multisubunit complex that plays a central role in translation initiation. We show that fission yeast Sum1, which is structurally related to known eIF3 subunits in other species, is essential for translation initiation, whereas its overexpression results in reduced global translation. Sum1 is associated with the 40S ribosome and interacts stably with Int6, an eIF3 component, in vivo, suggesting that Sum1 is a component of the eIF3 complex. Sum1 is cytoplasmic under normal growth conditions. Surprisingly, Sum1 is rapidly relocalized to cytoplasmic foci after osmotic and thermal stress. Int6 and p116, another putative eIF3 subunit, behave similarly, suggesting that eIF3 is a dynamic complex. These cytoplasmic foci, which additionally comprise eIF4E and RNA components, may function as translation centers during environmental stress. After heat shock, Sum1 additionally colocalizes stably with the 26S proteasome at the nuclear periphery. The relationship between Sum1 and the 26S proteasome was further investigated, and we find cytoplasmic Sum1 localization to be dependent on the 26S proteasome. Furthermore, Sum1 interacts with the Mts2 and Mts4 components of the 26S proteasome. These data indicate a functional link between components of the structurally related eIF3 translation initiation and 26S proteasome complexes.